THURSDAY, SEPTEMBER 7 1 - CiteSeerX

THURSDAY, SEPTEMBER 7 1

INVITED COMMUNICATIONS

EN4.01 TEACHING OF LAPAROSCOPY USING ROBOTICS

EN4.01.01AESOP TECHNIQUEL. Mettler , Dept. OB/GYN, University of Kiel, Michaelisstr. 16, 24105Kiel, Germany

Objectives: The aim of the study was a comparison of robotic versushuman laparoscopic camera control.Study Methods: Utilizing robotic technology a robot has been designedspecifically for the purpose of holding and manoeuvring the laparoscopeunder the direct control of the surgeon. Directions are given using thefoot, hand or in most cases the voice control.Results: We tested AESOP (automated endoscopic system for optimalpositioning) in 50 patients undergoing routine gynaecologicalendoscopic surgical procedures. The elimination of the camera holderallows two doctors to perform complex laparoscopic surgery faster thanwithout the robotic arm. The timing of surgical procedures performed bysurgeons using the voice control was compared to the timing of similaroperations using the foot or hand control. The voice-controlled AESOPworks more efficiently and faster than the hand or foot control.Conclusions: A robotic assistant such as AESOP 3000 is seen to be acost effective device replacing the traditional assistant and providing thesurgeon with a more stable operating field.

EN4.01.02LAHYSTOTRAIN - INTEGRATION OF VIRTUALENVIRONMENTS AND INTELLIGENT TRAINING SYSTEMS FORLAPAROSCOPY AND HYSTEROSCOPYP. Oppelt (1), J. Stähler (1), W. Müller (2), M. Kaufmann (1),(1) University Hospital, Theodor-Stern-Kai 7, Frankfurt am Main,

Hessen, Germany, 60590,(2) Fraunhofer Institut, Darmstadt, Germany.

Objectives: “Learning by doing” is the traditional way in medicaleducation. One exception is the training of endoscopic surgery. Manyworkshops are offered for beginners and specialists to improve theirknowledge and manual skills. The main point of criticism of this methodof training is the unrealistic environment of the plastic models forhysteroscopy and laparoscopy.Study Methods: The idea was to overcome these traditional trainingmethods for laparoscopy and hysteroscopy by developing a computer-assisted simulator for training and for quality control in laparoscopic &hysteroscopic procedures using computer graphics and Virtual Reality,Multimedia technology, and Intelligent Tutoring Systems. Theoreticaland practical training program was designed Based on the trainingprogram of the “European Society of Human Reproduction andEmbryology” (ESHRE).Results: The Lahystotrain application is the result of two trainingsystems:Basic Training System: It covers the initial phase of training and isaccessed remotely by MS Explorer or Netscape. Advanced TrainingSystem: The VR simulator will run on a Silicon Graphics Octaneworkstation, which is supervised by an Assistant running on a separatePC under Windows NT.Conclusions: Lahystotrain is a new way of learning endoscopic surgery.It is more than a simulator for operation methods or complicationsmanagement. Through the theoretical part of the program the trainee hasthe possibility to acquire all additional information to perform a perfectoperation.

FM 4.01 MID-TRIMESTER LOSS

FM4.01.01MID-TRIMESTER LOSSH. Senanayake , University of Colombo Faculty of Medicine, Colombo,Sri Lanka

Mid-trimester abortion comprises a special group of pregnancy loss.After ‘selection’ of pregnancies by first trimester spontaneous abortionand induced abortion of fetuses diagnosed as abnormal, expectations forthose ‘selected’ become higher. Most second trimester losses occur in

such pregnancies, which are otherwise of low-risk. Until recently,mechanical weakness of the cervix received the most attention as a causeof mid-trimester abortion. However, a sizeable proportion of midtrimester abortions is unexplained. Infection may have a role in cervicalincompetence and it may not be a pure mechanical weakness. Whilecharacteristics of previous pregnancies may indicate cervicalincompetence, currently there are no criteria for the early recognition ofthe condition in a woman without risk factors. Risk has been related tothe sonographic length, rather than to digital assessment of the cervix.Cervical cerclage is the standard treatment for cervical incompetence,which is more likely to fail in the presence of intrauterine infection.Transabdominal cerclage is indicated in cases of repeated failure ofcervical cerclage. Occasionally, cervical cerclage needs to be performedas an emergency procedure, after the process of effacement and dilationof the cervix has begun. It is important to treat infection aggressively insuch cases. In cases where the fetus has died in utero, maternalserological tests for infection and autoimmune disease are important.Pathological examination of the placenta may reveal evidence of viraland bacterial infection. Mid-trimester loss is due to a multitude of causesof which many are treatable, but the condition appears to beinadequately researched.

FM4.01.02OBSTETRIC MANAGEMENT AND REPRODUCTIVE OUTCOMEAFTER HYSTEROSCOPIC METROPLASTY.E. Ferrazzi*, F.P.G. Leone *, G. Ragusa°, C. Lanzani*, A. Bulfoni°,G. Pardi°. Depts Obstetrics and Gynecology, ISBM L. Sacco andDMCO San Paolo, University of Milan, Italy.

Objective: To evaluate the obstetric management and reproductiveoutcome of women after hysteroscopic septum resection.Design: Prospective, observational study.Material and Methods: Thirty-four patients (5.7%) of 601 women withprevious miscarriages, and 12 patients (1.5%) of 806 women withprimary infertility, who underwent hysteroscopic metroplasty to treatsub-septate uteri were recruited for this study. Preoperative pregnancyloss rate in patients with previous pregnancy loss was 98%. Otherknown causes of miscarriages were excluded. The shortest follow-upafter surgery was nine months. Serial sonographic fundal thickness andcervical length were obtained every month from 16 weeks of gestation.aFP serum level was assessed at 16 weeks in patients with fundalplacentation. Cervical cerclage was performed only on ultrasoundindication. With normal sonographic findings, prostaglandins (PGE2)were used to induce labour when indicated.Results: Thirty four patients conceived 46 pregnancies. Mean maternalage at delivery was 34±4. Miscarriages, ectopic pregnancies, livebirthsand ongoing pregnancies were 18 , 3, 22 and 4 respectively. Theprevalence of these outcome was not significantly different in the twosubsets of patients. In 10 miscarriages of 18 a kariotype was feasible andin three cases chromosomal abnormalities were found. In four pregnantwomen with a fundal placentation a normal aFP serum level at sixteenweeks was found and serial sonographic exams revealed a normallyinserted placenta and normal fundal myometrial thickness. In six womena cervical cerclage was performed for ultrasound indication. Meangestational age at delivery in these six patients was 36±1. This wassignificantly lower(p<0.01) than in the 22 patients with normal cervicalultrasound at 16 weeks (39±2). Eleven women were delivered vaginally;in four of these patients a successful labor was induced withprostaglandins. Ten patients were delivered by cesarean section (48%).Median fetal weight was 3200g (range 1680-4000g). A perinatal deathoccurred after an emergency cesarean section performed for an acuteuterine fundal rupture during premature labor at 37 weeks.Discussion: Hysteroscopic metroplasty improved reproductive outcomefrom 2% before metroplasty to 56% after therapy, in spite of elevatedmaternal age and short follow-up period. Ultrasound cervical assessmentis a useful tool to select patients for therapeutical cercalge. PGE2 wassuccesfully used, although on a limited number of cases, to inducelabour in patients with uncomplicated hysteroscopic metroplasty. Aclose maternal monitoring must be provided at term for the risk ofuterine rupture which remains a rare but unpredictable complication.

THURSDAY, SEPTEMBER 72

FM4.01.03ROLE OF ULTRASOUND IN CERVICAL ASSESSMENTTae-Bok Song , Department of Obstetrics and Gynecology, ChonnamUniversity Medical School, Kwangju 501-190, Korea

Preterm birth (PTB) is an important cause of perinatal morbidity andmortality. Despite convincing evidence of continued improvement inboth maternal and infant outcomes, there has been no appreciablereduction in the incidence of PTB. Historic assessments of antecedentpreterm delivery (PTD) or even multifactorial risk scoring systems failto provide predictive correlates for subsequent pregnancy outcomes inhigh-risk populations.Detection of subtle cervical changes before the onset of clinicallyapparent preterm labor (PTL) may be an important element in themanagement of patients at risk for PTB. Recent prospective clinicalinvestigations have been reported that a significantly increased risk forPTD is highly correlated with the development of early effacement andmaturation of the cervix and lower uterine segment.Frequent digital examinations have not proved to be a consistentlyeffective way of recognizing early cervical changes. In contrast,sonographic assessment has the potential of providing precise, objective,and repeatable measurements of cervical length. Transabdominalsonographic measurement of cervical length is affected variably bymaternal body habitus and bladder filling, but transvaginal sonographywith an empty maternal bladder is unaffected by them.Patients with possible early PTL whose cervical dilatation is less than 3cm present a diagnostic challenge. Recently, two new methods ofimproving the accuracy of diagnosis in symptomatic women have beenreported: transvaginal sonography to measure cervical length and thepresence of fetal fibronectin in cervicovaginal fluid. Both tests are alsobeing evaluated as screening tests for risk of spontaneous PTB. Cervicalsonography appears to be useful both in the diagnosis and managementof PTL and in the identification of women at risk for PTB.

FM4.01.04ENDOMETRIAL FACTORS IN RECURRENT MISCARRIAGEMary D. Stephenson , MD, MSc, FRCOG(Canada), FACOG, BritishColumbia’s Women’s Hospital & Health Centre, University of BritishColumbia, Vancouver, B.C., Canada

Recurrent miscarriage, defined as three or more consecutive spontaneousabortions, is a devastating reproductive problem to couples trying toestablish a family. Genetic, endocrine, anatomical and autoimmunefactors are associated with recurrent miscarriage in up to sixty percent ofcases. Unexplained recurrent miscarriage, presently a diagnosis ofexclusion, proves to be the most challenging to manage. Recent clinicalevidence suggests that suboptimal implantation may be the cumulativeevent that heralds miscarriage.Human implantation appears to be spatiotemporally controlled andinvolves “cell to cell” and “cell to matrix” interactions, mediated bygrowth factors and cytokines. The “window of implantation” appears tobe restricted to a few days each cycle, otherwise the endometrium is notreceptive to the blastocyst. Cell adhesion molecules, including integrinsand cadherins, appear to be integral to implantation and the earlymaintenance of pregnancy.In addition, human implantation involves the immune system. Inparticular, implantation appears to be a T-helper 2-type (Th-2) cytokinemediated event. A decrease in the production of Th-2 cytokines, or anincrease in Th-1 cytokines may result in subopimtal implantationthrough trophoblast cell lysis. Alterations in uterine natural killer cellpopulations may favor a Th-1 environment, leading to local cytotoxicityand subsequent arrest of pregnancy.

FM4.02 NEW GENETIC TECHNIQUES

FM4.02.01FETAL CELLS IN CERVICAL MUCUSCharles H Rodeck , Department of Obstetrics and Gynaecology, RoyalFree and University College London Medical School, 86-96 CheniesMews, London, United Kingdom

The pressure of fetal cells in cervical mucus has been suspected since1978. It is only in the last few years, using modern moleculartechniques such as FISH and PCR, that this has been confirmed. At first

it was thought that they were degenerating cells from the chorionfrondosum but their healthy viable appearance suggests thet they are theresult of active trophoblastic invasion and migration through the deciduacapsularis covering the gestation sac.It has been possible to detect aneuploidies and the presence of normal ormutable genes in small numbers of these fetal cells, which often occur inclumps or aggregates. Hence there is great potential for non-invasiveprenatal diagnosis. However clinical application is hampered by (1) amethod for simply and consistently collecting enough cervical mucus toenable near 100% detection of fetal cells (currently the success rate is50-70%). (2) methods for purifying the fetal cells to avoid maternalcontamination.

FM4.02.03FLUORESCENCE IN SITU HYBRIDIZATIONK.Suzumori , Dept. OB/GYN, Nagoya City University Medical School,Nagoya, Aichi, Japan

Chromosomal analysis is the most common approach utilized forprenatal diagnosis. Looking back the history of prenatal cytogeneticdiagnosis, initial methods involved application of conventional bandingtechniques. When fetal samples, such as chorionic villus cells oramniocytes are used, such banding techniques can reveal almost allnumerical chromosome aberrations and usual translocations, but it issometimes difficult to identify supernumerary marker chromosomes andsmall de novo unbalanced rearrangements because they lack a distinctbanding pattern.Advances in molecular cytogenetics, especially the technique offluorescence in situ hybridization (FISH), have allowed generation ofmore precise information on chromosomal structure. Centomericsatellite DNA probes and whole-chromosome painting (wcp) probes,which are specific for most individual chromosomes, have been used toanalyze chromosomal regions which cannot be identified byconventional methods. However, it is still difficult to identify telomericregions in chromosomes by either conventional G banding or FISH withwcp probes, because most of the human chromosome terminal bands areG-band-negative, and the wcp probes are often of insufficientcomplexity to detect subtle chromosomal changes, especially in thetelomeric regions. Recently, a complete set of human chromosome arm-specific telomere probes has been developed to provide new region-specific unique sequence DNA FISH probes. FISH using these arm-specific telomeric probes (telomeric FISH) has provided us with asensitive method for diagnosis of subtle chromosome aberrations,including those in telomeric regions. Telomeric FISH is especiallyuseful in the prenatal diagnosis of an individual with such a subtlebalanced translocation, where is sometimes difficult making a goodpreparation for karyotyping from cultured amniocytes or chorionic villuscells.In addition, examples of successful use of multicolor spectralkaryotyping for prenatal cytogenetic diagnosis are documented.

ON4.01 CERVICAL INTRAEPITHELIAL NEOPLASIA –DIAGNOSIS

ON4.01.02MANAGEMENT OF LOW GRADE SMEARSH. S. Chen , Y. C. Yang, T. H. Su, Mackay Memorial Hospital, Taipei,Taiwan

Objectives: The purpose of the study was to present our clinicalexperienc using a repeat Papanicolaou (PAP) smear and humanpapillomavirus (HPV) DNA testing to evaluate patients with low-gradeabnormal PAP.Study Methods: We studied 474 women who had a PAP diagnosis ofatypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (SIL) were referred to thecolposcopy clinic. All women included in this study had a repeat PAPsmear, HPV DNA testing with the Hybrid Capture method or thepolymerase chain reaction, and colposcopically directed biopsies.Results: In the 252 women referred for ASCUS, the sensitivity andspecificity of repeat PAP for detecting CIN 2/3 were 0.70 and 0.74,respectively. The sensitivity and specificity of a HPV DNA test positivefor high risk HPC were 0.91 and .059 respectively.


In the 222 women referred for low grade SIL, the sensitivity andspecificity of repeat PAP for detecting CIN2/CIN3 were 0.77 and 0.68,respectively. The sensitivity and specificity of positive HPV test were0.96 and 0.32, respectively.Triage using an HPV DNA test only correctly identified 92%, 97% ofthe women with CIN2/CIN3, but 48%, 75% of the women would havebeen referred for colposcopy with this form of triage in women withASCUS or low grade SIL, respectively.Conclusion: HPV DNA test is a sensitive alternative to colposcopicexamination for the detecting CIN2/CIN3 in women referred for a lowgrade abnormal PAP smear. However, because of the low specificity ofthis approach, in places where colposcopy is inexpensive, the relativebenefit of adding a HPV DNA testing option to patient managementwould be diminished.

ON4.01.03HPV AS A FORM OF RISK ASSESSMENTHenry Kitchener , University of Manchester, Manchester, UnitedKingdom

The aetiological association between human papillomavirus and cervicalneoplasia is well known. This pathobiological relationship mayultimately yield a preventative strategy, but over the next 10 years HPVwill be exploited principally as a marker of risk for CIN. This is beingexplored in 3 areas:• Population screening• Triage of mild cytological abnormalities• Follow up protocolPopulation screening: The potential for primary HPV screening includesincreased sensitivity, increased intervals for screening rounds, greaterautomation in lieu of reading smears, and reduced costs. All of thesecould apply in developed and underdeveloped healthcare systems.Currently, there are 2 European randomised trials (Netherlands andSweden) and a third is planned in the UK. These trials will be veryimportant in determining the effectiveness and acceptability of HPV as aform of cerivcal screening.Triage of mild cytological abnormalities: The problem in this categoryof smears (eg ASCUS) is the large number and the difficulty indetermining the minority with high grade disease, without resorting tocolposcopy. HPV has been shown to have a very high negativepredictive value and high sensitivity for identifying women with CIN3.The recently completed ALTS trial has provided valuable data.Follow-up protocol: Only about 5-10% of women treated for CINexperience treatment failure due either to residual disease or newlesions. It is likely that HPV testing in follow up will be useful inidentifying women at greater risk of developing CIN for a second time.Several studies are being undertaken to address this question.The need for greater efficiency and the advent of quality assured HPVtesting will drive a move towards this approach, but it is necessary toidentify how test acceptability (because HPV is sexually transmitted)and age (because HPV is very common < 25 years) will influence itsutility.

ON4.02 TREATMENT OF CERVICAL CANCER

ON4.02.01CURRENT SURGICAL MANAGEMENT OF CERVICAL CANCERJuan E. Sardi , Buenos Aires University, Buenos Aires, Argentina

When cervical cancer treatment results published by the FIGO AnnualReport are analyse can be seen that they have not been substantiallymodified the survival indexes from 1950 till 1992, in spite of all theadvances achieved in surgery and radiobiology fields. For this reasonchemotherapy was introduced in the primary treatment by severalcentres, and a multiple randomized study with neoadjuvantchemotherapy was initiated in the Gynecologic Oncology Unit ofBuenos Aires University. Our goal was to determine if this therapeuticstrategy could increase survival in patients with bulky tumors and, ifsuch was the case, whether radiation therapy or surgery should be thepreferred definitive therapy.Up to now more than 650 patients were randomized (Stage Ib-IIIb) andresults shown after nine years follow up that statistically significantdifferences were seen between groups: the neoadjuvant group vs. thecontrol specially for Stage Ib-IIb due to an increase tumor resectability.

Among the patients that could be subjected to a Wertheim-Meigsoperation, severe complications were uncommon.Similar conclusions were obtained in stage IIIb patients, in whichsurgery had better results. However, the long-term follow up of thesepatients has demonstrated that an important percentage of cases showedlatest complications of such important radical surgeryAn interesting observation that could provide a clue to the futuretreatment of patients with advanced cervical cancer is that responders toneoadjuvant chemotherapy have better local control of the disease.Therefore, response to chemotherapy could represent a good predictor toradiosensitivity, and in patients with a poor response to chemotherapy,surgery might be the better second-line treatment. Some details onstrategies and surgical techniques will be analyzed and presented.Radical vaginal surgery will be discussed. Limiting factors forneoadjuvant chemotherapy will be presented.

ON4.02.02PLACE OF CONSERVATIVE SURGERY IN CERVICAL CANCERA. Schneider and M. Possover, Dept. Gyn., University Hospital, Jena,Germany

Since introduction of laparoscopy for staging and treatment of cervicalcancer, the paradigm that radicality of surgery implies automaticallyincreased morbidity and subsequent impairment of organ functionbecomes invalid.Surgical techniques have been described which allow partialpreservation of the autonomic innervation of bladder, rectum, and vaginain radical hysterectomy type 3. Radical resection of the vascular part ofthe cardinal ligament can be done without injuring the pelvic splanchnicnerves. This allows complete preservation of the motoric function of thebladder.In early cervical cancer with less than 2 cm diameter and absence oftumor embolization in blood vessels radical trachelectomy according toDargent combined with laparoscopic pelvic and parametriclymphadenectomy allows preservation of fertility. Pregnancy rates of upto 50% can be achieved. Premature delivery through ascending infectionmust be prevented. Tumor recurrence is not more frequent than inpatients operated conventionally. In 90% of patients with early invasivecancer sentinel lymph nodes can be identified following injection ofPatent Blue or colloid Albumin labelled with 99Technetium. The falsenegative rate of this technique has to be evaluated prospectively.Thus, there are several options to preserve organ function withoutrisking radicalness and oncologic safety. Prospective evaluation of thesetechniques in combination with prognostic markers will help to identifypatient groups who profit most from these approaches

ON4.02.03CONCOMITANT CHEMORADIATIONEdward L. Trimble , Clinical Investigation Branch, Cancer TherapyEvaluation Program, Division of Cancer Treatment and Diagnosis,National Cancer Institute, Bethesda, MD, United States

Radiation therapy has been used for in primary treatment of women withcervical cancer, as well as in the adjuvant treatment of women whoundergo primary surgery. Recently, five randomized, controlled phaseIII clinical trials have demonstrated a survival advantage associated withplatinum-based chemoradiation. The patient populations in these studiesincluded women with FIGO stages IB2-IVA cercial cancer treated withprimary radiotherapy and women with FIGO stage I-IIA disease foundto have poor prognostic factors (metastatic disease in pelvic lymphnodes, parametrial disease, or positive surgical margins) at time ofprimary surgery. Although the trials vary somewhat in terms of stage ofdisease, dose of radiation, and schedule of cisplatin and radiation, theyall demonstrate significant survival benefit for this combined approach.The risk of death from cervical cancer was decreased by 30% to 50% byconcurrent chemoradiation. Based on these results, women who requireradiation therapy for treatment of cervical cancer should receivedcisplatin-based chemoradiation.


ON4.03 MANAGEMENT OF VULVAL CANCER

ON4.03.01ROLE OF PATHOLOGY IN DETERMINING MANAGEMENT OFVULVAL CANCERR. Kaufman , Baylor College of Medicine, Houston, TX, USA

The management of the patient with a malignant vulval neoplasm is verymuch determined by the pathology. This presentation will cover thefollowing neoplasms.

1. Intrapithelial neoplasia of the vulva· Invasive Squamous cell carcinoma of the vulva· Basel cell carcinoma of the vulva· Verrucous carcinoma of the vulva· Melanoma

The objective of this presentation is to alert the clinician to thesignificance of pathologic findings in planning treatment for patientswith vulvar malignances. For example, invasive carcinoma of the vulvawith invasion of less than 1 mm from the basement membrane of themost adjacent superficial papilla (stage 1A) requires only wide localexcision whereas invasion beyond this point requires more agressivetherapy including groin lymp node removal.

ON4.03.02PRIMARY SURGERY FOR VULVAL CANCERHans G. Bender , University Hospital, Düsseldorf, Germany

Radical vulvectomy in the gold standard for the treatment of vulvalcancer. But from the data of the 23rd Annual Report it is documented thatone third of surgical procedures for vulval cancer is not radicalvulvectomy. This fact may be explained by the trend towards an earlierdetection and treatment of cancerous lesions of the vulva. In additionwith smaller lesions the high short and long-term complications ofradical vulvectomy ae particularly unacceptable. Younger patients dofrequently not accept the consequences of radical surgery for sexualactivities and own body-image. In elder patients intra- and postoperativecomplications may not be acceptable under individual aspects.The considerations have led to an increasing tendency towards reducedextension of resection. When considering limited surgery two areas ofinterest have to be addresses and included into therapy planning. Theresetion concept for the primary tumor and its location it can bededucted whether at all and uni- or bilaterally lymph node resection hasto be performed. It is still under discussion under which conditionspelvic lymphadenctomy may be considered.Undoubtedly safety of therapy remains the most important aspect forpatients.

ON4.03.03MANAGEMENT OF RECURRENT VULVAR CANCERBG Lindeque , Dept Obstetrics and Gynaecology, University of Pretoria,South Africa

Recurrent vulvar cancer may be encountered in up to 25% of patientsfollowing treatment. As is the case with the first diagnosis of vulvarcancer, there is frequently a long lead time before diagnosis of arecurrence. Symptoms of recurrence may include pain, bleeding and thepresence of an ulcer. Local recurrences ususally appear as ulceration orexophytic tumours. Groin recurrences present with enlarged painfullymph nodes, frequently with legoedema present. Vulvar cancer may recur as systemic disease.The best predictors of local recurrence include narrow surgical marginsat the first operation, depth of invasion of 5mm or more, lymph-vascularspace involvement, and an infiltrative growth pattern. Predictors ofinguinal, pelvic or systemic recurrence include the number of positivegroin nodes and poor tumour differentiation.Therapeutic options for isolated local recurrence include resection or,when resection would lead to sphincter loss, radiotherapy. In such casesthe objective should be cure. In cases with regional and systemicrecurrence, resection has a very minor role to play, and radiotherapywith or without chemotherapy should be used to obtain control.The prognosis of recurrent vulvar cancer depends on the site. Isolatedlocal recurrences generally respond very well to treatment. Inguinal and

distant recurrences carry a poor prognosis. In many such cases thetreatment will be palliative. Local control is of evident benefit.Supportive measures including proper pain relief, hygienic care andnursing care are of great importance.

RM4.01 ENDOMETRIOSIS

RM4.01.02ENDOMETRIOSIS AND INFERTILITYR. W. Shaw , Head Academic Department of Obstetrics & Gynaecology,University of Wales College of Medicine, Cardiff, UK

Some 30% of patients with endometriosis have amongst their variedcomplaints one to difficulty to conceive. When there is structuraldamage to the ovary, fixity the ovarian fossa or adhesion formation suchan association is easily explained and surgical correction may wellresolve the problem. When endometriosis is less severe involvingperitoneal lesions and often in otherwise asymptomatic patiens then thelink between causation of infertility and finding of endometrioticimplants is less clear. Indeed several randomised controlled trials ofvarying ovarian suppression treatments verses placebo show nodifferences in subsequent conception rate. Pregnancy rates in untreatedor placebo treated endometriosis patients seen comparable to those ofunexplained infertility couples at approximately 33% after 12 months.Medical treatment in asymptomatic patients is not justified wherefertility is the end point. Surgical treatment of early endometriosis(laparoscopic laser/electro destruction) has been studied in only 2 trialsto date where the results are at variance. More appropriate treatments forinfertility will be determined in the patient’s age and duration ofinfertility and might include controlled superovulation and I.U.I. aspreferred options.

RM4.01.03ENDOMETRIOSIS AND PAINJohn N. Bontis , Aristotelian University of Thessaloniki, Thessaloniki,Greece

Pain is frequently associated with endometriosis presenting either asdysmenorrhea, dyspareunia or more continous pain. It is estimated thatamong patients with endometriosis 20-70% complain of pain.The cause of the pain has not been well defined. Endometriosispotentially involves several pathogenetic mechanisms that could lead topain, including local peritoneal inflammation, deep infiltrations andtissue damage, release of chemical mediators of pain, adhesion and scarformation.Endometriosis – associated pain commonly persists throughout thereproductive years. There is not a consistent relationship between theseverity of pain and the stage of the disease but there appears to be apositive correlation between severe pelvic pain and deep endometrioticlesions. Dysmenorrhea is a cardinal symptom of patients withendometriosis. Severe dysmenorrhea is highly predictive ofendometriosis, whereas mild and moderate dysmenorrhea are not.Dyspareunia is a common symptom, particularly with deep penetrationand may play a role in any associated infertility. The pain associatedwith endometriosis may be acute or chronic, and although it is usuallyrestricted to the perimenstrual period, pain may actually occurthroughout the cycle. Moreover, pain can also be experienced whenendometriosis involves other organ systems, such as bladder, rectum,sigmoid colon etc.Numerous therapies, including both medical and surgical approaches areavailable to treat women with endometriosis – associated pain. Medicaltherapy includes the use of antiprostaglandin agents and oralcontraceptive, as well as medications that are specifically used for thetreatment of endometriosis such as progestins, danazol, GnRH-analogues with or without add-back estrogen and progestin. On the otherhand the options for surgical treatment of endometriosis associated painrange from conservative laparotomy or laparoscopic treatment(coagulation or excision of the lesions, adhesiolysis, uterine nerveablation, presacral neurectomy) to hysterectomy with or without,removal of the adnexa. Finally, the endometriosis – associated painfrequently has also a psychological aspect, so that occasionally multi-speciality approach, including psychiatric assessment, is indicated.


RM4.02 TEENAGE PREGNANCY

RM4.02.01PREVENTION OF UNWANTED TEENAGE PREGNANCY:THE DUTCH EXPERIENCER. H. W. Van Lunsen , Dept. Sexology & Psychosomatic Ob/Gyn,Division Ob/Gyn, Academic Medical Centre, University of Amsterdam,Amsterdam, Netherlands

Dutch teenage pregnancy rates as well as rates of unwanted pregnancyand abortion are among the lowest in the world. Oral contraceptives andmale sterilisation are the method of forst choice more often than in mostwestern countries. Condom use and oral contraceptive have increasedsimultaneously since the beginning of the AIDS-era illustrating agrowing – but still insufficient – awareness of the need of dualprojection («Double Dutch»). Determinants that have been identified tocontribute to the relatively favorable Dutch situation are:- general openness about sexuality and contraception within the

private and public domain- effective formal and informal sex education- acceptance of teenage sexuality as a fact- increasing cross-gender communication skills and female autonomy- easy access to non-judgemental services- the central role of the family physician (GP)- minimal medicalisation- typical Dutch pragmatismDespite the success of the Dutch model there are growing concernsabout unwanted pregnancy rates among teenagers in some sub-populations of the multi-cultural Dutch society such as socially deprivedteenagers and some ethnic minorities. New preventive strategiestherefore have to be tailor-made for specific risk groups.

RM4.02.02FACTORS THAT INFLUENCE ATTITUDESI. Milsom , Department of Obstetrics and Gynecology, GöteborgUniversity, Göteborg, Sweden

Teenage pregnancy influences not only the mother and child but also theyoung mothers immediate family as well as society. Concerns have beenexpressed for the health of the mother and child and for the mothersmissed educational and occupational opportunities, and possibly also forthe child in the future.There is an extremely large variation in fertility rates for teenagersbetween different countries, which is even apparent when comparingsome of the industrialised countries of the world. The age-specificfertility rate among women 15-19 years from the USA was 70/1000 and60/1000 in 1965 and 1995 respectively. In comparison the age-specificfertility rates among women from the Netherlands were 21/1000 and5/1000 and from Sweden 50/1000 and 10/1000 for the same years.Many factors influence the occurence of teenage pregnancies. Theintroduction of sex education in schools, the increasing use of effectivecontraceptive methods and the liberal availability of legal abortion areconsidered to be important factors that have contributed to a decline inteenage pregnancies in some countries.In Sweden there has been a positive trend regarding the occurence ofteenage pregnancies during the last 3-4 decades and the teenagepregnancy rate has decreased from 50 to 10/1000. An analysis of thereasons for this reduction in the number of teenage pregnancies will beused to illustrate different factors influencing the occurence of teenagepregnancies and how the attitude of teenagers, their parents and familiesand society could be changed which resulted in fewer teenagepregnancies.

SS4.01 GUIDELINES, AUDIT, AND EVIDENCE-BASEDPRACTICES

SS4.01.02CONFLICT IN INTERPRETING SCREENING TESTSDavid A. Grimes , University of North Carolina, Chapel Hill, NC, UnitedStates

Screening tests are ubiquitous in clinical practice — but often poorlyunderstood by both clinicians and patients. This can lead to emotionalanguish, inappropriate interventions, and squandered resources.

Screening is the testing of apparently well persons to find those whomight be at increased risk of having a disease. In contrast to diagnostictests, screening tests tend to be simple, of lower reliability, inexpensive,and often done by someone other than a physician. That a screening testexists does not imply it should be used. The disease in question shouldbe important, and diagnostic and treatment facilities must be available.The disease should be common, and the screening cost should beproportionate to the benefit derived. The test should be both valid (itmeasures what it sets out to measure) and reliable (reproducible).Four indices of validity measure test performance. Sensitivity is theability of a test to identify those with the disease, while specificity is theability to find those without the condition. However, predictive valuesare more useful to clinicians. The predictive value positive is thelikelihood that a person with a positive test has the condition, while thepredictive value negative is the opposite.The prevalence of disease in the population influences test performance.Even for tests with excellent sensitivity and specificity, the predictivevalue positive falls when the disease is rare. False-positive results cancause great harm and expense. Hence, clinicians need to know theapproximate prevalence of the disease in the population being tested.Two important biases, lead-time and length bias, can distort assessmentsof the usefulness of screening programs. Randomized controlled trialsare the only known way to avoid these biases when assessing screeningprograms.

SS4.01.03CONFLICT IN INTERPRETING RANDOMIZED TRIAL– THE EXAMPLE OF FETAL HEART RATE MONITORINGW Kuenzel , Dept. OB/GYN, University Giessen, Germany

During the past two decades the benefit of electronic fetal heart ratemonitoring (EFHRM) has been questioned again and again. It has beenclaimed that, it has not been shown to reduce perinatal mortality and that«it increases the chances of ceasarean section without any apparentbenefit in neonatal outcome».The following question will be analyzed: are the defined outcomeparameters – perinatal mortality (PM) and cesarean section rate –eligible parameters to appreciate the value of EFHRM in daily practice.In most developed countries PM fell during the past five decade from5.0% in 1950 to 0.5 – 0.6% in 1999.This fall was in Germany paralleled by many measures aimed toimprove maternal health care: financial support for hospital deliveries,guiding principles for prenatal care, care for high risk cases in level IIIunits, the foundation of neonatal intensive care units – and routineapplication of FHRM during pregnancy in high risk cases and duringlabor as well as the introduction of ultrasound.There are practical reasons for FHR-monitoring are:1. During gestation: Screening of high risk cases to reduce antepartum mortality by contraction stress test (empirical Bayes-condition)1.1 Strength of the method: continuous protocol of fetal cardio-vasculare behaviour and appreciation of borderline oxygenation.1.2 Weakness to prove the efficiency of the method: low ante partummortality of 0.3%; often applied in low risk cases; patients demand forsecurity reason.2. During labor: Screening to prevent fetal hypoxia during laborStrength of the method: continous record of feta cardiovaasculareresponse to labor (reduction of uterine blood flow and fetal Oxygendeprivation): Objective record and documentation of FHR – (the valueof FHR observation during labor has a long tradition and has not beenquestioned); early information of deterioration of fetal condition; rarefetal death during labor (Hesse 1999: 0.03%) 6.4% of PM (0.54%); notbeing dependable on untrained medical personal (young doctors andmidwifes).2.1 Weakness of the methd: wrong interpretation of fetal heartalterations by the observer leads to an increase of section rate or tointrauterine fetal death (IUFD).Conclusion: It is unethical to disregard fetal heart rate monitoring fromroutine medical practice for a lack of evidence in regard to perinatalmortality. The benefit of this method in daily practice concerning, «hardproof of evidence» of fetal condition should not be underevaluated.


SS4.01.04CHALLENGES WE FACE AND RESOLUTION OF CONFLICTS INTHE DEVELOPING WORLDJ . Riz v i , A g a K ha n U niv e r s it y, K a r a c hi, P a ki s ta n

In the last decade evidence practice medicine has become a “buzz” wordin the Western world. In our speciality, clinical practice guidelines havenow been developed but for various reasons, have not received universalacceptance. In some instances, they have served only to confuse clinicalpractice and not to clarify it.In the developing world, the culture of evidence based medicines has notyet taken roots, but it is inevitable that we will follow suit. It is thereforeprudent that we assess the situation critically and try to resolve theconflicts which have become apparent in the Western world.The problems we faceIn most of the countries of the developing world, the majority ofpopulation lives in rural areas (70%) and the literacy rate among thefemale population is less than 20%. Health care facilities are inadequate.The hospitals are under-staffed, under-funded, and poorly managed.Health care workers are overworked and poorly paid. One percent ofGNP goes toward health care. So under these circumstances, the practiceof “alternative” medicine including quackery is common. Treatmenttherefore depends on patients’ preferences, tolerance and degree oftrust—she may resort to opinions of friends and relatives in decidingwhether or not to accept a particular course of action, evidence based ornot.On the other hand, very few physicians actually understand whatevidence based medicine means. It is still perceived to be restrictive,which has a negative impact on incentives, financial or otherwise. Onecommonly hears remarks like, “Evidence based medicine is for juniors,experience based medicine is for seniors”, “Evidence based medicine isbetter suited to the classrooms than to the clinics”.Resolution of these problemsThe two major challenges we face are:a) teaching and learning of how to practice evidence based medicine(EBM); andb) the need to negate the divide between evidence based and experiencebased medicine.The message being that they can both grow together without going apart.As a matter of fact, they complement each other.We, at the Aga Khan University, have taken the first few tentative stepsto meet these challenges and to create a model of how to practiceevidence based medicine. If successful, this model can be replicated inother major centres of the country.Problem based learning and critical appraisal of literature has beenintroduced in the undergraduate and postgraduate curriculae. In the lasttwo years, the benefits of this move have become apparent. This will,hopefully, address the problem in the younger generation, andultimately, the divide between evidence based and experience basedmedicine will disappear.For our peers and senior colleagues, we are organising seminars,courses, and visits to various departments in the hospitals where EBM isbeing practised. They are encouraged to keep up-to-date in seeking outexamples of EBM produced by others, e.g. journal of evidence basedmedicine, the WHO reproductive health library. Finally, individualisedaudit and feedback is being introduced.The gap between evidence and our practiceWe fully recognise that scientific evidence alone cannot determineindividual and macro health care policy. Public values andcircumstances also influence decisions (thereby constituting evidence ofdifferent type).We don’t believe that we need to create and formulate our ownguidelines on major practice issues, e.g. anaemia, pre-eclampsia,management of haemorrhage, breastfeeding, etc. But we do need toincorporate flexibility. One plausible approach is to constitute acommittee which will include researchers and decision makers fromvarious sectors (district hospitals, teaching hospitals, community healthservices, NGOs, and local government).The functions of this committee would include encouraging physiciansto adopt evidence based practice, facilitate their educational programs,identifying and prioritising areas where there is a demonstrated need.Passive dissemination of research findings is not enough to changeeither clinical policy or clinical practice. The gap between the evidenceand our practice needs to be closed. This can only be achieved byintegrating researchers, physicians and health care workers. Open andunbiased discussions would need to take place on implementation issues

covering incentives and disincentives, and how any particular guidelinewould be evaluated. All this will then need endorsement from anorganisation with national credibility and respected physicians of thecommunity.Some aspects of this proposal are already in place. A lot of work stillneeds to be done before this model is labelled “doable”. We have to bepatient and extremely cautious in extrapulating and implementingsimilar models on a nationwide level in order to avoid the “burst bubble”effect.

SS4.02 EDUCATION AND TRAINING IN OBSTETRICS ANDGYNECOLOGY

SS4.02.01TEACHING THE ART OF MEDICINEC. R. Mc Lain, Jr. , University of Cincinnati College of Medicine,Cincinnati, OH, USA

The rapid expansion of biomedical science and technology combinedwith the new economic pressures of managed care have forcefully drawnattention to certain inadequacies of a physician’s education, training, andbehavior. Critical to the issue are demands for a more humane,committed, caring and compassionate approach to patients. Teachingmedical students the Art of Medicine – the application of the science andtechnology of medicine in a caring and compassionate manner so as tobnefit the well being of the patient – is a task that challenges medicaleducation. We have developed a culture of learning and training inwhich mentors and role models integrate the teaching of the Art ofMedicine, the science of medicine, physician responsibility andaccountability – all in the pursuit of excellence in patient care. Theprinciples are that if medical students are treated with respect andcompassion with clearly defined goals an objectives, and if the faculty isresponsive to the total needs of the medical sutdents, the students, inturn, will be more humanistic as advocates of the patients.The more innovative methods of teaching and learning that support thehumanistic approach to physician education and patient care,emphasizing the Art of Medicine are the following: AmbulatoryPreceptorship, Interactive Group Learning, Clinical Problem Solving &Case Presentations, Mid-clerkship Interviews, and The Practice ofMedicine in the New Millenium – The Challenge. Each student preparesan essay on The Practice of the Art of Medicine.The final message to the student is: May the humanistic qualities ofhonesty, trust, integrity, respect, and compassion prevail as you becomethe advocates of your patients. Listen to your patients for they willbecome your best teachers, and take care of yourselves so that you maycare for others.

SS4.02.02OPPORTUNITIES IN INTERNATIONAL EDUATION INOBSTETRICS AND GYNECOLOGYJ. J. Sciarra , Dept. of OB/GYN, Northwestern University, Chicago,Illinois, USA

Medical students in US medical schools have a strong humanitarianinterest in obtaining exposure to medical care and the problems of healthcare delivery in other countries, especially in the developing world. As aresult, many programs both formal and informal have evolved to allowmedical students the opportunity to have international educationalexperiences.Objectives: This presentation will review some if the internationaleducational experiences available to US medical students in developingcountries in all specialties, including obstetrics and gynecology.Study Methods: The three programs that will be presented are(1) The program at Northwestern University Medical School (NU-

AID)(2) The international medical education and research program at the

University of Minnesota(3) The International Health Organization (IHO) at Columbia

UniversityResults: The information on the above programs will be reviewed and avariety of educational experiences reported by students who haveparticipated in these programs will be presented.Conclusions: There is considerable interest among US medical studentsin international medicine. This is especially true in obstetrics and


gynecology. With the enormous problems in women’s health worldwide,our specialty is in a particularly advantageous position to allow USmedical students exposure to the medical problems of women in thedeveloping world and to participate in a limited way in the delivery ofpatient care. The ducational value of such international medicalexperiences cannot be over-estimated.

SS4.02.03A NATIONAL PROGRAM TO TEACH TEACHERS TO TEACHW. N. P. Herbert , Duke University Medical Center, Durham, NC, UnitedStates

The importance of teaching and learning in medicine has always beenhighly valued, yet the means to effectively educate those who teach havelargely been lacking. The Association of Professors of Gynecology andObstetrics (APGO), a national organization closely involved witheducation in the field of obstetrics and gynecology, has established anational program to prepare Ob/Gyn faculty to be more effectiveeducators in our field.Major financial support for this initiative was provided by SolvayPharmaceuticals, Inc. The basis for this program was a highly successfulfaculty development program at the University of North Carolina. Forthis national program, called the apgo/Solvay Educational ScholarsDevelopment Project, an Advisory Committee consisting of medicaleducators and clinical teachers was established. This group developedgoals, a curriculum, and a workable operations plan for this program.The rigorous, 15 month curriculum involves intense study in curriculumdesign, teaching methods, evaluation, and leadership in education. Eachof the 20 faculty participants («Scholars») selected each year mustcomplete a project involving some aspect of medical education.Activities include three meetings in conjunction with other APGOprograms, along with one two-day, free-standing meeting. A strong localmentorship program is also stressed. Upon graduation, these facultypossess the knowledge and skills to be superior medical educators for alllevels of learners in the field of obstetrics and gynecology. In addition,they provide a rich resource in education for their medical centers,particularly with respect to curriculum development and learnerevaluation.

SS4.03 MENOPAUSE AND QUALITY OF LIFE(SPANISH LANGUAGE SESSION)

SS4.03.04TERAPÍA REEMPLAZO HORMONAL Y CÁNCER DE MAMAJorge Tisné T. , Sociedad Chilena de Obstetricia y Ginecología, Santiago,Chile

En metanálysis hasta 1999, revela que el uso de terapía reemplazohormonal (TRH) por más de cinco años, se asoció con un aumentomoderado del riesgo relativo (RR) de incidencia (RR: 1.35, 95 CL =1.21-1.49). Este metanálysis muestra una tendencia a mayor proporciónde tumores localizados en usuarias de TRH; pero no se asumieron conmortalidad. Otra serie muy vasta revelaba que el Ca de mama con TRHtenían una histología más favorables que las no usuarias de TRH. Sededuce que TRH puedo promover crecimiento de tumores menosagresivos y de mejor pronóstico.Solo se incluyeron estudios randomizados, de cohorte y caro casocontrol. La información fue limitada en cuanto a dosis o uso combinadode TRH.El riesgo normal de adquirir Ca de mama sin TRH es de 1 a 8. A los 40años es de 10% y a los 70 años es de 4%.En metanálysis los Estrógenos sintéticos tendrían un leve mayor RR quelos conjugados. No habría asociación entre TR estrogénica e historiafamiliar de enfermedad benigna de mama.Los factores con RR de primigesta tardia (30 años) 1.48

Uso de alcohol 1.16Obesa 1.48Menopausia tardía 1.14 (5 años)TRH 1.12 (5 años)

Esto en 51 estudios que incluyeron 52 000 mujeres con Ca y 108 000 sinCa.No hubo aumento de Ca en usuarias con antecedentes de historiafamiliar de cáncer de mama.

El uso de TRH en pacientes con Ca de mama es controversial perohabrían evidencias de beneficios en términos de recurrencias y muerte.Instalado el Ca de mama, habría mejor sobrevida en las usuarias de TRHque las que no tomaron TRH.La ventaja del uso de TRH controlado es el diagnóstico precoz del Ca,mejorando el pronóstico y etapa, no así a las no usuarias en que ladetección es más avanzada.

SS4.03.05UROGENITAL AGINGO.Contreras Ortiz . "José de San Martín" School Hospital University ofBuenos Aires, Argentina.

There is not a consensual definition as regards the stages involved in"Urogenital Aging". We should consider two different stages: Disordersin Immediate Post Menopause.(Hot flushes, sweats, stress incontinence,insomnia, etc.); Disorders in Elderly Patients (> 65 years, vaginalatrophy symptoms, urinary incontinence, bladder dysfunctions, urinarytract infections, decreasing libido, etc.). The principal urogenital agingeffects are: Vulvo vaginal disorders; Urethro vesical dysfunctions;Pelvic floor dysfunctions.Vulvo Vaginal Disorders. Atrophy of the minor lips, Flattening of themajor lips (loss of fat), Hairiness decrease, Loss of elasticity. In thevagina there is: Thinning of mucosa, Dryness in the vagina, Ph Increase(3.5 to 6-8).Bladder changes Vesical capacity decrease, Voiding difficulties (poorurinary stream, straining to void, feeling of incomplete bladderemptying, post-micturition dribble), urinary tract infection, urinaryincontinence. Urinary tract infection Voiding dysfunctions, Loss ofBladder wall defense mechanisms, Low rates of urine flow, Causativeorganism (uropathogenicity), Impaired physical sataus.Urethral effects: Thinning mucosa, Vascular alteration, Collagen contentreduction, Anatomic support reduction (Pelvic floor muscles), Changesin the muscular morphology. The urethral clossure pressure at rest islower as age increases.Changes in collagen.In post menopause there would be a decrease incollagen fibers of type 3.Urethral incompetence. Stress incontinence with hypermobility (normalurethral clossure pressure at rest). Stress incontinence with intrinsecurethral clossure mechanism deficiency (low urethral clossure pressureat rest). Age effects on the intrinsec components of the urethra may beone of the causes of failure in its sphincter function. Urgencyincontinence and urgency / frequency syndrome may lead to theassumption of failure in the bladder storage function. Detrusor instabilityis the most common cause of incontinence in the elderly. Severalneurological alterations can produce over active bladder.

SS4.04 PERINEOLOGY: PRIMUM NON NOCEREA NEW APPROACH TO PELVIC FLOORDYSFUNCTIONS

SS4.04.01FROM UROGYNECOLOGY TO PERINEOLOGYJack Mouchel MD, Groupement Européen de Périnéologie, Le Mans,France

Urogynecology, focused on urinary complaints and genital prolapse, haslost all interest in genito-sexual complaints and those related to thecolorectal tract (dyschesia, anal incontinence).The anatomical approach, based on imaging and electrophysiologicaltechniques, bridges the (anatomical and functional) gap between thedifferent regions. It enables to explain and understand the incidence ofcombined disorders (urinary, colorectal, and sexual) and to understandthe iatrogenic consequences of procedures, like colposuspension, that donot leave the anatomy intact..Perineology, a logical deduction from the observation of the neuro-muscular-conjunctive anatomic unit of the entire pelvic floor and thefunctional interactivity of individual perineal areas, is more than just thefruit of the union between urogynecology and proctology. A realinterdisciplinary process, it combines in a singular concept the study ofperineal function disorders.As a united or singular approach, perineology must enable to understandbetter the balance that exists among individual perineal structures and


ensure the sustained functional balance among all perineal structureswhile avoiding iatrogenic attitudes.

SS4.04.02PERINEOLOGY: DEFINITION AND PRINCIPLESJacques Beco , Liège University, Department of Gynecology, CHU Sart-Tilman, Liège, Belgium.

1. Perineology is the result of a merger between urogynecology andcoloproctology. This "tri-axis approach" is becoming widely accepted.2. Perineology deals with the functional disorders of the perineum(including pain). All diseases that are non functional at any one of thesethree levels (cancer, stones, polyps, hemorrhoids...) should be treated bya urologist, gynecologist, or colo-proctologist.3. The aim of Perineology is the "ad integrum" restoration of theanatomy while not altering biomechanics and physiology. Ideally, eachdefect must be corrected without creating problems on other levels(primum non nocere). The benefit - risk ratio must be evaluated for eachprocedure.4. This approach must be interdisciplinary and not multidisciplinary.There can only be one boss, who must be the "architect of theperineum", somebody with extensive knowledge of the anatomy and thephysiology of the triple axis. This new specialist is called a"perineologist". He could be the surgeon or an individual who tells thesurgeon what to do. The perineologist must have a holistic view (onewhich includes psychology, lifestyle, and anatomy [eg abdominal wallmuscles] in the approach).5. The functional state of the perineum can be summarized with aT.A.P.E. (Three Axis Perineal Evaluation diagram):- gynecological axis = sexuality-prolapse- urological axis = urinary incontinence-dysuria- coloproctological axis = constipation-fecal incontinence.If the T.A.P.E has an hexagonal shape, the result of surgery is verygood. Using this tool it is possible to monitor the perineal deteriorationover time after surgery or reeducation.

SS4.04.03PRACTICAL PERINEOLOGY: EXAMPLESJacques Beco , Jack Mouchel , Groupement Européen de Périnéologie,Belgium

Based on clinical cases, the authors demonstrate the efficiency of anoverall perineological strategy. Subsequently, a standard visit forgenuine stress urinary incontinence can lead to the management ofassociated fecal incontinence, symptoms revealing a pudendal nervedisorder, which may be responsible for dysorgasmia, and pubo-rectalhypotonia that can lead to a descending perineum.Only a perineologist knowledgeable of the anatomic and functional unitof the pelvic floor is capable of managing these diseases etiologically,while avoiding iatrogenic methods that may disrupt perineal balance inthe long or short terms.From these clinical cases, the authors describe surgical procedurescapable of restoring ad integrum the anatomy and the biomechanics ofthe pelvic floor (sub-urethral support for stress urinary incontinence,vaginal lifting for prolapse, pudendal nerves neurolysis, myo-levator-plasty, and retro-anal myoraphy for ano-rectal static disorders).Perineological approaches are not necessarily surgical in kind : It mayseem irrational to some to try and reinforce an already contracted pubo-rectal muscle due to a coccygeal disorder with reeducation or toprescribe, in the event of bladder instability, an anticholinergic to awoman with dyschesia.For more information on Perineology, go to www.perineology.com

FM4.03 MATERNAL MORTALITY

FM4.03.01MATERNAL MORTALITY - AN OVERVIEWJerker Liljestrand , World Bank, Washington, DC, United States

While global infant mortality, life expectancy and total fertility rate haveimproved enormously during past decades, no significant overall declinein average maternal mortality has been shown. Maternal mortality alsoshows the starkest difference between the “haves“, with a life-time risk

of maternal death of 1/6000, and the “have-nots” with a risk of 1/10.One woman dies a maternal death every minute, unnecessarily..The main medical causes of maternal death are hemorrhage, eclampsia,infection, obstructed labor and abortion-related complications. Ofindirect causes, HIV/AIDS is increasing rapidly in some regions.Secondary determinants are poverty, lack of education, lack of women’srights, and lack of access to basic health services including familyplanning.In recent years, much has been learned about the key interventionsneeded. Reducing maternal mortality requires a functioning healthsystem, not isolated interventions. Most important is access to a skilledbirth attendant, who can prevent, manage and refer complications, and toreferral care at the district hospital level. Raising age at first birth,providing family planning education and services, and addressingabortion issues are also important components.Reliance on the training of traditional birth attendants, or use of the highrisk approach, are ineffective in isolation.Long-term commitment both among decision-makers and at thecommunity level are crucial to improve basic maternal health care.Maternal death reviews is an effective way to keep commitment strongat these levels, and is more important than attempts to establish exactlevels of maternal mortality.Governments and international agencies, as well as community leadersincluding obstetricians, are now gradually speaking up regarding theneed for massive increases in access to skilled attendants duringpregnancy and birth, and the need for accelerating access to effectivecare of emergencies at referral care level.

FM4.04 PERINATAL BRAIN DAMAGE

FM4.04.01PRETERM BIRTH AND PERINATAL BRAIN DAMAGE.Arne Ohlsson , Department of Paediatrics, Mount Sinai Hospital,Toronto, Ontario, Canada.

Background: Preterm infants are at risk ofischemic/hemorraghic/traumatic brain injury.Objective: To provide information on the etiology, epidemiology andprevention of perinatal brain damage in preterm infants.Anatomy: The developing brain contains a fragile network of bloodvessels (the germinal matrix) adjacent to the cerebral ventricles.Physiology: The ability of the neonate to auto-regulate cerebral bloodflow is limited. Cerebral blood flow is affected by numerous variablesincluding gestational age, postnatal age, blood pressure, hematocrit,acid-base status, assisted ventilation and drugs.Etiology: The unique anatomic features of the preterm brain and theinability of preterm infants to auto-regulate cerebral blood flow makethem vulnerable to haemorrhagic/ischemic injury. Maternal life style anddisease processes, obstetric and immediate postnatal neonatalmanagement, modify the risks of brain injury in the fetus/neonate.Traumatic brain injury is rare in the preterm neonate.Diagnosis: The most efficient and least painful/stressful diagnostic toolis ultrasound examination performed at the bedside. The optimalschedule to diagnose intra-cranial pathology in the preterm infant hasnot been determined. Examinations at 3 days, 2 and 6 weeks arecurrently recommended.Prevention: Maternal treatment with phenobarbital or vitamin K does notreduce the incidence of intra-cerebral hemorrhage in infants bornpreterm. Administration of antenatal corticosteroids to women withthreatened preterm birth reduces perinatal mortality and the incidence ofrespiratory distress syndrome, but their effectiveness in reducing intra-cerebral hemorrhage is less certain. Postnatal early administration ofindomethacin reduces the incidence of cerebral hemorrhage in extremelylow birth weight infants but does not alter the rate of death/impairmentat 18 months of age.Prognosis: Intra-parenchymal hemorrhages, periventricular leukomalaciaand post-hemorrhagic ventriculomegaly are strongly associated withlater neurodevelopmental impairments.Conclusions: There are currently no effective interventions to preventintra-cerebral pathology in the fetus and preterm neonate. Bio-psycho-socio-economic and cultural efforts should focus on prevention ofpreterm birth.


FM4.04.03CEREBRAL PALSY – MEDICO-LEGAL ISSUESA. H. MacLennan , Women’s & Children’s Hospital, University ofAdelaide, South Australia

Recent epidemiological, laboratory and clinical research suggests that inthe large majority of cases, the meuropathology of cerebral palsy beginsantenatally and in some very preterm babies can occur neonatally andrarely is due to primary asphyxia. The term «birth asphyxia» andprobably even the word «damage» are hard to define or prove and can beemotive words not accurately relfecting the underlying causation orpathology. Hereditary clotting disorders, intrauterine infection, chronicfetal blood obstruction and fetal cerebral thrombosis are some of theprobable silent mechanisms of cerebral palsy. The resultingdevelopmental brain dysfunction may only be detected indirectly for thefirst time in labour or soon after delivery if the neuropathology involvescentres controlling cardioresiratory function etc.There are no peripartum clinical policies that have been shown inrandomised trials to reduce cerebral palsy rates, eg, early induction,electronic intrapartum fetal monitoring or elective caesarean section.Although it is occasionally possible that prolonged acute asphyxia in aneurologically intact fetus can result in the neuropathology of cerebralpalsy, it can be hard to be sure that it did not exist prior to the labour,that the asphyxia was long enough and severe enough to causeirreversible neuropathology and that there was the opportunity to limitthe asphyxia to a period where the neuropathology could be avoided orameliorated. In this multidisciplinary area with little data to support thatdifferences in clinical management alter outcome some medico-legalwitnesses have opined their certainty about causation and that theoutcome could have been prevented with different management. Theeffect of non-evidence-based medico-legal opinion has had reachingadverse effects on obstetric practice and services.Recently in international multidisciplinary task force on cerebral palsymet over two years and reviewed the current literature on cerebral palsycausation. It offered a template of objective evidence to define the fewcases of cerebral plasy possibly associated with acute intrapartumasphyxia. It is another step to prove that this asphyxia was preventableand the the neuropathology could have been prevented. Witnessesshould be well-qualified, and well read, currently practising, keep totheir area of expertise and be well aware of the limitations of perinatalcare in this area.Reference: MacLennan AH for the International Cerebral Palsy TaskForce. A template for defining a causal relation between acuteintrapartum events and cerebral palsy: international consensus statement.BMJ 1999; 319: 1054-59

ON4.04 OVARIAN CANCER SCREENING

ON4.04.01SCREENING FOR FAMILIAL OVARIAN CANCERBeth Y. Karlan , Cedars-Sinai Medical Center, Los Angeles, California,USA

In 1994, the NIH consensus conference on ovarian cancer recommendedthat at least annual screening with pelvic examinations, CA125determinations, and transvaginal sonography be performed for womenwhose pedigrees suggested a hereditary ovarian cancer syndrome. Thisstatement was based on expert opinion due to the lack of datademonstrating a reduction in ovarian cancer mortality as a result of theseinterventions. Since that time, BRCA1 and BRCA2 have been identifiedas genes responsible for the majority of hereditary ovarian cancers, andclinical genetic testing for mutations in these genes in unaffected andaffected individuals has become widely available. Althoughconfidentiality issues and questions regarding clinical recommendationsstill remain, we can now identify a cohort of presymptomatic womengenetically at high risk for ovarian cancer. This rapidly growingpopulation of high risk women presents an opportunity and obligation tofind an effective means of ovarian cancer screening.Strategies for the early detection of ovarian cancer in this heritable riskcohort need to take into account the growing body of data pointing to a“field effect” or multifocal origin of disease in a significant proportionof these cases. This peritoneal serous papillary carcinoma phenotypewould favor screening strategies that focus on serologic testing earlytumor biomarkers rather than “end organ” imaging techniques such asultrasound. In contrast, the “acquired risk” cohorts, such as infertile

nulliparous women and older postmenopausal women, seem predisposedto accumulate somatic mutations leading to the development of the morecommon monoclonal ovarian cancer with early morphologic changes inthe ovary. This pattern of disease may be more amenable to earlydetection using modalities such as transvaginal sonography and/or colordoppler imaging.Intensive efforts are underway to identify new biomarkers for ovariancancer. Lysophosphatidic acid is one such marker which is elevated inearly stage ovarian cancer as well as in peritoneal serous papillarycarcinomas. Molecular techniques such as representational differenceanalysis are being used to discover other potential markers, which maybe useful for early detection. Newer imaging techniques such as 3-Dultrasound, PET and spectroscopy are being studied for their earlydiagnostic capabilities. Screening with peritoneal cytology and “ovarianpap tests” are in early clinical trials. These approaches and others will berequired to overcome ovarian cancer’s diagnostic obstacles, but theirsolutions will yield high dividends in potential targets for prevention andtreatment.

ON4.04.03EARLY DETECTION OF OVARIAN CANCER:METHODOLOGICAL CONSIDERATIONSNicole Urban , Fred Hutchinson Cancer Research Center, Seattle, WA,United States

Introduction. A screening strategy should be cost-effective in a publichealth context as well as feasible for testing in a randomized controlledtrial (RCT). Strategies have been identified that are potentially cost-effectivei but the expected costs of a RCT to test their efficacy have notbeen reported.Methods. For several candidate strategies we estimated 1) the size of thetrial required for specified length and power, and 2) the costs of the trialfor specified protocol, length and size. The required size of the trial wasestimated using a previously described microsimulation model ofovarian cancer screening, revised to simulate a RCT.Various trial designs were simulated to optimize trial length. Theendpoint for the trial was cause-specific mortality. The power wascalculated for an unweighted logrank statistic. Total direct costs of thetrial were estimated using a previously described model of the costs of alarge prevention trial, revised to reflect the design and protocols for thescreening trial strategies.Cost-effectiveness of the strategies is reported for a scenario in whichthe screening strategy is used in all women aged 50-80 outside thecontext of a trial. Costs and benefits are discounted at 3%.Results. Trial costs increase with trial size, which decreases as themortality reduction expected from a screening strategy rises. Expectedmortality reduction varies 2-fold among strategies, while estimates oftrial costs vary about 3-fold.Conclusions. Choice of a screening strategy to test in a RCT depends onits expected mortality reduction as well as its cost-effectiveness

ON4.05 CERVICAL INTRAEPITHELIAL NEOPLASIA –TREATMENT

ON4.05.01TREATMENT OF CIN: BURN FREEZE OR CUT?Grainne Flannelly , National Maternity Hospital, Dublin, Ireland

The ultimate test of any treatment of pre-invasive cervical abnormalitiesis the number of women who develop invasive cancer of the cervixdespite treatment. Other criteria include the recurrence of cervicalintraepithelial neoplasia (CIN) as well as the physical and psychologicalimpact of the procedure on women. Any treatment should be safe,effective and cost efficient.In the fifty years since Papanicolau described the smear test manytreatments have been described. In the pre-colposcopy era, hysterectomywas commonly utilised to treat the woman with an abnormal smear. Thecone biopsy allowed successful treatment while retaining fertility.Ablative treatments including radical diathermy, cryotherapy, coldcoagulation and laser ablation facilitated outpatient treatment under localanaesthetic. While these treatments are reasonably effective they areonly applicable to selected women with a satisfactory colposcopicexamination, an ectocervical lesion and no colposcopic suspicion ofinvasive cancer. These treatments provide an incomplete histological


diagnosis with no information on the state of the surgical margins andcan result in inadvertent under treatment of invasive cancer. Theseconcerns led to the re-emergence of excisional methods including theLaser cone biopsy and the diathermy loop excision or LLETZ. Currentlythe LLETZ has evolved as the most common treatment of CIN. Itcombines the ease of an outpatient treatment with the opportunity toexamine the entire transformation zone and does not compromisesubsequent fertility. Future developments should focus on allowing amore tailored excision.

ON4.05.02VACCINES AGAINST CERVICAL NEOPLASIAJ. Paavonen , Dept. OB/GYN, University of Helsinki, Finland

Papillomaviruses (HPV) cause a remarkable number of benign andmalignant epithelial lesions. There are more than 80 HPV types whoseDNA genomes have been completely sequenced, and at least 110additional HPV types have been less well characterized. The relationshipbetween HPV infection and cervical cancer has been studied in greatestdetail because it is such an important cancer worldwide. Almost all thesecancers contain high risk HPV types. A single type, HPV16, is present inhalf of them, and other high risk types are present in an additional 30%.Longitudinal studies have shown that HPV infection precedes thedevelopment of virtually all high grade cervical dysplasias and thatdistribution of HPV types in dysplasias is similar to that found incervical cancer. Worldwide, there are approximately 400,000 cases ofcervical cancer, 10 million cases of high grade dysplasia, 30 millioncases of low grade dysplasia, and 300 million cases of other cervicalinfections. HPV infection has also been closely linked to a variableproportion of other tumors. It has been estimated that approximately85% of anal cancer, close to 50% of cancers of the vulva, vagina, andpenis are attributable to HPV infection, as well as approximately 20% oforopharyngeal cancers, and 10% of cancers of the larynx andaerodigestive tract. The large disease burden from HPV infection hasstimulated interest in the development of an effective prophylactic andtherapeutic HPV vaccine. It was discovered that the L1 major structuralviral protein, expressed in eukaryotic or prokayotic cells can self-assemble into virus-like particles (VLPs), thus allowing mass productionof VLPs. VLPs resemble the conformation of authentic virions andinduce high levels of neutralizing antibodies. The neutralizing antibodiestend to be type-specific. Phase I/II clinical trials are currently underwayto evaluate the safety and immunogenicity of monovalent andmultivalent HPV VLP vaccines. The vaccine is well tolerated and safe,and induces high titers of neutralizing antibodies when systemicallyadministrated. In addition, other viral polypeptides are being added tothe vaccine (chimeric VLPs) with the hope of improving the therapeuticpotential. Large scale efficacy trials will be initiated in the next twoyears. Such trials require large numbers of individuals, studied overseveral years. Young women who are initiating sexual activity willrepresent the target groups. However, vaccination of both men andwomen will ultimately be needed to break the cycle of sexualtransmission. Multivalent HPV vaccine has the potential to interferewith the establishment of HPV infection and to prevent benign HPV-related lesions, cervical neoplasia, and other anogenital neoplasias.

ON4.05.03FOLLOW-UP AFTER TREATMENTJ. Lou Benedet , Vancouver Cancer Centre, BC Cancer Agency,Vancouver, Canada

Follow-up intervals after treatment for CIN have evolved empirically.This monograph will review the purpose and rationale for follow-upprotocols for CIN. Follow-up strategies for CIN are based on twofundamental themes “was the intervention successful” and secondly “arethe intervals appropriate”.Follow-up enables one to determine if the observed outcome is similar tothat which was anticipated for a given modality and if results from a newtherapy are comparable to established treatments. Studies have revealedthat successful therapies are dependent on several factors, which broadlyfall into two categories – those that are related to either the treatment orthe disease itself. Disease-related factors that have been identified forCIN include lesion size, histopathology, and factors adversely affectingthe immune response of the patient. Treatment related factors arespecific to the modality used and also the expertise of the therapist.

Follow-up intervals should be based on our knowledge of the biology ofthe disease and in CIN, where the usual transit times are measured interms of years, the intervals can be longer.Another factor important in determining follow-up intervals is thelikelihood of new disease developing. Our knowledge of the evaluationand genesis of CIN would suggest that if the precursor lesions are trulyeradicated the likelihood of new or further disease is extremely low.Patient compliance is important and, if resources are limited, toofrequent follow-ups may utilize resources best deployed for primarydetection or treatment. A vast literature shows success rates in excess of90% for cryotherapy, laser vaporization/excision or electrosurgicalexcision of CIN with most treatment failures being apparent within thefirst two or three visits of the first follow-up year. If lesions are trulyeradicated they could be followed as individuals who had a negativecytology at the outset. Individualization is appropriate if all of thepreceding factors are considered.

ON4.06 TREATMENT OF ENDOMETRIAL CANCER

ON4.06.01WHAT IS OPTIMAL SURGERY FOR ENDOMETRIAL CANCER?M. Quinn , Oncology/Dysplasia Unit, The Royal Women’s Hospital,Melbourne, Victoria, Australia.

Recommendations as to optimal surgery for endometrial cancer are besetby a lack of randomized trials. The adoption of the 1998 FIGO SurgicalStaging requirements have led to anxieties as to who should perform theprimary surgery and whether there is any therapeutic benefit from thestaging procedure itself. The following key points should be noted:The extent of surgery should be dictated by key prognostic factors suchas tumour histology, tumour size and grade, depth of myometrialpenetration, presence of lymph vascular space involvement, andinvolvement of the cervix/tubes/ovaries.The mainstay of surgical treatment is total abdominal hysterectomy andbilateral salpingo-oophorectomy. This is sufficient treatment for “lowrisk” tumours, although in the obese/medically unfit, vaginalhysterectomy is a reasonable option.1. There seems little place for lymph node sampling vs complete

lymphadenectomy given the fact that <30% of involved nodes aredetected by palpation, and almost half of positive nodes are <1 cmin diameter.

2. Good survival rates are still possible even with positive lymphnodes.

3. The morbidity of lymphadenectomy seems acceptable.4. Pre-operative imaging investigations may prove to be useful in

selecting patients for lymphadenectomy.5. Cost-effective analysis supports the option of lymphadenectomy.6. The use of laparoscopic surgery holds great promise, but needs to be

subjected to a randomized trial.

ON4.06.03MANAGEMENT OF SARCOMASP. Scollo , Department of Obstetrics and Gynecology, “Cannizzaro”Hospital, Catania, Italy

Uterine sarcomas account for the 3-4 per cent more or less of malignanttumors of uteri corpus. Leiomyosarcomas arise in miometrium; whereasendometrial stromal sarcomas and mixed Mullerian malignant tumors(MMT) (mixed mesodermal tumors or carcinosarcomas) arise in theendometrium or in the endocervix.Annual incidence of leiomyosarcomas is 0.64 out of the 100000 women;the one of endometrial stromal sarcomas is 0.19 out of the 100000 andthat of MMT is 0.82 out of the 100000 women.Up till now such numbershave been slightly changed.As far as leiomyosarcomas are concerned the reported average ageranges from 43 to 54. For endometrial stromal sarcomas, instead, theaverage age ranges from 41 to 63; whereas almost every patient affectedby MMT is post-menopausal.Etiopathogenesis of these neoplasms is hardly known. The role ofsteroids is controversial.The alteration of the gene p53 might have animportant role in the pathogenesis of leiomyosarcomas. They invadetissues mostly for contiguity and hematologic diffusion. Besides, theyare characterized by local recurrence and, above all, by metastases.


In the different istotypes initial symptoms are similar to one another andnonspecific. They can often be asymptomatic and are usuallyencountered on occasion, during an histologic examination, soon after aconservative and destruens surgery for leiomyomas.The anamnesis and the objective observation do not let us distinguishbetween uterine leiomyomas and leiomyosarcomas. Unfortunately, atthis respect, ultrasound, MRI, CT cannot be precise enough.Histologic parameters for the classification of uterine smooth-muscletumors are based on mitosis count,expressed as 10 or more per 10 HPFand the presence of atipic cells.There is no FIGO official stage on uterine sarcomas.The most performed treatment of uterine sarcomas is total abdominalhysterectomy with bilateral adnexiectomy.For MMT an intensive surgical stage is suggested:peritoneal washing,total hysterectomy, bilateral adnexiectomy, omentum removal, multipleperitoneal biopsy and pelvic and para-aortic lymphadenectomy.Radiation therapy, as adjivant therapy after surgery, has been successfulin reducing local recurrences in uterine sarcomas.Natural history of uterine sarcomas, which there is a high incidence ofrecurrences of, underlines a post-surgical medical therapy is reqired.

RM4.03 REGULATION OF FERTILITY TREATMENTAND RESEARCH

RM4.03.01THE CASE FOR REGULATIONBrian A Lieberman , St. Mary's Hospital, Manchester, United Kingdom

In the United Kingdom, treatment by invitro fertilisation or with the useof donated gametes, and research using human embryos, is regulated bythe Human Fertilisation and Embryology Authority (HFEA). The HFEAct was passed by the UK Parliament in 1990 and became operativefrom August 1991.Have infertile couples who require such treatment been disadvantagedby regulation or has the quality of research using human embryos beenadversely affected? The categorical answer to these questions is aresounding NO!Treatment services:i. HFEA require high standards of patient care. The Act has set in placea system whereby best practice is expected in all units.ii. Best practice encompasses:a. The most appropriate and cost effective method of treatmentb. The clinic must publish their results in a format that is user

friendly, accurate and comprehensive.c. Patient information must be accurate and reflect current working

practicesiii. Consumer confidence is enhanced in the knowledge that the clinicmust be licensed and inspected at regular intervals by personsindependent of the centre.iv. The outcome of treatment is audited and published annually by theHFEA. This provides a national data bank.iv. Serious complaints contrary to the Act may be brought to theattention of the Authority.Research: The Act allows for research on human embryos. This is offundamental importance as in some countries such research is banned.Regulation of research using human embryos ensures that a scarceresource is utilised in the most appropriate and ethical manner.There is no evidence that regulation has impeded scientific advancementWhat is the downside to regulation?Interference to clinical freedom? No evidence that this is a validargument or that this so called limitation has disadvantaged patients.Limiting the number of embryos replaced? Yes, this is the case but thishas been to the advantage of the children conceived by reducing thenumber of multiple pregnancies and high order multiple births. Thenumber of instances of serious disability, cerebral palsy and learningdifficulties has been reduced at a massive cost saving to the coupleconcerned and the community. The ultimate number of healthy, non-handicapped children has been increased.Unnecessary cost to the infertile? A small price to pay for the obviousbenefits.Stifling research? No evidence to support this argument. Better andhigher quality research is far more likely with regulation.

RM4.03.02REGULATION OF FERTILITY TREATMENT AND RESEARCHM. Aboulghar , The Egyptian IVF-ET Center, Maadi, Cairo, Egypt

Objectives: The aim of the study was to evaluate the legal and ethicalaspects for regulation of fertility treatment and research.Study method: Review of the world literature through a Medline Searchas well as manual review of journals dealing with infertility treatment.Results: There is a marked variation in the rules which regulate fertilitytreatment in different parts of the world. In the United States thesurveillance and regulation are greatly influenced by the US constitutionwhich provides no niche for national regulation. In UK, the HumanFertilization and Embryology authority regulates fertility treatment. InGermany, comprehensive regulations have been established forprotection of the embryo. France had a law concerning ART since 1994.In most of Asia and Africa, the fertility treatment is regulated by anethical code.Conclusions: Laws governing fertility treatment and research showsurprising variability all over the world. As this field is continuouslydeveloping, control of various aspects of laboratory and medical detailsof ART by legislation is less desirable.

RM4.04 UTERINE RECEPTIVITY - IMPLANTATION

RM4.04.01AN OVERVIEW OF UTERINE RECEPTIVITYI D Cooke , K Lim, Department of Obstetrics and Gynaecology,University of Sheffield at the Jessop Hospital for Women, Sheffield S37RE, U.K.

The human endometrium develops under the influence of oestrogen andprogesterone. By mid-luteal phase there is tight regulation of cellularcomponents ready for implantation, the so-called ‘window’. Theconceptus and the luminal epithelium each express integrins whichfacilitate the binding of the two structures (the adhesion phase).Proteases allow embryonic trophoblast to insinuate itself betweenluminal cells and into the stroma, lysing the extracellular matrix withmatrix metalloproteinases (MMP). IgF-II seems to be a significantgrowth factor from the invading trophoblast. Natural killer cells (NK)comprise 70-80% of the large granular lymphocytes in the stroma in themid-luteal phase. They may be responsible for decidualisation. HLA-Gmay protect trophoblast from attack by NK cells via killer inhibitoryreceptors (KIR) on the NK cells. Some T cells may be of T-helper 1type which secrete the cytokines IFN gamma, IL-2, IL-12 and TNF-betaand can promote cytotoxic rejection of the trophoblast antigen. Othersmay be of T helper 2 type which secrete IL-4, -6, -10 and –13 andnormally maintain a positive balance over Th1 helping to support thelater phase of trophoblast invasion. Trophoblast invades vessels toestablish the early circulation of the placenta. Clarke hypothesizes thatthe maternal organisms senses the genetic make-up of the embryo(including paternal antigens selectively expressed on trophoblast byimprinting) and her response is determined by her own genetic responseto stress. Th1 cytokines may upregulate a prothrombinase whichactivates coagulation mechanisms. These lead to a vasculitis of thematernal embryonic blood supply and subsequent abortion.Clarke D A et al (1999). Amer J Immunol, 41: 5-22.

RM4.04.02IGF SYSTEMM. R. Gazvani , Aberdeen Maternity Hospital, Aberdeen, UK

Endometrial stromal cells produce insulin-like growth factors I and II(IGF-I and IGF-II) as well as the high affinity IGF binding proteins(IGFBPs), whereas epithelial cells and stromal cells contain cellmembrane receptors for IGFs. The IGF family is believed to beimportant in the process of implantation. Members of the IGF familyinclude the IGF peptides (IGF-I, IGF-II), seven IGF binding proteins,and two IGF receptors.IGF-I and IGF-II are low molecular weight single chain polypeptides,that are regulated by oestrogen. The properties of IGFs and their bindingproteins, as well as their spatial and temporal expression in cyclingendometrium, suggest that they may participate in endometrial growth,differentiation, apoptosis, and perhaps angiogenesis. IGF-I is assumed to


mediate oestrogen action whereas IGF-II gene expression is associatedwith endometrial differentiation.All IGFBPs are expressed in human endometrium, the most abundantbeing IGFBP-1. It is a major protein product of non-pregnantendometrium during the mid-late secretory phase and occurs inabundance in decidua. Its roles as an IGF-binding protein and as atrophoblast integrin ligand suggests that it may have multiple roles inendometrial development and in interactions between the decidua andthe invading trophoblast.Available evidence suggest multiple roles for IGFBPs in supportingimplantation, regulating the extent of decidualisation, modulating localevents of vascular IGFs, and regulating uterine muscular growth. Betterunderstanding of the IGF family and its function will aid ourunderstanding of the mechanisms involved in implantation.

RM4.04.03INTEGRINS AS MARKERS OF ENDOMETRIAL RECEPTIVITYBruce A. Lessey PhD, MD, Division of Reproductive Endocrinologyand Infertility, Department of Obstetrics and Gynecology, University ofNorth Carolina, Chapel Hill, NC 27599

Endometrial receptivity is the culmination of complex temporal andspatial modifications by the endometrium that is regulated by ovariansteroids. Synchronous development of the endometrium and the embryoallows for precise timing of implantation, a feature that is necessary forsuccessful pregnancy. As part of evaluation of the infertile couple, it hasbeen reported that numerous cases of sterility may be due to aninadequate endometrium. These include luteal phase defect (LPD),endometriosis, hydrosalpinges, and possibly polycystic ovariansyndrome (PCOS). The biomarkers that have used to address suchdefects includes the integrins which are heterodimeric glycoproteinsmade up of a and b subunits. Recently, other markers have beensuggested including LIF, HB-EGF, HOXA-10 and calcitonin. We arenow in the process of correlating the usefulness of these markers aloneor in combination with other markers such as integrins. Theidentification of true defects in uterine receptivity will likely lead toimprovements in diagnosis and treatment of the infertile couple andenhance our ability to apply Assisted Reproductive Technologies (ART)to improve success rates and outcome. Much work still needs to be donein order to validate the use of biomarkers for this purpose andprospective randomized trials need to be designed that can ascertain thebest way to use such biomarkers.

SS4.05 REACHING THE UNREACHABLE IN AFRICA:HOW CAN WE PROVIDE NEEDEDREPRODUCTIVE HEALTH

SS4.05.01INTRODUCTION TO THE SESSIONDr. Florence Manguyu , Session Chair, Nairobi, Kenya

This is an overview paper introducing the subject theme of the panel.The paper highlights the basic facts about women's health in Africa. Itposes the questions to be addressed by the panelists, namely: Who arethe unreachable, the clients, the medical workers or the healthinstitutions? Do the health services available respond to the needs of thecommunity? What choices do the communities have when seekinghealth services? What health policies need to be in place in order toaddress the needs of those hard to reach? The paper briefly discusses thereasons behind the social environments that stratify communities inAfrica, and suggests ways on how health policies might change in orderto be responsive to the needs of the people they purport to serve. Itexamines the disease burden in RH in different social situations andaddresses the gender disparities that deny women the enjoyment of thehighest attainable standard of health. Finally the paper outlines howwomen's health advocates could work in collaboration and in partnershipwith the health consumers and other stake holders in order to beeffective in reaching the unreachable.

SS4.05.02THE FUTURE ROLE OF HEALTH MINISTRIESEunice Brookman - Amissah, Ambassador of Ghana to the Netherlands,Past Minister of Health, Ghana

Health service development in many African countries has been andcontinues to be state-led and centrally planned. Two common offshootsof this pattern of development are the undue bias towards cities and bigtowns; and the lack of recognition of the unique contribution ofstakeholders other than Ministries of Health. Cities, big towns, andvillages along major and trunk roads tend to be better served with healthservices than rural communities. Health service coverage in rural areas iseither low or non-existent. This is well known and documented. Lesswell known are the increasing numbers of unreachable women in bigtowns and cities. As a result of economic migration, big cities attract agrowing army of uneducated or poorly educated unskilled young people,who even though they work in cities, live in slums on the outskirts ofthese cities. Among this population, sexually transmitted disease, the useof abortion as a means of contraception, and repeated unwantedpregnancy are rampant and yet this increasing group of unreachablesattract very little attention in the design of health services. An excitingdevelopment over the last two decades in developing countries has beenthe increasing contribution of the International donor community, theNGO and Private sector and the Research community in health sectordevelopment. In many African countries these groups contribute morethan half the public health expenditure. The NGO communities with thePrivate for profit group together probably reach a larger proportion ofthe population than the Ministries of Health. Yet the role of theMinistries of Health have changed very little to reflect this new reality.These vital partners are still seen as competitors, are not included in theformulation of sector policies and are more or less left to continue tofocus their efforts in isolated projects and areas. The limitations ofMinistries of Health are not well known and there is no real dialoguebetween the different partners in the health sector. Funding for healthservices is scarce and in the main not efficiently or equitably utilized.This paper will examine how Ministries or Health can enter into newPartnership with other stakeholders to develop a holistic programme tomeet the dual challenges of expanding health services to the unreachedand also improving the quality of existing services.

SS4.05.03THE ROLE OF PROFESSIONAL ORGANIZATIONSDr. Friday Okonofua , Secretary - General, Society of Gynaecology andObstetrics of Nigeria, and Professor of Obstetrics and Gynaecology,University of Benin, Nigeria.

Several countries in sub-Saharan Africa are characterized by poorreproductive health with high rates of maternal mortality, unsafeabortion, sexually transmitted diseases including HIV, and infertility. Amajor factor that perpetuates the poor reproductive health in many ofthese countries is the limited access to reproductive health informationand services of several disadvantaged populations. The most badlyaffected are adolescents, poor women who live in rural and suburbanareas, and women and men with limited or no education. This paperdescribes the role that professional organizations in medicine and thesocial sciences can play in creating access to qualitative health care for alarge segment of under-served populations in many African countries.Professional organizations can develop technical and ethical standardsfor the practice of reproductive health in Africa that would encourageincreased utilization of services. They can foster relevant reviews ofcurricular and training for the widespread dissemination of modernconcepts in reproductive health to practitioners across Africa. They canfunction as trainers of junior and medium level manpower in the formaland informal sector, and engender systematic integration of traditionaland orthodox systems of reproductive health care. Finally, professionalorganizations can serve as advocates for improved health care deliveryand costs alleviation, and encourage the enunciation of laws and statutesthat would improve access to reproductive health for large populationsin Africa. Clearly, the large burden of reproductive ill-health in Africa isa major professional challenge to practitioners in Africa. A measure ofthe success of professional organizations in Africa in the comingdecades is an evaluation of the way in which they contribute toimproving access to reproductive health to the large segment of under-served populations in the continent.


SS4.05.04THE VIEW FROM THE OBGYN IN RURAL PRACTICEDr. Godfrey Mbaruku , Regional Hospital Maweni, Kigoma, Tanzania

This paper develops a picture of the reproductive health services mostdesired and needed by poor rural women in Africa but also oftenunavailable to them for many reasons. The services most needed, but notall, include lack of services for adolescents who are left to explore forthemselves issues concerning their sexuality. Consequently adverseoutcome demonstrated by teenage pregnancies, sexually transmittedinfections and HIV/AIDS become rampant.Services for abortion management are non-existent for this group of thepopulation and the few available are too far to be reached due to costs ordistance. As a result, complications of abortions account for a largeproportion of the causes of maternal mortality and morbidity.Comprehensive obstetric services are almost non-existent. Whereavailable they constitute of mostly rudimentary routine antenatal care.No wonder, more than 60% of all deliveries take place outsideinstitutions and attended by untrained personnel such as Traditional birthattendants and relatives. Due to lack of equipment and manpower, eventhe institutional services are of poor quality resulting in many avoidablematernal deaths and high morbidities. More seriously, postnatal careservices are non-existent which contribute to a further death toll andmorbidity.Family planning services are non-existent in the rural areas.Consequently poor rural families are characterized by large non-manageable families, high infant and child mortalities and morbiditiesand overcrowded social services such as schools and dispensaries.Several problems exist which are endured silently by women. Theyresult from obstetric complications clandestine abortions, genitalinfections or traditional practices. These include obstetric festulae,chronic pelvic pain, genital prolapse or gynaetraesia due to femalecircumcision and infertility.No comprehensive services are available in the rural areas to addressthese conditions. And when available in a few places such as ruralmission hospitals, they are either too far, expensive or overcrowded toan extent of being almost inaccessible.This paper also outlines some ways whereby these problems have beenaddressed inorder to improve the deploring situation.

SS5.05.05CAMPAIGNING FOR WOMEN'S SEXUAL AND REPRODUCTIVERIGHTSZanele Hlatshwayo, Women's Health Project, University of theWitwatersrand, South Africa

South Africa is considered to have one of the highest rates of maleviolence committed against women for a country not at war. It isestimated that 1,000 women in South Africa are raped daily and that onein six women are in abusive relationships. A recent survey in theGauteng Province found young boys not yet in their teens think rape is agame and declaring themselves openly in favour of sexual violence. As aresult of unequal power relations between women and men, women arevulnerable to coerced or unwanted sex which places them at risk forsexually transmitted diseases, including HIV/AIDS and teenagepregnancy. The campaign aims to create awareness about sexual rightsamong South Africans to proactively address violence against women,HIV/AIDS and other sexually transmitted diseases and unwantedpregnancies among youth. In addition, the campaign intends for keystakeholders to commit to a charter of sexual rights and implementationof policy proposals and action plans on violence against women, teenagesexual health and HIV/AIDS, informed by gathering people’s views onbarriers and necessary actions. The campaign is developing a core cadreof trained trainers and strengthened capacity and networking betweenorganisations of civil society, and between these organisations andgovernment; and interdepartmentally within government. The campaignis ongoing. The impact of the training to date is that girls report beingmore able to communicate assertively with boys and boys recognisegirls’ rights and choices in their relationships. Men report an increasedawareness of abusive relationships and commit to respect the rights andchoices of their partners. Women are gaining communication skills notonly to negotiate for the use of condoms in the home, but also tochallenge local government on issues pertaining the handling of cases ofviolence against women by police. The campaign is further expected tobuild a greater understanding of sexual rights and barriers to achieving

these amongst government and organisations of civil society; developrecommendations for policy and intersectoral action; develop a sexualrights charter; identify obstacles and gaps in policy implementation inrelation to violence against women, teenage sexual health andHIV/AIDS; increase the understanding and acceptance by the media ofthe need to promote a sexual rights perspective in general and in relationto these three critical areas.

SS4.06 EDUCATION AND TRAINING IN OBSTETRICS ANDGYNECOLOGY

SS4.06.01TAKING THE TEACHING OF OB/GYN SURGICAL SKILLS INTOTHE LABORATORYR. Kung , L. Allen , Dept of Ob/Gyn, University of Toronto, Toronto,ON, Canada

Technical skills in surgical training programs including Obstetrics andGynecology have been traditionally taught in clinical setting, under staffand/or fellow supervision in the operating room and/or in labour anddelivery. The residents are exposed to more difficult cases as theyprogress in their training and are permitted to perform more difficultsurgery at the senior level. Evaluation of technical skills is based on aglobal assessment by the staff usually at the end of a 3 to 6 monthrotation. The following factors have resulted in reduced clinicalexposure for junior residents over the last 5 to 10 years: (1) a reductionin surgical case load, (2) increased difficulty of cases (largerly as a resultof increased use of medical therapies, decreased operative delivery rates,(4) decreased vaginal breech deliveries, (5) a greater number of residentsper hospital, and (6) current medical legal issues, etc. One potentialsolution is to shorten their learning curve by providing them with theopportunity to develop their surgical technique in a lab setting. Thisallows junior residents to acquire new skills by providing intense,repetitive exposure to specific tasks using inanimate and animal modelswith a high staff to resident ratio (1:4).A Surgical Skills Curriculum was developed. This consisted of 27sessions, 2 hours in duration starting from July 98 to June 99. Obstetricalsessions included shoulder dystocia, external cephalic version, vaginalbreech delivery, forceps, vacuums, scalp pH sampling, scalp electrodes,intrauterine pressure lines, and neonatal resuscitation. The remaining

SS4.06.02THE K.O.A.L.A.™ PROGRAM: AN INTERNET-BASED LEARNINGPORTFOLIO FOR RESIDENTSM. Fun Kee Fung , The Ottawa Hospital, Ottawa, Canada

Launched in January 1997, the Computerized Obstetrics andGynecology Automated Learning Analysis (K.O.A.L.A.™) programwas the first, Internet-based, dynamic, relational database in obstetricsand gynecology. It allows residents to integrate learning and practice andto keep a record of cases/patient encounters and of teaching activitiesthat lead to critical incidents of learning. Immediate access to on-lineresources, including MEDLINE, encourages the habit of seekinganswers to questions raised while managing patients and facilitates theacquisition of information literacy skills. K.O.A.L.A.™ teachesresidents the basic skills of self-directed learning and self-managementof learning through the use of a learning portfolio. The systemencourages residents to share learning items with peers and, likephysicians in practice, to use knowledge of what peers are learningabout to motivate their continuing learning. The database of clinicalquestions recorded by residents in K.O.A.L.A.™ is used to maintain abank of evidence-based summaries that can be accessed by residents.K.O.A.L.A.™ has the potential to enhance the in-training evaluation ofresidents. It creates opportunities for residents to receive timely (email)feedback from the program director directly related to their entries. Thesystem provides opportunities for ongoing assessments of residentlearning activities. Equally important, the system provides opportunitiesfor research studies into the types of clinical encounters that generatelearning opportunities for residents and studies on how best to providefeedback on learning after the immediacy of the case has passed and thelearner is in a more reflective mode.From January 27, 1997, to January 1, 2000, 45,527 cases/patientencounters and 18,775 critical incidents of learning (outside the zone of


mastery or experience) were recorded by users at 15 Canadian residencytraining programs.As an Internet application the K.O.A.L.A.™ Program can be modifiedaccording to the needs of individual groups (all specialties and usergroups e.g., medical students, residents, practicing physicians) and canbe accessed by any individual from any computer with Internetconnectivity, regardless of country.

SS4.07 GYNÉCOLOGIE SANS FRONTIÈRES: OUR N.G.O.(FRENCH SESSION)

SS4.07.01DÉPISTAGE DU CANCER DU COL UTÉRIN DANS LES PAYS ENDÉVELOPPEMENT: POSSIBLE, RAISONNABLE?B. Guillon , Gynécologie Sans Frontières, Paris, France

Introduction: Gynécologie sans Frontières s’est donné pour but d’agirsur les items médicaux de la santé des femmes à travers le monde, etparmi eux ceux relevant de la gynécologie obstétrique. La médecine desfemmes ne pouvant être réduite à la médecine de la gravido-puerpueralité, il nous a paru naturel et nécessaire de se pencher sur leproblème des cancers féminins.Pourquoi le cancer du col:• Les raisons médicales et économiques• Choix des méthodes de dépistages:• Deux méthodes de dépistage des lésions du col se discute dans ce

cadre:• La colposcopie, avantages, inconvénients• Le frottis cervical avec coloration de papanicolaou, avantages et

inconvénients.Conditions de mise en place: Analyse des conditions locales de mises enplace des programmes, le rôle de la mission exploratoire.L’exemple de l’Albanie: Une expérience de terrain pour GSFConclusion: Prendre en charge un aspect de la santé des femmes c’estaussi leur permettre de prendre conscience de leur propre rôle dans lasanté, la leur, mais aussi celle de la collectivité.

SS4.07.02THE CULTURAL AND SOCIAL CONSEQUENCES OFEXPORTING TECHNOLOGY AND KNOWLEDGES. Kousmine , Gynécologie Sans Frontières, Paris, France

Transferring technology, knowledge or values to another country doesnot only impact a specific identified field but a whole social culturalsystem.Indeed, a nation is a structure which is organized according to a socialproduction to which each individual participates.Human groups in order to live must respond to their different types ofneeds. But any of these needs require to be integrated and organized in acollective project.A regulation according to the group's logic has to take place for thecollective project to be possible.It is what sociologists and anthropologists name culture : the wholeproduction of the group responding to its whole needs inside a collectiveproject submitted to regulation.According to the social and cultural scheme of analysis of Dr. RolandColin, a French anthropologist, there are six different levels of culture:(1) Technology, tools(2) Economy(3) Politics(4) Family(5) Psychological organization, education(6) Ideology, valuesThe content of each level is interrelated to the other levels. Any changeat any level will impact the whole system.It is why the consequences of cultural influence, by technologicaltransferring for instance, may well be figured out:- The other levels may adapt and change to create a new coherence- The other levels may react to stop the changeTherefore, a society to get its whole system regulated or balanced maygo through a more or less long crisis.We will look at how different cultures perceive healthcare and howhealing is a full part of their social production.

Some study cases will give clues to understand how medical help toanother country can sometimes have negative social consequences or besimply inefficient.

SS4.07.03LA MORTALITÉ MATERNELLE: ESPOIRS D’UNE RÉDUCTIONDE LA FRÉQUENCE?Pr Henri-Jean Philippe , Gynécologie Sans Frontières, St-Germain,France

C’est un problème majeur de santé publique.Les solutions ne sont pas simples. On peut se demander si l’améliorationdu niveau économique du pays n’est pas la condition préalableobligatoire.La proposition habituellement proposée consiste à mettre en place unréseau périnatal autour d’une maternité de référence, ce qui signifie:• mettre à niveau en terme d’équipement et de personnel, cette maternitéet les dispensaires qui l’entourent,• établir des protocoles pour le suivi et le dépistage de situations à risqueet les indications de transferts,• mettre en place un système de connexion.La mise en place d’un réseau périnatal pose des problèmes de pérennité.Le projet "Save the Mothers" inclut un partenariat entre sociétéssavantes de chaque pays ceci devrait faciliter la poursuite du projet.Il nous semble que la solution complémentaire nécessite d’entreprendreune éducation des populations et la mise en place d’une participation descommunautés locales.

EN4.02 MANAGEMENT OF MENORRHAGIA

EN4.02.01PATHOPHYSIOLOGY OF ENDOMETRIAL FUNCTIONHilary OD Critchley , Obstetrics and Gynaecology, University ofEdinburgh Centre for Reproductive Biology, 37 Chalmers Street,Edinburgh EH3 9ET, U.K.

The endometrium is distinctive in both structure and function. Steroidhormones are the primary and systemic factors driving the endometriumthrough the orchestrated phases of the menstrual cycle. Oestrogen andprogesterone act sequentially to regulate cellular concentrations of theirrespective receptors. Interaction with receptors initiates genetranscription. A cascade of local morphological and physiological eventstakes place that prepares the endometrium for implantation, and in theabsence of pregnancy, menstruation and subsequent repair. The sexsteroid receptors exist in more than one isoform, but it is yet to bedetermined which steroid receptor subtype mediates specific localfunctions.Oestrogens play a major role in cell proliferation. Progesterone isessential for the establishment of a successful pregnancy. Antagonism ofprogesterone regulated processes is associated with early pregnancy loss.Withdrawal of progesterone is the initiating event for the cascade ofmolecular and cellular interactions that lead up to the onset of menses.Specifically progesterone withdrawal up-regulates locally producedinflammatory mediators (prostaglandins, chemokines) and enzymesresponsible for tissue breakdown (matrix metalloproteinases).Coincident hypoxia due to local arteriole vasoconstriction independentlyup-regulates expression of angiogenic mediators. Lines of evidence existto suggest a complex interplay between the endocrine and immunesystem and other locally produced factors critical for normal endometrialfunction. Specific endometrial factors implicated in normal menstrualand aberrant endometrial bleeding remain to be defined.

EN4.02.02DRUG THERAPYD. Tank , Dept. Obstetrics & Gynecology, Ashwini Maternity & SurgicalHospital, Mumbai, India

As many as seven options are available for the medical management ofDUB. Most of them like ethamsylate, combined OC pills, danazol,GnRH analogues and progesterone releasing IUCD’s either are noteffective or are associated with other problems like side effects orincreased cost.


Progestogens remain the drugs of choice. We are of the opinion that theproblems are two: the first is the type of progesterones used and thesecond is the protocol of administering the drug.Dydrogesterone a new progesterone we thought was capable of fulfillingthe criteria demanded from a drug in the treatment of DUB. We alsomodified the protocol starting from the drug from 11th day of the cyclefor 15 days instead of from the 15th day as reported for the other drugs.With the Assumption that oestrogen are intercepted early and the drugwill not affect ovulation.We have so far had a study published from our encouraging results on acohort of 30 patients and after the publication we have recruited afurther 50 patients. Our entire group of 80 patients have given usextremely heartening results. Further to this a multicentric trial cariedout all over India has recruited 400 patients where the results of ourinitial study have been reproduced.

EN4.02.03INTRAUTERINE SYSTEME-M Rutanen , R. Hurskainen, Department of Obstetrics andGynecology, Helsinki University Hospital, Helsinki, Finland

The intrauterine system that releases levonorgestrel 20 g/24 h into theuterine cavity for a time period of 5 years was originally developed forcontraception. Many studies have been published during the past decade,describing the system as one of the most effective treatments in reducingthe amount of menstrual blood loss in women suffering frommenorrhagia. High dose of levonorgestrel in the uterus has strongsuppressive effect on the endometrium. Endometrial epithelium becomesatrophic and the underlying stroma is decidualized. This change isconstant during the use of the system but reversible in one month afterits removal. The concentration of levonorgestrel is high in theendometrium but very low in the circulation, and ovarian functionremains almost unaffected. There are several mechanisms that mayaccount for the reduction in menstrual blood loss. The morphologicalchanges in the endometrium are followed by changes in endometrialfunction. It has been shown that production of many local factors thatare involved in the regulation of endometrial proliferation, shedding,remodeling and haemostasis, may undergo changes under continuousprogestin stimulation. These changes are likely to favor the reduction ofendometrial bleeding. The most common side effects of levonorgestrelintrauterine system are spotting and mild irregular bleeding, which aremostly reported during the first months of treatment. However,levonorgestrel intrauterine system is an alternative to surgical treatmentof menorrhagia and especially in women who still want to becomepregnant and have an increased risk of iron deficiency anemia. It is alsosuitable during premenopausal years, since only estrogen needs to beadded when climacteric symptoms appear, and if the woman wants tostart hormone replacement therapy.

EN4.02.04VARIATIONS IN SURGICAL TREATMENTJ. A. Rock , Emory University School of Medicine, Woodruff MemorialResearch Building, Dept. of Gynecology and Obstetrics, Georgia,United States

Over 250, 000 hysterectomies are performed for dysfunctional uterinebleeding each year in the United States. Some surgeons have suggestedthat endometrial ablation is now a realistic alternative to hysterectomy.The goal of most ablation techiniques is to remove or destroy theendometrium creating an Asherman like scar. This session will criticallyassess and compare the techniques of endometrial ablation. Currentindications and current contraindications will be presented. Moreover,the complications and percentage of women requiring additionaltreatment will be reviewed. The goals of this presentation is to bring intofocus a realistic appraisal of the role of endometrial ablation ingynecology.

FM4.05 RECURRENT EARLY PREGNANCY LOSS

FM4.05.01GENETIC CAUSES ARE RESPONSIBLE FOR MOST FIRSTTRIMESTER PREGNANCY LOSSESJoe Leigh Simpson , Baylor College of Medicine, Department ofObstetrics & Gynecology, Houston, Texas, United States

Pregnancy loss occurs very commonly, both pre-clinically and clinically.At least 25-50% of embryos die before implantation; another 30% ofimplanted embryos are lost. The likelihood of losing a clinically evidentpregnancy is 10-12%, two-thirds occurring before 8 weeks. Despite ahost of potential explanations (endocrine, anatomic, infectious,psychologic, autoimmune, alloimmune), genetic factors are accepted asthe most important cause for both sporadic as well as recurrent abortion.Using fluorescent in situ hybridization (FISH) with chromosome-specific probes, 25-50% of morphologically normal and 75% ofmorphologically abnormal preimplantation genetic embryos arechromosomally abnormal. At least 60-70% of first trimester clinicalabortuses are cytogenetically abnormal. The frequency is the same inrecurrent as well as sporadic abortuses. Aneuploidy may also berecurrent in successive clinical and successive preimplantationpregnancies, indicating heritable factors. Distinct from cytogeneticcauses are single gene mutations and polygenic factors, both morecommon genetic explanations for anomalies in liveborns than arecytogenetic causes. Non-genetic factors doubtless are occasionallycausative for first trimester losses and could also be relatively moreimportant in recurrent losses; however, overall the attributable risk dueto non-genetic factors is low in both recurrent as well as sporadic firsttrimester abortions.

FM4.05.02THROMBOPHILIA: AN EXAGGERATED PROTHROMBOTICRESPONSE TO PREGNANCY UNDERLIES MANY CASES OFRECURRENT PREGNANCY LOSSLesley Regan, ICSM at St. Mary’s, London UK

1) Pregnancy is an hypercoagulable state2) Microthrombi identified in the placental vasculature of women with

recurrent miscarriage.3) Prospective studies demonstrate an increased prevalence of

antiphospholipid (aPL) antibodies amongst women with recurrentmiscarriage and a high rate of early fetal loss.

4) Pregnancy outcome in women with aPL is significantly improvedwhen thromboprophylaxis is prescribed during pregnancy.

5) Retrospective studies of women attending haemostasis clinicssuggest that thrombophilias are a risk factor for miscarriage andstillbirth

6) Placental histology demonstrates widespread thrombosis andinfarction in some women who carry the factor V Leiden genemutation

7) Prospective pregnancy outcome studies in women with inheritedand acquired thrombophilic defects are urgently needed

8) Conventional haemostasis tests fail to identify all women withthrombophilic defects. Future research should include globalmarkers of haemostatic function such as thromboelastography

9) Protocols need to be established to 1) avoid diagnostic pitfallswhen screening

10) for thrombophilic defects and 2) determine the basis for futureprospective therapeutic studies

Suggested references : Backos M, Rai R, Chilcott I, Cohen H, Regan L(1999) Pregnancy complications in women with recurrent miscarriageassociated with antiphospholipid syndrome treated with low dose aspirinand heparin. Br J Obstet Gynaecol; 106, 102 -107Brenner B, Mandel H, Lanir N et al (1997). Activated protein Cresistance can be associated with recurrent fetal loss. Br J Haematol 97,551 -554.Cumming AM, Tait RC, Fildes S et al (1995) Development of resistanceto activated protein C during pregnancy. Br J Haematol 90: 725.Dizon-Townson D, Meline L, Nelson L, Narner M, Ward K. (1997)Fetal carriers of the factor V Leiden mutation are prone to miscarriageand placental infarction. Am J Obstet Gynecol; 177: 402 - 405.Grandone E., Margaglione D., Colaizzo D., and D’Addedda M. (1997)Factor V Leiden is associated with repeated and recurrent unexplainedfetal loss. Thrombosis Haemostasis 77, 822 – 4.


Kupferminc MJ, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A,Fait G, Lessing MD (1999). Increased frequency of geneticthrombophilia in women with complications of pregnancy. NEJM 340;9 – 13.Kutteh WH.,(1996) Antiphospholipid antibody associated recurrentpregnancy loss: Treatment with heparin and low-dose aspirin is superiorto low-dose aspirin alone. Am J Obstet Gynecol 174, 1584- 1589Metz J., Kloss M., O’Malley C.J., Rockman S.P., DeRosa L et al (1997)Prevalence of Factor V Leiden is not increased in women with recurrentmiscarriage. Clin Appl Thrombosis/ Hemostasis. 3, 137-140.Preston, F.E., Rosendaal, F.R., Walker, I.D., Briet, E. & Berntorp, E.(1996) Increased fetal loss in women with heritable thrombophilia.Lancet 348 913-916.Rai, R.S., Clifford, K., Cohen, H & Regan, L. (1995a) High prospectivefetal loss rate in untreated pregnancies of women with recurrentmiscarriage and antiphospholipid antibodies. Hum Reprod.10,3301-3304.Rai, R.S., Regan, L., Clifford, K., Pickering, W., Dave, M., Mackie, I.,McNally, T. and Cohen, H. (1995b) Antiphospholipid antibodies andBeta2-glycoprotein-I in 500 women with recurrent miscarriage: Resultsof a comprehensive screening approach. Hum. Reprod. 10, 2001-2005.Rai, R., Regan, L (1996) Thrombophilic defects and pregnancy loss. In:Infertility and Reproductive Medicine Clinics. Daya S, Guest Editor.WB Saunders, Philadelphia. Eds, Diamond MP & DeCherney AH.Volume 7: Number 4 :pp745 – 758.Rai R, Regan L, Chitolie A, Donald J, Cohen H (1996) Placentalthrombosis and second trimester miscarriage in association withactivated protein C resistance. Br Journal Obstet Gynaecol:103:842-844Rai, R., Cohen, H., Dave, M. and Regan, L. (1997) Randomisedcontrolled trial of aspirin and aspirin plus heparin in pregnant womenwith recurrent miscarriage associated with phospholipid antibodies (orantiphospholipid antibodies). Br Med J 314 253-257.Rai R, Chilcott I, Tuddenham E & Regan L. (1999) Computerisedthromboelastographic parameters amongst women with recurrentmiscarriage – evidence for a prothrombotic state. Hum Reprod 14, 73Sanson, B., Freiderich, P.W., Simioni, P et al (1996) The risk of abortionand stillbirth in antithrombin-, protein C-, and protein S-deficientwomen. Thromb Haemostasis 75, 387-388.Vincent T Rai R Regan L Cohen H ( 1998) Increased thrombingeneration in non pregnant women with recurrent miscarriage. Lancet352: 118

FM5.05.03IMMUNOLOGICAL ASPECTS OF RECURRENT MISCARRIAGEH.J.A. Carp ., Departments of Obstetrics & Gynecology; Sheba MedicalCenter, Tel Hashomer, and Department of Embryology, Tel AvivUniversity, Israel

Alloimmunization prevents fetal loss in the reproductively compromisedCBA/J x BA2J mouse combination, and in women with recurrentmiscarriages. It has been shown that maternal immunostirnulationdecreases the incidence of structural anomalies in pregnant miceexposed to teratogens and the teratogenic effect of maternal diseases.Alloimmunization leads to modulation of cytokine expression, such asTNFa (and its receptor), CSF-l and TGFâ2, both at the uteroplacentalinterface and in the embryo itself, with subsequent activation orinhibition of natural killer cells. The serum of recurrently abortingwomen has been shown to be toxic to rat blastocysts in vitro andteratogenic to mouse embryos in vivo. This embryotoxic effect isreversed in a high proportion of cases by IgG interchange. This IgGinterchange is analogous to the effect of intravenous immunoglobulin orseroconversion to antipaternal antibody production after paternalleucocyte immunization in humans.We recognize three types of recurrent miscarriage: inherently abnormalembryos due to chromosomal aberrations, those due to maternal factorssuch as antiphospholipid antibodies or uterine anomalies, and thosemade abnormal be maternal embryotoxic factors. Alloimmunization canonly work on the latter group. However, all trials on alloimmunizationhave tested women with three or more unexplained abortions and foundeither a small or no benefit. No trial has corrected the results forchromosomal aberrations in the embryo, or even for maternal factorssuch as the recently described thrombophilias. When these results arecompared to the high live birth rate of above 60% in women with threemiscarriages, it is not surprising that the beneficial effect is small.

Our approach has been different. We defined a group with a poorprognosis, i:e five or more abortions, and failure of other therapies.Paternal leucocyte immunization has given a 56% live birth rate inprimary and tertiary aborters. As opposed to 27% in the control group.This live birth rate increases to 80% when immunoglobulin is added.Therefore, immunization is effective in patients with a poor prognosisthat no other treatment has helped, even if double blind trials cannotprove that this treatment is a panacea for all patients.

FM4.05.04PSYCHOLOGICAL ASPECTSBabill Stray-Pedersen , Dept Ob/Gyn, National Hospital, University ofOslo, Norway

Recurrent miscarriages have been ascribed to many different causes ofwhich none should be regarded as absolute. In spite of intensiveinvestigation the aetiology is still unknown in more than half of thecases. All women who miscarry go through a bereavement process, butthe emotional consequences in those where no explanation is found, isexceptional. These women are usually distressed, frustrated anddesperate, and willing to try any treatment which may offer the slightestchance of success. Thus for the physician unexplained recurrentmiscarriage represents a therapeutic, but often frustrating challenge.During the last 20 years several treatment regimens such asimmunisation therapy, treatment with steroids, aspirin, human choriongonadotrophin and immunoglobulins have claimed to have success ratesof 75-85%.In our series of 811 couples with > 3 spontaneous, consecutivemiscarriages, a systematic postabortion screening, specific treatment,preconceptional counselling and psychological support during nextpregnancy have given an overall success rate of 86%.Furthermore, our most recent studies have shown that in the group ofwomen with unexplained aetiology, supportive care, including close,frequent contact with a dedicated physician, repeated ultrasounds scans,reassurance and encouragement during early pregnancy may improvethe clinical outcome, resulting in a success rate of 90%. This sucess rateseems to be inversely related to the number of previous abortion and theage of the woman.Our studies indicate that psychological support alone, can facilitate asuccessful pregnancy in women with recurrent abortion of unknownaetiology. Moreover before claiming any new treatment to be a success,the psychological aspects of therapy alone should be considered. In ourexperience the beneficial effect of supportive care emphasises theimportance of establishing miscarriage clinics where these women maybe offered special psychological support by dedicated care providers.

FM4.06 FETAL GROWTH RESTRICTION

FM4.06.01FETAL GROWTH RESTRICTION: A SURVIVAL PROCESS BUTWITH INCREASED RISK FOR PERINATALMORBIDITY/MORTALITY AND LONGER TERM ILLNESSBryan S. Richardson , Professor Obstetrics/Gynecology, Physiology andPediatrics, University of Western Ontario, London, Canada.

Fetal growth accounts for a consequential fraction of total substrateconsumption, resulting in a variable ‘savings’ in both energyrequirements and substrate building needs with a fall-off in tissuegrowth when oxygen and substrate availability to the fetus becomeslimited. In the ovine fetus with induced IUGR, total O2 consumption isreduced ~ 20%. This decrease in fetal oxidative metabolism againrepresents the energy ‘savings’ from decreased tissue growth and alsochanges in behavioural activity and associated energy requirements. Theovine fetus thus demonstrates an adaptation to a limitation in substratedelivery with a decrease in growth rate and thereby substrate needs,resulting in remarkable metabolic normality with a variable degree ofhypoxemia and usually little evidence of metabolic acidosis or anaerobicmetabolism. If decreased fetal growth is sufficient, the fall off in O2

consumption may balance that for O2 delivery such that fetal PaO2 is infact normalized. The human fetus is obviously also capable ofintrauterine growth restriction and cordocentesis data indicate variabledegrees of fetal hypoxemia, although in many instances blood gas valuesare within the normal range, again suggesting a degree of normalizationwith the fall off in growth. As such, movement activity and blood flow


redistribution as monitored with ultrasound in some growth restrictedfetuses may be little affected. However, while growth restriction mayhave survival value by decreasing substrate requirements for energy andgrowth, pathologic development may ensue depending on the timing,severity and type of substrate deficiency. In a hospital-based cohortstudy we found both growth restricted (< 3rd %) and borderline growthrestricted (3rd – 10%) infants to have an increased perinatal mortality(~5x and 1.5 x) , and risk for spontaneous preterm delivery (~2.5x and1.5x). In the growth restricted human fetus there is a developmentaldelay in the appearance of well-defined behavioural states which mayreflect underlying neurologic dysfunction and contribute to the minimalcerebral dysfunction noted in follow-up studies of these infants. There isadditionally increasing evidence that the intrauterine environment duringfetal life can ‘programme’ the development of risk factors for illness inlater life, including coronary heart disease and pancreatic dysfunction inthose infants born with low birth weight.

FM4.06.03INVESTIGATION AND PREDICTION OF FETAL GROWTHRESTRICTIONHein Odendaal , Dept OB/GYN, University of Stellenbosch,Stellenbosch, South Africa

It is a challenging problem to reduce the high perinatal mortality indeveloping countries with limited resources. As the prevalence ofhypertensive diseases is high in African countries, placentalinsufficiency is a common cause of perinatal mortality. Ultrasound andfetal monitoring facilities are not readily available to these countries.Therefore, one has to rely on other techniques to identify the motherwith placental insufficiency. As nutrition during pregnancy may beinadequate and as many mothers smoke, it is necessary to distinguishbetween the normal small fetus and the one with an insufficient placenta.We rely heavily on the obstetric history and serial measurement of thesymphysis pubis(SF) height to identify the mother at risk. When the SFmeasurement falls below the 10th percentile line for our population, theresistance index(RI) in the umbilical artery is assessed by a trainedmidwife, using a continuous wave Doppler machine. Mothers with an RIbelow the 75th percentile are regarded as normal, unless the clinicalcondition changes, and do not require any further tests. An RI betweenthe 75th and 95th percentile is regarded as doubtful and is repeated aftertwo weeks. When the RI is above the 95th percentile, a nonstress test isimmediately done to exclude fetal distress and the tests are repeated afterone week. Mothers with absent end diastolic velocity(RI=1) areimmediately admitted for further investigations or delivery. Patients withreversed flow are delivered when there are abnormal fetal heart ratepatterns or 24-48 hours after corticosteroids have been given. Patientswith absent end diastolic flow are delivered at 34 weeks or sooner ifthere are indications of fetal distress. The clinical condition of thepatient and fetal viability are always considered in the decision as whento deliver.We found the risk of intrauterine death due to insufficiency was justmore than 1 in 1000 of high risk mothers with normal SF growth. Therisk of intrauterine death of causes other than abruptio placentae inmothers with an RI <75th percentile is also very low(0.14%). It istherefore safe to screen patients with the use of SF measurements first,followed by Doppler flow velocity waveforms.

ON4.07 GYNECOLOGICAL PATHOLOGY: OVARY

ON4.07.02HOW DO PATHOLOGICAL RISK FACTORS AFFECT OUTCOME?P. A. van Dam* , L. Verkinderen* and L. Y. Dirix§, Dept. OB/GYN andMedical Oncolgy§, Sint Austinus Hospital, Antwerp, Belgium

The outcome of patients with epithelial ovarian cancer is mainlydetermined by the stage of the disease at the time of diagnosis,resectability of the tumor and its metastasis, and chemosensitivity of thetumor. We differentiated and ovarian tumors of borderline malignancytend to spread intraperitoneally at a later stage in the progression of thedisease then poorly differentiated and serous papillary tumors. Theunderlying molecular biological mechanisms are unknown. Interleukin 6and VEGF production by the tumor cells may for example play animportant role in driving the matastatic potential of a cancer. It remainscontroversial whether resectability of ovarian cancer is a function of

tumor biology or surgical skill. Optimal cytoreduction is easier toachieve in young patients with low-grade tumors, small metastasis, noascites and negative lymph nodes. Multivariate analysis shows that olderage, poor degree of deffirentiation and the presence of 20 or moreresidual lesions are independent unfavourable prognostic variables. Arecent EORTC study in 141 patients with stage IIB-IV epithelial ovariancancer indicates that the volume percentage epithelium (>65%, HR: 2.2,CI: 1.2-3.9; p=0.008) was the most prognostic important variablefollowed by mean nuclear area (>80, HR: 3.6, CI: 1.1-4.3; p=0.03).residual tumor size (5-10 cm compared to <5cm, HR: 2.3, CI: 1.0-5.2;p=0.04) and S-phase fraction (>6%, HR: 0.6; CI: 0.3-1.0; p=0.04). Theexpression of p53, p21, bcl-2, c-erbB-2, c-ras, insulin like growth factor1, c-myc, MIB1 and DNA ploidy does not seem to play an independentprognostic role in patients with advanced ovarian cancer. However, inpatients with stage I disease DNA ploidy is of major prognosticimportance. The response to chemotherapy is influenced by the age ofthe patient, the growth rate of thye tumor end the amount of rediualtumor after surgery. P-Gluthation, topoisomerase and markers of DNArepair are curently poor prognostic indicators.

ON4.07.03THE PATHOPHYSIOLOGIC CHARACTER AND TUMORFORMATION OF HUMAN OVARIAN SURFACE EPITHELIALCELLS IN OVARIAN EPITHELIAL CARCINOGENESISH. Katabuchi , H. Okamura, Kumamoto University Shcool of Medicine,Kumamoto, Japan

Objectives: The free surface of the ovary is covered by a single layer offlat or cuboidal cells, termed ovarian surface epithelium (OSE). Ovarianepithelial carcinoma is thought to arise from neoplastic formation ofOSE cells. In the viewpoint of ovarian epithelial carcinogenesis, thisstudy was focused on human OSE cells and cells lining inclusion cysts.Study methods: Human OSE and inclusion cysts were morphologicallyobserved in normal ovaries. Isolated OSE cells by a scraping methodwere cultured in a three-dimensional collagen gel culture system. Theywhere also immortalized by transfecting simian virus 40 large T antigen.Results: On grossly normal human ovaries, paillary and glandularstructures were observed in the OSE cells of invagination occured afterovulation. They frequently changed into cilial, mucinous, endometrioid,or transitional cells. Estrogen and progesterone receptors were expressedon their nucleus. In the collagen gel culture system, the OSE cellsformed a lumen in the estrogen-rich environment. In seven immortalOSE cell lines obtained, one cell line, which was cloned in soft agar,produced rapidly growing tumors and ascites after it wasintraperitoneally injected in athymic mice. Histologically the tumorsshowed undifferentiated carcinoma. The tumor cells wereimmunohistochemically positive for estrogen receptor. Although nomutant sequence of p53 gene was shown in both cell lines with positiveand negative tumorigenisity from the same patient, LH/hCG receptormRNA was deleted and mRNAs of ICAM 1, N-cadherine and integrinebeta 1 were less expressed in the tumorigenic cell line.Conclusion: Ovarian epithelial cancer may originate from OSE cellsthroughout their molecular alterations.

ON4.07.04HOW DOES PATHOLOGY INFLUENCE MANAGEMENT – GERMCELL TUMOURSFelix Wong , Department of Obstetrics and Gynaecology, University ofNew South Wales, Liverpool Hospital, Sydney, Australia

Germ cell tumours of the ovary represent a rare type of ovarian cancer.These tumours fall into two groups: dysgerminomas and non-dysgerminomas. The management of these tumours includes exploratorylaparotomy, which permits surgical resection or debulking, and definesthe extent of the disease. Subsequent chemotherapy will be assigned onthe basis of the histology and the findings at the laparotomy. Despite theadvance of chemotherapy, which offers an improved cure rate for thetreatment of these germ cell tumours. Its prevalence in youngreproductive women has a great impact to the reproductive potential ofthese young women. More conservative surgical approach has beenadopted for some germ cells tumours. The appropriate selection of atreatment plan requires two essential elements. First, a histologicaldiagnosis and second, the extent of disease at the time of diagnosis areboth critical. The extent of disease is expressed in term of the


International Federation of Gynecology & Obstetrics (FIGO) stagingsystem. The ensuing presentation focuses on the use of the histologicaland laparotomy information to make a treatment decision and theiroutcome. The present data suggest that patients with completely resectedstages I to III diseases, adjuvant chemotherapy (to be discussed) is thetreatment of choice for specific histology: immature teratoma grades 2and 3, endodermal sinus tumour, mixed cell tumour, and probably alsoembryonal carcinoma and choriocarcinoma. For other histology, definiterecommendations cannot be made. For patients with advanced orrecurrent disease, evaluation of responses to various platinum basedchemotherapy regimens will be presented.

RM4.05 PRIMARY OVARIAN FAILURE

RM4.05.03FERTILITY MANAGEMENTA.R. Genazzani , F. Cristello, F. Taponeco, G. D’Ambrogio, P.G. Artini,Department of Reproductive Medicine and Child Development, Divisionof Obstetrics and Gynaecology, University of Pisa, Pisa, Italia

Premature ovarian failure is a condition all in all similar to menopausethat occurs in women before the age of 40 years. It is estimated that 1-3% of women experience premature menopause. This is associated with10-20% of cases of primary amenorrhea and up to 18% of cases ofsecondary amenorrhea.The main causes of premature ovarian failure are: idiopathic, when oneisn’t able to establish a definite aetiology; genetic, like Turner’ssyndrome, pure gonadal dysgenesis and familial; immunological;iatrogenic, including surgical oophorectomy, chemotherapy andradiotherapy. Iatrogenic premature menopause is increasing becausepatients survive longer as a result of advances in cancer chemotherapyand radiotherapy.It is very important, for these women, to consider the involvement ofreproductive function, with the ultimate objective to guarantee both aphysical and mental health. In fact in most of these women themenopause condition is definite, only in some, in particular cancerpatients after chemotherapy or radiotherapy, may there be a partialrestoration of gonadal function.We may propose many solution to a woman in relation to the cause ofher condition. An early diagnosis is very important, especially inidiopathic and genetic disease, which enable us to intervene withassisted reproductive medicine protocols (ART); in women with an earlydiagnosis of secondary amenorrhea we can propose cryopreservation ofmature oocytes, embryo or ovarian tissue.It is important to think positive and to preserve the young women’sreproductive function also in neoplastic patients, which are frequentlyvery young, with cryopreservation techniques. For the remaining womenwho don’t have ovarian tissue any more, or in which it’s impossible towait for a gonadal stimulation, we can propose ART with donation ofgonadal cells or of embryo.

RM4.06 PRE-IMPLANTATION DIAGNOSIS

RM4.06.01PREIMPLANTATION GENETIC DIAGNOSISPeter Braude , Guy’s and St Thomas’ Centre for Preimplantation GeneticDiagnosis, Guy’s and St Thomas’ Hospital, London SE1 7EH

Preimplantation genetic diagnosis (PGD) is an early alternative toprenatal diagnosis that is suitable for patients who are at substantial riskof conceiving a pregnancy affected by a known genetic defect. PGD canbe performed for four broad groups of genetic disorders: recessive ordominant monogenic disorders - (PCR based tests), gender selection forsex chromosome linked disorders (generally using FISH) andchromosomal rearrangements (FISH). The range of genetic disordersdetectable at the single cell level is increasing, but the indications forPGD are still not clear cut and there has been public concern over itsmisuse, especially for social gender selection.It is our strong belief that PGD is should be seen as a natural extensionof a clinical genetic service rather than as an arm of assisted conception.Although some of the technology needed falls within the domain of theACU, diagnosis, molecular and cytogenetic expertise, precedingcounselling, decision making, diagnosis and post diagnosis support areall part of the day to day routine of a modern effective clinical genetics

unit. Although simple in concept, clinical implementation of PGD ismuch more labour intensive and demanding than any aspect of eitherassisted conception or clinical genetics.

RM4.06.02EMBRYO SELECTION BY PREIMPLANTATION GENETICDIAGNOSIS AND CYTOGENETIC ANALYSIS FOR INFERTILEMALESH.Kubo , 1stDept.OB/GYN, Toho University, School of Medicine,Tokyo, Japan

Objectives: The remarkable developments over the last twenty years inhuman genetics and assisted reproductive technology have made rapidprogress in preimplantation diagnosis. To examine the frequency ofchromosomal abberation ,we performed cytogenetic evaluation ofembryos fertilized by IVF or ICSI, ejaculated sperms and lymphocytesof infertile males.Study Methods: The subjects were 121 embryos of 47 IVF/ICSI cylesfor FISH analysis of embryonic aneuploidy and sperm & lymphocytes of1170 infertile male for chromosome abberation. Chromosomal analysisperformed on blastomeres with use of a multi colour FISH, and onlymphocytes with G-banding technique, FISH,Q-banding and C-bandingwere combined in certain cases.Results: The incidence of mosaic was 25% in IVF, 34% of ICSIembryos. There was no difference on aneuplody of embryos betweenIVF and ICSI.The incidence of aneuploidy was higher in infertile malesthan in subjects of proven fertility (P_0.002). The incidence of YY- andXY-bearing nuclei was increased in severe oligozoospermia.Conclusions: These results suggest an increased risk of aneuploidy in theembryo fertilized by IVF/ICSI, and also infertile male.

RM4.06.03PREIMPLANTATION GENETIC DIAGNOSIS: ETHICALCONSIDERATIONS.Klaus Diedrich, Michael Ludwig, Department of Gynecology andObstetrics, Medical University of Lübeck, Ratzeburger Allee 160, 23538Lübeck, Germany

Preimplantation genetic diagnosis (PGD) offers the opportunity todiagnose genetic disorders in embryos before their transfer. This is anoption for couples at high risk to have children with a special severegenetic disease. One might criticize, that with PGD there is a possibilityto diagnose also genetic conditions, which have no impact on childrenshealth. Others fear, that the logic consequence of PGD on a slipperyslope will be a manipulation of the embryonic genome, i.e. germlinetherapy and a „baby design“. However, if one realize, that pregnancytermination for whatever reasons nowadays is a widely acceptedprocedure, it is difficult to accept, that an embryo at the 8- to 10-cellstage in vitro is more protected than a fetus in the 2nd trimester. Even theargument, that pregnancy itself is a special situation which may lead toan otherwise not solvable conflict of the pregnant woman does not helpto overcome this controversy. Finally, one should discuss, why thepossible misuse of a technique must consequently lead to its prohibition,even if there are several advantages for certain couples in single cases.In our mind, there must be regulations before the introduction of PGD.These regulations should be designed to prevent misuse of PGD likediagnosis of conditons without impact on childrens health, sexing forsocial reasons or genome manipulation. Furthermore history has taught,that after 10 years of PGD worldwide, there are still only a limitednumber of couples, who really undergo this treatment. This shows, thatthe expected risk of a slippery slope might be overestimated.


SS4.08 SAFE MOTHERHOOD: IMPROVING ACCESS TOESSENTIAL OBSTETRIC CARE AT REFERRALLEVEL

SS4.08.01EXPERIENCES OF THE PMM NETWORK IN WEST AFRICAA. Kamara, Regional Prevention of Maternal Mortality Program,Mamprobi, Ghana

Though Maternal Mortality is said to be a rare event, the realities inAfrica is that it is not. The problem was highlighted in 1987 when theSafe Motherhood Initiative was launched. Since then various groups andorganizations have been trying to address the problem in diverse ways.One such group is the Regional Prevention of Maternal Mortality(RPMM) Network which is based in Africa. From 1988 -1996 thisNetwork (then known as the PMM Network) developed, implementedand evaluated projects that focused directly on improving emergencyobstetric care at health facilities, and facilitating early referral of casesfrom the community, to prevent maternal deaths. The Network did so byreducing barriers to appropriate care when obstetric complications occur,resulting in low Case Fatality Rates. This paper describes how this wasachieved. The first phase of the research was conducted in elevenselected rural communities in Nigeria, Ghana and Sierra Leone mainlyby university-based multidisciplinary teams. In the second phase, thethree countries registered as national NGOs and were pooled together asthe RPMM Network, an international NGO with headquarters in Ghana,by its director. The Network has embarked on expanding the programand providing technical assistance to other countries in Africa. The mainfocus is capacity development, in order to reduce the high numbers ofmaternal deaths in the Region.

SS4.08.03SAVE THE MOTHERS FUND PROJECT: COUNTRY PROJECTSAndré B. Lalonde , MD, MSc, FRCS, Executive Vice President, Societyof Obstetricians and Gynecologists of Canada (SOGC);Coordinator/Administrator, FIGO Save the Mothers Uganda-CanadaProject

In 1997, thanks to financial support received from the World Bank,UNFPA and Pharmacia & Upjohn, FIGO launched its Save the MothersFund Project. This initiative aims to mobilize the obstetric andgynecological community, in both developed and developing countries,to work in partnership to demonstrate the most cost-effective andsustainable way to reduce maternal mortality and morbidity.On the basis of set criteria, the project’s Steering Committee selectedfour(4) countries (Ethiopia, Mozambique, Pakistan and Uganda) and onegeographical area (a group of countries from Central America: ElSalvador, Guatemala, Honduras and Nicaragua) within which to conductneeds’ assessments and subsequently, demonstration projects.Each country or geographical area project is led by a “Country Team”composed of international experts of both a society of obstetric andgynecology of a developed and a developing country. Consequently,experts from Canada are twinned with colleagues from Uganda, Italywith Mozambique, Sweden with Ethiopia, the United Kingdom withPakistan and the USA with Central America.Each Country Team then conducted its own country situational analysisin order to determine the magnitude of maternal mortality and its maincauses, to evaluate the accessibility and efficiency of the existing healthinfrastructure as to essential obstetric care and finally, to establish theneeds as to facilities, equipment, supplies, training and availability ofpersonnel to provide easy access to emergency obstetric care.Followed the development of a proposal for a demonstration projectwithin each country or geographical area, which identified, as its mainmeasurable output, the number of cases of life-threatening complicationsadmitted to the health facilities and the outcome of their management.These projects were approved by the Steering Committee in September1998 and implemented in early 1999.Within the context of this presentation, the participants will have anopportunity to learn more about each Country Project as to:• The country’s maternal mortality and healthcare situations at the timeof the conduct of the 1998 situational analysis;• The project’s goal, objectives and main interventions;• Progress to date on the project’s activities;• Constraints;• Findings to date.

SS4.08.04GUIDELINES, TRAINING MATERIALS AND MONITORINGTOOLS (WHO)Jerker Liljestrand , World Bank, Washington, DC, United States

A national Safe Motherhood program requires a set of standards formaternal-newborn care at different levels, tools for training staff in-service and pre-service to achieve these standards, monitoring tools tofollow up, and a strategy and plan for the implementation including apackage for health system requirements.The WHO is developing a consistent set of materials to meet the aboveneed. A pocket manual on the management of complications inpregnancy and childbirth has recently been developed for use at thedistrict hospital level, and training materials are forthcoming. A similarmanual is under way for newborn care at this level. A set of 5 moduleson Life-saving skills for midwives is available, and used in training bothpre- and in-service. They cover hemorrhage, eclampsia, sepsis,obstructed labor and abortion complications. A set of basic standards forthe essential, minimum level of maternal health care has been developedtogether with an adaptation guide. A computer soft ware is beingdeveloped to help countries assess health system requirements and thecost for implementing above norms and standards and improve qualityof care.WHO will provide support to countries in order to adapt these materialsaccording to their needs and feasibility. This process is necessary forownership and country commitment for implementation."Guidelines for monitoring the availability and use of obstetric services"and a guide for district managers on the selection of reproductive healthindicators are available. An important tool to raise awareness of thepreventability of maternal deaths, and help to discuss local action, is theMaternal Death Review Tool.A series of important guidelines are available on family planning andpostabortion care. In the important area of blood safety, a set ofguidelines and training tools are available.The presentation will illustrate the above tools and guidelines, and howthey can be accessed.


FREE COMMUNICATIONS

FC4.01 CERVICAL INCOMPETENCE

FC4.01.01PREMATURE RUPTURE OF THE MEMBRANES (PROM) AT LESSTHAN 28 WEEKS OF GESTATION – EFFICACY OF FIBRINESEALING AND DOUBLE SHIRODKAR’S PROCEDUREK. Oura , K. Maitoko, E. Kimura, K. Ochiai, T. Tanaka, Dept. OB/GYN,Jikei University School of Medicine, Tokyo, Japan.

Objective: The fibrin sealing method involves sealing the rupturedmembranes by injection of fibrin glue into uterine cervix. We havedeveloped our own method for treating PROM, which consists of fibrinsealing and double circumferential suture of the cervix. We comparedour method with the conventional methods and results are shown here.Study methods: The subjects were 45 women who had leakage amnioticfluid at less than 28 weeks of gestation from January 1988 to December1997 at the Jikei University School of Medicine Hospital. These patientsgave informed consent to the study and were followed up for 2 years.They were divided into three groups: group A was 33 women treatedwith only using beta2-stimulant and antibiotics, group B was 5 womentreated with circumferential suture of the cervix, and group C was sevenwomen treated with our method. These groups were compared withrespect to the prolongation of pregnancy, fetal or neonatal death, and thesequelae of the offspring until 2 years of age.Results: Pregnancy was prolonged by a mean of 5.5 days in group A,63.4 days in group B and 110.0 days in group C. Eight out of 33 infantssurvived in group A and three had sequelae. In group B, four out of fiveinfants survived and three had sequelae. All seven infants survived ingroup C and none had sequelae.Conclusion: Our method seems to be useful for managing PROM at lessthan 28 weeks of gestation. Therefore, this method should be selectedfor the treatment of PROM.

FC4.01.02UMBILICAL TAPE FOR CERVICAL CERCLAGEU.L. Nagarseker , Dept. OB/GYN, Vasco-Clinic, Vasco-da-Gama, Goa,India.

Objectives: Cervical incompetence is a major cause of second trimesterabortions and cervical cerclage is the operation of choice using variousmethods. In this study, umbilical tape was used for tightening of cervicalOs.Study Methods: One hundred and twelve women had cervical cerclagedone in the last ten years using umbilical tape (Ethicon) as the suturematerial. Using a round body 45-mm needle, this tape was placed insubserous layer at the level of internal Os all around the cervix andtightened posteriorly. The procedure was done under general anesthesiaand was completed within 7-10 minutes.Results: 96.4% of women had live birth babies above 37 weeks. 22% ofwomen had elective cesarean for definite indications while another 11%had cesarean for either fetal distress or malrotation of head during labor.One patient had herniation of membranes at 28 weeks. The stitch wascut & the patient was given bed rest with tocolysis. She delivered at 35weeks a live healthy baby. In 5 women, the stitch was to be cutprematurely because of IUFD and congenital anomalies diagnosedbetween 22 and 32 weeks respectively.Conclusion: Umbilical tape, a simple & cheap material was used forcervical cerclage between 14 – 18 weeks of pregnancy in indicatedcases. 96.4% of women had full-term live babies without anycomplications of the tape.

FC4.01.03TRANSVAGINAL ULTRASONOGRAPHY IN DETECTION OFCERVICAL INCOMPETENCYM. Podobnik , M. Podgajski, B. Gebauer, Dept. OB/GYN, UniversityHospital Merkur, Zagreb, Croatia

Objectives: To examine the relationship between transvaginal ultrasoundcervical changes and pregnancy outcome in women at risk of cervicalincompetency and preterm delivery.Study Methods: In 100 pregnancies with clinical and ultrasonic signs ofcervical incompetency, the length of the cervix, the thickness of the

anterior wall of a lower uterine segment and the wide of theendocervical canal have been evaluated ultrasonically. These parameterswere followed longitudinally from the 10th to 36 gestation week in thehealthy pregnancies and pregnancies at risk for cervical incompetencyand preterm delivery.Results: In patients from 10 weeks to 14 weeks the cervix issignificantly longer than in the 25 to 36 week group and the anterior wallof the lower uterine segment in the 10 to 14 week group is significantlythicker than in the 20 to 36 week group. In pregnancies at risk forcervical incompetency, cervical lengths and wall thickness, weresignificantly different from those in comparable controls. Forty-fivepercent of the patients in the at-risk group, with cervical cerclage,delivered at 37,5 weeks and 8,5% of pregnancies ended in abortion whenthe amniotic membrane herniated into the cervical canal. The frequencyof preterm delivery was 60%, 38% and 15% for cervical length of <10mm, 10-20mm, and 20-30mm.Conclusions: A shortened cervix with decreased thickness of the anteriorwall of lower uterine segment and dilatated endocervical canal shows astrong association with cervical incompetency and preterm birth.

FC4.01.04PLASMA PROSTAGLANDIN CONCENTRATION AFTERCERVICAL CERCLAGE AND AFTER TRANSVAGINALULTRASOUND EXAMINATION DURING PREGNANCYH.S. Jamal , Dept. OB/GYN, King Abdulaziz University Hospital,Jeddah, Saudi Arabia.

Objectives:§ To investigate whether cervical cerclage technique at different

gestational age could raise the peripheral plasma level of 13, 14dihydro-15 ketoprostaglandin F (PGFM) to a significant level.

§ To investigate the relation between the magnitude of elevation anddifficult cases in duration of procedure of cervical cerclage.

§ To investigate the risk of transvaginal ultrasound examination inelevating the prostalglandin F2a

Design: Clinico-chemical prospective study.Setting: King Abdulaziz University Hospital, Jeddah, Saudi ArabiaSubjects: 35 patients having cervical cerclage at different gestational ageranging from 14-22 weeks and an other group of 15 having transvaginalultrasound examination at similar gestational age.Intervention: Peripheral plasma level of 13, 14 dihydro-15ketoprostaglandin F(PGFM) was measured before and after eachprocedure.Main outcome measure(s): Change in the level of Serum PGRM afterthe procedure.Results: A significant level of elevation of PGFM as found whencervivcal cerclage inserted particularly in difficult insertion and durationof procedure. There were no significant changes in PGFM aftertransvaginal ultrasound examination.Conclusion: Despite significant cleval of PGFM, no significant uterinecontractions justify the routine use of tocolytic drugs in cervicalcerclage. There is no risk of transvaginal ultrasound examination duringpregnancy.

FC4.01.05ASSESSMENT OF EFFICIENCY THE RECONSTRUCTION OF THEUTERINE ORIFICE OF CERVIX BEYOND THE PREGNANCYMaria Brzozowska, Elzbieta Lipecka-Kidawska, Wojciech Kazimierak,Teresa Pajszczyk-Kieszkiewicz

In the group of 72 patients the reconstruction of the interne orifice ofcervix was done because of infertility. The surgery was performedbefore the planned pregnancy.Until this study 67 of these women got pregnant. From among of them62 (92,5%) women delivered 6 of them (8,9%) twicely, 7 (10,4%) ofthem spontaneously aborted (2 of them delivered at term the next child).In the group of 67 pregnant women the time following the operation tothe conception, course of pregnancy, symptoms of thretened abortionand/or premature labor and symptoms of cervical insufficiency wereobserved. The cervices were clinically assesed and measured byultrasound - the length of cervix, width of orifice interne. The cerclagewas aplicated when the length of cervix was below 3,5 cm and/or thewidth of orifice interne was above 6 mm confirmed by ultrasound. Inspite of the operation in the group of 17 women there was a necessity of


cerclage application because of symptoms of cervical insufficiency.Inthe study group the incidence of the premature labors decreased to 8,9%comparing with 73,6% in the preoperative period. After the operationthe incidence of spontaneous abortion diminished to 10,4% from 90,2%in the preoperative period. The reconstruction of the orifice interne ofcervix beyond the pregnancy is a succesful method to protect the womenaffected by infertility from the loss the succeding pregnancy. It notprevents the cervical insufficiency in all cases. The verification byultrasound the clinic diagnosis of cervix insufficiency and an applicationthe cerclage seem to be a good way to improve the efficiency of theoperative reconstruction of the orifice interne of cervix with regard toduration of pregnancy.

FC4.01.06CERVICAL LENGTH MEASUREMENT AND PRETERMDELIVERYI.Hoesli , E.Daly-Grandeau, S.Ledermann, S.Tercanli, W.Holzgreve,Women’s University Hospital, Schanzenstrasse 46, Basel, Switzerland,4031.

Objectives: In symptomatic women cervical length measurement is aknown marker for the risk of preterm delivery, but cutoff values aredefined variably.Study Methods: A prospective observation study, approved by ourinstitutional review committee, included: 45 singleton pregnancybetween 20 and 33 + 6 weeks of gestation, preterm contractions (fourper 20 min), sonographic examination of the cervix at the time ofadmission before starting therapy. Controls consisted of 240uncomplicated singleton pregnancies with cervical length measurementbetween 20 and 34 weeks of gestation, who delivered all after 37 weeksof gestation spontaneously. In both groups cervical length was measuredunder standardized methods. Statistical analysis: Wilcoxon and Student’s T-test.Results: Rate of preterm delivery was 36% (16/45) in the study groupand 0% (0/240) in the control group. Cervical length in the study groupwas significantly shorter than in the control group (25.07mm ± 12.4 vs.37.4 mm ± 8.331, p = 0.001) at the same gestational age atultrasonographic examination (27.87 ± 4.0 vs. 28.97 ± 3.6). Those, whohad preterm labor and preterm delivery had a significantly shorter cervixcompared to the subgroup with preterm labor but term delivery: 18.5mm± 13.45 vs. 27.56mm ± 10.32, p = 0.02. With a cutoff value of 25 mmthe sensitivity, specificity, PPV and NPP were 81%, 61%, 59% and 82%respectively.Conclusion: Cervical length measurement is a reliable marker forprettier delivery in patients with prettier contractions. Nevertheless wepropose to search for concomitant markers to ameliorate its accuracy.

FC4.01.07EVALUATION OF RISK FOR PRETERM DELIVERY BY FETALFIBRONECTIN AND TRANSVAGINAL ULTRASONOGRAPHICMEASUREMENT OF CERVICAL LENGTHT.A. Oliveira (1), E. Souza (2), C.M.P. Carvalho (2), C. Mariani-Neto(1), L. Camano (2)Hospital Leonor Mendes de Barros, São Paulo, BrazilFederal University of São Paulo, Brazil

Objective: The purpose was to evaluate the risk of pre-term deliveryusing the fetal fibronectin test and transvaginal ultrasonography of thecervix in pregnant women with previous pre-term delivery.Study Methods: One hundred and seven women were enrolled in thestudy at 24th and 28th weeks’ gestation to detect the presence of fetalfibronectin and to measure the length of the cervix. Cervical length andfetal fibronectin were compared to assess the risk of pre-term birthbefore 34 and 37 weeks.Results: The spontaneous pre-term delivery rate was 37.4% (40/107).The analysis made by receiver operating characteristic curve indicated30 mm as the best cutoff to maximize sensitivity and specificity at 24and 28 weeks. The positive test of fetal fibronectin had a significantrelative risk (1.8; 95% confidence interval 1.1 – 2.8) to predict delivery< 37 weeks only at 28 weeks. The presence of short cervix (£ 30 mm) at24 and 28 weeks showed a significant relative risk for birth before 37weeks. In addition, short cervix at 24 weeks increased the risk fordelivery < 34 weeks (4.4; 95% confidence interval 1.3 – 15.6).

Conclusion: Cervical length measured by transvagianal ultrasonographyis better than fetal fibronectin for evaluating the risk of pre-term deliveryin women with previous pre-term delivery.

FC4.01.08EVALUATION OF CERVICAL INCOMPETENCE DURINGPREGNANCY USING TRANSVAGINAL ULTRASOUNDEXAMINATION WITH TRANSFUNDAL PRESSUREA. Makhlouf , A. Sabra, E. Hamed, G. Hamed, K. Zahran, Dept.OB/GYN, Faculty of Medicine, Assiut University, Assiut, Egypt.

Objectives: To evaluate the efficacy of transvaginal U/S exam of thecervix with transfundal pressure (TFP) in managing pregnant womenwith history, or with risk factors for cervical incompetence.Study MethodsOne hundred and fifty pregnant women without history or at risk factorfor cervical incompetence were chosen as control and scanned oncebetween 12-26 weeks gestation using ultrasound and TFP. Control groupshowed normal cervices and did not respond to TFP test and 96% ofthem reached term. Fifty pregnant women with history suggestive ofcervical incompetence or at risk factors for this condition were subjectedto transvaginal ultrasound examination with TFP test at the first visit at12 – 26 weeks gestational age. Patients whose cervices appeared normalultrasonographically before and after TFP were managed conservatively.Both the circlage and conservatively managed groups were subjected toserial transvaginal U/S exam with TFP every 2 weeks until 26 weeks ofgestation.Results: Eight women showed ultrasonic findings of cervical funneling,but did not respond to transfundal pressure. All underwent circlageplacement and 5 of them reached term. There were 15 women whosecervices initially appeared normal. Nine of then had circlage placementof which 7 reached term. The pregnancy in the 6 women who refusedcirclage ended in one term delivery and 5 preterm deliveries, there werethree women whose cervices showed ultrasonic findings of cervicalincompetence and further showed positive response to transfundalpressure. All of them miscarried in spite of having circlage placement.Twenty-four women showed no ultrasonic findings of cervicalincompetence and did not respond to transfundal pressure. They weremanaged conservatively and 22 of them reached term.Conclusions: Fundal pressure during vaginal U/S evaluation of thecervix assisted in detection of asymptomatic cervical incompetence, inthe decision of placement of a cervical circlage and in postoperativeprediction of the success of circlage.

FC4.02 CHLAMYDIA TRACHOMATIS

FC4.02.01APPLICATION OF NESTED PCR FOR THE DETECTION OFCHLAMYDIA TRACHOMATIS IN DIAGNOSING ANDMONITORING THE PATIENTS WITH PELVIC INFLAMMATORYDISEASE AND VAGINITISK. T. Choi (1), D. H. Bae (1), S. R. Cho (2)(1) Dept. OB/GYN and Clinical Pathology, Soonchunhyang University,

Chunan, Korea.(2) Dept. OB/GYN College of Medicine, Soonchunhyang University,

Chunan, Korea.

Objectives: PCR has generally been more sensitive than theconventional microbiological test for the detection of C. trachomatis,which has been a leading cause of sexually transmitted disease. Thepurpose of this study was to evaluate the prevalence of C. trachomatisinfection in the patients with pelvic inflammatory diseases (PID) and theusefulness of nested PCR as a follow-up test in the patients with C.trachomatis infection after administration of antibiotics.Study Methods: Cervical swab specimens were obtained from 187patients with PID and vaginitis attending the Soonchunhyang ChunanHospital. From the C. trachomatis positive patients, cervical swabspecimens were obtained one a week after treatment until PCR testednegative. We performed the nested PCR with Chlamydia-CR kit(Bioneer, Korea).Results: From 6(5.8%) of 187 cervical swab specimen, C. trachomatiswas detected by nested PCR. These patients were treated withdoxycycline and metronidazole for 7 to 14 days. All of 6 C. trachomatis


positive patients revealed PCR-negative immediately after thecompletion of antibiotic treatment.Conclusions: With the above results, the nested PCR is a relativelysimple, fast, and practical tool for the detection of C. trachomatis andmay be a useful follow-up test for monitoring the treatment effect.

FC4.02.02CHLAMYDIA TRACHOMATIS AND SPONTANEOUS ABORTIONP. Vigil , S. Zacharías, A. Tapia, R. Riquelme, J. Varleta.CEBRE and Faculty of Biological Sciences, P. Catholic University ofChile, Cruz del Sur 177, Las Condes, Santiago, Chile.

Objectives: Genital Chlamydia trachomatis (Ct) infection is the mostcommon sexually transmitted asymptomatic disease. It has also beensuggested as a dangerous pathogen for pregnancy. The objective of thiswork is to evaluate the incidence of Ct infection and determine itsprevalence and correlation in couples presenting with spontaneousabortions.Study Methods: A total of 961 women and 750 men attending at ourreproductive clinic (CEBRE, Santiago, Chile) were studied for thepresence of Ct using direct immunofluorescense. The incidence of Ct inthe general population, was compared with the incidence in women andcouples who had a history of one or more spontaneous first trimesterabortions.Results: The general incidence of Ct infection was 11.3% (194/1771). Inwomen it was 9.4% (90/961) and in men 13.9% (104/750). In womenwith spontaneous abortion, it was 21% (14/66) as compared to 8,9%(23/59) for women with a term pregnancy (Chi-square, P<0.05).Considering the couple (one or both infected), the incidence raised to68.8% (22/32) (Chi-square, P<0.001).Conclusions: The incidence of Ct infection was higher in women andcouples with spontaneous abortions than in the general populationattending our Clinic. These results show a correlation between Ct activeinfection and spontaneous abortion. Further studies should be done toelucidate the role in the pathogenesis of early abortions of the immuneresponse to heat shock proteins, present in human cells and expressed bythe zygote, which is triggered by Ct infections.

FC2.02.03THE CONDITION OF MICROBIOCENOSIS OF THE SEXUALORGANS IN PATIENTS WITH CHLAMYDIA INFECTIONT. V. Sevostyanova , V. K. Chaika, B. A. Iotenko, Donetsk StateRegional Center of Maternity and Child Protection, Donetsk, Ukraine

Objectives: To study the condition of microbiocenosis of the sexualorgans in women with chlamydia infection. We carried out the study ofmicrobiocenosis of the sexual tracts in 138 patients of the reproductiveage, with chlamydia infection.Study Methods: The diseases of the cervix uteri were revealed in 59patients (pseudoerosion, endocervicitis, leukoplakia, and dysplasia of theepithelium), relapsing candidiasis vulvovaginitis (42 patients); infertility(20); abortions in different terms of pregnancy were noted in the history7 women. Twenty-eight persons had genital chlamidiosis in their history,and they received specific treatment in special medical institutions.Serological investigations of blood serum for revealing specificchlamydia and herpetic antibodies IgG,M,A were carried out withimmunofermental and immunoperoxidatic methods. Bacterioscopy andbacteriology, pH-metry were used. In the study of microbiocenosis ofthe cervical canal in 109 (78.9%) women with Chlamydia infection theother pathogenic and conditionally- pathogenic micro-organisms(enterococi, colibacillus, ureaplasms) were revealed.The highest percentage of the infection associated with urogenitalchlamidiossis is viral (CMV, VPH) and candidosis in 45 (41.2%), virusherpes and chlamydia in 11 (10%).In the investigation of the saprophytic microflora of the urogenital tractin the patients with chlamydia infection it was established thepredominance of colibacillus in the discharge from the sexual tractsamong examined persons. More seldom protein, staphyloccus aureusand different types of staphylococci were cultured. pH change toalkaline side (pH>4.5) was observed in 42 (30%) cases.Conclusions: The women with different impairments of the reproductivefunction, the chlamydia infection in 87% of cases associated with otherinfection. And it is evident that affect on the success in the cure ofchlamydia infection.

FC2.02.04THE PECULIARITIES OF CURRENT OF GENITALINFLAMMATORY PROCESS IN SEXUALLY ACTIVEADOLESCENTS AND WOMEN OF FERTILE AGEA. Rudenko, O. Romashchenko , A. Romanenko, M. Spivak,L. Yakovenko, E. Shalkovsky. Institute of Urology and Nephrology,Institute of Ped., Obst/Gyn, Kiev, Ukraine

Objectives: The aim of our study was to carry out the comparativeanalysis of the current of pelvic inflammatory disease in sexually activeadolescents and women of fertile age.Materials and Methods: Blood, scrapes of urethra and cervical channels,fragments of uterine tubes obtained during laparotomy. There wereexamined two hundred and twelve sexually active adolescents aged from15 to 18 years who were admitted for conservative treatment and twentypatients – for surgical one, one hundred and twenty eight women agedfrom 24 to 35 years with chronic genital inflammation, 28 among themwere operated in connection with tube infertility.Results: The carried analysis showed the predominance of chlamydia(43,4%), mycoplasma (21,7%), ureaplasma (12,7%), gardnerella(23,1%), trichomonade (13,7%) in etiological spectrum during genitalinflammatory disease in sexually active adolescents. These factors in96,7% of cases were presented in associations. Ureaplasma (22,7%),mycoplasma (16,4%), chlamydia (14,8%), gardnerella (10,4%) wererevealed in women of fertile age with chronic genital inflammation in55,5% of cases in microbial associations. The changes of cytokinesstatus caracterized by oppression of a- and g-interferon production weredetermined during immunological study in both groups of patients. Theincrease of FNP production and disorder in links of local (decrease ofSIgA level), cellular and humoral immunity during prolongedinflammation were more expressed in women than in sexually activeadolescents. In tissue of uterine tubes of sexually active adolescents andwomen of fertile age (accordingly) there were found out chlamydia(25,0% and 28,6%), mycoplasma (15,0% and 14,3%), enterobacteria,staphylococcus, streptococcus (30,0% and 21,4%). The significantchanges of hystoarchitectonics of tube were determined duringchlamydiosis (the expressed destruction of organ) and mycoplasmosis.Resume:Sexually active adolescents represent the high risk group as toreproductive health in the future. The determined disorders ofhystoarchitectonics of uterine tubes according to the nature of etyologicfactor of inflammation on the background of immune disorders are thebasis of development of deep changes of reproductive organs in womenof fertile age. This fact leads to the infertility or fetus and newbornpathology.

FC4.02.05REPRODUCTIVE TRACT INFECTION, SYMPTOMS ANDSYNDROMIC MANAGEMENT IN RURAL GAMBIAN WOMENR Bailey1, R Coleman 1 , B West1, L Morison2, G Walraven1

1. Medical Research Council Laboratories, P.O. Box 273, Banjul, TheGambia

2. London School of Hygiene and Tropical Medicine, Keppel Street,London WC1E7HT, UK

Objectives: Assessment of reproductive tract infections (RTIs),relationship to symptoms and implications for syndromic managementin a rural Gambian population.Study methods: Women of reproductive age were questioned aboutcurrent RTI symptoms, screened for RTIs including bacterial vaginosis(BV), trichomonas(TV), N.gonorrhoeae, Candida, and C.trachomatis,and assessed for depressive symptomatology using the Edinburghdepression scale (EDS) (abstract Coleman et al). The sensitivity,specificity and predictive values of the WHO primary care algorithm forabnormal vaginal discharge (AVD) were examined.Results AVD was reported by 102/1344(8%) of women. BV was foundin 36%, Candida in 11%, TV in 6%, and Chlamydia in 1.5% of womenscreened. TV and EDS>11, but not BV, Candida or Chlamydia wereassociated with a complaint of AVD. The WHO primary health AVDalgorithm would have treated all 102 women for BV, TV, Candida andcervical infections meaning that 48 proven infections and 60 subjects inwhom no infection was demonstrated would have received treatment.Only 1/11 chlamydial infections, 11/68 trichomonas infections, and29/380 cases of BV would have been treated. Depressive symptoms(EDS>11) were not significantly associated with a proven RTI. Use of


the WHO speculum algorithm with bedside tests would have treated agreater proportion of BV and TV but none of the chlamydial infections.Conclusions: The syndromic management approach has low sensitivityagainst laboratory proven infection in this low risk rural population. Riskassessment for depression did not significantly improve the positivepredictive value of the algorithm.

FC4.02.06AN ASSESSMENT OF DIAGNOSTIC TESTS FOR THEDETECTION OF ASYMPTOMATIC Chlamydia trachomatis-ASYSTEMATIC REVIEWE.J.Honey* , I.T. Russell, A.A Templeton**Dept of Obstetrics and Gynaecology, Aberdeen University, Aberdeen,Scotland, UK and Dept of Health Sciences, York University, York,England, UK.

Objectives: Screening women for lower genital tract infection withChlamydia trachomatis(CT) is important in the prevention of pelvicinflammatory disease, ectopic pregnancy and infertility. This systematicreview aims to state clearly which of the available diagnostic tests forthe detection of CT would be most effective.Study Methods: The review included all studies published from 1990onward that evaluated diagnostic tests in asymptomatic, young, sexuallyactive populations. Medline and Embase were searched electronicallyand key journals were hand searched. Further studies were identifiedthrough the internet and contact with experts in the field. All studieswere reviewed by two reviewers and were scored using Irwig’sassessment criteria (Annals of Internal Medicine 1994;120). Additionalquality assessment criteria included a documented sexual history andrecording of previous CT infection. The reviews were subject to meta-analysis and meta-regression.Results: The 30 studies included examined DNA based tests, LigaseChain Reaction (LCR), Polymerase Chain Reaction (PCR) and geneprobe as well as Enzyme Immuno-Assay (EIA). The results showed thatwhilst specificities were high, sensitivities varied widely across the testsand was also dependant on the tissue sample tested. Pooled sensitivitiesfor LCR, PCR, gene probe and EIA on urine were 96.5%, 85.6%, 92%and 38% respectively whilst on cervical swabs PCR, geneprobe and EIAwere 88.6%, 84% and 65%. Meta analysis demonstrated that DNAamplification techniques performed best both in urine and on swabs inlow prevalence populations.Conclusions: Nucleic acid amplification tests used on non-invasivelygathered samples such as urine are very effective at detectingasymptomatic CT infection. Further studies are required inasymptomatic women evaluating self-obtained vulval swabs.

FC4.02.07DETECTION OF CHLAMYDIA TRACHOMATIS INTRAUTERINEINFECTION BY USING CHORIONIC VILLOUS SAMPLING ANDPOLYMERASE CHAIN REACTIONZ.W. Dong (1), S.Y. Zhou(2), R.M. Liu(1)(1) Dept, Molecular Biology, National Research Institute for FamilyPlanning, Beijing, China.(2) Dept Medical Genetics, Henan Research Institute for FamilyPlanning, Zhengzhou, China.

Objectives: Chorionic villous sampling (CVS) and Polymerase chainreaction (PCR) were used to detect Chlamydia Trachomatis(C.Trachomatis) Intrauterine infections in the early pregnancy.Study Methods: In order to detect the C.Trachomatis intrauterineinfections in pregnant women, the cervix specimens, CVS and PCRwere used to detect C.Trachomatis in DNA of chorionic villi andcervices specimens was amplified by PCR.Results: 11 cervix specimens in 100 pregnant women were positive ofC.Trachomatis infections. In this study, the prevalence of C.Trachomatisinfections is about 11.0%. 100 specimens of CVS were analyzed byPCR, and 7 samples of chorionic vili were positive of C.Trachomaticinfections. The incidence of C.Trachomatis intrauterine infections in theearly pregnancy was 7.0%Conclusions: The transmission of C.Trachomatis from mother to fetus inthe early pregnancy is a possible pathway of the intrauterine infections.CVS in the early pregnancy and PCR method could be developed atechnique for prenatal diagnosis of C.Trachomatis intrauterine infectionsin the first trimester of pregnancy.

FC4.02.08CHLAMYDIA TRACHOMATIS AND HABITUAL ABORTIONS. ISTHERE ANY RELATION?M. Bogavac (1), S. Milosevic (1), M. Pavlov-Mirkovic (1), E. Mrdja (2),J. Jovanovic-Privrodski (1), A. Radulovic (1).(1) Dept. OB/GYN, Clinical Center of Novi Sad, Novi Sad, Yugoslavia.(2) Institute of Health Protection, Unit for Virology and Immunology,

Novi Sad, Yugoslavia.

Background: The role of chlamydial infection or abnormal colonizationof the genital tract has been recognized as an important factor of habitualabortions in the past years.Objective: The aim of this study was to evaluate possible involvement ofChlamydia trachomatis infection in habitual abortions and to estimatethe incidence of habitual abortions in the patients infected by Chlamydiatrachomatis in relation to normal course of pregnancy.Patients and Study Methods: The investigation comprised a randomchoice sample of 67 pregnant women. The procedure of directfluorescent microscopy (DIF) and ELISA test were used in diagnosis ofChlamydia trachomatis.Results: Investigation comprised a random choice sample of 67 pregnantwomen. The investigated group included patients with habitual abortions(N=37) versus the control group of patients with normal pregnancy(N=30). In the investigated group of patients with habitual abortions(N=37), a positive DIF test to Chlamydia trachomatis was recorded in 10(27.02%) versus 5 (16.67%) patients from the group of normal coursepregnancy. Nevertheless, when the ELISA test applied, the IgG titer wasequal or more than 1/32 in 6 (16.22%) patients with habitual abortions.All patients with normal pregnancy had negative ELISA – test.However, the difference between the values of the ELISA –test inpatients with habitual abortion and with normal pregnancy wasstatistically significant (c2=5.34; p<005).Conclusion: The results of our investigation point to the need ofdiagnosis and treatment of Chlamydia trachomatis infection, particularlyin the women with habitual abortions. In order to prevent habitualabortions and poor outcome of pregnancy and successfully manageChlamydia trachomatis infection, it is necessary to apply a directprocedure of identification of the antigen in endocervical smears andindirect procedure of identification of specific antibodies in the serum.

FC4.02.09REASSESSING RISK ASSESSMENT IN PREDICTINGCHLAMYDIA RACHOMATIS GENITAL INFECTIONS INADOLESCENT FEMALESA. Markovic (1), K. Sedlecki (2), Lj. Markovic (3), M. Markovic (2), G.Rajin (2)(1) University Clinic of Obstetric and Gynecology, Belgrade,Yugoslavia, 11000(2) Mother and Child Health Care Institute of Serbia, Belgrade,Yugoslavia, 11070(3) Microbiological Institute of Medical Faculty, Belgrade, Yugoslavia,11000

Objectives: The aim of the study was to investigate the significance ofvarious socio-demographic characteristics, sexual behavior indicatorsand clinical features in predicting Chlamydia trachomatic genitalinfections (CTGI) in adolescent females.Study Methods: Three hundred sexually active girls aged 19 wereinterviewed and investigated for the presence of CTGI by directimmunofluorescence test. For reassessing risk assessment step-wisemultivariate linear regression avalysis was performed.Results: The rate of CTGI is study group was 30.3%. Significantassociation with DTGI was estimated for: the presence of cervicalectopy, the negative attitude toward the condom use of either one of thesexual intercourse, the nondiscriminating approach to sex partnerrecruitment, and the older age of first sexual partner. These variables,however, had low predictive value (S R2 = 0.2701).Conclusions: There are various risk factors that are significantlyassociated with CTGI in adolescent females, but these findings are oflow predictive value. The prevalence of CTGI in the population ofsexually active adolescent girls in Belgrade is very high. Because of that,the screening of all sexually active adolescent females is the only way toidentify those that are infected.


FC4.03 ENDOMETRIOSIS – THERAPEUTICS

FC4.03.01VAGINAL ENDOMETRIOSIS MANAGEMENTSafwat Tosson , I. Hassan. Hartlepool General Hospital, Holdforth Road,Hartlepool, UK TS24 9AH.

Endometriosis usually affects pelvic peritoneum, uterosacral ligaments,adnaxa and rectovaginal septum. Vaginal endometriosis occurs in 1-3%of all cases of endometriosis.A 38 years old woman who is known to have endometriosis, who failedto respond to medical treatment including 6 months of GnRH analoguewith add back HRT therapy. Her residual symptoms were dysparunia,dysmenorrhea and lower abdominal pains.She opted to have total abdominal hysterectomy and bilateralsalpingoopherectomy. On removing the uterus spots covering an areameasuring between 7x 5 mm of endometriosis on the posterior vaginalwall was suspected.To visualise the lesions better, we used the laparoscopic camera. Therewere no nodules felt in the rectovaginal space so we consider this as acase of superficial vaginal endometriosis. Patient was seen 3 months later, all her symptoms has improved.Vaginal endometriosis is considered a secondary implantation of pouchof Douglas or rectovaginal septum endometriotic foci. The mostcommon localisation is the posterior vaginal fornix and cyclicdevelopment produces dysparunia. It is of paramount importance toinspect the vagina thoroughly in those women who complain mainly ofdysparunia.Oestrogen is usually prescribed following TAHBSO. We recommendthe use of combined continuous HRT to suppress the residualendometrial tissues, to protect against development of endometriomaand malignant transformation of vaginal endometrioses which is welldocumented in the literature with the prolonged use of exogenousunopposed oestrogen. We recommend patients whom main symptom isdysparunia a thorough preoperative assessment and intraoperativeexamination of the vagina.

FC4.03.02GONADOTROPIN-RELEASING HORMONE AGONIST PLUS'ADD-BACK' FOR THE TREATMENT OF ENDOMETRIOSIS. APROSPECTIVE, RANDOMIZED, PLACEBO CONTROLLED,DOUBLE BLIND TRIAL.H.R. Franke, Dept. OB/GYN, Medisch Spectrum Twente HospitalGroup, PO Box 50000, 7500 KA Enschede, The Netherlands; P.H.M.van der Weijer, Dept. OB/GYN, ZCA Hospital Center, PO Box 9014,7300 DS Apeldoorn, The Netherlands; T.M.M. Pennings, Dept.OB/GYN, Gemini Hospital, Huisduinerweg 3, 1782 GZ Den Helder,The Netherlands; M.J. van der Mooren, Dept. OB/GYN, AcademicHospital Vrije Universiteit, De Boelelaan 1117, 1007 MB Amsterdam,The Netherlands.

Objectives: To assess the effects of continuous combined estrogen-progestin as add-back therapy compared to placebo on the gonadotropin-releasing agonist (goserelin) induced hypoestrogenic state (climactericcomplaints and loss of bone) while maintaining effectiviness onendometriotic lesion healing.Study Methods: Forty one premenopausal women with laparoscopicallydiagnosed endometriosis with AFS-R (American Fertility SocietyRevised classification of endometriosis) scores of 2 or more wereincluded in this prospective, randomized, placebo-controlled, doubleblind trial.A follow up laparoscopy was performed at the end of the 24 weeks oftreatment.Results: There was a statistically significant reduction of endometrioticimplants in both groups. The decrease in the GnRH agonist plus placebogroup was 78.6% and in the GnRH agonist plus HRT group was 69.0%.This difference was not statistically significant (P = 0.64). In the GnRHagonist plus placebo group there was a decrease of 5.02% of the bonemineral density of the lumbar spine, compared to an increase of 0.18%in the GnRH agonist plus HRT group. This difference was statisticallysignificant (P<0.001). The subjective side effects in the GnRH agonistplus HRT group was statistically significantly less compared with theGnRH plus placebo group (P = 0.0004).Conclusions: The effectiviness of GnRH agonist treatment forendometriosis was not decreased by the addition of continuous

combined HRT treatment as add-back, while the bone mineral density ofthe lumbar spine was maintained and the subjective side effects werediminished.

FC4.03.03SAFETY AND EFFICACY PROFILE OF A HIGH DOSETREATMENT OF ENDOMETRIOSIS WITH 20 MG DIENOGESTPER DAYC. Moore (1) , A.E. Schindler (2), A.Müller (1), B.Christensen (2), (1)Jenapharm GmbH & Co. KG, Otto-Schott-Strasse 15, Jena, Thuringia,Germany, D-07745, (2) Center of Gynecology and Obstetrics, Essen,Germany.

Dienogest (DNG) is a unique 19-norprogestin. In rat endometriosisDNG is 10 times more effective than Danazol. These effects were alsoevident in women. With a low dose of 2mg DNG/day we foundexcellent results. The aim of this study was to test DNG in a higher dose.In former studies 100mg metroxyprogesterone acetate daily was used inendometriosis patients. The equivalent for DNG is 20mg daily.Therefore, this study was conducted to investigate the efficacy and thesafety profile of 20mg DNG per day as a endometriosis treatment.In a clinical study 21 patients with histologically proven endometriosis(rAFS score stages I-IV) were treated with 2x10mg DNG daily over 24weeks.The treatment outcome was evaluated on the basis of laparoscopicalfindings and the reported symptoms. The safety was judged by sideeffects, bleeding pattern and well-being. Possible influences onmetabolic pattern and endocrine system were monitored by subsequentserum analyses.The clinical findings confirme the expects, i.e. that DNG is very wellsuited for treatment of endometriosis. The reduction of the rAFS scoreand the clinical symptoms was significant. Mostly, the changes inmetabolic parameters were in the normal range. An increase in HDL3-cholesterol indicates a lower cardiovascular risk. Side effects occuredvery seldom with. The rate of 65% spottings was into the limit ofexpectance during a progestin only treatment.On account of reported side effects, the laboratory and laparoscopicalfindings these results show that 20mg DNG per day is an effective, andwell-tolerated treatment of endometriosis.

FC4.03.04TREATMENT OF ENDOMETRIOSIS AND INFERTILITY BYLONG ACTING GONADOTROPIN RELEASING HORMONEANALOG SOLELY vs LONG ACTING GONADOTROPINRELEASING HORMONE ANALOG WITH PREDNISOLONEM.Colakoglu , A. Acar Dept.OB/GYN, Selcuk University Hospital,Konya, Turkey

Objectives: The aim of the study was to investigate the effectiveness ofadditional immunologic suppression of endometriosis with prednisoloneto long acting gonadotropin releasing hormone analog (LA GnRH).Study Methods: Ninety-two infertile women with endometriosis AFSscore 2 and lupus anticoagulant positive (LAP) in peritoneal fluidincluded in this study.Patients divided into two groups.Results: In group A there were thirty-seven pat_ents and the mean agewas 31.8 +/- 4.4 (range 26-41 years) , duration of infertility was 8.2 +/-2.1 (range 2-15 years)treated with LA GnRH plus prednisolone and ingroup B there were fifty-five patients and the mean age was 34.3 +/- 3.2(range 24-42 years), duration of infertility was 9.1 +/-3.2 (range 5-12years) treated with LA GnRH solely. The pregnancy rates were 32.3%to25.7% respectively. in the first twelve months after ceasing thetreatment.Conclusions: Additional prednisolone to LA GnRH is promising in thetreatment of infertility due to endometriosis in LAP cases.


FC4.02.05ROLE OF LOWDOSE ORAL CONTRACEPTION IN TREATMENTOF ENDOMETRIOSISM. Bendova , Dept. OB/GYN, 1st Faculty of Medicine, CharlesUniversity, Prague, Czech Republic.

Objectives: Pelvic edometriosis can or need not be connected withfertility disease. Nearly always it creates problems (dysmenorrhoe,dyspereunia and pelvic pain) requiring gynecologic examination.Disease stages of endometriosis express AFS-score and are determinatedby laparoscopy. Present conservative therapy of endometriosis is basedon several month long application of inhibitors hypophyseousgonadotropins or analogues of gonadoliberins. After completing maintherapy symptomless period follows but hormonal activity again appearsand endometriosis again occurs.Study Methods: Goal: to fix an optimal status achieved by treatment forwhich eliminating or decreasing endometriotic lesions (lower stagesaccording to AFS classification) is characteristic and correlates withabsence of clinical manifestation of the disease. After successfulcompleting the main treatment confirmed by second look laparoscopy,women not wishing immediate gravidity are changed to low dose oralcontraception. It secures contraceptic affect, regulates cycle (frequencyand blood loss) and fixes absence of clinical manifestation ofendometriosis. Those parameters are monitored.Results: Low dose drug Mercilon started to be applied in a group ofwomen treated for endometriosis with appearance of hormonal activity(menstrual cycle). It has fixed satisfactorily clinical effect of treatmentby inhibitors of hypophyseous gonadotropins and by analogues ofgonadiliberins for the whole period of applying Mercilon.Conclusions: Secured therapy of low dose oral contraception has beenapplied to women not wishing to be pregnant treated by analogues ofgonadoliberins and by inhibitors of hypophyseous gonadotropins forendometriosis. Low does of estrogen did not stimulate evaluation ofendometriosis, on the contrary, balanced level of hormones fixed effectreached by the main therapy. At the same time it also fulfillscontraceptive effect. It has no side androgenic effect in comparison withonly gestagen therapy. After stopping Mercilon probability of plannedpregnancy increases.

FC4.03.06ESTROGEN «ADD-BACK» AND SOME MENOPAUSAL CHANGESASSOCIATED WITH GnRHa THERAPYWR Al-Omari , UN Nassir, B. Izat, WR Sulaiman. Medical College,University of Baghdad, Bab Al-Mutham, Baghdad, Iraq.

Objectives: To confirm the effects of GnRHa therapy on lipid profileand investigate the reversibility of these changes by adding estrogen.Study methods: Twenty patients with documented endometriosis wereincluded in this prospective study, all were treated for 24 weeks withTriptorelin 3.75mg «Decapeptyl» every 4 weeks, and alone for the first 8weeks, after which «add-back» estrogen «Premarin 0.625mg/day» wasadded. Three blood samples were obtained for each patient beforestarting treatment, 8 weeks and 20 weeks later.Results: Adverse biochemical effects on lipid profile were confirmed,symptoms of hot flushes and anxiety were greatly relieved after addingestrogen, however no significant beneficial statistical evidence wasattained regarding the adverse biochemical effects on lipid profilemainly LDL and LDL/HDL ratio.Conclusion: These results confirm the estrogen threshold hypothesis byshowing that estrogen add-back at the dose used will relievehypoestrogenic symptoms but will not prevent the possible atherogenicrisk.

FC4.03.07EFFECTIVENESS OF LONG TERM GN-RH AGONISTADMINISTRATION FOR TREATMENT OF ENDOMETRIOSISCOMBINED WITH ESTROGEN-PROGESTOGEN ADD BACKTHERAPYK. Aisaka , K. Nakagawa, T. Uesato, A. Miwa, T. Koshino, F. Ooka, M.Nishihira, M. Sadatsuki, S.G. Liang, M. Kaibara and H. Mori, Dept.OB/GYN, Ichihara Hospital, School of Medicine, Ichihara, Chiba,Japan.

Objectives: To elucidate whether the long term Gn-RH agonistadministration with add back therapy was effective for treatment ofsevere endometriosis.Study Methods: Fifty-three cases treated with Gn-RH agonist(leuprorelin) were subjected under the enough informed consent. Theywere divided into two groups at random; A: performed add back therapyusing EP preparations (Sophia-AÔ, containing mestranol 0.05mg andnorethisterone 1mg/tab, 1tab/day), 29 cases, and B: control, without addback therapy, 24 cases. Leuprorelin was administered for 3 years ingroup A, and for 6 months in group B, and the improvements ofhypoestrogenic symptoms, changes of serum various hormone levels, r-AFS scores and effects on the bone mineral density (BMD) usingDEXAÔ (L1-L4) were investigated between two groups.Results: The hypoestrogenic symptoms (hot flush, headache, etc.) wereimproved significantly by the add back. Serum gonadotropins, estroneand estradiol levels in the subjected patients of both groups decreasedmarkedly during Gn-RH agonist treatment. Slight but significantincreases were observed in serum estrone and estradiol levels (estrone;24.7±8.4 ®43.8±19.6, estradiol; 9.9±0.7®24.5±10.7pg/ml, p<0.01,before ® during) with add back therapy. There was no significantchange in r-AFS score of the severe endometriosis after 6 months of thetreatment, however, the significant improvements were observed after 3years of the treatment in the group A compared to those before treatment(n=11: 110.3±62.5®43.2±21.1, p<0.001). The BMD values showed asignificant decrease during Gn-RH agonist administration without theadd back (A: 1.08±0.17®1.07±0.18, B: 1.09±0.15®0.87±0.20g/cm2,p<0.05).Conclusions: Long term administration of Gn-RH agonist with EP addback therapy is very effective for the treatment of severe endometriosiswithout any complications.

FC4.03.08EFFECTS OF ESTROGEN REPLACEMENT ISOLATED ANDASSOCIATED WITHGESTRINONE IN OOPHORECTOMIZEDADULT RATS WITH EXPERIMENTAL ENDOMETRIOSISVR Lobo ; E Schor; EC Baracat; CE Lang; V Freitas; MJ Simões; JMSoares Jr; G Rodrigues de Lima.Department of Gynecology - Escola Paulista de Medicina, FederalUniversity of São Paulo, Brazil.

Objective: The aim of this work was to analyze the effects of conjugatedequine estrogens and gestrinone in oophorectomized adult ratspreviously submitted to endometrial implants.Study Methods: 50 adult female rats in which an endometrialimplantation was made on the lateral abdominal wall. After four weeks anew laparotomy was achieved where implant sizes were measured,followed by bilateral oophorectomy. After six weeks, the animals wererandomly divided into five groups: G I (n=10) received 0,5 ml/day ofpropylenoglycol (control), GII (n=10) received CEE (50 mg/day), GIII(n=10) received CEE (25 mg/day), G IV (n = 10) received CEE (25mg/day) associated with gestrinone (2,5 mg/day); GV (n = 10) receivedCEE (50 mg/day) associated with gestrinone (2,5 mg/day). All animalswere daily treated for 21 consecutive days by subcutaneous route. Afterthis period the animals were submitted to a new laparotomy and theimplants were measured and resected for light microscopy analysis.Results: The results showed a meaningful growth of endometrialimplants group GII, which presented as vesicles with clear liquidcontent. Light microscopy showed the presence of endometrial tissuecontaining stroma, glands and well-developed cysts. There wasregression of implant in groups GI, GIII, GIV and GV, and itslocalization was possible only due to the presence of surgical material.Conclusion: Only 50mg CEE promote growth of endometrial implantsand gestrinone opposed the CEE effects.


FC4.03.09COLOUR DOPPLER ULTRASOUND ANALYSIS OF UTERINEBLOOD VESSELS IN WOMEN WITH ENDOMETRIOSISTREATED BY GONADOTROPHIN RELEASING HORMONEAGONIST ZOLADEXM. Vasiljevio , Dept. OB/GYN, Clinic of GYN/OB, Belgrade,Yugoslavia.

Objectives: The aim of the study was to evaluate if and how thehormone changes which happen during the application of GnRH agonistZoladex in treatment of women with endometriosis influence blood flowin uterine blood vessels.Materials and Methods: We examined 18 patients with endometriosis.The average age of the patients was 29 ±4 years (range of 23-35 years).The degree of endometriosis was evaluated according to the rAFS score(stages I-IV). All patents were treated with Zoladex 3.6mg, 1 ampuleevery four weeks during three months. A hormone analysis (FSH, LH,E2, PRL, T) and evaluation of chemodynoamic changes at the bloodflow level in A. uterine and in A. spiralis was done for all patients beforeand after therapy. We analyzed the resistance index, the pulsatility indexand maximum velocity of low in systole by using the transvaginal colorDoppler ultrasound.Results: The serum concentrations of the above mentioned hormoneswere several times lower, after a three month Zoladex therapy. Theaverage hormone concentrations before therapy were: FSH 15 IU/ml,LH 12 mIU/ml, E2 118 pg/ml, PRL 20 mg/ml, T 1,2 nmol/ml and aftertherapy these values were: FSH 6 mIU/ml, LH 1.2 mIU/ml, E2 14 pg/ml,PRL 8 ng/ml, T 0,4 nmol/ml.The average values of the chemodynamic parameteres in the A. uterineblood flow before therapy were: RI=0.76, PI =2.5, PSV=4.8 cm/sec,while these values after therapy were: RI=0.89, PI=3.6, PSV=32 cm/sec.Similar chemodynamic changes were found in the A. spiralis bloodflow, but they were slightly lower.Conclusion: The application of GnRH analog Zoladex leads to asignificant increase of resistance in the uterine blood vessels, whichsignificantly lowers the blood flow of the uterus. These changes occurdue to the changes in the hormone status, as a result of the decrease ofthe oestradiol serum level.

FC4.04 HUMAN IMMUNODEFICIENCY VIRUS

FC4.04.01CLINICAL AND VIROLOGICAL FEATURES OF HIV-ASSOCIATED GENITAL LESIONS IN HIV INFECTED WOMENR. Sposetti (1), M. Franzetti (2), A. Del Mistro (2), E. Bonldi (3)(1) Dept. OB/GYN, S. Bortolo Regional Hospital, Vincenza, Italy.(2) Dept. Path/Anat., S. Bortolo Regional Hospital, Vincenza, Italy.(3) Dept. Infectious Diseases, Padua University, Padua, Italy.

Objectives: The aim of the study was to evaluate the evolution of genitallesions in HIV-infected women in relation to the degree ofimmunodeficiency and the antiretroviral treatment.Study Methods: Between August 1994 and December 1998, 229 HIV-positive patients had been enrolled and a case of invasive vulvarcarcinoma in a 13-year old girl with vertically acquired HIV infectionhave been observed and followed up since July 1996. At each visit,colposcopy, PAP smear test and PCR-based HPV detection and typingwere performed.Results: At inclusion, SIL prevalences were 31% for low-grade (LG)and 14.4% for high-grade (HG), while 2.6% presented carcinoma in situ(CIS). HPV prevalences were 65.7% for LGSIL, 93.3% for HGSIL and83.3% for CIS, also 21.2% of women with a negative PAP test and36.5% of those with an uninterpretable pap test were positive for HPVsequences.Follow-up data are available for 119 (52%) of the women, 28 have beenlost to death, the remaining have been evaluated only once. At follow-up, 11 of the 83 women with LGSIL or negative PAP smear showprogression while the remaining 72 show persistence. Most of thepatients with HGSIL/CIS (24 of whom underwent conization) showpersistence. The girl with vulvar carcinoma underwent surgery and sheis alive with persistent CIS. Of the 229 women evaluated, 116 have beenenrolled in 1994-1996 and 113 in 1997-1998. Death had occurred in14% of the first group and in none of the second one (most of whom areunder HAART regimen), but no marked difference between the twogroups has emerged in reference to the evolution of the genital lesions.

Conclusions: These preliminary data seem to suggest that HAART doesnot influence the clinical evolution of HPV-associated genital lesions.

FC4.04.02E-CADHERIN AND CD44 EXPRESSION IN CERVICAL INTRA-EPITHELIAL NEOPLASIA: COMPARISON BETWEEN HIVPOSITIVE AND HIV NEGATIVE WOMEN AND CORRELATIONWITH HPV STATUSE. Daraï (1), F. Walker-Combrouze (3), J-L. Bénifla (1), D. Hénin (3),G. Feldmann (2), P. Madelenat (1), J-Y. Scoazec (2)(1) Service de Gynecologie, Hôpital Bichat-Claude Bernard, Paris,

France.(2) Laboratoire de Biologie Cellulaire, INSERM U327, Facultée de

Medicine Xavier Bichat, Paris, France.(3) Service d’Anatomie Pathologique, Hôpital Bichat-Claude Bernard,

Paris, France.

Objectives: To evaluate the immunohistochemical expressions of E-cadherin and CD44 isoforms in cervical intraepithelial neoplasia (CIN)according to the human immunodeficiency virus (HIV) status.Study Methods: An immunohistochemical technique has been applied toformalin-fixed, paraffin-embedded samples of 138 CIN (74 from HIV-negative and 64 from HIV-positive patients).Results: The mean percentages ± SD of E-cadherin immunostainingaccording to CIN of grade I, II and III were: 33%±4, 63%±5, and 91%±9respectively. The difference was statistically significant between thethree groups of tumors (p<0.0001). The mean percentages ±SD ofCD44 H immunostaining according to CIN of grade I, II and III were37%±7, 57%±8, and 90%±11 respectively. The difference wasstatistically significant between the three groups of tumors (p<0.0001).In CIN, no difference in E-cadherin and CD44 expressions was notedbetween HIV + and HIV- women. No relation was found betweenhuman papilloma virus (HPV) types and (a) the grade of CIN, (b) theexpression of E-cadherin, (c) the expression of CD44 and CD44 variantsv3 and v6 and (d) the HIV status.Conclusions: A relation was observed between quantitative alterations ofE-cadherin and CD44 and the severity of CIN but not with the immunestatus.

FC4.04.03ASSISTED REPRODUCTION OF HIV-NEGATIVE WOMEN WITH“WASHED” SPERM OF THEIR HIV-POSITIVE PARTNERS – RISK-REDUCTION OR SAFE PROCEDURE?F. Melchert , M. Beichert, M. Gentili, M. Weigel, Dept. OB/Gyn,University Hospital Mannheim, University of Heidelberg, Mannheim,Germany

Objectives: Aim of the study was to investigate the safety and efficacyof sperm-„washing“ of HIV-infected men for assisted reproductionprocedures (ART) of their HIV-negative partners.Study Methods: A total of 80 ejaculate samples of 56 HIV-infected menof our child desire project were investigated. The preparation wasperformed by density gradient centrifugation with following swim-up.The native semen as well as the utilized sperm fraction was tested byPCR for viral RNA and pro-viral DNA.Results: In native semen HIV-RNA was detected in 30 samples andHIV-DNA was detected in 17 samples. 19 men were investigated severaltimes: The native semen proved constantly negative in only 6 (35%). In13 (65%) changing findings were detected, e.g. negative for RNA andDNA, positive for RNA or DNA up to positive for RNA and DNA. Inthe ultimately utilized fraction of motile spermatozoa pro-viral DNAwas detected in no case. However, three samples revealed traces of viralRNA. This corresponds to 3,8% of all samples, but to 10% of all nativesemen samples with proven HIV-RNA.Conclusions: The utilized sperm preparation method reliably eliminatespro-viral DNA of predominantly leukocytic origin. The proof of HIV-RNA does not mean at all that the sample is infectious. But not least outof liability reasons each sample should be tested again before use forART, since despite of subtle processing techniques traces of viral RNAcould be detected in the fraction of motile spermatozoa. Earlierinvestigations are not reliable because of the intra-individually changingvirus load and -distribution in native ejaculate. The here describedsequence of sperm preparation - PCR testing - ART provides amaximum of safety and is much more than merely a risk reduction.


Nevertheless, each HIV discordant couple desiring a child has to beinformed that hypothetically there still exists a remaining risk for virustransmission.

FC4.04.04HIV INFECTED WOMEN: IMPACT ON CONTRACEPTIONJ.Magalhaes , P.Giraldo, E.Amaral, J.A.Simoes, State University ofCampinas-UNICAMP, Rua Alexandre Coelho 22, Mogi Mirim, SãoPaulo, Brazil, 13.800-000.

Objectives: The study was developed in order to evaluate the impact ofknowledge of HIV infection (diagnosis), with regards to contraceptioninformation and choice for HIV+ women.Study Methods: Cross seccional descriptive study.A questionaire wasapplied to 140 HIV infected women.Statistical analysis was performedby chi-square test, Fisher's exact test and McNemar test for pairedsamples(significance of 5%).Results: Most of studied population included young women, with a loweducation level. A significant increase in the knowledge ofcontraceptives methods after being told that they were HIVpositive,wich include injectables,IUD, and tubal ligation, shows thepatients had a chance to receive information, never received before. Asignificant increase in the prevalence in the use of contraceptivemethods was found, specially for condoms and tubal ligation. However,30% of the HIV+ women still did not use any contraceptive methods.The "double protection" method (combined method)was used by only asmall percentage of women, despite counseling.Conclusions: The fact of knowing themselves to be HIV infected had astrong impact on contraceptive practice among HIV infected women. Itis expected that Family Planning services could address HIV+ womenneeds and be prepared to be integrated with HIV/HIV services forwomen.

FC4.04.05SQUAMOUS INTRAEPITHELIAL LESIONS IN HIVSEROPOSITIVE PREGNANT WOMENA. Hakim , R. Gueglio, A. Paganini, A. Dunaiewsky, Hospital RamosMejia, Lugones 2045, Buenos Aires, Argentina, 1430.

Objectives: The aim of the study was to evaluate the presence of lesionsin the lower genital tract of pregnant women and the relationshipbetween squamous intraepithelial lesions (SIL) with HIV seropositivityduring a cyto-colpo-histologyc screening.Study Methods: We evaluated 110 consecutive HIV seropositivepregnant women that attended to Cervical Pathology’s Oficce, fromOctober 1996 to December 1999. Cervicovaginal Papanicolau smears,colposcopy, vulvoscopy and eventual biopsy were performed. Thecontrol group was composed of 110 HIV seronegative pregnant women.Results: We found 31 SIL in the 110 HIV positive group (28.18%),while only 8 out of 110 (7.27%) HIV negative had SIL. This differencewas statistically significant (p< 0.05, c2 test). The pathology found inthe 31 HIV seropositive patients was: Low grade SIL: 27 (87.10%)including 10 condylomatosis, 11 flat condyloma and 6 low grade SILwithout HPV; High grade SIL 3 (9.68%); Invasive carcinoma 1 (3.22%).Treatment in HIV seropositive patients with low grade SIL, was 90%trichloracetic acid during pregnancy and reexamination 90 days afterdelivery. For patients with high grade SIL, conization 90 days afterdelivery was used as treatment. In the patient with carcinoma,stadification after delivery was made.Conclusions: We found a significant association between SIL and HIVseropositivity in pregnant women. We believe that it is important toscreen cyto-colpo-histologically all HIV seropositive patients duringpregnancy.

FC4.04.06EFFECT OF VAGINAL DOUCHING ON GENITAL TOLERANCETO NONOXYNOL-9U. Jaisamrarn , P. Thasanapradit, S. Limpongsanurak. S.Taneepanichskul, Dept. OB/GYN, Chulalongkorn University, Bangkok,Thailand.

Objectives: The aim of this study was to evaluate the effect of vaginaldouching with water on the tolerance of genital epithelium toNonoxynol-9 (N-9).Study Methods: 60 healthy women were recruited in this randomizedcontrolled trial. 30 women were assigned to each of the study groups –A and B. Vaginal administration of a film containing 72 mg of N-9 threetimes per day for 14 consecutive days was done in both groups. Onlywomen in Group B practiced vaginal douching with water 30-60minutes after insertion of each film. Colposcopic examination andlaboratory testing for STDs were done on the admission day, day 7 andday 14 in all women.Results: There were no significant differences in base-linecharacteristics of women and laboratory results for STDs between thesetwo groups. Disruptions of cervical epithelium were observed in 20% ofwomen in Group A. Only 1 case (3.5%) of epithelial disruption wasfound in Group B. This difference was statistically significant (<0.05).Conclusions: Vaginal douching with water 30-60 minutes after insertionof N-9 vaginal film was found to decrease the incidence of genital side-effects of N-9.

FC4.04.07INVASIVE CERVICAL CANCER AMONG WOMEN WITH AIDS INEUROPE AND USA, 1994-1998Ebrahim SH ,* Selik R, McKenna M, Hamers F, Seeff L.European Centre for Epidemiological Monitoring of AIDS, France

Objective: To assess the trends in invasive cervical cancer (CCA) as anAIDS-defining condition.Methods: We analyzed the AIDS surveillance data from Europe(reported by16 countries of the WHO-European region) and the USA,among women aged 15 years or older, 1994 through 1998.Results: During 1994-1998, CCA was the most common malignancyamong women with AIDS in both Europe (2.7%, 393/14,348) and theUSA (2.1%, 580/28,024). In Europe and the USA, among women withCCA and AIDS, CCA was the only AIDS-defining condition for 90%.Over the period 1994 to 1998, the percentage of women who had CCAas the AIDS-defining condition remained stable in Europe whereas itdeclined in the USA from 2.7% to 1.7% (p=<0.001). Overall, thepercentage with CCA was significantly higher among women whoacquired HIV through intravenous drug use (Europe 3.5%, USA 2.3%)or heterosexual contact (Europe 2.1%, USA 2.1%) than the remainder ofthe women (Europe 0.7%, USA 1.6%). In Europe, CCA peaked amongwomen aged 31 to 35 years (3.5%), whereas in the USA CCA declined(p<0.001) with increasing age, from 2.7% (15-20 years) to 1.2% (51years old or older).Conclusions: Women with HIV/AIDS have a disproportionately highrisk of invasive cervical cancer in both Europe and the USA. Women ofall ages who are at risk of HIV should be targets for cervical screening.

FC4.04.08IMPACT OF AN INTERVENTION TO IMPROVE TREATMENT-SEEKING BEHAVIOR AND PREVENT SEXUALLYTRANSMITTED DISEASES AMONG NIGERIAN YOUTH: ARANDOMIZEED CONTROLLED TRIALF.E. Okonofua (1,3), P. Coplan (2,5), F. Oronsaye (1), D. Ogunsakin (1),J.T. Ogonor (3), S. Collins (4), J.A. Kaufman (6), K. Hegenhougen (4)1. Women’s Health and Action Research Center, Nigeria.2. Merck Research Laboratories, Blue Bell, PA, USA.3. University of Benin, Nigeria.4. Dept. of Population and International health, Harvard School of

Public Health, MA, USA.5. University of Pennsylvania Medical School, USA.6. Ford Foundation, Beijing, China.

Objective: The aim of the study was to evaluate the impact of anintervention on the prevalence and treatment-seeking behavior forsexually transmitted diseases among Nigerian youth.


Methods: A randomized controlled trial in 12 schools in Edo State wasconducted to evaluate an intervention to improve STD treatment-seekingand STD treatment provision. The intervention, consisted of communityparticipation, peer education, public lectures, health clubs in highschools, and training of STD treatment providers including those with noformal training. A questionnaire measured outcomes before and 10months into the intervention. The effect of the intervention among 4randomly-selected intervention schools compared to 8 randomly-selected control schools was assessed using multiple logistic regressionwith Huber’s formula to account for school clusters.Results: 1896 and 1858 youth 14-20 years of age were enrolled in thepre and post-intervention surveys. Youths in the intervention schoolscompared to control schools reported statistically significantimprovements in knowledge of STDs, condom use, partner awarenessthat the youth had a STD, and treatment-seeking behavior. Treatment byprivate physicians increased (OR=2.1, 95% CI = 1.1-4.0) and by patentmedicine dealers or pharmacists decreased (OR =0.44, 95% CI = 0.22-0.88). The reported prevalence of STD symptoms in the past 6 monthswas significantly reduced in the intervention compared to controlschools (OR = 0.68%, 95% CI=0.48-0.95).Conclusion: Significant improvements in treatment seeking for STDsymptoms can be effected among Nigerian youth. The prevalence ofreported STD symptoms can be decreased by a peer educationalprogram to improve treatment-seeking for STD.

FC4.04.09PREVALENCE OF GYNAECOLOGICAL RISK FACTORS FORHETEROSEXUAL TRANSMISSION OF HIV AMONG WOMENATTENDING CENTERS FOR COUNSELLING AND SEROLOGICTESTING IN BRAZILA.D. Ribeiro-Filho , J.R.Gabiatti, P.C. Giraldo, State University ofCampinas – UNICAMP, National Health Ministry - Brazil

Objectives: To determine the prevalence of gynaecological risk factorsamong women once exposed to HIV transmission.To stablish a possible correlation between behavioral andgynaecological risk factors for HIV heterosexual transmission.Study Methods: Among women visiting a Center for counselling andserologic testing in Brazil during a six month period, 253 accepted agynaecological consultation where a questionary defined theirbehavioral risks and a gynaecological and complementary examsdefined their biological risk to heterosexual transmission of HIV.Statistical analisis were used to search any correspondence betweenthose risk factors.Results: Overall prevalence of gynaecological risk factors for HIVheterosexual transmission among the sample were 62,7%, most of themassymptomatic.Statisticaly, it was not possible to determine a greater risk of having agynaecological risk factor for HIV transmission by analising only thebehavioral risk through a standart questionary.Conclusions: Any effort to diminish risk among women exposed to HIVtransmission should include not only advertising and counselling butalso a gynaecological check up even if assymptomatic. Teatching theimportance of genital health on fighting agains heterosexualtransmission of HIV should be part of the speach of every profissional atCenters for counselling and serologic testing in Brazil and all over theworld.

FC4.04.10HIV-CHALLENGES AND CONTROVERSIESA. Patil , H. Divakar, Divakars Hospital, BTM Layout, BannerghattaRoad, Bangalore, Karnataka, India, 560076.

This paper aims at presenting the management of '8' pregnant patientswho were referred to our hospital due to seropositivity to HIV , Ourhospital being one of the first private institutions accepting managementof HIV seropositive cases.Of the '8' HIV +ve pregnant patients, 4 patients opted for termination ofpregnancy at 10 weeks, 14 weeks, 28 weeks and 30 weeks of gestation.The patients who continued pregnancy were appropriately counselledand started on AZT Ziduvidine.One patient delivered vaginally and threepatients underwent elective casearean sections. The neonatal outcomes& followups will be presented. At present, we have two ongoing HIV+ve pregnancies, both of whom are on AZT.

The paper will also highlight the alarming numbers of HIV epidemic inIndia & the rest of the developing world, the testing policies, thepreventive strategies and the various anti retroviral drug regimens. Asobstetricians , our concern of vertical transmission to the foetus and thecontroversies regarding mode of delivery, breast feedingrecommendations and drug therapy will be discussed. HIV is grosslyunderdiagnosed and health care community is reluctant to manage theinfected persons in the developing world. Our Hospital is one of thepremier institutes in southern India who has taken the first step towardstreating HIV +ve patients and embarking on the goal of prevention ofvertical transmission.

FC4.05 OBSTETRICS: LABOR

FC4.05.01MISOPROSTOL VERSUS OXYTOCIN FOR LABOR INDUCTION:RANDOMIZED CONTROLLED TRIALJ.G. Cecatti (1), M.M.A. Aquino (1), G.M. Garcia (2),T.M.C. Rodrigues (2)(1) Dept. OB/GYN, Universidade Estadual de Campinas, São Paulo,

Brazil.(2) Dept. OB/GYN, Hospital-Maternity Leonor Mendes de Barros, São

Paulo, Brazil.

Objective: To compare the effectiveness and safety of intravaginalmisoprostol versus intravenous oxytocin for cervical ripening and laborinduction in pregnant women with unripe cervices.Study Methods: It was a randomized controlled trial, performed atHospital-Maternity Leonor Mendes de Barros (HMLMB), São Paulo,Brazil, from November 1998 to August 1999. 106 term pregnant womenwith intact membranes and with indication for labor induction wereselected. They randomly received 25 mg of vaginal misoprostol every 4hours, not exceeding 8 doses (53 women) or oxytocin in a continuousinfusion (53 women). The main outcome variables were: latent period,time from onset of induction to vaginal deilvery, route of delivery andoccurrence of hyperstimulation syndrome. To verify the statisticalsignificance of the differences among the groups, c2, Student t andMann-Whitney tests were used.Results: There were no significant differences between the groupsconcerning age, parity, race, literacy, initial Bishop Index and deliveryroute, although twice the amount of cesareans occurred in the oxytocingroup (39.6% against 20.7% for misoprostol). The latent period and theperiod from the onset of induction to vaginal delivery were significantlylower for the misoprostol group (p<0.0000). There were no differencesbetween the groups concerning alteration of uterine tonus, althoughhyperstimulation syndrome occurred in 4 cases with oxytocin and in 2with misoprostol.Conclusion: Misoprostol using a proper dose is safer and more efficientfor cervix ripening and labor induction that oxytocin.

FC4.05.02A COMPARISON OF ORAL AND VAGINAL MISOPROSTOLTABLETS IN THE INDUCTION OF LABOR AT TERMA. Shetty , P. Danielian, A. Templeton, Dept. OB/GYN, AberdeenMaternity Hospital, Aberdeen, UK.

Objectives: The aim of the study was to compare the efficacy ofequivalent doses of orally administered with vaginally administeredmisoprostol in the induction of labor at term.Study Methods: Two hundred and forty five pregnant women at term,with indications for labor induction were randomly assigned to receive50mgms of misoprostol tablets orally or vaginally four hourly to amaximum of 5 doses, if required. The main outcome measure was theinterval from induction to vaginal delivery.Results: The mean induction to vaginal deliver interval was significanlyshorter in the vaginal group as compared to the oral group (14.3hrs Vs25.1hrs;p<0.0001). There was no difference in the mode of delivery,analgesic requirements or neonatal outcomes in the two groups. Therewas, however, a higher incidence of uterine hyperstimulation in thevaginal group (4.9% Vs 0.8%) although this was not statisticallysignificant (P=0.12), and more operative deliveries were indicated forfetal distress in this group (23.8% Vs 9.8%, P=0.005). Patientquestionnaire analysis revealed that a significant number preferred the


oral route of administration, however its slower action was seen as adisadvantage.Conclusions: Misoprostol effectively induces labor with the vaginalroute of administration having a faster action than the oral route inequivalent doses. However, the more frequent occurrence ofhyperstimulation and the higher intervention rate for fetal distress in thevaginal group and patient choice could mean that the preferred routemight be oral. More trials are needed to find the right oral dosage thatcombines efficacy with safety.

FC4.05.03CERVICAL RIPENING AND INDUCTION OF LABOUR WITHMISOPROSTOL, PROSTAGLANDIN E2 OR PROSTAGLANDIN E2GEL: A RANDOMIZED COMPARATIVE CLINICAL TRIALNeveen M Nour El-Din and Diaa A.M El-Moghazy Dep.OB/GYN,Minia University, Egypt

Objectives: To compare the safety and efficacy of vaginallyadministered misoprostol, or prostaglandin E2 tablet or gel forpreinduction cervical ripening in patients with an unfavorable cervix.Study Design: One hundred and forty nine patients received either 50 mgmisoprostol (52 patients) or _ tablet prostaglandin E2 3 mg (prostin)intravaginally/4 hours (49 patients ) or prepidil gel (prostaglandin E2gel) intracervically/6 hours (Maximum 3 doses) (48 patients) for 24hours or until adequate labor was achieved (at least three contractiosn in10 minutes).Results: The start to delivery interval was shorter in the misoprostolgroup (13 hours) and prostin (15 hours) group than the gel group (21hours) (p<0.01). No differences were noted in the Caesarian rate amongthe three groups (11.5%, 14% and 10.4% in misoprostol, prostin andprepidil groups, respectively). Adverse effects as tachysystole andhyperstimulation syndrome were very low among the three study group.Abnormal FHR tracings were found in 19% in misoprostol group, 18%in prostin group and 12.5% in prepidil group (p=NS). however, this didnot affect the neonatal outcome .Conclusions: Misoprostol (50 mg/4 hours) is an effective, cheap and safemethod for both cervical ripening and labor induction . The use of halftablet of prostin/4 hours reduces the dose and cost of the drug withoutaffecting its efficacy.

FC4.05.04COMPARISON OF ORAL MISOPROSTOL ANDINTRAMUSCULAR SYNTOMETRINE IN THE MANAGEMENTOF THE THIRD STAGE OF LABOR – A MULTICENTERRANDOMISED CONTROLLED TRIALP.S. Ng (1), A.S.M. Chan (2), W.K. Sin (3), L.C.H. Tang (2), K.B.Cheung (3), P.M. Yuen (1)(1) Dept. OB/GYN, Prince of Wales Hospital, Hong Kong, China(2) Dept. OB/GYN, Kwong Wah Hospital, Hong Kong, China(3) Dept. OB/GYN, Tuen Mun Hospital, Hong Kong, China

Objective: To compare the efficacy and safety of oral Misoprostol withintramuscular Syntometrine in the management of the third stage oflabor.Study Methods: Two thousand and fifty-eight women with a singletonpregnancy and a vaginal delivery were randomized to receive either oralMisoprostol or intramuscular Synometrine in the management of thethird stage of labor. The outcome measures included the degree ofpostpartum hemorrhage, need for additional oxytoxics, and treatment ofrelated side effects.Results: There were no significant differences between the 2 groups inthe mean blood loss, the incidence of postpartum hemorrhage and in thechange in hemoglobin level. In the Misoprostol group, the incidence ofmanual removal of placenta was significantly lower and the incidence oftransient pyrexia (³ 38° C) and shivering were significantly higher.There were no differences in the incidence of nausea, vomiting,headache and chest pain.Conclusion: Misoprostol may be used as an alternative to intramuscularSyntometrine in the management of the third stage. There is, however,an increase in the need for additional oxytoxics. The morbidityassociated with its use is transient only and carries no significant clinicalsequalae.

FC4.05.05COMPARATIVE STUDY ON ROLE OF SYNTOMETRINE ANDPROSTAGLANDIN IN THE PREVENTION OF P.P.H.D.K. Dutta , K.K.Saha, Dept. OB/GYN, Naihati State General Hospital,Kalyani, India.

Objective: The aim of the study is to investigate and compare the role ofsyntometrine ad prostaglandin in the prevention of P.P.H.Study Method: Following complete placental expulsion, 450 cases wereinjected with 1 ml. IM syntometrine (Group A) and 220 women with250 mg of 15 methyl PGF2a (Carbo-prost; Group B). Observationswere made in both groups up to 2 hours to find out (1) Time of on-set ofuterine contraction, (2) Duration of uterine contraction, (3) Amount ofblood loss, (4) Change in blood pressure, (5) Change in hemoglobinlevel, (6) Maternal side effects.Results: Comparative study in both groups showed that onset of uterinecontraction within 2 minutes were observed 98.2% in group A and90.3% in group B. Uterine contraction appeared to be sustained 99.2%in group A as compared to 88.2% in group B. In group A 96.4% casesshowed blood loss less than 200 ml. In 3.6% it was between 200-500 mlwhereas in group B blood loss was less than 200 ml in 87.4% cases,200-500 ml. In 11.6% cases and more than 500 ml in 1% caserespectively which was significantly higher than that of group ‘A’. Allgroup A patients maintained their steady normal blood pressure whereasamongst group B patients although 96.3% showed normal bloodpressure it was high in 3.7% cases. Hemoglobin level in both the groupsdid not show any significant changes. Maternal side effects were nilamongst group A patients whereas 10.5% of group B showed nausea andvomiting.Conclusion: This study shows that syntometrine have significantadvantage over prostaglandin due to its early onset of uterine contractionwhich sustained up to 2 hrs. associated with comparatively less bloodloss, maintaining normal blood pressure with no maternal side effects.

FC4.05.06MISOPROSTOL AND THE 3rd STAGEA. Chatterjee , Dept. OB/GYN, N.R.S. Medical College, Calcutta, India.

Objectives: To compare the efficacy of oral Misoprostol and I.V.Ergometime in the management of 3rd stage labor.Study Methods: 200 parturient women were included in a randomizedprospective trial with 100 in a study group and 100 controls, (whoreceived I.V. Engometime only), both given following the delivery ofanterior shoulder.Results: Misoprostol produced shorter 3rd stage, less need for additionaloxytocic and blood transfusion, i.e. less incidence of P.P.H. The Hb%drop was lower in this group than in the control group.Conclusion: Misoprostol – PGE1 analogue – is a strong uterotonic, noninvasive, safe, orally effective and can be given by any traditional birthattendant – a special advantage for the least developed and thedeveloping countries.

FC4.05.07RANDOMISED CONTROLLED TRIAL OF INTRAVAGINALMISOPROSTOL VERSUS INTRAVAGINAL DINOPROSTONE FORTHE INDUCTION OF LABOUR.N. V. Jackson , V. Terzidou, R.E. Irvine, D.K. Edmonds, S. Paterson-Brown. Queen Charlotte’s and Chelsea Hospital, London, England

Objectives: To compare intravaginal misoprostol with our currentregime (intravaginal dinoprostone) for induction of labour at term.Study methods: 400 women were randomly allocated to receive eitherProstin gel 1-2mg six-hourly or 50mg Misoprostol four-hourly. Primaryoutcome measure was the time interval from initiation of induction todelivery, with secondary outcomes need for oxytocin augmentation,analgesic requirements, mode of delivery, adverse maternal and neonatalevents and cost of induction agents.Results: Induction-delivery interval was significantly shorter withmisoprostol (14.98 hours vs 21.83, p<0.0001). There was alsosignificantly less need for oxytocin augmentation (37% vs 52%,p=0.01), with no significant difference in requirements for analgesia ormode of delivery. There was, however, a significant increase in theincidence of tachysystole (p<0.0001), with a non-significant trendtowards increased incidence of hyperstimulation in the misoprostol


group, but no significant differences in neonatal outcomes. There werefewer failed inductions in the misoprostol group. Use of misoprostol forinduction of labour would represent a significant saving in the cost ofinduction agents.Conclusions: Intravaginal misoprostol is at least as effective asdinoprostone in the induction of labour at term, but further research isneeded to confirm its safety and to establish the optimum dose regime.

FC4.05.08VAGINAL MISOPROSTOL FOR LABOR INDUCTION 25 ugVERSUS 50ug DOSE REGIMENSM. El-Sherbiny . Dep OB/GYN, General Hospital Cairo, Egypt

Objective: To compare the efficacy and safety of two doses ofendovaginal misoprostol for cervical ripening and induction of labor.Study Methods: The study group included 185 cases of induction oflabor during the period from May 1997 through October 1999. Theywere randomly divided into group A, 93 and B, 92 cases. Group Areceived 25 ug and group B 50 ug intravaginal misoprostol respectively.The doses were repeated every 4 hours until active phase or a maximumof 6 doses.Results: Abnormal uterine contractions were significantly higher ingroup b. The hyperstimulation was absent in group A. The meaninduction to delivery interval was 17.18 in group A compared to 9.37hours in group B (P <0.05). There were more frequent abnormal fetalheart rate patterns in group B than group A. Antipartum meconiumpassage was significantly more frequent in group B (P < 0.05). TheCaesarian section rate was 17.20% in group A and 14.13% in group B(P< 0.05). Postpartum hemorrhage and 3rd degree perineal tear weremore frequent in group B, (9.78% versus 2.15%) and (2.17% versus 0%)respectively. Also, there were slightly more frequent 1- or 5- minuteapgar score <7, admission to neonatal care unit, or hyperbilirubinemia ingroup B.Conclusion: The authors recommend the 25 ug dose regimen every 4 hrsfor bringing cervical ripening and labor induction.

FC4.05.09ROLE OF ESTRADIOL AND PROGESTERONE RECEPTORS INMYOMETRIUM DURING LABOURN. D. Gasparian , E. K. Kareva, L. S. Logutova, I. P. Laricheva, I. I.Levasbova, Regional Research Institute of Obstetrics and Gynecology,Moscow, Russia

Objectives: A main mechanism determining the progression ofpregnancy is the content of genital steroids in the blood and thesensitivity of myometrium to them. To investigate the content ofestradiol (RE) and progesterone (RP) receptors in the uteromyocytesduring the normal labor depends on the concentration of genitalhormones in the blood.Study and Methods: We examined 19 patients with 39-41 weeksgestation who were delivered by natural maternal passages. We studiedthe content of estradiol and progesterone in the blood as well as RE andRP concentration in the late pregnancy and during the final stage oflabor.Results: The dates suggested that the level of cytasol RE in the latepregnancy was 10.9 fMole/mg and it progressively dropped during thelabor. Content of Estradiol in the blood remained unchanged in latepregnancy and during the labor. RP concentration in cytosol increaseddevelopment of labor activities while plasma progesterone dropped.Conclusion: Progressive decline of RE level in the niyomelrium inunchanged content of estradiol in the blood shows that the receptors ofestrogens in myometrium are involved in the regulation of uterinecontractions.

FC4.06 HRT: CARDIOVASCULAR AND OTHER EFFECTS

FC4.06.01CAN THE RISK OF ISCHAEMIC HEART DISEASE BE ASSESSEDFROM HYSTERECTOMY SPECIMENS?A.Weeks , Dept. OB/GYN, The Jessop Hospital for Women, Sheffield,U.K.

Objectives: As the degree of artherosclerosis in uterine and cardiavasculature is closely related, examination of the uterine vessels at thetime of hysterectomy might indicate the risk of death from ischaemicheart disease (IHD). A case control study was performed to see ifwomen who died from IHD had more arcuate artery atherosclerosis(AAA) at the time of hysterectomy than controls.Study Methods: Post-mortem reports from women who had diedbetween 1993 and 1997 were studied to identify women who hadpreviously undergone hysterectomy in the same hospital. Cases werewomen with severe coronary artery atherosclerosis at the time of deathwhilst controls had minimal atherosclerosis. Controls were matched forage of both death and hysterectomy. Stored myometrial sections were re-cut and stained with Elastin van Geison. The medial thickness anddegree of lumen occlusion of the arcuate arteries were analyzed usingcomputerized morphology and compared using the paired t-test.Results: From over 500 reports studied, only 12 women fitted the strictcriteria for analysis. The cases showed a trend towards smaller medialarea than controls (-9.7%, 95% CI –22.2 to +2.9). The two cases whodied <60 years old had severe AAA and marked lumen occlusion whilsttheir controls had neither. The degree of AAA was related to age athysterectomy, but there was no difference between cases and controls.Conclusions: Arcuate artery morphology at the time of hysterectomymay be predictive of death from IHD. A larger case control study is bothfeasible and promising.

FC4.06.02TRANSDERMAL HORMONE REPLACEMENT THERAPY FORSECONDARY PREVENTION OF CORONARY ARTERY DISEASEIN POSTMENOPAUSAL WOMENS.Clarke (1) , M.Slack (2), J.Kelleher (1), P.Schofield (1), (1) PapworthHospital, Papworth Everard, Cambridge, Cambridgeshire, UnitedKingdom, CB3 8RE, (2) Hinchingbrooke Hospital, Huntingdon,Cambridge, UK.

Objectives: The use of hormone replacement therapy (HRT) in theprimary and secondary prevention of coronary artery disease (CAD)remains controversial. This study evaluated transdermal HRT in thesecondary prevention of CAD.Study Methods: 255 postmenopausal women with angiographicallyproven CAD were recruited between 1995 and 1999 and randomised totransdermal HRT (17b-oestradiol alone or 17b-oestradiol with cyclicnorethisterone), n=134, or control, n=121. Patients were seen at 6monthly intervals. Primary end-points were unstable angina, myocardialinfarction or death. Analysis was by 'intention-to-treat'.Results: Follow-up over 4 years included 340 patient-years in the HRTgroup and 310 patient-years in the control group. 52 (39%) HRT patientswithdrew at a median of 206 days (range 0 to 976 days) and 8 (7%)control patients withdrew and commenced HRT at a median of 267 days(range 25 to 433 days). Over the 4 year period, the average primary end-point rate for the HRT group was 15.6 per 100 patient-years comparedwith 12.6 per 100 patient-years in the control group ('perprotocol'analysis:16.5 vs. 11.8, respectively). This represents an eventrate of 1.23 (95%CI: 0.82-1.86, p=0.3) for the HRT group compared tothe control group. Event rates were highest in the first 2 years. Each yearthe HRT group had a higher, but not statistically significant, event ratethan the control group for all except MI events.Conclusions: Transdermal HRT does not appear to offercardioprotective benefit to postmenopausal women with CAD.


FC4.06.03LONG-TERM TREATMENT WITH THE PROGESTOGENSMEDROXYPROGESTERONE ACETATE (MPA) ANDNORETHISTERONE ACETATE (NETA) DISPLAYS DIFFERENTVASCULAR EFFECT.S. Pedersen , N.G. Pedersen, T. Dalsgaard, L. Nilas, B. OttesenClin. Research Unit and Dept. of OB/GYN, Hvidovre Univ. Hosp.(H:S), Denmark

Objectives: The secondary preventive effect of Hormonal ReplacementTherapy (HRT) on ischemic heart disease (IHD) has been questioned bythe HERS trial. It has been suggested that the lack of a preventive effectmay be due to the use of the progestogen MPA. This study elucidates thevascular effect of various hormonal regimes.Study methods ;Fifty-six non-atherosclerotic, ovariectomized NewZealand White rabbits were randomized into 7 groups (n=8) receivinghormonal treatment in phytoestrogen free chow for 4 weeks:MPA(10mg/day); NETA(3mg/day); conjugated equine estrogens(CEE)(1,25mg/day); 17-b-estradiol(E2)(4mg/day);MPA+CEE(10mg/day+1,25mg/ day); NETA+E2(3mg/day+4mg/day) orplacebo.Ring segments from the distal left anterior descending coronary artery(LAD) and the posterior cerebral artery (PCA) were microdissected andmounted for isometric tension recordings in a myograph. The maximumelectro-mechanical response was measured by depolarisation andactivation of the artery segments by replacing normal Krebs buffer witha single dose of 124mmol/l K+-Krebs buffer.Results: Treatment with MPA alone caused a significant increase in themaximum electromechanical response (mN/mm, mean±SEM) whencompared to treatment with NETA alone in bothLAD(6.36±0.36vs.4.31±0.42,P<0.005) and PCA(3.18±0.19vs.2.47±0.18,P<0.05). This difference was neutralized in thegroups receiving the combined treatment of MPA+CEE or NETA +E2in LAD (4.86±0.61vs.3.86±0.45,NS) and inPCA(2.64±0.20vs.2.66±0.17,NS). No signi-ficant differences wereobserved in the groups receiving estrogen treatment only.Conclusion: Treatment with MPA alone seems to be able to augment theelectromechanical response in coronary and cerebral arteries comparedto treament with NETA. This indicates that the preventive effect of HRTon IHD may depend on the hormonal regime applied.

FC4.06.04ENDOTHELIN-1 INDUCED VASOCONSTRICTION VARIATESWITH THE PROGESTOGEN USED FOR PRETREATMENTN.G. Pedersen , S. Pedersen, T. Dalsgaard, L. Nilas , B. OttesenClin. Research Unit and Dept. OB/GYN, Hvidovre Univ. Hosp. (H:S),Denmark

Objectives: The HERS trial showed no secondary preventive effect ofHormonal Replacement Therapy (HRT) on Ischemic Heart Disease(IHD). This may be explained by the use of medroxyprogesteroneacetate (MPA). The aim of this study was to assess the vascular effect ofendothelin-1(ET-1) after long-term treatment with various hormonalregimes.Study methods: Fifty-six non-atherosclerotic, ovariectomized NewZealand White rabbits were randomized into 7 groups (n=8) and givenhormonal treatment in phytoestrogen free chow for 4 weeks:MPA(10mg/day); norethisterone acetate (NETA)(3mg/day); conjugatedequine estrogens (CEE)(1.25mg/day); 17-ß-estradiol (E2 )(4mg/ day);MPA+CEE (10mg/day+1.25mg/day); NETA+E2 (3mg/day+4mg/day)and placebo. One ring segment from the left proximal coronary artery(PROX) and the distal part of the left anterior descending coronaryartery (DIST), the basilar artery (BA) and the posterior cerebral artery(PCA) were microdissected and mounted for isometric tensionrecordings in a myograph. The dose-response relationship between ET-1(10-11 to 10-6mM) and vessel tone was established. The Emax and the EC50

were determined.Results: Treatment with MPA alone caused a significant increase in Emax

(mN/mm,mean± SEM) when compared to treatment with NETA alonein DIST(9.41±0.82vs. 6.43±0.73, P<0.05) and inBA(7.08±0.61vs.5.54±0.32,P<0.05). This difference was neutralized inthe groups receiving the combined treatment of MPA+CEE compared toNETA+ E2 in DIST(6.65±0.73vs.5.94±0.53,NS) and inBA(6.32±0.36vs. 7.05±0.49,NS). No significant difference wasobserved between the estrogen only treatment groups. PROX and PCA

showed no significant difference in Emax in any of the treatment groups.No differences in EC50 were observed.Conclusion: Treatment with MPA alone seems to enhance the responseto ET-1 in certain arteries when compared to treatment with NETAalone. This suggests that the progestogen applied affects the preventiveeffect of HRT on IHD.

FC4.06.05FAT DISTRIBUITION AND RISK FACTORS FORCARDIOVASCULAR DISEASE IN POST MENOPAUSAL WOMEND.Filip Raskin , A.Pinto Neto, J.Neves Jorge, L.Costa Paiva, CampinasCatholic University/Medical Faculty, John Boyd Dunlop Ave,Campinas, Sao Paulo, Brazil, 13059740.

To study the distribution pattern of body fat, the factors related to thepresence of obesity and android profile; to discover the variablesassociated with the risk factors for cardiovascular disease in menopausalwomen, an observational cross-section study was carried out on 518patients, between 45 and 65 years old, attending the Climacteric Out-Patients Clinic of the Medical Faculty of Campinas Catholic University.Age, color, menopausal status, lifestyle, habits, personal and familyantecedents for cardiovascular disease were assessed. Anthropometricmeasures of weight, height and the circumference of the waist and hipswere used to calculate the body mass rate and the waist/hip ratio. Thenumerical data of blood pressure measurements and plasma evaluationsof total cholesterol, LDL, HDL, VLDL cholesterol, triglycerides andglycaemia in a state of fast were considered. In the statistical analysis,the unilateral Wilcoxon test, Pearson’s correlation coefficient with a 5%level of significance and a multiple analysis using the LogisticRegression model were applied . The majority of the women were notobese, presented android profile, white, post-menopausal and sedentary;a quarter were smokers, half reported an inadequate diet and one fifthwere alcoholics. Women with android profile presented higher averageage. Personal antecedents of obesity, arterial hypertension and diabetes,family history of diabetes and post menopausal status werecharacteristics associated with obesity and android pattern. Menopausalstatus, personal antecedents of arterial hypertension,hypercholesterolemia and diabetes, android profile and family history ofdyslipidemia were the main characteristics associated with most of therisk factors for cardiovascular disease.

FC4.06.06HORMONE REPLACEMENT THERAPY DECREASESNOREPINEPHRINE PLASMA LEVELS IN POSTMENOPAUSALWOMEN.C.Molina , G.Arata de Bellabarba, E.Velazquez, V.Villarroel,Universidad de Los Andes, Apartado 42, Merida, Venezuela, 5101.

Objectives: This study was planned to evaluate the effect of hormonereplacement therapy (HRT) on blood pressure (BP) and norepinephrine(NE) plasma levels in normotensive postmenopausal women.Study Methods: Twenty- two normotensive postmenopausal womenwere studied. Fourteen women received cyclic oral combined HRT(group I) and 8 hysterectomized women received estrogen withoutprogesterone (group II). NE plasma levels, body mass index (BMI) andBP in supine posture were measured at baseline and after 8 weeks oftreatment.Results: The administration of estrogen with or without progesteronecaused a significant decrease of systolic BP (p< 0.05) and NE plasmalevels (p < 0.01) without any significant change in BMI. A decrease ofNE plasma levels was observed in 55% of group I and 86% of group II.Conclusions: Our results show that HRT has a beneficial effect on bloodpressure by decreasing the sympathetic activity in postmenopausalwomen and might decrease the risk for hypertension and cardiovasculardisease in these women.


FC4.06.07THE EFFECTS OF TWELVE MONTH USE OF ANESTRADIOL/NORGESTREL PREPARATION BYPOSTMENOPAUSAL WOMEN ON LIPID METABOLISM ANDHEMOSTATIC PARAMETERSI.H. El-Nashar (1), G.H. Sayed (1), M. El-Kabsh (2), A. Nasr (1), M.M.Shaaban (1), Departments of (1) OB/GYN and (2) Clinical Pathology,Assiut University Hospital, Assiut, Egypt

Objectives: To evaluate the effects of a 12-month use of a cycliccombined postmenopausal hormone therapy (PHT) preparation on serumlipids, lipoproteins and some hemostatic parameters.Study Methods: Two hundred postmenopausal women were randomlyallocated to use a PHT preparation containing estradiol valerate 2 mg for21 days, plus norgestrel 0.5 mg for the last 10 days, or a multivitaminpreparation (controls) to study their effect on certain lipids, lipoproteinand coagulation parameters. Blood samples were taken at admission andafter 3, 6 and 12 months of use. Only the findings in 95 women whocompleted the 12 month treatment are included in this analysis whichwas determined by Student-t test and X2 test.Results: At admission, no difference between the 2 groups wasobserved. In women not using PHT, only serum total cholesterol showeda significant increase in HDL and apolipoprotein-A and a significantdecrease in LDL after 12 months. Serum triglycerides, on the otherhand, showed an early and sustained increase. Only coagulation factorsV and X showed a significant increase with time in women not usingPHT. In those using PHT, the activity of factors V and X decreasedsignificantly while antithrombin III and plasminogen increasedsignificantly after 12 months. No change was observed in prothrombintime or activated partial thromboplastin time.Conclusion: The postmenopausal use of combined estradiol/norgestrelPHT for 12 cycles results in favorable changes in a number ofparameters of cardiovascular risk. The present study confirms that theoverall beneficial effects of estrogen on lipid and hemostatic profiles arepreserved with norgestrel coadministration.

FC4.06.08COMPARISON OF THE EFFECTS OF ESTROGEN VS ESTROGENPLUS PROGESTERON REGIMENS ON CRP ANDHOMOCYSTEINE LEVELSH. Yarali , A. Yildirir, F. Aybar, L. Tokogözoglu, H. yarah, G. Kabaker,O. Bükülmez, I. Sinici, I. Ünsal, A. Oto, T. Gürgan, HacettepeUniversity, Faculty of Medicine, Ankara, Turkey.

Objective: Increased plasma homocysteine is an independent risk factorfor occlusive arterial disease and deep venous thrombosis. High Creactive protein (CPR) is a risk factor for future cardiovascular eventsand is a marker of artherosclerotic plaque instability. In this study, theeffects of hormone replacement therapy (HRT) on plasma CRP andhomocysteine levels were investigated.Study Methods: 46 postmenopausal women (age 48±5, range 40-60)were prospectively evaluated for the effects of 6-month HRT on lipidparameters, CRP and homocysteine levels. HRT regimens werecontinuous 0.625 mg/day conjugated equine estrogen (CEE) + 2.5mg/day medroxyprogesterone acetate (MPA) or 0.625 mg/day CEEalone depending on the hysterectomy status. Paired sample t-test wasused for statistical analysis.Results: CEE alone significantly increased CRP levels, but CEE + MPAdid not have significant effect on CRP. However, a significant decreasein homocysteine levels was maintained with both regimens. The HDLincreasing effect of estrogen was blunted by the addition of progesteronethat also increased the triglycerides (see Table 1).

CEE

(n=16)

CEE + MPA

(n=30)

Pre Post Pre Post

CRP (mg/dl) 0.66±0.48 0.81±0.35* 0.77±0.64 0.88±0.80

Homocysteine (mmol/l) 10.7±4.9 8.8±3.0 12.0±5.8 9.1±3.2**

Cholesterol (mg/dl) 217±41 224±46 217±42 215±39

LDL (mg/dl) 132±37 123±34 125±30 116±26

HDL (mg/dl) 52±7 64±13** 60±12 55±12

Triglyceride (mg/dl) 121±34 150±82 137±69 188±88**

*p<0.05, **p<0.01Table 1: The effects of HRT on plasma, CRP, homocysteine and lipidparameters.

Conclusions: Plasma homocysteine levels were significantly decreasedby both CEE and CEE plus MPA. Of interest, the increase in CRP levelsdue to estrogen was blunted by the addition of progesterone.

FC4.07 LAPAROSCOPIC SURGERY: FALLOPIAN TUBEAND OVARY

FC4.07.01DIAGNOSIS AND ENDOSCOPIC MANAGEMENT OF FALLOPIANTUBE TORSION: PRIOR HISTORY OF TUBAL STERILIZATIONAND PELVIC INFLAMMATORY DISEASE (PID) ASINDEPENDENT RISK FACTORSI. Sozen , A. Arici, Dept. OB/GYN, Yale University School of Medicine,Connecticut, USA.

Objectives: Fallopian tube torsion is a rare but serious gynecologicalemergency. Its occurrence following Pomeroy tubal ligation andlaparoscopic tubal cauterization has been reported. We are presenting acase of tubal torsion that is the first one described in the literaturefollowing an Irving tubal ligation in a patient who also had a history ofPID. We present the etiologic risk factors and clinical features that areessential in the diagnosis. We also demonstrate the laparoscopic viewand management of fallopian tube torsion. In addition, we areintroducing an algorithm to help in selecting the appropriate procedureof tubal sterilization to reduce the risk of subsequent tubal torsion amongpatients with a history of PID.Study Methods: This study includes the presentation of a case of tubaltorsion that is diagnosed and managed laparoscopically and the reviewof the literature through a computerized search of MEDLINE forrelevant cases in the English literature published between January 1966and July 1999.Results: This case appears to be the first tubal torsion following anIrving tubal ligation that is reported. A number of etiologic risk factorsincluding prior tubal sterilization have been suggested in tubal torsion,but history of PID and related tubal occlusion as an independent riskfactor is rarely, if at all, mentioned in the literature. Laparoscopicdiagnosis and management seem to be the ideal approach and treatmentin the cases.Conclusions: Tubal sterilization procedures and PID may play asignificant role in the pathophysiology by creating a complete closedloop of distal tube, making it vulnerable to subsequent formation ofhydrosalpinx and then torsion. We propose that patients with history ofPID who want to undergo a tubal sterilization procedure should becarefully evaluated intra-operatively to select the most appropriateprocedure to reduce the risk of subsequent tubal torsion. We also want tourge physicians to have a high level of suspicion for diagnosis of tubaltorsion in a post-tubal sterilization patient presenting with acute orintermittent pelvic pain, especially if the patient has a history of PID.

FC4.07.02HYPEROSMOLAR GLUCOSE INSTILLATION VERSUSSALPINGOSTOMY BY LAPAROSCOPY IN UNRUPTUREDTUBAL PREGNANCY WITH SERUM ßHCG LEVELS <2500 UI/LMG Arikan , HS Scholz, B Jelinek, A Basver, K Tamussino, A Giuliani,J Haas , P Lang, Dept. OB/GYN, University of Graz, Auenbruggerplatz14, 8036 Graz, Austria

Objectives: To compare laparoscopic instillation of hyperosmolarglucose solution and salpingostomy in treatment of unruptured ectopicpregnancy (EP) concerning short-term outcome measures in aretrospective cohort.Study Methods: The patients with unruptured EP who were operatedbetween 1994 and 1999 were selected by following criteria: desire offertility, intention of tubal preservation, hematoperitoneum <400 ml,preoperative serum ßhCG levels <2500 IU/L. Based on our previousexperience, glucose instillation was considered as effective assalpingostomy in treatment EP with serum ßhCG levels <2500 IU/L andthe method was chosen according to surgeon’s preferences. Thepatients´ outcome who were treated by glucose instillation orsalpingostomy were compared concerning operation time, intraoperativeand final tubal preservation, reinterventions.Results: In 79 of 168 eligible patients a hyperosmolar glucoseinstillation and in 89 a linear salpingostomy were initially performed.There were significant differences (p<0.05) between the glucose group


and the salpingostomy group concerning the operation time (minutes;34±12 vs. 57±20) and the rates of intraoperative tubal preservation(100% vs. 82%, OR: 0.00, CI; 0.00-0.253), operative reinterventions(0% vs. 5%, OR: 0.00, CI; 0.00-1.204) and final tubal preservation(100% vs. 77.5%, OR: 0.00, CI; 0.00-0.187). The rate of methotrexatetherapies did not differ significantly (3.8% vs. 3.4%, respectively).Conclusions: Uncontrolled bleeding during salpingostomy causes aconversion to salpingectomy in a considerable part of patients withectopic pregnancy where initially tubal preservation is intended.Hyperosmolar glucose solution seems to be a simpler procedure thansalpingostomy and is superior to salpingostomy concerning tubalpreservation in therapy of unruptured ectopic pregnancy with serumßhCG levels < 2500 IU/L.

FC4.07.03LAPAROSCOPIC TUBAL END-TO-END ANASTOMOSIS AFTERSTERILIZATIONL. Mettler and E. Lehman-Willenbrock, Dept. OB/GYN, University ofKiel, Kiel, Germany

Objectives: Evaluation of 35 laparoscopic end-to-end anastomosesperformed in sterilized females from 1996-99.Study Methods: Thirty-five patients underwent a laparoscopic tubal end-to-end anastamosis using the isthmic-isthmic or isthmic-ampullaryprocedure.Results: In 35 patients a laparoscopic two-stitch end-to-end anastomosiswas performed, the first stitch for the adaptation of the parametrium andthe second for the adaptation of the muscularis mucosae. This procedurewas performed over a catheter introduced transuterine through theworking channel of a hysteroscope with a careful slice to slice resectionof the tubal end. All patients showed a postoperative tubal patency witha pregnancy success rate of 61% after one year.Conclusions: Laparoscopic microsurgical tubal anastomosis is analternative procedure to microsurgical tubal anastomosis by laparotomyin patients requesting tubal reversal and has replaced the laparotomyprocedure.

FC4.07.04LAPAROSCOPIC ELECTROCAUTERIZATION OF POLYCYSTICOVARIES: PREDICTION OF THE OUTCOMEH. Kamel , M. Zakhira, S. Mostafa, S. Selim, S. Abullah, Dept.OB/GYN, Assiut University Hospitals, Assiut, Egypt

Objectives: To detect the predictors of ovulation and pregnancy afterlaparoscopic electrocautery of polycystic ovaries (PCO).Study Methods: One hundred and fifty infertile women with PCOsyndrome who did not ovulate with clomiphene citrate were subjected tolaparoscopic electrocauterization. Clinical, sonographic and biochemicalassessment receded and followed the operation. Such variables weretested against the outcome: ovulation and pregnancy rates –usingstepwise logistic regression analysis.Results: Galactorrhoea, menstrual pattern, LH/FSH ratio, ovarian stromaappearance and hirsuitism were the predictors of ovulation. The samefactors except menstrual pattern predicted the occurrence of pregnancysignificantly.Conclusions: The estimated probability of outcome (ovulation-pregnancy) could be determined by a regression equation includinggalactorrhoea, ovarian stroma appearance, hirsuitism and menstrualpattern.

FC4.07.05LAPAROSCOPIC OVARIAN DRILLING OF POLYCYSTICOVARIAN DISEASE (PCOD): COMPARISON BETWEENENDOCOAGULATION AND ELECTROCAUTERIZATIONS.A. Abdullah (1), S.A. Mostafa (1), S.M. Selim (2), M.S. Zakhera (1),Faculty of Medicine, Assiut University, Assiut, Egypt.(1) Dept. OB/GYN(2) Dept. Physiology

Objectives: To compare between two methods of laparoscopic ovariandrilling of polycystic ovaries (endocoagulation and electrocauterization)as regards postoperative menstrual cycle, ovulation and pregnancy rateand outcome.

Study Methods: 150 patients with clomiphene citrate resistant PCODwere recruited for this study. They were randomly allocated either toendocoagulation (70 patients0 or electrocauterization (80 patients).Results: Overall postoperative clinical outcome was as follows: Normalmenstrual cyclicity was observed in 91.2% of patients, spontaneousovulation was recorded in 70.3% of patients, increased to 80.4% afteraddition of clomiphene citrate (CC). The pregnancy rate was 99.3%,81.3% were spontaneous. Abortion rate was 22.9%, 75% of themoccurred in the first trimester. Postoperative regular menstrual cycle,ovulation rate and pregnancy rate were 88.4%, 78.3% and 48.5% vs.93.7%, 82.3% and 50% for endocoagulation and electrocauterization,respectively.Conclusions: There is no significant difference between endocoagulationand electrocauterization as regards menstrual cyclicity, ovulation andpregnancy rate. Endocoagulation is effective as electrocauterization inmanagement of CC resistant PCOD.

FC4.07.06LAPAROSCOPIC OVARIAN ELECTROCAUTERY FORMANAGEMENT OF POLYCYSTIC OVARIAN DISEASEA. Kriplani , N. Agarwal, D. Takkar, Dept. OB/GYN, All India Instituteof Medical Sciences, New Delhi, India.

Objectives: To evaluate the efficacy of laparoscopic ovarianelectrocautery on ovulation and pregnancy rates in cases of polycysticovarian disease, (PCOD) resistant to medical induction of ovulation.Study Methods: Forty eight anovulatory infertile subjects wit clinicalendocrine and ultrasonographic characteristics of PCOD underwentlaparoscopic electroagulation of ovarian surface using a triple punctureapproach at operative laparoscopy. Bilateral ovarian drilling was donewith an unipolar diathermy needle (Karl Stroz). Chromopertubation toconfirm tubal patency was done in all the cases. Additional procedureslike laparoscopic tuboplasty, endometrioma fulguration, adhesiolysis,hysteroscopic septum incision and hysteroscopic cannulation offallopian tubes were done at the same sitting in 11 (22.9%) cases.Results: Forty three (89.55%) of PCOD patients ovulated spontaneouslyor following ovulation induction after the procedure. Pregnanciesoccurred in 31 out of 48 (64.5%) of patients.Total pregnancies reported in the serious were 38 in 31 patients as 7patients conceived twice (n=6) and thrice (n=1) including 5 afterabortion and 2 after term pregnancy and delivery.The miscarriage rate was 5.38(13%, no case of multiple pregnancy orectopic pregnancy was reported. None of the cases had anyintraoperative or postoperative complication related to the procedure.Conclusions: Laparoscopic ovarian, electocautery appears to be a useful,safe , easy to perform and cost effective alternative treatment for patientswith polycystic ovarian disease resistant to medical induction ofovulation.

FC4.07.07CHROMOPERTUBATION WITH FLEXIBLE CANNULA INLAPAROSCOPIC EXAMINATION AND RECONSTRUCTIVESURGERY TREATMENT FOR DISTAL TUBAL DISEASEA. Efimenco , M. Ivasi, L. Nacu, F. Bejan, Reproductive MedicineCentre “Gynesource,” Chisinau, Rep. Of Moldova.

Objectives: The evaluation of an easy diagnostic technique and theidentification of its advantages in treating distal tubal disease.Study Methods: 122 women who had laparoscopic surgery wereincluded in this study. Chromepertubation consisted of two stages:Initially, about 20ml of saline solution was injected through the flexiblecannula with the help a Foley type. Then the tubal reconstruction wascarried out through the same cannula and 30-40ml Methylene bluesolution was injected.The average age of the women was 27.8 years (19-39 years). The pre-condition for laparoscopic surgical treatment or all women was primaryor secondary infertility of 2-17 years.Results: Before performing the laparoscopic surgery, all patientsunderwent transcervical cannulisation of the uterine cavity by means offloppy cannulas of a Foley type.For 103 patients (84.4%) the cannula was inserted through the cervixwithout preliminary instrumental dilation. For 97 patients (79.5%) theintra-operative status of the identified Fallopian tubes corresponded tothose on pre-operative stage appreciated by metrosalpingography.


For 69 patients (56.6%), laparoscopic surgery was performed for distaltubal obstruction and peri-adnexal adhesions. In the post-operativeperiod, 26 patients with bilateral occlusional processes in the tubalregion required irrigation of the uterine cavity and reconstruction of theFallopian tubes through same cannula by use of an Aminocapronic Acidsolution with an addition 1.0g of Metronidazolum. The total volume ofacid solution used for irrigation (2.0 liters) was introduced over a 12hour period.Conclusions: From our experience using the tubal chromopertubationwith flexible cannula technique, we have found the procedure to beeasily implemented and effective in the diagnosis and treatment of tubo-peritoneal infertility.

FC4.07.08CHARMONIC SCALPEL IN LAPAROSCOPIC CYSTECTOMY ININFERTILITYE. Garalejic , N. Antic, B. Arsic, M. Vasiljevic, R. Maglic, B. Vasic,Dept. OB/GYN, Clinic of Gynecology and Obstetrics, University ofBelgrade, Belgrade, Yugoslavia.

Objectives: The objective was to prove the preference and conveniencesof using the charmonic scalpel in laparoscopic cystectomy.Study Methods: We operated on 46 patients with ovarian cysts (18simplex, 19 endometriotica and 9 adenofibrosis papillare). We usedultracision made by Johnson’s and Johns.Mechanical cut and coagulation was not used on any patient.We gave Cephalosporin 3.th generation (Longaceph 2 g) to all patientsonce during operation.Results: A second look was done after 6 months. We had no conversionin open operation. In the group of patients with cystis endometriotica 11patients were treated with GnRH (Zoladex-Zeneca) and 8 were not.We did not get recidivism in patients with simplex cystis, adenofibromapapillare and in patients with cystis endometriotica treated with GnRH.Recidivism appeared in 3 untreated patients with cystis endometriotica.Length of hospitalization was 2.2 on averageConclusions: Results show that usage of charmonic scalpel inlaparoscopic cystectomy is effective, certain secure, low cost, beneficialand demands minimum days for hospitalization.

FC4.08 MATERNAL MORTALITY

FC4.08.01MANUAL VACCUM ASPIRATION: REDUCING UNSAFEABORTION AND MATERNAL MORTALITYAdesse, Leila ; Trottier, Dorée; Martins, Jose Francisco

This study examines the effect of manual vacuum aspiration (MVA) inthe treatment of incomplete first-trimester abortions on women'sreproductive health.Since 1994, Ipas, a non-profit women’s health organization, hasimplemented a post-abortion care (PAC) program in partnership withBrazilian public hospitals. The program, which includes training inappropriate uterine evacuation techniques, counseling, equipment, andevaluation, seeks to improve the quality of care for incomplete abortion.Ipas established a data management system to track informationregarding PAC at each of the program sites. Currently, this managementinformation system (MIS) contains data from 14 public hospitalsthroughout Brazil.The objectives of the PAC program include reducing pain, and post-procedure time spent in hospitals. The methods of pain control andcounseling used during the MVA procedure help the woman to be morecomfortable and less stigmatized. Counseling also provides informationabout contraception and reproductive health, thus helping to preventfuture unwanted pregnancies.The results of a total of 7337 MVA procedures show that the majority ofwomen seeking post-abortion care were younger than 39 (94%); and thatalmost a fifth were adolescents (19%). Most (89%) were first timepregnancies; almost half (45.4%) had had no previous abortions.Virtually all of the MVA procedures (99%) occurred by the12th week ofpregnancy and most of the cases (93%) used less invasive pain controlmethods such as sedation, paracervical block, and verbal counseling.Less pain control requires short admission period and reduces hospitalcosts contributing to improve unsafe abortion treatment thus reducingmaternal mortality.

FC4.08.02MATERNAL MORTALITY IN INDIA AND STRATEGIES FORREDUCTIONS. Swain , A. Agrawal, S.S. Raghavan, A. Oumachigui. P. Rajaram,Dept. OB/GYN, Jawaharlal Institute of Postgraduate Medical Educationand Research, Pondicherry, India.

Objectives: This hospital based retrospective study aims at analyzing thematernal mortality at a teaching hospital from South India; studying thedeterminants and formulating strategies for reducing maternal mortalityrate (MMR) in India.Results: There were 193 maternal deaths at the Jawaharlal Institute ofPostgraduate Medical Education and Research Hospital over a period of10 years and there were 36,850 deliveries during the same period. TheMMR in our study was 546/100,000 live births. Most of the directdeaths were attributable to sepsis, pre-eclampsia and eclampsia andhemorrhage. Hepatitis, heart disease and severe anemia were leadingcauses of maternal deaths due to indirect obstetric cause. Most of thedeaths occurred among unbooked cases (95%), illiterates and amongthose who came from far off places and reached the hospital inmoribund condition.Conclusions: This unacceptably high maternal mortality reflects pooroperationalisation of maternal and child health (MCH) care in thecommunity. We recommend a multi-pronged approach includingcomprehensive MCH care for quality antepartum and intrapartum care;timely referral and transportation; education regarding need forsupervised pregnancy and child birth to adolescents in particular and thecommunity in general through the media; competence based curriculumfor medical graduates; monitoring of reproductive behavior throughregional research centers and above all, the state should ensure everywoman a “Right to Safe Motherhood.”

FC4.08.03MATERNAL MORTALITY IN ECLAMPSIAP. Nobis , Dept. OB/GYN, Silchar Medical College, Assam, India

Objectives: The objective of the study was to find out the maternalmortality in eclampsia, to identify the factors responsible for high deathrate and the ways to minimize it.Study Methods: Eclamptic patients admitted in Gauhati Medical Collegefrom 1981 – 1996 and in Silchar Medical College, India from 1978 –1981 and 1997 to 1998 were studied. There were 1706 cases ofeclampsia among 91 706 deliveries. During study period anticonvulsantused were lytic Cocktail (611 cases), diazepam (920), MgSO4 (110) andphenytoin sodium (65 cases).Results: Overall incidence of eclampsia was 1.85%. Maternal mortalitywas 11.54%. It constituted about 30.0% of all maternal death. Theprincipal causes of death were Pul. Edema (19.3%), Heart failure(14.7%), Shock (14.2%), Renal failure (12.7%), Hyper-pyrexia (11.6%),CVAV (7.6%), Broncho pneumonia (10.6%). Factors responsible forhigh mortality were delay in hospitalization, high maternal age,multiparity, lack of antenatal care and low income.Death rate was low in patients treated with MgSO4 (3.7%) in comparisontoe Phenytoin sodium (4.6%) and diazepam (9.0%).Conclusion: MgSO4 is the drug of choice.To minimize the mortality rate we have to improve socio-economiccondition, transport facility, to make Medical facilities available toeverybody. Community health worker should encourage the pregnantwomen for antenatal care and above all to improve the status of womenin society.

FC4.08.04DIRECT MATERNAL DEATHS AND HEALTH CARE FACILITYR. Bagga , S. Gopalan, D. Malhotra, V. Jain, Dept. OB/GYN,Postgraduate Institute of Medical Education and Research, Chandigarh,India

Objectives: The aim of the study was to analyze the causes of directmaternal deaths and the appropriateness of medical care provided atvarious levels.Study Methods: Forty-eight direct maternal deaths which occurred overa 2 year period (Jan. 1993-Dec. 1994) and 58 deaths over another 2 yearperiod 5 years later (Jan. 1998-Dec. 1999) at a tertiary care hospital werestudied. Data recorded included the condition of the woman on


admission, treatment received at various medical centers and reason forreferral. The management received in the tertiary care hospital andsequence of events preceding death were analyzed.Results: Of the 48 direct maternal deaths in the initial 2 year period, theobstetric causes were haemorrhage (16), Septic abortion (14), puerperalsepsis (9), chorioammnionitis (3) and hypertensive disorders ofpregnancy (6). Nearly 90% of the women were referred from primary ordistrict healthy care facilities and most (75%) were in a moribundcondition on admission. Medical facility failure was a significant factorcontributing to maternal deaths in 69% of the women. This was presentin all deaths due to hypertensive disorders of pregnancy; n three-fourthswomen who died of hemorrhage; in two-thirds of deaths due to septicabortion and chorioammnionitis and about half deaths due to puerperalsepsis. The comparison of these results with another 58 direct maternaldeaths 5 years later showed no significant difference.Conclusion: In spite of the existing good infrastructure provided by theGovernment of India, failure of health care providers to give quality careresulted in maternal death.

FC4.08.05AN ANALYSIS OF THE MATERNAL MORTALITY AT ATERTIARY LEVEL REFERRAL CENTERK. P. Tilwani , Dept. OB /GYN, Indira Gandhi Medical College,Nagpur, Maharashtra, India.N. P. Kulkarni, Dept. OB /GYN, Indira Gandhi Medical College,Nagpur, Maharashtra, India.

Objectives: The aim of the study was to analyse the causes of maternalmortality in a tertiary level referral center, i.e. a medical college, in adeveloping country(India).Study Methods: The aim of the study was to analyse the causes ofmaternal mortalities at Indira Medical College, Nagpur, Maharashtra,India, from 1st January 1999 to 31st December 1999, when there were 4,044 deliveries, 423 abortions, 350 medical terminations of pregnancy(MTP) and 27 maternal deaths. the maternal mortality rate (MMR) of 5 -6 per 1000 was extremely high when compared with the National Targetof 2 per 10,00 by 2000 A. D. and with other institutions, probablybecause a majority of these cases were unsupervised pregnancies fromremote, rural areas, low socio-economic strata and illeteratebackgrounds. More than 50% cases came in a moribund state and diedwithin 24 hrs. of admission.Results: The causes of these deaths were eclampsia and itscomplications (29%), infections (17.5%, 10.5% of which were due tocriminal abortions), haemorrhage (14%), pulmonary embolism(7%),intra-operative cardiac arrest(7%), metabolic encephalopathy(3-5%),MTP related deaths(3.5%),vesicular mole with massive trophoblasticembolisation(3.5%) and anaemia(3%).Conclusion: High MMR is directly related to poverty, illeteracy,unawareness, poor general condition of women and lack of propermedical facilities in remote, rural areas, of the community, so MMR canbe reduced by improving them.

FC4.08.06MATERNAL MORTALITY & MORBIDITY IN ACUTE RENALFAILUREN. Chavan , Lecturer, Dept. of OB/GYN, Lokmanya Tilak MedicalCollege & General hospital, Sion, Mumbai India.K.N. Chavan, S.D. Shirodkar, V.R. Badhwar

Objectives: The aim of the study is to evaluate obstetric outcome andincidence of Acute Renal Failure (ARF).Study Methods: Total number of patients delivered from Jan. 1998 toJune 1999 in our institute were 10,189. 32 patients were diagnosed withARF. The obstetric and medical etiologocal factors causing ARF andpatients outcome were studied.Results: The incidence of ARF is 0.314%. 53.34% patients were ANCunregistered while 46.87% were ANC registered. 43.75% wereprimigravidas. 14 patients were in age group of 25-30 yrs. 50% patientsdelivered vaginally, 25% underwent LSCS, 1 patient of tubal ectopicpregnancy, 3 patients underwent spontaneous abortion, 1 MTP & 1undelivered. PIH & Eclampsia (40.625%) is commonest obstetric causewhile Cerebral Malaria (18.75%) is commonest medical cause of ARF.65.62% patients received ventilatory support and 18.75% received

dialysis. Maternal mortality was observed in 21 cases (65.625%). Deathusually is due to multisystem organ failure.Conclusion: Even at doorstep of tertiary center ARF has a majormaternal mortality & morbidity. Initiation of management should startwith early ANC registration, prompt treatment, rapid delivery inuntreatable cases, teamwork efforts of Obstetrician, Nephrologist withadvanced AKD facility, Blood bank facility and paramedical help.

FC4.08.07CAUSES OF MATERNAL MORTALITY(1975-1999): RESULTSFROM THE LARGEST MATERNITY HOSPITAL OF TURKEYE.G.Yapar Eyi, C.Gulerman, O.Gokmen, High Risk Pregnancy Unit,Zekai Tahir Burak Women's Health Education & Research Hospital, IcelSokak, No:4/8, Ankara, Turkey, 06420.

Objective: Although maternal mortality has declined, it still continues tobe a major health problem. This paper reports the maternal deaths overthe last 25 years at Zekai Tahir Burak Women's Health Education &Research Hospital, Ankara, Turkey.Materials & Methods: All maternal deaths from 1975 to 2000 werereviewed and classifiedResults: There were 439 maternal deaths in 518067 live births, giving anoverall maternal mortality rate of 84.7/100.000. Maternal mortality ishighest in 1980 with a ratio of 234.0/100.000(52/22.248) and lowest in1996 with a ratio of 4.8/100.000(1/20.770). Hemorrhage(37%), sepsisdue to abortion(15%) and eclampsia/preeclampsia(37%) constituted themajor causes of deaths between 1974 & 1980. The causes of death wereeclampsia/preeclampsia (31%), hemorrhage(15%) and embolism(10%)inthe recent 5 years.Conclusion: Maternal deaths declined at our institution; however the rateis still high and further improvements are needed.

FC4.09 NEONATALOGY

FC4.09.01PERINATAL SUBSTANCE ABUSE TREATMENT DECREASESNEED FOR NEONATAL ASSISTED VENTILATIONMA Armstrong , DM Carpenter, L Lieberman, LT Midanik, VMGonzales, and GJ Escobar, Division of Research, Kaiser Permanente,Oakland, CA 94611, USA.

Objectives: This study evaluated neonatal outcomes among womenserved by the Early Start Program, an obstetric clinic-based perinatalsubstance abuse treatment program in a managed care organization.Study Methods: We identified 30,858 women who delivered infantsfrom 7/95-6/98 and who completed Early Start Prenatal SubstanceAbuse Screening Questionnaires (screeners). We electronically linkedscreeners, patient assessments, treatment data, pregnancy toxicologyscreen (tox) results, and neonatal outcomes. Women were categorizedinto six groups for comparisons. Women assessed by an Early Starttherapist were either (1) assessed positive as substance abusers and hadfollow-up treatment (n=989) or (2) assessed positive with no treatment(n=442). Women who were not assessed were divided into 4 groups: (3)positive screener and positive tox (n=225), (4) positive screener but nopositive tox (n=3,247), (5) negative screener but positive tox (n=306),and (6) negative screener and no positive tox (controls, n=25,649). Oneoutcome evaluated was neonatal assisted ventilation (vent).Results: Infants of treated women had vent rates (1.8%) similar tocontrol infants (2.2%, p=0.5), but infants of untreated women assessedas substance abusers had higher vent rates (3.4%) than controls (p=0.08).Infants of women who screened negative but had a positive tox hadsignificantly higher vent rates (6.2%) than either controls (2.2%,p=0.001) or infants of treated women (1.8%, p=0.001).Conclusions Substance abusing women who receive counseling duringpregnancy have infants who do almost as well as infants of non-substance abusing women and are less likely to require assistedventilation than infants of untreated substance abusers.


FC4.09.02CEREBRAL PALSY AND CORD AROUND THE NECK AT BIRTH-A SPURIOUS ASSOCIATION?C E L Greenwood , L W Impey, S Sellers John Radcliffe Hospital,Oxford, UKE M McDonald, A Johnson, National Perinatal Epidemiology Unit,Oxford, UK.

Objectives: To investigate the association between nuchal cord at birthand the development of cerebral palsy (CP) in infants born at or near toterm.Study Methods: A population-based case control study covering 2former Health Authority areas, between 1987 and 1993, comparing theobstetric records of 75 children with spastic CP and 215 randomlyselected controls born at 36 weeks or more of pregnancy.Results: In hospitals where cord round the neck is recorded as free text,28.9% of 45 cases and 14.3% of 133 controls (18% overall) had a nuchalcord. There was an association between nuchal cord and CP (OR 2.44,95%CI 1.09-5.46) and Apgar score <5 at 1 minute (OR 2.78, 95%CI1.11-3.70).In hospitals where records included a tick box for nuchal cord, 26.7% of30 cases and 31.7% of 82 controls (30.5% overall) were recorded ashaving a nuchal cord. No association between nuchal cord and CP (OR0.78, 95% CI 0.31-1.99) or Apgar score <5 at 1 minute (OR 1.76, 95%CI 0.61-5.08) was evident.Conclusions: The presence of nuchal cord is subject to recording biasunless it is recorded after all deliveries. In a retrospective study this canlead to an apparent association of CP with nuchal cord, which is nolonger evident where documentation is more systematic.

FC4.09.03AETIOLOGY AND OUTCOME OF FETAL HYDROPS:RETROSPECTIVE CASE SERIESK. M. K. Ismail ,W. L. Martin, S. Ghosh, M. J. Whittle,M. D. Kilby, Dept. OB/GYN, Birmingham Women’s Hospital,Birmingham, UK

Objectives: To identify the aetiology and pregnancy outcome of hydropsfetalis (HF) referred to a tertiary maternal fetal medicine referral centre.Design: A retrospective review of casenotes.Setting: A regional referral fetal medicine unit at a university hospital.Population: Sixty-three consecutive cases of HF over a 31-month period(from September, 1996 until March, 1999).Methods: information from case notes were entered on Microsoft Excelspread sheets. Comparisons were made using its statistics package.Main outcome measures:Aetiology of fetal hydrops, gestation at diagnosis, gestation at delivery,patterns of distribution of effusion fluid in the different aetiologies andpregnancy outcome.Results: Eight pregnancies (12.7%) were associated with an ‘immune’aetiology. Of these, 62.5% had fetal anaemia due to anti-D, 25% anti-Kell and 12.5% anti-c antibodies.The remaining 55 cases (87.3%) had a non-immune cause. Of these14.5% were due to severe in-utero anaemia associated with maternalhuman Parvovirus B19 infection. Fourteen cases were associated withaneuploidy, and in a further 4 (7.3%), a primary hydrothorax(subsequently chylothoraces) was the cause of the non-immune hydropsfetalis (NIHF). Fetal cardiac causes accounted for 9.1% of cases. Four ofthese five cases were either incessant tachyarrythmia (supraventriculartachycardia in 3 cases) or in one case, complete heart block. Cystichygroma was associated with HF in 6 cases, fetal akinesia and twin twintransfusion syndrome were represented in two cases each. Massivetransplacental feto-maternal haemorrhage was identified in one case. In14.5% of cases no obvious cause was identified and were classified as’idiopathic’. Three other cases could not be classified because parentsdeclined investigations (unclassified). In the NIHF the outcome wasfavourable in 27.3% of cases.Conclusion: The prognosis of hydrops fetalis differs markedly betweendifferent aetiological groups. Prenatal diagnosis of the aetiology ofNIHF is crucial in determining outcome, counseling parents andplanning management. Aetiologies range from treatable causes with agood outcome and probably no long-term side effects (as in case ofParvovirus B19), to others, which are incompatible with life or areassociated with considerable perinatal morbidity and mortality.

FC4.09.04INHALED NITRIC OXIDE IMPROVED SURVIVAL IN HIGH-RISKCONGENITAL DIAPHRAGMATIC HERNIAZ. Stranák , J. Janota, K. Pycha, J. Snajdauf, M. Rygl, J. FeyereislInstitute for the Care of Mother and Child, Dept. OB/GYN, PostgraduateMedical School, Prague, Czech Republic.

Objectives: We evaluated effectiveness of inhaled nitric oxide (INO)during preoperative stabilisation in left-sided congenital diaphragmatichernia (CDH) with respiratory distress syndrome (RDS) up to 6 hr afterdelivery.Study Methods: Forty-seven CDH patients were admitted to our NICU.A total of 39 newborn infants met our inclusion criteria. Our criteria forusing INO were these: alveolo-arterial oxygen difference (AaDO2) >550 mm Hg at FiO2 = 1.0, ultrasonographic evidence of pulmonaryhypertension, pre-ductal and post-ductal differences in SaO2 and/orPaO2. Patients inhaled an initial dose of 20 ppm NO. A failure in INOsuggested an immediate use of ECMO. The start of ECMO waspreceded by a therapeutic trial using high frequency oscillatoryventilation (HFOV) together with INO. Surgery was not started before24 hr after delivery.Results: Criteria indicating the use of INO were met by 22 patients(56%). INO was effective in 11 patients (50%) and all of thesessurvived. 10 patients (45%) of the INO treated group died despite usingHFOV and ECMO in 3 cases. Total mortality of the study group was26%. A comparison of surviving infants with out INO (n=17), INO-treated surviving patients (n=12) and INO-treated non-surviving patients(n=10) there occurred significant differences in oxygenation index (OI)and alveolo-artereial oxygen difference (AaO2) among groups(p<0.0001). In these groups, a significant difference in time wasobserved in AaDO2 (p<0.01) and in the course of time 2 hr and 12 hrafter admission of OI and AaDO2 in all groups (p<0.0001 resp. p<0.05).Conclusions: In conclusions, in our study group INO was effectiveduring preoperative stabilisation in patients with reversible RDS. Nopositive effect of INO seemed to be early predictor of mortality in CDHpatients with severe pulmonary hypoplasia.Supported by grants IGA MH CR 4733-3 and 4735-3

FC4.09.05LOW APGAR SCORES – CAUSES AND SIGNIFICANCEV. Jain (1), R. Bagga (1), S. Gopalan (1), A. Narang (2)(1) Dept. OB/GYN, Postgraduate Institute of Medical Education and

Research, Chandigarh, India.(2) Dept. Neonatology, Postgraduate Institute of Medical Education and

Research, Chandigarh, India.

Objectives: To identify the obstetric causes of low Apgar scores at oneminute and to ascertain their significance in the development of hypoxicischaemic encephalopathy (HIE).Study methods: In a prospective study from January to August 1998 allsubjects (222) with Apgar scores less than 7 at one minute wererecruited. The most probable obstetric cause was ascertained and theneonatal outcome was studied.Results: The incidence of low Apgar score was 11.7%. Of these 64%had Apgar scores between 4 – 6 and only 36% had Apgar score less than4 at one minute. In 84.09% cases the Apgar score improved to 7 or moreat five minutes of life. APH and PIH together accounted for about 50%cases of low Apgar score. Signs of acute fetal distress were absent in61% and 42% cases of Apgar score 4 – 7 and less than 4 respectively.HIE developed in 8% neonates with Apgar score 4 – 7 and in 27% withApgar score <4 at one minute. The incidence of HIE was significantlyhigher when Apgar score at 5 minutes was 4 – 7 (26%) and <4 (54%).Conclusions: Low Apgar scores may be anticipated in patients withAPH and PIH even in the absence of signs of acute fetal distress. Apgarscore at one minute may be used as a screening procedure for furtherresuscitative measures. However, Apgar score at five minutes is morepredictive of neonatal outcome.


FC4.09.06PECULIARITIES OF IMMUNE SYSTEM OF NEONATES OFMOTHERS WITH ANTIPHOSPHOLIPID SYNDROMEL.P. Ponomarova , L.V. Vanko, O.E. Bondar, N.K. Matveeva,N.S. Loginova, Russian Research Center for Perinatology, Obstetric andGynaecology, Moscow, Russia

Antiphospholipid syndrome includes habitual miscarriages withhyperproduction of specific antiphospholipid autoantibodies anddisorders of haemostasis. complex therapy includes prednisolon in lowdosage and lets women save pregnancies. the aim of research was toreveal the peculareties of immune system of neonatis born from motherswith antiphospholipid syndrome. was examined immune status of 84mature newborn of mothers with antiphospholipid syndrome and 32newborn of control group. we examened subpopulational division oflymphocytes by flowing cytometria. functional activity of leucocyteswas checked with luminoldepended chemiluminescention. we evaluatethe interferon status by the method of soloviev-bechtemirov. wasrevealed significantly higt number of cd3+, cd4+, cd19+ lymphocytesand cells with adhesive molecules (cd11b+) in 5-7 days, high level ofserum interferon, significant decrease of g-interferonproductive activityof umbilical and venouse blood cells in 5-7 days and elevated level ofspontaneus chemiluminescention of leucocytes. level of umbilicalcd11b+ correlattes with every day dosage of hormone taken by motherduring the pregnancy. our results demonstrate tensive immunity ofchildren born to mothers with antiphospholipid syndrom in first 7 daysof neonatal adaptation.

FC4.09.07MATERNAL AND UMBILICAL CORD BLOOD LEAD LEVELS INTEHRAN, IRANA. Akbarian , A. Mehdizadeh, M. Khalilipour, M. Moshfegi, M.Mogtahedi, R. Alaghehbandan, Dept. OB/GYN, Iran University ofMedical Sciences, Nyayesh Street, Sattarkhan Avenue, Tehran, Iran

Objectives: In Tehran, as in many other capitals in the world,environmental lead exposure with its concomitant risk of neurotoxicityremains a major health hazard for the population. Prenatal exposure tolead has been associated with abnormal neurobehavioral development inchildren. The lack of safe and cost-effective treatments for low-levellead poisoning has promoted environmental interventions to controldifferent sources of lead. The aim of this study was to evaluate thematernal and umbilical cord blood lead levels in 80 consecutive mother-infant pairs in order to determine whether neonates in Tehran are in thehigh -risk group.Study Methods: During 1997-98, we conducted a survey of maternal andumbilical cord blood lead levels of 80 pregnant women and their healthynewborns at two teaching hospitals affiliated to Iran University ofMedical Sciences, Tehran. Lead levels in umbilical cord blood andmaternal venous blood were measured by atomic absorptionspectrophotometry.Results: The mean maternal age was 25.7 years, ranging from 17 to 39years. The mean of parity was 2. Maternal blood lead levels ranged from3.7 to 57.6 mg/dl with a mean of 26.8 mg/dl and a standard deviation of2.9 mg/dl. The umbilical cord blood lead levels varied between 0.3 to110 mg/dl with a mean of 31.7 mg/dl and a standard deviation of 2.9mg/dl. Concentrations of above 10 mg/dl were found in 86% of theneonates. There was significant correlation between the maternal andcord blood lead levels (r = 0.3, P < 0.02). There was also significantcorrelation between the cord blood lead levels and birth weight (r = 0.2,P < 0.05). However no significant correlation was found betweenmaternal lead levels and birth weight.Conclusions: It seems that prenatal lead exposure has become animportant health issue for young children in Tehran. It is necessary toreduce atmospheric lead as one of the most important primaryenvironmental sources of lead by replacing leaded gasoline withunleaded gasoline.

FC4.09.08THE EFFECT OF MODE OF DELIVERY ON NEONATALOUTCOME OF TWINS WITH BIRTHWEIGHT UNDER 1500g.S.M. Ziadeh , E. Sunna, L.F. Badria, Dept. OB/GYN, Jordan Universityof Science and Technology, Amman, Jordan.

Objective: The purpose of this retrospective study was to evaluate themode of delivery on neonatal outcome of twins weighing < 1500g.Study MethodsWe reviewed the effect of birth order, presentation, and method ofdelivery on neonatal outcome in twin gestation under 1500g. at PrincessBadeea’ Teaching Hospital in North Jordan over the 6 years from 1994 –1999.Results: During the study period, there were 51, 475 deliveries of which695 were twin gestations. One hundred and eight (108) sets of twinsweighing < 1500g. were included in this study (15.5%), of which 41were in vertex-vertex presentation, 40 in vertex-nonvertex presentation,and 27 with first twin in nonvertex presentation. The second twinpregnancies characterized by a higher incidence of respiratory distresssyndrome (82 vs 70%; P=.02), more neonatal mortality (23 vs 17.6%),and lower Apgar score at 1 and 5 minutes. Cesarean delivery for vertex-vertex presentation did not improve the neonatal outcome. Rather, theincidence of RDS was significantly greater in this group delivered bycesarean section (65.6 vs 42%; P=.012).For nonvertex presentation, those delivered by cesarean section had alower incidence of neonatal mortality.Conclusion: We concluded that there was no advantage for cesareandelivery could be demonstrated after multivariate analysis to correct thedifferences in birthweight between the groups. Therefore, the differencesin the neonatal outcome of nonvertex twins presentation accounted forthe difference in birthweight, rather than in mode of delivery.Keywords: Twin pregnancy <1500g., mode of delivery, neonataloutcome

FC4.10 OVARIAN CANCER: RISK OF MALIGNANCYASSESSMENT

FC4.10.01OVARIAN CANCER DETECTED NON-INVASIVELY BYCONTRAST ENHANCED POWER DOPPLER ULTRASOUNDT. D’Arcy , Dept. Gynaecology, CoombeWomen’s Hospital.Dublin 8V. Jayaram, Dept. Imaging, Imperial College of Science Technology andMedicine Hammersmith Hospital, London W12 OHS.M. Lynch, Dept. Imaging, Imperial College of Science Technology andMedicine Hammersmith Hospital, London W12 OHS.P. Soutter, Dept. Gynaecology Oncology. Imperial College of ScienceTechnology and Medicine Hammersmith Hospital, London W12 OHS.D. Cosgrove, Dept. Imaging, Imperial College of Science Technologyand Medicine Hammersmith Hospital, London W12 OHS.

Objectives: the purpose of this study was to assess the effect ofintravenous contrast enhanced high-resolution grey-scale ultrasoundwith power doppler in detecting small ovarian malignancies.Methods: Twenty women undergoing a laparotomy for suspected earlyovarian malignancy were scanned with high-resolution grey-scaleultrasound and power Doppler before and after the administration ofLevovist. A vascular morphological score was devised, based on ovariantumoral vessel location, complexity and density. A score of 8 or abovewas used to identify malignancy. This was compared with the relativemalignancy index described by Jacobs in which a value greater than 250was regarded as suspicious of malignancy.Results: There were 13 benign, 3 borderline and 4 malignant tumours.Their respective mean diameter and range were 9cm (5 to 17 cm), 10cm(8 to 11 cm) and 10cm (7 to 13 cm). Half the invasive tumours wereidentified before contrast enhansement. All were identified after contrastenhansement with excellent interobserver agreement. The RMIidentified 2 of the 4 invasive lesions. The 3 borderline tumours wereindistinguishable from the benign lesions by all parameters.Conclusion: A vascular morphology score, facilitated by intravenouscontrast enhanced Power Doppler may be an accurate way of selectingwomen who require surgery


FC4.10.02USING LOGISTIC REGRESSION MODEL TO PREDICT OVARIANMALIGNANCY: WHICH PARAMETER PERFORMS BEST?H. Marret (1), R. Ecochard (2), F. Golfier (3), D. Raudrant (3)(1) Dept. OB/GYN, Bretonneau University Hospital, Tours Cedex,

France(2) Dept. of Medial computing and Biostatistics, Lacassagne center

University, Lyon, France(3) Dept. OB/GYN, Hôtel Dieu University Hospital, Lyon, France

Objective: Multivariate logistic regression analysis was used to improvethe preoperative diagnosis of ovarian malignancy using color dopplerenergy, Gray-scale sonographic parameters and CA125 serum level.Methods: One hundred and forty three adnexal masses were studied withtransvaginal B-mode ultrasonography and color doppler energy. We hadincluded each ultrasonographic variable (tumor size, wall thickness,septal structure, echogenicity, papillary projection, density (solid ornot)). Intratumoral blood flow velocity waveforms were obtained todetermine resistance index and location of the tumor vascularity.Menopausal status and serum CA 125 levels were also entered ascategorical variables.Results: Eighteen adnexal masses (12.7%) were malignant or lowmalignant potential ovarian tumors. Multivariate analysis showed thatpapillary projection of the tumor wall and blood flow central location,were the only factors to be independent predictors of malignancy. Allother parameters were not independent factors. Sensitivity, specificity,predictive positive value and negative predictive value were 94%, 84%,46% and 99% respectively, with a cut off value of 25% probability ofmalignancy. Only one ovarian cancer but 16% of the benign masseswere misclassified.Conclusion: Sonographic analysis using color doppler energy andmorphologic parameters is a simple but not perfect method todiscriminate benign and malignant ovarian tumors. In our experience theparameters that performed best were papillary projections and bloodflow location.

FC4.10.03CLINICAL EVALUATION OF COMPUTER AIDEDMULTIVARIATE PATTERN ANALYSIS SYSTEM II (CAMPAS OVII) FOR DISCRIMINATING MALIGNANT FROM BENIGNOVARIAN MASSES (BOM)E. Kimura , S. Kobayashi, K. Oura, M. Yasuda, K. Ochiai, T. Tanaka,Dept. of OB/GYN, Jikei University, School of Medicine, Tokyo Japan.

Objectives: We previously reported that CAMPAS using biomarkerswas developed and a prospective clinical study of CAMPAS OV II wasperformed (ASCO ABST #261, 1994). In this study, we confirm theusefulness of CAMPAS OV II retrospectively after clinical application.Study Methods: Between Oct. 1994 and March 1999 CAMPAS OV IIwas applied to patients with ovarian masses (POM) for discriminatingmalignant ovarian tumors (MOT) form BOM. Serum samples werecollected from 2876 POM at outpatient department (OPD) of the Jikeiuniversity hospital and simultaneously measured level of CA 125,Immunosupressive acidic protein, tissue polypeptide antigen, alkalinephosphatase, albumin and Fe for analysis by CAMPAS.Results: 680 out of 2876 POM were operated on, and the other 2196POM are being followed at OPD. The results of CAMPAS OV II werecompared with the histopathological diagnosis in operated POM. Thesensitivity of CAMPAS OV II was 96.7%(89/92) for MOT and 33.3%(6/18) for tumors of borderline malignancy. The specificity was 90.2%(514/570) for all BOM and 82.6% (133/161) for endometrial cyst. Of the36 stage I MOT, 32 cases had a positive result with CAMPAS OV II andthe sensitivity was 88.9% (32/36). Totally, the accuracy of CAMPASOV II was 91.1% (603/662).Conclusions: It was confirmed that CAMPAS OV II is an effectivediagnostic method for discriminating malignancy including early stagecases from BOM at general OPD.

FC4.10.04A NEW HISTOPATHOLOGIC GRADING SYSTEM FOR OVARIANCARCINOMAY. Shimizu (1), K. Hasumi (1), S. Kamoi (2), S. Amada (3),S.G. Silverberg (4)(1) Dept. OB/GYN, Cancer Institute Hospital, Tokyo, Japan.(2) Dept. OB/GYN, Nihon Medical School, Tokyo, Japan(3) Dept. OB/GYN, Kyushu University Hospital, Fukuoka, Japan.(4) Dept. Pathology, University Maryland Med. Syst., Baltimore,

Maryland, USA.

Objectives: To assess whether a new histopathologic grading system,which was previously proposed by authors, works as a prognostic factorfor ovarian carcinoma (OC).Study Methods: For the above purpose, clinicopatholigical analyseswere made on 538 consecutive patients with OC treated in a uniformmanner between 1980 and 1994 with surgery and platinum-basedchemotherapy. All sides were reviewed and the tumors graded asfollows: architectural pattern (predominant): glandular=1, papillary=2,and solid=3; nuclear pleomorphism: slight=1, moderate=2, andmarked=3; mitotic figures /10 high power fields: 0-9=1, 10-24=2, and25£=3; total score 3-5=Grade 1, 6 or 7=Grade 2, and 8 or 9= Grade 3.Results: The new tumor grade significantly correlated with survival inboth early (FIGO stage I/II) and advanced (III/IV) OC except clear cellcarcinoma (CCC). Results for CCC approached but did not reachstatistical significance. By multivariate analysis, only this tumor gradeand performance status (PS) were significant in early stage OC. Foradvanced OC, the new tumor grade also was significant, as were PS,residual tumor size, response to chemotherapy, and mucinous(unfavorable) or transitional cell (favorable) histologic type. FIGO grade(based primarily on architectural features) did not work as a significantprognostic factor in either early or advanced stage OC.Conclusion: The present study confirmed the clinical utility of the newgrading system for all clinical stages and histologic types except CCC.

FC4.10.05FINE NEEDLE ASPIRATION CYTOLOGY IN DIAGNOSIS OFPELVIC ADNEXAL MASSESS. Goyal , J. Kalra, S. Gopalan, Dept. OB/GYN, Nehru Hospital,Postgraduate Institute of Medical Education and Research, Chandigarh,India.

Objectives: The aim of the study was to determine the accuracy of fineneedle aspiration cytology (FNAC) in evaluation of the nature of pelvicadnexal masses.Study Methods: Sixty-one women with a clinical diagnosis of adnexalmass were recruited in this prospective blinded study. FNAC was carriedout with or without ultrasound guidance and a cytological diagnosis wasmade. Exploratory laparotomy and excision of adnexal mass was done in43 women to confirm the diagnosis histologically. FNAC diagnosis wascorrelated with the final histological diagnosis using McNemar’s ChiSquare test.Results: The age of the women ranged from 15 to 76 years with 37.7%of them being postmenopausal. FNAC was carried out transabdominallyin 93% of the cases with sonography guidance in 41%. Inadequateaspiration material was obtained in 5 women. Histological confirmationof diagnosis after excision of the adnexal mass in 43 women showedFNAC to have a sensitivity and specificity of 87.5% and 100%respectively for prediction of malignancy with an overall accuracy of94.7%. FNAC was also able to diagnose specifically the type ofmalignant pathology accurately. Benign lesions such as endometriosis,dermoid and inflammatory masses were also accurately diagnosed in allcases.Conclusions: FNAC is a simple and safe procedure for evaluation of anadnexal mass with an excellent accuracy of diagnosis when done underultrasound guidance and this can be beneficial in planning themanagement of and adnexal mass particularly in younger women.


FC4.10.06USING A LOGISTIC REGRESSION MODEL TO PREDICTOVARIAN MALIGNANCY BASED ON GRAY-SCALE ANDCOLOR DOPPLER ULTRASOUND FINDINGS COMBINED WITHANGIOGENIC CYTOKINES SERUM LEVELS.A.Czekierdowski, H. Zrubek and J.KotarskiIst Department of Obstetrics and Gynecology, Univ.School of Medicinein Lublin, POLAND

Background: Clinical and experimental data clearly indicate acorrelation between new blood vessel formation, metastatic spread andaggressiveness of ovarian cancer. Currently, the development of thesevessels can be studied with the use of color Doppler sonography or bymeasurements of several specific factors involved. Potential serummarkers may include angiogenin (ANG) and vascular endothelial growthfactor (VEGF), both of which have been identified as importantangiogenesis modulators.Objective: We sought to investigate whether a combination of serumangiogenin and VEGF levels along with several currently used gray-scale criteria and color Doppler blood flow assessment can be useful inpreoperative discrimination of ovarian tumors.Methods: Patient’s age, menopausal status, ultrasound gray-scale andcolor Doppler sonography combined with serum CA-125 (Roche,Switzerland) antigen and two cytokines: angiogenin and VEGF (R&DSystems, USA) measurements were evaluated in women who weresubsequently operated because of adnexal tumors. Logistic regressionanalysis was then used to determine which of the 14 independentvariables had prognostic significance in the constructed predictivemodel.Results: There were 65 benign and 13 (3 stage I) malignant tumors in 78patients. Median serum values in benign tumors were as follows: ANG –410,8 pg/mL (range: 98,3-956,3 pg/mL), VEGF-274,3 pg/mL(range:52,1-1142,0 pg/mL); CA-125 – 20,3 IU/ml (range 3,1-999,3 IU/ml).Median serum concentrations in women with malignant tumors were asfollows: ANG – 469,1 (range: 65,3-1103,0 pg/mL), VEGF-365,4 pg/mL(range: 67,4-1243,1 pg/mL); CA-125 – 88,1 IU/ml (range 8-943 IU/ml).A logistic regression analysis revealed that the important prognosticfactors included: patient’s age and menopausal status, presence ofpapillary projections in the tumor wall, color Doppler vascularityassessment and resistive index measurements. Other variables appearedto be non-predictive.Conclusion: Angiogenin and vascular endothelial growth factor serummeasurements do not seem to add prognostic value to the establishedsonographic criteria of ovarian malignancy.

FC4.10.07THE ABILITY OF DYNAMIC CONTRAST ENHANCED MRI (DCE-MRI) TO PREDICT MALIGNANCY OF OVARIAN CARCINOMAG.H. Hall (1), S.L. Atkin (2), L.W. Turnbull (1)(1) Dept. Radiology, University of Hull, Hull, UK.(2) Dept. Medicine, University of Hull, Hull, UK.

Objectives: The diagnosis of ovarian malignancy with CT andconventional MRI has been extensively studied, and whilst bothtechniques have good sensitivity, the specificity and hence the ability todiscriminate benign from malignant disease is limited. We investigatedthe ability of DCE-MRI to improve the specificity of malignancydetection using pharmacokinetic modeling.Study Methods: 86 women with suspected ovarian pathology on USSwere referred for DCE-MRI. A region of interest was selected from asolid component of the tumor and pharmacokinetic modeling appliedusing an open linear 2 compartment model. Data was acquired foramplitude of the upslope, exchange rate, maximum enhancement factorand distribution volume for all tumors.Results: 21/86 women did not have ovarian pathology on MRI. Of theremaining 65 women, 31 lesions were classified as benign on the basisof morphology alone (simple thin walled cysts with no solid componentsor endocystic projections). The 34 remaining lesions underwentpharmacokinetic modeling. Using the amplitude of the upslopecombined with morphology to differentiate benign from malignantdisease the total accuracies obtained were sensitivity 74%, specificity97%, PPV 87%, NPV 93% and overall accuracy 92%.Conclusions: DCE-MRI is a valuable tool in the pre-operativeassessment of an adnexal mass – allowing differentiation of non-ovariandisease and more accurate classification of the malignant potential of the

ovarian tumor. Dynamic assessment of the vascular properties of thetumor may allow prediction of which tumors will respond to anti-angiogenic therapy.

FC4.10.08COMPARISON OF ACCURACY OF DIAGNOSTIC OVARIES CYSTBETWEEN VAGINAL SONOGRAPHY AND CYTOLOGY FINDINGA.Aflatounian 1,2 and R. Aflatounian2 1Department of Obs. & Gyn. Medical Sciences University, Yazd-Iran.2Madar Hospital for Women, Mahdieh Square, 89167, [email protected]

Objectives: To compare accuracy of vaginal sonography and cytologyresults on ovary fluid before ovarian cyst aspirationStudy Methods: Eighty-two women who were undertaken contraceptivepills for 3 months without effect on cyst were enrolled in our study. Cystfluid aspiration under vaginal sonography guided was performed. Beforeaspiration sonography pattern, color and volume of aspirated fluid andcytologic results were analyzed.Results: The accuracy of sonography pattern about cyst functional(94.9%), in endometrium (97.5%) and in benign epithelial (97.5%) werein agreement with cytological finding.Conclusions: Vaginal songraphy is a cost effective, simple and withoutcomplication. From these finding it could be suggested that according tothe sonography pattern when there is not evidence of malignancy, in thecase of persistent cyst can be aspirated by vaginal.

FC4.10.09THE INTERVENTIONAL ULTRASOUND IN DIAGNOSTICS ANDTREATMENT OF OVARIAN MASSESV. Artyomenko , A. Zelynsky, V. Lebedenko, Dept. Perinatal Medicine,Child and Adolescent Gynecology, Odessa State Medical University,Odessa, Ukraine.

Objectives: The aim of our research was to study the effectiveness ofnew method of the ovarian masses differential diagnosis. During 1996-1998, the ultrasound examination of 2692 patients of the gynecologicaldepartment was performed with the ovarian masses evaluation in 238women (8.8%).Study Methods: Common clinical and paraclinical data were examinedin all patients. The ultrasound examination was performed by means ofKranzbuhler-20 H Dornier systems using abdominal (3.5 and 5 MHz)and vaginal (5MHz) probes. The transvaginal puncture of the ovarianmasses under the sonography control with following cytologicalexamination and serum both aspirate CA-125 determination was carriedout in 72 patients.Results: In 34 women (I group) the monochamber cysts withanechogenic homogenous ultrasound structure with smooth internalcapsule’s surface was found. The diagnosis of the ovarian follicular cystwas evaluated by aspirate cytological examination. The CA-125 levelvaried from 15-45 N/ml in serum up to 90 N/ml in aspirate. In 15patients (II group) the single ovoid masses with internal septums –multichamber ovarian tumors –were observed. The ovarian masses ofmixed structure and decreased echogenics with cytologicaldetermination of endometriosis were found in 11 women. In 8 cases (IVgroup) the dermoid cysts were defined. The atypical cells in aspiratecytological examination along with CA-125 levels of 240 H/ml andmore were found in 4 patients (V group). All women of II – V groupsunderwent laparotomy and ovarian masses surgical treatment. Thediagnosis verification of histological and cytological punctureexamination was 94.5%. In 29 women of the I group after the follicularcysts puncture with ultrasound control in 2, 6, and 12 months there wereno pathological adnexal masses at all. In 5 patients form the above-mentioned group in 6 months the new ovarian masses were found andpuncture treatment was repeated in 3 women, laparotomy – in 2 cases.Conclusions: The ovarian masses puncture biopsy under the ultrasoundcontrol with parallel aspirate cytological and CA-125 levelsexaminations is a highly effective method of the ovarian tumorsdifferential diagnosis to determine treatment tactics and surgery volume.


FC4.11 OVARIAN STIMULATION AND IVF

FC4.11.01COMPARISON OF STANDARD AND LOW DOSE LONG ACTINGGONADOTROPIN RELEASING HORMONE AGONIST(TRIPTORELIN) ADMINISTRATION PRIOR TO OVARIANSTIMULATION FOR IN VITRO FERTILIZATIONC.J. Haines , S.F. Yim, L.P. Cheung, C.M. Briton-Jones, T.T.Y. Chiu,Dept. OB/GYN, The Chinese University of Hong Kong, Hong Kong,SAR China.

Objective: The objective of this study was to compare the effectivenessof use of standard dose and low dose treatment with a long actinggonadotropin releasing hormone against (GnRHa) (triptorelin) todownregulate the pituitary-ovarian axis prior to ovarian stimulation forin vitro fertilization (IVF). Long acting GnRH agonists are moreconvenient to use than short acting nasal sprays or daily subcutaneousinjections, but they appear to provide a greater degree of suppression.Over suppression may adversely affect the ovarian response by makingthe ovaries more resistant to stimulation with gonadotropins.Study Methods: Twenty-seven patients were allocated at random totreatment with either standard dose (3.75mg) or low dose (1.8mg)triptorelin. Outcome was measured by hormonal evidence of pituitary-ovarian suppression.Results: Concentrations of luteinizing hormone were significantly lowerafter standard dose treatment both 14 and 21 days after GnRHaadministration (p<0.05, p<0.01 respectively). There were no significantdifferences in oestradiol concentrations between groups at either 14 or21 days. There were no premature LH surges in either group and thetotal doses of gonadotropins used for ovarian stimulation were notsignificantly different. Pregnancy rates did not significantly differbetween groups (5/14=35.7%) with low dose vs 9/20=45% with normaldose [per embryo transfer]).Conclusions: These results suggest that lower than standard doses oflong acting GnRHa may be used effectively for downregulation prior toIVF treatment. The sample size of this study will be expanded todetermine whether the lower dose will significantly improve ovarianresponse to stimulation with gonadotropins.

FC4.11.02CO-APPEARANCE OF PROGESTERONE RECEPTOR (PR) DOWN-REGULATION AND PINOPODIUM FORMATION ASIMPLANTATION WINDOW MARKERS IN REC-FSH / GnRHANALOGUE INDUCED CYCLESG. Ugocsai , E Berecz, E Pászty, M. Rózsa, Dept. OB/GYN and CentralLaboratory, Academic Teaching Hospital Orosháza, Hungary

Objectives: The study aimed to investigate the parallel appearance of thebiological endometrial receptivity markers PR down-regulation andsurface protrusion pinopodia in ovulation induction cycles usingrecombinant FSH preparate (Puregon, Organon) and gonadotrophinreleasing hormone analogue (Decapeptyl, Ferring).Study Methods: 5 anovulatory infertile women underwent as adiagnostic step ovulation induction to reveal the presence or absence ofsome endometrial receptivity markers around day LH peak +8, as noother than endometrial factor had been suspected behind theirunsuccessful attempts of homologeous insemination treatments. Rec-FSH was given to assist follicular maturation, GnRH analogue toprovoke ovulation. Serum progesterone levels were measured on daysLH +7, +8 and +9 respectively. On day LH +8 endometrial biopsy wastaken for PR immunohistochemistry and pinopodium studies withscanning electron microscope. Their own, other, not induced cycle wasused as control and comparison.Results: In with rec-FSH / GnRH analogue induced cycles allendometria displayed simultaneous disappearance of PR expression andappearance of typical epithelial apical protrusions pinopodia, along withgood luteal phase progesterone serumlevels. In non-induced cyclesovulation, anovulation or defective luteal phase was diagnosed, but in allcases the implantation markers failed to appear in this particular groupof infertile women.Conclusions: As additional diagnostic tool after failed insemination/IVFtreatments the investigation of specific implantation window markersmay reveal the best personalzed ovulation induction protocol in infertilewomen.

FC4.11.03RANDOMIZED COMPARATIVE STUDY OF RECOMBINANTVERSUS HIGHLY PURIFIED URINARY FOLLICLESTIMULATING HORMONE IN CONTROLLED OVARIANSTIMULATION: OUR EXPERIENCEB.N. Chakravarty (1), R. Chattopadhyay (1), S. Ghosh (1), S.K.Goswami (1), S.N. Kabir (2) 1) Institute of Reproductive Medicine,Calcutta, India. 2) Indian Institute of Chemical Biology, Calcutta, India.

Objectives: A randomized assessor-blind, comparative study was carriedout to compare the efficacy of recombinant (r-FSH) and highly purifiedurinary FSH (u-FSH) in women undergoing IVF-ET including ICSI.Study Methods: A total of 381 patients enrolled under IVF programwere subjected to long GnRH-agonist down regulation followed by FSHstimulation. The patients received r-FSH (n=123) or u-FSH (n=258),respectively at the dose levels of 200 IU and 225 IU per day for the first6 days followed by dose adjustment according to the individual dose-response scheme. The follicular criteria for HCG (10,000 IU)administration include at least 1 follicle of 18 mm and 1 follicle between16-18 mm in diameter. Wherever available, a maximum of 3 embryoswas transferred in the index cycle, while the supernumerary embryoswere cryopreserved for subsequent transfers.Results: There was no drop out in either group. Except 2 cycles in the u-FSH group, all patients achieved the criteria for HCG administration.The mean numbers (±SD) of oocytes (r-FSH: 10.2±3.1 vs. u-FSH:10.4±4.5) and embryos (r-FSH: 6.2±2.2 vs. u-FSH: 5.9±3.1) did notdiffer significantly. The total dose of FSH was likewise identical.Importantly, however, an increase in the number of grade 1 embryos wasobserved in the r-FSH group (68% vs. 52%). In the patients treated byICSI (13 and 34 in the r-FSH and u-FSH groups, respectively),metaphase II oocytes obtained were in favor of r-FSH group (53% vs.38%). The numbers of grade 1 embryos available for cryopreservationwas significantly higher in the r-FSH group (1.6±0.9 vs. 0.6±0.4). Theclinical pregnancy rates (PR) per transfer in the index cycle (r-FSH: 32%vs. u-FSH: 26%) was identical. However, PR per transfer includingfrozen-thawed embryos was higher in the r-FSH group (29% vs. 18%).There was only one (0.4%) case of OHSS in the u-FSH group.Conclusion: Both forms of gonadotropins appear equipotent in respect ofovarian response and oocyte yield. However, r-FSH was possibly infavor of producing better quality oocytes that have a positive impact onthe cumulative pregnancy rate.

FC4.11.04TWO-PHASE HORMONAL PREPARATION IN POORRESPONDERS: HOW IT AFFECTS THE CANCELLATION RATEIN IVF & ICSI CYCLESW. El Deeb , S. Farid, E. Darwish, S. El-SahwiInternational Fertility Center (IFC) Lauran, Alexandria, Egypt.

Objectives: To evaluate the efficacy cyclic combined hormonaltreatment in poor responders.Study Methods: The design was a descriptive prospective study.Material and Methods: Twenty patients from our IVF & ICSI programwith one or more previous dropped cycles due to poor ovarian responsewere included in this study. Their ages ranged from 28.37 years and allhad normal FSH, LH, Prolactin, and free testosterone levels on day 3 ofthe cycle. Ovarian stimulation in their previous dropped cycles was doneusing follicular phase short GnRHa protocol. They received 0.5 mlsuperfact S.C/day starting from day 2 of the cycle and 4 amps of FSH(Metrodin) per day starting from day 3 of the cycle. Monitoring startedfrom day 6 by ultrasound and E2 measurement. Cancellation was done if<4 follicles <10 mm in diameter and E2 < 100 pg/ml was found. In thepresent study, patients with one or more cancelled cycles received twophase hormonal preparation in the form of 2 mg E2 valerate per daystarting from day 5 of the cycle for 11 days and bot hE2 valerate 2mgplus 0.5 norgestrel per day for the next 10 days (cycleo-Progynova) fortwo successive cycles. Then the patients were stimulated suing the sameshort GnRHa protocol as in their previous dropped cycles.Results: Out of the twenty cycles. We had 13 complete cycles (65%) andthe others were cancelled. On day 6 we had 4-7 follicles in both ovariesmore than 12mm in diameter & E2 ranged from 140 – 228 pg/ml. Day ofhCG we had 5-9 follicles and E2 range from 700 – 1320 pg/ml. Theaverage number of oocytes retrieved was 41 oocytes ranged from 2-6oocytes and the average number of embryo transferred was 26 embryos


ranged from 1-4 embryos. We had 3 ongoing pregnancies out of 20patients 15% per cycle and 23% per transfer.Conclusion: These preliminary results indicate that administration ofcyclic hormonal treatment for poor responders may increase theirresponsiveness to stimulation protocols.The mechanism might be at the cellular level, stimulating and increasingthe number of hormonal receptors at the cell membrane. Further trialsshould be attempted for proper assessment of the statistical significanceof these encouraging results.

FC4.11.05A PROSPECTIVE RANDOMISED STUDY TO ASCERTAIN IFGONADOTROPHINS WITH DIFFERING FSH:LH RATIOS AFFECTOOCYTE MATURATION, FERTILISATION AND OUTCOME INASSISTED CONCEPTION CYCLESRE Irvine , HI Abdalla, JW Studd, IVF Unit, Lister Hospital, London,UK

Objectives: Purer forms of follicle stimulating hormone (FSH) are nowbeing used in controlled ovarian hyperstimulation to improve oocytematuration, fertilisation, embryo quality and hence outcome. The aim ofthis study was to ascertain if gonadotrophins containing more exogenousluteinising hormone (LH) affected outcome.Design: A prospective, randomised study involving 153 couplesundertaking assisted conception treatment. All entered had to fulfil thecriteria of: age < 37; <5 attempts at assisted conception and normalsemen parameters.Materials and Methods: All patients underwent pituitary down-regulation in a long protocol followed by controlled super-ovulationwith 150iu of each gonadotrophin. 153 couples were randomly allocatedto three groups to receive gonadotrophins with ratio of FSH:LH 1:0;1:1;and 3:1. Prior to egg collection all patients received HCG. The outcomemeasures were total number of ampoules used, number of oocytescollected, fertilisation rate and pregnancy rate.Results: There was equal distribution between all 3 groups for age,duration and cause of infertility, the treatment type – in vitro fertilisation(IVF) or gamete intra fallopian tube transfer (GIFT) and the numbertransferred. The clinical pregnancy rates were 40.0% (FSH:LH 1:0),40.4% (FSH:LH 1:1) and 31.4% (FSH:LH 3:1). There was no significantdifference in any of the other outcome measures.Conclusion: The study failed to show that increased exogenousluteinising hormone adversely affects outcome.

FC4.11.06CABERGOLINE FOR POOR RESPONDERS. A NEW APPROACHH. Shawky , Dept. OB/GYN, ART Unit, Nile Badrawi Hospital, Cairo,Egypt.

Objectives: Cabergoline is a potent dopaminergic agent that interactswith dopamine receptors. It has a positive effect in improving the uterineblood flow (Fertility & Sterility Vol. 71, No 2, February 1999). The aimof this study is to detect the effect of Cabergoline in euoprolactinemicpoor responders under running ICSI.Patients and Methods: 18 patients are enrolled in this study. Their agegroup (36-39 years). They all had normal prolactin levels, borderlineFSH levels, and poor response to long protocol of ovarian stimulationfor ICSI.All patients underwent the routine steps foe ICSI program. Hormonalconcentration profile (FSH, LH, prolactin) was done in addition toassessment of uterine & ovarian blood flow, at the day starting theanalogue, 2nd day of the cycle, day of oocyte retrieval. Cabergoline0.5mg orally (one tab) was given once per week starting from the sameday of the analogue ending one week after the day of embryo transfer.Results: The results of this study were compared with the results of theprevious trial of these patients done within 3 months before but withoutusing Cabergoline. The cancellation rate before the usage of Cabergolinewas 85%, but after Cabergoline it was decreased to 69%. Mean numberof follicles per patient was 2, but with Cabergoline it became 3.Decrease in uterine and ovarian pulsatility index. Other parameters thatwere also compared were: hormonal level variations, number of ampsused, mean days of stimulation, fertilization, implantation, andpregnancy rates.

Conclusion: Cabergoline is a useful drug to be added to the protocols ofpoor responders as it improves most of the parameters, (blood flow,hormonal levels, number of occytes. Etc.), leading to a better outcome.

FC4.11.07OOCYTE RETRIEVAL RATE THROUGH REPEATEDCONTROLLED OVARIAN HYPERSTIMULATION CYCLES INDONORS.Caligara C. 1, Vargas G. 1, Cuneo S. 1, Rodríguez M. 1, Simón C. 1,2,Pellicer A. 1,2, Remohí J. 1,2

1Instituto Valenciano de Infertilidad, 2Dpt. of Pediatrics, Obstetrics andGynecology, Valencia University School of Medicine, Valencia, Spain.

Introduction: Oocyte donation has become a common treatmentmodality for a large spectrum of infertility conditions. The purpose ofthis study was to determine the effect of the repetition of the controlledovarian stimulation (COH) by assessing the oocyte retrieval rate throughrepeated cycles of COH in donors.Material and methods: A retrospective analysis of data from donors whounderwent multiple retrievals. The table shows the characteristics of thepatients through the cycles. The statystical analysis used was a Pearson'spartial linear correlation, controlled by age, days of stimulation, anddosis of gonadotropins used for COH, of all of the donors through alltheir cycles.

Cycle n Age(years)*

Daysstimulated*

Total IU(FSH+hMG)*

Retrievedoocytes*

1 286 25,0 ± 4,2 9,5 ± 1,9 1707 ± 596 16,8 ± 7,82 286 25,4 ± 4,1 9,8 ± 2,2 1881 ± 698 17,4 ± 8,33 169 26,0 ± 3,9 9,5 ± 1,8 1937 ± 720 18,1 ± 9,04 80 26,6 ± 3,9 9,6 ± 1,5 1999 ± 597 17,9 ± 8,25 47 26,9 ± 3,9 9,8 ± 1,4 2109 ± 632 18,9 ± 8,36 25 26,9 ± 3,4 10,0 ± 1,3 2258 ± 635 20,6 ± 8,37 10 28,7 ± 3.0 10,0 ± 1,3 1822 ± 692 25,1 ± 11,98 6 29,3 ± 3,7 10,5 ± 0,8 2212 ± 306 19,3 ± 6,79 3 30,3 ± 2,1 10,7 ± 1,1 2475 ± 666 21,7 ± 7,4

*mean ± SDResults: 286 donors consented to at least two cycles. Statystical analysisshowed a significative (r2 <0.001) positive correlation between thenumber of oocyte retrieved trough the progressive number of cycle, evenwhen controlled for the effect of age, days of stimulation and total dosisof gonadotrophins.Conclusions: Donors mantain a high oocyte retrieval rate throughrepeated cycles, independent of the age at donation, and the duration anddosis of stimulation. This supports the physiology of COH of rescue ofmost of the follicle cohort otherwise destined to become atretic. There isno evidence that repeated COH has an adverse effect over the ovarianfollicular pool, neither that there is any gonadotropin resistance overtime.

Graphic 1. Linear correlation between the number of cycles and thenumber of oocytes retrieved (each dot and rod correspond to a case).

Cycle

109876543210

Oocyte

60

50

40

30

20

10

0

-10


FC4.11.08OVARIAN RESPONSE DURING USE OF HORMONE AGONISTPROTOCOLSE. S. Isjanovska (1) , S. Adamoska-Klisaroska (2), S. Isjanovski (1), (1)GYN. Clinic “Ultra Medica”, Ilindenska 97, Skopje, Macedonia, 91000,(2) Medical center Prilep, Prilep, Macedonia.

Objectives: The aim of the study was to investigate the effect of ovarianresponses with two groups of women age 38-43 years, which had beentreated with two kinds of stimulative protocols with the use of GnRHagonist: long protocol &Improved boost protocol.Study methods: Thirty women were included in this ovarian responsestudy.Group A: consists of 15 women between 38-43 year, all treated withlong protocol. The administration of GnRHa started at day 1 to day 14from the cycle in daily doses of 0,6 ml Suprefact sc. In the next 9 days300 I.u. Methrodine were used per day + Suprefact in 0,6 ml. dose.Group B: Consists of 15 women between 39 and 42 years, treated byimproved boost protocol. The administration of GnRHa (Suprefact),started at day 2 of the cycle, in doses of 0,9 ml sc. per day. From day 5-started with 300 I.u. of Methrodine in the next 9 days + 0,9 ml Suprefactcontinuously.Hormonal analysis: Serum LH, E2 and P4 were measured during theboth protocols continuously. The growth of the follicles was observed byUltrasound equipment.Results: Group A: At the critical day, just before administrating theHCG, 2 or less follicles bigger or equal to 18 mm were detected at 86.5% of woman, and 300- 500 pg/l of serum E2 levels were measured.Group B: At the critical day, just before administrating the HCG, morethan 2 follicles, bigger or equal to 17 mm were detected at 93.5 % of thewomen. E2 levels were 500-1400 pg/l.Conclusion: At the more mature women group, the usage of GnRHawith modificated boost protocol of ovarian stimulation gives much betterresults. However, the danger of early luteinization of the follicles is stillpresent as result of inadequate desenzibilisation of ovaries. That dangerwas avoided by adequate administration of the long protocol, which,however, gave a poor ovarian response in our case.

FC4.12 RECURRENT MISCARRIAGE

FC4.12.01RECURRENT MISCARRIAGE - AN ASPIRIN A DAY?R. Rai , M. Backos, L. Reagan, Imperial College School of Medicine atSt Mary's, Norfolk Place, London, United Kingdom, W2 1NY.

Introduction: Pregnancy is a hypercoaguable state. Recent evidencesuggests that (a) some women with recurrent miscarriage (RM) are in apro-thrombotic state outside of pregnancy and (b) some cases of RM aredue to an exaggerated haemostatic response during early pregnancy.Low dose aspirin (acetylsalicylic acid; 75mg daily) is frequentlyprescribed on an empirical basis to women with unexplained RM. Thepurpose of this cohort study was to determine the efficacy of thisintervention in improving the subsequent live birth rate amongst thesewomen.Subjects and Methods: The prospective pregnancy outcome of 1055women with a history of either (a) 3 or more consecutive first trimestermiscarriages (n=805) or (b) at least 1 second trimester miscarriage(n=250) was studied. All women had persistently negative tests forantiphospholipid antibodies (lupus anticoagulant and anticardiolipinantibodies) and a normal peripheral blood karyotype as did theirpartners.Results: Amongst women with recurrent first trimester miscarriage, thesubsequent live birth rate was similar amongst those who took low doseaspirin from the time of a positive pregnancy test (251/367; 68%)compared with those who those who did not take aspirin (278/438; 64%:p=0.14). There was no significant difference in either the ages or thenumber of previous miscarriages between the two groups of women. Incontrast, amongst women with a previous second trimester miscarriagethe subsequent live birth rate was significantly higher amongst womenwho took aspirin (122/189; 65%) compared with those who did not takeaspirin (30/61; 49%: p=0.03;OR 1.88; 95%CI 1.04- 3.37). Again,women in the two groups were of similar age and had a similar numberof previous miscarriages. Amongst pregnancies that resulted in a livebirth, there was no significant difference in either the median gestational

age at delivery {aspirin: median 36.4 weeks (24.1 - 40.4); no aspirin:36.2 (24.6 - 39.6): p=0.50} or in birth weight {aspirin: median 3.14 kg(0.55 - 4.4); no aspirin 3.22 (0.86 -4.2: p=0.42)} between the two groupsof women.Discussion: Low dose aspirin, which irreversibly inhibits plateletthromboxane synthesis, significantly improves the subsequent live birthrate amongst women with unexplained second trimester miscarriage.This finding supports the hypothesis that this condition has anunderlying pro-thrombotic aetiology. Whilst there is no benefit from lowdose aspirin amongst women with unexplained recurrent first trimestermiscarriage, a heterogeneous group, it is possible that aspirin may be ofbenefit to a sub group with a proven thrombophilic abnormality

FC4.12.02PRE PREGNANCY THROMBOPHILIC ABNORMALITIES AREASSOCIATED WITH SUBSEQUENT MISCARRIAGEL. Regan (1) , R. Rai (1), E. Tuddenham (2), M. Backos (1), (1) ImperialCollege School of Medicine at St Mary's, Norfol Place, London, UnitedKingdom, W2 1NY, (2) MRC Haemostasis Unit, HammersmithHospital, London, United Kingdom.

Introduction: The haemostatic pathways play a crucial role inimplantation, trophoblast invasion and placentation. Pregnancy itself is ahypercoaguable state and recent evidence suggests that recurrentmiscarriage (RM) and later pregnancy complications are in some casesdue to an exaggerated haemostatic response. Thromboelastography is asensitive and reproducible means of assessing whole blood haemostasis.We have previously reported that 30% of non-pregnant women with ahistory of RM have an increased clot strength (MA), as assessed bythromboelastography, compared with parous controls. The MAcorrelates significantly with both platelet reactivity and aggregationresponses to collagen and adenosine diphosphate.Subjects & Methods: The prospective outcome of untreated pregnanciesamongst 32 women (median age 33 years; range 19-42) with RM(median 4; range 3-12) who had pre-pregnancy thromboelastographyperformed was studied. All women had persistently negative tests forantiphospholipid antibodies (lupus anticoagulant and anticardiolipinantibodies) and a normal peripheral blood karyotype as did theirpartners. No woman received pharmacological treatment duringpregnancy, apart from folic acid as prophylactic against neural tubedefects.Results: The pre-pregnancy MA was significantly higher {median 69mm(56 - 73)} amongst the 10 women who miscarried compared with the 22women who had a live birth {(median 63mm (54 - 73; p = 0.02)}. Therewas no significant difference in either the ages or the number ofprevious miscarriages between the two groups of women. Furthermore,serial thromboelastographic assessments during early pregnancydemonstrate that an increase in the MA precedes pregnancy loss in somecases. In all pregnancies that resulted in a live birth, there was nosignificant change in the MA between 5 and 12 weeks gestation.Discussion: A sub-group of women with RM are in a thrombophilic stateoutside of pregnancy which predisposes them to future pregnancy loss.This hypercoagulability is in some cases amplified by the knownhaemostatic changes that occur during pregnancy and lead to subsequentpregnancy loss. Serial thromboelastography during pregnancy allows thedetection of the development of a hypercoaguable state prior topregnancy loss which may be amenable to correction withthromboprophylaxis. Whether this is the case is under investigation in arandomised placebo controlled study.

FC4.12.03RECURRENT MISCARRIAGE ; WHEN TO INVESTIGATEM.Formosa , M.Brincat, St Luke's Hospital, University, Gwardamangia,Malta, MSD07.

Objectives: Following an audit of an ongoing Miscarriage Clinic thequestion of whether it is justified to allow patients to suffer threemiscarriages before investigation was put.Methods & Materials: Because of the increasing awareness of theproblem of recurrent miscarriage a dedicated miscarriage clinic was set-up in the Department of Obstetrics & Gynaecology , St Luke`s Hospital,Medical School, Malta. The clinic is a referral service for patients withat least two miscarriages. The aims of the clinic are to investigate thesepatients with a view to making a diagnosis and advising on appropriate


treatment. The couple are also provided with information, counsellingand support which is an integral part of the management of this problem.A review of the clinical notes of one hundred and twenty patients whowere assessed at the clinic were reviewed. Patients are investigatedaccording to a standard protocol. The causes of recurrent miscarriagethat were encountered were: anatomical, endocrine (including PCOS),immunological, genetic, unexplained and chronic maternal illness. Thepatients concerned were divided almost equally into those who had hadtwo and those who had had three miscarriages. The causes of themiscarriages and the eventual outcome of the two groups werecompared.Results: 120 cases from the clinic were suitable for this study. Thegreater majority of patients were nulliparous and had two miscarriages(64), while 56 had had at least three miscarriages. The age range of thepatients was 19-44 years with a mean age of 31 years at referral. Thepercentage of 1st trimester miscarriages was 86.6% while 13.4%represented the 2nd trimester miscarriages. No differences wereencountered in the assessment of the two groups of patients. Patientswith either two or three miscarriages did not differ significantly in eitherthe type of pathology encountered or the eventual outcome.Conclusion: Recurrent miscarriage is a very distressing condition for thepatient and one associated with much frustration for the investigatingphysician. The condition is a homogenous one and different causes canaccount for successive miscarriages in the same patient.Recurrent miscarriage is classically defined as three successivemiscarriages. It is our contention that this is not justified and patientsshould be investigated after two successive miscarriages. This willreduce much unnecessary anxiety on the part of the patient and possiblyalso unjustified fetal loss.

FC4.12.04PREDICTIVE VALUE OF 3 DIMENSIONAL VOLUMETRY OFGESTATIONAL AND YOLK SAC FOR PREGNANCY OUTCOMEIN TIE FIRST TRIMESTERA.Babinszki(1) , T. Nyari(2), T. Mukheriee(3), A.B. Copperman(3)(1) Dept. of OB/GYN(2) Dept. of Medic. Inform. University of Szeged, Ilungay; Div. of

Reproduction Endocrinology.(3) Dept. of OB/GYN and Reproduction Sciences, the Mount Sinai

School of Medicine, New York, USA.

Objectives: We proposed that first trimester volume calculations of thegestational sac (GS) and yolk sac (YS) using transvaginal 3 dimensionalultrasound technique might have predictive value for adversereproductive outcome.Study Methods: 49 consecutive patients (treated for infertility) withsingleton pregnancies were included in this prospective study. 94examinations were performed in pregnancies with normal, and 14 withabnormal outcome. GS and YS volumes as well as CRL were plottedagainst gestational age (GA) (25-65 days post ovulation) to createnomograms for normal outcome. Measurements of abnormalpregnancies were compared with these nomograms. Specificity,sensitivity, positive and negative predictive values were also calculated.Results: Regression analysis revealed a power correlation between GSvolumes and GA and a logarithmic relationship between YS volumesand GA. CRL showed logarithmic correlation with GA as well. Both GSvolumetry and CRL measurements proved to have statisticallysignificant predictive value for adverse outcome (p<0.05). Nostatistically significant prognostic value was found in case of YSvolumetry. Specificity, sensitivity, positive and negative predictivevalues of GS volumes and CRL were similar. Results of ongoingexaminations in case of spontaneous pregnancies are also presented.Conclusions: Volumetry of GS proved to be a sensitive predictor forpregnancy outcome and can be a good supplement to CRLmeasurements.

FC4.12.05THE PATTERN OF RECURRENT PREGNANCY LOSS IN KUWAITF.M.E. Diejomaoh (1), M. Al-Azemi (2), J. Jirous (2), A. Bandar (2), P.Egbase (2), N. Al-Sweih (3), S. Al-Othman (2)(1) Dept. OB/GYN, Faculty of Medicine, Kuwait University, Kuwait.(2) Dept. OB/GYN, Maternity Hospital, Kuwait.(3) Dept. Microbiology, Faculty of Medicine, Kuwait University,

Kuwait.

Objectives: The aim of this study was to identify the etiological factorsand the pattern of recurrent pregnancy loss in Kuwait.Study Methods: 90 patients attending the special recurrent spontaneousabortion clinic were studied prospectively. A comprehensive history ofall previous abortions and pregnancies, past medical and gynecologicalevents were established. A physical examination was undertaken.Extensive investigations including immunological and endocrinologicaltests, Karyotype and radiological studies and transvaginalultrasonography and Doppler studies were undertaken. Pregnancieswhich occurred during the study were monitored carefully. Statisticalanalysis was by c2 and Fisher’s exact two-tailed test.Results: 60% of the patients were Kuwaitis. The mean age of thepatients was 30.46 ± 6.04 years. The patients were subdivided into thegroups of secondary (57%) and primary (43%) recurrent abortions. 85%of all previous abortions occurred in the first trimester. The mainetiological factors were uterine anomaly 2.2%, chromosome anomaly2.2%, PCO 13.3%, antiphospholipid syndrome 38.9% and unexplainedin 33%. Although the incidence of cesarean section was significantlyhigher in primary recurrent abortion cases (P<0.01), the overall outcomefor both groups were essentially similar. The live birth rate was 82% andmaternal morbidity was quite low and no maternal death occurred.Conclusion: Antiphospholipid syndrome is a major cause of recurrentpregnancy loss in Kuwait, information to be emphasized in teaching,patient care and further research.

FC4.12.06EPIDEMIOLOGY OF SPONTANEOUS RECURRENT ABORTIONM.Y. El-Zibdeh , Dept. OB/GYN & Infertility, Islamic Hospital,Amman, Jordan.

Recurrent abortion is defined as a loss of three or more consecutivepregnancies. The incidence and the prevalence of this problem dependon the gestational age accepted as lower limit for the fetal viability. Datafrom various studies indicated that after two miscarriages, the risk ofthird miscarriage is about 30%. The possible etiological causes ofrecurrent pregnancy loss (PRL) are numerous and many of them arecontroversial.Objectives: The aim of this study was to identify the etiologic causes ofRPL as seen in patients attending our hospital.Study Methods: 142 women with RPL were included in this study. Theclinical, laboratory sonagraphic and radiological assessment werereviewed to identify the possible causes.Results: Hormonal abnormalities were found in 35 patients (25%),anatomical abnormalities were seen in 14 patients (10%), immunologicalabnormalities in 18 patients (12.6%), maternal infections in 8 patients(5.6%). In 44 patients (31%) no causes were identified.Conclusion: Evaluation of women with RPL should be comprehensiveand treatment should be curtailed accordingly.

FC4.12.07LOW LEVELS OF ENDOMETRIAL DECAY ACCELERATINGFACTOR (CD55) MAY BE AN INDICATOR OF SPONTANEOUSABORTIONM.Martens (1) , A.Kaul(2), D,Brown (2), R.Kaul (2), (1) HennepinCounty Medical Center, 701 Park Avenue, Minneapolis, United States,55415-1829, (2) Minneapolis Medical Research Foundation,Minneapolis, Minnesota, U.S.A.

Objective: Immunologically a fetus is a semiallogenic graft and for asuccessful pregnancy, it needs to be protected from the autologouscomplement cascade. Decay accelerating factor (DAF; CD55) is acomplement regulatory protein that inhibits complement activation andthus protects the autologous tissues from the cytotoxic effects ofcomplement. To investigate the possible role of DAF during pregnancy,we investigated its expression in the endometrium of pregnant women.


Method: Endometrial samples were obtained from 51 pregnant womenincluding 34 undergoing elective and 17 undergoing spontaneousabortion. Six micrometer sections were stained with anti-human DAFIgG by immunohistochemistry. DAF expression was quantitated by acomputer-based image analysis system. The relative increase in theoptical density (OD) value was calculated as percent of increase incumulative OD values. The baseline was measured in a parallel sectionwhere buffer replaced the antibody. Results: The relative increase inintegrated (OD) of DAF in patients undergoing spontaneous abortionswas 2.7% (n=17). The density of DAF expression was substantially increased to 16.75% (p < 0.0001) in patients undergoing electivetermination of pregnancy (n=34). About 97% of pregnancies withendometrial DAF level lower than 10%, terminated spontaneously.Conclusion: Endometrial DAF levels were significantly lower in thespontaneous abortion group suggesting that DAF may protect thesemiallogenic conceptus from autologous complement cascade and lowlevels of DAF may be responsible for spontaneous abortions, at least in asignificant number of women. Secretory DAF levels may serve as anovel diagnostic

FC4.12.08THREATENED ABORTION OUTCOME IN RELATION TOINTRAUTERINE CLOT SITE AND NOT ONLY VOLUMEB.I. Patel , V. Trivedi, Dept. OB/GYN Sonoscan Centre, Shacki NursingHome, Ahmedabad, Gujarat, India.

Objective: Predicting the outcome of the threatened abortion dependsmore on the site of clot and not the size of the clot only.Study Method: A study of 100 cases having bleeding P/V in earlypregnancy was carried out with high resolution TVS probe. Site of thehematoma and volume of the same hematoma were studied.Results: Those early pregnancies were the hematoma was not disturbingthe chorionic frundosum or site of placenta, the outcome was good eventhough the size was larger.Conclusion: Site of hematoma is a more affecting factor in comparisonto the size of it in predicting the outcome.

FC4.12.09G-CSF CONCENTRATIONS OF MOTHERS’ SERUMS AS THEMARKER OF THE PROGNOSES OF PATIENTS WITH GS BUTWITHOUT FHBH. Tomizawa , Y-L. Guo, K. Ohshima, R. Fujii, T. Iura, S. Makinoda,Dept. OB/GYN, Kanazawa Medical University, Uchinada, 920-0293Japan.

Objectives: As an Obstetrician, it is very difficult to predict theprognoses of the pregnancies when we examine the patients withGestational Sac (GS) but without Fetal Heart Beat (FHB). Although thecourses of pregnancies will become clear only in 1~2 weeks, somepatients urge us to give more information about the prognoses. In suchcases, hCG that is produced at chorion is usually used. In the presentstudy, we have examined the usefulness of G-CSF concentrations ofmothers’ serums that was produced in chorion and decidua to predict theprognoses of the pregnancies.Study Methods: Under the informed consents, 28 patients who visitedthe Department of Obstetrics and Gynecology, Kanazawa MedicalUniversity Hospital with chief complaints of amenorrhea and weredetected GS without FHB at first visit participated in this study. Themothers’ serums were collected and determined G-CSF concentrations.Based on the prognoses of pregnancies, the patients were divided intonormal group (n=21) and abortion group (n=6). G-CSF concentrationswere compared between 2 groups. Statistical analysis was performedusing unpaired t-test.Results: G-CSF concentrations of normal group were 51.7 Å} 4.1 pg/ml(MÅ}SEM) and distributed between 25 and 105. In contrast, those ofabortion group were distributed between 11 and 55 and MÅ}SEM was27.8 Å} 6.6 pg/ml, which was significantly lower than that of normalgroup (p<0.01). All cases below 23.7, which was M-1.5S.D. of normalgroup, showed unfavorable prognosis.Conclusions: These results demonstrate that G-CSF concentrations ofmothers’ serums are very useful markers to predict the prognoses ofpregnancies.

FC4.12.10

KARYOTYPE OF THE ABORTUS IN RECURRENTMISCARRIAGEH.J.A. Carp , V. Toder, S. Orgad, A. Aviram, S. Mashiach, G. Barkai.Departments of Obstetrics & Gynecology; Transplantation Immunology;& Institute of Genetics; Sheba Medical Center, Tel Hashomer, andDepartment of Embryology, Tel Aviv University, Israel

Objectives: To assess the incidence of chromosomal aberrations in theabortus in cases of recurrent first trimester miscarriage, and to assess thelive birth rate after a euploidic or aneuploidic miscarriage.Study Methods: Karyotyping was attempted on 158 abortuses of womenwith three or more miscarriages. Material was collected at curettage,suspended in culture medium and analysed by standard G-bandingtechniques. The outcome of the subsequent pregnancy was assessedaccording to the karyotype of the index pregnancy.Results: Karyotyping was successful in 116 of the specimens.Chromosome aberrations were found in 33% (38/116) specimens. 67%were chromosomally normal. 84% of the aberrations were aneuploidy,16% (n=6) were structural. The most prevalent anomalies werechromosome 16 and 21 trisomy, triploidy and monosomy X. After ananeuploidic miscarriage, there was a 67% subsequent live birth rate(14/21) compared to : 37.8 (14/37) after a euploidic abortion.Conclusions: 33% aberrations is less than the 60% expected in sporadicmiscarriages. It indicates that alternative mechanisms are responsible forthe majority of recurrent miscarriage. These figures provide a baselinefor assessing other forms of therapy for recurrent miscarriage. If 60% ofrecurrent miscarriages are followed by a live birth, and 33% of the 40%who abort are chromosomally normal, any therapy can only increase thelive birth rate from 60% to 87%. Karyotyping of the abortus also allowsthe patient to be given an accurate prognosis, and allows an informeddecision to be made as to whether further investigations and treatmentshould be undertaken.

FC4.13 REPRODUCTIVE SCIENCE

FC4.13.01DO MAST CELLS PROPAGATE SUB-ENDOMETRIALCONTRACTIONS?R. Tetlow , Academic Department of Radiology, University of Hull,Hull, UK.

Objectives: Sub-endometrial (Junctional Zone) contractions have beenshown to assist in the transport of gametes and the expulsion of theproducts of menstruation. The intensity and direction of the contractionschange throughout the menstrual cycle and may have a hormonal basis.However, the cervix to fundal contractions associated with the transportof spermatozoa are not dependent on cyclical hormones. Mast cells(MC) are known to be responsible for releasing factors that causesmooth muscle contractions. The aim of this study was to compare thedistribution of MC in the junctional zone (JZ) with the outermyometrium.Study Methods: Thirteen ex vivo uteri removed for treatment ofmenorrhagia were studied (mean age of patient 39.9 years). Fullthickness blocks of the anterior uterine wall were taken and standardserial 5mm tissue sections prepared. Adjacent sections were stained withtoluidine blue for granulated MC or MC tryptase antibody (murinemonoclonal antibody), for total MC count. Wilcoxon signed rank testwith Bonferroni’s correction was used to analyze the results.Results: There were significant differences between the JZ and the outermyometrium in the total number of MC counted, when stained witheither toluidine blue or MC tryptase antibody. The median differenceswere respectively, 904.76, 95% CI (492.88, 1915.57)p=0.002 and–287.26, 95% CI (-640.25, -115.51)p=0.010.Conclusions: The results demonstrated that there were more activatedMC in the JZ than the outer myometrium. We conclude that MC couldbe responsible for the releasing factors that cause smooth musclecontractions in the junctional zone.


FC4.13.02KINETICS OF IGFBP-1 IN CERVIX DURING MEDICALTERMINATION OF EARLY HUMAN PREGNANCYH. Honkanen , E.-M. Rutanen, O. Heikinheimo, Dept. OB/GYN,University Hospital, Helsinki, Finland

Objectives: To study the kinetics of decidual and amniotic fluid isoformsof insulin-like growth factor binding protein-1 (IGFBP-1) in cervicalsecretion during abortion process induced by mifepristone andmisoprostol.Study methods: The concentrations of IGFBP-1 were measured incervical swab samples of 24 patients undergoing medical termination ofearly pregnancy with 200 mg of mifepristone orally followed by 0.8 mgof misoprostol orally or vaginally two days later. The samples werecollected on day 0 (before mifepristone), twice on day 2 (before and 3hours after misoprostol), day 14 and day 42. Two immunoenzymometricassays were used. Assay 1 detects the nonphosphorylated and lesserphosphorylated isoforms, those present in amniotic fluid (AF). Assay 2detects the highly phosphorylated isoform of IGFBP-1, which is theprimary isoform in decidua but is not present in AF.Results: IGFBP-1 concentrations in cervical samples started to rise afterintake of mifepristone to reach the peak value after administration ofmisoprostol. The median values by assay 1 were 3 (day 0), 40 (day 2),560 (day 2 +3 hours) _g/l. By assay 2 they were: 6 (day 0), 73 (day 2),200 (day 2 + 3 hours) _g/l. By day 14, the concentrations of IGFBP-1had declined to basal levels.Conclusions: In intact early pregnancy, decidual isoforms of IGFBP-1predominate in cervical secretion. Slight decidual bleeding after intakeof mifepristone results in an increase of cervical IGFBP-1 concentration.Rupture of fetal membranes, which is likely to occur after administrationof misoprostol, is switching the ratio of decidual/amniotic fluid isoformsto opposite.

FC4.13.03CONGENITAL MALFORMATION OCCURRING AS A RESULT OFPRE-IMPLANTATION EXPOSURE OF MOUSE EMBRYOS TOAMMONIUM CHLORIDES. Sinawat , Dept. OB/GYN, Faculty of Medicine, Khon KaenUniversity, Amphur Maung, Thailand.

Objectives: To investigate the effects of pre-implantation exposure toammonium chloride on the development of (F1xF1) strain mouseembryos.Study Methods: A total of 280, two-cell stage mouse embryos wererandomly allocated to culture in either M16 medium or M16 added with0.3mM ammonium chloride for 2 days before being transferred to 2.5day pseudopregnant recipients. Embryo morphology was assessed after1 and 2 days of culture. The recipient females were sacrificed on day15.5 of gestation. The number of implantation sites, fetuses, moles andany gross abnormality found were noted.Results: Pre-implantation exposure to ammonium chloride gave rise to asignificant increase in the number of embryos reaching the morula stageafter two days of culture (c2=8.93, P<0.05). The implantation rate andthe pregnancy loss rate between the two groups were within comparableranges. Both weight of fetuses and crown-rump length were significantlyhigher in the group of embryos exposed to ammonium chloride (t=3.76,P<0.001; and t=4.28, P<0.0001, respectively). There was one grossabnormality, pre-axial polydactyly of the left hind limb, detected in theexperimental group (2.94% per fetus obtained).Conclusions: This study shows that exposing pre-implantation embryosto ammonium chloride results in long-term adverse effects such asabnormal increase in the body mass and fetal dysmorphogenesis. Furtherstudy of this aspect, therefore, has the potential clinical benefit inpreventing unwanted abnormalities that could arise from human IVFpractices.

FC4.13.04ULTRASTRUCTURAL IMAGING OF HUMAN IN VITROFERTILIZATION AND EARLY EMBRYOGENESISS. Makabe (1), T.Naguro (2), P.M. Motta (3) (1) Dept. OB/GYN,University of Toho, Tokyo, Japan. (2) Dept. of Anatomy, Faculty ofMedicine, Tottori University, Tottori, Japan. (3) Dept. of Anatomy,Faculty of Medicine, University of Rome “La Sapienza”, Rome, Italy.

Objectives: The aim of the study was to investigate ultrastructuralmorphodynamic events in human in vitro fertilization (IVF) bytransmission (TEM) and field emission scanning electron microscopy(SEM).Study Methods: The materials (obtained with patients informed consent)included early human embryos and blastocysts after conventional IVF orintracytoplasmic sperm injection (ICSI). In addition ten cases ofspontaneous parthenogenesis (2-cell stage) were also observed for thefirst time.The samples were first frozen/cracked and studied by SEM followingthe ODO maceration method (1,2). The specimens were observed with aSEM (Hitachi S-4500) and a TEM Zeiss M10.Results: Great amounts of smooth endoplasmic reticulum (SER)aggregates were found in 4,5 and 6-cell embryos after ICSI. On thecontrary, such structures were never found in embryos at the samedevelopmental stages obtained after conventional IVF. Furthermore theinside overview of the three-dimensional (3-D) blastocysts was shown.Spontaneous parthenogenesis (2-cell) stage revealed a number ofcoritcal granules still assembled in the cytoplasmic cortex ofparthenogenetic eggs.Conclusions: The Large SER aggregates often present in the blastomoresof early embryos (4-6 cell stage) following ICSI procedures werepeculiar structures never detected so far in similar studies in humans.Their significance remains unknown and highly speculative. The abovetechniques represent a useful and valid guideline to compare andcorrelate more exactly physiological and pathological events (3) ofclinical relevance in assisted reproduction.References1) Tanaka K. and Naguro T., Biomed Res. 2:63-70, 1981; 2) Makabe Set al., Arch. Hist. Cytol. 57:389-394, 1994; 3) Motta P.M. et al,Protoplasma 206:270-77, 1999.

FC4.13.05ASSISTED REPRODUCTION IN HISTOPATHOLOGICALLYPROVEN ENDOMETRIAL KOCHSS. Desai , P.G. Roy, M.D. Hansotia, Dept. OB/GYN, Fertility Clinic &IVF Center, Mumbai, Maharashtra, India.

Objectives: Genital tuberculosis causes devastating effects on thereproductive functions of the woman. It causes irreparably damagedfallopian tubes. The problem mounts when the endometrium is alsoaffected. We present our experience with infertile women affected withhistopathologically proven endometrial tuberculosis who underwentART at our Center, Fertility Clinic, Mumbai, India.Methods: 42 patients in the age group of 25-40 years underwent ARTafter proper evaluation including hysteroscopy to exclude intrauterineadhesions. All these women had received prior multidrug chemotherapyfor TB endometritis and were free from the disease prior to ART. All butone were cases of primary infertility. 35 women had irreparably blockedtubes, 12 had frozen pelvis, 11 had bilateral T-O masses and oneunderwent unilateral salpingo oophorectomy for TB abscess. 5 patientsunderwent hysteroscopic adhesiolysis prior to IVF. Cycle monitoringalso included measurement of endometrial thickness and color dopplerstudy of the endometrium.Results: In 39 patients, 53 ovum pickups were done. 3 patients werecancelled due to poor ovarian response. There were 11 clinicalpregnancies. Pregnancy rate was 20%/OPU and 28%/Patient. Nopregnancies were recorded in those who had endometrial thickness of 8mm or less at the time of HCG injection. 4 women in the age group of24-29 years responded poorly, possibly due to diseased ovaries.Conclusion: This series represents a comparatively encouraging successrate in these carefully selected patients of tuberculous endometritis. ARToffers hope to this problematic group.


FC4.13.06MORPHOLOGIC ENDOMETRIAL STUDIES OF ADULT RATSSUBMITTED TO CONTINUOUS LIGHT AND AFTERMELATONIN ADMINISTRATIONMA Haidar , EI Hinoue, CE Lang, JM Soares Jr, MJ Simões, GRodrigues de Lima, EC BaracatDepartment of Gynecology - Federal University of São Paulo, EscolaPaulista de Medicina, São Paulo, Brazil.

Objective: The aim of this work was to evaluate the morphologicalendometrial changes of adult rats submitted to continuous light and aftermelatonin administration.Study Methods: Thirty adult rats were divided in three groups after threenormal cycles: GI - control group; GII - rats submitted to continuoslight; GIII - rats submitted to continuos light and received melatonin intheir drink water (40mg/liter). The water was only given during 12h ineach group in the same schedule. All animals were also submitted tovaginal smear diary to feature estral cycle. After three months, allanimals in estrous phase were sacrificed and the uterus was removed andfixed in 10% formaldehyde. The material was proceed and colored byH.E. and Masson Trichrome.Results: The superficial glandular epithelium and stroma cells showedwell development with squamous metaplasia in GII compared with GI.In GIII, we do not find significant cell changes when they werecompared with GI.Conclusion: Melatonin replacement may block the continuous lighteffect under the endometrium of adult rats.

FC4.13.07INFLUENCE OF ALLOIMMUNIZATION ON THE CELLULARAND HUMORAL IMMUNE RESPONSE IN WOMEN WITH RSA OFUNKNOWN CAUSE.O. Stukalova , National Medical University, Ostrovskogo15, apt.69,Kiev, Ukraine.

Objective: There are many evidences that cellular and humoral immuneresponse during pregnancy are changed in women with history ofreccurent spontaneous abortion (RSA) of unknown cause. The aim ofthis study was to evaluate the influence of immunotherapy with paternalleucocytes and conventional treatment on immune response in womenwith RSA.Methodes: We have investigated immunophenotypic profiles ofperipheral blood leukocytes ( CD 3+, CD 4+, CD 8+, CD 56+) andlevels of immunoglobulins (IgG, Ig M, IgA) before and 2 weeks aftertreatment in pregnant women with RSA. Patients with abortions owingto genetic, structural, endocrine, infections and autoimmune causes wereexcluded from our study. We studied 10 pregnant with RSA who weretreated by alloimmunization with paternal leukocytes (I group), 15pregnant with RSA who took conventional therapy (II group), 15 healthypregnant (control group).Results: Pregnant of I group demonstrated significant increase CD 3+,CD 8+ cells, decrease CD 4+, CD 56+ cells and ratio CD 4+/CD 8+after alloimmunization. The same data were seen in control group. Thelevel of CD 3+, CD 22+, CD 4+ cells has been found to be unchanged inwomen of II group after treatment, the level of CD 8+ cells increased,ratio CD4+/CD8+ decreased slightly. Pregnant women with RSA ofboth groups have demonstrated significant decrease the level of IgM,IgA after treatment. The level of IgG has increased significantly aftertreatment in women of I group in comparison with slight enhancing ofIgG level in women of I group.Conclusion: Immunotherapy results in returning the parameters ofcellular and humoral immune response to normal level moresignificantly than conventional therapy.

FC4.14 STRESS INCONTINCENCE SURGERY

FC4.14.01PERIURETHRAL AUTOLOGOUS FAT INJECTION AS ATREATMENT FOR FEMALE STRESS URINARY INCONTINENCEP. Lee , Dept. OB/GYN, Sunnybrook & Women’s College HealthSciences Centre (S&WCHSC), Toronto, ON, Canada, R. Kung, Dept.OB/GYN, S&WCHSC, H. Drutz, Dept. OB/GYN, Mount SinaiHospital, Toronto, ON, Canada

Objective: To evaluate the effectiveness of periurethral autologous fatinjection as a treatment for female stress urinary incontinence.Study Methods: Women with stress incontinence were randomized in adouble blinded fashion, to receive periurethral injections of eitherautologous fat (treatment group) or saline (placebo group). Postinjection, patients were evaluated monthly for three months,with a validated standardized incontinence questionnaire, a one hour padtest and a cough test. Patients who remained incontinent were offered re-injection using the same initial agent to a maximum of three injections.Every three months post injection, patients were assessed with astandardized questionnaire, a pad test, a cough test, and urodynamics.Those who did not qualify for re-injection at 3 months were thenfollowed at 6, 9, 12, 18, and 24 months (or until failure).Results: Of 68 women enrolled, 35 received fat and 33 received salineinjections. Both groups were comparable in baseline parameters. 56patients completed the study (27 in the fat group and 29 in the placebogroup). A total of 189 injections (91 fat, and 98 saline) were performed.At 3 months there was a cure/improved rate of 6/27 (22.2%) in the fatgroup and 6/29 (20.7%) in the saline group. Complicationsincluded: cystitis (9/189 injections), urinary retention (6/189 all from thefat injection group), urge incontinence (9/68 patients) and pulmonary fatembolism resulting in death (1/189 procedures).Conclusions: In this study, periurethral fat injection does not appear tobe more efficacious than placebo for the treatment of stressincontinence.

FC4.14.02URETHRO-RAPHY – A NEW TECHNIQUE FOR SURGICALMANAGEMENT OF STRESS URINARY INCONTINENCE (SUI)M.A.A. El Hemaly , I.M. Kandil, M.M. Radwan, Dept. OB/GYN,Faculty of Medicine, Al Azhar University, Cairo Egypt

Objectives: A new concept was described in 1996 explaining micturitionand urinary continence. It depends on a strong, sound and intact internalsphincter; and an acquired behavior of keeping a high and sympathetictone. Weakness of the internal sphincter causes SUI. Weakness is mostlydue to rupture and/or split of the wall.A new surgical technique to manage SUI is tried (El Hemaly). Itdepends on trying to repair the rupture in the wall and restore theintegrity of the internal sphincter, hence its strength and its ability tomaintain urinary continenceStudy Methods: 60 patients suffering from SUI grade II are evaluatedclinically by urodynamics and ultrasonic studies. Urethro-raphy wasdone with repair of the sphincter wall by longitudinal 5-8 stitchesapproximating the torn edges together. Lateral ruptures are sutured byseparate stitches. Patients were re-evaluated clinically, U.P.P and by USstudies 1,6 and 12 months after surgery.Results: 90% success is obtained immediately and during the follow-upperiod.Conclusions: Urethro-raphy is a simple and effective operation thatrestores the normal anatomical construction of the internal sphincter, sothat it can perform its physiological function.

FC4.14.03EFFICACY OF LAPAROSCOPIC BLADDERAUTOAUGMENTATION FOR WOMEN WITH DETRUSSORINSTABILITY AND LOW BLADDER COMPLIANCEA.W.M. Afify (1), M. Rasheed (2)(1) Dept. OB/GYN, Banha University Hospital, Banha, Egypt.(2) Dept. of Urology, Tanta University Hospital, Tanta, Egypt.

Objective: The aim of this study was to investigate the outcome oflaparoscopic bladder auto-augmentation as a less invasive procedure for


treating women with urodynamic diagnosis of detrussor instability orlow compliance after failure of conservative management.Study Methods: Prospective clinical study included fifteen women withurodynamic diagnosis of detrussor instability (13 women) or low bladdercompliance (2 women). Standard operative laparoscopy under generalanesthesia was done and the peritoneum and detrussor fibers or amoderately filled bladder had been divided till the bladder epilitheliumwas exposed. The procedure was continued until a thin quite largediverticular parch of bladder epithelium bulging from the bladder domeas it filled up was done.Results: During the follow-up period, the mean diurnal frequencydecreased among the study group from 9 ±3 to 5 ±3 and the meannocturnal frequency decreased from 5±2 to 2±1. Repeated urinary tractinfection reported in all patients preoperatively improved dramaticallyfollowing auto-augmentation. On urodynamic evaluation, the bladdercapacity increased in all cases with a mean percentage of 21% and themean bladder capacity increased from 219.5±54.6 ml to 265±56.7 mlpostoperatively. A statistical significant improvement (p<0.05) ofbladder volume was noticed at 40 cc water intravesical pressure wherethe bladder capacity increased by 130% from 102.5±86.4 ml to235±61.4 ml after auto-augmentation. The leak point pressure eventuallymarkedly decreased following laparoscopic auto-augmentation by 34%from 61±4.9 cm water to 40.5±8.7 cm water.Conclusion: Laparoscopic bladder auto-augmentation has been shown tobe technically feasible and safe acceptable procedure after failure ofmedical and pharmacological therapy of urinary incontinence as a resultof detrussor instability and low compliance. Laparoscopic auto-augmentation avoids the potential morbidity of using bowel forenterocystoplasty for bladder augmentation. Moreover, it offersadvantages over other surgical approaches of shorter operative time,shorter operative stay with early return to normal activity as well asbetter cosmetic outcome.

FC4.14.04CONVALESCENCE RECOMMENDATIONS FOLLOWINGVAGINAL SURGERY FOR UTERO-VAGINAL PROLAPSEM. Ottesen 1,2,3, C. Moeller1,2, H. Kehlet4 & B. Ottesen1 Department ofGynecology and Obstetrics1, Laparoscopic Unit2, Clinical ResearchUnit3 and Department of Surgical Gastroenterology4, CopenhagenUniversity Hospital, Hvidovre, Denmark.

Background: Convalescence recommendations after vaginal surgery arenot evidence based.Objective: To investigate clinical practice of convalescence recommen-dations following vaginal surgery for utero-vaginal prolapse.Study methods: Questionnaires were sent to hospital-employedgynecologists (HG) n=356, private practicing gynecologists (PPG) n=79and a random sample of general practitioners (GP) n=491.Results: 291 HG (82%), 64 PPG (81%) and 300 GP (61%) replied. Afteruncomplicated posterior and anterior repair the recommendedpostoperative hospital stay was median 2 and 3 days (0-7) respectively.The recommended convalescence was median 4 weeks (1- > 8) if thepatient had physically light work. If the patient had physically strenuouswork GP recommended a median of 6 weeks (2-12), HG 6 weeks (3-12)and PPG 8 weeks (4-12) of convalescence. About 70% gave specificadvice about lifting restrictions. The variability of lifting restrictionsranged from 1 kg for 1-8 weeks, 5 kg for 1-12 weeks to 10 kg for 1-12weeks. There was also a marked variability in recommendations onwhen to resume activities such as tub baths, pelvic floor exercises,driving, intercourse and house cleaning. In general PPG tended to be themore restrictive.Conclusion: There is an evident variability in convalescencerecommendations given to patients following vaginal surgery for utero-vaginal prolapse. A scientific evaluation and consensus need to beestablished.

FC4.14.05THE COMBINATION OF KOVAC-PROCEDURE WITH PELVICFLOOR REPAIR IS AN IMPROVED METHOD FOR CORRECTINGSTRESS URINARY INCONTINENCEU. Retzke , H.-J. Hagemeier, M. Skrobol, R. Illing, H. Graf, Dept.OB/GYN, Zentralklimikum Hospital, Suhl, Sudthuringen, Germany

Objectives: The pubic bone suburethral stabilization sling according toKOVAC is a most logic and highly successful method for the treatmentof correcting stress urinary incontinence. The aim of our study was toinvestigate if this sophisticated procedure can be combined with theclassic pelvic floor repair according to RICHTER (Munich). Thisoperative combination seems to be meaningful because most incontinentpatients suffer from problems arising from deficient pelvic floor too.Study Methods: 105 women with deficient pelvic floor and stressurinary incontinence because of urethral hypermobility were included inthis clinical study. During the same procedure, the RICHTER-methodfollowed by the modificated KOVAC-method has been performed. Thefollow-up time was 3-18 months. Before and after the operation, acomplete urodynamic assessment was done in more than 70% of thecases.Results: In all cases, this combined procedure was practicable. Thecolpotomy should be done longitudinally instead of transversally toprevent vaginal dehiscence with all its consequences. The success-ratewas more than 90%.Conclusions: A combination of the KOVAC-method and the classicpelvic floor repair according to RICHTER is a practicable andrecommendable procedure. The profit by this combined therapy of stressurinary incontinence is much higher than the profit by the KOVACprocedure alone.

FC4.14.06A NEW ADJUSTABLE BALLOON (ACT) FOR FEMALEINCONTINENCEA.M. Pacetta , M.V. Sadi, S. C. Carramão, F.M.R. Almeida, Dept. ofGynecology and Urology, Universidade de Santo Amaro, São Paulo,Brazil.

Objectives: Balloons inserted around the urethra represent a new methodfor treating women with stress urinary incontinence (SUI). The currentballoons do not permit an adjustment of the urethral compressionnecessary to promote continence and rely solely on the surgeon’ssubjective impression. Usually, more than a single procedure isnecessary to keep the patients dry. We present a new speciallydeveloped device (ACT) used to correct female SUI.Methods: Six patients with ages varying from 34 to 52 years had noprevious therapy for urinary incontinence underwent the procedure. Fivehad type II and one type III SUI. All had video-urodynamic studies donepre-operatively. The device is a small silicon balloon filled with 1-2 ccof diluted contrast, with a valve in its extremity. Through this valve, onecan percutaneously adjust the volume of the balloon post-operatively, ifnecessary. One balloon was positioned on each side of the urethra closeto the bladder neck using specially developed introducers. The valvularsegment of the device was placed subcutaneously in the major labia.Patients were discharged on the second PO day and kept on oralcefalosporins for 7 days.Results: All patients became totally dry after the procedure. Theballoons were easily positioned in the proximal urethra. One patient withno complications demanded to have the device removed on the sixthpost-operative week. Complications included one bladder perforationduring balloon implantation; distal migration of one balloon and oneballoon and valve extrusions. All complications were easily correctedand after a mean follow-up of 6 months, all patients remained dry andapt.Conclusions: The ACT device promotes urinary continence in women. Itis easily adjustable and if necessary can be removed without difficulties.Complication rates were similar to other previously reported peri-uretraldevices and were easily manageable. All patients remain totally dry onfollow-up.


FC4.14.07ABOUT 2244 URINARY STRESS INCONTINENCE OPERATIONSM.Lazarevski , V.Iliev, N.Badzakov, V.Antovska, Medical Faculty,Partizanski Odredi 109/1-3, Skopje, Macedonia, 91000.

Objectives: The aim of the study is to present our 33 years (1968-1999)experiences with the urinary stress incontinence surgery following theconceptions of our "Theory of the non-permanently acting suburethralsupportive structure", elaborated in 1968.Study methods: All patients were submitted to a standard protocolconsisting of detailed history and clinical tests, followed bycolpocystographic (+ultra sound 1996), cystometric (+ urodynamic1986), cystoscopic and, if necessary, neurologic and/or nephrologicinvestigations. The surgery consisted of two original operations realizingthe requirements of our theory: 1255 (55,9%) slinglikecolposuspensions, by abdominal and 989 (44,1%) suburethralduplications of the vagina, by vaginal approach.Results: Results were evaluated 24 months after the procedure in 1982(88,3%) cases. The control examination consisted of detailed history andclinical tests, cystometry and flowmetry. The radiologic and completeurodynamic investigations were carried out in 430 cases incorporated ina particular project study - in the remainder patients of the series, ifnecessary. There were 78 (3,9%) recurrent cases in all the series: 29 (2,6%) after 1114 slinglike colposuspensions and 49 (5,6 %) after 868suburethral duplications of the vagina. A series of 42 (2,1%) iatrogeniccomplications was registered, too.The technical details and pathogenesis of iatrogenic complications andrecurrences are discussed extensively.Conclusion: The stress incontinence surgery should not elevate theproximal urethra in the intra-abdominal pressure zone, nor it shouldverticalize, elongate, narrow and angulate this canal. It should onlycerate a resistant and live lasting suburethral structure under theproximal urethra, just below the bladder neck, over which the proximalurethra will be compressed during its dorso-caudal physiologicdisplacements.

FC4.14.08STUDY OF THE RESULTS OF SURGICAL TREATMENT OFINCONTINENCE ON PATIENTS WITH PROLAPSE OF THEGENITALSS.N. Buyanova , V. Petrova, M.N. Ioseliani, I.D. Rizhinashvili, V.I.Balashov, Moscow Regional Scientific Research Institute of Obstetricsand Gynecology, Moscow, Russia

Objectives: To determine the optimal method of surgical treatment ofincontinence in patients with prolapse of the genitals.Study Methods: We have performed operations in 300 patients with II-III degree prolapse of the genitals. In 211 women with predominanthypermobility of the urethra underwent aponeurotic vaginopexy incombination with Berch operation; in 68 patients with sphincterinsufficiency – aponeurotic vaginopexy was combined with the slingsurgeries. Elderly patients (over 70) with cystocele, stress incontinence(tipeI-II) underwent various retropubic vesicovaginopexies.Results: Full effect was observed within 3 years in 86.7% of patientswho had undergone aponeurotic vaginaopexies in combination withBerch operation. The effect was observed in 91.1% after aponeuroticvaginopexies combined with sling operations. Retropubic operationsshowed 78.6% success rate.Conclusions: The most effective treatment for patients with prolapse ofgenitals accompanied by incontinence involves combined operations.

FC4.14.09LAPAROSCOPY FOR SURGICAL TREATMENT OF GENITALDESCENT AND URINARY INCONTINENCEV. Kulakov , L. Adamyan, B. Sashin, M. Blinova, Dept. Operative GYN,Scientific Center for OB/GYN/PERINAT, Moscow, Russia.

Objectives: To determine effectiveness of laparoscopy on the steps ofsurgical correction of uterus descent, pelvic floor relaxation and urinaryincontinence.Study Methods: Retrospective analysis of 598 cases of expressedperineal anatomic distortion, vaginal descent, cysto-urethro- andrectocele, st.II uterine prolapse and stress urinary incontinence inpatients aged 28-62 years, has been carried out. 486 patients underwent

conventional vaginal surgery including hysterectomy or cervixamputation, if indicated (148 cases), with or without shortening andreinforcement of cardinal ligaments, anterior colporrhaphy and vaginalreinforcement of bladder and urethral fascia (Figurnov-type),colpoperineorrhaphy and levatoroplasty. 112 laparoscopic proceduresincluded 48 hysterectomies or cervical stump extirpation, accompaniedby Burch (14) or McCall (21) technique, shortening of round ligamentsby bringing them through the holes in broad ligaments and suturing tothe opposite utero-sacral ligaments (32); laparoscopic reinforcement ofutero-sacral ligaments by suturing their medical aspects together afterreduction of the posterior cul-de-sac space by CO2 laser, bipolar orargon-enhanced coagulation (22).Results: Operating time ranged from 100 to 140 minutes. Vaginal stepsof surgery appeared to be the most prolonged lasting 30-40 min. NOintra or postoperative complications occurred. No recurrences wereobserved in course of the 0,5 –6 yrs follow-up.Conclusions: Combined laparoscopic vaginal approach to correction ofgenital descent or prolapse associated with stress urinary incontinencepermits to reestablish distorted pelvic anatomy, and seems especiallybeneficial in young patients preserving their menstrual and reproductivefunction.

FC4.15 VAGINAL HYSTERECTOMY

FC4.15.01USE OF A NEW VESSEL LIGATION DEVICE DURING VAGINALHYSTERECTOMYB. Levy , University of Washington School of Medicine, 34503 NinthAvenue South, #330, Federal Way, WA, USA, 98003

Objectives: A new energy-based hemostatic device was evaluated foruse in gynecologic surgery.Study Methods: Eighty vaginal hysterectomies were performed using theLigaSure™ Vessel Sealing System instead of sutures. Effectiveness andpost-operative outcomes were evaluated.Results: Outcomes were favorable. Follow-up has been from one toeighteen months. Uterine weights varied from 36 to 1130 grams.Seventeen patients were nulliparous. There has been no cuff cellulitis,hematoma, or post-operative bleeding. Operative time was consistentlydecreased by 10 to 20 minutes. Patient length of stay averaged 0 to 1days. Lateral thermal spread was approximately 1 to 2 mm from the sealsite. Blood loss was decreased in all cases compared to average orexpected loss. In five cases, suture was used on one side and theLigaSure™ System on the opposite pedicles. In comparison, both timeand bleeding were reduced when the LigaSure™ System was used.Timed comparisons demonstrate a savings of 30 seconds per pediclewith the LigaSure™ device.Conclusions: Use of this system allows control of vessels in spaces withlimited access. It is particularly valuable for vaginal surgery in patientswith a small pelvis and narrow pubic arch. It also allows easy salpingo-oophorectomy at vaginal hysterectomy.These results indicate the LigaSure™ Vessel Sealing System is a viablealternative to sutures for ligating vessels quickly and reliably duringgynecologic surgery.

FC4.15.02587 CASES OF VAGINAL ADNEXECTOMYS.L. Larson , Minneapolis, MN, USA

Objective: The aim of this study was to evaluate success of removal oftubes and ovaries at time of vaginal hysterectomy, and to reportcomplications.Study Methods: The study evaluated 587 private practice patients whounderwent vaginal hysterectomy and adnexectomy. The surgicaltechniques used have been described by Sheth and others.Results: Of 1126 vaginal hysterectomy cases, 587 had salpingo-oophorectomy. Success was found to be age dependent: 0-44 years(98.1%), 45-54 years (90.9%), 55-64 years (88.9%), 65-74 years(58.7%), 74+ years (27.3%). The following factors had little influenceon successful oophorectomy:1) History of prior cesarean delivery or nulliparity2) Findings of enlarged uterus, endometriosis, or pelvic inflammatorydisease. One complication (transfusion) occurred as a direct result ofoophorectomy.


Conclusion: Adnexectomy is feasible at most vaginal hysterectomies. Itssuccess related inversely to patients’ age but not to other factors.Complications are rare. Desire for oophorectomy should not be regardedas a contraindication to vaginal hysterectomy.

FC4.15.03ATTITUDE CHANGE IS ALL THAT IS REQUIRED TO REVERSETHE RATIO OF ABDOMINAL TO VAGINAL HYSTERECTOMIES.A PROSPECTIVE STUDY.R. Varma , S. Tahseen, Dept OB/GYN, Basildon Hospital, UK.

Objective: To increase the rate of vaginal hysterectomies in patients withbenign disease in the absence of prolapse.Study Methods: 272 patients undergoing hysterectomy for benigngynecologic disorders. The ratio of vaginal vs. abdominalhysterectomies as well as any complications and conversion toabdominal procedure intraoperatively was recorded.Results: At the start of the study, the route of surgery was 68%abdominal and 32% vagina. By the end of the fifth year pattern was 5%abdominal and 95% vaginal. There was no change in the case mixduring this period. In the fifth year of study the majority of associatedoophorectomies were also performed vaginally. Electing for vaginalhysterectomy did not increase operating time and conversion toabdominal hysterectomy was needed in only two cases. There was noincrease in patient morbidity.Conclusion: The predominant route of hysterectomy can be changedfrom abdominal to vaginal just by a willingness to alter practice and asimple decision to do so. There is no significant increase in risks for thepatient and no adverse economic or logistic consequences for theinstitution. Widespread use of this approach would have significantimpact on the use of health care resources. The major determinant of theroute of hysterectomy is not the clinical situation but the attitude of thesurgeon.

FC4.15.04AUDIT OF ASSESMENT OF FEASIBILITY OF VAGINALHYSTERECTOMYN Deshpande , K.S.J. Olah, Dept OBGYN, Warwick Hospital, Warwick,UK

Objectives: Vaginal hysterectomy for benign gynecological disease isknown to be associated with a lower morbidity and a quicker recoveryrate. Many patients, especially parous patients will have a sufficientlymobile uterus to facilitate a vaginal hysterectomy. Yet, many casesundergoing abdominal hysterectomy have the procedure withoutundergoing a formal assessment for suitability for a vaginalhysterectomy. The aim of this study was to audit the number of casesundergoing such an assessment prior to having their surgery, as well asto determine the possibility of attempting a vaginal hysterectomy inspecified cases.Methods: All hysterectomies performed between April 1999 and Sept.1999 were identified and the notes were reviewed. Points taken intoconsideration were the primary diagnosis in clinic, the vaginalassessment in clinic, the operation planned, assessment in theatre forvaginal hysterectomy, and the actual operation performed. Intra-operative and post-operative complications, as well as the finalhistological diagnosis were noted. A final note was made of reasons whya vaginal hysterectomy was deemed not possible when an abdominalhysterectomy was carried out.Results: 121 hysterectomies were performed between April 1999 andSept. 1999. 68 patients had a total abdominal hysterectomy, 21 had asubtotal abdominal hysterectomy while 32 patients had a vaginalhysterectomy. 80% of patients undergoing an abdominal hysterectomyhad an assessment under anesthesia, but, only 10% were assessed with aview to performing a vaginal hysterectomy. There were 2 cases wherean attempted vaginal hysterectomy failed and an abdominal procedurehad to be resorted to. In 70% of cases undergoing a subtotalhysterectomy the option of vaginal hysterectomy was not discussed eventhough the uterus was normal in size and appearance.ConclusionsThere is a need to recognize that vaginal hysterectomy can be performedin most cases undergoing an abdominal procedure. All patients withbenign gynecological disease should be assessed under anesthesia todetermine the feasibility of a vaginal hysterectomy even though

significant descent may not be present. Consent should be obtained for avaginal hysterectomy in the first instance and in case of difficulty theoption of an abdominal procedure should be considered

FC4.15.05VAGINAL HYSTERECTOMY: SAFE WITHOUTPOSTHYSTERECTOMY VAULT PROLAPSE.G. Lotfi , MD, MRCOG. Obstetrics & gynecology Department, Facultyof Medicine, Suez Canal University, Ismaila, Egypt.

Objective: The purpose was to study the safety of vaginal hysterectomyin patients without uterine descent and the modification of the techniqueto avoid unnecessary laparotomy and post hysterectomy vault prolapse.Study Methods: The proposed modified technique of vaginalhysterectomy was applied on 279 women with no uterine descent.All women were subjected to the modified technique, where the firstligature of uterosacral ligament is fixed to the vaginal angle on bothsides. The three pedicles on each side are attached together in astepladder pattern to give more secure hemostasis and to let all pedicleseasily accessible if any bleeding occurred. Complications during andafter operation were recorded. Most of these women were followed upfor more than 2 years.Results: All operations were completed and there was no shift toabdominal operations in all our cases. Major bleeding during or after theoperation was not a problem with our cases. Minor bleeding thatimproved conservatively occurred in 4%, Post operative fever in 3%,Urinary tract infection in 1%, and Stress incontinence in 1%. No caseswith traumatic injury of other organs and no cases showed posthysterectomy vault prolapse during the follow up period.Conclusions: The proposed modified technique helps in prevention ofpost hysterectomy vaginal vault prolapse as it assists in keeping thevaginal axis in its normal situation parallel to the levator ani. The stepabove step suturing is important to keep any pedicles in quick reachonce it becomes necessary to do so. The technique helps to prevent thetragic abdominovaginal approach; if bleeding pedicle is retracted out ofreach and helps to prevent the occurrence of the frustrating posthysterectomy vaginal vault prolapse. Vaginal hysterectomy is a safe andskilled technique that should be considered during assessment of everypatient planned to have hysterectomy.

FC4.15.06TRANSVAGINAL OVARIAN CYSTECTOMYH.S. Choi , S.M. Kim, J.S. Byun, Dept. OB/GYN, Chonnam UniversityHospital, Kwangju, Korea.

Objectives: The aim of the study was to compare transvaginalcystectomy with laparoscopic cystectomy in the treatment of benignovarian tumors.Study Methods: We performed 84 cases of ovarian cystectomy throughculdotomy between November 1997 and November 1999. Histologicdiagnosis was 55 cases mature cystic teratomas (65.5%), 11 serouscystadenomas (13.1%), and 7 endometriomas (8.3%). We comparedtransvaginal cystectomy with laparoscopic cystectomy in the 40 cases ofmature cystic teratomas. Complication, operation time, amount ofbleeding, and cost were compared.Results: The two groups were similar in patient age, complications,tumor size, amount of blood loss, and postoperative self-satisfaction.Complications were 1 case culdotomy site hematoma (1.2%) and 2 casespelvic infections (2.4%). But operation time was shorter in transvaginalcystectomy (38.8 ± 5.06 minutes) than in laparoscopic cystectomy (96.9± 43.5 minutes, p<0.001). Especially the cost in transvaginal cystectomy($385) was about half of that in laparoscopic cystectomy ($770,p<0.001).Conclusions: Transvaginal ovarian cystectomy was a very usefulsurgical technique in some patients.


FC4.15.07VAGINAL HYSTERECTOMY FOR THE UNDESCENDED UTERUS– ANALYSIS OF FACTORS PREDICTING FEASIBILITYR. Sinha , Dept. OB/GYN, Medwin Hospital, Hyderabad, India.

Objective: To asses the factors predicting the feasibility of performing avaginal hysterectomy for indications other than prolapse and todemonstrate its superiority to abdominal hysterectomy.Study Methods: Retrospective analysis of 110 consecutive casesbetween January 1999 and July 1999 was performed with respect to thedemographic data, uterine volume, history of cesarean section andparity. Cases with a clear indication for abdominal/laparoscopicapproach such as possible malignancy, adenexal pathology, or a uterinelength of >15cm were excluded. Examination under anesthesia (EUA)included assessment of uterine mobility (score 0, 1, 2 and 3 dependingon number of planes in which mobility was noted), and uterus-free spaceor the operative space around the uterus (score absent or present). 99patients with complete data were included in the study. 57 (58%)underwent vaginal hysterectomy (VH) and 42 abdominal hysterectomy(TAH). Indications for hysterectomy were fibroid (19 and 24respectively), adenomatous hyperplasia (13 and 4), cervical dysplasia(12 and 4), adenomyosis (6 and 7), pelvic inflammatory disease (1 and3) and dysfunctional bleeding (6 and 0). Multiple logistic regressionanalysis (SPSS software) was used to predict the feasibility of VH. Outcome in terms of operation time, blood transfusion, parenteral analgesicsrequired (in days), hospital stay and morbidity (graded absent or present)was analyzed using Fisher’s exact test and T test.Results: Uterine mobility and uterus-free space were strong independentpredictors of feasibility of VH (p<0.001 for both). Uterine volume,parity and cesarean section were not independent predictors, althoughuterine volume was significantly smaller in VH patients as compared toTAH (197ml vs 314ml, t = 2.048, p<0.05). VH was superior to TAH interms of hospital stay (4.5 vs 8.1 days), parenteral analgesic requirement(1.1 vs 2.8 days) and time taken for surgery (50 vs 106 min) (p<0.001).Morbidity was comparable in both groups (15.9% vs 19.0%) Bloodtransfusion was required in 6 patients of TAH group only (c2 = 8.668,p=0.005). VH was feasible in patients with large uterus with fibroidfollowing pervaginal myomectomy provided mobility and uterus-freespace were favorable.Conclusions: EUA findings of mobility in 3 planes and presence ofuterus-free space are highly predictive of feasibility of VH. Majority ofuterus without descent can be removed vaginally without the need forlaparoscopy. Outcome of VH in this setting is clearly superior to TAH.VH should be considered in all patients without a clearly definedindication for TAH and the EUA findings should guide this choice.

FC4.15.08VAGINAL HYSTERECTOMY ON NON-PROLAPSED UTERI: OURCLINICAL EXPERIENCE.P. Bratila , O. Nicodin, N. Niculescu, Gynecology Clinic, CentralMilitary Hospital of Bucharest, Romania.

Objective: The goal of our study is to report our clinical experience withvaginal hysterectomies in non-prolapsed uteri. We focused on technicaland economic factors affecting this type of surgery.Methods and MaterialsOur study is based on 1130 patients with non-prolapsed uteri. All 1130cases underwent vaginal hysterectomy representing 34.6% ofhysterectomies performed in our gynecology department at the militaryclinics.Results: Procedures done in conjuncion with vaginal hysterectomyincluded: 13% incontince surgery, 21% unilateral or bilateraladnexectomy, 21% anterior and posterior colporrhaphy and 5%enterocele repair. We studied selection criteria, prophylactic antibiotictherapy, surgical technique, surgical technique with larger uteri, surgicaltime, pre and post-operative complications and hospital stay. In 37patients (3.27%) the post operative stay was limited to one day only.Conclusions: Vaginal hysterectomy on the non-prolapsed uterus is a lessinvasive technique with benefits which include shorter hospital stay. Ourexperience shows that vaginal hysterectomy is the surgical method ofchoice in benign conditions other than utero-vaginal prolapse.

FC4.15.09WIDESPREAD INDICATION OF VAGINAL HYSTERECTOMYWITH SCHURCHARDT'S INCISION.A.Matthes , H.Marana, A.G.Matthes, Faculty Medicin, Av. bandeirantes,3900, Campus Universitário, 8º A. Ginecologia, Ribeirão Preto, SãoPaulo, Brazil, 14049-900.

SummaryObjectives: Our purpose to demonstrate that Vaginal hysterectomy ispossible when we use the Schuchardt incision in women with a non-prolapsed uterus then permitting a wide indication of this via.(way).Study Design: A study of retrospectively 116 vaginal hysterectomy withSchuchardt perineal incision carried out on patients without prolapse ofthe uterus and the authors reviewed the indications and morbidity of thissurgery technique during 9 years, since august 1990 till august 1999.The most common pre-operatory diagnosis were dysfunctional uterinehemorrhage about 37% followed of myomata of the uterus, endometrialpoly, cervical “ïn situ” carcinoma and endometrial carcinoma.Results: Most of the patients were in the 40 to 49 year-old group withabout 54,34%.and 30% was alone 1 or 0 parity. About 39 % hadn’t anyprevious surgery. Leiomyomas was most frequent pathology found.Theyhad 39% of complications, but anyone was serious.Conclusion: On the basis of the results obtained, we concluded that thevaginal hysterectomy method with Schuchardt perineal incision is areasonable conduct for removal of the uterus, and permit a rapidrecovery of the patient and this surgery could be expanded since theoperation proved to be safed.

FC4.16 ASSISTED REPRODUCTION MEDECINE: BASIC

FC4.16.01PREGNANCIES AND LIVE UNINFECTED CHILDREN BORNFROM COUPLES WITH AN HIV-1 SEROPOSITIVE MAN AFTERINTRACYTOPLASMIC SPERM INJECTIOND. Loutradis , R. Bletsa, L. Michalas, K. Kallianidis, P. Drakakis. E.Patsoula, S. Michalas.First Department of Obstetrics and Gynaecology, Athens UniversityMedical School, Athens, Greece.

Objectives: The aim of the study was to investigate the effectiveness ofintracytoplasmic sperm injection (ICSI) in order to achieve a safepregnancy in seronegative women, using processed semen from theirhusbands who were seropositive for human immunodeficiency virustype 1 (HIV-1).Study Methods: Four HIV-1 seropositive men and their HIV-1seronegative female partners, who gave their informed consent inwriting were included in this study. Men provided semen samples thatwere processed with the use of Percoll and swin-up techniques. Ovarianstimulation in women was performed with long-protocol GnRHanalogues and recombinant FSH. Oocytes were fertilized by ICSI andthe embryos obtained were transferred.Results: In the first case, 7 mature oocytes were collected and fertilizedwith ICSI, 3 embryos were transferred, a single pregnancy was achievedand a healthy boy was born. Testing for HIV-1 antibodies in the womanand the baby game negative results. In the second case, 10 matureoocytes were collected and fertilized with ICSI, 4 embryos weretransferred and a single pregnancy was achieved. Testing for HIV-1antibodies in the woman 3 months after transfer also gave negativeresults. In the two other cases, mature oocytes were fertilized with ICSI,embryos were transferred but no pregnancies were achieved. Testing forHIV-1 antibodies in the women after embryo transfers gave negativeresults.Conclusion: In women with infertility due to fallopian tube obstructionor when the semen is of poor quality for artificial insemination, ICSI canbe carried out using processed semen. This method involves use of onlyone spermatozoon/oocyte and provides HIV-1 seropositive men with theopportunity to have children with a lower risk to infect their femalepartners.


FC4.16.02FIRST HUNGARIAN PREGNANCIES-DELIVERIES AFTER ICSIUSING ORIGINALLY UNMOVING SPERMATIDS OBTAINEDFROM CRYOPRESERVED TESTICULAR TISSUEK. Kanyó , J. Konc: Infertility and IVF Unit, St. John Hospital, Budapest,Hungary

Objectives: The authors report about the first four Hungarianpregnancies,- deliveries, when the ICSI was performed by originallyunmoving sperms what was obtained from cryopreserved testiculartissue. In the institute of the authors the cryopreservation of testiculartissue is performed routinly.Study methods: In our institute we perform diagnostic testicular biopsyso, that we divide the obtained tissues into two parts. First part is usedfor hystological examination, second part will be homogenized inmedium and will be placed into incubator. After a few hour incubation,the embriologists examine the material and decide the freezing. Whenthe embriologists find moving spermatids, we routinly freeze it by slowprotocol and store the tissue. When we have only unmoving spermatids,we decide the freezing according to the number of spermatids. Thefreezing also happens by slow protocol.Results: Last two years we used originally unmoving spermatidsobtained cryopreserved testicular tissue for ICSI at 16 cases. Fourwomen became pregnant. Two patients delivered healthy babies bycesarian section. The third patient has an ongoing pregnancy and at thefourth patient a missed abortion occurred in week 10.Conclusions: According to our practise we think that by the help ofcryopreservation a further operation can be avoided. Recently a lot ofART-study reports that the cooling process ruins a part of the sperm.These publications underline too strongly the fact, that cryopreservationdecreases the motility, fertilisation ability, viability of sperms. By thisway many doubts occurred about the usefullness of cryopreservation.Opposite of it our four pregnancies, when the ICSI was performed withunmoving sperms, - prove the real value of cryopreservation. Today atesticular biopsy should not be performed without a cryopreservationbackround.

FC4.16.03THE SIGNIFICANCE OF ENDOMETRIAL THICKNESS ONIMPLANTATION AND NUMBER OF EMBRYO TRANSFERREDON PREGNANCY OUTCOME IN AN INTRACYTOPLASMICSPERM INJECTION PROGRAMC. Tantoco , L. Almeda, T. Vera, Dept OB/GYN, Cardinal SantoMedical Center, San Juan, Philippines.

Objectives: The study was undertaken to correlate the endometrialthickness and number of embryos transferred with the pregnancyoutcome in an intracytoplasmic sperm injection program.Study Methods: A prospective observational study was conducted on115 infertile women who underwent intrtacytoplasmic sperm injection atthe Reproductive Medicine lab. From January 1996 to November 1997.Indications for inclusion were semen problem, tubal infertility,endometriosis, and unexplained infertility. All patients underwentcontrolled ovarian hyperstimulation using a protocol on GnRH agonist,human menopausal gonadotropin, purified urinary follicle stimulatinghormone or recombinant FSH. Endometrial Thickness during embryotransfer was measured by transvaginal ultrasound. Estradiol level priortransferred was also recorded. The patients were divided into 2 groups:group A with negative pregnancy and group B with positive pregnancywhether biochemical or clinical.Results: A total of 115 infertile women were included in the study. 88(76.6%) were negative for pregnancy while 27 (23.5%) women becamepregnant. Using chi-square, measurement of endometrial thickness wasnot significantly significant. The peak estradiol level by itself was notsignificant however when correlated with the number of embryostransferred using logistic regression will have a 39-46% probability of apositive pregnancy. Among the three variables, groups A and B differsignificantly in terms of the mean number of embryo transferred with thegroup B having a larger mean at 3.5185 as against 3.0909 for group A.Using chi-square, the higher the number, of embryos transferred, thehigher the probability of pa positive pregnancy (p=0.045).Conclusions: The higher the number of embryos transferred the higherthe probability of a positive pregnancy. The lower the peak estradiollevel and the higher the number of embryos transferred the higher thechances of a positive pregnancy.

FC4.16.04ASSISTED OOCYTE ACTIVATION BY ELECTRICALSTIMULATION AFTER INTRACYTOPLASMIC SPERMINJECTIONM-S Lee (1), C-C Huang (2), C-I Chen (1) (1) Dept. OB/GYN, Chung-Shan Medical and Dental College Hospital, Taichung, Taiwan (2) Dept.Infertility, Lee Women’s Hospital, Taichung, Taiwan.

Objectives: The aim of our study is to investigate a method for assistingactivation of human oocytes which result from the deficient capacity ofsperm-deriver oocyte activation in intracytoplasma sperm injection(ICSI) treatment cycles.Study Methods: Criteria for admission to the electrical stimulation weresevere oligozoospermia, TESA or low fertilization rate (<50%) inprevious ICSI cycles. The oocytes were stimulated electrically ~3hrsafter ICSI. After 18hrs culture in vitro, oocytes with the second polarbody and two pronuclei were considered normally fertilized.Results: The average maternal age in this study is 32.4. The averagecycle number, fertilization rate and pregnancy rate of the ICSI cases inthis study is 2.3, 51.5% and 0% respectively. After electrical activation,the fertilization rate and pregnancy rate were 69.0% and 37.5%respectively.Conclusions: In the present study, we activated the oocytes with a singleelectric pulse to create a rapid rise in [Ca2+]i. By this artificialstimulation, the ICSI fertilization rate increased sharply from 51.5% to69.0% in eight ICSI cycles with compromised fertilization resultspreviously. Furthermore, the average pregnancy rate also increased from0% to 37.5%. From our preliminarily results, both the fertilization rateand pregnancy rate were improved by activating the oocytes with asingle electric pulse immediately after the procedure of ICSI. Theseresults show the extra-activation procedure can be considered to performon all the ICSI cases with low fertilization rates previously.

FC4.16.05A PROSPECTIVE STUDY COMPARING TESTICULAR ANDEJACULATED SPERMATIDS FOR PREDICTING THEPROBABILITY OF TESTICULAR SPERM EXTRACTION IN MENWITH NON-OBSTRUCTIVE AZOOSPERMIA.U.I.O. Ezeh 1, H.D.M. Moore2 ,3 and ID Cooke2 . The Department of OBGYN, The State University of New York at Buffalo, USA1 and TheDepartments of OBGYN2 and Molecular Biology and Biotechnology 3,University of Sheffield, Sheffield, UK.

Objective: There is lack of good clinical or laboratory methods forpredicting the probability of testicular sperm extraction in men with non- obstructive azoospermia. However, previous studies have shown agood correlation between testicular and ejaculated spermatids withtesticular sperm extraction. We conducted a prospective study tocompare the accuracy of ejaculated and testicular spermatids inpredicting the probability of testicular sperm extraction in men with non- obstructive azoospermia.Study Methods: Data on the visualisation of testicular spermatids ontesticular histology and outcome of testicular sperm extraction wereavailable from 40 consecutive patients. Semen samples were obtainedfrom 28 consecutive patients. Sperm extraction was performed usingboth mincing and in vitro culture of testicular tissues. Biopsy samplesfor histology were preserved in Bouin’s solution and stained withHematoxyline and Eosine stains. Ejaculated spermatids were identifiedimmunologically using monoclonal antibodies specific to an acrosomalmoiety. The diagnostic accuracy of visualisation of at least one testicularor ejaculated spermatid in discriminating patients with successful andfailed testicular sperm extraction was assessed using Receiver OperatingCharacteristic Curve.Results: The presence of ejaculated spermatids gave the overallprediction of successful testicular sperm extraction. The accuracy ofprediction was 91%, the sensitivity was 87% and the specificity 100%for the visualisation of ejaculated spermatids compared with testicularspermatids (accuracy of 77%, sensitivity of 72% and a specificity of92%).Conclusion: The visualisation of spermatids in the ejaculate is betterthan testicular spermatids in predicting the likelihood of testicular spermextraction. The data herein will serve as a basis to discuss the emergingrole of spermatids as a good predictor of testicular sperm extraction inmen with non - obstructive azoospermia


FC4.16.06DOES TUBAL SPERM PERFUSION IMPROVE THE RESULTS OFINTRAUTERINE INSEMINATION?A.El-Adawy , M. Ibrahim, F. Abd El-Hady, Dept. OB/GYN, Kasr El-Aini Hospital, Cairo University, Cairo, Egypt.

Objective: Attempting to answer the question: does tubal spermperfusion improve the results of intrauterine insemination?Materials and Methods: The study included 60 stimulated cycles from63 infertile cases diagnosed as simple anovulation, cervical factor ofinfertility or unexplained infertility. Controlled ovarian hyperstimulationwas done using combined clomiphene citrate and human menopausalgonadotropins. 1000 IU of hCG was given on the presence of 2-4follicles ³ 18 mm and measured serum E2 > 250 pg/ml per maturefollicle. The patients were then randomized to perform either theconventional intrauterine insemination (group 1, 30 cycles) or tubalsperm perfusion. If there was delay in menses, a quantitative serumassay of b subunit of hCG was performed to confirm pregnancy andtransvaginal ultrasound was done two weeks later to confirm fetalheartbeat. Another scan was done at twelve weeks of gestation toexclude 1st trimesteric pregnancy miscarriage. Analysis of data was doneusing the Student t test, Chi square test with Yates correction.Results: Clinical pregnancy had occurred in 13 out of 30 cases (43.3%)in group I in 14 out of 30 cases (46.7%) in group II with abortion rate of15.4% and 21.4% respectively. Only one case in group I (7.7%) and twocases in group II (14.3%) had twin pregnancies and no ectopics hadoccurred. No significant difference (p<0.05) was found in the pregnancyrate and outcome.Conclusion: Tubal sperm perfusion offers no advantage over theconventional intrauterine insemination as regards pregnancy rate oroutcome.

FC4.16.07ICSI EXPERIENCE IN PAKISTAN: MALE INFERTILITY,AZOOSPERMIA, ICSIY. Khan , S. Siddiq, M. Khan, The Infertility Advisory Centre, Lahore,Pakistan.

Objective: Intracystoplasmic sperm injection is a micromanipulationtechnique in which a single sperm is injected into the oocyte to achievefertilization. Our experience is that the sperm disorders cannot besuccessfully treated by IUI or IVF to help these couples. So to helpsevere make factor infertility we introduced ICSI technology inPakistan.Study Methods: All cases of severe sperm disorders that were booked inout center between Jan. to Dec. 1999 are included in the study for ICSItreatment. In cases of azoospermia, sperms are collected either fromepididymus (PESA) or from testicular biopsy (TESE).Results: Total Number of Cases 102Number of Pregnancies 44Success Rate 42%Group A: Age of wife less than 35 years

No. of Cases 80No. of Pregnancies 39Success rate 49%

Group B: Age of wife 35 years & aboveNo. of Cases 22No. of Pregnancies 5Success rate 22%

ICSI in Azoospermia (PESA-TESE)No. of Cases 22No. of Pregnancies 9Success rate 41%

Conclusion: The results are very encouraging so we strongly recommendthis treatment for male factor infertility.

FC4.16.08SURGICAL SPERM RETRIEVAL IN CASES OF AZOOSPERMIA:MALE INFERTILITY, TESA, PESA, TESE, AZOOSPERMIAS. Siddiq , M. Khan, K. Siddiqi, The Infertility Advisor Centre, Lahore,Pakistan.

Objective: Previously it was thought that sperm retrieval was possibleonly in cases of obstructive azoospermia. Recent reports however have

shown that some somniferous tubules are producing few sperm cellseven in cases of non-obstructive azoospermia. The aim of this study is toselect the cases among azoospermia group for positive, meaning thesperm are available on aspiration & the couple is booked for ICSIprogram, a retrospective study. This tells us the chances of spermretrieval in cases of obstructive azoospermia.Study Methods: All the cases of azoospermia that were booked forinvestigation from Jan. to Dec. 99 in our center. All those cases aftercomplete history & examination underwent a trial run of surgical spermaspiration (TESA/TESE).Results: Total cases of azoospermia booked 71Obstructive azoospermia 47 casesTesticular aspiration performed on trial basisSperms retrieved 40 cases (85%)No sperm obtained 7 cases (15%)Non-Obstructive azoospermia 24 casesTest run testicular aspiration/TESA performedSperm retrieved 8 cases (33%)No sperm obtained 16 cases (67%)Cases that are positive for sperm are booked for ICSI program.Detailed procedure of TESA (testicular sperm aspiration), PESA(percutaneous sperm aspiration), MESA (micro equididymal spermaspiration) and TESE (testicular sperm extraction) and results will bediscussed.Conclusions: There was very little that a doctor could do treat spermdisorders but over the past few years there have been majorbreakthroughs in the field of assisted reproduction in the form of ICSI.Treatment of azoospermia is now possible. Men who previously couldnot think of becoming biological fathers now can.

FC4.17 BREAST CANCER: EPIDEMIOLOGY ANDMOLECULAR PATHOLOGY

FC4.17.01TAMOXIFEN TREATMENT OF BENIGN MAMMARYDYSPLASIA: A 6-YEAR FOLLOW UPF. Gargiulo , Dept. OB/GYN, San Filippo Neri Hospital, Rome, Italy.

Objectives: To determine the long-term objective efficacy andtolerability of cyclic treatment with 3-month courses of tamoxifen inpremenopausal women with benign breast disease.Study Methods: 181 premenopausal women with benign breast diseaseconfirmed by mammography or echography were treated with tamoxifen10mg/day for three months. Objective response was evaluated bymammography or echography. At recurrence, the treatment was repeatedwith the same schedule.Results: At the end of the first treatment cycle, 55.3% of patientsshowed complete remission of the lesions, and 23.7% significantreduction. 65.7% of the responding patients relapsed during a meanfollow-up of 74 months.Further 3-month courses of tamoxifen treatment induced a newremission in all the relapsing patients for the whole follow-up period.The treatment was well-tolerated, and no relevant adverse reaction wasrecorded.Conclusion: Cyclic treatment with 3-month courses of tamoxifen is along-term effective therapy for premenopausal women with benignbreast disease.

FC4.17.02EVOLUTION OF INVASIVE BREAST CANCER BETWEEN1989-1998 IN THE HOSPITAL OF BARBASTRO (SPAIN)R. Oncíns , C. Fuente, A. Bitrián, M. Alonso, M. Matute, J.A.Carrasquer, J. Florián. Breast Cancer Committee. Hospital of Barbastro.22300 Barbastro (Spain).

Objectives: To describe invasive breast cancer (IBC) along a 10-yearperiod in the Hospital of Barbastro (Spain) highlighting the effect of theBreast Cancer-Screening Program (BCSP) over the last two years.Study Methods: 370 IBC cases diagnosed in the period 1989-1998 werestudied. Data was obtained from Hospital Tumor Registry (HTR) andanalysed variables were age, residence, mode of detection, histology andstage. Bilateral tumors represent only one primary. The BCSP started the1st January 1997.


Results: The mean age was 65.05 ± 13.06 (range 31, 96) and 99.46%lived in the area covered by the hospital. Although 5.68% of cases wasdetected by the BCSP the most frequent mode of detection was thesymptoms associated with the disease. The most frequent histologicaltypes were ductal carcinoma in 72.43% cases and lobulillar carcinoma in10%, 6.76% had only cytological confirmation and 1.62% had nopathological study. Localised tumor was found in 43.24% cases, 39.19%had extended to lymph nodes, 9.73% had distant metastasis and 7.84%had unknown extent. 31,62% were T1 cancers.During the last two years an annual increase of 8.13% cases and also anincrease of 2.9% of T1 tumors were detected. The rate of metastaticdisease decreased 2.21% per year but positive nodes increased 2.87%.Conclusions: There is a high incidence of IBC in the HTR of theHospital of Barbastro being the mean age higher than in other HTR.Starting to screen highlights a temporary increase in the number ofwomen with IBC

FC4.17.03EARLY DETECTION OF BREAST CANCER BY ANALYSIS OFP43 POSITIVE LYMPHOCYTES FROM PERIPHERAL BLOODL. Auerbach (1), M. Hellan (1), M. Stierer (1), A.C. Rosen (2), R.Obwegeser (1), E. Kubista (1), G. Wolf (1), C. Moroz (3), H. R. Rosen(2), S. Panzer (1)(1) Dept. Special GYN, University of Vienna Medial School, Vienna,Austria.(2) Dept. Surgery, Dept. GYN, SMZ-Ost Vienna, Vienna, Austria.(3) Dept. Immunology, Beilinson Hospital, Tel Aviv, Israel.

Objectives: Regular screening mammographies and increasingknowledge of high-risk groups have resulted in an improvement in therate of detection of smaller malignant lesions. However, uncertainminimal mammographic features frequently require further costly andoften uncomfortable investigation, including repeat radiological controlsor surgical procedures, before cancerous lesions can be identified. Areliable diagnostic marker is therefore useful to differentiate betweenwomen with early stage breast cancer and women with benign breastlesions.Study Methods: In a double blind, randomized, multicenter study weevaluated the sensitivity and specificity of the expression of p43-positivelymphocytes as a marker in early stage breast cancer and alsoinvestigated its expression on T-cell sub populations. The presence ofp43-positive lymphocytes was investigated using the monoclonalantibody CM-H-9 and flow cytometry in 214 women with controversial,non palpable mammographic findings who were undergoing surgicalbiopsy.Results: Patients with early breast cancer (n=96) had significantly higherp43-postivie cell values (median 3.98%, range 0.98 to 19.4) thanpatients with benign lumps (n=118 median 1.22%, range 0.17% to3.7)(p<0.0001). At a cut-off level of 2% p43-postive cells a sensitivityof 89.7% and a specificity of 89.1% for detection of early breast cancercould be reached. While the median ratio of total CD4+/CD8+ cells was2.6, a ratio of 1.3 was found for the p43-positive subpopulation(p<0.001), thus indicating a significant link between p43 and CD8+cells.Conclusions: The determination of p43-positive lymphocytes inperipheral blood could serve as a additional diagnostic tool in patientswith controversial mammographic findings and could also reduce theneed for cost-intensive and often uncomfortable management of thesepatients.

FC4.17.04THE ASSOCIATION BETWEEN BREAST CANCER ANDTHYROID DISEASE.W. Tjalma, I. Cooremans, Ph. Buytaert , University Hospital Antwerp,Wilrijkstraat 10, 2650 Edegem, Belgium

Objectives: To study the impact of thyroid disease on tumor size, tumordifferentiation, axillary node status, metastasis, receptor status,recurrence and survival rate in patients with breast cancer.Study Methods: A retrospective study including 40 breast cancerpatients with any kind of thyroid disease compared to a controlpopulation of 40 patients with breast cancer.Results: A significant higher amount of relapses and a worse survivalrate were seen in the study group. No significant difference between thestudy groups was found for the other factors.

Conclusions: Our results indicate the importance of screening patientswith thyroid disease for breast cancer.Prospective studies and further research are needed to confirm theseresults.

FC4.17.05FREQUENT EXPRESSION OF c-erbB-2 AND p53 IN ITRADUCTALCOMEDOCARCINOMA OF THE BREASTW. Xu (1), X. Tu (1), T. Zhang (1), D. Shi (1) and H. Ji (2), Dept. ofPathology, Cancer Hospital, Shanghai Medical University, ShanghaiChina and (2) Dept. of Pathology, The Johns Hopkins Hospital,Baltimore, Maryland, USA

Objectives: Ductal carcinoma in situ (DCIS) is a heterogeneous group ofpreinvasive breast lesions mainly detected by mammography, in whichthe comedo subtype has been associated with aggressive clinicalbehavior leading to recurrence and invasion after consecutive surgicalmanagement. Expression of c-erbB-2 and p53 is frequently seen in avariety of solid tumors with aggressive behavior or poor prognosis,including invasive breast carcinomas. The aim of the study was toevaluate c-erbB-2 and p53 expression in comedo and non-comedo DCISlesions.Study Methods: A total of 31 cases of pure DCIS from the Departmentof Pathology, Cancer Hospital, Shanghai Medical University wereincluded. Eight cases were classified as comedo subtype and 23 cases asnon-comedo types. Expression of c-erbB-2 and p53 were detected withimmunohistochemical methods. Chi-square tests were applied forstatistical analysis. A p value of less than 0.05 was consideredstatistically significant.Results: Histologic examination revealed moderate to marked centralnecrosis, high nuclear grade and high mitotic activity (>3 / 10 highpower fields) in all eight (100%) comedo lesions. However, only 5 of 23(22%) non-comedo lesions showed some degree of central necrosis. Inaddition, none of the 23 (0%) non-comedo lesions presented highnuclear grade or high mitotic activity. Positive immunoreactivity of c-erbB-2 was seen in 75% (6/8) of comedo lesions but only in 26% (6/23)of non-comedo lesions (p<0.05). Furthermore, p53 positivity wassignificantly higher in comedo lesion (6/8, 75%) compared to that innon-comedo subtypes (6/23, 26%) (p<0.05). Dual immunopositivity forc-erbB-2 and p53 were detected in 50% (4/8) of comedo lesions, butonly in 4% (1/23) of non-comedo subtypes (p<0.05).Conclusions: The more aggressive clinical behavior of comedo DCIScompared to non-comedo lesions is probably biologically determinedand associated with c-erbB-2 and p53 expression. Therefore, intraductalcomedocarcinoma might warrant radical management such asmastectomy, or conservative surgery followed by radiation therapy.

FC4.17.06CORRELATION BETWEEN PLASMA TAMOXIFENCONCENTRATION AND TUMOR RESPONSE IN PATIENTS WITHBREAST CANCERA.Matthes (1) , S.Bighetti (1), V.Lanchote (2), H.Carrara (1), (1)FacultyMedicin, Av. bandeirantes, 3900, Campus Universitário, 8º A.Ginecologia, Ribeirão Preto, São Paulo, Brazil, 14049-900, (2) FacultyFarmacology, Ribneirão Preto, São Paulo, Brazil.

Summary: We studied 27 elderly patients (age range: 62 to 82 years)with advanced breast carcinoma who were treated with 20 mg oraltamoxifen per day, the dose considered to be ideal, for 3 months.Responders were followed up for 19 months and non-responders for 21months. The tumoral response also was associated with staging and thiswasn’t significant. We measured plasma tamoxifen citrate levels inplasma in order to determine their possible correlation with objectiveremission of the disease. The correlation was found to be significantamong responders (37%), whose median plasma tamoxifen level was187.40 ng/ml, as compared to non-responders, whose median plasmatamoxifen level was 99.52 ng/ml. The frequency distribution of patientsin both groups with concentration of tamoxifen lower and upper 182,60ng/ml was significant by Fisher’s test ( p<0,0011). On the basis of thepresent results, we suggest that patients whose plasma tamoxifen levelsreach 182,60 ng/ml after 3 months of treatment, with no tumor response,should stop treatment because they will probably not benefit from it.


FC4.17.07A STUDY OF APOPTOSIS IN NORMAL BREAST TISSUE INTAMOXIFEN-TREATED PREMENOPAUSAL WOMEN WITHFIBROADENOMAL.H. Gebrim , M.T. Seixas, E.C. Baracat, G.R. Lima, Dept. ofGynecology, University Federal of São Paulo, São Paulo, Brazil.

Objectives: Tamoxifen (TAM/20mg/day) has been used in breast cancerchemoprevention and exerts a long-term suppressive effect on humanbreast cancer cell proliferation. The aim of the study is to determine theapoptosis rate in the normal human breast epithelium adjacent tofibroadenoma during TAM treatment (10 and 20 mg/day).Study Methods: We evaluated a group of 40 premenopausefibroadenoma patients during 22 days of therapy. By using a double-blind randomized study patients were divided according to the followinggroups: Group I – 14 patients used as a control group. Group II – 13patients receiving 10 mg of TAM/day and Group III – 13 patientsreceiving 20 mg TAM/day. Treatment was started on the first day ofmenstrual cycle and biopsies were performed on the 22nd day of therapy.Serum levels of estradiol, progesterone, prolactin, FSH, LH and SHBGwere measured on the 22nd of the last cycle as well as on the biopsy day.Mammary samples were immediately fixed on 10% buffered formalinand included in paraffin. H.E. staining was performed in order toquantitate the number of apoptotic cells in 10 different fields at 400xmagnification.Results: The mean number of apoptotic cells in group I was 34.8 cells.Group II (10 mg/day) 12.9 and group III (20 mg/day) 12.0 apoptoticcells. Statistical analysis showed significant reductions in groups II andIII when compared to the control group. On the other hand, there wereno differences between groups II and III (Fisher’s test p<0.001).Conclusions: According to our findings, tamoxifen (10 or 20 mg/day)reduced the apoptosis rate on the human normal breast epithelium after22 days of treatment.

FC4.17.08TUMOR CELLS IN BONE MARROW OF BREAST CANCERPATIENTS WITH LOCOREGIONAL RECURRENCE OR DISTANTMETASTASESW. Janni , S. Gastroph, F. Hepp, Ch. Kentenich, D. Rjosk, Ch.Schindlbeck, H. Sommer, S. Braun. I. Universitaetsfrauenklinik,Klinikum Innenstadt, Munich, Germany

Objectives: Using cytokeratin (CK) as histogenetic marker to identifytumor cells in bone marrow (BM) of breast cancer (BC) patients, asubgroup of patients with poor clinical outcome can be identified. Thisstudy was designed to evaluate the frequency and prognostic relevanceof such cells in BC-patients at the time of either locoregional or distantrelapse.Study Methods: BM-aspirates from 65 consecutive patients with eitherlocoregional recurrence (n=32) or distant metastases (n=33) wereanalysed immunocytochemically for the presence of cytokeratin(CK)-positive cells. We used a quantitative immunoassay with monoclonalantibody A45-B/B3 andevaluated 2 x106 bone marrow cells per patient. For prognosticevaluation a cut off level of the number of detected tumor cells wascalculated in analogy to classification and regression tree (CART)analysis. Patients were monitored prospectively for a median of 32months.Results: BM-micrometastases were present in 5 of 32 patients (15.6 %)with locoregional recurrence, while significantly more patients (24 of 33patients [72.7 %]) had positive BM-results. No prognostic relevance wasfound in patients with locoregional recurrence. Significant separation ofprognosis for patients with distant disease was found at a cut off level of5 CK-positive cells per 2 x 106 screened BM-cells. The mean overallsurvival in patients with higher micrometastatic tumor load was 5.6months (2.0-9.1, 95 % CI) compared to 16.8 months (11.6-22.0, 95 %CI) in patients with 5 or less cells (P= .0004). Multivariate analysisallowing for hormone receptor status, disease free interval prior torecurrence, manifestation site of metastases, age and micrometastases inBM, revealed BM-status to be an independent risk factor for reducedoverall survival (RR 4.66 [1.63-13.32, 95 % CI]).Conclusions: Number of micrometastases present in BM of patients withmetastatic BC represents an independent prognostic indicator withpotential influence on therapeutic strategies.

FC4.17.09PROGNOSTIC IMPACT AND THERAPEUTICAL OPTIONS FORBREAST CANCER PATIENTS WITH MICROMETASTATICDISEASE.I.J. Diel , E.F. Solomayer, Ch. Gollan, F. Schütz, G. Bastert. Dept.OB/GYN, University Hospital, Voss-Str. 9, 69115 Heidelberg,Germany.

Objectives: The detection of disseminated tumor cells in the bonemarrow of patients with breast cancer is associated with a poorerprognosis. These cells are also the focus of new treatment modalities.Because detection methods are not only diverse but have also usuallybeen tested in only small groups, our aim was to investigate a detectionmethod in a large number of patients under standardized conditions.Study Methods: Intraoperative, bilateral iliac crest biopsies wereperformed in 1338 patients with primary breast cancer. The aspiratedbone marrow was subjected to differential centrifugation, smeared ontoslides and stained with a monoclonal antibody that recognizes the MUC-1 gene and targets the tumor-associated glycoprotein TAG 12. Patientsunderwent follow-up examinations at regular intervals. The results werestatistically evaluated.Results: After a median follow-up period of 56 months, distantmetastasis was observed in 368 patients (28%). 225 (61%) were tumor-cell positive at the time of surgery. Of the 238 patients who died 161(68%) were positive. In a multivariate Cox regressions analysis tumorcell detection was by far the best prognostic factor in patients with smallbreast tumors (T1). In women with tumors larger than 2 cm nodal statusand tumor cell detection had the same prognostic value.Conclusions: Our investigations show that the dissemination markermicrometastasis has a greater important for the prognosis of the diseasein women with small breast tumors than the classic prognostic factors. Inthis group of patients it might be better to dispense with axillarylymphadenectomy in favor of tumor cell detection. The goal must be todestroy these individual cells in the bone marrow, which are notaccessible to standard cytotoxic treatments, by means of a newtherapeutic modality (immunotargeting, gene therapy, bisphosphonates).

FC4.17.10ANTI-HER-2/NEU ANTIBODY INDUCES APOPTOSIS INHER-2/NEU OVEREXPRESSING BREAST CANCER CELLSINDEPENDENT FROM INTACT P53T. Brodowicz1, s. Tomek1, d. Kandioler-eckersberger.3, m. Rudas4, w.j.Köstler1, c. Ludwig3, a. Budinsky1, m. Hejna1, m. Krainer1, c. Wiltschke1, c.c. Zielinski1,2,5

1Clinical Division of Oncology and 2Chair of Medical ExperimentalOncology, Department of Medicine I, 3Department of Surgery and4Department of Clinical Pathology, University Hospital, and 5LudwigBoltzmann Institute for Clinical Experimental Oncology, Vienna,Austria.

Objectives: Anti-HER-2/neu antibody is known to induce apoptosis inHER-2/neu overexpressing breast cancer cells. However, exactregulatory mechanisms mediating and controlling this phenomenon arestill unknown.Methods: In the present study, we have investigated the effect of anti-HER-2/neu antibody on apoptosis of HER-2/neu overexpressing humanbreast cancer cell lines SK-BR-3, HTB-24, HTB-25, HTB-27, HTB-128,HTB-130 and HTB-131 in relation to p53 genotype and bcl-2 status.HER-2/neu density and bcl-2 expression were determined by flowcytometry, p53 status by sequence analysis and apoptosis was measuredflow cytometrically using a DNA fragmentation assay.Results: SK-BR-3, HTB-24, HTB-128 and HTB-130 cells exhibitedmutant p53, whereas wild type p53 was found in HTB-25, HTB-27 andHTB-131 cells. All seven native HER-2/neu positive cell lines (SK-BR-3, HTB-24, HTB-25, HTB-27, HTB-128, HTB-130, HTB-131) weaklyexpressed bcl-2 protein (10-20%). Anti-HER-2/neu antibody,irrespective of p53 and bcl-2 status, induced apoptosis in all 7 cell linesdose-and time-dependently. Incubation of the cell lines with anti-HER-2/neu antibody did not alter p53 or bcl-2 status. Furthermore, anti-HER-2/neu antibody did not induce apoptosis in HER-2/neu negative HBL-100 and HTB-132 cell lines.Conclusion: Our results indicate that within the panel of tested breastcancer cell lines, anti-HER-2/neu antibody induced apoptosis seems tobe independent of the presence of intact p53.


FC4.18 CHALLENGES FOR US ALL IN OBSTETRICS ANDGYNECOLOGY

FC4.18.01MANAGEMENT OF RECTOVAGINAL FISTULA AT DR. CIPTOMANGUNKUSUMO GENERAL HOSPITALD. Suskhan , B. Santoso, Z. Yunizaf, Division of UrogynecologyReconstructive, Dept OB/GYN, University of Indonesia, Dr. CiptoMangunkusumo Hospital, Jakarta, Indonesia

Objective: To evaluate the management of the cases rectovaginal fistulaein Dr. Cipto Mangukusumo Hospital from 1988 to 1998.Study Methods: Design/data identification: Retrospective description.Setting: Division of Reconstruction Urogynecology, Department ofOB/GYN, Faculty of Medicine, University of Indonesia / Dr. CiptoMangunkusumo Hospital.Subjects, patients, participants: Patients with rectovaginal fistulae.Main outcome measures: The success of rectovaginal fistulae managedat the Department of Obstetrics and Gynecology, Faculty of Medicine,University of Indonesia / Dr. Cipto Mangunkusumo Hospital.ResultsIn 1988 - 1998, there were 10 cases of rectovaginal fistulae. Most of thepatients were 21-30 years of age (70%), 90% cases were assisted bymedical personnel and paramedics, and one case assisted by traditionalbirth attendant. In the only case helped by the traditional birth attendant,there was found rectovaginal fistulae accompanied by vesicovaginalfistulae. Reparation was conducted for ten cases, and with one-timereparation it proved to be successful.Conclusions: The cases of rectovaginal fistulae were relatively few,approximately I case each year in Dr. Cipto Mangunkusumo Hospital.(1) Of the ten cases of rectovaginal fistulae managed in Dr. CiptoMangunkusumo Hospital, all turned out to be successful.(2) The assessment of location, size of fistulae, timing of reparationand the acquisition of adequate operation technique are the determinantsof success in fistulae operations.Keywords: Rectovaginal fistulae.

FC4.18.02EVALUATION OF LAPAROSCOPY: HOW EFFICIENTLY CAN ADEVELOPING COUNTRY COPE?H.E.F. Abdel-Rahim , M.N. Younis, A.M.A. El-Hemaly, A.F. Hamed,Dept. OB/GYN, Al-Azhar University, Cairo, Egypt.

Objectives: In the era of new laparoscopic procedures being introducedevery day, the question arose whether developing countries can copewith the progress or not. This study evaluated the efficacy and safety ofgynecological laparoscopy in 2 large University Hospitals in CairoEgypt and compared them with those of 2 hospitals in England as‘representatives’ of the developed world.Study Methods: This prospective observational study was carried out inthe period between 4/1996 and 4/1997. 624 laparoscopic procedureswere evaluated at El-Hussein and Bab El-Shareya University Hospitalsin Cairo, compared to 824 procedures at Eastbourne District GeneralHospital and Benenden Hospital in southeast England.Results: Diagnostic laparoscopy established a new diagnosis in 69.5% ofcases in the 2 Egyptian hospitals, compared to 73% of cases in the 2British hospitals, with no statistically significant difference. Operativelaparoscopy successfully achieved its aim of 67% of cases in the 2Egyptian hospitals, compared to 83.9% of cases in the 2 Britishhospitals, with a statistically significant difference. Categorization of theprocedures showed no difference in success rates in minor procedures asadhesiolysis and ovarian ‘drilling’, but big differences in complexprocedures as laparoscopically-assisted vaginal hysterectomy.As for safety, laparoscopic procedures had significantly morecomplications in the 3 Egyptian hospitals, especially hemorrhage,anesthetic complications, infection and injury of the urinary tract. Nomortalities were recorded.Conclusions: Some changes in policies, training and instrumentation areneeded to achieve better results. Whether financial resources could coverthose changes remains the big question.

FC4.18.03OBSTETRIC TRAUMA IN KENYA (A CONTINUINGCHALLENGE)M. A Omamo-Nyamogo , Dept. OB/GYN, Nyanza Provincial TeachingHospital, Kisumu, Kenya

Objective: Illustrate factors associated with the predominant type ofvesicovaginal fistula (vvf) in Kenya and repair outcome.Study Methods: This was case study of 200 women with VVFResults: The mean age of subjects was 16.2 years with a range of 14-40.96% of fistulae were obstetric and sustained intra partum. 94.75% ofobstetric VVF were sustained by primigravidae. In obstetric VVF, themean duration of labor was 36.8 hours with a range of 18-72 hours. Themean maternal height was 141.8 cm. The mean shoe size was “4.8”or“35.8”. Pelvic configuration was gynaecoid in 88% platypelloid in 8%and android in 4% of cases. The mean true conjugate (T.C.) was 8.9 cm.90% of fistulae were juxtaurethal with a diameter of 2.5 cm. In obstetriccases, repair 3 months post delivery had a success rate of 92%.Conclusions: The majority of VVf in Kenya are obstetric in aetiology,occur in underage primigravidae with a minority-defying repair. Shoesize and height are simple reliable indices of CPDRecommendations: Education on contraception and pregnancyphysiology should be incorporated in school. Curriculi targeting studentsfrom age 14 to curtail VVF in Kenya. Shoe size and height are guidersof CPD when pelvic assessment and partogram are not feasible.

FC4.18.04EXTRA AND INTRA PERITONEAL ABDOMINAL REPAIR OFV.V. FISTULAEA.H. Abbo , Dept. OB/GYN, University of Khartoum, Khartoum, Sudan.

Successful repair of V.V. Fistula still constitutes quite a surgicalchallenge to the operating gynecologist, urologist and urogynecologist.Different ways and methods of repair with varied modificationsincluding plastic repair were adopted by multitudes of operators withdifferent rates of success. The vaginal approach was mostly the route ofchoice adopted by most operators especially the gynecologists.Objective: For the last 10 years we deviated a great deal from thevaginal route and adopted the abdominal approach (extra peritoneal intravesical and intra peritoneal extra vescial repair). The indications for suchan approach were so many, namely: Vaginal Vault Fistula, the high V.V.Fistula, the Vesico-uterine Fistula, the Fistula hidden behind the pupicrami, the failed vaginal repair Fistula, and the Fistula with extensivevaginal scarring and fibrosis.Result: The success rate for repair of those cases were definitely higherthan merely adopting the vaginal approach.Conclusion: The abdominal route for repair of V.V. Fistula proved to bemore superior than the vaginal approach in the repair of most of theFistula cases.

FC4.18.05LONG TERM RESULTS OF RECTOVAGINAL FISTULA REPAIR:RETROSPECTIVE ANALYSIS OF 48 CASESE. Darai , D. Soriano, A. Lemoine, C. Laplace, B. Deval, L. Dessolle, P.Poitout, Service de Gynécologie, Hôpital Hôtel-Dieu, Paris, France.

Objective: To evaluate the long-term anatomic and functional outcomeof recto-vaginal fistula (RVF) repair performed by Musset technique.Study Methods: During the years 1992-1998, 48 women underwentrecto-vaginal fistula repair. A retrospective study in a university tertiaryreferral center was conducted.Results: The main etiologies were obstetrical trauma (25), local infection(11), inflammatory disease (7), and post surgery (3). Thirty women(62.5%) had a previous fistula repair failure. The mean ± SD fistuladiameter was 1.4±1.0, and in 39.9% of the patients the fistula diameterwas ³2.5cm. In 19 cases (39.6%) there was a complete opening of theperineum and the anal sphincter. Gas incontinence and stoolincontinence before the operation were noted in 85.4% and 75% of thepatients respectively. Successful anatomic results were achieved in allthe patients. Five patients were re-operated due to gas and stoolincontinence, all these women but one had anatomic and functionalsatisfactory results. The success rates in women with Crohn’s diseaseand in women with previous RVF repair failure were 100% and 97.9%respectively. No major intra or postoperative complications were noted.


Conclusion: Our experience suggests that Musset procedure providesexcellent anatomic and functional results. Women with Crohn’s diseaseor previous RVG repair failure have comparable long-term results.

FC4.18.06THE DAMAGING EFFECTS OF ESTROGEN-ACTIVESUBSTANCES ON WOMEN – ANALYSIS OF CONCENTRATIONLEVELS IN URINE THROUGH USE OF GASCHROMATOGRAPHY – MASS SPECTROMETRY (GC-MS)P. Frigo , C. Worda, J.C. Huber, Dept. OB/GYN, Division ofGynecologic Endocrinology and Reproductive Medicine, University ofVienna, Austria.

Objectives: The concentrations of different xenoestrogens weremeasured in the urine of women living in Vienna (Austria) in order todetermine the levels of these compounds present in the urban (female)population.Study Methods: We measured the levels of bisphenol A, nonylphenol,octylphenol, methylphthalate, butylphthalate, benzylphthalate,ethylhexylphthalate, dimethylphthalate, dibutylphthalate,benzylbutylphthalate, diethylhexylphthalate (all compounds in freeform, sulfated and glucoronides) and PCB’s 28, 52, 101, 153, 138, 180(free forms) in urine prospectively among 15 women, living in Viennafor at least 10 years. 24-hour urine was collected from these probands in1999. In order to detect these substances and their conjugates, we usedgas chromatography-mass spectrometry.Results: We were unable to find octylphenol, dimethylphthalate,benzylbutylphthalate, benzylphthalate, and free PCB’s in the urine of thewomen. Bisphenol A was detectable in 6 women at concentrations <40ng/ml. Nonylphenol was detectable in all women at concentrationsbetween 8 ng/mL and 972 ng/mL (mean: free form 366.09 ng/mL) andmethylphthalate at mean concentrations of 83 pg/ml. Butylphthalate wasdetectable in all women, as well as ethylhexylphthalate anddiethylhexylphthalate, which were found in concentrations at <16ng/mL. Dibutylphthalate was found in all except one woman.Conclusions: The results demonstrate that we were able to detect variousxenoestrogens in the urine of women living in an urban environment.Up-to-date, these xenoestrogens have never been found and measured inunexposed women before. These compounds correlate with varioushealth problems, including cancer, as a result of occupational exposureto high levels of these chemicals. Little is known, however, about theadverse effects of low-level environmental exposure to these chemicals.

FC4.18.07THE HYSTERECTOMY AFTER CESAREAN SECTION – THEANALYSIS OF INDICATIONS, POST-OPERATIVE PERIODCOURSE AND PATHOPMORPHOLOGICAL OUTCOMEM. Gajeuska , L. Marianowski, 1st Dept. OB/GYN, Medical Universityof Warsaw, Warsaw, Poland.

The aim of this study was the analysis of indication for histerectomyafter cesarean section, the analysis of post-operative period course andpatomorphological examination outcome of women, who had deliverycomplicated with histerectomy. The study group was 15 women whodelivered in Clinic Medical Academy in Warsaw in 1990-1999.By 7 of 15 women (46.6%) the supravaginal uterine amputation wascarried on, for the rest 8 (53.4%) corpus and cervix uterine was resected.The main indication for histerectomy was uterin atonia with all patients.By 4 (26.6%) women didn’t receive significant placenta tissue duringthe operation, because of its growth into uterine muscular. By one(6.66%) weak contract of uterine was cased by myoma. By 2 patients(13.3%) urinary bladder was damaged. One or two adnexa was resectedby 4 women (26.66%). Patomorphological examination indicatedtrofoblast growth into uterine muscular by 6 patients (40%). By one(6.66%) was found carcinoma praeinvasivum of uterine cervix, also byone (6.66%) – tumor of right ovary.In the study there was analyzed obstetric anamnesis, course of currentpregnancy, week of its ending, the indications for cesarean section, thecourse of post-operative period and the condition of baby.Conclusion: The main indication for histerectomy after cesarean sectionis uterine atonia. By 40% women patomorphological examination wasfound placenta tissue growth in uterine muscular.FC4.18.08

DOMICILIARY CARE FOR ONCOLOGICAL PATIENTS WITHOUTTHERAPEUTIC CHANCEJ.J.R. Mottola , L. Diniz, A.C. Santos, N. Garcia, C. Felipe,F.M. Laginha, I.N. Alercin, J.A. Marques, Center of Reference forWomen’s Health, São Paulo, Brazil.

Objectives: To show how palliative medicine with domiciliare care hasan increasing importance in the medical practices of developingcountries, actuating with a multidisciplinary team in this field.Study methods: The author studied 600 patients with gynecologicalcancer considered without therapeutic chances who were attended indomiciliare care during the period of January 1993 to August 1998 at theUnit of Palliative Care in the Center of Reference for Women’s HealthCenter.Results: The mean age of patients was 55 years old and breast cancer(71,6%) was prevailing, followed by cervical cancer (14.6%), andovarian cancer (7,5%). The patients were cared for by amultidisciplinary team. The acting professionals at their domiciles were:assistant physician head and residents, social workers, psychologists,nurses, pharmacists, physiotherapists, volunteers of the community and agroup of administrative support, 2400 domicile visits were made fortreatment and control of pain or associated disease (diabetes,hypertension, eschars, cardiac congestive insufficiency, depression,respiratory insufficiency), palliative therapy support such asparacenteses, physiotherapy, oxigenotherapy supply of supporting andtherapeutic materials besides socio-psychological interventions. Theaverage period of the patients’ permanence in this program was 150days. The domicile palliative care procedures were accepted by 95% ofthe patients and 87% of their relatives.Conclusion: The authors conclude that this program, with a specializedmultidisciplinary team as well as daily orientation of relatives, is able toobtain domicile palliative care for patients with gynecological cancerwithout therapeutic chances of the highest level. The program will alsomaintain the motivation of the relatives, avoiding the patients’ isolationat the hospital, and thereby humanizing the care and assuring betterquality of life with full control of pain and general symptoms.

FC4.18.09HURDLES OF GYNECOLOGICAL ONCOLOGY IN SOUTHERNAFRICAT. Maseela , L.V.M. Moja, Dept. OB/GYN, Medunsa, Bloemfontein,South Africa.

Objectives: An alarming degree of insecurity among both patients andhealth personnel with regard to the management of cancer is growing,fueled by controversies created by ethnomedicine.Study Methods: We studied the histories of 2154 patients admitted to theInstitute of Gynecological Oncology at MEDUNSA over a period of 5years. The questionnaires on admission sought to establish the origin ofthe patients (periurban or rural), duration of symptoms before diagnosis,the first healthcare provider consulted and the treatment administered.Results: The malignancies admitted were 82.30% Ca-cervix, 7% Ca-ovary, 4.5% Ca-corpus, 2% Ca-vulva and 4% GTC (Chorio-Ca). 80% ofthe patients with Ca-cervix had advanced stages. The ratio was in favorof rural-origin and low socio-economic group. 60% of the collectiveconfessed consultation with providers of alternative or traditionalmedicine and 26% primarily consulted orthodox medical practitionersand/or peripheral hospitals.Conclusion: The extreme delay in diagnosis as well as the intractabledifficulty to win patients to conventional methods of cancer managementresults in insurmountable high costs of therapy. Failure to tackle thisproblem reflects a culpable negligence of emotional and socio-medicalrequirements of cancer patients.


FC4.19 GENERAL OBSTETRICS AND GYNECOLOGY

FC4.19.01QUALITY OF PATIENT INFORMATION ON FEMALESTERILIZATION AND MENORRHAGIA ON THE INTERNETP. Latthe , M. Latthe, K. Khan, Birmingham’s Women’s Hospital,Birmingham, UK.

Objectives: To assess the quality of information available on-line onfemale sterilization and menorrhagia.Study methods: The search consisted of the phrases “femalesterilisation” OR “female sterilization” which were entered into thequery box of seven Internet search engines: Altavista, Excite, Hotbot,Infoseek, Lycos, Northern Light and Webcrawler. We assessed the mostrelevant sites as found by each search engine. For menorrhagia, the keyphrases used were “heavy periods” and “patient information”.All the Web pages of the selected sites were printed out and two of theauthors assessed them independently for inclusion in the study and forfulfillment of quality criteria (credibility and content). For assessingaccuracy of contents, specific items were derived from the Evidence-Based Clinical Guidelines of the Royal College of Obstetricians andGynecologists, UK, 1999.Results: None of the Web sites complied with all of the criteria forquality. Credibility was assessed by source that was described in 9 & 7Web sites, currency in 5 sties each and review process in none. Weassessed the content by hierarchy of evidence that was fulfilled by 5 & 4sites and accuracy of content by 1 site each respectively for femalesterilization and heavy periods.Conclusion: There is a need to be vigilant about the quality of healthinformation before incorporating it in health-care decision-making.

FC4.19.02NEURAL NETWORK ANALYSIS OR PREOPERATIVEVARIABLES AND OUTCOME IN ANAL SPHINCTER REPAIRA. Gardiner , A. Baxter, G. Kaur, K. Phillips, G.S. Duthie, Castle HillHospital, Hull, United Kingdom

Objectives: Appropriate patient selection is essential for achievingsuccessful outcome after anterior repair (ASR) and there is need formore sensitive methods of predicting postoperative continence controlthan are provided by standard multivariate techniques, which have beenonly 75-80% accurate. Artificial intelligence techniques, includingneural networks (ANN), have been used for analysing complex data andhave been successful in predicting surgical outcome; to date, this has notbeen used in data from incontinent patients. We use a neural networkalgorithm to assess probability of success after ASR.Method: Prospectively collected anal physiology data of patients havingundergone ASR was used. Information from about 75% of the studygroup was used to train an ANN and the remainder was used forvalidation. Change in continence, categorised as improvement, was theoutput result.Results: Outcome at 3, 6 and 12 months was assessed. ANN achieved amean overall accuracy of 95%. The correlation between ANN and actualdata values was best at 12 months (r = 0.931; p = 0.0001). Strongcorrelations were also found at 3 months (r = 0.898; p = 0.0001) and 6months (r = 0.742; p = 0.002).Conclusion: ANN’s are more accurate than statistics in predictingoutcome after anterior sphincter repair. The next stage is a prospectiveapplication on patients selected for sphincter repair.

FC4.19.03INFLUENCE OF FETAL HEART RATE DECELERATIONS, IN THECOMPUTERIZED STUDY OF FETAL HEART RATEVARIABILITY DURING LABOR.L. Briozzo 1, J. Alonso1, A. Martinez1, A.1 E.R. Migliaro. 2 1 Clinica Ginecotocológica “C” Prof. J.C. Cuadro Maternidad del CentroHospitalario “Pereira Rossell” Facultad de Medicina. Universidad de laRepública. Montevideo. URUGUAY2 Departamento de Fisiología Facultad de Medicina. Universidad de laRepública. Montevideo. URUGUAY

Objectives Short-term Fetal Heart Rate Variability (sFHRV) is anindicator of fetal wellbeing. The uterine contractions induce vagal-related reductions in fetal heart rate (HR) often called as DIPs.

Reduction of HR related with DIPs (of either mechanisms) is not strictlyrelated with fetal heart function. The aim of this work is the comparisonof sFHRV measured including changes induced by DIPs, and thoseobtained and after its elimination. Methods HR and uterine contractionswere measured in 18 fetus during the last 30 min of labor. Measurementswere made by means a of cephalic electrode connected to a commercialequipment. Digital acquisition was performed using original software.sFHRV was assessed using the index rMSSD (which estimates STV).After the first measurement of rMSSD, changes in HR related with DIPswere eliminated in each case,. Then a new rMSSD was calculated. Theidentification DIPs was performed by an experimented obstetrician.Results Mean values of RR intervals were (451.78 ± 39.92) in originalrecordings and (434.44 ± 34.06) after removal of DIPs (p=0.0026).Mean values of rMSSD were 18.18 ± 12 before and 9.34 ± 7 after DIPsremoval (p = 0.0046). Conclusions The inclusion of HR changes relatedwith DIPs could induce an erroneously evaluated variability. Therefore acorrect evaluation of sFHRV should eliminate the influence of DIPs.Our results show strong differences between values of sFHRV beforeand after removal of influences DIPs. We believe that sFHRV measuredwithout DIPs influence will provide a better picture of the fetus HRregulation.

FC4.19.04DO FETUSES “AT RISK” BENEFIT FROM HOSPITAL STAY?B. Petrikovsky (1) (2), E. Schneider (2), B. Rochelson (2)(1) Nassau County Medical Center, Dept. OB.GYN, East Meadow,

NY, USA.(2) North Shore University Hospital, Manhasset, NY, USA.

Objective: To study neonatal outcome in fetuses at risk depending on themode of management (in-patient vs. out-patient).Study Methods: Neonatal outcome, live births, cesarean section rateswere analyzed in 2 groups of potentially viable fetuses greater than 24weeks; those managed in the hospital (Group I) and those who refusedadmission (Group II). Indications for admission: fetal growth restriction(FGR) – 112 fetuses, pre-term PROM- 98, abnormal antenatal testingresults – 67. Admission was offered to all patients (278), 211 accepted,67 refused or signed out against medical advice within 7 days ofadmission.Results: Live births were achieved in 207 fetuses in Group I vs. 64 inGroup II (96%) (NS). Adverse neonatal outcome was reported in 23fetuses in Group I (11%) versus 9 fetuses (13%) in Group II. Cesareansection rate was 36% in Group I versus 24% in Group II (p<0.05).Conclusion: In-hospital management of high-risk fetuses was associatedwith statistically significant increase in cesarean section rate, withoutsignificant difference in perinatal morbidity or mortality.

FC4.19.05ANTIPHOSPHOLIPID ANTIBODIES IN PREECLAMPSIAMourashko L.E ., Gorodnitcheva J.A., Khodova S.I., Sukhikh G.T.Research Center of Obstetrics, Gynaecology. & Perinatology, Oparinastreet, 4, Moscow, 117815, Russia

The aim of this study was to examine spectrum, frequency and levels ofantiphospholipid antibodies (aPLs) in sera of preeclamptic women.Materials and metods: 74 preeclamptic women with family history ofsevere preeclampsia were observed. aPL was detected in sera byenzymoimmunoassay, using agents of 6 phospholipids: cardiolipin (CL),phosphatidylserine (PS), phosphatidylcholine (PC),phosphatidylethanolamine (PE), phosphatidylinositol (PI),sphyngomyelin (SPH).Results: according to the analysis conducted, the pregnant women weredivided in two groups: I - 47 patients with the abnormal levels of aPL(IgM and IgG); II - 27 patients with normal levels of aFL.Having studied the spectrum and frequency of aPL, it was established,that most often aPL idiotypes of IgM and/or IgG occured to CL (45.9%and 21.6% accordingly), PS (36.5% and 16.2% accordingly) and PC(40.5% and 23.0% accordingly).The evaluation of aPL IgM and/or IgG idiotypes in these groupsshowed, that in the first group they were significantly increasedbeginning from the first trimester and they were twice as large (254.9 + 40.0 and 166.9 + 22.9 accordingly), as in normal pregnancy (140.5 + 5.4and 111.7 + 6.2 accordingly). Abnormal levels of aPL remained during


the whole pregnancy in these women. Data obtained in pregnant of thesecond group didn’t differ from ones in normal pregnancy.In women with abnormal levels of aFL most early and severepreeclampsia at 20-24 gestational age - 45.9%, and high frequency ofplacental insufficient and fetal growth retardation (FGR) - 43.2%, and inthe second group these data were 14.9% and 37.8% accordingly.Conclusion: Thus, abnormal levels of aFL took place in 63.5%preeclamptic women. The most frequent are aFL to CL, PS and PC, thatis unfavourable prediction of severe preeclampsia

FC4.19.06DIFFICULTIES IN ADAPTATION FOR PREGNANCY IN WOMENAFTER 35 YEARS OLDUczak-Wawrzyniak J ., Szczepa_ska M., Skrzypczak J., Department ofGynaecology and Obstetrics, Division of Reproduction K.Marcinkowski University of Medical Sciences, Pozna_, Poland

Pregnancy wish of women who are 35 years or older is becoming muchmore common in clinical practiceThe aim: The aim of the study was to asses problems which influencethe adaptation to pregnancy in women 35 years and older.Material and methodsThe study group included 183 pregnant women who were 35 years andolder. Detailed interview was conducted with every participant of thestudy group.Results· 103 (56,3%) women had not planned pregnancy· 60 (32,8%) didn’t accept pregnancy till 12 week of gestation· 15 (8,2%) of husbands didn’t accept the pregnancy· 96 (52,5%) asked for genetic amniocentesis· 49 (51%) of these women said they would terminate the pregnancyin case of unfavourable amniocentesis outcome· 161 (88%) emphasised not feeling well during the first trimester· Out of 117 women with children 42 reported that their childrendidn’t come to terms with their mothers next pregnancyConclusion: Process of adaptation to pregnancy of women is often verydifficult life experience. For those women it is important to providespecialised medical care and also friendly and caring atmosphere duringthis particular time of the life.

FC4.19.07THE INTERNET, THE WORLD WIDE WEB AND BEYOND IN THEOBSTETRIC & GYNAECOLOGICAL PRACTICE TODAYMaarof Haj Mohideen * , Lisa Kessler, Sabah Abdul Salam

We are at the turn of a new century, new millennium, and a new era! Anera of new technology has dawned on us. The way we live is changingand will change forever! Electronic media will replace paper.Communication will be enhanced by internet and the world wide web.He heaviest growth will be experienced in the fields of ecommerce andacademics. The obstetrician and gynaecologist is blessed with excellentsites which are not only well designed but also very informative. Thededicated obgyn.net ( www.obgyn.net ) is growing by the day and thewealth of information and links. Eventually it is these electronic linksthat will hold together the whole wide world, shrink the distances andhelp overcome the differences and make us into a global village.Other important sites include the Royal College of Obstetrician andGynaecologists of UK ( www.rcog.org.uk ) not only conducts its day today administrative work, such as announcing examination results butalso provide a wealth of knowledge based and evidence basedinformation for the professionals. Medscape Women’s Health( www.medscape.com ), American College of Obstetrician &Gynaecologists ( www.acog.org ). Royal Australian New ZealandCollege of Obstetricians & Gynaecologists ( www.ranzcog.edu.au ) andSociety of Obstetrician of Gynaecologists of Canada( http://sogc.medical.org/ ) are some good examples of institutionsdedicated to provide information to the obgyn professionals.International organization such as WHO ( www.who.int ), IPPF (www.ippf.org ), CDC ( www.cdc.gov ) have launched campaigns on avariety of women’s health issues specially safe motherhood( www.safemotherhood.org ). The FIGO set a good example byconducting the entire FIGO2000 administration on the netThe fetus net ( www.fetus.net ) is another excellent site providing liveinformation on patient for educational purposes. Those who are

practicing obstetrics and are using U/S imaging in their the practice Dr.Joe Woo’ s Obstetric imaging site ( www.ob-ultrasound.net )Several journals are available n line notably BMJ ( www.bmj.com ) andlancet ( www.thelancet.com ).Client oriented site for patient education are on the net by the hundreds.They are dedicated to women’s health issues. The FDA has created anexcellent link resource site specially on this issue( www.fda.gov/womens/informat.html ).A “walk through” the world wide web will make us realize theabundance of contemporary medical and technical information availableon line and eventually understand why the dust collects on the 2000 orso page text book that was written only 2 years ago!

FC4.19.08NEW TECHNOLOGY FOR THE OBSTETRICIAN IN THE NEWMILLENNIUMM.Haj Mohideen, S.Abdul Salam, L.Kessler, King Fahd Hospital, P.O.Box 10176, Jeddah, Western, Saudi Arabia, 21433.

The immense growth of technology in the last decade or so has resultedin redefinition of literacy. If one does not know to use the computer orInternet one could be even labeled “illiterate” in the new millennium.The advances in improved performance of computers with lesser cost toonly a fraction of what it was before has made it even more important tobe used in our day to day life. The development hand held device withrelatively extensive memory has opened new vista in computing. Thecomputer itself has undergone a metamorphosis for the better. Itoptimizes the day to day life by its performance and efficiency.Increased portability of computers (notebooks) has made it possible forpersonalization and used in the care of the clientele and in normal life.The Internet technology is holding the whole world together and willcontinue link all corners of the world and beyond. New technology inthe areas involves low earth orbit satellites that could interact highbandwidths up 30 Mbits/sec. About 500 times faster than the 56 Kmodem.Such wide bandwidth will involve several clinical possibilities fromtelemedicine, telesurgery to tele consultation. In addition the largestorage media will help us develop storehouses for clinical data in themultimedia format (Audio/Video/3D). These data warehouse not onlycould be accessed around the world but also could be used by enterpriseinformation systems to enhance clinical care.The standard communication of the new millennium will be eitherelectronic mail or voice mail. Microsoft’s Net meeting will usher in anew era in videoconferencing, which could be used simultaneously byunlimited number of persons, within network of a single establishment(Intranet) or in the wide world (www).Distance learning and interactive training will provide a new concept ineducation and multimedia Departments are popping around the worldwhere the quality of learning has been greatly enhanced. Even thetraditional pregnancy wheel is being replaced by the electroniccounterparts the hand held “visors” with never ending possibilities ofdeveloping programme for these “pal” devices to store complete textbooks like “Harrison’s Principle of Medicine”.The immense potential of technology giving birth to superhuman talentsis already here. It is only a short while before we feel the effects of it inour day-to-day life of obstetric & gynaecological practice. Smart cardsand electronic precision instruments have made not only quality into thepractice but also have helped us to work together from remote regions!

FC4.20 EDUCATION

FC4.20.01IMPROVING TRAINING FOR OBSTETRICS AND GYNECOLOGYRESIDENTS IN ABORTION AND FAMILY PLANNING IN THEUNITED STATESU. Landy , P. Darney, USCF, San Francisco, CA, USA.

In the United States, abortion is one of the most frequently performedgynecological procedures, yet the majority of training programs do nothave a specific resident rotation in abortion or family planning. Over thepast 15 years, the number of training programs offering or requiringabortion training has declined.Objectives: In 1999, a national program was launched to increase thenumber of training programs offering routine training in abortion and


family planning (The Kenneth J. Ryan Residency Training Program inAbortion and Family Planning).Methods: Our approach is to identify and describe successful programs,and provide technical assistance, advice and financial support toteaching hospitals for the establishment of a formal rotation.Results: Since May 1999, we have established six training programs inteaching hospitals, including:A. First-trimester outpatient services within a gynecological clinic withor without second trimester OR abortions,B. Outpatient first and second trimester services in a dedicated space,C. Rotation through outside providers.Conclusions: It is evident that training opportunities can be increased by:1) Working closely with department chairs, training directors andfaculty with expertise in abortion and family planning,2) Providing information, technical assistance, i.e. business plans,treatment protocols, curriculum materials, skill evaluation tools,3) Offering financial assistance to cover start-up expenses fordepartments, and4) Requiring evaluations of the trainers and residents.

FC4.20.02ATTITUDES ON FAMILY PLANNING IN MEDICAL SCHOOLSTUDENTSG. Pierdant , Universidad Autónoma de San Luis Potosí, Vallarta No.130, San Luis Potosí, Mexico, 78250.

We are aware of the need for family planning specially in third worldcountries. We know that the physician plays an important role in familyplanning programs. In third world countries specially the physician is avery repected membr of the society and his opinions are very importantin helping the patients to make decisions about family planning. Wewere interested in finding out whether the medical school students hadany change in their attitudes towards family planning as they progressedthrough medical school. In order to find that out we designed a writtensurvey. We asked some questions relating the students attitudes aboutfamily planning. We applied the questionaire to all medical schoolstudents of the "Facultad de Medicina" of the "Universidad Autónomade San Luis Potosí". To our surprise we found out that attitudes towardsfamily planning didn´t improve much along the five years that lasts theschool. For example, 28% of the students believe that it is not acceptableany kind of family planning and this figure wasn´t different in any yearfrom first to fifth. Besides, 11% accepted only "natural" family planningmethods. Only 9% agree with elective abortion and this doesn´t changealong the different years. We believe this should call our attentio to theway we are teaching in our medical schools and a more appropiatefamily planning courses.

FC4.20.03LESSONS LEARNED FROM TWO YEARS OF IN-SERVICE-TRAINING FOR MIDWIVES AT ONANDJOKWE HOSPITAL INNORTHERN NAMIBIAT. Meguid , O. Ikeakanam, V.A. Petrova; Onandjokwe LutheranHospital, Private Bag 2016, Ondangwa, Owamboland, Namibia, 9000.

Objectives: To evaluate In-Service-Training efforts for midwives in asemi-rural African hospital.Methods: In early1998 we introduced regular In-Service-Trainingsessions for midwives at our 450-bed district- and referral hospitalserving a population of approximately 240.000 people delivering about4000 babies annually. The staff suggested the topics of the training. Adoctor and a midwife presented each monthly session together. Alllessons were summarized with a sheet of five to ten ‘take-home-messages’. An blinded exam, consisting of 46 true-false questionsderived from all ‘take-home-messages’, was held in late 1999.Results: On average 63% of all questions were answered correctly while26% were answered wrongly and 11% were not at all answered. Therange of correct answers was 91%-26%. If we choose a pass score of60% then 62% would have passed while 38% would not.Conclusions: Considering the fact that the questions were only derivedfrom the ‘take-home-messages’ these results are disappointing. Ourattention should focus on the following aspects of In-Service Training:Make In-Service-Training an integral part of the work routine:Compulsory participation, Participation and preparation during workinghours. Motivate staff to take actively part in training sessions: Encourage

individual research and presentation of findings within the own service,Sanctions against non-participation, Evaluation of participant-performance, Participation in In-Service-Training to be an importantaspect of general evaluation of staff

FC4.20.04PATIENT MANAGEMENT PROBLEMS (PMPS) AS A LEARNINGTOOL FOR CONTINUING MEDICAL EDUCATION FORPHYSICIANS AT PRIMARY CARE SETTING IN BANGLADESHS. Tasnim , Dept. OB/GYN, Institute of Child and Mother Health,Dhaka, Bangladesh.

Objectives: The aim of the study was to develop and evaluate a PMPsworkbook in common life-threatening obstetric problems in the contextof Bangladesh in order to encourage active learning through problemsolving and to resolve acceptability of PMPs in promoting continuingmedical education.Study Methods: This was an action research carried over a period fromMay 1997 to August 1998 among a sample of 30 doctors in the primarycare setting of different rural areas of Bangladesh. The workbook wasneeded based and developed using an educational Research andDevelopment strategy. Standard technique for construction of linear andbranching type of PMPs was adopted in a slightly modified way. Theproduct was validated through expert review and field-testing.Evaluation was done using a specially developed questionnaire and freecomments of the respondents.Results: The participants (90%) regarded PMPs as promoting self-directed active learning and self-assessment. It is reported that the PMPspromote problem solving (93%) and decision-making skills (100%) anduseful in triggering higher order thinking skills (80%). The knowledgeobtained form PMPs can be suitably applied into clinical practice (97%).PMPs received high acceptance for continuing medical education (83%).Conclusion: The Patient Management Problems was found to be anacceptable learning tool for continuing education to update andstrengthen clinical competence of doctors. The relevance of the method,convenience of use and the feedback potential was highly appreciated.

FC4.20.05LIFE SAVING SKILLS TRAINING IN MALAWI: IS IT ANY USE?J. A. Makawa, M. Jonazi, J. Hussein, M. BokosiSafe Motherhood Project, P.O. Box 3, Blantyre, Malawi.

Objectives: Surveys in Malawi indicate that 20-40% of health staffperceive that their knowledge and skills in management of majorobstetric complications requires improvement. In response, life savingskills training was developed from WHO and American College ofNurse-Midwives training manuals. This study investigated effectivenessof the training.Study Methods: The study included 73 health workers who underwentlife saving skills training. Duration of training was for two weeks,consisting of theoretical and practical components. Each candidate satfor a pre and post multiple choice examination. Both tests were thesame, and pre-test results were not revealed until completion of thetraining. Differences between the scores in the two groups werecompared.Results: Pre-test scores ranged from 23% to 81% (mean=53.5%) andpost-test scores from 43% to 97% (mean=73.7%). Candidatesexperienced a mean increase in their knowledge of 20.2% (p<0.001). Ofthose scoring less than 50% in the pre-test, mean increase in knowledgewas 29.3%, while average knowledge levels increased only 12.2% inthose with a pre-test mark of 60% or more (p<0.00006). The cost oftraining each candidate was US$357 indicating that US$12 is spent perpercentage increase in knowledge for those with a pre-test mark of lessthan 50%. This doubles if a pre-test score of 60% or more is obtained.Conclusions: This study demonstrates that life saving skills trainingincreases knowledge levels, with more pronounced benefit in those withpoor pre-test scores. The cost effectiveness of training health workerswith good pre-test results will be determined when larger numbers aretrained. Future efforts will be directed towards assessing clinical skills oftrainees and their knowledge levels six months after training.


FC4.20.06TRAINING MODEL BASED ON COMPETENCY IN MEDICALEDUCATION IN TURKEY: LESSONS LEARNED FORM FAMILYPLANNING TRANING EXPERIENCEB. Ozek(1) , T. Tuzer(1), S. Bahar(2), N. Sahin(2),1) JHPIEGO/Turkey Office, Ankara, Turkey.2) Hacettepe University Medical School Public Health Dept. Ankara,

Turkey.

Objectives: The aim of the study was to establish competency-basedmodel in medical education by gaining experience from a specific area,which applied the training such as family planning.Study Methods: Hacettepe University Public Health and JHPIEGO,using a modified version of JHPIEGO training methodology ran thestudy. A training package was developed. Training methodology, criteriaand structure were identified. The methodology used was competencybased training. Criteria were fixed for each category (all-level trainers,students). The structure was established in accordance with the level oftrainers’ knowledge and skills. The content was based on 7 main topic:Approach to Clinical Training. Creative Positive Training Climate,Using Audiovisual Aids, Using Interactive Techniques, UsingCompetency Based Assessment, Coaching in Clinical Training,Combining Coaching with Other Training Techniques. 26 trainers fromdifferent clinical departments of Hacettepe Medical School were trained.Results: Paired samples T test was used for statistical analysis. Themean difference between individual pre and mid course evaluationscores was 14.630 (t=5.001, p=0.000). The mean difference between preand mid course evaluation of the group according to seven main topicsrevealed a significant increase in scores (19.757; t=4.334, p=0.005).Conclusions: This study was a trigger for realizing the need to have achange in training approach in medical school education. The results ofthe first batch as stated above were promising.

FC4.20.07EVALUATION OF STRENGTHENING FAMILY PLANNINGTRAINING CONDUCTED IN EIGHT MIDWIFERY VOCATIONALHIGH AND TWO UNIVERSITY BASED MIDWIFERY SCHOOLSB. Ozek (1), T. Tuzer (1), Z. Saat (1), G. Aybas (2), G. Demir (2), A.Temiz (2)(1) JHPIEGO, Turkey Office, Ankara, Turkey.(2) Health Training and MCH/FP General Directorates, Ministry of

Health, Ankara, Turkey.

Objectives: The objectives of the study were to evaluate the results ofthe project for strengthening family planning training curricula of lastyear students in midwifery departments of vocational high anduniversity based schools.Study Methods: This study was carried out by Ministry of Health Turkeyand JHPIEGO. 15 trainers selected according to pre-determined criteriawere trained in 3 weeks. Training was conducted by National MasterTrainers with standardization of clinical skills in the first week andclinical training skills in the second week. The training was competencybased, using humanistic approach, adult learning principles andinteractive training techniques. The trained trainers implemented thestudy in the schools in the following educational season and trained 182students in 10 schools. Trainers’ and students’ performances wereobserved and evaluated throughout the year.Results: The differences between mean pre-course and mid-courseevaluation scores of trainers for clinical skills and training skill werestatistically significant (t=3.888, p=0.004 and t=4.816, p=0.003,respectively). The difference between mean pre and midcourse scoredfor IUD insertion skills of trainers was statistically significant as well(29.20 and 98.80 respectively, t=-10,835, p=0.000). In the students’training, mean number of pelvic examinations per student was 34 andmean accuracy rate according to checklist was 90%. The differencebetween mean pre and mid-course evaluation scores for students wassignificant as well (t=6.898, p=0.000).Conclusion: It has been proven that all trainers, students and serviceproviders that attended that type of training acquire family planningcounseling and IUD insertion knowledge and skills at competency level.

FC4.20.08A STRUCTURED TRAINING PROGRAM FOR FAMILYPLANNING AND REPRODUCTIVE HEALTH CAREJ. Newton , S. Walton, Dept. OB/GYN, Faculty of Family Planning andReproductive Health Care of the RCOG, London, England, UK.

Objectives: A 3-year structured modular training program in familyplanning and reproductive health care with quality assessment of skilltargets.Study Methods: Following the development of a syllabus, a structuredtraining log book of clinical competence, using a simple 5 point scalefrom (1) observation, (2) assistance, (3) direct supervision, (4) indirectsupervision and (5) independent practice, has been developed to addressthe skill required within a 16 module, 3 year training program in familyplaning and reproductive health care. This is directly applicable to the9,000 doctors working in family planning and reproductive health carewithin the United Kingdom and contains, for the first time, directobservation of the skills requires to perform at a senior level within oursubject. The log book contains skill targets for education, all branches offamily planning, genito-urinary medicine, sexual health, healtheducation, reproductive health care, including imaging, fertility,management of menstrual problems, urogynecology, oncology andforensic gynecology. It also included a module on the service provisionof family planning and reproductive health care. In addition to thedevelopment of syllabus and the skill targets log book, we havedeveloped a package of services required by centers wishing to developthis training program and accreditation of those centers.Results: Following the development of this program in 1999, the initialpilot sites have validated the program and the results from these 29centers, looking at the skill targets achieved in each of the 16 moduleswill be presented. The results show that it is possible to achieveindependent practice in all of these modules within the 3 year trainingprogram, provided approximately 50% of time is devoted to routinefamily planning and reproductive health care clinics throughout the 3year training program.Conclusions: This program is directly applicable to any country thatwishes to have a quality family planning and reproductive health careprogram, which integrates family planning, sexual health andreproductive health care items in a modular fashion using qualityassessment of the clinical skill targets reached using a structured logbook. In addition, the trainees have an induction assessment in order todefine aims at the start of each module and then a summative assessmentto monitor their progress at the end of each module or every year,whichever occurs first.

FC4.20.09TRENDS AND PERSPECTIVES OF THE WRITTEN PART IEXAMINATION OF THE OBSTETRICS AND GYNECOLOGYACCREDITATION EXAMINATION IN A DEVELOPINGCOUNTRYV. De Jesus , Dept. OB/GYN, University of the Philippines, Manila,Philippines

A total of 750 questions of the Philippine Board of Obstetrics andGynecology Written Part I Examination for the years 1995-1999 wereanalyzed. The content representativeness of the tabulated questions, theextent to which the test measure, the higher level cognitive domain wascompared with the content and domain specification for the PBOGblueprint. The effect of the composition of the Board on the test was alsoanalyzed.Results showed no consistency in item distribution through the five-yearperiod. In 1995, six of the content areas were over represented and fivehad less than the required number. The over represented content areasfrom 1996 to 1999 are 3 in 1996, 3 in 1997, 5 in 1998, 4 in the 1999examination. The undersampled content areas numbered 8 in 1996, 8 in1997, 5 in 1998, 7 in 1999.With regards to the cognitive domain, half of the questions were recallquestions. The distribution of questions per year of testing are: 52% for1995; 59 % for 1996; 53% for 1997; 45 % for 1998 and 55% for 1999.The type of subspecialization and the education background of theBoard affected the content representativeness of the test.The presence of the test blueprint did not guarantee a consistentdistribution of items in all the Part I Examination reviewed.


FC4.21 ENDOMETRIAL AND OVARIAN CANCER: TUMORBIOLOGY

FC4.21.01SIGNALING PATHWAYS INVOLVED IN EPIDERMAL GROWTHFACTOR (EGF) INDUCED PROLIFERATION OF OVARIANCANCER CELL LINES.Sundborg2, MJ , Manzano1, RG, Carlson2, JW, Birrer1, MJMolecular Mechanism Section, Cell and Cancer Biology Department,National, Cancer Institute, Rockville, MD, Division of GynecologicOncology,, Department of Obstetrics and Gynecology, Walter ReedArmy Medical Center, Washington, D.C.

Objective: To evaluate the role of specific signal transduction pathwaysin EGF mediated proliferation of two ovarian cancer cell lines.Methods: Western blot analysis, using phospho-specific antibodies, wasutilized for the detection of the activated forms of Extracelluar Signal-Regulated Protein Kinase (ERK), Jun N-terminal kinase (JNK), p38 andERK-5 kinases under EGF stimulation. Cell proliferation assays viaMTT were performed to detect quantitative differences with EGFstimulation in conjunction with specific pathway inhibitors of ERK, p38,Phosphatidylinositol-3'-Kinase(PI3K), and ERK-5 kinases and theActivator Protein-1 (AP-1) transcriptional complex.Results: EGF mediated proliferation was detected in two cell linesexpressing EGF receptors. Western blot analysis detected activation ofthe ERK, JNK, ERK-5, and PI3K kinase pathways after the addition ofEGF; however, minimal p38 kinase activity was noted. Inhibition ofERK, p38, and PI3 kinase activities did not block cell proliferationmediated by EGF. Additionally, overexpression of a c-jun dominantnegative in one cell line did not block proliferation.Conclusions: ERK, p38, and PI3K kinases are not involved in thesignaling pathways that mediate EGF induced proliferation in these celllines. Additionally, AP-1 complexes do not appear to play a role in thesepathways. However, the role of JNK requires further investigation asAP-1 complexes are not the only target of JNK. ERK-5 is activated bytreatment with EGF and could be a mediator of EGF stimulatedproliferation.

FC4.21.02BCL-2 EXPRESSION IN NORMAL, HYPERPLASTIC ANDMALIGNANT ENDOMETRIUMMagda S. Monayeri , T. Eldeep, N. Bayoumi, M. Hassan, M. Wahab,T.Eldeeb, H. Aly, Ain Shams University, 39 Sheikh Aly MahmoudStreet, Heliopolis Cairo, Egypt, 11351.

Objective: To evaluate the role of Bcl-2 expression as a key regulator forprogrammed cell death (Apoptosis) in normal, hyperplastic andmalignant endometrium. Moreover, evaluating the possible role of Bcl-2persistence as a prognostic marker in endometrial carcinoma.Study design: 52 endometrial samples including 11 normal, 15hyperplastic, 10 endometrioid carcinomas (UEC), 10 papillary serouscarcinomas (UPSC), 1 squamous cell carcinoma, 3 stromal sarcomas, 1uterine lymphoma, and 1 mixed Mullerian tumor, were studiedimmunohistochemically for Bcl-2 in paraffin embedded tissue. Bcl-2persistence was correlated with various pathological and clinicalparameters.Results: Bcl-2 staining predominated in glandular cells, with cyclicchanges in its expression. Hyperplastic endometrium had a significantlyhigher Bcl-2 staining score than did the cyclic and malignantendometrium. The staining intensity of Bcl-2 is markedly diminished inUEC and UPSC with down regulation of its expression. Six of 26 (23%)malignant endometrial lesions were negative. No significant correlationwas found between tumor type, histologic grade, surgical stage and Bcl-2 gene.Conclusion: The current study indicated an upward regulation of Bcl-2expression from normal cyclic to hyperplastic endometrium,demonstrating its role for cell survival. The down regulation of Bcl-2persistence in malignancy suggests that its role is bypassed by otherfactors controlling programmed cell death. The role of Bcl-2 relatedApoptosis is less important in late stage endometrial carcinoma.

FC4.21.03ABSENCE OF p51 ALTERATION IN HUMAN OVARIANCARCINOMAH. Shinozaki (1) , A. Okamoto (1), T. Tanaka (1), K. Ochiai (1), K.Shimizu (2), M. Saito (1), S. Takakura (1,2), J. Yokota (2), (1) The JikeiUniversity School of Medicine, Nishi-Shinbashi 3-25-8, Tokyo, Japan,105-8461, (2) Biology Division, National Cancer Center ResearchInstitute, Tokyo, Japan.

Objective: The p51 gene encodes a protein with a significant homologyto p53, thus, is a candidate tumor suppressor gene mapped tochromosome 3q28. To investigate the involvement of the p51 gene inhuman ovarian carcinogenesis, the p51 gene alteration was examined inprimary ovarian cancers and ovarian cancer cell lines.Methods. Mutation analysis of the p51 genes was performed in 40primary ovarian cancers and 7 ovarian cancer cell lines by PCR-SSCPand sequencing analyses. Expression of p51 mRNA was examined in 9primary ovarian cancers and 5 ovarian cancer cell lines by Northern blotand/or RT-PCR analyses.Results: Rare polymorphisms were detected in 3 primary ovariancancers and 3 ovarian cancer cell lines, whereas, no mutations of the p51gene causing amino acid substitutions or frameshifts were found byPCR-SSCP analysis of the entire coding region. Allelic imbalance wasdetected in 3 of 19 (16%) primary ovarian cancers. No p51 geneexpression was detected in 9 primary ovarian cancers, correspondingnormal ovarian tissues, and 4 ovarian cancer cell lines by Northern blotand RT-PCR analyses. One of 5 ovarian cancer cell lines showed p51gene overexpression by Northern blot analysis (20%).Conclusion: These results indicated that p51 gene expression was silentin normal ovarian tissues and primary ovarian cancers, and that mutationof the p51 gene does not play a major role in the d

FC4.21.04LOW SPECIFICITY OF CYTOKERATIN 19 mRNA EXPRESSIONIN THE PERIPHERAL BLOOD CELLS FROM PATIENTS WITHOVARIAN TUMORS.A. Okamoto , H. Takano, T. Tanaka, K. Ochiai, M. Saito, S. Isonishi,The Jikei University School of Medicine, Nishi-Shinbashi 3-25-8,Minato-Ku, Tokyo, Japan, 105-8461.

Objectives: It has been reported that cytokeratin 19 (CK19) is notexpressed in the peripheral blood cells from the healthy subjects, anddetection of CK19 mRNA in the peripheral blood suggests the existenceof epithelial malignant tumor cells in cancer patients. In this study, weexamined CK19 mRNA expression in the peripheral blood from patientswith ovarian tumor by reverse transcriptase-polymerase chain reaction(RT-PCR).Methods: Peripheral blood specimens were collected from 20 healthyvolunteers, 14 patients with benign ovarian tumors, and 25 patients withovarian cancers. Two samples were collected from each subject, with 10ml of peripheral blood in the first tube and 20 ml in the second tube. Theonly second tube was assayed , because the first tube could becontaminated with epithelial cells picked up by the needle when itpierced through the skin. mRNA was isolated from each samples, andRT-PCR was performed using primers which did not cross-amplify thepseudogene of the CK19.Results: The incidence of positive CK19 mRNA expression in peripheralblood from healthy individuals, patients with benign ovarian tumor andpatients with ovarian cancers are 60% (12/20), 71% (10/14) and 84%(21/25), respectively. Although the frequency of positive CK19 mRNAexpression in peripheral blood from patients with ovarian tumor washigher than that from healthy individuals, there was no statisticallydifference between the frequencies. Moreover, one healthy volunteershowed positive CK19 mRNA expression only in her menstrual period,not in her proliferative or secretory phases.Conclusions: These results suggested that CK19 is not a suitable targetto detect the presence of tumor cells in the peripheral blood frompatients with ovarian tumors.


FC4.21.05EXPRESSION OF MATRIX METALLOPROTEINASES ANDRELATED TISSUE INHIBITORS IN OVARIAN NEOPLASMSM. Furuya , H. Ishikura, T. Yoshiki, Dept. Pathology, HokkaidaUniversity School of Medicine, Sapporo, Japan.

Objectives: The aim of the study was to analyze species,interrelationship and clinical significance of matrix metalloproteinases(MMPs) and tissue inhibitors of MMPs (TIMPs) in ovarian tumors.Study Methods: Fluids and surgical specimens of ovarian tumors wereobtained from 57 patients with informed consent. MMPs and TIMPswere examined using zymography (in situ zymography, gelatin/caseinzymography), immunohistochemistry, ELISA and Western blotting.Results: Matriolytic activity was demonstrated within cystic contentsand cytoplasms of carcinoma cells. The concentration of MMP-9 washigher in carcinomas (p<0.05) than in benign tumors. The ratios ofMMP-9/MMP-2 and activated MMPs correlated with malignancy(p<0.05). The ratios of TIMPs/MMPs were higher in benign ones.Expression of trypsin was accompanied by activation of MMP-7.Conclusions: These results supported the concept that the tumor-derivedenzymes may play a part in demonstrating biological aggressiveness ofovarian neoplasms. Cyst fluids would become an important indicationfor analyzing matriolytic activities of ovarian cystic tumors.

FC4.21.06TAMOXIFEN MODULATES THE APOPTOTIC PATHWAYOF PRIMARY ENDOMETRIAL CELL CULTUREL. Drucker * , R. Stackievicz*, S. Yarkoni*, J. Radnay**, Y. Beyth***

and I. Cohen***,.*Oncology Laboratory, **HematologyLaboratory and ***Dept of Obs & Gyn, Sapir Medical Centre,Kfar-Saba, Sackler School of Medicine, Tel Aviv University, Israel.

Objectives: To evaluate the apoptotic effect of tamoxifen onprimary endometrial cell cultures with or without priming influenceof estrogen.Study methods: 14 different primary endometrial cellcultures were established. Each was split into 2 subculturesmaintained in the presence or absence of estrogens. The cells weretreated for 24 hours ith the following substances: tamoxifen (10-20mM), cisplatin (50mM) and a combination of tamoxifen (20mM)and cisplatin (50mM). Percentage of the apoptotic cells measured aspreG1 peak and the expression of the anti-apoptotic protein bcl2 wasstudied using flow cytometry.Results: Cells maintained in a medium containing estrogens showeda significant rise of the preG1 peak in response to tamoxifentreatment. Cells maintained in an estrogen free enviroment showed avariable response to tamoxifen. While 57% of the proliferativeendometrium cultures displayed a decrease in preG1 fraction, only25% of secretory endometrium cultures showed a similar response.The known pro-apoptotic effect of cisplatin on endometrial cells wasaugmented by tamoxifen. Bcl2 protein expression failed todemonstrate an obvious trend, regardless of the steroid content ofcellular environment.Conclusions: 1) Tamoxifen affects endometrial cells viability throughthe apoptotic pathway. 2)Estrogenic environment modulatestamoxifen’s apoptotic effect on endometrial cells. 3) Our results mayexplain the relatively high incidence of endometrial pathologies inpostmenopausal women compared to the relatively low incidence inpremenopausal women.

FC4.21.07IMMUNOHISTOCHEMICAL RESEARCH OF THYMIDINEPHOSPHORYLASE IN HUMAN ENDOMETRIAL CANCERY.Guo , L.Wei, Q.Fu, Y.Yu, People’s Hospital, Beijing MedicalUnivesity, Beijing, China, 100044.

Objectives: To investigate correlations between the expression ofthymidine phosphorylase (TP) and the dessity of microvessels within thetumors(MVD), the clinicopathologic features and prognosis inendometrial cancer.Study Methods: Surgical resected specimens from 40 patients withendometrial cancer were used. All patients underwent total abdomenhysterectomy and bilateral salpingo-oophorectomy. Pelvic lymph nodesamples with or without paraaortic lymph node sampling were removed

in 33 patients.The expression of TP and MVD were determined byimmunohistochemistry using monoclonal antibodies to TP and CD34 ,respectively.We investigated the relationship between the expression ofTP and MVD,the clinicopathologic features and prognosis inendometrial cancer.Results: Of the 40 patients,the expression of TP was positive in 24 cases(60%).TP immunoreactivity was rarely observed in histologically benignendometrium adjacent to endometrial cancer.The microvesel count wassignifically highter in TP-positive tumours than that in TP-negativetumours (P<0.05) . TP was significally highter in tumours limited toendometrium or invasive to ¡Ü1/2 myometrium than in tumours invasiveto> 1/2 myometrium (P<0.01) . TP was significally highter inendometrial cancer of Grade 1 than in that of Grade 2 or Grade 3.Therewas no significant correlation between TP and menopausal status , tumorsize, operation stage, lymph node metastasis, cervical invasive andprognosis.Conclusions: TP was associated with MVD, histologic grade andmyometrial invision in endometrial cancer.TP should play an importantrole in angiogenesis, especially in the early processs of invasion or well-differentiated endometrial cancers.

FC4.21.08IMPAIRED PRODUCTION OF TUMOUR NECROSIS FACTOR-a,DEFECTIVE EXPRESSION OF ICAM-1 IN HEALTHY WOMENWITH GERMLINE MUTATIONS OF BRCA1.Christoph Wiltschke1 , Alexandra C. Budinsky1, Teresa m.u. Wagner4,Roswitha M. Wolfram1, Wolfgang J. Köstler1, Marion Kubista3,Thomas Brodowicz1, Ernst Kubista3,4 and Christoph C. Zielinski1,2,3.1Clinical Division of Oncology, 2Chair for Medical ExperimentalOncology, Department of Medicine I, and 4Clinical Division of SpecialGynaecology, Department of Obstetrics and Gynaecology, UniversityHospital, and 3Ludwig Boltzmann Institute for Clinical ExperimentalOncology, Vienna, Austria.

Background: Tumour necrosis factor-a (TNF-a) is a potent cytokinesecreted primarily by activated cells from the monocyte/macrophagelineage which exhibits various antitumoral effects including theinduction of apoptosis, necrosis and the activation of lytic effector cells.Previous studies from our laboratory have indicated impaired productionof tumour necrosis factor-a (TNF-a) by monocytes derived frompatients with various stages of breast cancer.Methods: In the present experiments, we have now investigated theproduction of TNF-a a and the expression of ICAM-1 by monocytesderived from healthy women with germline mutations of BRCA1.Results: We report that monocytes derived from healthy women withvarious germline mutations of BRCA1 had significantly decreasedspontaneous (p=0.03, respectively) and lipopolysaccharide (LPS)-induced (p<0.001, respectively) production of TNF-a, as compared tomonocytes derived from healthy control females. We found nodifference in production of interleukin-6 (IL-6) induced by TNF-a onmonocytes derived from women with germline mutations of BRCA1.Conclusion: We conclude that the presence of germline mutations ofBRCA1 was associated with a selective deficiency in spontaneous andLPS-induced production of TNF-a by peripheral blood monocytes.Moreover ICAM-1 expression necessary for the interaction withlymphokine-activated killer cells with their ligand LFA-1 couldcontribute to defective lytic effector cell function in this population thuspossibly contributing to the development and propagation of the disease.

FC4.21.09HORMONE REPLACEMENT THERAPY AFTER ENDOMETRIALCANCER TREATMENT: PRELIMINARY RESULTSP.Moroy , O.Gökmen, T. Özdener, A. Aktulay, F. Türkçapar, C.Gülerman. Zekai Tahir Burak Women’s Health Education and ResearchHospital Menopause Clinic, Ankara, Turkey.

Objectives: Adenocarcinoma of he endometrium is considered to be anestrogen-dependent neoplasm. However hormone replacement therapy(HRT) can be indicated because of various conditions due tohypoestrogenic status after surgical treatment. According to few datafrom literature, there is no substantial evidence that estrogen increasesthe risk of recurrence of endometrial carcinoma.Methods: Between 1996-1999, 34 patients, underwent surgical treatmentfor endometrial carcinoma were included in this study. Surgical


carcinoma stages were Stage I or II. Majority of the cases were well ormoderately differentiated. Pathohistologic examination revealedadenocarcinoma in 96 % of cases. After 6 months of close observation,estrogen in combination with progestogen were administered. In most ofthe cases HRT was indicated because of menopausal complaints. Allpatients gave their informed consents for this study.Results: Menopausal vazomotor and other complaints were resolved inthe majority of the cases, receiving HRT. Lipid-lipoprotein levels wereimproved after 6 months of treatment. Significant increase in bonemineral densities at lumbar and femur sites were observed at 12 monthsof treatment. There was no evidence of recurrences in the patientsreceiving HRT.Conclusion: This preliminary data suggests that estrogens can be used inthe patients with a history of endometrial carcinoma for the sameindications as for any other postmenopausal women. Howeverprognostic factors must be emphasized and benefits and risks oftreatment must be explained to the patient.

FC4.22 HRT AND THE SKELETON

FC4.22.01THE SPECIFIC ACTIVITY OF DELTA-8,9-DEHYDROESTRONEON BONE RESORPTION AND OTHER PHYSIOLOGICALPROPERTIES ASSOCIATED WITH MENOPAUSEJ. Pickar (1), E. Baracat (2), M. Haider (2), F.J. Lopez (2), M. Dey (2),A. Negro-Vilar (2),(1) Wyeth-Ayerst Laboratories, St-Davids, PA, USA.(2) Escola Paulista de Medicina, San Paulo, Brazil.

Objective: Hormone replacement therapy with conjugated equineestrogens (CEE) significantly decreases the loss of bone mass. Delta-8,9-dehydroestrone sulfate (D8,9-DHES), a ring b unsaturated estrogen,is a component of CEE. The effects of D8,9-DHES on bone resorptionwere evaluated in an open-label study performed with estrone sulfate, amajor component of CEE, used as a comparator.Study Methods: Thirty post-menopausal women received either D8,9-DHES (0.125 mg/day), estrone sulfate (1.25 mg/day), or a combinationof the two for 12 weeks. Bone resorption was quantified by measuringurinary excretion of N-telopeptide. Vasomotor symptoms and hormonelevels were monitored.Results: Delta-8,9-DHES and estrone sulfate had similar effects on theinhibition of bone resorption. Each reagent alone decreased N-telopeptide secretion by approximately 40% despite the fact that a 10-fold higher dose of estrone sulfate was used. Delta-8,9-DHES, likeestrone sulfate, significantly decreased vasomotor symptoms by as muchas 95%. Each study group has similar decreases in levels of follicle-stimulating hormone and luteinizing hormone in peripheral blood. Totalcholesterol, low-density lipo-protein cholesterol, and high-densitylipoprotein cholesterol were unchanged, whereas serum globulins (sexhormone-binding globulin) increased marginally after D8,9-DHEStreatment.Conclusions: Delta-8,9-DHES, a component of CEE, was as efficaciousas estrone sulfate in decreasing bone resorption and vasomotorsymptoms.

FC4.22.02OSTEOPOROSIS SCREENING ON HIGH DOSE STEROID USINGPOSTMENOPAUSAL FEMALES: A LETTER OUTREACH STUDYM. Binstock, OB/GYN, A.Khoury, Ohio Permanente Medical Group,3733 Park East, Beachwood, Ohio 44122

Objectives: The purpose was to evaluate the response to a letter outreachadvising bone densitometry (DXA) on postmenopausal females onsteroids.Study Methods: Computerized records on demographics, medicationsdispensed and radiological procedures were merged on 33,662 femalesover 50 of a Health Maintenance Organization (HMO). Inclusion criteriawere having Prednisone 2,000 mg or more cumulative dispensed fromthe HMO pharmacies in the prior year. Exclusion criteria were priorDXA ordered through the HMO or having been dispensed in the last 3months a bone protective drug (any oral or transdermal estrogen,Raloxifene, Alendronate, Didronel, Calcitonin or Tamoxifen). Outreachletters for 194 patients were sent out on 11/5/99 to their (55) personal

physicians for review of appropriateness and signature. By 12/31/99,110 letters were signed, returned and mailed to the patients.Results: DXA screening was performed on 25 patients by 1/21/00 and anadditional 10 had future appointments scheduled for an overall responserate of 32 % (35/110). Of those 25 screened, 8 (32%) had osteoporosis(T score < -2.5) and 11 (44%) had osteopenia (T score < -1.0). Boneprotective medication new starts by 1/21/00 (dispensed from the HMOpharmacies) were 71% (5/7) for those with osteoporosis and 18% (2/11)for those with osteopenia.Conclusions: A letter outreach is an effective strategy for getting highrisk patients screened and initiating appropriate drug therapy on thosewith osteoporosis/osteopenia.

FC4.22.03THE IMPACT OF ESTROGEN DEFICIENCY AND THERAPY ONWOMEN’S ORAL HEALTHBJ Steinberg , DDS, Medical College of Pennsylvania HahnemannSchool of Medicine, Philadelphia, PA, USA.

The positive systemic effects of estrogen replacement therapy (ERT)have been well documented in the medical literature. However, untilrecently little has been published regarding the effect of estrogendeficiency and ERT on structures of the oral cavity and its effects onperiodontal disease. Increased systemic bone loss may be a risk factorfor tooth loss by contributing to the resorption of tooth-supportingalveolar bone. Women with severe osteoporosis are more likely to beedentulous as compared to healthy, age-matched controls. Recent studiesnow demonstrate that estrogen deficiency places most postmenopausalwomen at “high risk” for tooth loss and periodontal disease. Estrogenreplacement therapy appears to have a protective effect on the severityof periodontal disease and in preventing bone loss.

FC4.22.04HORMONE REPLACEMENT THERAPY ON SPECIALCONDITIONS: RHEUMATOID ARTHRITISRosas, FC; Fonseca, AM; Bagnoli, VR; Cardim, HJP; Poveda, E; Assis,JS & Pinotti, JA; Dept. OB/GYN, São Paulo University Medical School,São Paulo, Brazil

Objectives: To evaluate clinical and laboratorial parameters inclimacteric patients with Rheumatoid Arthritis (RA) who received 3different regimens of Hormone Replacement Therapy (HRT).Methods: A total of 37 postmenopausal patients with RA, who received3 different oral HRT regimens were included in this study. Ages rangedfrom 39 to 61 years (average 51,6 years). Patients were divided into 3groups according to the HRT regimen: Group A – 9 patients receiving17b estradiol 2 mg/day plus norethisterone 1 mg/day continuously;Group B 6 histerectomized patients receiving conjugated estrogens0,625 mg/day continuously; and Group C – 22 patients receivingconjugated estrogens 0,625/day continuously plus medroxiprogesterone5mg/day for 10 days. The Kupperman Menopausal Index (KMI), withspecial attention to complaints score (0=absence, 1=weak, 2=moderrate,3=severe) about arthralgies/mialgies (joints pain), and the Bone MineralDensity (BMD) for lumbar spine and femur neck were evaluated byDensitometry.Results: The mean KMI score was 20,11 at the first visit and 14,85 at thefinal visit (mean follow-up time 30,96 months). The meanarthralgies/mialgies score was 2,19 at the first visit and 2,17 at the finalvisit (mean follow-up time 19 months). The mean lumbar spine BMDwas 0,907 g/cm2 at the first visit and 0,931 g/cm2 at the final visit (meanfollow-up time 16,3 months), and that for femur neck was respectively0,771 g/cm2 and 0,762 g/cm2 (mean follow-up time 17,5 months).Conclusions: This study shows that HRT increases spinal BMD andmaintains femoral BMD in climacteric women with RA. HRT seems tobe also effective to improve these patients’ joints pain.


FC4.22.05CLINICAL AND LABORATORIAL EVALUATION IN ELDERLYWOMEN SUBMITTED TO LOW DOSES OF HORMONEREPLACEMENT THERAPY (HRT)Fonseca, AM ; Massabki, JOP; Arie, MHA; Margarido, PFR; Hayashida,SAY; Bagnoli, VR & Pinotti, JADept. Ob/gyn, São Paulo University Medical School, São Paulo, Brazil.

Objective: To evaluate the clinical and laboratory findings before andafter one year of low doses of HRT in elderly women.Methods: The mean age of the 30 elderly women studied was 65 years(range 60 - 75 years). The clinical symptoms were evaluated byKuppermann Menopausal Index (KMI) and divided into mild (<19),moderate (20-35) and severe (> 35). The blood pressure (mmHg), height(m), Body Mass Index (kg/m2) and Bone Densitometry were analyzed.The laboratory findings were evaluated by measuring fasting glucose(mg/dl), total cholesterol, HDL, LDL, VLDL and triglycerides. All theparameters were analyzed before and after 1 year of continuous lowdoses of HRT (0.3 mg of conjugated equine estrogens associated with2.5 mg of medroxyprogesterone acetate).Results:Mean values Initial After 1 yearKMI 20 13Blood pressure (mmHg) 140x80 130x80Height (m) 1,552 1,541Body Mass Index (kg/m2) 28,1 28,3Fasting glucose (mg/dl) 93 98Total cholesterol (mg/dl) 240,5 230,3 HDL (mg/dl) 45 47 LDL (mg/dl) 164 148 VLDL (mg/dl) 31,2 35,2Bone Densitometry (L1 - L4) 0,730 0,734Bone Densitometry (femur neck) 0,638 0,658Triglycerides (mg/dl) 156 176

Conclusions: There was an improvement of clinical symptomatology,lipids screening, bone densitometry, and a slight improvement intriglycerides.

FC4.22.07BONE DENSITY AND SKIN THICKNESS CHANGES INPOSTMENOPAUSAL WOMEN ON LONG TERMCORTICOSTEROID THERAPYY. Muscat Baron , R. Galea, M. Brincat, University of Malta, MedicalSchool, Gwardamangia, Malta, MSD07.

Introduction: Long term steroid therapy is complicated by osteoporosisand generalised thinning of the skin. These two complications of longterm steroid therapy are routinely assessed at the menopause clinic of StLuke's Hospital.Patients and methods: A cross-sectional study was performed on 164postmenopausal women who had been on long term corticosteroidtherapy. A longitudinal study on 38 postmenopausal women on longterm steroid therapy was performed. Each woman had the skin thicknessmeasured by high resolution ultrasound (22MHz) and the bone densitymeasured by a DEXA-Norland 386.Results: The cross-sectional study showed that steroid therapy wasassociated with the thinnest skin measurements (0.83mm) obtained forall patients screened at the menopause clinic. Similarly low bone densitymeasurement, lumbar spine (0.81g/cm)2, hip (0.71g/cm)2 were obtainedfor patients on long term standing therapy. Twelve women had sustainedsingle or multiple fractures. Since the establishment of the bone densityunit 38 patients who had been on long term steroid have been followedup after the administration of oral hormone replacement therapy[Prempak C 0.625 mg]. This longitudinal study revealed a constantincrease in skin thickness [6% per year] and bone density [left hip 5%,Lumbar spine 4%].Conclusion: In postmenopausal women taking long-term corticosteroids,skin thickness and bone density were both decreased, but the addition ofHRT as add-back improved the situation dramatically. Skin thicknessand bone density in women taking long-term corticosteroids werecomparable to those in women who had sustained osteoporotic fractures.It is therefore suggested that HRT be used as add-back therapy inpostmenopausal women taking long-term corticosteroid therapy.

FC4.23 HUMAN SEXUALITY

FC4.23.01SEXUAL BEHAVIOR AMONG ADOLESCENTS IN SWEDEN – ATEN-YEAR FOLLOW-UP STUDYE. Häggström-Nordin (1), U. Hanson (1), T. Tydén (1) & (2)(1) Dept. of Women’s & Children’s Health, Uppsala University andCenter of Clinical Research, Uppsala University, Central Hospital,Västerås, Sweden(2) Dept. of Public Health and Caring Sciences, Uppsala University,Döbelsgatan, Sweden

Objectives: The aim of the study was to investigate the sexual behavioramong high-school students in Sweden and compare it was a similarstudy performed ten years earlier. Another aim was to relate the findingsto gender and education.Study Methods: A questionnaire was delivered to a random sample ofclasses (n=20) in senior high school, in two medium-sized cities inSweden. The participation rate was 100% (n=408).Results: The results of the previous Swedish study are given in squarebrackets [ ]. The mean age was 16.5 years. 40% [54%] of the teenagersthought that the AIDS debate had affected their attitudes towards sex.45% [47.5%] of the students had intercourse. There were somedifferences between gender and study programs. More teenagers intheoretical (90%) than in practical programs (64%) had usedcontraceptives at their first intercourse. More girls in practical programs(49%) had had intercourse compared to the girls in theoretical programs(34%). Daily smoking was more common in the practical (24%) than inthe theoretical classes (14%). About one fourth of the teenagers wereunder the influence of alcohol at the time of first intercourse, this was adecrease compared to 1989. 23% of the teenagers were under theinfluence of alcohol at the time of first intercourse, this was a decreaseamong boys compared to 1989. 60% of the boys and 38.9% of the girlsclaimed that their parents had never talked to them about sex. The mainsource about sex was through newspapers and friends.Conclusion: The tendency that appeared ten years ago – that studentsattending practical programs put themselves more at health risks than dostudents at theoretical programs seems to continue. This could be turnedto the best account for while planning for counseling and sex education.

FC4.23.02SEXUAL SYMPTOMS AT MENOPAUSE AND THEIRRELATIONSHIP WITH OTHER CLIMACTERIC COMPLAINTSR.E. Nappi (1) , F. Polatti (1), J. Baldaro Verde (2), A.R. Genazzani (3),(1) University of Pavia, Piazzale Golgi 2, Pavia, Italy, 27100, (2)Interdisciplinary Center for Research in Sexology, Genoa, Italy, (3)University of Pisa, Pisa, Italy.

Objectives: Conflicting results have been reported regarding the effectsof menopause and HRT on several aspects of sexuality. The presentstudy aimed at investigating sexual symptoms in relation to the presenceof vasomotor, psychological and physical climacteric complaints.Study Methods: A Visuo-Analogic Scale (score from 0 to 10)comprising 38 items was filled in by 355 postmenopausal women (agerange: 46-60 yrs) recruited from several clinics located in different partsof Italy.Results: The major findings were: a) vaginal dryness was significantlyhigher in women suffering from loss of interest in things (p<.001), panic(p<.02), sleep difficulties (p<.004), loss of fitness (p<.04), involuntaryloss of urine (p<.04); b) fear for intimacy was significantly higher inwomen suffering from breathlessness (p<.02), anxiety (p<.04), loss oninterest in things (p<.002), depression (p<.006), feeling like being onyour own (p<.01), panic (p<.005), inability to concentrate (p<.02),headache (p<.02), fatigue (p<.003), weight gain (p<.04), increased hairon the face (p<.001), loss of fitness (p<.007), involuntary loss of urine(p<.02); c) need for tenderness was significantly higher in womensuffering from increased urinary frequency (p<.02), itch/burning in thegenital area (p<.01), involuntary loss of urine (p<.02), recurrent vaginalinfections (p<.01); d) reduction of sexual pleasure was significantlyhigher in women suffering from loss of interest in things (p<.008),depression (p<.05), feeling suddenly hungry (p<.04), increased hair onthe face (p<.001), loss of fitness (p<.005), recurrent vaginal infections(p<.0.04); e) pain during intercourse was significantly higher in womensuffering from anxiety (p<.04), loss of interest (p<.002), depression(p<.004), feeling like being on your own (p<.01), panic (p<.03), inability


to concentrate (p<.02), sleep difficulties (p<.04), headache (p<.05),increased hair on the face (p<.000), loss of fitness (p<.02), involuntaryloss of urine (p<.03); f) increased libido was significantly higher inwomen who did not suffered from climacteric complaints with theexception of breathlessness, inability to concentrate, bloating of theabdomen, lower abdominal pain, muscular and joint pain, skin dryness.Conclusions A complex interplay of biological, psychological and socio-cultural factors decrease the opportunities for a pleasurable perception ofsexual intimacy by affecting discrete components of female sexualresponse.

FC4.23.03HISTORY OF SEXUAL ABUSE AND GYNECOLOGICALEXAMINATION IN DANISH PATIENTS VISITINGGYNECOLOGICAL IN-AND OUT-PATIENT CLINICM. Hilden , Dept. OB/GYN,Glostrup County Hosp., Uni. ofCopenhagen, Denmark.K. Sidenius, Dept.OG/GYN,Glostrup County Hosp., Uni. ofCopenhagen , DenmarkU. Pikarinen, Dept. OB/GYN, Helsinki University Hosp., FinlandH. Stoum, Dept.OG/GYN, University Hosp., Trondheim, NorwayK. Offerdal, Dept.OB/GYN, University Hosp., Trondheim, NorwayT. Steingrimsdottir, Dept OB/GYN, Ladspitalinn,Reykjavik, IcelandK. Svahnberg, Dept.OB/GYN, IHM, Linköping, Sweden

Objectives: The aim of the study is to determine how many patients whohas been sexually abused and how this influenced the gynecologicalexamination.Study methods: 1000 patients visiting our in-and out-patient clinicaccepted to participiate in a mail distributed questionnarie. The responserate was 76 %. The study is the Danish part of the ”The Five CountryNordic Study” (Norvold-study).Results: Preliminary analysis of 200 questionnaires demonstrated that 20% had a history of sexual abuse. 47 % of these women felt ”strongdiscomfort” when being examined by the gynecologist, whereas only 16% of women who were not sexually abused experienced ”strongdiscomfort”. Yet 89 % of the abused women felt they had positivecontact with the gynecologist. There was no difference whether thepatient was examined by a male or a female gynecologist. 58 % of thewomen with a history of sexual abuse reported that they felt violatedduring contact with the health care system. Less than 5 % reported thatthey had informed the gynecologist of their history of sexual abuse, andeven fewer that they had been asked by the gynecologist.Conclusions: Patients with a history of sexual abuse more often feel”strong discomfort” when being examined. Very few patients reportsexual abuse to the gynecologist and gynecologists rarely ask thepatients about this issue. This study shows the need to openly discussissues such as sexual abuse with patients, in order to minimize the riskof retraumatisation.

FC4.23.04A STUDY OF JAPANESE DYSPAREUNIA IN PATIENTS WITHENDOMETRIOSISM.K. Seki , K. Hamazaki, M. Kashimura, Dept OB/GYN, University ofOccupational and Environmental Health, Kitakyushu, Japan.

Objectives: Dyspareunia is known to be associated with endometriosis.In this study, we focus our interest on physical and psyschologicalexamination in order to manage patients who have hyspareunia withenodmetriosis.Study Methods: 42 Japanese women with endometriosis below the ageof 40 years were included in this study. The subjects were divided into 2groups presenting with dyspareunia (n=20) and in those withoutdyspareunia (n=22).Results: In comparison with the women without dyspareunia, patientswith dyspareunia were noted to have a significant different in terms ofthe scarring of the uterosacral ligament significant differences betweenthe sate of rAFS.Conclusions: Local lesions of uterosacral ligament may play animportant role when associated with dyspareunia especially for patentswith endometriosis and could account for the high incidence ofpsychological conflicts in such patients.

FC4.23.06SEXUAL BEHAVIOR IN CLIMATERIC WOMENPenteado, SRL ; Fonseca, AM; Cavalcanti, AM; Parellada, CI; Bagnoli,VR; Pasqualotto, EB & Halbe, HW, Dept. OB/GYN, São PauloUniversity Medical School, São Paulo, Brazil

Objective: To determine the sexual behavior of a group of climatericwomenMethods: Thirty-seven sexually active climateric women wereinterviewed in this study. Patients’ age ranged from 43 to 60 years(mean age 51,8 years). The following parameters were evaluated: sexualdesire, masturbation, self – confidence (to feel sexually desirable by herpartner), knowledge of her and her partners erotical body parts, sexuallyopen dialogues with her partner, and different types of sexual activities.Results: Out of 26 women (70,3%) who reported sexual desire 21(56,7%) reported decrease of it in the past years. Twenty-eight (76,7%)denied masturbation and most patients felt desired by their partners (22patients – 59,4%). Most women reported to know their and their partnerserotical body parts, respectively 26 (70,3%) and 22 (60,5%). Twenty-two women reported an open dialogue with their partners. Finally, 31women (83,8%) reported to have only vaginal intercourse, 3 (8,2%)vaginal and oral, and the last 3 (8,2%) reported vaginal, oral and analintercourse.Conclusion: Studies about sexuality and the impact of aging physicalchanges on performance and behavior of climateric women mustcontinue being carried out.

FC4.23.07A PILOT STUDY OF THE EFFECT OF VIAGRAÒ ON VAGINALBLOOD FLOW (VBF) IN FEMALE SUBJECTSEllen Laan , MD; Rik HW van Lunsen, MD; Alan Riley, MD; Liz Scott,MD; Mitra Boolell, MD

Objective: Viagra, a selective inhibitor of cyclic guanosinemonophosphate (cGMP)-specific phosphodiesterase type 5, is anefficacious and well-tolerated treatment for erectile dysfunction. It hasbeen hypothesised that the nitric oxide (NO)-cGMP pathway may befunctionally important in the female sexual arousal response (Burnett etal, 1997). The effects of Viagra on female sexual arousal wereinvestigated in a randomised, double-blind, placebo-controlled, two-waycrossover study in 23 healthy female subjects (age range, 18-38 years)conducted at two centres. Methods: VBF, measured byphotoplethysmography during visual sexual stimulation (VSS; Laan etal, 1995), and a subjective arousal score (Wincze et al, 1976) wereassessed after a single dose of Viagra (50 mg) or placebo. VBF datafrom one centre were not analysable due to a technical failure. Results:For the 12 subjects at the second centre, there was a statisticallysignificant increase (p value less than 0.05) from baseline in VBF withViagra treatment (mean 160%; 95% CI, 104%-217%) compared withplacebo treatment (mean 112%; 95% CI, 74%-150%). There was nosignificant difference between the two treatment groups for the meansexual arousal score, which was 1.8 (range, 0-4) for subjects receivingViagra and 2.0 (range, 0-4) for those receiving placebo. The mainadverse events reported were headache, flushing, and nasal congestion.Conclusion: Viagra is well tolerated in healthy female subjects and mayincrease VBF during VSS but does not appear to increase the subjectivearousal score.

FC4.23.08EVALUATION OF THE EFFECTS OF PHENTOLAMINEMESYLATE ON VAGINAL BLOOD FLOW RESPONSE INPOSTMENOPAUSAL WOMEN WITH FEMALE SEXUALDYSFUNCTIONRubio EA , Lopez M, Lipezeker M, Rampazzo C, Hurtado de MendozaMT (Mexico City, Mexico), Lowrey F, Loehr LA, Lammers PI (TheWoodlands, Texas)

Objectives: Studies have shown that Female Sexual Dysfunction (FSD)in postmenopausal women is characterized by weak clitoral erections,vaginal dryness, and diminished vaginal sensations. This study wasconducted to collect both physiological and subjective diary informationon the effects of phentolamine mesylate, a non-selective alpha-adrenergic receptor antagonist, in postmenopausal women with FSD.


Study Methods: A double blind, placebo controlled, randomized, four-way crossover study conducted at two investigational sites in Mexico.Vaginal blood flow changes after study drug administration to berecorded with a photoplethysmograph unit (PPU) in 48 postmenopausalwomen with FSD, 24 using Hormone Replacement Therapy (HRT), 24Non-HRT (NHRT), during four separate video stimulation sessionsincluding neutral and erotic scenes. Patients were asked to recordsubjective changes (arousal, engorgement, lubrication, warmth, tingling,and pleasurable feelings) using a Video Assessment Questionnaire(VAQ). Four treatments were tested using a double-dummy fashion:vaginal solutions containing 5 mg (V5) or 40 mg (V40) phentolamine,an oral 40 mg (O40) phentolamine tablet, and placebo. The PPU canprovide a measure of vaginal pulse amplitude (VPA), reflecting short-term changes in vaginal engorgement.Results: Forty-one (41) evaluable patients were enrolled (19 HRT, 22NHRT). Statistically significant drug effects were observed in the HRTgroup for VPA and VAQ response variables. A 45 % difference betweenV40 and Pl was recorded for the neutral to erotic video change in VPA(relative to baseline). For the VAQ, both V40 and O40 were found to bestatistically significantly better than Pl for 5 of the 6 response variables(approx. 25 – 45 % improvement when compared to Pl). As expectedpharmacologically, V5 results were in between Pl and V40, for bothVPA and VAQ. There was a moderate degree of correlation betweenobservations made with PPU and VAQ. No drug effects were observedin NHRT patients with either the PPU or the VAQ.Conclusions: This study indicates that phentolamine mesylate,administered either orally or vaginally, increases genital blood flow andsensations in patients on HRT with FSD. Furthermore, these data are inagreement with phentolamine-induced blood flow changes reportedpreviously in a pilot study of FSD, as well as in men with ErectileDysfunction. The notable differences observed between HRT and Non-HRT users is hypothesized to be attributed to differences in local andsystemic drug absorption, and in differences in receptor availability,however, this requires further study.

FC4.24 HYSTEROSCOPY DIAGNOSIS AND TREATMENT

FC4.24.01MICROWAVE ENDOMETRIAL ABLATION IN WOMEN WITH AFIBROID UTERUSM.A. Ellard , T. Hayes, N.C. Sharp, Dept. OB/GYN, Royal UnitedHospital, Bath, UK.

Objective: Hysterectomy is commonly performed for women withfibroids who complain of menorrhagia. We report the use of MicrowaveEndometrial Ablation (MEA) as an alternative method of treatment.Study Methods: Prospective observational study.388 pre-menopausal women underwent microwave endometrial ablationbetween October 1994 and June 1999. 78 (20.1%) were noted to havefibroids <5 cm diameter on pre-operative ultrasound scan.The main outcome measures were avoidance of hysterectomy and asubjective change in menstrual pattern.Results: Mean follow-up time was 33.8 months. Of the 78 patients withfibroids (2.6% of total patients treated) were noted to distort the uterinecavity. The mean fibroid size was 2.5 cm diameter and 21 (5.4% oftotal) had more than one fibroid noted on ultrasound scan. 84% reportsatisfaction at six months with 25.3% reporting amenorrhoea. 15 patientsrequired further surgery, 7 (8.9%) of which had a hysterectomy. Therewas no difference in mean survival time to hysterectomy in patients withor without fibroids (18.7 vs. 17.7 months respectively). Cox regressionanalysis identified fibroids as not increasing the risk of further MEA orhysterectomy.Conclusions: 91% of patients with fibroids avoid hysterectomy withMEA. Multiple fibroids and fibroids causing slight distortion of theuterine cavity does not adversely affect outcome. Pre-operativeassessment including the use of ultrasound to measure fibroid size isessential in determining patient suitability for Microwave EndometrialAblation (MEA).

FC4.24.02ENDOMETRIAL HYDROTHERMAL ABLATION: A NEW, SIMPLETREATMENT FOR MENORRHAGIAM. Hefni , T. El-Toukhy, A.E. Davies, E. Morris. Benenden Hospital,Kent, UK

Objective: To evaluate the safety, tolerability and effectiveness ofendometrial hydrothermal ablation (HTA) in treatment of menorrhagia.Patients: Thirty-two pre-menopausal women with menorrhagia resistantto different modes of treatment were recruited to the study betweenJanuary 1999 and January 2000. Pre-operative transvaginal scan,endometrial sampling and Pap smear were performed. All patients hadendometrial preparation with 2 injections of depot GnRH agonist 4weeks apart with the operation scheduled 3 weeks after the secondinjection. When laparoscopy was concomitantly performed, intra-peritoneal temperature around the uterus was measured throughout theprocedure.Intervention: Coagulation of the endometrium at 90 C for 10 minutesunder hysteroscopic control and general anaesthesia.Results: Mean (range) age was 42.7 (30-56), median (range) parity 2 (0-5), mean (range) body mass index 27.1 (19-43) and mean (range)duration of symptoms was 4.5 (1-10) years. No morbidity related to theprocedure was noted. In six laparoscopies performed at time of HTA, norise of temperature around the uterus or leakage of fluid through thetubes were reported. The operation was well tolerated and accepted byall patients. Preliminary results are encouraging with 87.5% of womenare either amenorrheic (62.5%) or hypomenorrheic (25%) after 6months. Results at 12 and 18 months will be presented.Conclusion: In this study, endometrial HTA was a safe well toleratedand effective method of treating menorrhagia. It offers promise as asimple technique to treat resistant menorrhagia and may help to avoidhysterectomy.

FC4.24.03PREMALIGNANT/MALIGNANT OUTCOME IN ABNORMALUTERINE BLEEDING EVALUATED BY HYSTEROSCOPY,ULTRASONOGRAPHY & TISSUE SAMPLING: A COHORTSTUDYDr Shagaf H Bakour, Birmingham Minimal Access and SurgicalTraining (MAST) Centre Academic Department of Obstetrics andGynaecology, University of Birmingham. UK.

Objective: To determine the accuracy of outpatient hysteroscopy in thediagnosis of premalignant and malignant endometrial lesions.To evaluate the risk of premalignant and malignant pathology amongendometrial polyps.To examine the relative significance of hysteroscopic andultrasonographic evidence of endometrial atrophy in relation toinsufficient sample on outpatient endometrial biopsyDesign: A prospective cohort study (1996-97).Setting: Minimal Access Surgical Training centre in a large teachinghospital.Study Methods: Outpatient hysteroscopy and endometrial sampling wasperformed on 248 patients with abnormal uterine bleeding. Comparinghysteroscopic findings with histological diagnosis “gold standard”, thediagnostic accuracy of hysteroscopy was computed using likelihoodratios (LRs).To determine the magnitude of malignant potential among polyps, wecompared the pathological findings in polyps (cases) with non-polypoidal specimens (controls).Multiple logistic regression modeling was used to evaluate theindependent effects of age, menopausal status, hysteroscopic findingsand sonographic endometrial thickness on outpatient endometrialsampling (sufficient or insufficient) used as the binary dependentvariableResults: For normal hysteroscopy the LR was 0.7 (95% CI 0.5-0.9)while for abnormal hysteroscopy the LR was 51.1 (95% CI 7.9-326.9).62/248 patients had endometrial polyps. Hyperplasia was more frequentin endometrial specimens with polyps than in those without (11.3% vs4.3%, p=0.04), but the incidence of carcinoma in the two groups was thesame (3.2% vs 3.2%, p=1.0).Insufficient sample on endometrial biopsy was associated withhysteroscopic finding of endometrial atrophy (odd ratio 4.79, p=0.04)and sonographic endometrial thickness above 5mm (odd ratio 0.19,


p=0.001). There was no association with patient’s age and menopausalstatus.Conclusions: If the hysteroscopic findings were definitely abnormal, theposttest probability is substantially increased.Hyperplasia was, but cancer was not, more common in women withendometrial polyps than in those without.If the hysteroscopic and sonographic endometrial assessment isconsistent with endometrial atrophy, insufficient sample on outpatientendometrial biopsy is reassuring

FC4.24.04ENDOMETRIAL ABLATION AND UTERINE ARTERY BLOODFLOW: RESULTS OF A PROSPECTIVE LONGITUDINAL STUDYS. Okolo (1) , K. Mohammed (2), (1) Royal Free & University CollegeMedical School, Pond Street, London, United Kingdom, NW3 2QG, (2)North Middlesex Hospital, London, United Kingdom.

Introduction: Endometrial ablation is now established as a first linetreatment for menorrhagia. Reduced endometrial thickness and intra-uterine synechiae contribute to the reduction in menstrual loss but littleis known of the associated changes, if any, in uterine artery blood flowwhich is ultimately responsible for endometrial perfusion.Subjects & Methods: We therefore monitored uterine artery pulsedDoppler blood flow before and after endometrial resection with loopdiathermy in 11 non-obese (body mass index < 28 kg/m2) women aged42.2 + 1.25 years (mean + sem) who had gonadorelin (Zoladex, ZenecaUK) down-regulation four weeks before surgery. Assessments weremade before down-regulation, immediately pre-operatively, and at 1, 6,12 and 24 weeks post-operatively.Results: 10 women (90.9 %) experienced satisfactory reduction in theirmenstrual loss at 24 weeks but one woman requested a hysterectomy forcontinuing menorrhagia. mean uterine volume was unchanged.endometrial thickness decreased from 6.0 + 0.47 mm (mean + sem)before down-regulation to 3.2 + 0.43 mm at 24 weeks whilst pulsatilityindex increased by 36 % from 2.245 + 0.156 to 3.051 + 0.025 in the leftuterine artery (p = 0.004) and by 30 % in the right artery from 2.386 +0.227 to 3.098 + 0.114 (p = 0.034). in the patient with continuingmenorrhagia, the increase in mean pulsatility index was much less at14% and 19% for the left and right arteries respectively.Conclusion: Endometrial ablation is associated with reduced uterineartery blood flow, and Doppler blood flow measurements may predictwomen whose ablation will fail.

FC4.24.05OPERATIVE HYSTEROSCOPY, AN ANALYSIS OF 286 CASESC. Prevedourakis , N. Makris, M. Dachlythas, 1st Dept. OB/GYN,University of Athens, Alexandra Gen. & Maternity Hospital, Athens,Greece.

Objectives: The contribution of operative hysteroscopy in endometrialproblems.Study Methods: Two hundred and eighty six non pregnant women 21 to49 years of age with several uterine pathology (169 adhesions, 48polyps, 24 myomas, 17 septated uteri and 28 dispaced IUD’s) weresubmitted to operative hysteoscopy from 1992 to 1999.The procedure was done after hospital admission, under generalanesthesia and cervical dilation with a double channel sheath operativeendoscope or a resectoscope. Sodium Chloride 0.9% or Dextrose 5%were applied according to the use of monopolar or bipolar currentthrough Hysteromat as distention mediums, a cold light source of 250watts and a video camera connected with a video and monitor of WolfCompany. The duration of the intervention ranged between 15-40 min,and the consumption of the distention medium was between 400-950 mlrespectively.Results: Successful hysteroscopic surgery in all the presented cases withno side-effects or complications during or after the above operations andthe follow-up 2 moths later revealed a normal cervical and uterine cavityin all the presented cases with 42 term pregnancies until now.Conclusions: Operative hysteroscopy is the method of choice for thetreatment of the endometrial abnormalities.

FC4.24.06ENDOMETRIAL LASER INTRAUTERINE THERMAL THERAPY(ELITT): A NEW APPROACH TO THE TREATMENT OFMENORRHAGIAJ. Donnez , M. Nisolle, R. Polet, Dept. OB/GYN, Catholic University ofLouvain, University Clinic, Brussels, Belgium

Objectives: We have developed a new global endometrial ablationtechnique – Endometrial Laser Intrauterine Thermo-Therapy (ELITT).This study is conducted to confirm the clinical applicability of thismethod.Study Methods: The technique involves a diode laser system (21W,830nm), and a disposable applicator designed to conform to the innershape of the uterus. The applicator includes three optical light diffusersthat are designed to transmit laser light in all directions. During the 7-minute procedure, the laser light fills the uterine cavity assuringcomplete therapy of the endometrium including the cornua.Results: After the first phase of development (1994-1996) 100 patientswere included in a prospective study started in February 1997. Theresults in terms of amenorrhea and spotting are 86% at 6 months and90% at 12 months.There were no uterine perforation and serious adverse affects during orimmediately postoperatively. In 2 cases, cornual hematometra wasdiagnosed by echography.Conclusions: The ELITT procedure, which can be performed in anoutpatient setup, is a safe, effective and simple method offeringexcellent alternative to conventional endometrial ablation techniques andhysterectomies.

FC4.24.07THERMAL ENDOMETRIAL ABLATION WITH FOLEYCATHETER BALLOONSingh K C , Sengupta R, Agarwal N, Misra K*Department of Obstetrics & Gynaecology and Pathology*,University College of Medical Sciences and GTB Hospital, Delhi, India.

Objective: To evaluate the effectiveness and safety of a technique forthermal endometrial ablation.Method: A simple device comprising a Foley catheter No. 14F, a three-way cannula and a 20-cc syringe was used for thermal endometrialablation. The balloon of the catheter was inflated within the uterinecavity with boiling normal saline for 9 minutes. The safety andeffectivity of the technique was assessed in three steps; on uterinespecimens, on intact uteri during hysterectomy and two weeks prior tohysterectomy. In step IV, this technique was used as primary treatmentin 10 patients with menorrhagia, who were followed for 6 to 48 months.Results: The mean maximum endometrial cavity temperature was 910 Cwhereas serosal temperature was below 370 C. None of the balloonruptured in all the steps. In 13 of 14 specimens in step II, there was azone of hyperaemia with a depth of 3 to 7 mm. The correspondinghistological picture was extensive haemorrhage and fragmentation ofglands throughout the endometrium including the cornual regions.Consistent findings were noted in step III. There was a statisticallysignificant positive correlation between the volume of fluid injected anddepth of hyperaemia. In step IV, all 10 patients were relieved ofsymptoms for a period ranging from 6 to 48 months. None hadamenorrhea. 2 patients underwent hysterectomy for recurrence ofsymptoms; one in 6 months and the other in 42 months. First patient hada small submucous fibroid on histology whereas in the second, theendometrium was proliferative.Conclusion: This technique could be a simple, effective, inexpensive andsafe alternative to hysteroscopic endometrial ablation.

FC4.24.08TOOLS AND TECHNIQUES TO FACILITATE OFFICE BASEDENDOMETRIAL SAMPLINGR. Jackson , Dept. OB/GYN Peace Arch Hospital, White Rock, BC,Canada.

Objectives: The aim of the study was to identify tools and techniques tofacilitate office based endometrial sampling.Study Methods: The patients received pre-procedure information. Non-steroidal anti-inflammatories were administerd 30 minutes prior to theprocedure. The cervix was sprayed with Hurricaine spray (20%


benzocaine Beutlich Pharmaceuticals). The anterior lip of the cervix andthe endocervical canal was pained with Hurricane gel. Injectablexylocaine 2% in the anterior lip, endocervix and paracervix (usingneedle adapters 3”, 4” or 5” at 4 and 8 o’clock positions) enabledaccurate placement of the injection as well as withdrawal to ensure non-vascular injection. 2mm (extra thin) laminaria placed in the endocervicalcanal for extremely stenotic cervixes. Atraumatic teflon reusable osdilators enabled the external cervical os to be successfully located theendocervical canal located and dilated in a gentle atraumatic fashionwith the gradual increments of the dilators. False passage creation wasavoided the plastic endometrial biopsy curette introduced. Syringe orplunger based curettes are available. Diameter, flexibility, access holesfor ports on distal ends, pre-formed shapes, cutting edges, vary fromcurette to curette.Results: Uterine cavity was accessed and endometrial samplingperformed in 95% of patients in the study.Conclusions: Uterine Cavity access and endometrial biopsy can beaccomplished in a simple, safe and efficacious manner in an officesetting.

FC4.24.09DILATION OF CERVIX IN OUTPATIENT HYSTEROSCOPY: ARANDOMIZED DOUBLE-BLINDED CONTROLLED STUDY OFLOCAL LIGNOCAINE EFFECT ON PAIN SCORINGA.Y.K. Wong , K.S. Wong, L.C.H. Tang, Dept. OB/GYN, Kwong WahHospital, Hong Kong, SAR China.

Objectives: To assess the efficacy of lignocaine gel to reduce the painduring outpatient hysteroscopy in patients requiring dilation of cervix, incomparison to placebo group (no anesthesia).Study Methods: Six hundred Chinese women undergoing outpatienthysteroscopy in Kwong Wah Hospital were included in this prospective,randomized double-blinded, placebo-controlled study. 300 patients wererandomized into the lignocaine group which received lignocaine gelapplication to the cervix. The other 300 patients in the placebo groupreceived KY Jelly. All of them underwent the usual hysteroscopicexamination (rigid hysteroscope, 5mm sheath, CO2 as inflating medium)in which dilation of cervix was performed when insertion of thehysteroscope was difficult due to tight cervical os. Each patient gradedher pain severity throughout the procedure at every 1-minute intervalusing the Present Pain Intensity Scale (score 0-5).81 patients in the lignocaine group and 94 in the placebo group requireddilation of the cervix and their mean pain score, overall pain score andduration of the procedure were compared using the significance testing.Failed procedure rate was compared using the chi square test.Results: The mean pain score, overall pain score, and duration ofprocedure in the lignocaine group were 1.91±0.79, 12.98±9.14, and6.21±3.17 minutes respectively; whereas, in the placebo group were2.00±0.74, 13.90±8.10 and 6.55±2.34 minutes. There was no significantdifference in these parameters between the groups.The procedure was abandoned due to excessive pain in one patient in thelignocaine group, and another one in the placebo group. No significantdifference was observed.Conclusion: In our study population, dilation of cervix during outpatienthysteroscopy is well tolerated in the absence of local anesthesia; and thatlocal application of lignocaine gel has no significant effect in reducingthe pain scoring.

FC4.25 INDUCTION AND LABOR

FC4.25.01AN OBJECTIVE MEASURE OF CERVICAL RIPENESS ATINDUCTION OF LABOUR USING ELECTRICAL IMPEDANCEMEASUREMENTSMP O’Connell , S Wisher*, NJ Avis**, BH Brown***, SR Killick and SWLindow, Department Obstetrics & Gynaecology, University of Hull,UK,* Department of Applied Statistics, University of Hull, UK, **TheCentre for Virtual Environments, University of Salford, UK,***Department of Medical Physics and Clinical Engineering, Universityof Sheffield, UK.

Objective: To produce an objective measure of prelabour cervicalchange (ripeness) at induction of labour using electrical impedancemeasurements.

Method: Electrical impedance measurements were made in 86 patients atthe time of induction of labour. Digital examination of the cervix wasperformed and a Bishop’s score was recorded. Each patient had at leastfour readings taken. The measurements were made using an 8mm pencilprobe, with four gold electrodes mounted flush with the face of theprobe. The probe was applied to the external cervical Os anteriorly and acurrent of 10mA was passed between an adjacent pair of electrodes. Theresulting potential was measured between the remaining pair. Thispotential equates to the cervical resistivity Measurements were made at afrequency of 4.8kHz.Results: An average value for resistivity was obtained by taking themean of all the readings made in each patient. The mean resistivity forthe unfavourable group (Bishop score £4) was 7.03Wm, and 5.34Wm forthe favourable group ( Bishop score>4). Independent t-testsdemonstrated significant difference between the two groups (t=2.714,p=.008).Conclusion: This preliminary study demonstrates the ability of electricalimpedance measurements to characterise cervical ripeness at inductionof labour, and raises the possibility of a clinical use for this technologyin the prediction of labour onset and perhaps more importantly inpreterm labour.

FC4.25.02GROUP B STREPTOCOCCUS ACQUISITION AND INFECTIONRATE AFTER UNDER WATER DELIVERYR.A. Zanetti Dällenbach 1, I.Hösli1, R Frei2, W.Holzgreve1. 1Dept.OB/GYN, Women’s University Hospital, 4031 Basel, Switzerland;2Dept. of Central Laboratory, University Hospital, 4031 Basel,Switzerland

Objectives: Deliveries under water are becoming more popular. It isunclear if this birth method implies an increased risk of infection to themother and the neonate. The aim of the study was to investigate theacquisition and infection rate with Group B Streptococcus (GBS) afterwater deliveries.Study Methods: 53 women with a spontaneous cephalic delivery at termwere included in this case control study. 29 women entered the studygroup and delivered in water. 24 women took a tub bath during laborand entered the control group for delivery. We took vaginal and rectalswabs antenatally, examined 1liter of water postnatally and took swabsfrom the neonates nose and pharynx. We used a highly sensitive culturein a selective broth and a hybridisation method for GBS detection(AccuProbeTM). GBS positive women received intrapartumchemoprophylaxis.Statistical analysis: two tailed Fisher exact test for 2x2 tables.Results: The prevalence of intrapartum maternal GBS carriers was37.93% (11/29) for the study group versus 37.5% (9/24) for the controlgroup (p=1). The neonate acquisition rate was 10.34% (3/29) versus12.5% (3/24) (p=1). The water was contaminated in 24.14% (7/29)versus 16.66% (4/24) (p=0.74). We did not observe maternal or neonatalinfections.Conclusion: The prevalence of intrapartum maternal GBS carriers wereidentical. The neonates showed no statistical difference in GBSacquisition rate. There was no significant difference in thecontamination rate of the water.Our data suggest that a delivery under water does not imply an increasedrisk of GBS infection or acquisition.

FC4.25.03PHASE II TO DETERMINE THE POTENTIAL EFFICACY ANDSAFETY OF NITRIC OXIDE FOR CERVICAL RIPENING INPREGNANCY AT TERMB. Chanrachakul , Y.Herbutya. Dept. OB/GYN, Ramathibodi Hospital,Mahidol University, Rama VI Road, Bangkok 10400, Thailand.

Objective: To determine the efficacy and safety of nitric oxide forcervical ripening.Study Methods: Thirty pregnant women were randomized to receiveintravaginally either 500 mg glyceryl trinitrate, 40 mg isosorbidemononitrate or 3 mg prostaglandin E2 tablet for cervical ripening.Results: The changing of Bishop score was not significant differenceamong the glyceryl trinitrate group, the isosorbide mononitrate groupand the prostaglandin E2 group, but the effect of glyceryl trinitrate andisosorbide mononitrate was predominantly on the changing of the


cervical consistency while prostaglandin E2 group. Nitric oxide groupshad more vaginal delivery than prostaglandin E2 although there was nosignificant difference. There was no adverse side-effect in this study.Conclusions: The nitric oxide in both forms can induce cervicalripening. The cervix becomes favourable before the onset of labour andonly need a short period of uterine contraction before achieving vaginaldelivery.

FC4.25.04PREINDUCTION CERVICAL RIPENING: A COMPARISON OFEXTRAAMNIOTIC FOLEY CATHETER BALLOON ANDINTRACERVICAL PROSTAGLANDIN E2 GELV. Suri , R. Dalui, I. Gupta, P. Ray, Dept. OB/GYN and Microbiology,Postgraduate Institute of Medical Education and Research, Chandigarh,India

Objectives: To compare the efficacy and safety of extraamniotic Foleycatheter balloon with intracervical PGE2 gel for pre-induction cervicalripening.Study Methods: One Hundred women, who needed induction of labourwere randomly allocated at >33 weeks of gestation to receive eitherextraamniotic Foley catheter or PGE2 gel. Cervical swabs were takenbefore pelvic examination and again at the onset of labour or after 12hours. Placental membranes were sent for bacteriological study afterdelivery in all patients.Results: The mean Bishop score at 12 hours and the difference in changeof Bishop score over 12 hours were significantly higher (p < 0.001) inFoley catheter group and was associated with significant decrease indose of intravenous oxytocin for augmentation/induction of women whodid not go into spontaneous labor before 12 hours. Preparation deliveryinterval was also significantly shorter (p<0.05) with Foley cathietergroup. No statistically significant difference was noted in the duration oflabor, duration of rupture of membranes, mode of delivery, side effectsand complication between change in Bishop score and mode of deliveryin Foley catheter group. No patient in both the groups had clinicalevidence of chorioamnionitis. There was no correlation of growth ofmicroorganisms between the cervix swabs and placental membranescultures of both groups.Conclusion: This study concludes that extraamniotic Foles catheter wasan effective, safe mechanical method of preinduction cervial ripeningand its use was not associated with any complication.

FC4.25.05A RANDOMISED CONTROLLED TRIAL OF EXTRA AMNIOTICSALINE INFUSION AND INTRACERVICAL FOLEY CATHETERFOR CERVICAL RIPENING.M.P. Jasper , S. Blossom and A. Peedicayil. Dept OB/GYN, ChristianMedical College and Hospital, Vellore, India 632 004

Objectives: The aim of the study was to compare the efficacy of extraamniotic saline infusion with intra cervical Foley catheter balloon aloneto ripen the unfavourable cervix before induction of labor at term.Study Methods: Two hundred and forty two women were randomized toreceive either extra amniotic saline infusion or intra cervical Foleycatheter for ripening the unfavourable cervix at term before induction oflabor, in this randomized controlled trial.Results: One hundred and forty primigravidae (75 in the saline and 65 inthe Foley group) and 102 multigravidae (54 in saline and 48 in Foleygroup) were included in the study. The initial Bishop score at the time ofrecruitment was less than 5. The change in cervical dilatation, length,position and consistency after treatment were uniform in both groups.Conclusions:1. Extra amniotic saline infusion ripens the cervix as much as theintracervical Foley catheter.2. Both methods showed similar induction delivery intervals.3. Intrapartum and neonatal complications were minimal when theseagents were used.

FC4.25.06INDUCTION OF LABOR WITH INTRACERVICALPROSTGLANDIN E2 IN WOMEN WITH ONE PREVIOUSCESAREAN SECTIONS.M. George (1), A. Rai (2), P. Gadiyar (2)(1) Dept. OB/GYN, Kasturba Medical College, Manipal, India.(2) Dept. OB/GYN, Kasturba Medical College, Mangalore, India.

Objectives: To review the outcome of induction of labor with a singledose of intracervical prostaglandin gel in women with one previous lowtransverse cesarean delivery.Study Methods: 50 pregnant women in their 3rd trimester were inducedwith a single 0.5-mg dose of intracervical prostaglandin E2 gel. Group Acomprised of 25 women with one previous LSCS while Group Bcomprised of equal number of women with unscarred uteri. They werematched for age, duration of pregnancy and Bishop score.Results: 17 patients (64%) in group A and 23 patients (92%) in group Bdelivered vaginally. Post induction Bishop scores at eight hours weresignificantly better in Group B (64% vs. 80%). All five patients inGroup A who were induced for intrauterine deaths delivered vaginally.There was no uterine dehiscence or rupture. Shorter duration ofpregnancies, lower birth weights and higher Bishop scores werepredictive of successful vaginal delivery. A repeat cesarean was threetimes more expensive than a successful vaginal birth after cesarean withintracervical prostaglandin.Conclusions: Induction of labor with intracervical prostaglandin is a safeand effective method in properly selected patients with one previous lowcesarean delivery. It also entails substantial cost savings with outcompromising on safety.

FC4.25.07MECONIUM STAINED AMNIOTIC FLUID FULL TERMSINGLETON VERTEX PRESENTATION – APPROPRIATEBIRTHING CARESundravalli.A , Joshna S, Shanmuga G, Shanti A, Department ofObstetrics & Gynecology, Kilpauk Medical College Hospital, Chennai,India

Aim: To asses the management practices for MSAF casesTo evaluate meconium aspiration syndrome babies in msaf cases.Study method: A prospective study was conducted from august 1999 todecember 1999 at kilpauk medical college hospital, chennai, india – 500msaf cases.Amnio infusion for 50 thick msaf casesRetrospective analysis of 25 msaf babies. For each msaf two controlsmatched with age and parity taken. 1. Full term babies born to motherswithout msaf 2. Full term babies born to mothers with msafResults: 50% in 25 years. 33% primie-para. 40 weeks 80%. 42 weeks22%. Pih 5%, prom 1%, referral 10%. After arm 30%. Spontaneousrupture 40%. While doing lscs msaf diagnosed.Practice: Llp, fhr, amnio infusion, oxygen, delivery forceps, lscs. Thinmeconium 60%, moderately thick 14%, thick 26%. Amnio infusion 50cases for thick. 200 – 500 ml normal saline – 3cm cervix infant feedingtube. Delivery interval after incision _ hr 30%, more than 1 _ hrs 20%.Apgar score 1 minute – thin & moderate – 6/10 40% , 8/10 60%. 5minute apgar 8/10 100%. Thick 1 minute 4 – 5/10 80%, 6/10 – 10%. 5minute apgar 5/10 70%. Suctioning 60%, endotracheal 10%. Vaginal70%, lscs 20%. Less than 2 kg babies 20%, more than 2 kg babies 20%.Deceleration 10%. 26 masf babies – 9 died, 16 alive hale & healthyfollowed for 90 days doing well. 50% vaginal, 50% lscs. Postdated, pih,referral, prom, noted.

FC4.25.08DETERMINANTS OF PERINATAL MORTALITY AMONGBREECH DELIVERY IN A DEVELOPING COUNTRYA. W. O. Olatinwo - Dept. OB/GYN, University Teaching Hospital,Maternity Wing - Ilorin, Nigeria., M. Anate - Dept. OB/GYN,University Teaching Hospital, Maternity Wing, Ilorin, Nigeria.

Objectives: The aims of this study are to determine the incidence ofBreech Delivery, to determine the breech perinatal mortality and toidentify the social characteristics of the mothers and the majordeterminants of the perinatal mortality.


Study Methods: A retrospective study of the determinant factors ofperinatal mortality among Breech Delivery in the University TeachingHospital, Ilorin, Nigeria over a period of twelve months (January 1996to December 1996) was conducted. The patients were identified from thedelivery records of the hospital. The case notes were retrieved from therecords department of the hospital and were analysed with emphasis onmaternal age and parity, booking status, type of Breech delivery, birthweight, Apgar score and the fetal outcome. Chi-square statisticalanalysis was used to test the significance and P-value less than 0.005was taken as statistically significant.Results: The incidence of singleton Breech Delivery was 3.2% with aperinatal mortality rate of 204.2 per thousand as against the overallperinatal mortality rate of 32.0 per thousand.Conclusion: Perinatal mortality rate in Breech Delivery is higher in ourenvironment. Multiparity seems to adversely affect the perinatalmortality rate in Breech and prematurity further complicates breechdelivery as it occurs more frequently in Breech. Adequate antenatal careand proper assessment by experienced obstetrician will help in decidingthe route of delivery in Breech presentation. Caesarean Section offers agood resort for reducing perinatal mortality in Breech if usedjudiciously. These measures will assist in reducing the perinatal deaths

FC4.26 OBSTETRICS: MEDICAL COMPLICATIONS

FC4.26.01MATERNAL AND PERINATAL OUTCOME IN PREGNANCIESWITH RHEUMATIC HEART DISEASEK. Vasishta a, H. Sawhneya, N. Aggarwala, V. Suria, A. Groverb, R. Dhaliwalb, Dept. OB/GYNa; Cardiologyb and Cardiothoracic surgeryc,Postgraduate Institute of Medical Education and Research, Chandigarh,India

Objective: To study maternal and perinatal outcome of pregnancy inpatients with rheumatic heart disease.Study Methods: Five hundred pregnancies were studied retrospectivelyin four hundred and eighty patients during the years 1987-1999.Results: Three hundred and four (83.3%) patients had single valveinvolvement and mitral stenosis was the most predominant lesion(89.1%). One hundred and seventy one patients had undergone surgicalcorrection prior to pregnancy, closed mitral valvotomy (CVM) in 122,Balloon mitral valvotomy (BMV) in 18 and valve replacement surgeryin 31 patients. One hundred and thirteen (22.6%) patients were inNYHA class III-IV during pregnancy and majority of them (85.8%) hadnot undergone surgical correction of lesion period to pregnancy in 48patients (CMV in 39; BMV in 39) and mean gestational age atvalvotomy was 27.82 weeks. Mean gestational age an birth weight atdelivery were significantly lower in patients in NYHA class III & IV,35.22wks and 2290 gms. There were 29 maternal deaths.Conclusion: Mitral stenosis is the predominant lesion. Surgicalcorrection of lesion prior to pregnancy improves maternal and perinataloutcome.

FC4.26.02INDIAN SCENARIO IN PREGNANCY WITH HEART DISEASEV. Chinnakannu , D. Srinivas, RSRM Lying-in Hospital,14/15,Venkatachelam Naicken St, Chennai, Tamil-Nadu India, 600 021.

Cardiac disease in pregnancy remains as one of the important cause ofmaternal mortality. Study of cardiac cases were taken for a period of 3years from January 1997 to December 1999 at Goverment RSRM lying-in Hospital. Chennai. The objective was to study the prognosticvariables with respect to the nature of cardiac lesion, functional status,age, parity, antenatal care, associated complications, management,perinatal and maternal mortality. During this period there were 35,557deliveries of which 225 were cardiac patients giving an incidence of0.63%. In this series 65% were booked and 35% were unbooked. 92% ofthe patients belong to class v. 56.44 % of the cardiac patients werebetween to 24 years. 81.33% were para 2 to 3. 82.67% had rheumaticheart disease and 17.33% had congenital heart disease. Mitral stenosiswas isolated in 25.80%. Among 39 cases of congenital heart disease 23patients had atrial septal defect. Among the complications, 24% hadcongestive cardiac failure, 1 patient had atrial fibrillation and 5 patienthad pulmonary oedema. Anaemia were in 50 cases (22.22%). Pregnancyinduced hypertension was seen in 6.66%. 2(0.88%) patient had

caesarean section. 66.66% had forceps delivery and 32.44% had vaginaldelivery. Perinatal death was 4% and maternal mortality was 0.44%.Perinated death were seen in non operated congenital disease in terms ofIUGR and stillbirth. 21 patients underwent cardiac surgery prior topregnancy. 55 patients accepted permanent method of sterilisation and20 patients accepted temporary methods. This shows 33.33% acceptanceof family planning method.The maternal and foetal prognosis in the heart disease with prior surgeryis better than non operated women. Thus booking, early identification,better stabilisation, bed rest, intensive monitoring and promptmanagement have contributed in reducing the perinated and maternalmortality.

FC4.26.03MATERNAL AND PERINATAL OUTCOME IN 300 PREGNANTWOMEN WITH HEART DISEASE. ICU MANAGEMENT.A.Sundaravalli (1) , S.Gajalakshmi (2), D.Famidha (2), S.Manimekalai(2), (1) Kilpauk Medical College Hospital, 3, First Floor, RengapillaiGarden Street, Chennai, Tamil Nadu, India, 600 021.

Objectives: The aim of the study was carried out to assess the need forICU in Obstetrics to give optimal care to pregnant women with heartdisease, anti-natally and during labor in order to reduce MMR and PNM.Study Method: 1. Retrospective analysis on ICU management in 300pregnant women with heart disease from January 1997 to August 1999at Government Women & Children Hospital and IOG, Egmore,Chennai, India.2. Retrospective analysis of pregnant women with heart disease beforeICU setup in IOG, Egmore, Chennai, India.Results: After ICU in IOG, Egmore, Chennai, India, 300 pregnantwomen with heart disease were closely monitored during anti-natal visitsand managed during pregnancy and labor.46% belong to age group 21 to 25. 41% were primie- para. 33%diagnosed first time at anti-natal clinic/ emergency room. 87% were inthird trimester. 22% had grade 3 & 4 failure. 70.8 % rheumatic disease.14% congenital heart disease. 6% had other risk factors. 73.6 % directICU admissions. 1.6% required ventilator support. 46.8% had vaginaldelivery. 64.4% babies weighed more than 2.5 Kgs. 32% needed 10 daysstay in ICU. 53.6% had 4 to 6 weeks hospital stay.Before ICU 50% of heart disease were referred. PMR & MMR hadincreased and maternal outcome was poor before ICU.Conclusion: The intensive care sets new guidelines, especially inObstetrics for management of pregnancy with Heart disease. By thisstudy the essentiality of an Intensive Care Setup in an Obstetrics unit isemphasized.

FC4.26.04STUDY OF THE PREGNANCY IN ADOLESCENTS WITH HEARTDISEASE IN A SPECIALIZED SERVICE OF HEART DISEASEAND PREGNANCYC. Watanabe , J. Andrade, J. Sousa, Dept. Heart Disease and Pregnancy,Instituto “Dante Pazzanese” de Cardiologia-SP, Osasco, Brazil.

Objective: The aim of this study was to report the incidence ofpregnancy in adolescents with heart disease (HD).Study Methods: In the Dept. of Heart Disease and Pregnancy, Instituto“Dante Pazzanese” de Cardiologia-SP (a reference center in São Paulo),in the period from 1993 to 1998, we studied prospectively a group ofpregnant adolescents with HD.Results: We attended 1499 pregnancies with HD in the period 1993 to1998 and 177 (11.8%) of these patients were adolescents. Annualincidence was in 1993 (10.2%), 1994 (11.5%), 1995 (11.1%), 1996(13.3%), 1997 (10.3%), 1998 (15.6%). HD most observed wascongenital 32.2%, rheumatics 21.6%, mitral valve prolapse 20.5% andmitral insufficiency 19.3%. We observed 87.5% of patient had 16 YO,78.8% were primigravidae and 64% were in functional class I (NYHA).It was realized that 4 cardiacal surgery proceeding (1 valvoplasty, 3replacement prosthetic heart valve).Conclusion: We observed an increase in the incidence of pregnancy inadolescents with HD.


FC4.26.05THROMBOPROPHYLAXIS WITH LOW-MOLECULAR-WEIGHTHEPARIN IN WOMEN WITH CARDIAC PATHOLOGY DURINGPREGNANCYV.O. Bitsadze , S.G. Ismailova, I.V. Khamami, A.D. Makatsaria, Dept.OB/GYN, Moscow Medical Academy, Moscow, Russia.

Objective: Our investigation was aimed to find the advantages of usinglow-molecular-weight herapin (LMWH) Fraxiparin in pregnant womenwith different cardiac disorders and with a history of thrombosis.Cardiovascular pathology is known to be related with the developmentof thrombotic complications. The association of cardiac pathology andpregnancy makes this risk factor more significant. We tried to apply theLMWH to prevent this risk.Study Methods: We examined 26 pregnant women with a history ofthrombosis, 12 patients with prosthetic heart valves (PHV) and 14 – withdifferent cardiac disorders. 50% of patients had the history of wastageand 15% fetal retardation syndrome.Results: We have revealed that 79% of our patients had the chronic fetalloss syndrome. The thrombophylic state, which took place in 100%, wasconfirmed with special coagulation tests: elevated TAT, F1+2 in 100%;PDFF in 61%. The lupus anticoagulant (LA) circulation was detected in100% of the pregnancies with PHV by screening tests PTT-LA(STAGO, France), correction probes and conformational probes withPNP (STAGO, France) and in 50% with the history of thrombosis.LMWH Fraxiparin in the dose of 250 ICU/kg was administered oncedaily in the case of PHV. The dose of Fraxiparin in the case of thethrombosis in the history was 150 ICU/kg in the same regimen. Thetherapy was continued after 8 hours postpartum (postoperatively) andlasted 10 days.Conclusions: In-time deliveries, absence of any thrombotic event duringour study have proved the high benefit of LMWH. It was found effectiveand safe for thromboprophylaxis in women with cardiac pathology andpregnancy.

FC4.26.06COURSE AND FETAL OUTCOME OF PREGNANCIES INPATIENTS WITH THE SURGICAL CORRECTION OFCONGENITAL OR ACQUIRED HEALTH DISEASES. Plesinac , D. Plecas, Institute of OB/GYN, Belgrade, Yugoslavia.

Objectives: The aim of the study was to analyze the influence of theheart disease and administered medication on pregnancy, delivery andneonates.Study Methods: 146 pregnancies were analyzed during twenty years ofinterval. They were divided in four groups according to the type of theheart disease. Group one includes 4 patients with surgical repair ofCoartaction of Aorta. Group two includes 27 patients operated on forvalvular stenosis. Group three includes 68 patients with surgical repairof congenital heard disease. Group four includes 47 patients withartificial heart valves. Statistical methods used on the study were:chitest, Student’s T distribution, Fischer and variance analysis.Results: The incidence of thromboembolic complications is 2% duringpuerperium: all in group four (2 thrombosis of artificial heart valve and2 cerebral emboli). In 10% of all pregnancies occurred the worsening ofNYHA status (1 in group two, 3 in group 3, 12 in group 4). 14% of allwomen had arrhythmia (absolute or extrasystolic). One patient in grouptwo and 6 patients in group four suffered the heart failure duringpregnancy and 1 patient in group two and 5 in group four during thelabor. We had three maternal deaths, all in group four. 2 died of heartfailure and 1 of ventricular carcinoma. Premature labor occurred in 13%cases (7% in group four). In 20% of cases labor was operative . 80% hadvaginal delivery (in 15% of cases forceps were applied and in 13%vacuum). Neonatal mortality rate is 3%. Three died because of HIE andone had hydrocephalus (group four). Intrauterine growth retardationoccurred in 4% of cases in group three and 4% in group four.Conclusions: The pregnancy in patients with artificial heart valves is atthe highest risk for thromoembolic and hemorrhagic complications aswell as the insufficiency.

FC4.26.07VAGINAL ULCERATION (BECHET’S DISEASE) IN PREGNANCY:A CASE REPORTV. Kesic , T. Bozanovic, L.J. Vukmirovic, J. Opalic, J. Atanackovic,Institute of OB/GYN, University Clinical Center, Beograd, Yugoslavia.

Beçhet’s syndrome is a multisystem disorder presenting with recurrentoral and genital ulcerations, as well as uveitis. The etiology andpathogenesis of this syndrome remains obscure. Vaginal ulcers areusually painless and detected during routine gynecological examination.Objectives: The aim of this report is to present the case of large,symptomatic vaginal ulceration in pregnant women and to discusstreatment modalities of this condition in pregnancy.Case Report: 21 years old primigravida presented in 20 weeks ofgestation with severe, blood stained vaginal discharge. In patient’shistory, no previous major diseases were present, but she mentionedrecurrent oral aphtosis and one episode of large vulvar ulceration of“unknown origin” a year before the pregnancy. Gynecologicalexamination, which was extremely painful, revealed large ulcerationsituated in anterior vaginal fornix. Ulceration had diameter of 3x2 cm, itwas deep, filled with central yellowish base, surrounded by red inflamedrim. Vaginal discharge was abundant and blood stained due tosuperimposed bacterial infection. Except the isolation of E. Coli invaginal smear, all other laboratory blood tests as well as microbiologicaltests (including CT, HSC, CMV, HPV, TP, TBC and HIV) werenegative. Histologic examination of biopsy taken from the ulcerationshowed non-specific inflammation. Except vaginal ulceration, thepregnancy was otherwise normal. Detailed examination of other organsystems, including ophtalmologic one, was performed and the resultswere normal. After initial treatment for E. Coli, further managementconsisted of local, nonspecific treatment that included rinsing with salineand application of Fibrolan ointment. The vaginal ulceration healedspontaneously after six weeks without any scarring. The patient wasdelivered vaginally. A year after the delivery, ophtalmologicalexamination revealed iritis.Conclusions: Vulvovaginal manifestations of Beçhet’s disease are notfrequently seen, particularly in pregnancy. Treatment of Beçhet’ssyndrome is symptomatic and empirical. Mucous membraneinvolvement may respond to topical corticosteroids. The topical forms ofsteroids are systematically absorbed, especially through inflamedhyperemic tissues, thus making their application in pregnancyundesirable. Bearing this in mind, the management of our pregnantpatient with vaginal ulceration consisted of local, non-steroid treatmentthat appeared to be successful.

FC4.26.08TRIMETAZIDINE IN THE TREATMENT OF CHRONIC FETALHYPOXIA IN PREGNANT WOMEN WITH CONGENITAL HEARTDISEASESV. Medved , E. Islamova, N. Solonets, V. Podolsky, Inst. PED/OB/GYN,St. Kiev, Ukraine.

The incidence of congenital heart diseases in pregnant women is beingincreased. In mothers with congenital heart diseases without cyanosisand the heart failure, the fetus state is almost normal and the fetal risk isslightly higher than in the healthy women. In all the other cases weobserve the chronic hypoxia, the fetal growth retardation, seldom theantenatal death, spontaneous aborts rate.Circulate failures are caused on maternal congenital heart diseases leadto the uterine-placenta blood disturbance an after to the placenta failure,there is a lower oxygen exchange across the placenta and the fetus getsless oxygen than normal. The oxidative stress develops, the intracellularcontent ATP and kreatin phosphate leads to transmembrane transport ofions, the deep disturbance of metabolism and function of cells in thiscondition. It’s showing clinically the fetus’ hypoxia of different levels.Trimetazidine was used for the decrease of the hypoxia’s level, this drugpreparation contributes to increase the energetic potential of cells incondition of hypoxia.48 pregnant women with congenital heart diseases (atrial septal defects –25, ventricular septal defects- 23) with the heart failure (NYHA FCII–28, FC III – 20) were under observation. Trimetazidine was prescribedto 24 women 60 mg daily during third trimester in 4 weeks (maingroup).Group of comparison was created from 24 women who had obtainedduring the same time ascorbinic acid in tables 150 mg/daily. The


treatment efficacy had been evaluated on the background ofcarditokography (CTG) data.Before the treatment the CTG data didn’t differ in both groups andtestified about fetal hypoxia of medium degree (evaluation after H.Crebs sale – 6,6±0,70 bal. In the main group, 6,45±0,686 in the group ofcomparison, P<0.05). In the main group after 4 weeks course weobserved the sufficient improvement of CTG indices (up to 9.64±0.41bal., P<0.05), in women of the group of comparison the indices didn’tdiffer (6.53±0.68 bal., P<0.05).The better status of newborns after delivery has been found in women ofthe main group. The mild asphyxia was observed only in 5 cases inmain, in the group of comparison – 11, the severe asphyxia wasobserved only in the group of comparison - 3.Therefore Trimetazidine activity could reduce the expression ofplacental insufficiency and fetal hypoxia degree without impact onuterine-placental blood circulation.

FC4.26.09PSYCHOSOCIAL AND OBSTETRIC RISK FACTORS FORPOSTPARTUM DEPRESSIONF.El- Kak , M.Chaaya, American University of Beirut, POBox 11-0236,Beirut, Lebanon.

Objectives: In Lebanon as in many developing countries, the focus ofthe prenatal and delivery phase is on women’s medical and obstetricalproblems and the well being of the fetus. The social and psychologicalneeds of the pregnant women are rarely addressed. Accordingly, the aimof this study is to assess the prevalence and risk factors of postpartumdepression.Study Methods: The study is a prospective investigation of 397 womendelivering in hospitals in Lebanon over a period of two months. The firstphase involved collecting information within 24 hours of delivery usinga structured questionnaire, on predictors of postpartum depression. Thewomen were asked to agree to a home visit for interview 2 to 3 monthsafter delivery. In the second phase, data on postpartum depression werecollected using Edinburgh Postnatal Depression Scale (EPDS) and otherinformation on the health of the mother and the baby.Results: One in five women (21%) were found to have postpartumdepression according to the EPDS. In the bivariate analyses postpartumdepression was significantly related to depression during pregnancy,social support, type of delivery, fetal monitoring, episiotomy, educationand health of the mother, and stressful life events. In the multivariateanalysis, depression during pregnancy and chronic illness predictedsignificantly postpartum depression.Conclusions: Findings from this study are consistent with other studies.Obstetrical procedures and care during pregnancy are not adequatelytargeting the issues of post-partum depression. Implications for researchand action concerning antenatal package, labor and delivery practicesare raised.

FC4.27 OVARIAN CANCER: CHEMOTHERAPY ANDADVANCED DISEASE

FC4.27.01PRIMARY APPENDICEAL MALIGNANCY MIMICKINGADVANCED STAGE OVARIAN CARCINOMA: A CASE SERIESJ. McBroom , M.Parker, T. Krivak, G.S. Rose, Walter Reed ArmyMedical Center, 6825 16th Street NW, District of Columbia,Washington, United States, 20307-5001.

Background: Primary appendiceal malignancies constitute 0.5% of allintestinal tumors. Non-carcinoid malignancies represent 15% of theseand include mucinous cystadenocarcinoma (8%), colonicadenocarcinoma (4%), adenocarcinoid (2%), and other (1%). Excludingwell-differentiated mucinous appendiceal tumors, only about 30appendiceal tumors with ovarian metastasis have been reported in theliterature.Cases: Three patients referred to our institution from 1994-1999 forpresumed late stage ovarian cancer were found to have primaryappendiceal adenocarcinoma, adenocarcinoid and mucinouscystadenocarcinoma metastatic to the ovaries at laparotomy. Wedescribe the clinical course of these patients and review the relevantliterature.

Conclusions: It is important for the gynecologic oncologist to be awareof the clinicopathological features and surgical management of thesemalignancies as appendiceal tumors may be discovered duringgynecologic surgery.

FC4.27.02A DOSE FINDING STUDY OF DOCETAXEL/CARBOPLATIN ASFIRST-LINE. CHEMOTHERAPY FOR EPITHELIAL OVARIANCANCER – FINAL RESULTSR.Atkinson , P.A.Vasey, R.Coleman, M.Crawford, M.Cruickshank,P.Eggleton, D.Fleming, J.Graham, D.Parkin, J.Paul, N.S. Reed and S.B.Kaye on behalf of the Scottish Gynaecological Cancer Trials Group.

This was a prospective, non-randomised, multicentre, open, dose findingstudy of a carbo-platin docetaxel (C-D) combination as first-linechemotherapy in FIGO stage Ic-IV epithelial ovarian cancer.C-D was given 3-weekly for 6 planned cycles, with a 3-day prophylacticdexamethasone regimen (8 mg b.i.d.). 140 eligible patients (Pts) (medianage 56 years, range 28-85) were given a total of 750 cycles ofchemotherapy in 5 cohorts: Col, 32 pts, 169 cycles (C at AUC 5 + D60mg/M2), Co2, 22 pts, 122 cycles (5 + 75), Co3, 29 pts, 156 cycles (6 +75), Co4, 27 pts, 146 cycles (7 + 75), Co5, 30 pts, 157 cycles (6 + 85).110 patients (78%) completed 6 cycles, 17 (12%) stopped due totoxicity. 104 patients (74%) had CTC grade IV neutropenia, and 5patients (5%) had this associated with fever. Only 8 patients (5.7%)experienced grade II-III neurotoxicity (all sensory, no motor > grade 1).The MTD was reached in cohorts 4 and 5, and the Dose LimitingToxicities were myelosuppression and diarrhoea. Overall Response Ratefor all patients was 66% (49/74), CA125 response was 75% (70/93).Median progression-free survival was 16.6 months (95% CI 13.3-19.1).Recommended doses are Carboplatin AUC 5 (via51 Cr EDTA) or AUC 6(if calculated) plus docetaxel 75mg/m2. Significant myelosuppression iscommon but rarely associated with sepsis. A very low incidence ofperipheral neuropathy was observed. A randomised trial comparing withcarboplatin-paclitaxel is underway – SCOTROC.

FC4.27.03CISPLATIN, EPIRUBICIN AND PACLITAXEL COMBINATIONCHEMOTHERAPY IN PREVIOUSLY UNTREATED PATIENTSWITH ADVANCED EPITHELIAL OVARIAN CANCER.C.Papadimitriou1, D.Lazaris 2 , A.Rodolakis2,C.Kiamouris1, G-M.Gourgoulis1, E.Galani1, E. Diakomanolis2, S.Michalas2 andM.A.Dimopoulos1.Department of Clinical Therapeutics1st Department of Obstetrics and Gynecology«Alexandra» Hospital, School of Medicine, Athens University, Greece.

Objectives : The combination of paclitaxel with cisplatin or carboplatinhas become the preferred chemotherapy regimen in the treatment ofadvanced epithelial ovarian cancer (AEOC). Anthracyclines also haveactivity in the disease. We conducted a phase II study using thecombination of cisplatin, epirubicin and paclitaxel (CEP) for thetreatment of AEOC.Method: Fourty consecutive patients with optimally (n=7) orsuboptimally (n=33) debulked advanced ovarian cancer (FIGO stage IIIor IV) were treated with cisplatin 75 mg/m2 IV, epirubicin 50 mg/m2 IVand paclitaxel 135 mg/m2 as a 3-hour intravenous infusion on anoutpatient basis, every 3 hours.Results: Among 28 women with measurable disease, 24 (86%) achievedan objective response including 19 complete and 5 partial responses.Among 18 patients who underwent re-assessment laparotomy,pathological complete remission was confirmed in 9 (50%). With amedian follow up of 40 months the median overall survival has not beenreached yet, whereas the median overall time to progression was 18.7months. The median remission duration was 14 months. The treatmentwas well tolerated; the most common toxicity was neutropenia (WHOgrade 3+4) which occurred in 30% of patients. Neuropathy (WHO grade> 2) developed in only 8% of patients.Conclusion: CEP at the dose levels given is a very active well toleratedregimen in the treatment of AEOC.


FC4.27.04CURRENT STATUS OF GENE THERAPY FOR OVARIANCANCERS.A. Farghaly , The Medical College of Cornell University, New York,New York, USA.

Cancer is generally viewed as a genetic disease arising from a series ofgenetic changes successively transforming the cell from a normal tomalignant state. Molecular genetic changes, important in ovarian cancer,involve both classes of tumor associate genes: oncogenes and tumorsuppressor genes. Alterations of MYC1, ERBB2, AKT2, and P53 havebeen described in some ovarian cancer. Mutation of the P53 gene hasbeen identified in 30-79% of epithelial ovarian cancer evaluated. Studieshave shown that restoration of P53 function in tumor cells often inducesgrowth arrest or growth inhibition in vitro and loss of reduction oftumorgencity in vivo. Adenoviral–mediated delivery of the anti-erb-2sFv, and adenovirus-mediated gene therapy, enhanced by using theCMV promoter, showed their effectiveness in ovarian cancer. Anotherapproach to gene therapy of ovarian cancer is to use combination antigentherapy of anti-c-myc and anti P53 oligos. C-myc functions as oncogenevia DNA amplification and over expression: P53 may also function as anoncogene when mutationally inactivated and overexpressed. C-myc hasbeen shown to be expressed in 30-50% of primary ovarian cancer. Thecombination approach makes it potentially more effective thanindividual gene targeting. Data concerning the current methods of genetherapy of ovarian cancer will be presented and discussed.

FC4.27.05EXPRESSION OF DRUG RESISTANCE-ASSOCIATED MARKERSP-GP, MRP1, MRP2 AND LRP IN OVARIAN CANCER: CLINICALIMPLICATIONS.D.Katsaros (1) , H.J.G.Arts (2), M.Massobrio (1), A.J.H.Van der Zee (2),(1) University of Turin, via Ventimiglia, 3, Turin, Italy, 10126, (2)University of Groningen, Groningen, Netherlands.

Objective: The aim of the present study was to investigate the prognosticvalue of drug resistance associated proteins P-glycoprotein (P-gp),multidrug resistance related protein (Mrp1), canalicular multispecificorganic anion transporter (c-MOAT or Mrp2) and lung resistance protein(Lrp) in ovarian carcinoma.Methods: Expression of P-gp, Mrp1, Mrp2 and Lrp was determined byimmunohistochemistry of frozen tissue sections of 115 ovariancarcinoma patients and associated to clinicopathological factors,response to chemotherapy and (progression free) survival.Results: Expression of P-gp was observed in 20 of 115 (17%), Mrp1 in51 of 115 (44%), Mrp2 in 19 of 115 (16%) and Lrp in 85 of 115 (74%)tumors. Expression of Mrp1 was related to Mrp2 (p<0.0001) and P-gp(p<0.001) expression, while Lrp expression was more frequentlyobserved in patients with stage I/II versus stage III/IV tumors (p<0.01),grade I/II versus III tumors (p<0.05) and residual tumor <2cm versus>2cm after laparotomy (p<0.05). Lower stage (p<0.001), small residualtumor after first laparotomy (p<0.001) and lower differentiation grade(p<0.05) were related to longer (progression free) survival. P-gp, Mrp1,Mrp2, and Lrp expression were neither related to response to first linechemotherapy, nor to survival. On multivariate analysis only stage andresidual tumor after first laparotomy were independent prognosticfactors.Conclusions: In ovarian carcinoma Mrp1 expression is associated withMrp2 and P-gp expression, while Lrp expression is associated withfavorable clinicopathological characteristics. Assessment of P-gp, Mrp1,Mrp2 or Lrp does not allow prediction of response to chemotherapy or(progression free) survival in ovarian carcinoma.

FC4.27.06A PACLITAXEL-CONTAINING CHEMOTHERAPY IN PATIENTSWITH OVERIAN CANCER DOES NOT CAUSEENCEPHALOPATHY: A PROSPECTIVE RESTING-EEG (R-EEG)MAPPING STUDY IN 28 PATIENTSK. Mayerhofer (1), K. Bodner (1), B. Saletu (1), B. Bodner-Adler (1), P.Anderer (3), M. Schindl (1), A. Kaider (2), L. Hefler (1), S. Leodolter(1), C. Kainz (1)(1) Dept. OB/GYN, University of Vienna Medical School, Austria.(2) Dept. Medical Computer Sciences, University of Vienna MedicalSchool, Austria.(3) Division of Sleep Research and Pharmacopsychiatry, Dept.Psychiatry, University of Vienna Medical School, Austria.

Objectives: The aim of this study was to evaluate possible adverseeffects of a paclitaxel containing chemotherapy on the central nervoussystem (CNS) in women with ovarian cancer.Study Methods: Twenty-eight women with histologically documentedepithelial ovarian carcinoma and treated with a combinationchemotherapy consisting of paclitaxel and carboplatin entered the study.Patients were tested with resting EEG (R-EEG) before and afterchemotherapy. Additionally, a battery of different neuropsychologicaltests before, after 3 cycles and at the end of the chemotherapy wasperformed.Results: Twenty of the 28 patients responded to he chemotherapy (71%).Eleven patients (39% developed peripheral neurotoxity. A decrease ofbeta power and an increase of delta and theta power and a decelerationof the total centriod clearly demonstrate a reduced vigilance in patientswith ovarian cancer before chemotherapy compared to healthy women.The increase of beta power and the decrease of delta and theta powerand the acceleration of the total centroid from pre- to post-treatmentclearly demonstrate and improvement of vigilance in patients withovarian cancer after treatment with paclitaxel/carboplatin. The results ofthe R-EEG are in accordance with the psychometric test results. Patientswith deviant test result at the beginning of the statistically significantimprovement of the alphabetical cross out test from the first to the thirdmeasurement (mean increase=4.07; 95% confidenceinterval=[0.99;7.15]) (p<0.05), indicating an improvement of the short-term attention, the concentration and the constancy of working duringchemotherapy.Conclusions: Our data of a prospective study refute previous case-reports describing encephalopathy as an adverse affect of a paclitaxel-containing chemotherapy: A chemotherapy consisting of paclitaxel andcarboplatin does not cause central nervous adverse affects and proves tobe an effective antitumor agent.

FC4.27.07WHOLE-BODY FDG PET FOR THE DETECTION OF RECURRENTSITES IN ADVANCED GYNECOLOGICAL MALIGNANCIESM. Murakami (1), H. Maeda (1), T. Hirasawa (1), T. Muramatsu (1),T. Miyamoto (1), T. Shinozuka (1), T. Makino (1), S. Yasuda (2),Y. Suzuki (3), M. Ide (4), A. Shohtsu (4)(1) Dept OB/GYN, Tokai University School of Medicine, Isehara,

Japan.(2) Dept. Surgery, Tokai University School of Medicine, Isehara,

Japan.(3) Dept. Radiology, Tokai University School of Medicine, Isehara,

Japan.(4) HIMEDIC Imaging Center, Lake Yamanaka, Japan.

Objectives: In advanced gynecological malignancies, many tumorsspread over the pelvis and/or to retroperitoneal lymph nodes.Unfortunately current diagnostic techniques, including CT, MRI andultrasonography (US) lack sensitivity and specificity for accuratediagnosis of metastases. Recently, fluorine-18 fluoro-deoxyglucose (18F-FDG) positron emission tomography (PET) has been taken for patientswith cancer. We examined the availability of whole-body FDG PET fordetection of metastases in patients with gynecological malignancies. Wealso examined if the availability depended on the sites of recurrence(intraperitoneal or retroperitoneal tumors).Study Methods: Thirty patients (21 ovarian cancer, 6 uterinemalignancies and 3 cervical cancer) took PET scan and other methods(CT, MRI, and US) including specific tumor makers. All patients hadpathological diagnoses in gynecology. Post-void static images wereobtained in all patients to minimize bladder FDG activity. The final


diagnoses of metastases were established by surgery (n=15) or clinicalfollow-up for at least 6 months (n=15) after the PET scan.Results: Twenty-one patients were confirmed of the metastasis orrecurrence in 30 patients. The sensitivities of PET/CT/MRI/US/Markersfor the detection of the intraperitoneal metastases were91%/68%/75%/58%/45%, respectively. The sensitivities ofPET/CT/MRI/US/Markers for retroperitoneal recurrence were100%/63%/50%/55%/44%, respectively. The specificities ofPET/CT/MRI/US/Markers for the detection or recurrence were89%/83%/71%/78%/71%, respectively.Conclusion: FDG PET had a higher sensitivity for detecting bothintraperitoneal and/or retroperitoneal metastases.

FC4.27.08A TEN YEAR ANALYSIS OF 600 CASES OF OVARIAN CANCERS.K. Banerjee , K.Gupta, N.R. Mondol. Dept. of Gynecology, CancerCenter Welfare Home & Research Institute, Calcutta, India.

Objectives: The aim of the study is to find the ideal method of treatmentof ovarian cancer during a ten-year period in a referral oncology institutein India.Study Methods: 600 cases of ovarian cancer admitted to this institutehave been analyzed from January 1990 to December 1999.Results: Ovarian carcinoma was found to be the second most commongynecological cancer at this institution, following cancer of the cervix.Most ovarian cancer was of epilithelial origin and present themselves inthe advanced stage (Stage III & IV). Follow-up has been found to beunsatisfactory, and a five-year survival rate was dismal (6%).Conclusions: Effective screening to detect ovarian cancer early enoughis unfortunately not economically viable in India. Though surgery isregarded as the gold standard, better results have been achieved withconcomitant chemotherapy, particularly with regimes containingcisplatin, carboplatin and paclitaxel. Radiotherapy has been found to beof very limited use in the management of ovarian cancer.

FC4.27.09GEMCITABINE (G) + CARBOPLATIN (C) AS 2nd LINE THERAPYIN GYNAECOLOGIC CANCER PATIENTS: A PHASE I/II STUDYOF THE ARBEITSGEMEINSCHAFT GYNÄKOLOGISCHEONKOLOGIE (AGO) STUDY GROUPJ. Quaas , (Dept. OB/GYN, University Hospital, Greifswald, Germany),H.J. Lück, W. Schröder, J. Blohmer, R. Kimmig, V. Möbus, J. Pfisterer,A. du Bois for the Arbeitsgemeinschaft Gynäkologische Onkologie(AGO) Study Group

Objectives: Platinum (P) sensitive malignant tumors of the ovary(relapsing > 6 month after P and paclitaxel [T]) are usually treated withP monotherapy. An advantage for monotherapy vs. a combinationtherapy is not yet established. Due to a persisting neuropathy at the timeof relapsing (caused by the primary P/T therapy), non-neurotoxicsubstances for a P combination are wanted. G is an improved activesubstance in ovarian cancer (OC). To establish a study arm for arandomized phase III trial we performed a phase I/II trial with G/C.Study Methods: 26 previously P and T treated patients (mostly OC) witha relapse > 6 months were treated on day 1 with C (dose: AUC 5according to the Calvert formula); G (doses escalating 800-1000-1200mg/m2) was given on day 1 and 8. Maximum tolerable dose (MTD) wasconsidered to be reached if 2/6 pts. experience dose-limiting toxicity(DLT) defined as: Neutropenia grade 4 > 7 days, febrile neutropenia,grade 4 thrombocytopenia or major organ toxicity grade 3 or higher.Results: Neutropenia grade 3/4 in level I (12 pts./48 courses) and level II(6 pts./31 courses) was observed in 26% vs. 30%. Due to a grade 3/4thrombocytopenia of 28% vs. 29% level 3 was cancelled and a Level IIa(G 1000 mg/m2 day 1 and 8/C AUC 4 day 1) was established. Therewere no grade 4 hematologic and non-hematologic toxicity’s to observe(7 pts.)Conclusions :The combination of G (1000 mg/m2 day 1 and 8) with C(AUC 4 day 1) q21x6 is safe to be recommended for phase III trials. Aprospective randomized trial, comparing G/C with standard C inrelapsed OC, has been initiated by the AGO OC Study Group inSeptember 1999.

FC4.28 PREGNANCY COMPLICATIONS

FC4.28.01RESISTANCE TO ACTIVATED PROTEIN C DURINGPREGNANCY: LOW MOLECULAR WEIGHT HEPARIN FOROBSTETRIC THROMBO PROPHYLAXISP. Barjot , G. Beucher, Y. Lindet, M. Herlicoviez, Dept. OB/GYB,University of Caen, Caen, France.

Objective: Utilization, during pregnancy, of low molecular weightheparins for obstetric thromboprophylaxis for patients with activatedprotein C resistance, following Factor V Leiden mutation.Study Design: Prospective study enrolling 16 pregnant patientsheterozygote or homozygote for Factor V Leiden mutation. They allhave familial or personal history of severe thrombotic disease andreceived 40 mg per day of enoxaparine.Results: No thrombosis or hemorrhage was recorded during pregnanciesor deliveries. All the infants were doing well. After birth, low molecularweight heparin were continued for 6 to 12 weeks, accordingly allelicstatus and history and no complications during post-partum wererecorded. We reviewed literature on this subject.Conclusion: This series confirms the efficacy, safety and tolerance oflow molecular weight heparins which will probably become next goldstandard for obstetric thromboprophylaxis.

FC4.28.02THE PREVALENCE OF THE FACTOR V LEIDEN MUTATION INPREECLAMPSIA AND SUPERIMPOSED PREECLAMPSIA:IMPLICATIONS FOR CLINICAL OUTCOMESJ. Rigó , B. Nagy, Z. Ban, Z. Papp, Semmelweis University, Budapest,Hungary

Objectives: The higher prevalence of Factor V Leiden mutation amongwomen diagnosed with preeclampsia has been well-documented butamong those with superimposed preeclampsia its role remains unclear.The aim of the study is to compare the prevalence of Factor V Leidenmutation in both severe and superimposed preeclampsia in order toinvestigate perinatal outcome in both Leiden positive and negativegroups.Study Methods: One hundred and fifty-four pregnant caucasian womendiagnosed with hypertension and proteinuria were recruited toparticipate in the study and classified according to ACOG (AmericanCollege of Obstetrics and Gynecology) guidelines. DNA was extractedfrom whole blood of ninety-nine preeclamptic and fifty-fivesuperimposed preeclamptic patients. Factor V Leiden mutation wasdetected using Bertina’s PCR-RFLP methods modified with silverstaining. Perinatial outcome (mean gestational age at deliver, mean birthweight, intrauterine growth retardation, HELLP syndrome, eclampsia)was then evaluated in the two groups. Statistical analysis was performedusing SPSS (Windows Version 6.0). Intergroup comparisons wereconducted using Mantel-Haenszel Chi square (c2) test while intragroupcomparison were performed using unpaired Student’s t-test (p<0.05, CI95%).Results: In the preeclamptic study group series (n=99), 16 (16.2%) weredetermined to be positive for Factor V Leiden mutation versus 13(23.6%) in the superimposed preeclamptic group (n=55); all Leidenpositive patients were heterozygous.We found no significant difference in perinatal outcome (birth weight,gestational age at delivery, rate of intrauterine growth retardation,HELLP syndrome and eclampsia) between Leiden positive preeclampticand superimposed preeclamptic groups.Conclusions: As has been reported with respect to the prevalence ofFactor V Leiden mutation among preeclamptic women, Factor V Leidenmutation also appears to play a role in superimposed preeclampticpopulations. These results suggest that Factor V Leiden mutation mayplay a significant pathyophysiologic role and should be among thefactors taken it into consideration when superimposed preeclampsia isdiagnosed.


FC4.28.03FACTOR V LEIDEN AS A RISK FACTOR FOR MISCARRIAGEAND REDUCED FERTILITYR. Póka , S. Baré, I. Balogh, Univ.of Debrecen, PO Box 37, Debrecen,Hungary, 4012.

Objectives: The aim of this study was to investigate the effect ofcarrying heterozygous Leiden mutation on fertility and miscarriagefrequency.Study methods: One-hundred and twenty-eight heterozygous Leidencarrier and four-hundred and sixty-one women who were not carriers ofthe mutation were included in the case-control study. Both cases andcontrols were identified from our Leiden-mutation screening databaseand approached with a postal questionnaire regarding fertility andpregnancies.Results: The risk of having at least one miscarriage or infertility was 1.5(95%CI 1.2-2.7) times greater for Leiden mutation carriers than controls.The risk of having at least two miscarriages or infertility was 2.5(95%CI 1.2-5.13) greater for cases than controls.Conclusions: The Leiden mutation may have a role in the developmentfertility problems and early pregnancy complications.

FC4.28.04FACTOR V LEIDEN MAY BE RESPONSIBLE FOR WORSENINGPERINATAL FETAL OUTCOME IN WOMEN WITH VENOUSTHROMBOSIS AT YOUNG AGEA. Pajor 1, L. Nemes 2, Z. Fontanyi1, L. Szen2, T. Sebök1, G.M. Fodor1, A. Cegledi 2, F. Paulin 1. 2nd Dept. OB/GYN, Semmelweis University1,Budapest, and National Institute of Hematology and Immunology2,Budapest, Hungary

Objectives: Aim of this study was to investigate the effect of early-onsetvenous thromboembolism on the relative risks of low birth weight andperinatal fetal loss in patients who had not received adequateanticoagulant therapy during pregnancy.Study Methods: From the obstetrical patients 101 women with venousthromboembolic event were assigned and fetal outcome of their 333pregnancies were compared to that of 2943 pregnancies in 1000 womenwithout history of thromboembolism, randomly selected. Furthermore,from the women presenting with their first early-onset venousthromboembolism 47 were assigned who had factor V Leiden mutation(FVL) without additional inherited and acquired thrombophilic riskfactors and had already been pregnant. Fetal outcome of 158 pregnanciesin these patients were also compared to that of the age-matched controlgroup.Results: The relative risk (odds ratio with 95% confidence interval) oflow birth weight was found to be 1.74 (1.15-2.64) in the obstetricalpatients with thromboembolism and 1.89 (1.06-3.36) in the symptomaticFVL women. The relative risk of perinatal loss was 2.82 (1.28-6.30) inthe obstetrical patients with thrombosis and 3.13 (1.07-9.17) in the FVLwomen.Conclusions: Perinatal mortality and the rate of low birth weightincrease in patients suffering from venous thrombosis before the age of40, if not treated with anticoagulants during pregnancy. FVL proved tobe responsible for worsening perinatal fetal outcome in patients withvenous thrombosis.

FC4.28.05EFFECT OF ANTIPHOSPHOLIPID ANTIBODY TYPES ONPREGNANCY OUTCOMEM. Backos (1), R.Rai (2), C.Tower (2), L.Regan (2), St Mary's Hospital,Winston Churchill Wing, Praed Street, London, United Kingdom, W21PG, (2) Imperial College School of Medicine at St Mary's, London,UK.

Objective: To determine the prospective pregnancy outcome of womenwith primary antiphospholipid syndrome (PAPS) according toantiphospholipid antibody (aPL) types.Subjects & Methods: The pregnancy outcome of 150 women with ahistory of recurrent miscarriage (median 4; range 3-9) in associationwith persistently positive aPL; lupus anticoagulant (LA) and/oranticardiolipin antibodies (aCL), were studied. The study populationwere divided into 4 groups according to aPL type: 16 (11%) were LApositive, 61 (41%) IgG aCL positive, 64 (42%) IgM aCL positive and 9

(6%) were LA and aCL positive. All women were treated with aspirin(75mg daily) and heparin (Clexane 20mg daily) during pregnancy.Results: There was no significant difference between the four groups ofthe study population in mean age, previous number and type ofmiscarriages.The live birth rate amongst women with IgG aCL was 69% (42/61), 54%(34/64) in IgM aCL group, 56% (9/16) in LA group and 33% (3/9) inLA and aCL group. Pre-eclampsia complicated 22% (2/9) ofpregnancies in LA group, 14% (6/42) of pregnancies in IgG aCL groupand 0% (0/34) of pregnancies in IgM aCL group. The preterm deliveryrate was 67% (2/3) in LA and aCL group, 22% (2/9) in LA group, 17%(7/42) in IgG aCL group and 6% (2/34) in IgM aCL group. All the 3infants in the LA and aCL group were were small for gestational age(SGA) (<10th centile for gestation). Of the 9 live born infants to motherswith LA, one resulted in a neonatal death due to prematurity and 3(33%) were SGA. In contrast, only 10% (4/42) of infants in the IgGgroup were SGA (p = 0.09), and none of the 34 infants in the IgM groupwere SGA (p = 0.006).Conclusion: In women with PAPS treated with aspirin and heparin,pregnancies associated with lupus anticoagulant or lupus anticoagulantand anticardiolipin antibodies are more likely to be at risk ofcomplications than those associated with anticardiolipin antibodies only.

FC4.28.06ANTIPHOSPHOLIPID ANTIBODIES (APA) AND PREGNANCYOUTCOMEE. Fernandez , T. Surapaneni, Fernandz Maternity Hospital Pvt. Ltd.,Hyderabad, Andhra Pradesh, India.

Objectives: To evaluate the incidence and risks of Anticardiolipinantibodes (ACL) and Lupus anticoagulant (LAC) on pregnancyoutcome.Study Methods: Prospective analysis of 480 high risk pregnancies fromMay 1995 to August 1999. Detection of ACL by combined Elisatechnique and LAC by APTT. Treatment Protocol: Group A (Low doseAspirin); Group B (Aspirin + Prednisolone); Group C (Aspirin +Heparin).Results: Incidence of ACL positive was 20% (n=96) and LAC positivewas 2.2% (n=11). Treatment group A consisted 77 patients (80.2%),group B 6 patients (6%) and group C 13 patients (13.5%). Neonataloutcome in the treatment group as a whole was 98% live births, termdeliveries were 93.5% and preterm deliveries 6.4%. One patient withpersisting antibodies despite treatment had an IUD at 28 weeks.Conclusion: The poor obstetric outlook for women in association withAPA may be improved with low dose Aspirin. The presence ofpersistently elevated AP A in spite of Aspirin requires treatment withHeparin.

FC4.28.07EFFECTS OF FOLIC ACID SUPPLEMENTATION DURINGPREGNANCY AND THE RISK OF SEVERE PREECLAMPSIAM.L. Cañete , A. Sanchez-Dehesa, P. Lafuente. O. Rodriguez, J.M.Sanchez, E. Muñoz, M. Sanchez-Dehesa, Dept. OB/GYN, HospitalVirgen de la Salud, Toledo, Spain

Objectives: Our purpose was to evaluate the effectiveness of folic acidsupplementation on the prevention of maternal preeclampsia, sincefolates are known to decrease plasma homocysteine concentration,which is increased in preeclampsia and associated with endothelialactivation.Study Methods: In a retrospective study, a total of 2000 pregnantwomen’s medical charts were reviewed and divided into two cohorts: A(n=1000): women with folate supplementation, B (n=1000): womenwithout folate supplementation. A statistical analysis was performedusing the Fisher exact test, chi-square test and multiple logisticregression analysis. Differences were considered significant whenp<0.05.Results: Multiple logistic regression analysis showed a lower incidenceof severe preeclampsia in the folate supplemented group (odds ratio(OR) 0.5; 95% confidence interval (CI) 0.17 – 0.8). Incidence ofpreeclampsia was 2.2% in the folate supplemented group and 3% in thenon-supplemented group, showing no significant difference (p>0.05).We didn’t find correlation between the development of preeclampsia andthe dose of folic acid used.


Conclusions: Our data suggests that folate supplementation duringpregnancy reduces the risk of developing severe preeclampsia.

FC4.28.08PREGNANCY, LABOR AND POSTPARTUM PERIOD INPATIENTS WITH FACTOR V LEIDEN MUTATIONK.V. Starchenko , V.O. Bitsadze, A. Sincha, A.D. Makatsaria, Dept.OB/GYN, Sechenov Moscow Medical Academy, Laboratory ofHemostasis Pathology, Moscow, Russia.

Patients with hereditary hemostasis predisposing to thrombosis representhigh risk of obstetrics and thrombotic complication during pregnancy.Under our observation were 12 patients with factor V Leiden mutation.10 patients first came to our attention during pregnancy from 10 to 39weeks of gestation. 2 patients were administered in postpartum period on11th and 29th days, Clinical manifestations which entailed administrationto the hospital included thrombosis of different localization, primarydeep vein thrombosis. In one patient with factor V mutation electiveabortion was performed on 10th week after angiography (suspicion ofpulmonary thromboembolism). The age of the patients was 25 – 35years old. Family history for thrombotic episodes was positive in 50% ofcases.First step of APC-R test was based on APTT ratio, using activatorAgkistrodon billineatus of Protac. Second step included genetic studyusing PCR (primes by Dallbeck and Soller) with further restriction byMnl and electrophoresis in 3% PAAG. Increased level of TAT, F1+2were detected in all cases, 15% patients demonstrated decreased level ofAT-III and 30% had platelets hyperactivation.Treatment included low molecular weight heparin (Fraxiparine) from themoment of diagnosis verification in therapeutic doses 250 ICU/kg 2/timedaily. Therapy was conducted through all pregnancy and 10 days inpostpartum period. 9 pregnancies were carried out to full term and endedwith liveborn healthy infants. All patients had vaginal delivery. No caseof recurrent thrombotics episodes occurred.

FC4.28.09PREVENTION OF REPEATED THROMBOSIS IN PREGNANTWITH HEREDITARY AND ACQUIRED THROMBOPHILIAA.D. Makatsaria , V.O. Bitsadze, M.G. Genievskaya, K.V. Starchenko,T. Matveeva. Dept of Ob/Gyn, Sechenov Moscow Medical Academy,Bolshaia Pirogovskaya St.2/6, Moscow, 119881, Russia.

Objectives: The aim of the study was to detect underlining hemostasisdefects and evaluate efficiency of LMWH (Fraxiparine) anticoagulationin pregnant with repeated thrombosis.Study Methods: Since 1995 under our observation were 47 pregnant age20-32 y.o. with history of one or more episodes of thrombosis withdifferent localization (including MI – 1, acute cerebral ischemia –2) withconfirmed APS. Among them 10 patients had valvular heart disease. 21(44,6%) patients had history of fetal loss. L A w a s a s s e s s e d b y d R V V T , d P T a n d A P T T w i t h p l a t e l e t s n e u t r a l i z a t i o n p r o c e d u r e ( S t a g o , F r a n c e ) . ). ACL (anticardiolipin antibody) IgMand IgG were detected by ELISA.). Level of AT 111 (nor-Patrigen At111 Behringwerke, Germany). Detection of Factor V Leiden mutationincluded 2 steps. At first step phenotypic Activated Protein C resistancewas evaluated based on APTT ratio with activator Agkistodonbillineatus instead of Protac. Second step included genetic study usingPCR (primers by Dallbeck and Soller) following by Mnl restriction andelectrophoresis in 3% PAAG. Therapy included LMWH (Fraxiparine)from the first antepartum visit at 3-17 weeks. Dose was 150 ICU/kg 1time/day s.c. Thromboprophylaxis with LMWH started 8 h. Post-op andcontinued 10 days postpartum with switch on oral anticoagulants. Incase of planed CS last injection of LMWH was 24 hours pre-ope.Results: In 21 cases hereditary hemostasis defects were detected(including Factor V Leiden mutation, sticky platelets syndrome, AT 111deficiency and Pr C deficiency), in 26 patients APS as single cause ofthrombotic state was diagnosed. 6 patients (12,7%) had combineacquired and hereditary defects.During observation no thromboembolic complications or fetal loss havebeen seen. No case of thrombocytopenia occurred. 14 patients had CS,33 – natural delivery.Conclusions: LMWH (Fraxiparine) is considered first choice treatmentfor prevention repeated thrombosis and obstetrics complications inpregnant with acquired and hereditary hemostasis defects.

FC4.29 PRENATAL DIAGNOSIS

FC4.29.01THE FREQUENCY AND NATURE OF BIRTH DEFECTSUNDETECTED BY MIDPREGNANCY ULTRASOUNDSCREENINGP. Ogburn , Mayo Clinic, 3B Charlton Building, Rochester, MN, USA,55905.

Objectives: The aim of this study is to determine the frequency andtypes of birth defects missed by obstetric ultrasound done at 18-20weeks gestationStudy methods: All pregnancies cared for at the Mayo Clinic in 1997-1998 were evaluated by ultrasound at 18-20 weeks gestation. All birthdefects detected in the neonatal period were categorized and comparedto the ultrasound findings.Results: There were 125 birth defects from 2,903 births (4.3%). Birthdefects missed by ultrasound were 38 (30.5%). However, the majority ofthese missed defects were hypospadius (10), hip or knee dyslocation (5),cleft lip and/or palate (4), and clubbed feet (3). This gives an adjustedrate of 12.8%. Missed isolated cardiac defects were limited to ASD,VSD, and Pulmonary Stenosis(n=7); 4 cases of Down syndrome werenot detected. Only one missed prenatal diagnosis was associated withneonatal death, a rare case of congenital absence of the diaphragm.Conclusions: Ultrasound screening detects the majority of birth defectsin a obstetric population. Those defects which are missed usually areisolated and not life threatening.

FC4.29.02RENAL ARTERY HEMODYNAMIC RESPONSE TO INVASIVEPROCEDURES AND THE EFFECT OF ANALGESIAJ. M.A. Teixeira , V. Glover, Dept. of Materno-Fetal Medicine, ImperialCollege School of Medicine, London, UK.

Objectives: To investigate the renal and middle cerebral arteriespulsatility index (PI) changes associated with invasive proceduresinvolving transgression of the fetal body and to evaluate the effect ofanalgesia on preventing this response.Study Methods: The renal artery and the middle cerebral artery PImeasured by Doppler ultrasound before and after invasive procedures(fetal blood sampling (FBS), transfusion (Tx), shunt insertion, tissuebiopsy, ovarian cyst aspiration. The response of fetuses submitted toinvasive procedures involving transgression of the fetal body, such asintrahepatic vein (IHV) blood sampling and transfusion was comparedwith that of control procedures at the placental cord insertion (PCI). Theeffect of analgesia was assessed by administering fentanyl beforeintrahepatic vein transfusions.Results: The renal artery PI increased significantly with proceduresinvolving transgression of the fetal body (mean D=0.26, SD = 0.61, 95%CI = 0.005 to +0.53, p=0.04, paired t test), but not with non-fetal bodytransgression (mean = -0.15, SD=0.49, 95% CI = -0.47 to +0.15,p=0.29). The middle cerebral artery PI, measured in the same fetuses,fell significantly with procedures involving transgression of the fetalbody. The ratio between the MCA and renal arteries PI decreasedsignificantly (p=0.0006, paired t test) after procedures involvingtransgression of the fetal body. The MCA and renal artery PI did notchange when fentanyl analgesia was administered before IHVtransfusions.Conclusions: Fetal renal artery PI increased after procedures involvingtransgression of the fetal body while the MCA PI in the same fetusesfell. This is consistent with previous findings that invasive proceduresinvolving transgression of the fetal body may induce the “brain sparingeffect”, where blood is preferentially directed to the brain. Fentanylprevented the MCA and renal arteries PI changes associated withprocedures involving transgression of the fetal body.


FC4.29.03A FIVE YEAR REVIEW OF AMNIOCENTESIS PROCEDURESD. R. Urquhart , Forth Park Hospital, Kirkcaldy, Scotland, UK

Objectives: The aim of the study was to review indications foramniocentesis, look at demographic data and document outcome –particularly with regard to miscarriage risk.Study MethodsData was collected on all women having an amniocentesis in the 5 yearperiod from 1/1/95 to 31/12/99. Patients’ age, gestation, indication forprocedure, data about the procedures itself, results of karyotyping andsubsequent miscarriage were all noted. The procedures were carried outby 4 operators using the same ultrasound guided techniques with a 22gauge spinal dose of anti D immunoglobulin.Results: 429 amniocentesis procedures were carried out on 418 women.Four operators carried out all the procedures. 18 (4.3%) chromosomalabnormalities were detected, 3 were of minor nature and thought to be ofno practical significance. 15 were major and comprised: Trisomy 2 (8cases), Trisomy 18 (2), Trisomy 13 (1), Turner’s syndrome (3), triploidy(1). 14 of 15 women diagnosed with a major chromosomal abnormalityopted for termination or miscarried. One woman whose baby hadDown’s syndrome elected to continue the pregnancy. The baby was liveborn at term. There were 6 miscarriages following amniocentesis. Twowere in women who subsequently were shown on amniocentesis to havechromosomal abnormalities. In 4 cases, the chromosomes were normal.Conclusions: The pick up rate for serious chromosomal abnormality was3.6% (15 cases from 418 primary procedures), i.e. 28 procedures wererequired to diagnose one abnormal karyotype. Over the 5 years periodthere was an increasing tendency for women with borderline raised riskof trisomy to decline an amniocentesis procedure if no “soft markers”were seen on a pre-procedure detailed scan (data to be presented). Thismay in future reduce the number of procedure carried out and increasesspecificity of the test. Four miscarriages of chromosomally normalfetuses followed the 429 procedures (0.9%). Our background loss rate isnot known, therefore the true procedure related loss rate (actual loss rateminus background loss rate) is probably slightly less than this. Wecontinue to quote a 1% risk of miscarriage following amniocentesis.

FC4.29.04INTERACTIVE MULTIMEDIA CD ROM TO TEACH FETALANOMALY RECOGNITIONP.Loquet (1) , M.Deutchman (2), (1) Antwerp University Hospital,Wilrijkstraat 10, Edegem, Antwerpen, Belgium, b-2650, (2) Universityof Colorado, Denver, Colorado, United States.

Objectives: The sonographic diagnosis of fetal anomalies is a complextask facing beginning learners and experienced ultrasound practitionersalike. Major fetal anomalies affect only about 1% of pregnancies andhundreds of anomalies and their variants are possible. Therefore, anyone individual will only rarely encounter a specific anomaly. Theconsequences of missing a fetal anomaly may be significant from thestandpoints of both medical management and legal liability. Standardtextbooks cannot present images in the video medium.Aim: To aid the process of learning sonographic recognition of fetalanomalies.Methods: The multimedia platform makes it possible to present acombination of text, diagrams, still images and moving video imagesthat enable the learner to recognize abnormal fetal sonographic anatomyso that when live patients are subsequently scanned, abnormalities canbe more readily recognized. This technique is well-suited to experiencedindividuals as well as beginners, presenting them with more abnormalfindings than they are likely to encounter in years of scanning livepatients. These findings are seen in a video medium closely matched tothat actually seen on diagnostic ultrasound machines. Over 600 staticimages and 120 ultrasound video segments are presented.Conclusions: this tool complements learning of sonographic fetalanomaly recognition for beginning and experienced ultrasoundpractitioners alike using a low-cost medium (cd rom) that operates oncommonly available consumer computer hardware.

FC4.29.05EXTENSIVE PRENATAL DIAGNOSIS: ANTENATAL GENETESTS FOR PREGNANT WOMEN ELIGIBLE FOR CHORIONVILLUS BIOPSY OR AMNIOCENTESIS.Kallinen J , Heinonen S, Palotie A, Ryynanen M, Departments ofObstetrics and Gynecology, Oulu and Kuopio University Hospitals,Finland, Gonda Neuroscience and Genetics Research Center, LosAngeles, California, USA

Objectives: Approximately one in 5 subjects in Finland carries somegene for 30 main Finnish heritage diseases and about one in 500 childborn are affected. Almost all carrier women and men are unaware oftheir condition. To day still in the most chorion villus biopsies (cvs) oramnios only chromosomes are investigated. Because of the fetus isexposed to miscarriage risk one should consider investigating the fetalmaterial so extensively as possible. This means offering gene tests to themother (and secondly to the father), in order to find out the risk couple.In that case the fetal material is already at hand for prenatal diagnosis.Study methods: During the year 1998 429 mothers wished to have eithercvs or amnio at antenatal maternity clinic of Kuopio University Hospital.All those women were offered free of charge and on a strictly voluntarybasis the gene tests for Finnish heritage diseases, AGU and CLN1syndrome, and for fragile X syndrome. All women found to be carriersof those gene mutations underwent detailed genetic counseling andscreening of the partner were offered. If the both partners wouldappeared to be carriers, prenatal testing was offered.Results. A total of 422 (98%) women elected to undertake the gene testfor AGU, CLN1 and for fragile X. Seven carriers for AGU, 2 for CLN1and one for fragile X were ascertained. None of the tested husbands wasa carrier of those diseases.Conclusions: The mapping of the human genome will make it possiblein the near future to detect carriers of many recessive gene defects. Therecent discoveries of the different Finnish heritage disease genes hasoffered the possibility of population based carrier screening. All womenwith mutations of the Finnish heritage diseases and fragile X gene couldtheoretically be detected before they have any pregnancies. Thecontinuous education of antenatal clinic personnel and closecollaboration between antenatal clinics and the screening providers arevery important. The most important part of high-quality screeningservices is appropriate patient information and skillfully performedcounseling. The screening provides an effective way of identifyingcarriers of genetic diseases and incorporating prenatal testing into thisprocess. Those women registering for CVS or amniotic fluid samplingshould at least consider carrier screening.

FC4.29.06PRENATAL DETECTION OF SINGE UMBILICAL ARTERY ANDHYPOPLASTIC ARTERY: REVIEW OF 51 CASESC. G. Gagaev , I. N. Kostin, S. M. Semyatov, Dept. OB/GYN, MaternityUniversity, Moscow, Russia.

Objectives: This study was under taken to determine the frequency ofsingle umbilical artery (SUA) in general obstetrical population and toassess the clinical significance of antenatal SUA detection.Study Methods: In a prospective cross-sectional mode sonographicinvestigation of 9623 pregnancies in II and III trimesters were carriedout.Results: 48 cases of SUA and 3 cases of hypoplastic umbilical artery(artery-to-artery diameter difference of more than 50%) were detected(0.53%). Gestational age (GA) at time of diagnosis ranged from 18.5 to40.8 weeks. Seven of 51 pregnancies were twin (14%), polyhydramnioswas detected in 22%, oligohydramnios in 9%. In 65% of SUA cases leftartery was absent, in 35% - right artery . The length of umbilical cord(UC) ranged from 65 to 90cm in 80% of cases. One or severalmalformation were detected in 8 cases (15%), perinatal deaths occurredin 5 cases (9%) – all in fetuses with malformations. Average birthweight (with exclusion of one case of acardius acephalus twin pregnancyterminated at 22 weeks) was 3260g. and GA at delivery was 39.3 weeks.Cesarean section was performed in 30% of cases. Nuchal cordentanglement had occurred in 23%. In 16% of SUA insertion of UC wasmarginal or velamentous. Artery flow Doppler patterns did not differfrom those obtained from three-vessels cords.Conclusions: SUA is associated with high rate of perinatal complicationsincreasing the level of perinatal mortality and morbidity. In the absenceof additional sonographically detectable anomalies, an isolated SUA


does not seem to affect clinical outcome and therefore should not alterroutine obstetric management.

FC4.29.07TRANSABDOMINAL FETOSCOPY; POSSIBLE ROLE FOR EARLYDETECTION OF FETAL ANOMALIESS.Rakic , Z.Mikovic, N.Antic, D.Filimonovic, OB/GYN UniversityClinic "Narodni Front " Beograd, Yugoslavia, Narodni Front St 62,Beograd, Serbia, Yugoslavia, 11000.

Objectives: Early prenatal dianosis often approach the limits ofultrasonography in precise assesment of the fetus in the first and secondtrimestar of pregnancy.Further evaluation of a malformed fetus can bedone with fetoscopy.Study Methodes: The semi rigid 0 straightfoward fetoscope fourmillimtres in diameter and 25cm in length was placed in uterin cavity.Several instruments, including puncture needle, biopsy forceps can usedthrough the side operative channel under full endoscopic vision.Results: We did 25 transabdominal fetoscopies in pregnacies with earlierfetal anomalies.We found: 1 Patau syndrome, 1 craniofacial anomalies,2 annencephallus and had one miscarriage.Conclusions: Transabdominal fetoscopies could be important in earlydetedtion of fetal malformation 12 weeks of pregnancis, when it difficultto make the precise diagnosis with ultrasound examinations.

FC4.30 REPRODUCTIVE SCIENCE

FC4.30.01THE EFFECT OF PRE AND POSTOVULATORY TREATMENTWITH LEVONORGESTREL AND MIFEPRISTONE ON UTERINEPINOPODES DURING THE IMPLANTATION PERIOD.L. Marions and K.Gemzell DanielssonDept of OB/GYN, Karolinska Hospital/Institute, Stockholm, Sweden.

Objectives : Current research shows better and safer alternatives to theYuzpe method for emergency contraception. Levonorgestrel only as wellas mifepristone has proved to have fewer side effects in addition tohigher efficacy. The mechanism for postcoital treatment requires effecton ovulation as well as implantation depending on when the unprotectedintercourse has occurred . Several factors have been suggested asmarkers of endometrial receptivity and uterine pinopodes have been oneof those. The aim of our study was to find out if the occurrence ofpinopodes were affected by levonorgestrel or mifepristone given beforeor after ovulationStudy methods: Eighteen fertile women were given treatment with either1.5 mg levonorgestrel (n=6) , 1mg mifepristone (n=6) or 10 mgmifepristone (n=6) approximately 2 days before or after ovulation. Anendometrial biopsy was performed 6 to 8 days after the LH peak in allcycles, including one control cycle. The biopsy was examined usingSEM for the appearance of pinopodes.ResultsIn almost all controls (72%) pinopodes were present but in differentstages of development. After treatment there were no significantdifferences between treatment groups.Conclusions: Since no significant inhibition of the formation of uterinepinopodes could be detected, the mechanism of these regimens foremergency contraception must be due to other factors.

FC4.30.02ELEVATED NK CELL ACTIVITY IS NOT ASSOCIATED WITHPOSITIVE TEST OF ANTICARDIOLIPIN ANTIBODIES INWOMEN WITH RECURRENT SPONTANEOUS ABORTIONST. Takeshita , G. Ishikawa, M. Satomi, A Ishikawa, S. Akira, M.Kitagawa*, J. Matsumoto*, T. Araki, Dept. OB/GYN, Nippon MedicalSchool, Tokyo, *Sannoh Clinic, Saitama, Japan

Objectives: The aim of this study is to investigate correlations betweenperipheral NK cell activity and the level of anticardiolipin antibodies inwomen with recurrent spontaneous abortions.Study Methods: Sixty-nine women with a minimum of two unexplainedearly miscarriages were included. The level of anticardiolipin antibodiesof IgG and IgM classes in patient sera were measured by enzyme-linked

immunosorbent assay. NK cell activity in peripheral mononuclear cellswere assayed by the standard 4-hr chromium-release assay.Results: Positive test results were detected in 13 patients (18.8%) withIgG class and 21 patients (30.4%) with IgM class. Patients with elevatedNK cell activity (>40% of specific lysis) were 19 (46.3%). Significantlevel of anticardiolipin IgG antibodies was not detected in sera frompatients who had elevated NK cell activity (>40%).Conclusions: Elevated NK cell activity is not associated with increasedlevel of anticardiolipin antibodies, suggesting that the alloimmunedisorder and the autoimmune disorder do not coexist in same patientwith recurrent spontaneous miscarriages.

FC4.30.03OREXINS SUPPRESS THE PULSATILE SECRETION OFLUTEINIZING HORMONE IN OVARIECTOMIZED FEMALE RATSM.Irahara , T.Tamura, T.Matsuzaki, T.Aono, University of Tokushima,3-18-15 Kuramoto-cho, Tokushima, Japan, 770-8503.

Objectives: The aim of this study is to investigate the effect of orexins,the novel hypothalamic neuropeptides that stimulate feeding behavior,on the pulsatile secretion of LH in order to clarify their influence on thereproductive function.Study methods: We administered 3 nmol of orexins (orexin-A or -B) orsaline (control) into the third ventricle of bilaterally ovariectomized rats,and measured the serum LH concentration by RIA in blood samplesdrawn every 6 min for 2 hours to analyze the pulsatile secretion.Results: Administration of either orexin-A or -B significantly reducedthe mean LH concentration ( control: 8.15 Å} 0.26 mg/l , orexin-A: 5.04Å} 0.19 mg/l, orexin-B: 6.57 Å} 0.22 mg/l ; p < 0.01 ) and the pulsefrequency ( control: 5.38 Å} 0.32 pulses/2 h, orexin-A: 2.75 Å} 0.37pulses/2 h, orexin-B: 3.75 Å} 0.56 pulses/2 h ; p < 0.01 ). Furthermore,there was a significant decrease in the mean LH concentration in theorexin-A treated group compared with the orexin-B treated group (p <0.01). There were no significant differences in the pulse amplitudeamong the three groups ( control: 4.77 Å} 0.42 mg/l, orexin-A: 4.08 Å}0.43 mg/l, orexin-B: 4.96 Å} 0.36 mg/l ).Conclusions: Orexins suppress the pulsatile secretion of LH, and thesuppressive effect of orexin-A is stronger than that of orexin-B. Orexinsmay modulate the reproductive function at the hypothalamic level.

FC4.30.04THE EFFECTS OF HUMAN CHORIONIC GONADOTROPIN ANDINTERLEUKIN-1BETA ON PRODUCTION OF MACROPHAGEMIGRATION INHIBITORY FACTOR BY HUMAN GRANULOSA-LUTEAL CELLS.M.Minami , M.Mikuni, J.Nishihira, S.Fujimoto, Hokkaidou University,n-15, w-7, Kita-Ku, Sapporo, Hokkaidou, Japan, 060-8638.

Objectives: Macrophage migration inhibitory factor (MIF) is known as amediator of macrophage adherence, phagocytosis and tumoricidalactivity as well as important inflammatory mediator._@Ovulation isconsidered to be inflammatory events. The aim of this study was toinvestigate the effects of HCG or IL-1 on MIF production of humanperi-ovulatory granulosa cells.Study Methods: Granulosa cells obtained from in vitro fertilization andembryo transfer patients were cultured with HCG or IL-1. MIFconcentration in the culture media from each experimental group wasmeasured, and compared with controls (culture media only).Results: The concentrations of MIF without HCG nor IL-1beta(controls) were consistent in different patients. MIF production of HCGgroup was 7.2(3.8-15.9); median(range) ng/ml, which was significantlyhigher than that of controls 3.2(2.8-4.1) ng/ml. Administration of IL-1beta alone presented variant MIF concentrations in different patients,and concurrent administration of IL-1beta with HCG did not alter theMIF production stimulated by HCG alone.Conclusion: These results suggesting that HCG stimulates MIFproduction by peri-ovulatory granulosa cells, although IL-1beta may notplay sufficient role for MIF pro


FC4.30.05A WOMAN WITH ISOLATED PROLACTIN DEFICIENCYM.Nakae , T.Douchi, S.Yamamoto, Y.Nagata, Kagoshima UniversityHospital. University Hospital, 8-35-1 Sakuragaoka, Kagoshima, Japan,890-8520.

Background: There are reports that prolactin (PRL) oversuppression tobelow-normal levels causes the impairment of progesterone synthesis innormal cycling women. It appears that a certain plasma levels of PRL isrequired for progesterone synthesis to proceed normally. However, thisconcept is based on the circumstances where PRL deficiency wasoperation or medical induced. Thus, the clinical significance ofhypoprolactinemia ramains to be elucidated. In the present study, wereport a very rare case with isolated PRL deficiency, and discuss therelationship between hypoprolactinemia and reproductive function suchas lactogenesis and ovarian function.Case A 26-year-old Japanese woman complained of post-partumamenorrhea. She experienced menarche at 17 years. At 24 years, sheconceived spontaneously despite persistent oligomenorrhea, and thendelivered uneventfully. However, she showed absolute lactation failure.Serum LH, FSH, and estradiol levels were 9.5 mIU/mL, 8.0 mIU/mL,and 39 pg/mL, respectively. Repeated serum PRL levels were all < 0.1ng/mL. Pituitary stimulation test with GnRH showed normalgonadotroph response, while PRL was still undetectable in TRHstimulation test. TSH and ACTH levels were within normal limit. Shewas successfully treated by clomiphene citrate.Conclusions: In a patient with isolated prolactin deficiency, absolutelactation failure is more characteristic than ovarian dysfunction.

FC4.30.06A ROLE OF THE NIEMANN-PICK C1 PROTEIN (NPC1)-CONTAINING COMPARTMENT IN THE INTRACELLULARTRAFFICKING OF CHOLESTEROL SUPPORTINGSTEROIDOGENESIS IN HUMAN GRANULOSA-LUTEIN CELLSHidemichi Watari , J. Strauss. University of Pennsylvania, Center forResearch on Reprodution and Women's Health, Room 1355 BiomedicalResearch Building II/III, Philadelphia, PA, USA, 19104

Objectives: The aim of this study was to explore the expression,regulation and function of the Niemann-Pick C1 protein (NPC1),encoded by a gene which when mutated produces a lysosomal storagedisease, in the intracellular trafficking of cholesterol contributing tosteroidogenesis.Study Methods: Proliferating human granulosa-lutein were maintainedin a culture medium supplemented with 2% lipoprotein deficient serum.Cells were treated with the indicated drugs in the presence of addedLDL (50 mg/ml). Cells were examined cytologically and analyzed forprotein and sterol content, Western blotting and Northern blotting.Secreted progesterone (P4) was quantitated by RIA.Results: NPC1 protein was localized in a subset of lysosome-associatedmembrane glycoprotein (LAMP)-2-positive vesicles. NPC1 proteincontent, the morphology and cellular distribution of the NPC1-containing compartment were not affected by 1 mM 8-Br cAMP, whichstimulates cholesterol metabolism into P4. Treatment with ahydrophobic amine, U18666A (2 mg/ml) caused accumulation of freecholesterol in granules, identified by filipin staining, that containedLAMP-2 and NPC1. These granules also stained for neutral lipid withNile red, reflecting accumulation of LDL-derived cholesterol esters.LDL-stimulated P4 synthesis was completely blocked by U18666A,leaving steroid output at levels observed in the abscence of LDL.U18666A also blocked the LDL augmentation of 8-Br-cAMP-stimulatedP4 synthesis , reducing steroid production to levels seen in the presenceof 8-Br-cAMP alone. U18666A treatment caused a 2 fold increase inNPC1 protein and mRNA levels, suggesting that disruption of NPC1function activates a compensatory mechanism resulting in increasedNPC1 synthesis.Conclusions: The NPC1 compatment plays an important role in thetrafficking of LDL-derived substrate in steroidogenic cells. NPC1expression is upregulated when NPC1 action is blocked. The NPC1compartment can be functionally separated from other intracellularpathways contr

FC4.30.07ESTROGEN AND PROGESTOGEN LEVELS AND THEIRRECEPTORS ON THE OVARIES OF THE PINEALECTOMIZEDADULT RATSEI Hinoue*; JM Soares Jr, *; EC Baracat*; CE Lang*; MJ Simões*;CTF Oshima **; G Rodrigues de Lima**Department of Gynecology - Escola Paulista de Medicina, FederalUniversity of São Paulo, Brazil.**Oncocentro Fundation of São Paulo, Brazil.

Objective: The aim of this work was to study the status of estrogenicreceptor (ER) and progestogenic receptor (PR) on the ovarian of adultrats after pinealectomy (Px) and to dose the blood hormonal levels ofestradiol (E2) and progesterone (P4).Study Methods: 25 adult Wistar rats maintained on 12/12 light/darkcycle were randomly divided into three groups: GI) control group - 7rats; GII) sham (SPx) group - 8 rats; and GIII) pinealectomy (Px) group -10 rats. After two months post surgery, the animals was sacrificed andthe ovaries were dissected and put in liquid nitrogen. ER and PR weredeterminated by dextran-coated charcot method (DCC). Their bloodwere collected. E2 and P4 were determinated by 125I radioimmunoassayCoat-A-CountÒ.Results: The results showed the following means for ER (fmol/mg/prot):GI (control) = 11.2 ± 3.2 GII (Sham) = 14.6 ± 1.5 and GIII(pinealectomy) = 13.13 ± 2.3. For PR (fmol/mg/prot) were: GI (control)= 37.5 ± 5.7 GII (Sham) = 39.0 ± 5.0 and GIII (pinealectomy) = 32.50 ±3.0 (p=0,01). Blood dosage for E2 (ng/mg):GI = 22.7 ± 10.9, GII = 30.2± 17.6, GIII = 50.8 ± 25.5 and for P4: GI = 5.5 ± 2.6, GII = 6.6 ± 2.6,GIII = 5.8 ± 3.0Conclusion: Estrogenic receptors (ER) did not demonstrated variationsin the groups and progestogenic receptors (PR) decreased inpinealectomized group. However, estrogenic levels was increased inpinealectomized group.


V4.01 VIDEO SESSION: MISCELLANEOUS TOPICS

V4.01.01ENDOSCOPIC FINDINGS IN PELVIC TUBERCULOSIS (WADIASYNDROME)Prof. B. J. Wadia , Dept. OB/GYN/Family Planning, Sir J. J. Group ofHospitals, Mumbai, Maharashtra, INDIA.N. U. Joshi, Dept. OB/GYN/Family Planning, Sir J. J. Group ofHospitals, Mumbai, Maharashtra, INDIA.R. D'Souza, Dept. OB/GYN/ Family Planning, Sir J. J. Group ofHospitals, Mumbai, Maharashtra, INDIA.K. P. Tilwani, Dept. OB/GYN/Indira Gandhi Medical College, Nagpur,Maharashtra, India.

World Health Organisation notifies that 50% of Indian adults havetubercular infection. We feel that almost 90% of undiagnostic sterilityhas tubercular infection. Diagnosis of these cases is very difficult toprove. We have tried to combine these as Wadia Syndrome under theheadings of:1) Symptoms2) Signs and pelvic examination3) Laparoscopic findings and lesions4) Hysteroscopic findings and Lesions5) Special investigations.After performing over 350, 000 endoscopic procedures and correlatingthe signs, symptoms and investigations, several lesions came withdefinite regularity on endoscopic examinations. These cases underwentanti-tubercular treatment.sterility cases underwent had a pregnancy rate of 56%. These lesionshavebeen on video tape and the clips show the lesion distinctly.This study was started at Sir J. J.Group of Hospitals (BombayUniversity) in 1975. During sterilization camps conducted all over ruralIndia we found many cases undergoing laparoscopic sterilization, havingthese lesions, often resulting in post operative tubercular flare-up. Overthe years over 10, 000 cases reported for infertility during our visits ofthe sterilization camps. Most of these cases showed parts of the Wadiasyndrome. These cases were treated with anti-tubercular therapy and hada pregnancy rate of over 54%. Many of these cases were treatedemperically putting together various parts of the Wadia syndrome evenwithout endoscopic findings who had patent tubes and a good post coitaltest. Even these cases gave us a pregnancy rate of over 50% within 1year of treatment.

V4.01.02ENDOSCOPIC VIEWS OF TUBERCULOSIS OF FALLOPIANTUBESN.M. PATEL, C.N. PATEL, MAHALAXMI Institute of MedicalTeaching, Gujrat, India.

Objectives: Tuberculous infection of tubes is perisalpingitis and hencetubes remain patent in spite of its millary infection. Fimbrial phimosis isone of the early lesion seen in tuberculous salpingitis.We present video recording of endoscopic views in 3 cases ofhistologically proven cases of genital tuberculosis.In the first case, the fluid bubble was not able to pass through the leftosteium due to non canalized first 1.5 inch of the tube. The Rt. Tube hadfimbrial phimosis causing hydrosalpins. A solitary tubercolous nodulewas seen on tube but intestines had multiple tubercles. These are earlychanges seen due to genital tuberculosis.In the second case, there were milliary tubercles involving all genitalorgans. In spite of such involvement, there was fluid collected due toHysteroscopy procedure done prior to laproscopy with ringer lactate, asdistending media.Third case of uterine septum Hysteroscopy resection was planned withringer lactate as distending media and under laproscopic control. Atlaproscopy, all the pelvic organs had millary tubercles, but tubes werepatent, as ringer lactate collected in Douglas pouch. Septum resectionwas postponed.Conclusion: Terberculus involvement of tubes is perisalpigitis the tubesremaining patent in spite of millary involvement in many cases. Thisvideo shows all three cases.

V4.01.03MULTICENTRE COMPARATIVE STUDY BETWEENFLUCONAZOLE AND ITRACONAZOLE IN VULVOVAGINALCANDIDIASIS (VVC)N.S. Carvalho , E. Baract, P. Naud, P.C. Giraldo, J.A. Simoes, G. Duarte,I.M. Linhares, N. Cruz.Dept OB/GYN, Clinic Hospital, Federal University of Parana, Parana,Brazil.

The aim of the study was to compare the effect of fluconazole anditraconazole in VVC.In Multicentre comparative study, 181 patients were randomized toreceive one of two treatments: fluconazole 150 mg per single dose orItraconazole 400 mg per daily dose. Clinic and mycologic (culture)evaluation was made with 8-10 ds and 28-32 ds after the treatment.Clinic efficacy was 100% and 95.16% for first control (p=ns), 85.11%and 74.50% for second control (p=ns), to fluconazole and itraconazolerespectively. When compared first and second, the recidive rate wasmore frequent to itra than to fluco (p<0.001). Micologic efficacy was88.64% and 82.98% for first control (p=ns) and 68.1% and 65.96% forsecond control (p=ns) respectively to fluco and itraconzole.Conclusions: The clinic and micologic efficacy when we comparefluconazole and itravonazolein VVC was the same, but the clinicrecurrence after the first control was more frequent to itraconazole.

V4.01.04LONG-TERM RESULTS OF ABDOMINAL SACRAL COLPOPEXYWITH MERSILENE MESH IN PATIENTS WITHPOSTHYSTERECTOMY VAGINAL VAULT PROLAPSES.Kaleli , K.Ayd_nl_, T.Erel, T.Atasü, _stanbul University, Cerrahpa_aMedical Faculty, Murat villa apt. No:14/1, _stanbul, Bak_rköy, Turkey,34830.

Objective: Vaginal vault prolapse is observed in many women who hadhysterectomy before. Although so many type of operations are describedand performed, long-term results of these technics are not well known.The aim of this study is to evaluate the long-term results of abdominalsacral colpopexy operation in patients with posthysterectomy vaginalvault prolapse.Study method: 20 patients with vaginal vault prolapse developing aftertotal hysterectomy were enrolled into the study. Vaginal vault wassuspended to cartilage of sacral promontory with mersilene meshthrough a retroperitoneal tunnel Abdominal sacral colpopexy operationwas completed with Moschowitz procedure and Burch/Marshall-Marchetti-Kranz procedure.Results: These patients were followed up for at least five years with 6months intervals. Nineteen of 20 patients showed excellent suspensionand urinary functions at the end of the fifth year.Conclusion: Abdominal sacral colpopexy with mersilene mesh inposthysterectomy vaginal vault prolapse is method of choice for long-term success.

V4.01.05VAGINAL HYSTERECTOMY FOR NON-PROLAPSED UTERUS-MODIFIED TECHNIQUES. Rajagopalan , Bangalore Hospital, 202 RV Rd., South End Circle,Bangalore, Karnataka, India, 560004.

Procedure: The pouch of Douglas and the uterovesical pouch are directlyentered with two seperate, small transverse incisions, in place of thecircular incision and reflection of the vaginal mucosa, which istraditionally done. The bladder is carefully dissected off the loweruterine segment prior to entering the uterovesical pouch. The vaginalmucosa is not dissected and reflected laterally. Uterosacral and cardinalligaments are clamped, cut, and suture ligated along with the vaginalmucosa. The uterine vessels are also clamped, cut, and suture ligated asusual. Following this, a vertical incision is made on the anterior surfaceof the body of the uterus until the cavity is reached. The cut edges of theuterine musculature are now grasped pulling the fundus forwards anddownwards to facilitate easy delivery of the body of the uterus. Thetubo-ovarian ligaments, or the infundibulo pelvic ligaments, are nowclamped, cut and suture ligated, depending on whether the tubes andovaries are to be removed or not. Peritonisation and closure of thevaginal vault are now completed as usual.


Stats:Total Number of Cases at Bangalore Hospital-59Diagnosis- 1. symptomatic uterine fibroids-322. Adenomiosis-323. Severe cervial displacia-1Prior abdominal surgery-10 cases Hospital stay- 36 to 48 hoursPost-op Morbidity-noneConclusion: This minimizes dissection, reduces bleeding, and helps easydelivery of the uterus. This results in a reduction of morbidity.

V4.01.06LAPAROSCOPIC MANAGEMENT OF OVARIAN REMNANTSYNDROME USING THE HARMONIC SCALPELC. Nezhat (1) , F. Nezhat (2), C. Nezhat (1), (1) Stanford University,5555 Peachtree Dunwoody Road, Suite 276, Atlanta, GA, United States,30342, (2) Mt. Sinai School of Medicine, New York, NY, U.S.A.

We present a case of laparoscopic management of ovarian remnant in a48 year-old woman with a history of multiple abdominopelvic surgeriesand worsening pelvic pain unresponsive to conservative management.Adhesiolysis and pelvic sidewall dissection by harmonic scalpel wasperformed with successful excision of the ovarian remnant. The patientis pain free postoperatively without evidence of recurrence.

V4.01.07FILM: MITRA OPERATION FOR CANCER OF THE CERVIXEXTRA-PERITONEAL PELVIC LYMPHADENECTOMY ETRADICAL VAGINAL HYSTERECTOMYN. Roy Chowdhury , Dept. OB/GYN, C.M.R.I., Calcutta, India.

Projection Time - 25 minutesLanguage of Film - EnglishAbstract of FilmThe film demonstrates systematic bilateral removal of pelvic nodesextra-peritoneally together with ligature of ovarian and uterine vesselsand blunt dissection of parametria. The vaginal part demonstrates thesteps of radical vaginal hysterectomy with massive removal ofparametria.


POSTERS

P4.01 ANTENATAL CARE AND DIAGNOSIS

P4.01.01CAN THE NEW ZEALAND ANTENATAL SCORING SYSTEM BEAPPLIED IN THE UNITED KINGDOM?H. Mohamed , C. Martin, A. Smith, L. Carpenter, C. Mann, R. Haloob,Dept. OB/GYN, Basildon Hospital, Essex, UK.

A pilot study comparing Knox antenatal scoring system designed inNew Zealand with the antenatal scoring system in the UK at bookingand at 36 weeks gestation.Objectives: To assess the sensitivity and predictive values of using Knoxscoring in the British community, in order to assign correctly the level ofantenatal care needed and to reduce the unnecessary hospital referral.Study Methods: 166 pregnant women were assessed at booking clinic bythe current antenatal scoring as well as by Knox scoring systems andthen the same women reassessed again at 36 weeks of gestation. Thehigh risk pregnancy was identified using the exact sum of logisticcoefficients used by Knox score. Data sheets were analyzed in respect ofagreement and discrepancy of the two systems for predicting maternaland perinatal outcomes.Results: At booking visit Knox scored 11.7% of women as high risk and88.3% as low risk while the current antenatal system scored 48.9% ashigh and 51% of women as low risk pregnancy. At 36 weeks ofgestation Knox scored 1.4% of the same pregnant women as high whenthe clinical opinion identified 37.9% as high risk women. A totalagreement was 54.5% in both systems at booking and 62% at 36 weeksof gestation. One case of perinatal death at 25 weeks of gestation andnine cases of perinatal morbidity with total bad outcome of 6.8%. Knoxscore showed a higher positive predictive value (17.6% vs. 12.1%) butless sensitivity (30% vs 90%) than the current UK antenatal scoringsystem.Conclusion: Despite the agreement of both systems, in more than 50%of the pregnant women the Knox scoring system resulted in a higherpredictive value than the current antenatal scoring system used in theUK. This leads to a dramatic reduction in hospital referrals at bookingvisits - from 48.9% to 11.7%, and late in pregnancy from 37.9% to1.4%. A consideration is required to apply Knox antenatal scoringsystem in Britain only after a larger number of pregnant women havebeen scored in a randomized study.

P4.01.02CHANGES IN CA130 LEVELS DEPENDING ON THE FORM OFNORMAL PLACENTAL SEPARATION (PS) OF DELIVERY ANDCLINICAL SIGNIFICANCE OF CA130 LEVELS IN DIAGNOSINGPLACENTAL ABRUPTION (PA)M. Shigeru , Dept. OB/GYN, Chugoku Rousai General Hospital,Hiroshima, Japan.

Objective: In the present study, changes in serum levels of CA130 wereinvestigated depending on the form of PS. The clinical significance ofCA130 levels in PA was considered.Subjects and Methods: 23 women were examined by normal vaginaldelivery, of whom 8 had form –(I) separation of the placenta, in whichthe placenta is smoothly separated, 7 had form –(II) in which separationof the placenta began at the margin and 8 had form –(III) in which theplacenta was separated during hematoma formation. Blood specimenswere collected before 30 min, 60 min, 120 min, and 180 min. after PSand on day 1 and day 5 of puerperium and serum CA130 levels weredetermined by the RIA method.Results: (I) The mean serum CA130 levels were 22 (U/mL), 218, 202,165 and 136, measured before 30 min, 60 min, 120 min, and 180 min,respectively observed values were: 78 on day 1 and 20 on day 5 ofpuerperium. (II) The levels were 25, 232, 215, 160, and 142, measuredbefore, after PS, and found to be 88 on day 1 and 30 on day 5 ofpuerperium, which returned to the normal level. (III) The levels were 30,488, 434, 402 and 375 measured before, after PS and 128 on day 1 and30 on day 5.Conclusion: The serum CA130 levels after PS in women with (III) wereabnormally higher than those in women with (I) and (II). Since the (III)which is associated with hematoma is identical to the form of PA, theabove results suggest that determination of serum CA130 levels can beof practical use in diagnosing PA.

P4.01.03COMPLEX STUDY OF PREGNANCY WITH THE APPLICATIONOF ECG, DOPPLER ULTRASONOGRAPHY ANDIDENTIFICATION AFP BLOOD LEVEL.Z. Sinauridze , Dept OB/GYN, Tbilisi State Medical University, Tbilisi,Georgia

Objectives: The main goal of the present research is identification ofdiagnostic significance of fetal ECG with the combination of Dopplerultrasonography and identification of blood AFP level.Study Methods: We investigated 47 pregnancies with differentpathologies. Particularly: IUGR (23), different types of gestosis (14,normal pregnancy (10). The following technical devices were used forthe research : “COROMETRICS – 100” (USA) for Fetal ECG;“ALOKA fsd – 1800” for Doppler ultrasonography; Chromatographyfor AFP level identification. In accordance with the gained results, allpregnancies were divided into 4 groups: Group 1: ECG shows dip II(types U); ultrasonography –normal; Group 2: ECG shows dip II (typesU & W); ultrasonography indicates blood flow speed increase in arteriesof fetus umbilical cord and aorta; AFP level stays normal; Group 3:ECG shows dip II (type W), monotonous rhythm; ultrasonographyindicates pathologic curves of blood flow in veins and arteries of fetusumbilical cord and aorta; AFP level is above 200 mkg/l; Group 4:normal pregnancy.Results: One case of fetus intra-brain hemorrhage was observed in thegroup 1. It was successfully rehabilitated at the clinical stage of neonatalperiod. In the group 2, there were two cases of intranatal and one case ofearly neonatal death. In 3 cases, there was hard post-hypoxy trauma ofCNS in the neonatal period. In the group 3, just one infant has survivedwith the hard trauma of CNS; in the rest of the cases, fetus death wasobserved.Conclusions: Complex study of pregnancy with the application of ECG,ultrasonograply, and hormone test is the only was to establish a fullpicture of the state feto-placental system and fetus.

P4.01.04CRITERIA FOR PREDICTION OF ANTENATAL FETAL DEATH INDIABETIC PREGNANT WOMENN. Solonets , V. Medved, I. Gordienko, E. Romanenko, Dept. Internalpathology of pregnant, Institute of PED/OB/GYN, Kiev, Ukraine.

Objectives: High rate of perinatal losses in diabetic patients provides thenecessity of elaboration of the new criteria for evaluation of the fetalwell being. Usually the deterioration of fetal status begins from the 2nd

trimester and in the severe cases leads to the antenatal death after 30weeks of gestation.Study Method: Retrospective analysis of the maternal blood cortisol,placental lactogen and pregesterone levels, urinary estriol amniotic fluidurea, creatinine and bilirubin levels in 250 patients with diabetesmellitus type 1 at 30-36 weeks of gestation has been investigated.Results: Antenal fetal death occurred in 10 patients (I group), 240females gave birth to live children (II control group).In patients of the I group 1-2 weeks before an antenatal fetal deathversus II group a rapid increase of cortisol leve (1509,5±60,6 nmol/l vs.1056,9±43,6 nmol/l ; p<0.001) and decrease of placental lactogen(192,0±1,41 nmol/l vs. 218,5±1,85 nmol/l; p<0.001) and progesterone(305,6±18,4 nmol/l vs. 390,9±10,5 nmol/l; p<0.001) contents have beenobserved. Urinary estriol excretion was low (28.8±3,01 mmol/24h vs.41,7±3,58; p<0.001). The levels of creatinine, urea and bilirubin inamniotic fluid obtained by transabdominal amniocentesis were374,0±46,7 mmol/l vs. 197,9±15,21 (p<0.001); 13,23±1,0 mmol/l vs.7,64±0,75 (p<0.001); 6,0±0,7 mmol/l vs. 2,4±0,2 (p<0.001) respectively.Conclusions: The indices of blood cortisol, placental lactogen andprogesterone urinary estriol excretion as well as those of urea, creatinineand bilirubin in amniotic fluid may be used for evaluation of the fetalstatus in patients with diabetes mellitus prediction of severe healthdeterioration and antenatal death.


P4.01.05DAWN RULE OF TEN COMPLETE ANTENATAL CAREM. Shrivastava , R. Shrivastava, A. Shrivastava, Shrivastava NursingHome, Gwalior, India.

Objective: To study the effect of antenatal care by Dawn rule of ten.These simple rules are made to take care of mother and child indeveloping countries which aim at 10 gm% hemoglobin, 10 kg wt gain,10 hour sleep, 5-10 visits, 10 hours labor, 10 months breast feeding,immunization of baby by 10 months, contraception by 10 weeks.Study Methods: A study of 320 cases of antental care from January 1998to December 1998 by Dawn rule of ten in Shrivastav Nursing Home,Gwalior. They were compared with the random study of 156 emergencycases.Results: The incidence of anemia was low, average hemoglobin was 9.5gm%, PIH was 5%. The cesarean section rate was only 15% while thesame figures were higher in unbooked emergency cases i.e. anemia was7 gm%, PIH in 25% of cases, cesarean section rate 40%.There was no maternal death in first group but here were 3 deaths inemergency group.Conclusion: Dawn rule of ten is a simple and easy to follow method indeveloping countries for reducing MMR and IMR.

P4.01.06DOPPLER INDICES FROM DUCTUS VENOSUS IN I.U.G.R.FETUSES BETWEEN 28 AND 32 WEEKSL.M. Lopes , R.A.M. Sá, H. Werner, M.J. Franco, R.N. Galluzzo, J.P.Pereira Jr., C.P.S. Werner, Laranjeira Clinica Perinatal, Rio de Janeiro,Brazil

Objective: The objective of this study was to assess the value of Dopplerindices calculated from ductus venosus in the identification of acidemiaas determined by cord blood pH.Study Methods: The study investigated the blood flow velocity of ductusvenosus in relation to the umbilical circulation and cerebral circulation(middle cerebral arteries) in the seriously growth-retarded fetus. Thestudy group of 40 fetuses (gestational week 28-32) had no chromosomalaberrations or structural malformations and had an ultrasound biometryof <2.5th centile and birth weight of <2.5th centile. All the fetusespresenting «centralization» (relationship umbilical/cerebral>1). All thepregnant women had been examined up to 5 hours before the delivery.For the umbilical arteries and cerebral artery averages were obtainedusing the following indexes: S/D, resistance index (RI) and pulsatilityindex (PI). For the ductus venosus the S/A (PVS/PVA) index was used.Cord pH and gas measurements in the umbilical vein (PO2 mmHg,PCO2 mHG and BE mMol/liter) were obtained in standard heparinizedblood syringes immediately following delivery of the baby.Results: Of the 40 «centralized» fetuses 32 presented normal ductusvenosus index (80%). Of these 6% (2/32) fetuses presented acidosis(pH<7,25) and 94% (30/32) had normal pH (>7,25). Of the 40 fetuses, 8(20%) had abnormal Doppler indices from ductus venosus and hadabnormal end-diastolic pulsating pattern in the umbilical vein. Of the 8fetuses, 7 (88%) had pH<7,20 and BE>-6 and only 1 (13%) had normalpH value (7,26) and BE –5.Conclusions: 1) The results support the assumption that the blood flowof the ductus venosus maintained within normal ranges as long aspossible during placental hemodynamic compromise, maintained at ahigh level, even in advanced stages of intrauterine growth retardation. 2)The results suggest that abnormal end-diastolic umbilical venouspulsation in cord is an ominous sign of a severely compromised fetus. 3)Although prospective studies are necessary to validate the results, theapplication of Doppler index of ductus venosus may be useful for non-invasive identification of their acid-base status and the selection of theproper timing of delivery.

P4.01.07EACH WOMAN SHOULD BE VERY CAREFUL IN MAKINGDECISIONS OVER TAKING MEDICATIONS DURINGPREGNANCY PERIODS. Pangovska , A. Dimitrovska, Medical Center Bit Pazar, Skopje,Republic of Macedonia.

Our previous experience shows that the only excusable reason for usingmedications during pregnancy period is to preserve women health, andto have a useful effect over fetus growth (evolution).Most of the medications taken during pregnancy pass the placenta. Thismay influence babies’ normal growth or cause its damage. Thereforecareful selection should be made before making any choice of whatmedications to use.Objective: Analyses about the most common situations as an examplewhy to use medications during pregnancy period.Methods and MaterialsUsed medical records for pregnancy control for 144 pregnant women inour dispensary and their laboratory results – as reason to usemedications.Results: In 39 (27.08%) patients as a result of prescribed Fe, Vita C., andfolic acid by the gynecologist. In 14 (9.72%) because of urinaryinfections – used antibiotics according to precise biographer whichrelates to the first group of medications in range of World HealthOrganization. 4 patients (2.77%) as a result of high blood pressure –which was defeated under therapy of simpatolitic and b blocks.As a result of taking metromidol, before establishing pregnancy only onepregnancy terminated intentionally during 8gw.Conclusion: W e have successfully managed to preserve the health ofpregnant women on one side, and to achieve a useful effect on babies’development on the other side. This was accomplished by selecting theright medications for all of the above-analyzed pregnancies.

P4.01.08EVALUATION OF MASS ANTENATAL CARE PROGRAM OFDELHIN. Agarwal , P. Yadav, UCMS & GTB Hospital, Shahdara, Delhi, India.

Antenatal Care was provided to pregnant women of Delhi residing inresettlement colonies and urban slums by organizing campaigns on asingle fixed day of every month. A total of 260 centers were identifiedeach time and about 4000 health staff was employed to provide completeantenatal care including ultrasound examination if needed.During each program, 20,000 – 25,000 women were examined and highrisk factors were identified in 42% of cases. Anemia was the commonestassociated complication. Congenital Malformation was diagnosed in3.2% of women. The breast lump was detected in 100 women and in 2of them, further investigation led to a diagnosis of breast carcinoma.Evaluation of the mass antenatal care has demonstrated a reduction inmaternal morbidity and mortality.

P4.01.09INTRAUTERINE GROWTH RETARDATION AS A SIDE EFFECTOF HIGH PARACETAMOL DOSESBurdan F1, Czekierdowski A 2 , Wyskiel M1.1Department of Anatomy and 2Department of Obstetrics andGynecology, University School of Medicine in Lublin, Poland

Paracetamol, because of its safety in low therapeutic doses for bothmother and fetus is routinely used over-the-counter analgesic andantipyretic drug during pregnancy. The aim of the study was to evaluatea possible effect of high paracetamol doses on fetal development.Paracetamol was administered to pregnant Wistar rats intragastrically inTween-80 water suspension. The animals were treated three times a dayduring the whole organogenesis period with three different doses: P1 -50 mg/kg body weight (n= 10 – pregnant females), P2 – 100 mg/kg b.w.(n=10), P3 – 200 mg/kg b.w. (n=10). Three control groups wereexamined: Cu- untreated control (n=10), Cw – animals receiving water,CT – animals receiving Tween 80 water suspension (n=10). The dameswere terminated on day 21 of gestation. The fetuses were delivered bycaesarean section and numbers of corpora lutea, resorptions, live anddeath fetuses were counted. The fetuses and the placentas wereweighted, and the length of fetuses and their tails were measured. There


were statistical differences (ANOVA, p<0.05) in body weight in allparacetamol-treated groups; body length in P2, P3; tail length andplacental weight in P3; compared to common control group. Thepreimplantation and postimplantation mortality factors were notstatistically different. We conclude that high doses of paracetamoladministrated in the entire second trimester of rat gestation may causedose-related intrauterine growth retardation.

P4.01.10LIPIN IN COMLEX THERAPY OF HYPOXIA IN PREGNANTSSUFFERING FROM DIABETES MELLITUSV. Lutsik , I. Akimova, I. Govorukha, Donetsk State Regional Center ofMaternity and Child Care, Donetsk, Ukraine.

Objectives: To investigate the dynamics of glucose metabolism activitylactatdehydrogenase (LDG), glucosa-6-phosphatedehydrogenase (G-6-PhDG), adenosintriphosphotase (ATPh-ase) in erythrocytes of pregnantssuffering from diabetes mellitus during pregnancy, before treatment,after treatment by traditional therapy, complex therapy with liposomalremedy “Lipin”.Study Methods: There were 118 pregnants suffering from diabetesmellitus at age 17 to 38 years in basic group. In control group there were40 pregnants with physiological pregnancy. Pregnants suffering formdiabetes mellitus were subdivided into two subgroups: 62 pregnants withhypoxia were treated by traditional remedies (the first subgroup); 56pregnants with hypoxia were treated by “Lipin” (the second subgroup).Results: The LDG, G-6-PhDG, ATPh-ase enzymes activities werereduced in pregnants of the second subgroup after treatment. The levelof G-6-PhDG was decreased in 9% in the first trimester, in 32% in thesecond trimester, in 30% in the third trimester. The level of LDG wasincreased in 21% in the first trimester, in 34% in the second trimester, in33% in the third trimester. The level of ATPh-ase activity was increasedin 24% in the first trimester, in 37% in the second and the thirdtrimesters.Conclusions: Use of “Lipin” in a complex treatment of hypoxiaincreased the enzyme activities in pregnants suffering from diabetesmellitus in comparison with traditional therapy.

P4.01.11MATERNAL AND NEONATAL SERUM LEPTIN LEVELS INNORMAL AND DIABETIC PREGNANT EGYPTIAN WOMENA.El-Adawy (1), M. Ibrahim (1), O. Gohar (2), Kasr El-Aini Hospital,Cairo University, Egypt.(1) Dept. OB/GYN.(2) Dept. Clinic. Path.

Objective: To study the relation of maternal and neonatal leptin levels tomaternal and neonatal weight and glucose level in non-diabetic as wellas diabetic cases.Materials and Methods: We have studied 96 mothers with term singletonpregnancies at delivery (65 non-diabetic and 31 diabetic). Maternal andumbilical cord venous blood were sampled at birth for determination ofmaternal and fetal plasma glucose and serum leptin levels. Analysis wasdone using Student’s t-test, Pearson’s correlation, and Spearman’scorrelation. Univariate/multivariate regression was used for analysisassociated with leptin concentration.Results: On comparing diabetic and non-diabetic, maternal weight,plasma glucose and serum leptin levels were significantly higher in thediabetic group (p<0.001); similarly neonatal weight and cord serumleptin were significantly higher in diabetics than non-diabetic cases.Also, cases with large for gestational age babies had a significantlyhigher serum leptin than those who were appropriate for gestational agefrom both diabetic and non-diabetic mothers. On the other hand,neonatal glucose level was significantly lower in the diabetic group (alldiabetic cases included in the study were noncontrolled). Correlation ofcord serum leptin had revealed a significant positive correlation toneonatal weight (p<0.01), but not with neonatal glucose level ormaternal serum leptin level. Similarly, maternal serum leptin level wassignificantly correlated with maternal weight but not glucose level.Conclusion: Serum leptin is well correlated to body weight for bothadults and neonates, however diabetic state and hyperglycemia have noinfluence except if it caused fetal macrosomia.

P4.01.12NITRIC OXIDE CONCENTRATIONS IN FETO-PLACENTALCIRCULATION IN PREGNANT WOMEN WITH CHRONICINTRAUTERINE INFECTIONA.Zelynsky , G. Manasova, Dept. Perinatal Medicine, Child andAdolescent Gynecology, Odessa State Medical University, Odessa,Ukraine.

Objectives: The aim of this study was to measure plasma concentrationsof total nitrites, as an index of nitric oxide (NO) synthesis, in maternaland fetal circulation of normal pregnancies and in pregnanciescomplicated by chronic intrauterine infection.Study Methods: We studied 26 women with infection in pregnancy suchas candida albicans, toxoplasma gondii, chlamidia trachomatis, herpessimplex and 24 with uncomplicated pregnancies. Maternal and umbilicalvenous blood samples were collected from all the patients. Also, westudied the placental damage rate morphologically.Serum NO concentrations were determined with Greiss reaction bymeasuring combined oxidation products of NO.Results: There were significant differences in maternal serum nitrateconcentration between the groups (control group 0.6 ± 0.015 mmol/L,infection group 0.47 ± 0.05 mmol/L; p<0.05). Significantly lower serumnitrite concentrations were found in the umbilical venous serum in theinfection group compared with the control group (0.4 ± 0.03 mmol/L vs0.7 ± 0.08 mmol/L; p<0.01). The placental damage rate in chronicinfection in pregnancies correlated with the NO synthesis activitysuppression rate.consequence with the chronic intrauterine infection in pregnancy.Conclusions: Total nitrites are decreased in the fetoplacental circulationin the chronic infection in pregnancy. These results support thehypothesis that decreased NO production may play a role inpathogenesis of the placental damage in

P4.01.13PARTIAL TRISOMY 12q15…q22Z. Yilmaz , M. Erman-Akar, S. Ceylaner, G. Ceylaner, S. Nabaei, O.Gökmen, Dept. OB/GYN, Zekai Tahir Burak Maternity Hospital,Ankara, Turkey.

Amniocentesis was performed to a woman at 41 as advanced maternalage. Ultrasonographic examination and pregnancy follow-up wasnormal. It was her third pregnancy and she has a healthy daughter and anectopic pregnancy. Maternal AFP and hCG levels were normal but UEwas low (0.64 MoM) 46, XX, 3p (+) was detected from culturedamniocytes at the 17th week of her gestation. Parental chromosomeanalysis was performed to detect the origin of extraband on 3p andmaternal balanced translocation was detected (46, XX, t (12:3) (12pter…12q 15::12q22… 12qter) (12q15… 12q22::3pter…3qter)Her pregnancy was terminated as trisomy 12q15…q22 region. Therewas no dysmorphic feature or any abnormal autopsy finding of fetusdetected.To our knowledge, this is the first case with partial trisome of12q15…12q22 region without any fetal abnormality. In summary:(1) Rearrangements of chromosome 12 could be seen detected without

any malformation.(2) Chromosome analysis must be done for intrauterine ex-fetuses and

still borns without malformation.

P4.01.14PECULIARITIES OF EARLY ADAPTATION OF INFANTS BORNBY MOTHERS WITH ANTIPHOSPHOLIPID SYNDROMEV.K. Chaika , T.N. Demina Y.A. Batman, G.V. Mesherinova , StateMedical University, Donetsk, Ukraine

Objectives: The aim of the investigation is to study peculiarities of earlyneonatal period in infants born by mothers with antiphospholipidsyndrome (APS).Study Methods: 10 infants aged 0-7 days were examined. Their mothershad clinical immunological APS markers and were treated. Newbornsunderwent complex examination including clinical, biochemical andimmunological methods. Simultaneously dynamic monitoring of vitalorgans and systems was done.Results: Newborns’ state with Apgar score less than 7 after 5 minuteswere recorded in 3 infants, in the others – more than 7. The urgent


adaptation period in the first hours of life had no peculiarities. Byinvestigating the peripheric blood thrombocytopenia (T/1), not sharplyexpressed anemia (100-110g/l), extension of coagulation time (7,5 –11.5 min), decreasing of prothrombin index (60-80%) were revealedmanifesting themselves in hemorrhagic syndrome in some infants. In 2newborns positive reaction to anticardiolipin antibodies (ACLA Ig J)was revealed, in the others ACLA tests were negative. Clinicalsymptoms of cardiopathy in 3 newborns were characterized byexpressed tachycardia, arterial pressure gradient was marked (96/44-40/22).During early rehabilitation period glucocorticoids (dexamethasone 1mg/kg for 24 hours), immunoglobulin (3 ml/kg intravenous for 3 days),fresh frozen plasma.Conclusions: In infants born by mothers with antiphospholipidsyndrome (APS) in consequence of autoimmune conflict and possibletransplacental transition of APS to the fetus specific clinical symptomsare absent. Thrombocytopenia, anemia, disseminated intravascularsyndrome (DIS) symptoms, tachycardia, arterial pressure gradient weremarked more often.These infants of the high risk group in perinatal morbidity and mortalityrequire further examinations.

P4.01.15PREGNANT WOMEN’S APPRECIATION OF PERSONAL HEALTHSTATUS AND ATTITUDES TO ANTENATAL CARE, SICKNESSABSENCE AND SOCIAL BENEFITSA. Sydsjö , G. Sydsjö, Div. OB/GYN, Dept. of Health and Environment,Linköping University, Linköping, Sweden.

Objective: Unexpectedly high rates of sickness absence have beenobserved among pregnant women. No clear medical causes have yetbeen identified with certainty. Instead, sickness absence duringpregnancy has been attributed to the pregnant women’s own attitudes.The aim of this study was to investigate the validity of this hypothesis.Material and Methods: 336 consecutively delivered women at theUniversity Hospital of Linköping were asked to answer a questionnaireanonymously in 1995. Information about sickness absence, socialbenefits as well as working conditions and the delivered women’s wellbeing were noted. The women’s attitudes to sickness absence and socialbenefits were registered on a visual-analogue scale.Results: 43% of the women stated that they had been sick-listed duringpregnancy for an average period of 47 days. The main reason motivatingsickness absence was back pain. The majority (74%) of the sick-listedwomen stated that they had experienced “good” or “excellent” healthduring pregnancy. Only 4.3% of all pregnant women stated they hadconsidered themselves as ill due to an obstetric disorder.The working conditions as well as personal relations at work weregenerally less appreciated among sick-listed women. Young women(<25 years) were most dissatisfied.Conclusion: In addition to actual disease and severe discomfort, certainsocial conditions associated with employment, and probably personalattitudes as well, are likely to explain the increase in the percentage ofwomen taking sick leave during pregnancy.

P4.01.16PRENATAL DIAGNOSIS WITH GENETIC AMNIOCENTESISK.Y. Choi , S.D. Choi, D.H. Bae.Dept OB/GYN, College of Medicine, Soonchunhyang Chunan Hospital,Chunan, Korea

Objectives: Amniocentesis for the diagnosis of prenatal geneticabnormalities is now the standard care for women who are at specialrisk. Because the application of population based maternal serumscreening to change of amniocentesis indications.Study Methods: 332 women who were attending the antenatal clinic ofSoonchunhyan Chunan Hospital had a amniocentesis between January1997 and December 1999. The result were analyzed in reference toindication of amniocenteses, gestational age, pregnancy outcome andkaryotype.Results: The major indications were abnormal maternal serum marker(182 - 54.8%), advanced maternal age (74 - 22.3%), previous fetalchromosomal anomaly (21- 6.3%) and the most common agedistribution at amniocenteses was 25-29 years (154 – 46.4%). Thepregnancy outcome was full-term delivery (266 – 80.1%), preterm

delivery (61 – 18.4%), spontaneous abortion (3 – 0.9%) and terminationof karyotype, structural aberration was 14 cases (4.2%) and numericalaberration was 8 cases (2.4%). Among the numerical aberration, fivecases of trisomy 21, one case of Edward’s syndrome, one case ofKlinefelter syndrome, one case of Turner syndrome were found. Amongthe structural aberration, insertion was most common (sic cases), andfour cases of inversion, three cases of translocation and one case ofdeletion were found.Conclusions: This is a report of generic amniocentesis, with analysis ofthe indication, gestational age, karyotype results and complication.

P4.01.17PROCENTUAL DECLINE OF FETAL HAEMATOCRIT BETWEENFETAL TRANSFUSIONS IN ALLOIMMUNISED PREGNANCIESD. Ivanovic , G. Ivanovic, D. Plecas, O. Vucinic-Kontic, S. Plesinac,A. Glisic, P. Momcilov, N. Radunovic, M. Popovic*, Institute ofOB/GYN, Clinical Centre of Serbia, *Institute of Transfusiology,Belgrade, Yugoslavia.

Objectives: To determine procentual decline of fetal haematocritbetween intrauterine intravascular transfusions (IUIVT).Study Methods: Between 1990 and 1998, 81 fetuses underwent 270IUIVT. Fetal anaemia was caused by alloimmunisation to Rhesusantigens. According to the presence of hydrops all fetuses were devidedin two groups. Fetal hematocrit (Hct) were determined before and afterIUIVT.Results: In hydropic fetuses procentual decline of haematocrit betweentransfusions 1 and 2 (5.61 ± 3.46) was significantly higher thenprocentual decline between 2 and 3 (2.92 ± 1.29) transfusions.Procentual decline between 2 and 3 transfusions was significantly higherthan procentual decline of fetal haematocrit between transfusions 3 and4 (2.01 ± 0.63) and between 4 and 5 (2.28 ± 0.55) (F=8.92; p < 0.01). Innonhydropic fetuses procentual decline of fetal haematocrit betweentransfusions 1 and 2 (3.44 ± 2.25) was significantly higher thanprocentual decline between 2 and 3 transfusion (2.26 ± 0.67) (F= 5.87; p< 0.05). In procentual decline between subsequent transfusions therewere no significant diferences.Conclusion: Our results indicate that it is necessary to use shorterintervals between the first and second transfusion than betweensubsequent ones. The wide range of calculated values necessiatesadditional criteria for retransfusion

P4.01.18RECIDIVE HYDROCEPHALY IN TUNISIAN. Jaballah , Policlinique CNSS, Sousse, Tunisia.

Objectives: The aim of this study was to investigate the frequency ofhydrocephaly among the newborns of parents with blood relationships(consanguinity) and to compare the results with the literature.Study Methods: A retrospective study of two cases of parents withrecidive hydrocephaly was made. The history of the patients, thepregnancy, the laboratory examinations and the caryotype of bothparents were normal.Results: The only common factor of the two cases was the consanguinity(this is very frequent in Tunisia and the Arabic world). The study of theliterature showed that the etiology of this pathology was congenital in70.7% and acquired in 29.3% of cases. These cases are respectively89.75% and 10.25% of cases in Tunisia.Conclusions: Recidive hydrocephaly is frequent by parents with bloodrelationships. Genetic counseling of these people is important to reducethe frequency of this pathology. Study of the localization of the gene ofthis anomaly will be very interesting.

P4.01.19STUDY WITH CLINICAL MANAGEMENT OF DELIVERIESAFTER 41 WEEKS OF GESTATIONK. Aisaka , K. Nakagawa, T. Uesato, A. Miwa, T. Koshino, F. Ooka, M.Nishihira, M. Sadatsuki, S.G. Liang, M. Kaibara, Dept. OB/GYN,Teikyo University, Ichihara Hospital, School of Medicine, Ichihara,Chiba, Japan.

Objectives: It has been reported that fetal distress (FD) based on theplacental dysfunciton occurs more frequently in over term delivery if the


gestational week is corrected accurately by ultrasonography in earlystage of pregnancy. Present study was performed to elucidate whether itis possible to decrease the frequency of FD by the induction of laborafter 41 weeks of gestation.Study Methods: 108 cases of primiparas delivered after 41 weeks ofgestation were subjected. They were selected from 1486 of full termdeliveries during recent ten years. They were divided into two groups;group A: naturally followed up till onset of labor, and the propertreatment was carried out if necessary, 46 cases, and group B: inductionof labor was performed after 41 weeks of gestation, 62 cases. Andparturition weeks, incidences of FD, rates of cesarean section (c/s) andApgar scores were compared between these two groups.Results: Parturition weeks (A: 42.2±1.9 vs. B: 41.3 ±1.5 weeks, p<0.01),incidences of FD (54.3 vs. 30.6%, p<0.025), rates of c/s (56.5 vs. 33.9%,p<0.05) and Apgar scores (7.0±2.1 vs. 8.4±2.3, p<0.05) were improvedsignificantly in the group B. There were no significant differences inmaternal age (28.4±3.7 vs. 29.0±2.6 years old), height (159.6±4.0 vs.160.1±3.5cm), body weight (63.8±6.2 vs. 64.5±5.7 kg).Conclusions: From these results, it was concluded that the induction ofthe labor after 41 weeks of gestation was suitable for the prevention ofFD due to the dysfunction of the placenta.

P4.01.20THIRD TRIMESTER INTRAUTERINE DEATHS – UNAVOIDABLERISK?T. Major , G. Juhász, J. Aranyosi, A. Borsos, Dept. OB/GYN, UniversityMedical School, Debrecen, Hungary.

Objectives: The assessment of third trimester intrauterine deaths in athird level referral center.Study Methods: Analysis of 211 intrauterine deaths out of 32,126deliveries.Results: As a causative factor, umbilical cork complication could beidentified in 58 cases (35%), while abruption of the placenta in 22 (13%)cases, severe IUGR in 24 (15%), other reasons in 27 cases. In 32 cases(20%), even with the help of all available information, no definitivecause could be identified.Conclusions: Regularly performed careful analysis of intrauterinedeaths, uniform data collection and routine autopsy would help usidentify underlying pathology and possibly prevent third trimesterintrauterine deaths and is strongly recommended to all departments.

P4.01.21UTERINE BLOOD FLOW WAVEFORM ANALYSIS TO PREDICTSOME COMPLICATIONS OCCURRING IN THE LAST MONTHSOF PREGNANCY.L. Gargiulo, V. Guerriero, L. Caserta, A. Soriano, A. Magliole, E. Nesti,R. Caserta , S. Panariello.

Objectives: The aim of this study was to assess the performance ofuterine blood flow waveform analysis to predict some complicationsoccurring in the last months of pregnancy (gestosis, IUGR, preterlabor)in a non-selected population.Study Methods: 310 pregnant women were assisted during pregnancyuntil delivery and submitted to transabdominal ultrasound examinationwith uterine artery velocimetry waveform analysis, at about 20-24weeks.Birth weight, gestational age at delivery and maternal blood pressureduring pregnancy were aslo reported too.Results: The test, with regard to gestosis and IUGR, was found to have asensibility of 43,2%, a positive predictive value of 27,8%, a specificityof 92,8% and a negative predictive value of 96,3%.No correlation was found between mean RI and gestation age atdelivery.Conclusions: We retain that Doppler uterine artery waveform analysiscan’t be used as screening test in unselected pregnant women, becauseof its low sensibility and positive predictive value.However, the high specificity and negative predictive value suggest thata normal test predict's an uncomplicated pregnancy.

P4.02 CERVICAL CANCER

P4.02.01ASSOCIATION OF RADIOSENSITIVITY WITH EXPRESSION OFTHYMIDINE PHOSPHORYLASE (TdRPase) IN CERVICALSQUAMOUS CELL CARCINOMAM. Sanezumi , H. Okada, T. Nakajima, T. Matsubara, K. Yasuda, H.Kanzaki. Dept. OB/GYN, Kansai Medical University, Osaka, Japan.

Objectives: To clarify the association between expression of TdRPaseand radiosensitivity in uterine cervical squamous cell carcinomas.Study Methods: The expression of TdRPase was evaluated byimmunohistochemical staining of tissue specimens from 27 patientsdiagnosed as stage III cervical squamous cell carcinomas followed byradiotherapy. They included 14 radiosensitive patients and 13 non-radiosensitive ones.Results: In radiosensitive group, the expression of TdRPase wasobserved in every 14 cases examined: 7 strongly positive cases, 3positive cases, and 4 weakly positive cases. In contrast, the expression ofTdRPase was seen only 7 out of 13 cases in non-radiosensitive group: 3strongly positive cases, 2 positive cases, 2 weakly positive cases, and 6cases were negative for the staining. The localization of TdRPase wasseen in both cytoplasm and nuclei, but the expression was not correlatedwith histological types of the cancers.Conclusions: In radiosensitive carcinomas, TdRPase expression wassignificantly higher and stronger than those in non-radiosensitivecarcinomas. This result suggested that TdRPase was a useful marker forpresuming the effect of radiotherapy in uterine cervical carcinomas.

P4.02.02CD40 IN CIN AND CERVICAL CANCER: ANIMMUNOHISTOCHEMICAL ANALYSIS REVEALING ANINTRIGUING EXPRESSION PROFILEG R Teale, Y-L Hock, D M Luesley, L S Young, Birmingham Women’sHospital, Birmingham, UK.

CD40 is a member of the tumour necrosis factor receptor superfamily.There is growing interest in the role of this antigen in carcinogenesis.CD40 positive carcinoma cell lines of ovarian, cervical, bladder andsquamous epithelial origin all respond to CD40 ligation with aninhibition of cell growth.Objectives: To investigate the expression of CD40 in a premalignantcondition, cervical intraepithelial neoplasia (CIN).Method Cervical specimens from 76 women were analysed byimmunohistochemistry.Results: In normal epithelium CD40 expression is either absent orconfined to basal cells. Expression in both low-grade and high-gradesquamous intraepithelial lesions and in advanced invasive cancer issignificantly increased above normal epithelium. Microinvasive lesionshowever show a consistently reduced expression despite the appearanceof high level expression in areas of CIN 3 from which the microinvasivedisease arose. HLA Class II expression is low in low-grade lesions andprogressively increases from CIN 2 to CIN 3 and remains high in bothmicro and advanced invasive disease.Conclusions: The increase in CD40 expression between normalepithelium and squamous intraepithelial lesions raises the possibility ofthis antigen having a role in the progression of HPV induced lesions.The consistent reduction in areas of microinvasion as compared withmore advanced cancer or high-grade CIN is a novel finding which doesnot appear to be the result of generalised immune upregulation asdemonstrated by the HLA Class II results. It may reflect an alteration inHPV directed transcription events. The finding of an alteration in theexpression of this antigen at the earliest stages of squamous cancer raisesthe possibility that this antigen has a pivotal role in carcinogenesis andmay be amenable to therapeutic intervention.


P4.02.03CERVICAL CANCER: FEASIBILITY AND PRELIMINARYRESULTS OF SIX CASES UNDERGOING LAPAROSCOPICASSISTED RADICAL VAGINAL HYSTERECTOMYM. Pinho de Oliveira , H. Carneiro de Oliveira, L.A. Melki, StateUniversity of Rio de Janeiro, R. Coelho neto 55/201, Laranjeiras, Rio deJaneiro, Brazil, 22231-110.

Objectives: The aim of the study was to evaluate any recurrency ofcervical cancer after laparoscopic assisted radical vaginal hysterectomyStudy Methods: Six women between 24 -48 years were prospectivelyfollowed for at least one year (1-4 years). Three cases were classified asFIGO Ia2 and three as Ib1 (< 3 cm). Five cases were epidermoidcarcinoma and one case adenocarcinoma. No adjuvant therapy wereused postoperatively.Results: Laparoscopic phase consisted of pelvic lymphadenectomy(common iliac, external iliac, hypogastric and obturatory vessels),uterine vessels ligature and ureteral dissection. One case was associatedwith a myoma (6 cm) and severe adhesion. The ovaries were preservedin one case (youngest patient) and they were fixed laterally and in ahigher position. Laparoscopic duration time was from 220 to 300 min(mean 240 min). The vaginal phase ranged from 60 to 120 min (mean 90min). No transfusion were necessary. Postoperatively no infections orfistulae were found. Hospital stay ranged from 3 to 7 days (mean 5days). Number of lymphonodes retrieved varied from 13 to 18. None ofthem were metastatic. In a follow up of 1 to 4 years (mean 2 years) allpatientes are alive and no recurrencies were noted.Conclusions: This study demonstrate the feasibility of the technique.Larger studies are encouraged with 5-year survival as the event ofinterest

P4.02.04CHEMOTHERAPY IN RECURRENT OR ADVANCED CERVICALCANCERM. Gonzalez Viciedo , C. Navarro, B. Certa, R. Yazigi, R. Castilla, J.Garrido, S. Prado, Dept. OB/GYN, Chemotherapy Group, NationalInstitute of Cancer, Santiago, Chile.

Objective: During the past years, treatment in cervical cancer has beenmainly surgery and radiation therapy and to a lesser degree,chemotherapy. Currently, the last one has become more important incoadyuvant treatment. Chemotherapy is the only treatment observed forthose cases with metastasic disease or local recurrence with noindication of surgical or radiation therapy. In a review of the literature,the rate of response to chemotherapy of the squamous tumors of thecervix reaches the 25% with no evidence of improvement in life qualityor survival. The aim of this study is to present the experience ofchemotherapy treatment in cervical cancer in the National Institute ofCancer in Chile.Study Methods: We analyzed 21 patients with cervical cancer in theperiod between January 1995 and July 1999 who met the followingcriteria: recurrence or persistence of disease during or after the standardtreatments with surgery or radiation. The data was collected from thepatients’ records and analyzed through the programs File Maker 4.0 andStatView 4.5.Results: Among the 21 patients, 16 presented recurrence of disease and5 presented disease persistence. In the recurrence group, there were 15cases of squamous cancer. The stages were 1 case lb1, 2 cases lb2, 8cases llb and 4 cases lllb. The treatments were 1 case surgery, 3 casessurgery plus radiation and only radiation 11 cases. The average free timeof disease was 36.8 months (6-240 months). The recurrence places weremostly cervix, vagina and paracervical tissues. The chemotherapy drugused was Cis platino in all cases, doses of 75 mg/m2 in 15 patients and100 mg/m2 in one case. There was no serious toxicity in our serie. Therewas one complete response, 2 partial response and no response in 12patients. In the persistence group, all the 5 cases were squamoushistologic type. The stages were lb1 2 cases, llb 1 case, lllb 2 cases. Thedrug used for chemotherapy was Cis platino in all cases at 75 mg/m2dose. All the patients presented mild or moderate toxicity. There was noresponse to chemotherapy in 4 patients.Conclusion: The standard treatments of cervical cancer are surgery andradiation with participation of chemotherapy especially in coadyuvanttherapy. The indications for chemotherapy are distant metastasiscdisease, recurrence disease which cannot be treated by surgery orradiation and coadyuvant with radiation therapy. The results of the use

of chemotherapy in recurrence and persistence disease have failed toshow improvement in quality of life or survival rate. The drug mostlyused is Cis platino. The results of the National Institute of Cancer inChile following the international guides have failed to show response orbetter survival rates.

P4.02.05COMPARISON BETWEEN HYDROXY-UREA (HU) ANDMITOMYCIN-C (MMC) AS CHEMOTHERAPY ADJUVANT ONCARCINOMA OF THE UTERINE CERVIX (CUC)RADIOTHERAPYM.T. Sutoto , H. Kristanto, E.W. Ambari, Dept. OB/GYN, DiponegoroUniversity, Dr. Kariadi Hospital, Semarang, Indonesia.

Sutoto et al. (1987) reported that MMC adjuvant gave better results inthe treatment of CUC radiotherapy. Piver (1989) also reported goodresults on CUC radiotherapy by giving HU as radiomimetic agent.Objective: To compare the results of treatment of HU and MMC aschemotherapy adjuvant on CUC radiotherapy.Study Methods: A prospective randomized clinical trial was carried outon epidermoid CUC patients stage III-B who were treated withradiotherapy. One group got high dose MMC (49) and the other group(34) got HU as described by Piver et al. The study began from June 1,1997 until December, 1998, and then followed-up until November,1999, at Dr. Kariadi Hospital. Survival of patients were calculated withKaplan Meier logrank test. Characteristics of patients and complicationswere calculated with X2 and t-Student tests as appropriate.Results: No difference in characteristics, which consist of age (p=0.98),hemoglobin level (p=0.994), histological radiation response (p=0.1),types of radiotherapy (external Co with/without Cs after loading)(p=0.517), were found. There were no differences in the survivalbetween those 2 groups (p=0.677). No differences in complications werefound: hematology (p=0.989), gastrointestinal (p=0.457), and cutaneus.No pelvic fistula was found.Conclusions: No significant differences were found between thecharacteristics among those 2 groups, resulting no significant differencein survival between those 2 groups. There were also no differences incomplications found among those 2 groups of patients, but MMC ismore expensive; on the other hand HU needs more discipline in takingregularly.

P4.02.06CONSERVATIVE SURGICAL TREATMENT OF INVASIVECERVICAL CARCINOMA IN YOUNGER WOMENL. Tasic , N. Prokic, N. Antic, S. Runic, V. Rajkovic, S. Jankovic, Z.Perisic, R. Radosavljevic, T. Moskovic, R.Lukic, F. Canovic, Dept.OB/GYN, Clinic “Narodni Front” School of Medicine University ofBelgrade, Belgrade, Yugoslavia.

Objectives: The aim of this study is to evaluate the possibility of anapplication of the conservative surgical treatment in younger patientssuffering form the invasive cervical carcinoma stage I-A according tothe FIGO classification, motivated for the childbearing.Study Methods: There were 12 patients under 30 years of age operatedin our Clinic during the three years period. In the first act, the conisationdue to the diagnosed invasive squamous epithelial carcinoma of theuterine cervix, stage I, N-1, was done in all the observed patients.Afterwards in the second act, the amputation of the cervix together withthe bilateral lymphadenectomy in the small pelvis was performed in allthe patients.Results: In seven patients (58%) the hystopathological diagnosis was:chronic cervicitis in the amputated part of the cervix; at the same timebetween 12 to 19 lymph nodes obtained from the obturatory fossaeswere without elements of tumorous tissue. For these patients theamputation and the bilateral lymphadenectomy was the definiteoperative treatment. In three patients (25%), the early stromal invasionup to 3 m was discovered; also there were between 12 and 18 lymphnodes without elements of the tumorous tissue. For these patients theamputation of the uterine cervix with bilateral lymphadenetomy was thedefinite treatment. In two patients (17%), the invasive squamousepithelium carcinoma of the uterine cervix (G-2, N-) was discovered inthe part of the uterine cervix. In one patient there were three positivelymph nodes on the left side out of totally 16 (3/16). Besides this, therewere no changes in 18 lymph nodes in another patient. Both patients


were subjected to the hysterectomy with the observation of the adnexa inthe third operative act. All patients had the controle check-up(colposcopy, PA, coller-doppler of the small pelvis) and all thelaboratory analyses are within the normal range of today.Conclusions: In the younger patients suffering form the invasivecarcinoma of the uterine cervix during the reproductive phase, motivatedfor the childbearing, the conservative surgical treatment with bilaterallymphadectomy in the small pelvis may be applied. In our group ofobserved patients it was the definite operative procedure in 83% ofcases.

P4.02.07DIAGNOSIS OF MINIMAL DEVIATION ADENOCARCINOMA OFTHE CERVIX: A REAPPRAISALT. Toki (1), K. Ito (1), S. Fujii (2)(1) Dept. OB/GYN, Shinshu University of Medicine, Matsumoto,

Japan.(2) Kyoto University Faculty of Medicine, Kyoto, Japan.

Objectives: A precise preoperative diagnosis of minimal deviationadenocarcinoma (MDA) or adenoma malignum of the uterine cervix isoften difficult because hey closely resemble normal cervical glands inhistological features. The aim of the present study was to investigate thebiological differences between MDA and normal cervical glands, and toestablish a rational clinical approach to the diagnosis of MDA based onimmuohistochemical, cytological, and magnetic resonance image (MRI)findings.Materials and Methods: Sixteen cases of histologically confirmed MDAwere studied. Immunohistochemical studies were performed on MDAand normal cervical glands using HIK 1083 (monoclonal antibodyspecific for pyloric gland mucin), anti-estrogen receptor (ER), and anti-CA125. In cytology specimens, cytologic findings were comparedbetween MDA and normal cervical glandular cells or gastric mucosalcells. MRI films were also reviewed in MDA cases.Results: Immunohistochemically, MDA expressed stomach-specificmucins and showed a loss or decrease of ER and CA125 expression, butno stomach-specific mucins. Cytologically, MDA cells often hadyellowish intracytoplasmic mucins, as did gastric mucosal cells, whilenormal cervical glandular cells had pinkish mucins. The yellowishmucins were positive for HIK 1083. MRI images of MDAs indicatedfluid accumulation within the endometrial cavity and/or the vaginalfornix, and cervical multi-cystic lesions often with irregular margins tothe cervical stroma.Conclusions: MDA loses müllerian-type differentiation and showsdifferentiation toward a gastric-type epithelium. Clinically, a correctpreoperative diagnosis of MDA can be achieved by synthetic evaluationof immunohistochemisty, cytology, and MRI in those suspected ofhaving MDA.

P4.02.08EFFECT ON HORMONAL THERAPY IN PATIENTS WITHINOPERABLE ENDOMETRIAL CARCINOMAU.U. Tabakman , A.G. Solopova, A.M. Chabrov, A.D. Makatsaria, Dept.OB/GYN, Sechenov Moscow Medical Academy, Moscow, Russia.

Under our observation were 31 patients with endometrial carcinoma. Allpatients were postmenopausal in age 51-80 years old (mean 67). In all31 cases was diagnosed 1 stage of endometrial carcinoma, confirmed byCT-scan and US. All patients were inoperable due to different extra-genital diseases and were recommended for conservative treatment.Seventeen patients received 17-oxyprogesteron and constituted the firstgroup. Fourteen patients of the second group refused all therapy optionsand had no treatment. There was no difference in age and options andcontradiction to radical treatment (specter of combined pathology)between these two groups.Rapid disease progression was mentioned in eight patients in the firstgroup and in 6 patients in the second group. In other cases, slow cancerprogression or no progression was seen. Six patients on hormonaltherapy had serious thrombotic complications including myocardialinfarction (2), deep venous thrombosis (2), thrombotic stroke (2), whichled to lethal outcome in 2 cases. No cases of thrombotic complicationswere seen in the second group.

Use of high dose progesterone as single agent treatment in patients withendometrial carcinoma is not effective and can cause serious thromboticcomplications, with a possibly lethal outcome.

P4.02.09EFFECT OF LOCAL HYPERTHERMIA COMBINED WITHPACLITAXEL ON MICE INOCULATED WITH U14 CARCINOMACELLSQ. Sun , L. Liu, Tianjin 2nd Central Hospital, Tianjin, China.

Objective: To investigate whether the paclitaxel and local thermotherapycombining therapy can delay the growing U14 (a kind of cervical cancercell).Study Methods: 40 mice, female, with weight of 25-30 g each wereinoculated with U14 in the thigh. When the volume of tumor wasreaching 110 mm3, these mice were divided into the paclitaxel group (20mg/kg injected into the abdominal cavity); thermotherapy group (treatedwith microwave hyperthermotherapy apparatus of Model 2450 MHz at44°C for 30 min, twice a week for only one week); paclitaxel andthermotherapy combining group (treated by the methods employed inabove 2 groups); control group (without any treatment).Results: Once the tumor volume reached 1000 mm3 and 2000 mm3, thetime of tumor growth delay (TGD) in combining therapy group was anaverage of 3 days and their inhibitive rate was 58% and 40%respectively. By optic microscope examination, the widespreadcoagulation necrosis, vacuole degeneration of cancer cell, interstitialfibrous hyperplasia, microvascular dilatation and venule blood stasis intumor tissues were mostly presented in combining therapy groupcompared with other groups. By electron microscope, the nucleusdegeneration of cancer cell, hyper-lysome, degranulation of roughsurfaced endoplasmic reticulum and membrane damage were obviouslydemonstrated in combining therapy too.Conclusions: It was found that the hyperthermotherapy can add to theeffect of mere treatment with paclitaxel and the combining effect is evenbetter than that it was treated by hyperthermotherapy and paclitaxelsolitarily.

P4.02.10GYNECOLOGICAL ONCOLOGICAL SURGERY WITHLIPECTOMYA. Olejek , D. Wala, J. Zamlynski, A. Michalska, J. Rzempoluch, Dept.OB/GYN, Silesian University School of Medicine, Bytom, Poland.

Objectives: Lipectomy is an operative procedure consisting of removalof adipose tissue from abdominal integument in order to facilitateexposure of the small pelvis in massively obese patients. The aim of thestudy was to establish the safety and efficiency of lipectomy at the timeof surgery for uterine cervix and body cancer.Study Methods: Between 1992 – 1999, 60 laparotomies with lipectomyin our department were performed: in 7 cases for cervical cancer I b or IIa, in 53 cases for endometrial cancer stage I-III G1-G3. The lipectomyprocedure was carried out using the modified method described bySchrimpf. Patients were aged 35-73 years, BMI was 32-62 (mean 42),mean body mass was 106.8 kg. Among these patients 47 women(78.3%) underwent brachy-HDR therapy before surgery. Most of theoperated women suffered additional coexisting ailments. 15 patients hadpreviously at least 1 laparotomy. All patients received antithromboticprophylaxis and antibiotics.Results: The following surgical procedures were performed: 11 radicalhysterectomies after Wertheim-Meigs method, 17 hysterectomies, 31hysterectomies with pelvic lymphadenectomy and 1 also with periaortallymphadenectomy. The mean surgery procedure time was 169 min.Blood transfusion was necessary in 22 patients, but it was connectedalso with the extent of abdominal procedure. The closed suction drainswere applied. In 50 (83.3%) patients wound healed up per primam, in 10(16.7%) cases per secundam. The mean time of final wound healing was15.8 days per primam and 30 days per secundam. One patient diedbecause of pulmonary embolism on 2nd day after surgery and anotherone because of myocardial infarction. Both of them had endometrialcancer, morbid obesity, diabetes mellitus, morbus ischaemicus cordis.They were disqualified from radiotherapy because of uterus enlargementand adnexal mass. In the studied group there was no injury of urinarytract, intestines or large vessels. In 15 patients (25%) metastatic cancerin lymph nodes was found.


Conclusions: The benefit of lipectomy is the improvement of operativeexposure for the gynecologic oncological procedures, which enablesaccess to small pelvis organs. Careful selection of those patients whowould benefit from this procedure is important.

P4.02.11HORMONE REPLACEMENT THERAPY (HRT) ON SPECIALCONDITIONS: CERVICAL NEOPLASIAMartins , FM; Fonseca, AM; Cambraia, CPP; Chuery, ACS; Bagnoli,VR; Poveda, E & Pinotti, JA. Dept. OB/GYN., São Paulo UniversityMedical School, São Paulo, Brazil

Objective: To determine the effect of HRT in patients treated forcervical carcinoma.Methods: A total of 15 patients who had been treated for cervicalcarcinoma (from cervical carcinoma in situ to stage IIIb) and receivedHRT were included in this study. Twelve patients were treated withWertheim-Meigs surgery and received conjugated estrogens 0,625mg/day continuously, 3 were treated with radiotherapy and receivedconjugated estrogens 0,625/day continuously plus medroxiprogesterone5mg/day for 10 days. The mean patients’ age was 45,7 years and thefollow-up time ranged from 6 months to 13 years (mean 3,6 years). Thefollowing parameters were evaluated and compared before and after 3,6years of HRT: Kupperman index (KI), body mass index (BMI), FSH,LH, prolactin, E2 , serum glucose, lipid-lipoprotein profile, testosterone,androstenedione, DHEAS, Bone Mineral Density (BMD), transvaginalultrasonography, and mammography. Results

Before HRT After 3,6 years ofHRT

All values are averagesKI 23,33 14,2BMI 25,56 25,6FSH 71,95 51,08LH 28,15 22,15Prolactine 6,38 7,56E2 24,44 38,3Serum glucose 88,07 89Total cholesterol 219 193,2HDL – chol 48,92 55,88LDL – chol 144 105,55VLDL – chol 31 21,11Testosterone 30,92 36,2Androstenedione 0,9 4,2DHEAS 306,9 97,2FSH 1,9 3,15

Only one patient had recurrence of the cervical neoplasia, and 3 patientspresented with benign breast nodule.Conclusions: This study showed an improvement in patients’ climatericsymptoms and laboratorial profile, with only one patient presentingrecurrence of cervical neoplasia.

P4.02.12HUMAN PAPILLOMA VIRUS (HPV) PLASMA DNA IN PATIENTSWITH CERVIX CANCER: A POTENTIAL MARKER OF MINIMALRESIDUAL DISEASE.C.López-Graniel , A. Dueñas, A. Carillo, L. Fresnedo, L.M. Hinojosa, C.Rojas, A. Sánchez-Navarro, C. Trejo, B. Segura, M. Lizano, InstitutoNacional de Cancerología, San Fernando No. 22, Mexico City, DF,Mexico, 14000.

Objectives: Cervix carcinoma is the main cause of cancer death inMexican women. HPV is implicated in its development. There is not yeta useful marker of minimal residual disease to detect early recurrences.We have determined the feasibility of amplifying HPV sequences fromthe plasma DNA in patients with cervix cancer.Study Methods: DNA was obtained from the plasma of 34 patients withuntreated cervix cancer irrespective to clinical stage, and 24 patientswith proven HPV infection but no invasive disease, using proteinase Kdigestion, phenol-chlorophorm extraction and ethanol precipitation. Toverify the quality of DNA a fragment of the b-globulin gene wasamplified. HPV sequences were amplified using the primers LICI-LIC2and the positive samples were also typified using primers specific fortypes 16 and 18.

Results: HPV sequences were amplified in 70% of the patients withcancer and the PCR was negative for the 24 control women. There wasno correlation between the DNA amplification and clinical stage or viraltype; however, adenosquamous tumors were more frequently negative.Conclusions: Detection of HPV DNA in plasma is specific for patientswith invasive cervix cancer. It could be a marker for minimal residualdisease and for early detection of relapse.

P4.02.13LATE RECURRENT CARCINOMA OF THE UTERINE CERVIXE. Miyagi (1), H. Nakayama (2), R. Onose (2), H. Kato (2), M. Hatta(2), K. Sugiura (2), K. Udagawa (1), T. Nakazawa (1), I. Gorai (1), F.Hirahara (1)Dept. OB/GYN, Yokohama City University School of Medicine,Yokohama, Japan.Dept. GYN, Kanagawa Cancer Center, Yokohama, Japan.

Objectives: The aim of this study was to reveal the clinicopathologicfactors associated with the late recurrent cervical cancer occurring in 1-2% of the cervical cancer cases.Study Methods: 25 patients with the late recurrent cervical cancer morethan 5 years after the initial treatment were reviewed. The modalities ofthe treatment for the initial and the recurrent tumors were evaluatedtogether with the clinical courses.Results: As for the initial treatment, hysterectomy was performed in 10cases (40%), and 15 cases (60%) received irradiation therapy. Thehistological types of the primary lesions consisted of squamous cellcarcinoma in 23 cases and adenocarcinoma in two cases. The recurrencewas noticed during 6-29 years after the initial treatment. The first relapselesions were found in the intra-pelvic cavity in 16 cases (64%), and inthe extra-pelvic sites in 9 cases. Vaginal cytology, tumor makers, chestX-rays were helpful to detect the lesions in the cases without anysymptoms. Irradiation therapy alone (13 cases) and the combination ofsurgery, irradiation and/or chemotherapy (6 cases) were performed totreat the recurrent diseases. 16 cases (64%) had died of the diseases, 6(24%) in remission, and 3 cases (12%) are alive bearing the recurrenttumors.Conclusion: Long-term careful follow-up is important to detect the laterecurrence. Although the prognosis was generally poor, combinedtreatments of surgery, irradiation and chemotherapy enable some casesto prolong the survival time.

P4.02.14MICROSATELLITE INSTABILITY IS A LATE EVENT IN THECARCINOGENESIS OF UTERINE CERVICAL CANCERM.Nishimura , H. Furumoto, T. Kato, T. Aono, The University ofTokushima, 3-18-15 Kuramoto-cho, Tokushima, Japan, 770-8503.

Objectives : The purpose of this study was to elucidate the role ofgenetic instability and LOH in the progression of cervical cancer, andalso to analyze for correlations between these genetic abnormalities andthe clinicopathological characteristics of cervical cancers.Study Methods: Seventy-eight DNA samples were obtained from 31carcinoma in situ(CIS), nine microinvasive carcinoma, 38 invasivecancers. Seven highly polymorphic microsatellite markers representingthe chromosome 3p, 6p and 6q arms were examined by PCRamplification.Results: Microsatellite instability was detected in eight of 35 (22.9%)invasive cancers, and in one of 37 (2.7%) early stage cancers(microinvasive cancer and carcinoma in situ). The incidence of MI wasstatistically higher in invasive cancers (P<0.02). On the other hand, lossof heterozygosity (LOH) of chromosome 3p was identified in 6/41(14.6%) invasive cancers and in 3/27 (11.1%) carcinoma in situ. Therewas no statistical difference between the two groups. There were nosignificant correlations between the presence of MI or 3p LOH andclinicopathological characteristics including the histological type, FIGOstage, depth of myometrial invasion, lymphovascular involvement,lymph node metastasis and recurrence.Conclusions: Our results indicate that genomic instability is a late eventduring the carcinogenesis of cervical cancer, and associated with theconversion of CIN to invasive phenotype. To the contrary, LOH ofchromosome 3p plays an early role in the development of cervicalintraepithelial neoplasia. No significant correlation was observed


between the presence of MI or LOH and clinicopathologicalcharacteristics.

P4.02.15P53 AND C-MYC EXPRESSION AS BIOLOGICAL MARKERS FORPOOR PROGNOSIS IN INVASIVE CERVICAL CARCINOMAS.Brenna (1) , L.Zeferino (2), G.Pinto (2), E.Martinez (2), (1) MaternityHospital Leonor Mendes de Barros, Av Celso Garcia 2477 – Belém, SãoPaulo, Brazil, 03015-000, (2) The State University of Campinas, BarãoGeraldo – Campinas, São Paulo, Brazil.

Objectives: The aim of this was determine the prognostic value of p53and c-myc protein expression in cervical carcinoma among Brazilianwomen.Study Methods: Two hundred and twenty women were included in thiscohort study, from 1992 to 1994, whose had cervical squamous cellcarcinoma, FIGO stage Ib to IIIb and followed at least 5 years. Theparaffin-embedded tissue was processed by immunohistochemistry forp53 (DO7) and for c-myc (9E10). Sample's characteristics werecompared by Anova or Pearson test, accepting p=0.05. Hazard ratio wascalculated. Disease free and overall survival were shown by Kaplan-Meier curves and compared by Wilcoxon or Log-rank test.Results: The age of women ranged from 25 to 89 years old and theywere diagnosed as 22%, 28% and 50% in stage I, II and III, respectively.P53 expression was detected in 35% and c-myc in 65% of them. Womenwho had positive p53 had higher risk of recurrence and shorter diseasefree survival (p<0.01), in stage II. However when they were studied aftertreatment, there were higher risk of recurrence among women who hadpositive c-myc, shorter disease free survival (p=0.01)and overallsurvival (p=0.06), in all stages.Conclusions: Protein expression of p53 and c-myc could be biologicalmarkers for poor prognosis in invasive cervical carcinoma and theymight be used as screening. Meanwhile, should be better to analyzemutations of these genes and their role in prognostic.

P4.02.16PHASE II STUDY OF IRINOTECAN COMBINED WITHCISPLATIN AS NEOADJUVANT CHEMOTHERAPY IN PATIENTSWITH LOCALLY ADVANCED CERVICAL SQUAMOUS CELLCARCINOMAK. Imaishi , T. Sugiyama, K. Ushijima, T. Kimura, Dept. OB/GYN,Kurume University, Kurume, Japan

Objectives: To evaluate the repose rate and toxicity of the combinationof CPT-11 and cisplatin in a neoadjuvant setting, a phase II study wasconducted regarding the regimen of this combination in patients withlocally advanced cervical cancer.Study Methods: patients with previously untreated stage Ib2, IIb, or IIIbsquamous cell carcinoma with good performance status. CPT-11 (60mg/m2) was administered intravenously on days 1, 8, and 15, followedby cisplatin (60 mg/m2) given intravenously on day 1. Treatment wasrepeated every 4 weeks for a total of two cycles. Following NAC,radical hysterectomy with lymphadenectomy (RH) was performed in allpatients with stage Ib2 and IIb disease. RH was used in patients withstage III disease only if they responded to chemotherapy and localdisease was considered resectable.Results: Among 28 eligible patients (median age: 58 years), 5 showedcomplete response (18%), 19 showed partial response (68%), for anoverall response rate of 82% (95% confidence interval, 64% to 92%).Stable disease was observed in 4 cases (14%) and progressive disease inone (4%). Of the 10 patients with stage IIIb disease responded to NAC,9 patients underwent RH because cancer-free space between the tumorand pelvis was observed on rectal examination and local disease wasconsidered resectable, and the other one patient received radiotherapybecause of the advanced age (75 years). The median time to failure andmedian survival time have not been reached. Of the 56 treatment cyclesadministered, diarrhea and grade 3 or 4 neutrophenia were observed in10% and 75% respectively. There were no therapy-related deaths.Conclusions: The combination of CPT-11 with cisplatin is a promisingregimen for NAC in locally advanced cervical cancer. The toxicities ofthis regimen are well tolerated.

P4.02.17POLYMORPHISM IN CODON 31 OF p21 AND CERVICALCANCER SUSCEPTIBILITYH.P. Lee , J.W. Kim, J.W. Roh, N.H. Park, Y.S. Song, S.B. Kang, Dept.OB/GYN, Seoul National University Hospital, Seoul, Korea.

Objectives: Recently it was suggested that p21 codon 31 arginine alleleappears to be associated with an increased risk for adenocarcinoma ofendometrium and lung, few studies have determined the allele frequencyand disease association in primary cervical cancers. Here we analyzedwhether the certain allele of p21 codon 31 might be associated withincreased risk of cervical cancer development in Korean women whetheror not infected with HPV16 or 18.Study Methods: We used the tissue or cytologic specimens derived frompatients with invasive cervical cancer (n=113) composed of twodifferent histologic groups; squamous cell carcinoma (n=69) andadenocarcinoma (n=44), cervical intraepithelial neoplasia (CIN) III(n=101) and noncancer control (n=98). The presence of HPV DNAs incervical specimens was ascertained by E6, E7-based PCR. For thedetermination of p21 polymorphism, genomic DNA extracted fromcervical specimens were examined by PCR-RFLP assay using BsmAI.We compared the distribution of p21 allele and analyzed the associationof this polymorphism with cervical cancer susceptibility. Statisticalanalyses were performed using the software package.Results: There was no significant difference in the frequency of codon31 alleles between the squamous cell carcinoma, CIN III, and noncancercontrol groups (c2 = 2.28, p=0.684, df=4). A significant increase of theSER/Ser genotype frequency was found in adenocarcinoma patientscompared with the noncancer control group (Student’s t test; two-sidedp=0.047) and when the patient’s group was stratified according to HPVinfection status, the significance increased further. The odds ratio was2.52, 95% CI = 1.1-5.54, when comparing adenocarcinoma patients withnoncancer control. Thus, the p21 codon 31 Ser allele appears to beassociated with an increased risk for adenocarinoma of uterine cervix.Conclusions: In contrast to previous studies suggesting increased risk ofcancer in patients with Arg allele, we found that codon 31 Ser allele ofthe p21 gene would be a risk factor for the development of cervicaladnocarcinoma. To clarify this point, further study is needed todiscriminate the possible functional difference between the two forms ofp21, especially in relation to high-risk HPV infection status.

P4.02.18RELATIONSHIP BETWEEN VASCULAR ENDOTHELIALGROWTH FACTORS (VEGF) AND TISSUE HYPOXIA INCERVICAL CANCERH. Tanaka (1), T. Musha (1), M. Jinno (1), H. Kosuge (1), M. Iwashita(1), Y. Nakamura (1), Y. Yasuda (2), T Nagai (3)(1) Dept. OB/GYN, Kyorin University School of Medicine, Tokyo,

Japan(2) Dept. Anatomy, Kinki University School of Medicine, Osaka,

Japan(3) Nagai Clinic, Tokyo, Japan

Objectives: Vascular endothelial growth factor (VEGF) generallycontributes to tumor proliferation and metastasis by paracrinemechanism in vivo. VEGF is activated by the tissue hypoxia. Weexamined immunohistochemically whether VEGF is involved inangiogenesis in uterine cervical cancer, and also examined the spacialdistribution pattern of capillary endothelium in malignant tumors andnormal controls. Since VEGF mRNA is activated by the tissue hypoxia,we determined the content of adenosine triphosphate (ATP) in themalignant and control specimens.Study Methods: Surgically resected materials were used, 15 cases ofsquamous cell carcinoma of the cervix and 10 corresponding controls.Specimens were processed for immunostaining. Monochronal antibodyto human VEGF (R&D) and to human factor VIII (DAKO) were used.Tissue ATP was separated by anion exchange column (Toyo Soda) inhigh pressure chromatography.Results: The content of ATP was obviously lower in cancer specimenthan in normal controls. In normal controls, VEGF was detected inepithelial cells of the cervix and epithelium of capillaries and arterioles.While in squamous cell carcinoma, additionally, core cells ofproliferating squamous cells and fibroblast-like cells in the stromashowed positive reaction to VEGF.


Conclusions: In this study, we present strong expression of VEGF withvivid angiogenesis in cervical cancer. VEGF in the cervical cancerappears to be produced by the malignant cells themselves and maycontribute to angiogenesis. Low ATP level indicates the hypoxia in thecervix and appears to be a cause of the activation of VEGF.

P4.02.19ROUTINE CYSTOSCOPY IN STAGING CANCER OF THECERVIX: IS IT A MUST?A.N. Kekre , L.Seshadri, N. Kekre, Dept. OB/GYN, Christian MedicalCollege Hospital, Vellore, India.

Objectives: The aim of the study was to evaluate the usefulness ofcystoscopy in staging of cervical cancer.Study Methods: Charts of 669 women with cervical cancer werereviewed. Data regarding the clinical staging histology and cystoscopyfindings were reviewed. Statistical analysis was carried out usingSPSS/PC + statistical package for IBM PC.Results: Overall 36 patients had positive cystoscopy findings. In stage Iand IIa none of our patients had positive findings on cystoscopy.Bladder involvement was seen in 0.41% in stage IIb, 15.38% in stageIIIa, 7.19% in stage IIIb, 75% in stage IVa, 6.6% in stage IVb.Conclusion: was not found to be useful as a staging procedure in earlycervical cancer (stage I & IIa). It can be used selectively in patients withadvanced local disease (stage IIIb and above) or in patients who haveother indications for cystoscopy. However, prospective study would benecessary to define the role of cystoscopy in staging cervical cancer.

P4.02.20SMALL CELL NEUROENDOCRINE TUMOUR OF THE CERVIXMin Li Yeap , E.H. Tay, T.H. Ho. KK Women's and Children's Hospital,100, Bukit Timah Road, Singapore 229899.

Objectives: To study the patient characteristics, clinical course,treatment response of patients with small cell neuroendocrine tumour ofthe cervix.Study Methods: This is a retrospective review of all cases of small cellneuroendocrine tumour of the cervix diagnosed and treated in ourhospital. Clinical information such as age, parity, disease presentation,clinical stage, primary/adjuvant treatments, tumour recurrence andsurvival intervals were analysed.Results: There were 12 cases of small cell neuroendocrine cancer of thecervix, which account for 0.94% of the 1270 cervical cancers diagnosedwithin the study period. Their mean age was 53.1 year (32-79 year),mean parity was 3.7 (1-8). All but one patient presented with abnormalper-vaginal bleeding. Two patients had stage 1B, 2 had stage 2A, 3 hadstage 2B and 5 had stage 3B disease. Two patients had Wertheim’sradical hysterectomy, adjuvant chemotherapy and radiotherapy. Sevenpatients had irradiation and 2 had chemotherapy as their primary modeof therapy. One patient defaulted any treatment. The mean follow-upperiod was 9.8 months (1 to 44 months), the mean survival time was22.5 months and the median was 18.0 monthsConclusions: Small cell neuroendocrine cancer of the cervix is anaggressive tumour with an extremely poor prognosis. Multi-modaltherapy with surgery, radiation and chemotherapy should be employedto improve patient’s survival.

P4.02.21SURGICAL TREATMENT FOR CANCER OF THE UTERINECERVIX WITH PREVIOUS RADIOTHERAPYANALYSIS OF HISTOLOGICAL SPECIMENS ANDCOMPLICATIONSMakabe, S ; Nisida, ACT; Pinotti, JA & Fonseca, AM. Dept. OB/GYN,São Paulo University Medical School, São Paulo, Brazil

Background: The best method of treatment for invasive cancer of theuterine cervix is still controverse. In this prospective non randomizedstudy, the patients were treated by radiotherapy, and afterwards, theyunderwent a less radical surgery. The objective was to analyse thehistological specimes and complications of this combined therapy.Methods: The patients were divided into two groups: group I (31patients) received HDR brachyterapy dose of 2800 cGy delivered topoint. A and group II (35 patients) received HDR total dose of 1200

cGy. The patients of both groups received external radiotherapy to thewhole pelvis a total dose of 4500 cGy. Four to eight weeks after the endor radiotherapy, they underwent a less extensive surgical procedure.Piver I hysterectomy for stage IB and IIA and Piver II histerectomy forstage IIB (initial).Results: Histological analysis of group I, 28 patients (90,3%) showed noresidual tumor, two (6.5%) had microscopic residual tumor.Parametrium and lymph nodes were negative for disease. Group II, 23patients (65,7%) showed no residual tumor and 8 (8,6%) hadmicroscopic residual tumor. Lymph nodes were negative in 34 (97,1%)patients and positive in one (2,9%) patient. Parametrium was negative inall patients. There was statistic difference between the groups in thisanalysis. The incidence of urinary complications in group I was 5(16,1%) cases of urinary tract infection and group II, 4 cases (11,4%).Hydronefrosis 4 cases(12,9%) in group I and 4 cases (11,4%) in groupII. Ureterovaginal fistula, 2 cases (6,4%) in group I and 1 case (2,8%) ingroup II. Gastrointestinal tract, 5 cases (16,1%) in group I and 3 (8,5%)in group II. One case (2,8%) of leg edema in group II and no case ingroup I. We found no statistic differences between the complications ofthe groups and also when compared with a group of patients whounderwent just surgery with no previous radiotherapy.Conclusions: This study concluded that the presence of residual diseasein the surgical specimes was related to the total dose of brachytherapyreceived. In the period of 25,5 Months, we found no statisticallysignificant correlations between the complications of the two groups andalso when compared the complications with a group of patients whounderwent Wertheim Meigs surgery (Piver II hysterectomy modified).

P4.02.22THE CLINICAL RELEVANCE OF PLASMA HPV DNA INCERVICAL CANCERHuey-Jung Chen , Dept. OB/GYN, Tri-Service General Hospital, Taipei,Taiwan

Objective: Recently, we have disclosed a significant correlation betweenlocal HPV viral load and the size/severity of cervical precancer andcancer lesions. This study extended our observation of HPV viral loadsin both cervical swab/tumor tissues and plasma specimens in a cohort of93 women with normal or low-grade squamous intraepithelial lesion(LSIL)(n=11), high-grade SIL (n=12) and invasive carcinoma (ICC,n=26, 23, 12, and 9 for stage I to IV, respectively) of uterine cervix.Study Methods: High-risk type HPV DNA was quantitatively (incalibration, R=0.9994) determined by using the Hybrid Capture II kit(DIGENE) with a modified procedure.Results:1) The plasma viral load (indicated by RLU ratio, in which ratio 1

equals to 5000 viral DNA copies) of high-risk HPV wassignificantly (p=0.016 higher in HSIL (0.49 + 0.34 and ICC (0.53+ 0.92) than in normal/LSIL (0.22 + 0.11) groups, whereas no suchdifference was observed between HSIL and ICC, and among ICCof different stages.

2) With a cutoff value of 0.2 (or 1000 viral copies), the plasma HPVtest was able to detect cervical HSIL/ICC with a sensitivity of87.8% and a specificity of 72.7%

3) With the same cutoff value, the presence of HPV DNA in plasmapredicted an odd ratio of 1.2 (95% C.I. of 0.2-6.2) and 6.0 (95%C.I. of 2.0-18) for HSIL and cervical cancer, respectively.

4) Elder (> 40 years old) patients tends to have a higher and plasmaHPV viral load than the younger ones (p=0.046).

Conclusions: Plasma HPV DNA seems to be a valuable markerindicating the presence of HSIL or invasive cancer of uterine cervix. Thefeasibility of this blood test may much improve the low screening rate ofthe traditional Pap smear.

P4.02.23THE ROLE OF SCREENING OF CERVICAL CARCINOMA INCOMMUNITYS. Qian , Tianjin 2nd Central Hospital, Tianjin, P.R China.

It is important for a cancer patient to get early discovery, early diagnosisand early treatment, so that the cancer patient can have a thorough-goingcure or a longer survival period after treatment.


For this purpose, it is necessary to develop a screening of cervical cancerin the group of women in the community health organization (CHO),such as in the factories, villages, districts, etc.The steps were designed as follows:1. A booklet of elementary knowledge of cervical carcinoma was

worked out and distributed to the persons suitable to be surveyedand who are within the high risk group.

2. The CHO organized the above persons to fill in a series of formsabout their medical history, present illness and family history.

3. They are examined by physicians in the different departments.4. They are given further examinations, such as ultrasonic

examination, X-ray, photography, cytological examination andbiopsy, etc.

5. A final conclusion will be given for each person according to theabove examinations.

6. Every person suffering from cervical carcinoma is introduced to aspecial hospital.

7. Every one who has the pre-cancerous lesion should be registeredand checked regularly.

8. The CHO is the unit to organize and to train staff for everyscreening, and to keep in touch with the persons who have pre-cancerous lesions. In this way, patients suffering from cervicalcarcinoma can get early discovery, early diagnosis and earlytreatment.

P4.03 CESARIAN SECTION/MIDWIFERY

P4.03.01A NEW CONCEPTION OF DYSTOCIALuoda Ling , Second Jospital, Chongqing University of MedicalSciences, Chong-Qing, Sichuan, P.R. China

A new conception of dystocia is to put the abnormal pelvis, fetus anduterine contraction as etiology of dystocia, and to classify dystociaclinically into cephalic dystocia (dystocia in cephalic presentation),breech, transverse lie, complex presentation and shoulder dystocia.Outline of the new conception of dystocia is as follows:1. General considerations2. Etiology

2.1 Abnormal pelvis2.2 Abnormal fetus2.3 Abnormal uterine contraction

3. Clinical classification3.1 Cephalic dystocia

3.1.1 Persistent occiput-posterior3.1.2 Persistent occiput-transverse3.1.3 Direct occiput anterior and posterior3.1.4 Anterior assynclitism of occiput-transverse3.1.5 Face presentation3.1.6 Brow presentation

3.2 Breech dystocia3.3 Transverse lie3.4 Complex presentation3.5 Shoulder dystocia

Dystocia is traditionally divided into 3 categories: abnormal uterninecontraction, abnormal fetus and abnormal passage. But we know none ofthese 3 factors operated independently of others, especially in cephalicdystocia. The fact is that either the size or the diameter of the fetal headwhich presents to the pelvis, in such, that it cannot readily pass through,the uterus is often very responsive to these minor abnormalities, and thefails to contract efficiently, so that the abnormal labor is resulted. Asbreech and transverse lie are easy to discover, while cephalic dystocia isdifficlt to diagnose. In cephalic presentation, there is no clear cutdifference between normal and abnormla labors, it needs a period of trylabor. The obstetrician should be very careful to find out the earlyabnormal signs and give proper treatment to prevent cephalic dystocia.As 85% of dystocia is cephalic dystocia, it is better to emphasize it as animportant topic in dystocia.

P4.03.02ANALYSIS OF HIGH CESAREAN RATES IN KERALA, INDIA –CAUSE FOR CONCERNV. P. Paily (1), V. Vigayakumar (2)(1) Mother Hospital, Trissur, Herala, India.(2) MMM Hospital, Hunnamkulam, Thrissur, Kerala.

Objectives: Kerala State has achieved high health standards and isprojected as an example to other developing countries. This study was tofind out the trends in Cesarean births and its reasons.Study Methods: Personal letters addressed to Obstetricians all over thestate were used to collect data on mode of delivery and the reason forhigh cesarean rates for 1985 and 1995.Results: Data for 49 311 births in 1985 and 101 333 births in 1995 (i.e.30% of all births in 1995) were available.Overall, the cesarean rates rose from 18.5% to 25.3% in the 10 years.Break up of results to different types of hospitals shows that in the largecenters it remained unchanged (22%) whereas in the smaller privatehospitals having less than 1000 deliveries per year, it rose from 16.5% to28.5%. Since the majority of the births not reported to us (70%) woldhave taken place in such hospitals, the actual cesarean rate of the wholeState could be 30% or more.In ability to do cesarean at short notice and far of litigation werereported to increase elective cesarean section and this contributed to thephenomenal increase in rates.Conclusions: This study emphasizes the importance of monitoringcaesarian rates and its causes in developing countries. Remedialmeasures should be taken early, otherwise, alarming rates may getestablished.

P4.03.03ANTIBIOTIC PROPHYLAXIS AGAINST POSTPARTUMINFECTIONS IN CAESAREAN SECTIONM.J-Aldea , I.Branisteanu, G.Costachescu, University of Medicine andPharmacy, Cuza Voda str 34, Iasi, Romania, 6600.

Objectives: To evaluate the efficacy of different protocols of antibioticprophylaxis against postpartum infections in cesarean section patients.Study Methods: Retrospective study on 3634 C-section patients operatedin the period 1993-1997 in a university clinic. Patients were divided inthree groups: A- 863 cases (23.74%) receiving single doseantibioprophylaxis with ampicillin 2g and gentamycin 80 mg afterumbilical cord clamping, B- 1317 cases (36.24%) receiving 5 dayspostoperative antibioprophylaxis with ampicillin 2 g and gentamycin160 mg daily and C- 1454 cases (40,01%) without antibioprophylaxy.Main outcome measures were: development of postpartum endometritis,wound infections, urinary infections, thrombophlebitis and thehospitalization time.Results: The incidence of postpartum endometritis was 1,96% in groupA, 2,05% in group B and 4,74% in group C. The percentage of woundinfections was 0,81% in group A, 0,83% in group B and 2,26% in groupC. Urinary tract infections occurred in 0,92% of group A patients, 1,06%of group B patients and 10,04% of group C patients. Thrombophlebitisdeveloped only in group C (1,37%). Average hospitalization durationwas 6 days for group A, 6,74 days for group B and 7 days for group C.Conclusions: Single-dose intraoperative antibioprophylaxis decreasespostpartum infection rate and hospitalization time without developingbacterial resistance to antibiotics. Multi-dose postoperativeantibioprophylaxis is decreasing postpartum infection rate as well, but athigher costs and with risk of increasing bacterial resistance toantibiotics.

P4.03.04BREAST FEEDING – HOW MUCH DO THE MOTHERS ANDEXPECTANT MOTHERS KNOW – AN OVERVIEWB. Dutta (1), A. Dutta (2), R. Shaikhetkar (3), JLN Hospital andResearch Centre, Bhilainagar Durg, India.(3) Dept. OB/GYN(4) Dept. Anasthesia(5) Dept. Neonate

Objectives: In our society breast feeding is a tradition; it is the rulerather than the exception. Since the time of Acharya Charak, the fatherof Aurveda, ancient Indian Medicine, breastfeeding has been


recommended and taught by our elders. But in the last decade thefragrance of modernization has hampered its acceptance in our society.The aim of this KAP study is to spread knowledge about the subject byinteraction with expectant mothers.Study Methods: This study was conducted in antenatal OPDs of BSPHospitals, with 340 women included here. A questionnaire containing 20questions pertaining to breastfeeding was given and the women wererendered help to fill them out. It was noted that certain facts were newfor many women who were screened on it.Results: About 23% of women did not know about the speciesspecificity of milk, another 30% were ignorant about the utility ofcolostrum. About half of them had no idea about the frequency ofurination and about the number of motions passed by the breastfedbabies. The ignorance about the continuation of breastfeeding during themother’s minor illness was quite high.Conclusions: From this study we could assemble certain facts aboutbreastfeeding that should be explained to every pregnant lady and ouraim is to extend this project to the real cross section of the population.

P4.03.05CESAREAN SECTION FOR CLINICAL FETAL DISTRESS:LIMITATIONS OF CLINICAL DIAGNOSIS IN DEVELOPINGCOUNTRIESJ.I. Ikechebelu , Dept. OB/GYN, Nnamdi Azikiwe University TeachingNnewi Hospital, Nnewi, Nigeria.

A retrospective analysis of the Apgar scores at one minute of babiesdelivered by cesarean section for clinically diagnosed fetal distress in126 parturients was undertaken. 46 (36.5%) had an Apgar score of 7 andabove, 54 (42.8%) had an Apgar score of between 4 and 6 and 21(16.7%) had an Apgar score of between 1 and 3.The perinatal mortality rate of 39.7/1000 was lower than the figuresreported for the general population.The cesarean delivery in 36.5% of these parturients was not justified.This demonstrates the limitation of using clinical parameters alone in thediagnosis of fetal distress and in the selection of cases for cesareansection. The introduction of modern labor – monitoring facilities into ourpractice and the training of labor assistants in its proper usage willimprove diagnostic accuracy of fetal distress, thereby reducing theincidence of unjustified cesarean section in developing countries whereaversion to cesarean section is very strong.

P4.03.06CESAREAN SECTION AND ABRUPTIO PLACENTAE IN PERIODFROM 1985 TO 2000J. Efremovski , B.Boskovski, J. Kostadinov , Special hospital forOB/GYN Cair,Dizonska bb, 1000 Skopje, Macedonija

Objectives: The aim of our work is determination the rate of caesareansection as a way of finishing pregnancy comparing with perinatalmortality in the cases with abruptio placentae.Study Methods: This is retrospective analysis of 63853 deliveries duringthe 15 years (from 1985-2000). Mild forms of abruptio placentae are notalways noted in our medical documentation. That is why in analysis areincluded only severe forms of abruptio placentae. These cases wereanalyzed in aspect of: way of delivery, the age of patient, parity andbody weight of fetuses.Results: There were 465 abruptio placentae or 0,73% in last 15 years.236 deliveries finished with SC (51,26%). 129 (28,01%) fetuses weredead before admitting in hospital. Overall perinatal mortality was 32,18%.Conclusions: Our results show that aggressive management with SC insevere abruptio placentae is the most appropriate way of finishingdelivery for the fetus. Only in the cases where we expect promptdelivery (usually in pluripary) we can allow vaginal delivery. In suchcases the close monitoring of fetus is mandatory and ability ofperforming urgent SC must be continuously available.

P4.03.07COMPLICATIONS OF HOMEOSTATIC CESAREAN IN HIV+PREGNANT WOMEN VS.PROGRAMMED CESAREAN IN HIV-WOMENS Hermosid(1 ), M. Pesaresi (2), C.Terrones (3), C.Militano(4), J.C.Nardin(5), M.Rodriguez(6) Tocoginecologia Hospital Durand (1-2-3)Avda Diaz Velez 5044.Buenos Airs Maternity Martin-Rosario ArgentinaObjectives: To compare surgical complications between HomeostaticCesarean and Programmed Cesarean section.

Methods: Two hundred pregnant women were included in a cohort studydividing them in two groups; both were at 38th weeks of gestation undercesarean section. Group 1) 100HIV+ treated with Homeostatic CesareanSection plus antirretroviral treatment. Group 2) 100 H.I.V- treated withprogrammedCesarean Section.Both Groups were compared forhaemogram, urinalysis, urine culture before and after surgery andnumber of staying days, surgical and infectological complications.Results: No statistically signficative differences could be demonstratedby the 'T" Student Test (p<0,18).Conclusions: In our experience Homeostatic Cesarean Section does notincrease possible surgical complications in HIV patients.

P4.03.08ELECTIVE REPEAT CESAREAN SECTION VERSUS TRIALLABOR AFTER PREVIOUS CESAREAN SECTION: A COST-EFFECTIVENESS ANALYSISM.L. Garcia-Tansengco , San Antonio Village, Phillipines.

Objectives: Data have shown that approximately 60-80% of eligiblewomen with a previous low segment cesarean section will successfullydeliver vaginally after a trial of labor. The advantages of vaginaldelivery over abdominal delivery have been firmly established. It hasbeen shown that while the overall risk for complications were similar inwomen who underwent trial of labor as compared to those whounderwent an elective repeat cesarean delivery, the failed trial of laborgroup requiring emergency repeat cesarean delivery had the greatest riskfor morbidity. It has also been shown that performing an elective repeatcesarean section may not really be indicated most of the time sincevaginal birth after cesarean (VBAC) can be accomplished safely. Manyobstetricians, however, routinely perform a repeat cesarean sectionbecause of fear of uterine rupture. This paper hopes to assess whether anelective repeat cesarean section is cost-effective as compared with a trialof labor in averting a uterine rupture. The objective therefore is todetermine whether an elective scheduled repeat cesarean section is cost-effective compared to a trial of labor in terms of averting a uterinerupture.Study Method: The options of trial of labor after previous cesareansection and outright elective repeat cesarean section were set out in adecision analytic framework. A decision tree was constructed togetherwith the key decisions and the consequence of rupture under eachalternative. The probabilities for each option and their outcomes werebased on a meta-analysis of a number of trials. To complete the decisionframework, unit cost data and their quantities were obtained from thePhilippine General hospital where it is assumed the hypotheticalpregnant patients were admitted. Sensitivity analysis was performed tomake allowances for the uncertainties of the estimates used in theanalysis.Results: 531 patients eligible for a trial of labor were admitted to thePhilippine General Hospital in 1997. 28.1% successfully deliveredvaginally while 69.4% underwent repeat cesarean section. Effectivenessdata based on a meta-analysis by Rosen showed that the number ofuterine rupture averted by a trial of labor was 0.979 per patient while itwas .981 per patient for an elective repeat cesarean section. The drivingcost for a trial of labor comes from that incurred from the labor anddelivery room which constitute 80% of the total cost. For an electiverepeat cesarean section, it is from the cost incurred at the operatingroom, which accounts for 78% of the total cost. The failed trial of laborwas most costly, followed by a repeat CS. A successful trial of laborresulting in vaginal birth was least expensive. The cost effectivenessratio for a trial of labor was P10,225.97 ($254.44) per uterine ruptureaverted, while that for an elective repeat cesarean section wasP12,447.40 ($309.71) per uterine rupture averted. While the differencein cost-effectiveness between the two procedures was small at P2,221.43($55.27) per uterine rupture averted, the incremental cost-effectivenessratio in selecting an elective repeat cesarean section is P1.2 million


($29,858.17) per uterine rupture averted. The difference in risk ofuterine rupture between the two procedures is very small despiteevidence indicating that a failed trial of labor would have the highestrisk of rupture. It would be difficult to comprehend spending P1.2million to avert a uterine rupture.Conclusion: The results of the analysis support the premise that a trial oflabor is a safe and cost-effective approach to a pregnant patient with oneprevious low segment cesarean section. Women with a previoustransverse scar and without contraindications should always bepresented the opportunity to undergo a trail of labor.

P4.03.09HOMEOSTATIC CAESAREAN SECTION: A NEW SURGICALTECHNIQUE TO DIMINISH THE VERTICAL TRANSMISSIONM. Pesaresi(1) , S. Hermosid(2), C.Terrones (3), L.Saenz Vicuña(4)M.Leguizamon(5) Tocoginecologia, Hospital Durand(1-2-3). Avda.Diaz Federal Velez 5044(1405) Capital, Maternity Martín , Rosario(4-5) Argentina

Objectives: To show the Homeostatic Cesarean section, as a newsurgical technique to manage pregnant women infected with HIV virus.This is an Elective cesarean section with technical modifications. It isused in all patients plus antirretroviral therapy and breast-feedinginhibition.Methods: This study includes 170 HIV + pregnant women, underretroviral therapy.Homeostatic cesarean section is done without laborand intact membranes at 38 pregnancy weeks. It consist in themanagement of lower uterine segment keeping integrity of membranes,avoiding the massive contact betwen maternal blood and the fetusConclusions: This technique has shown to be useful, as it decreasesvertical transmission to less than 2%.

P4.03.10INTEGRATION OF TRADITIONAL BIRTH ATTENDANTS (TBAs)INTO MODERN FAMILY PLANNING SERVICES IN 2 LOCALGOVERNMENT AREAS IN NIGERIAI.F. Abdul , S. M. Belgore, FWACS, Nigeria.

Objective: Our purpose was to evaluate the effectiveness of TraditionalBirth Attendant (TBAs) as facilitators of enhanced modern familyplanning service delivery in rural areas with limited medical facilitiesand manpower.Study Design: Information Education and Communication (IEC), FocusGroup Discussion (FGD) and Community Mobilization were carried outwith selected TBAs in 2 local government areas of Kwara State, Nigeria,having a combined population of 526, 884. The TBAs were then used tocounsel and deliver non-prescriptive contraceptives as well as referpatients in need of prescriptive methods to 2 sessional clinics run by theauthors at each of the local government headquarters.Results: Base line survey revealed a high patronage of Traditional BirthAttendants and Herbalists (62.8%). Awareness of modern familyplanning methods was mainly through radio programs. Only 1.5% ofadolescents and 6.8% of couples use non-prescriptive modern familyplanning methods. Promiscuity is low and is confined to adolescentswho are more mobile (18.0%). Married women at average age 25 have3.25 children per head and polygamy is practices extensively by men(2.7 wives). After 11 months, knowledge of modern family planningmethods increased to 88% among adolescents and 95% among couples.Adolescents and couples embraced modern family planning methods inthe order of 8.6% and 58% respectively. IUCD, BTL and Norplant wereused by 56, 12 and 5 patients respectively at 2 sessional clinics locatedin each local government area headquarters. Problems identified werethat of abuse by some TBAs. Patients’ inability to bear cost,transportation problems from the distant villages and problem ofsustainability in terms of financial support.Conclusion: In rural area lacking manpower and facilities, TBAs canserve as very effective agents for enhancing modern family planningservice delivery.

P4.03.11IS THERE A RISK OF LOWER SEGMENT SCAR RUPTURE INPREGNANCY AFTER MULTIPLE CESAREAN SECTION?EG. Tamale-Sali , Dept. OB/GYN, Ahmadi Hospital, Ahmadi, Kuwait.

Objectives: The purpose of this retrospective study was to examine thehypothesis that there is a risk of scar rupture during pregnancy after 3 ormore prior lower segment uterine scars.Study Methods: 309 supervised obstetric patients, mean age 32.3 years,(range 22-44), and mean parity 5.2, (range 4-13), who had between 3-7prior uterine scars were studied, between 1972-1999 inclusively. All hadelective abdominal delivery either at 38 weeks or within a short periodof commencement of labor. Complications, of uterine dehiscence,urinary system tree tissue damage was looked for. There were nopatients in this series with prior classical uterine scar. During the sameperiod, there were 14 classical uterine scar. During the same period,there were 14 proven cases of rupture uterus. All had been in well-established labor.Results: There were no cases of ruptured uteri or urinary system treedamage in this study where patients had undergone an elective orimmediate surgery when labor had commenced.Conclusions: Labor is the main denominator in the etiology of rupture ofuterus, provided patients with prior multiple sections can be fullysupervised and elective abdominal delivery is carried out at anappropriate moment before labor is established, there is very little risk ofuterine scar dehiscence as our study has shown. Arbitrary sterilization inpatients with 3 prior or more uterine scars should be based on otherfactors other than the fear of scar rupture.

P4.03.12LACTATION AFTER CESAREAN SECTIONI. Dragun , T. Gracheva, V. Saprikin, Dept. Obstetrics, Research Centerof OB/GYN, Moscow, Russia.

Objective: To study beginning and duration of lactation in postpartumperiod of patients delivered by cesarean section and to develop methodsof lactation correction.Material and Methods: The main group consisted of 40 patientsdelivered by cesarean section at term. Control group consisted of 10patients after vaginal delivery. To study lactate function in both groupswe used routine analyses, and determination of daily breast milkamounts and plasma hormone levels.Results: Lactate function in main group was characterized by a longerperiod of beginning. Number of patients with insufficient lactatefunction in main group was 74%. Daily amounts of breast milk on 7th

day in main and control groups were 250±40 ml and 527±44 ml,accordingly.Lactate function was corrected by adding of special protein-vitaminproduct – “Femilak 2”. By studying of plasma prolactin levels it wasshown that plasma prolactin levels were higher in patients gettingFemilak additive and they had an increase of daily amounts of breastmilk up to 495±32 ml on the 7th day of postpartum period. Duration ofbreast feeding in patients with and without correction of lactate functionwere 5.2±1 months and 1.3±0.5 months, accordingly.To correct disturbances in outflow of milk we also used sound“Bioacustic stimulator of lactation”.Conclusion: cesarean section were characterized by a longer period ofbeginning for lactate function and hypogalactia. For correction of thosedisturbances we successfully used “Femilak 2”and “Bioacusticstimulator of lactation.”

P4.03.13NON-CLOSURE OF PERITONEUM – RANDOMIZED TRIAL INCONDITIONS OF MUNICIPAL HOSPITALK. Sodowski , W. Cnota, P-K. Marek, B. Maciej, Foundation for EarlyOvarian Cancer Screening Godula-HOPE, ul. W.Lipa 2, Ruda Slaska,Poland, 41-703.

Objective: Study was performed to assess results of introduction of non-closure of peritoneum technique in cesarean sections carried inmunicipal hospital settings.Methods: 151 consecutive patients qualified to cesarean section wererandomized to closure (C)(n=83; age 26.7  5.2) (38 elective,45 urgent) and non-closure (NC) (n=68; age 27.55.1) (25


elective, 43 urgent). Following factors were assessed: operative time,opening time, complications requiring medicating (fever, pain), time ofrehabilitation start.Results: We noticed shortened operation time in NC group(339 min. vs. 4210 min. p=5x10-8). Complicationsrate was slightly lower in NC group (18% vs. 23% - p=0.12). NC groupstarted the rehabilitation after 48 hours while C group needed one daymore.Conclusions: Non-closure of peritoneum technique was successfullyintroduced in municipal hospital. The effects are in concordance withother reports coming from clinical centers

P4.03.14PERINATAL OUTCOME ON POSTMORTEM CESAREANSECTION DELIVERIES AT A SCHOOL HOSPITAL IN SÃOPAULOR. Mattar , L. Camano, A.C.E. Papa, Dept. OB/GYN, UniversityHospital, São Paulo, Brazil.

Objectives: Study the cases of post mortem cesarean section, thegestational age when the death occurred and the perinatal results.Study Methods: We analyzed all the cases in which the post mortemcesarean section (PMCS) was done from 1988 to 1998 in Hospital SãoPaulo – UNIFESP. In this period, 11 post mortem cesarean section caseswere made in 12,345 deliveries.Results: The lowest gestational age indicated for PMCS was 25 weeks.Three cases (27%) were under 26 weeks, six (55%) between 27 and 32weeks, one (9%) between 33 and 37 weeks and one (9%) at 38 weeks.We had 7 (64%) successful (live infants) cases and 4 unsuccessful (deadinfants). From the successful ones, two PMCS were done under 26weeks and 5 had more than 26 weeks.Conclusion: We had 64% of successful PMCS cases. Among these, 5had more than 26 weeks, and below this gestational age when thesurgery is not usually indicated, we had 2 successful ones out of 3.These results make us think about the validity of PMCS in earlygestational ages, especially when there is good newborn assistance care.

P4.03.15STUDY OF MINIATURE QUIVERING-TYPE AUTOMATICLACTOGENIC BRASSIERE AND ITS CLINICAL EFFECTIVENESSY.Y Song , Third Hospital JinZhou, Hu Bei, China.

In this article, a self-made miniature quivering-type automatic lactogenicis introduced and its clinical practice is reported. Based on the principleof centrifugal forge, it produces quiver to out on breasts and papillee,and to stimulate lacto-genesis by massage. It has been clinically appliedto breast feeding women 210 cases in all to do to constrastive study ingroups. The results showed that the average time of lacto-genesis inpostpartum of the study group is advanced twenty-seven hours than thecontrastive group. And that its great difference in the time of colostrumand the quantity of colostrum secretory between the two groups(p<0.001).According to stimulating the physiological and biologic character ofStimulation-Lactation the study provided a simple and effective way topromote lactation in postpartum in time and to sustain breast feeding.Key words: Quivering-type, lactogenic, colostrum, Breast-feeding.

P4.03.16THE EXIT PROCEDURE USED FOR AN INFANT WITHCERVICAL TUMORA. Yoshida , D. Nakayama, H. Masuzaki, T. Ishimaru, Dept. OB/GYN,University Hospital, Nagasaki, JapanM. Fuse, Dept. OB/GYN, M. Yoshinaga, Dept. PediatricsNational Nagasaki Central Hospital, Nagasaki, Japan

Objectives: The ex utero intrapartum treatment (EXIT) allows forcontinuance of fetoplacental circulation, so we can get enough time tosecure fetal airway. We report a case of fetal cervical tumor diagnosedprenatally by ultrasonography and MRI, and performed EXIT proceduresuccessfully.Study Method: The patient was 19-years-old primipara, and duringroutine sonographic examination, large cervical mass was suspected andtransferred to National Nagasaki Central Hospital at 27 weeks of

gestation. Ultrasonography at 28 weeks of gestation showed that themass size was 70mm_~70mm_~50mm and located on anterior neck.Amniotic fluid index was normal. In anticipation of difficulty withsecuring infant's airway, the decision was made to perform the EXITprocedure at 37 weeks of gestation.Results: A cesarian section was performed at 37 weeks of gestation bygeneral anesthesia. EXIT procedure was performed successfully andfetus was easily intubated. Total bleeding at delivery was 1170g andblood transfusion was not necessary. Newborn weighed 3040gr, and isstill hospitalized and intubated. The microscopic examination revealed acervical lymphangiohemangioma.Conclusion: The EXIT procedure was very useful to manage fetalairway in case of large fetal cervical mass which may obscure fetalairway

P4.03.17THE LONGITUDINAL HYSTEROTOMY ON THE CURRENTOBSTETRICSMassonetto , Júlio Cesar ; Freitas, Rodrigo Pereira de; Santos, FernandaErci dos; Cunha, Maria Luisa Diaz; Davoglio, Milton Vitor.Unilus – Maternal-Infantile Health Department - Hospital GuilhermeÁlvaro

Purpose: Demonstrate the importance of the longitudinal uterine sectionon the current Obstetrics.Pacients and method: We studied retrospectively 111 cases of patientswho were submitted to longitudinal hysterotomy in our Hospitalbetween July 1989 and June 1999. In this time, there were 16957deliveries. The analized variables were: maternal age, parity, indicationsof longitudinal uterine section, maternal diseases associated, anesthesiaand neonatal outcomes.Results: The incidence of the longitudinal uterine section was 2.18%.Maternal mean age was 26 years and 13.5% of the patients were youngerthan 20 years old. The fetal indications predominated in 74 patients(66.7% of the cases), mainly extreme prematurity. In 37 patients(33.3%), longitudinal hysterotomy was performed by maternalindication, mainly previous longitudinal hysterotomy. Twenty-fivepatients (22.5%) were primiparturients. The main maternal diseasewhich got to the obstetric resolution was hypertensive syndrome, mainlypregnancy-induced hypertension. Subarachnoid anesthesia wasperformed in 58 patients (52.2%); however, 20 patients were submittedto the general anesthesia. Seventy-two newborns (64.9%) presented low-weight and the majority was lower than 1500 g. Eighty-one babies(73%) were discharged and thirty (27%) died because of prematurity.Conclusion: Although it has restricted indications, the longitudinalhysterotomy plays an important role on the current obstetrics, mainly inthe high risk pregnancies. On this way, that surgical technique must berigorously standardized on the Schools of Obstetrics.

P4.03.18RUPTURA UTERI DURING DELIVERY SIX YEARS AFTERPREVIOUS DELIVERY WITH CESAREAN SECTION–CASEREPORTL. Jovcevska-Ivanovska, G. Adamova, S. Makarijoski, I. Avramovski,Dept. OB/GYN, Hospital in Kumanovo, R. of Macedonia

Objectives: In the present paper is described a case uterine ruptureduring the third delivery at the patient who has first delivery withCesarean section and normal second delivery. The patient washospitalized the last 19 days of her third pregnancy with dg. H-gestosis.When the delivery initiated, we decided to prepare the patient forvaginal delivery. One hour later fetal heart beats became slower and themother was shocked. Urgent laparotomy was performed and completeuterine rupture was found out. The baby, a half of placenta and lot ofblood were in abdominal cavity. The baby was dead twenty minuteslater and on the mother sutura uteri was carried out. Postoperative periodwas normal.Study methods: History of illness No 995 from OB/GYN dept. ofHospital in Kumanovo was used.Conclusion: Vaginal delivery after previous Sectio Cesarea could berelated with certain complication, including uterine rupture, threateningthe baby’s as well as the mother’s life.


P4.04 CONTRACEPTION

P4.04.01A QUANTITATIVE BIOMETROLOGICAL ASSESSMENT OFACNE AND HORMONAL EVALUATION IN YOUNG WOMENUSING A TRIPHASIC LOW-DOSE ORAL CONTRACEPTIVECONTAINING GESTODENEClaudine Piérard-Franchimont,* Ulysse Gaspard,† Paul Lacante,§Patricia Slachmuylders,§ Gerald Edgard Piérard *

Belgian SSTC Research Center 5596, Departments of*Dermatopathology, and †Gynecology, University of Liège, Liège,Belgium, §Wyeth Lederle Medical Department, Louvain-la-Neuve,Belgium

Objective: Acne is an androgen-driven disorder whose progression canbe influenced positively or negatively by oral contraception. Toinvestigate the effect of a triphasic low-dose oral contraceptive (OC) pillcontaining gestodene on acne severity using biometrological methodsand on hormone levels in young women.Study Methods: A total of 33 subjects aged 16–25 years (mean: 18.8years) with moderate facial acne were enrolled in this open, outpatientstudy over 13 menstrual cycles. The primary efficacy endpoints used toclinically assess acne were the overall severity grade and number oflesions, sebum secretion and superficial follicular biopsy. Acne statuswas evaluated by both physicians and patients. Blood levels of sexhormone–binding globulin (SHBG), estradiol, progesterone, andandrogens were monitored.Results: By cycle 13, the total lesion count was reduced by 80% and thenumber of comedones and papules by 87% and 62% respectively. Thearea and number of comedones per unit area, as assessed by follicularbiopsy, were decreased by 49% and 62% respectively. Both physicianand patient evaluations of acne status revealed 90% and 95% of cases,respectively, to be better or much better, with no cases of acne assessedas worse (p<0.001). At the end of the study, SHBG levels had increasedby 229% and total and free testosterone levels had decreased by 41%and 70%, respectively.Conclusion: It is concluded that an OC containing triphasic gestodenehas a beneficial effect on the severity of acne, effectively decreasesmajor circulating androgen levels and is well tolerated.

P4.04.02COUNSELLING BEFORE AND CARE DURING MEDICALABORTION WITH MIFEPRISTONEC. Fiala , L. Akinyemi, B. Laschalt, P. Safar, Department ofGynaecology and Obstetrics, General Public Hospital, Korneuburg,Austria

Objectives: What are the needs of women undergoing medical abortionand where are the differences in counselling and care during treatment?Study Methods: We performed 391 medical abortions between 27January and 30 September 1999 under a non-restrictive legal frameworkin Austria. Therefore we could orient the counselling and the careexclusively to the very different individual needs of the womanconcerned. After completion of the treatment, we asked the women, interalia through a questionnaire about their experiences.Results: Medical abortion does not essentially change the counselling inthe conflict case of an unwanted pregnancy. The previous counsellingonly has to be supplemented when it comes to the specificimplementation. Here, good information and counselling with sufficienttime are necessary, so that each woman can arrive at the best decisionregarding the method for her. This and sympathetic care during thetreatment form the basis for a good course of the process and a highlevel of satisfaction on the part of the women. Further, we have theexperience that the treatment proceeds essentially more calmly and lessdramatically than the public debate. In the specific work, we have foundno projections from the public debate.Conclusions: Pre-abortion counselling with sufficient time and careduring the process of treatment are essential for a high satisfaction. Thismakes medical termination with Mifepristone a sensible alternative formany women.

P4.04.03EFFICACY AND SAFETY OF FLUOXETINE IN PATIENTSTAKING ORAL CONTRACEPTIVESR. Judge (1), M. Bell (1), E. Brown (2), S. Koke (2)(1) Lilly Research Laboratories, Lilly Corporate Center, Indianapolis,

IN, USA.(2) Eli Lilly and Co., Nederland, CO, USA.

Objective: Because many females of childbearing potential areprescribed fluoxetine, it is interesting to note whether there are any druginteractions. Although a literature search yielded no case reports of suchan interaction, the US fluoxetine depression clinical trial database wasreviewed, specifically analyzing females aged 18-45 years.Methods: Females in the depression database who were being treatedwith fluoxetine or placebo and who were also taking OCs were analyzedfor improvement in HAMD scores (total, individual items andsubscales), safety and unintended pregnancies. These females werecompared with females in the same database who were not taking OCs.Results: No statistically significant interaction was detected between OCuse and treatment for all HAMD analyses. The only treatment-emergentadverse events showing a statistically significantly different odds ratiofor females on OCs versus females not on OCs were asthenia and pain.Incidence of unintended pregnancies showed no statistically significantinteraction between OC use and treatment.Conclusion: In the depression database for females 18-45, there is noclinical evidence that concomitant use of OCs and fluoxetine affects thesafety or efficacy of either agent. Furthermore, extensive post-marketingsurveillance has not shown evidence of interactions between fluoxteineand oral contraceptives

P4.04.04HEMATOLOGICAL AND ANGIOLOGICAL ASPECTS OF ORALCONTRACEPTION AND HORMONAL REPLACEMENTTHERAPY.I. Kalousek, J. Tosner, Dept. OB/GYN, University Hospital, CharlesUniversity, Hradec Králové, 500 05, Czech Republic.

Objectives: The aim of the study was to test the relationship of oralcontraceptive (OC) and hormonal replacement therapy (HRT) tothrombophilia and venous system of the leg.Study Methods: 76 women healed by HRT ( Klimonormâ; Jenapharm)and 75 women using OC (Triquilarâ; Schering). The examination hasdone before the treatment and after 3, 6 and 12 cycles of therapy.Among investigated parameters were: APTT, APTT p/c, fibrinogen, d-dimer, AT III., protein C and S, Leiden mutation of the factor V.Complete angiological examination with duplex ultrasonography of thedeep vein of the leg was done. Detail family and personal history wasrecorded in all cases.Results: After 12 cycles we have proved pathological APC resistance(obtained form) in 8 women using HRT (10,5%) and in 8 women treatedby OC (10,6%). Among theses women shorter APTT (p<0,01) andhigher level of fibrinogen (OC=p<0,01; HRT=p<0,05) was observed.AT III, protein C and S were normal. 2 women (1,3%) with Leidenmutation of the factor V (heterozygote form) diagnosed before thetreatment included to the study have no signs of thrombosis during orafter the treatment. Angiological examination proved deterioration in 4%subjects treated by OC a HRT. Discreet angiological changes weremostly of haemodynamic origin. In OC group, duplex ultrasonographywas normal in 94,7% before treatment and in 93,3% after 12 cycles oftreatment. In HRT group duplex ultrasonography was normal in 89,5%women before treatment and in 82,9% women after one year therapy. Nothrombosis was found during and after the hormonal treatment amongall of 151 tested subjects.Conclusions: After the 12 cycles of hormonal OC and HRT treatment10,6% (respectively 10,5%) APC resistance (obtained form) togetherwith significantly lower APTT and higher fibrinogen was observed.Despite of that no thrombosis was diagnosed during or after the one yearhormonal treatment. The effect of OC and HRT on coagulation systemwas similar. 2 women with positive Leiden mutation before the one yearOC treatment presented no signs of thrombosis after 12 cycles of thehormonal therapy. Discreet angiological changes were mostly ofhaemodynamic origin.


P4.04.05IUD PERFORMANCE AFTER ENDOMETRIAL BIOPSY.A.C.Cunha , C.R.Miranda, M.S.Wanderley, C.N. Resende, University ofBrasilia, SQN 114 Bloco A Ap. 201, Brasilia, DF, Brazil, 70764010.

Introduction: Several reports evaluate endometrial lining before andafter IUD placement. Therefore, there are no reports on if EndometrialBiopsy (EB) changes or not positioning or misplaces IUD into theuterine cavity.Objective: We evaluate the endometrial cavity handling (EB) alters themethod performance.Patients and Methods: During three years we followed 71 outpatientssubmitted to BE (rectal probe # 10) before and after IUD placement.They were followed up by clinical exam every six months, and transvaginal sonogram (TVS) once, a month after IUD insertion. The criteriawe used assessing the IUD performance were: pregnancy rate, IUDexpulsion, pain and bleeding, decision to get pregnant, personal reasons,compliance.Results: Unwanted pregnancy rate during the three years study was1.4%, expulsion rate was 5.6%, pain and bleeding was observed in 4.2%,and 4.2% wanted to get pregnant and eventually withdraw the device.Personal reasons were the motif for quitting the method for just onepatient. We observed an significant increasing in compliance from thefirst to the last year of study. At the end of the study, 84% of the patientscomplied to the method, very much similar to those reports were EB wasnot performed.Conclusions: We conclude EB is safe and do not harm the will to couplethe method or the IUD performance rate.

P4.04.06ORAL CONTRACEPTIVES (OC) PRESCRIBING PRACTICES INURBAN AREAS OF POLANDM.M. Lech , School of Public Health, Postgraduate Center of MedicalEducation, Warszawa, Poland.

Objective: In the more than 2 decades since OC have become availablein Poland, a wide spectrum of formulations has been introduced.However, little is known about the rationale behind OC prescribing. Theaim of the study was to recognize rationale behind OC prescribing inurban areas of Poland.Study Method: The survey contained a variety of questions about OCprescribing practices. The survey in a first instance was mailed to allgynecologists practicing in the Warsaw area of Poland. In a secondinstance, all gynecologists who had not answered before wereinterviewed by phone.Results: 42 of the 430 gynecologists surveyed returned questionnaires bypost. More than half the respondents were available by phone andanswered survey questions. Altogether, more than 65% of gynecologistsfrom the Warsaw area were interviewed.The majority of gynecologists preferred modern, low-dose OCs.Specifically, monophasic pills containing 20 to 35 mg of ethinyl estradioland low doses of desogestrel, gestoden, levonorgestrel or norgestimate.Over 80% of respondents said they prescribe OC primarily because of itstolerability and good hormonal contents. Less than 50% of gynecologistsnow prescribe OC to women over 40 years.Conclusions: The study, although not covering all parts of Poland,revealed that OC prescribing practice is not uninformed andgynecologists’ opinion in that matter is not homogenous.

P4.04.07PRELOADED INSERTER FOR LEVONORGESTREL IMPLANTSP. Holma (1), M. Haukkamaa (2), A. Kuukankorpi (3), M. Siljander (4),A-L Simpanen (5), I. Rauramo (6)(1) Dept. OB/GYN, Middle Finland Central Hospital, Jyvaskylä,

Finland.(2) Dept. OB/GYN, Helsinki City Maternity Hospital, Helsinki,

Finland.(3) Dept. OB/GYN, Tampere Health Care Center, Tampere, Finland(4) Dept. OB/GYN, Oulu Health Care Center, Oulu, Finland.(5) Dept. OB/GYN, Laboratorio Simpanen, Kuopio, Finland.(6) Dept. OB/GYN, Leiras Oy Clinical Research, Helsinki, Finland.

Objectives: The study evaluated the feasibility and performance of aninvestigational preloaded inserter in the insertion of the levonorgestrel(LNG) implants.Study Methods: This was an open, non-comparative, multi-center studyin 204 women seeking for long-lasting reversible contraception.Investigators and subjects assessed the performance and feasibility of theinserter by filling in relevant questionnaires and the background,efficacy and safety were assessed by using standard medical procedures.Results: All insertions were successful and totally 204 subjects receivedimplants. Only in three insertions a second set of implants was needed.Both implants were easily released in 85.6% of all insertions (95%confidence interval from 80.2 to 90.3%) and the usefulness of thepreloaded inserter, scalpel and the cut-off blade were assessed in over94% of the insertions as good. The median time taken by the insertionwas 35 seconds. The general assessment of the insertion by theinvestigators was easy in 75.5% and slightly difficult in 21.6% of theinsertions. All subjects assessed the insertions as easy and the painperception during the insertion was not common. Bleeding during theprocedure and bruising at the insertion site occurred rarely. 13% of theadverse events were localized skin reaction, which were mainly causedby the bandage used to cover the wound after insertion.Conclusion: The results suggest that the preloaded inserter is a safe andefficient method for the insertion of LNG implants and the insertiontechnique was easy to adapt. The method was also well tolerated andaccepted by the subjects.

P4.04.08RELIABILITY OF MODERN TECHNOLOGY AS AID TONATURAL FAMILY PLANNING FOR SPACING PREGNANCY.A. Saporosi , E. Giacchi, M.C. Squintani, E. Menini*, A. Cappella andJ.B. Brown°. Center for Study and Research on Natural FertilityRegulation, * Hormonal Biochemistry Laboratory Catholic University ofthe Sacred Hearth, Rome, °Department of Obstetrics and Gynaecology,University of Melbourne.

Objectives: Today natural family planning (nfp) can be supported bymodern technologies. We will compare the hormonal data provided bythe brown’s ovarian monitor (om) and by unipath persona system withthe information provided by the cervical mucus symptoms according tobillings ovulation method (bom).Study Methods: We studied 6 women, 26-45 aged, BOM users withregular cycles for 31 menstrual cycles. All combined the Persona system(Unipath Ltd, Bedford, MK443UP, UK) with the hormone assay byOvarian Monitor (St. Michael NFP Services Pty, Ltd, Melbourne). TheOM measures the urinary oestrogen glucuronide (E1G) or pregnandiolglucuronide (PdG) by “homogeneous enzyme immunoassay”.Results: The hormone assay by the OM correlated well with the BOMsymptoms. The first rise from E1G baseline agreed with the first mucuschange (87,1% cycles) to identify the beginning of fertile phase, the dayof maximum fertility (“Peak day”) by BOM correlated with theovulation day by OM within 24 hrs (83,9% cycles). The “PdG cut-off”=7 umol/24 hrs measured by OM identified the late infertile phase alleast one day earlier than the other two systems (80,6% cycles). ThePersona showed a good correlation with the BOM symptoms in theregular cycles. When Persona did not provide sufficient data to timeovulation (19,3% cycles), this could be timed only by the BOMsymptoms.Conclusions: The subjects integrated BOM rules and the “PdG cut-off”rule by OM for spacing pregnancy. The OM accurately identified thefirst estrogen rise, the timing of ovulation and the adequancy of theluteal phase also in unpredictable irregular cycles. Fewer days ofabstinence are required for pregnancy avoidance, but it is morecomplicated and time consuming then the two others. It does not replaceNFP methods but can support them in some difficult cases.


P4.04.09REVERSAL OF STERILISATION BY MICROSURGERY INSRINAGARIND HOSPITALK. Seejorn , M. Songthamwattana, S. Thailert, S. SinawatDepartment of Obstetrics and Gynecology, Faculty of Medicine, KhonKaen University, 40002, Thailand

Objectives: To assess the basic data of the patients who requestedsterilisation reversal, together with the success rate and the factorsinfluencing the success rate of the operation.Study Methods: A total of 206 patients who underwent microsurgicalsterilisation reversal in Srinagarind hospital Between January 1, 1984 toJune 30, 1993 were recruited. The medical records of these patients werereviewed. The letters were sent to these patients to obtain the results ofthe procedure.Results: Mean age of the patients was 32.0 years, most of them weregovernment officers and farmers. The main reason for reversal wasremarriage (68.0 percent). Ampulla to ampulla was the most commontype of reanastomosis. The mean duration of the operation was 135.8minutes. Success rate of the operation as determined by delivery of theliveborn was 58.7 percent while abortion rate and ectopic pregnancy ratewere 10.7 and 8.2 percent, respectively. This study revealed that thepatients with age under 35 years, operation performed within 5 yearsafter sterilisation, interval type of sterilisation, and isthmic-isthmicreanastomosis were the factors that resulted in the better success rate.Conclusions: Sterilization reversal in Srinagarind hospital hadsatisfactory success rate and factors that influenced the success were ageof the patients, time interval after sterilization, type of sterilization andpart of the uterine tubes being reanastomosed.

P4.04.10SHARING RESPONSIBILITY: WOMEN, SOCIETY AND UNSAFEABORTION IN DEVELOPING COUNTRIESY. Irfan , KDLB Campus Kemari, Karachi, Pakistan.

Introduction: Millions of women who live in countries that place severerestrictions on abortion nevertheless attempt to end their pregnancies byunauthorized and often unsafe means. The World Health Organizationdefines an unsafe abortion as a “procedure for terminating an unwantedpregnancy [carried out] either by persons lacking skills or in anenvironment lacking the necessary minimal medical standards or both.”Abortion carried out under such circumstances places women’s healthand lives at risk. For example, of the estimated 600,000 annualpregnancy related deaths worldwide, about 13% (78,000) are related tothe complications of unsafe abortion. In developing countries, whereabortion is often illegal or highly restricted, abortion mortality ishundreds of times higher than in developed countries (330 deaths per100,000 abortions compared with 0.2-1.2 per 100,000). Mortality due toabortions is higher in Africa.In the poorest countries, women are exposed to the highest risks of deathand disability from unsafe, usually illegal abortion – often leaving wholefamilies bereft of mothers and wives.The major of victims are women living on the edge of survival, with fewprospects that their government can or will do much to improve their lot(Jeannie Roses). The victims of illegal abortion are commonlyadolescents (2). In a study in Nairobi (2) it was found that 79% ofpatients were unmarried, 60% of girls were unemployed, 43% beingadolescent.Objectives: The aim of this presentation is to point out several policyresponses to reproductive health and social problems faced bydeveloping countries. The factors leading to this high incidence of theseunsafe procedures are failure of family planning program for all thecouples, misconceptions about family planning and contraceptionfailure. Sexual abuse or rape and lack of sex and family health educationespecially of adolescents (1) is also responsible.It is also very important to highlight the social and economic factors thatare again a big factor in developing countries. Beside these, lack ofadequate training, inadequacy of treatment including negative attitude ofhealth workers and improper contraceptive counseling after abortion areoften prevailing in these countries. The controversy about abortion lawshas yet to be resolved in these countries. This leads to the utilization ofillegal unsafe means in unsafe and unhygienic environments.References Abortion: A Tabulation of Available Information, 3rd edition,WHO, Geneva, 1997, in press.

Peter Adamson, Deaf to the Screams, Medical Spectrum, Vol. 19-August, 1998.

P4.04.11THE CHARACTERISTICS OF ABORTION BY REQUEST:PATIENTS IN IASI REGION, ROMANIA OVER A 10-YEARPERIOD (1989-1998)R. Socolov , F. Zenovia Pricop, S. Butureanu, 3rd OB/GYN Clinic, Iasi,Romania.

Objective: In Romania, abortion by request is still the most widely usedmethod of family planning ten years after the abolition of anti-abortionlaws. Iasi region, with low socio-economical conditions and specificpopulation conditions, has a particular situation with a slower decliningrate than the national average.Study Methods: We studied retrospectively the 45155 patients thatrequested first trimester abortion in our state service between 1989-1998. The statistical interpretation regarded age, occupation, socio-economic origins and comparison with national and international data.Results: The abolition of anti-abortion laws in 1989 resulted in a hugeincrease of abortions, mainly abortion by request. The top level was in1990, with almost 1 million or 2.91 abortions per live birth. In ourservice, the highest numbers were in 1990-1992, with around 6300abortion by request, or a rate between 3.59 and 4.32 abortions byrequest/live birth. Afterwards, the number decreased followed by somedelay, the national trends, with the lowest figure of 3577 cases and a rateof 1.81. We noticed a more important decline in patients between 20 and39 years and that the most important category of women requestingabortion are housewives (35.38%) and workers (30.21%).Conclusions: The lower economic situation in Iasi region is associatedwith a slower decrease of abortion by request number. The agecategories (<20 years and >40 years) and low-income occupationalgroups (housewives, workers) that keep a higher rate of abortion useshould be the focus of the contraception education from the familyplanning services.

P4.04.12ULTRASOUND ASSESSMENT OF THE BONE QUALITY OFNIGERIAN WOMEN USING NORPLANT CONTRACEPTIONAS. Sagay , Dept. Ob/Gyn ,University of Jos Teaching Hospital, Jos,Nigeria.RH, Glew, Dept. Biochem./Molecular Biol, University of New MexicoSchool of Medicine, Albuquerque, NM, USA.GE. Imade, Dept. Ob/Gyn, University of Jos , Jos, NigeriaS. Farmer, Dept. Biochem./Molecular Biol, University of New MexicoSchool of Medicine, Albuquerque, NM, USA.E. Madrid, Dept. Biochem./Molecular Biol, University of New MexicoSchool of Medicine, Albuquerque, NM, USA.D. VanderJagt, Dept. Biochem./Molecular Biol, University of NewMexico School of Medicine, Albuquerque, NM, USA.

Objective: To assess bone quality of Nigerian women using Norplant(levonorgestrel) implant contraception.Study Methods: Twenty-five women aged 24-40 years who have beenusing Norplant for two years and an equal number age-, parity-, andbody mass index (BMI) - matched controls were recruited. The stiffnessindex (SI) of the calcaneus bone, was measured using the Achilles +bone ultrsonometer (Madison, WI).We also measured the concentrations of two serum markers of boneturnover, the N-telopeptide of Type 1 collagen (Ntx), an indicator ofbone resorption, and bone-specific alkaline phosphatase (BAP), anindicator of bone synthesis.Results: There was no significant difference in the SI of the Norplantusers and the controls (106 + 15.3 vs. 98.1 + 18.4, respectively). Therewas no significant difference in the mean serum Ntx level of theNorplant users and the controls (15.5 + 4.9 vs. 17.5 + 7.7 nM BoneCollagen Equivalents). However, we did observe a statisticallysignificant lower mean serum concentration of BAP in the Norplantgroup (14.6 + 4.9 U/L) compared to the control group (23.0 + 14.0 U/L),p = 0.007.Conclusions: Overall, these data indicate that Norplant use for two yearshad no effect on bone quality of women as determined by SI. Althoughthere was no effect on bone resorption in Norplant users (>2Years)should be monitored for effects on bone quality.


P4.04.13WHY REPEAT ABORTIONS ARE STILL USED AS METHOD OFBIRTH CONTROL IN LITHUANIAR. Jakubcionyte , Dept. OB/GYN, Kaunas University Hospital, Eiveniu2, Lithuania.

Objectives: The purpose was to compare women having a repeatinduced abortion with women coming for a first induced abortion. Theaim was to determine whether it is possible to identify characteristics ofwomen at high risk for repeat abortions.Study Methods: Totally 494 women participated in the study. 221 hadthe first and 273 repeat induced abortions. Data were collected inKaunas City Kalnieciai, Silainiai and Raseiniai districts’ outpatientdepartments using anonymous semi-structured questionnaire forpregnant females until the end of 12 gestation’ weeks. Midwivesdelivered the questionnaires for women and they answered questionsthemselves. Respondents left answers in a special box at women’soutpatient department.Results: Women coming for repeat induced abortion were significantlyolder and having more children in city and countryside (p<0.5). Urbanfemales with repeat pregnancy interruptions comparatively often weremarried, at work and living in own flat/house under overcrowdedconditions too (p<0.05). There was no difference between groupsregarding reproductive life events, but rural women with repeat inducedabortion have started sexual activity later (p<0.05). Significantdifference between groups was found concerning age at starting of birthcontrol (p<0.05). Totally, usage of reliable contraception during first andlast sexual intercourse in both groups was low. There were differentattitudes between groups towards abortions under social circumstancesand concerning perception’ of abortion in Kaunas City (p<0.05).Conclusions: Women with first and repeat induced abortions are moresimilar though dissimilar. Considerable difference was found betweenurban and rural respondents.

P4.05 EDUCATION

P4.05.01COMPARATIVE STUDY OF THE KNOWLEDGE LEVEL OF"GUIDANCE-SCHOOL FEMALE STUDENTS" MOTHERSBETWEEN RURALS AND TOWN OF BIRJAND (EAST OF IRAN)ON HEALTH BEHAVIOURS REGARDING MENSTRUATIONP. Asadi (1), T. Farhadian (2), S. Mohammadzadeh (1), (1) AzadUniversity, P.O.Box: 16895-136, Daftar Omid, Tehranpars, Tehran,Iran, 16895, (2) Birjand University, Birjand, Khorasan, Iran.

Objectives: The aim of this study was descriptive the knowledge level ofmothers in rural and city of Birjand.Study method: In this research We collected data based uponinterviewing. The collecting tools was questionniare forms and then Weanalize findingsResults: The study conclusions indicate that between two rural and citysubject groups in relation to health behaviours at the time ofmenstruation, there is a significant different and unfortunately,Theknowledge level was very low.Conclusions: We Conclude that the related Organizations must followEducational programmes on health of menstruation.

P4.05.02CYBER-SOLUTIONS FOR GLOBAL PROBLEMS: PILOT TESTINGCOMPUTER-BASED INFECTION PREVENTION TRAINING FORLOW RESOURCE SETTINGSM. Barone , J. Tzanis, P. Harper, K. Levin, D. Silverman, C. Cook,AVSC International, New York, New York, USA.

Objectives: Computer-assisted instruction has enormous implications forthe future reach of training in the developing world. We have developedand tested two computer-based infection prevention training courses foruse in low resource settings.Study Methods: A CD-ROM and a web-based infection preventioncourse were developed from a print-based curriculum published byAVSC in early 1999. Pilot tests of the CD-ROM were conducted inNepal, Ghana, and South Africa, with a total of 138 participants. Aninstructor-led field test of the web-based course was conducted

with 16 self-selected participants from 12 countries. The instructor waslocated in Seattle, Washington.Results: The findings of the three CD-ROM pilot tests indicated that itwas very popular, with very high user satisfaction rates in all sites. Itwas clear from observation that participants enjoyed using the CD-ROMand were engaged by this method of learning. The pre-and post-testscores indicated that participants learned new information. On average,overall scores increased by about 10% for the 120 participants whocompleted the pre- and post-tests, with increases of up to 30% in somecases. Of the 16 participants in the instructor-led on-line course, fivedropped out early because of serious technical problems, two droppedout for other reasons and nine finished the course. Five out of the ninetook both the pre- and post- test, with results showing an overall averageincrease in scores of 15%.Conclusions: Access to computers and the internet will continue toincrease throughout the world. While computer-based approaches totraining will not be appropriate everywhere, they do have the potential tohelp meet the training needs of developing country health careinstitutions in many settings.

P4.05.03DIABETES EDUCATION IN PATIENTS WITH TYPE 1 DMDURING PRECONCEPTION CARE AND PREGNANCYN. Asatiania (1), R. Kurashvili (1), M. Natsvlishvili (1), L. Nikoleishvili(1), M. Dundua (1), E. Shelestova (1), T. Chanturia (2),(1) Georgian Diabetes Center, Tbilisi, Georgia.(2) Maternity Home, Tbilisi, Georgia.

Objectives: The aim of the present study was to evaluate the efficacy ofstructured outpatient education and treatment program in Type 1diabetes patients during preconception care and pregnancy and its effecton pregnancy outcomes.Study Methods: 42 women with Type 1 DM were supervised (age 21-46yrs., diabetes duration 2-18 yrs.). The program started with a 5-day (25hrs) group education: attention was paid to: self-monitoring, diet, shortand long term complications and their prevention, insulin therapy andinsulin dose adjustment rules. Patients were instructed on multipleinsulin injections to achieve and maintain euglycemia. Peculiarities ofdiabetes management in pregnancy were emphasized. Throughoutpreconception care and pregnancy individual training was used duringregular weekly visits to the Center. Once a month, 2/3 hr-group trainingtook place. At baseline, every 2 months, at the end of the preconceptioncare period and after conception, a questionnaire (65 questions) wasused to assess the patients’ knowledge and training results.Results: Following mean glycozilated hemoglobin (HbA1C) levels andinsulin doses were registered. HbA1C-preconception care – 10.1±0.2%;1st trimester – 7.6±0.5% (P<0.001); 2nd trimester – 7.9±0.3%; 3rd

trimester – 7.2±0.2% and insulin doses – 0.77±0.09 IU/kg; 0.55±0.06IU/kg (P<0.01); 0.72±0.06 IU/kg and 0.9±0.08 IU/kg, respectively.There were no new diabetes complication development or aggravation ofpre-existing ones observed. The pregnancies were not complicated andhealthy children were born at 36-38 weeks of gestation (weight range2400 – 3800 g). Cesarean section was mainly used.Conclusion: We recommend the following education schedule: 1st week– group education (25 hrs), then during weekly visits, 30-40 mini-individual classes and once a month (2-3 hrs) group classes. Thisschedule may be effectively used for patient education duringpreconception care and pregnancy. The use of the therapeutic educationin Type 1 DM women resulted in significant reduction of mortality andmorbidity rate both in mothers and their children.

P4.05.04MOTIVATING RURAL WOMEN FOR ANTENATAL CARE –INDIAN PERSPECTIVEM. Sali , Sali Hospital, Manchar, India

Objectives: Antenatal care is still not availed of by a majority of Indianwomen as evidenced by high maternal mortality rate of 120 as comparedto 0.5 in the United States. The total population of India is above 1billion, of which 800 million remain in rural areas. Of these, 700 millionare farmers and the remaining 100 million are closely associated withfarming. These rural people must be motivated to register for antenatalcare in order to reduce National Maternal Mortality.


Study Methods: The author, who has been practising in a rural area forthe past 20 years, explains how taking care of a growing fetus is liketaking care of growing crops by pointing out down-to-earth similaritiesbetween farming and antenatal care. Just as fertilizers and micronutrientsare given to the land to increase its fertility, a highly nutritious diet alongwith calcium and iron supplements must be given to the expectantmother. Just as timely spraying of the crops with insecticides isnecessary to prevent certain disorders, vaccination is necessary forpregnant women. The farmer visits his farms frequently at regularintervals to watch for proper growth of crop and disease, if any. So tooare antenatal visits essential and beneficial.Results: The above-mentioned, as well as many other similarities, existbetween antenatal care and farming and have a tremendous impact onrural women. Moreover, the fact that a child is more precious than a cropusually motivates these women for antenatal care.Conclusion: Poor attendance to the ANC services proves to be aninefficiency in present health education methods. This author’s methodis highly effective for rural people and may prove beneficial indeveloping countries.

P4.05.05PREGNANCY PLANNING AMONG DANISH WOMENV Rasch, Department of Obstetrics and Gynecology, Odense UniversityHospital, Odense, Denmark.

Objectives: To assess the influence of the women’s occupational andeconomical situation on the choice of planning and wanting to have achild.Study Methods: During a period of 15 month a total of 3516 pregnantwomen were included in the study. They were divided into two groups:3143 women with wanted pregnancies and 373 women with unwantedpregnancies.The association between socio-economic characteristics and the choiceof planning to have a child among Danish women was evaluated by acomparison between women stating they had a planned and wantedpregnancy (n=2137) and women stating they had an unplanned andunwanted pregnancy (n=342).Results: In the group of women with wanted pregnancies, 68% hadplanned to become pregnant. Women with planned and wantedpregnancies were more often married [OR: 54 (38.3-77.9)] and aged 25-34 [OR: 4.65 (3.61-6.00)] when compared to women with unplannedand unwanted pregnancies. Furthermore, they had more often a formaleducation [OR: 5.07 (3.81-6.74)], were more often employed [OR: 2.95(2.33-3.73)] and had more often a monthly income above 10,000 DKK[OR: 3.02 (2.07-4.42)].Conclusion: The decision to plan a pregnancy and have a child isdependent on the woman’s situation, as she may have to consider thepossibilities of completing her education and her future position on thelabour market before she establishes a family with child(ren).

P4.05.06STUDY OF FACTS & AWARENESS ABOUT ADOLESCENTHEALTH EDUCATION IN SCHOOL-GOING GIRLS IN INDIAS. Gupta , Jeevan Jyoti Medicare, Gorakhpur, UP, India.

Objectives: Study was conducted to outline real topics & approaches forhealth education in school-going adolescent girls based on factors &facts found in different social, economic & environmental settings.Study Methods: A questionnaire was prepared in local languagecontaining questions on (a) awareness of menstruation, sex, pregnancy& family planning (FP); (b) future plans; (c) awareness of social issuesesp. on women’s problems. In the FOGSI year of adolescent girl I, ashony. Secretary of FOGSI approached different girls schools, govt. aswell as public, situated in urban & rural areas. The questionnaire wasfirst explained and then they were asked to fill it up. 900 replies werereceived & analyzed. On the basis of the results, certain conclusionswere drawn.Results: Respondents were categorized according to their economic,social and environmental belongings. Participants of high & uppermiddle socioeconomic classes were found to be more aware of factsabout menstruation, sex, pregnancy and FP when compared to middleurban & rural class. Middle urban class had deep-rooted stigmas aboutmenstruation, sex and pregnancy but they were concerned aboutwomen’s social issues & keen for higher education. Rural girls had

natural acceptance of physical changes in adolescence and the secondarystatus of women in the family & society.Conclusion: Seeing the wide variations in awareness & concerns ofadolescent girls in different social groups, it is concluded that foradolescent health education, programs should be flexible and tailoredaccording to their specific requirements.

P4.05.07TEENAGERS AND SEXUALITY: THE ROLES OF FAMILY ANDSCHOOL IN THIS DISCOVERY.S. Dib , L. Parada, M. IOSSI,* F. Dib, **

* Nurses of “Students’ Health Care Program” from Health Secretariat ofRibeirão Preto City. ** Gynecologist from Health Secretary of RibeirãoPreto City. São Paulo State, Brazil. Address (in Portuguese): AvenidaPresidente Kennedy 2634, Ribeirão Preto, SP, Brasil, CEP: 14095-220.

Objectives: To determine the degree of information of teenagers aboutsome aspects related to sexuality, emphasizing the pregnancy,contraception, AIDS and other sexual related diseases.Study Methods: One hundred and one interviews of teenagers,containing dissertatives and multiple choices questions, educativeactions like conferences with audiovisuals and other group teachingtechniques.Results: The age of 85,15% varied from 13 to 15 years. Only a part ofthem have used contraceptive methods. The condom was preferred bymost of them. Most said that sex and related subjects are frequentlydiscussed in family environment, but they think that these subjects mustbe discussed at school.Conclusions: Condom is the most popular contraceptive method forteens. Family is fundamental in sex education, but the school plays animportant role in order to minimize the incidence of some“complications”, like undesired pregnancy and the incidence of AIDSand sexual related diseases.

P4.05.08THE EDUCATION OF MIDWIVES AT THE BEGINNING OF THENEW MILLENNIUMS. Bagdány , É. Tõrös, E. Mészáros, F. Tamási, G. Nyitray, J.T. Bartha,Dept. OB/GYN, Csepeli Weiss Manfred Hospital, Budapest, Hungary.

Objectives: Since the late 90’s there have been significant changes inMid-Eastern Europe. As a results of the family centric obstetrics and thebaby-friendly hospital program we have improved our health careeducation system.Study Methods: In our postgraduate hospital we began the graduateprogram ten years ago. At first these programs were offered once a weekthrough 5 weeks. The next step was to develop an intensive programwith a length of three days. Nowadays, there are intensive one-weekprograms for midwives and for obstetrical nurses. They get 25 creditpoints after successfully completing a course.Results: There are 30-32 women in every class. This number is ideal forboth the theoretical and practical lessons. In the last ten years, about 680women participated in our postgraduate programs, and 97 percent hadgraduated successfully. The authors present their postgraduate programand its changes in detail.Conclusions: These programs have had a significant role in therecognition of the family friendly program in Mid-Eastern Europe. Themidwives have an important role in the baby-friendly hospital program.As a result of this program the breastfeeding continues for more than 6months in about 70 percent of the women.

P4.05.09THE IMPACT OF HEALTH EDUCATION IN THE PROMOTION OFCERVICAL CANCER SCREENING IN DEVELOPING COUNTRIESA. Oladokun , I.F. Adewole, I.A. Barbarinsa, Dept. OB/GYN, UniversityCollege Hospital, Ibadan, Nigeria.

The impact of health education in the promotion of cervical cancerscreening was evaluated in a local government area of SouthwesternNigeria.Women in reproductive age group (15-49), were specially targeted atantenatal, infant welfare and family planning clinics, as well as marketplaces, by a team of physicians and health educators.


There was a sustained increase in attendance of women for cervicalcancer screening form 0.7% to 6% over a 3 months period. This wassustained for 2 months after discontinuation of the program before adecline to 2% was noticed at 6 months. A secondary attempt atreintroduction of health education produced another rise to 8% whichremained sustained while health education continued.We concluded that for health education to be effective in developingcountries, it must be sustained and intensive to ensure maximum impact.

P4.06 ENDOMETRIUM

P4.06.01CARCINOMA ENDOMETRIUM IS DIAGNOSED BYEXPLORATIVE CURETTAGE OF PHA FOR A PERIOD OF ONEYEARA. Dimitrovska , S.Pangovska, Dept. GYN, Health Center Bit Pazar,Skopje, Macedonia.

Objectives: Carcinoma Endometrium is frequent and serious malignantdisease of the uterus and its incidence shows significant growth withinthe last decades. Most frequently it appears in the post menopauseperiod and causes an extensive bleed mg. The purpose of this work is topresent how many of the patents, who suffered uterus bleeding, actuallyhad adenocarcinoma endornetrium.Study Methods: The study is a retrospective analysis of one year recordsfrom 870 PHA from samples of endometrium, acquired by fractionalexplorative curettage.Results: Carcinoma endometrium lifts been discovered in the PHA of 86patients (9.88%).

Adenocarcinoma in relation to age of the patients:age from 40-50 6 patients 6,98%age from 50-60 23 patients 25,99%age from 60-70 46 patients 53,48%over 70 years old 12 patients 13 ,95%

The disease is mostly present in the age group in the age group from 60to 70 years. The youngest patient has 42 and the oldest 78 years.Conclusions: The high percentage of women with carcinomaendometrium- 9,98%, from those who have suffered extensive bleeding,requires a fractional curettage for acquiring of a PFI verification anddiagnosis, as well as for an appropriate treatment.

P4.06.02CORRELATION BETWEEN BODY FAT DISTRIBUTION ANDSTEROID HORMONE RECEPTOR EXPRESSION INENDOMETRIAL CARCINOMAY.Fujie , T.Tsuji, T.Douchi, Y.Nagata, Kagoshima University Hospital,8-35-1 Sakuragaoka, Kagoshima, Japan, 890-8520.

Objectives: This study investigated whether body fat distribution inpostmenopausal women with endometrial carcinoma correlates withsteroid hormone receptor expression in endometrial carcinomaspecimens.Study Methods: We analyzed estrogen receptor(ER) and progesteronreceptor(PR) expression using immunohistochemical methods informaline-fixed, paraffin embedded endometrial specimens obtainedfrom 48 postmenopausal women with endometrial carcinoma. Baselinecharacteristics in including age, years since menopause(YSM), weight,height and body mass index(BMI) were recorded for each subject. Fourbody fat indices [total fat mass(g), percentage of body fat (total fatmass/BW,%),trunk fat mass(g),and the ratio of trunk fat mass to leg fatmass(trunk-leg fat ratio)] were measured by dual-energy X-rayabsorptiometry. These variables were compared by ER expression or PRexpression. In all subjects, the correlation of these variables with steroidhormone receptor expression in endometrial carcinoma specimens wasinvestigated by univariate regression analysis.Results: Baseline characterics and body fat indices the other than trunk-leg ratio did not differ with ER expression. The trunk-leg fat ratio in theER-positive group (n=35) was significantly higher than that in ER-negative group(n=13)(p<0.05). The trunk-leg fat ratio was significantlycorrelated with ER receptor expression(p=0.0275), while there was nosignificant correlation between trunk-leg fat ratio and PR expression.Conclusion: ER expression in endometrial carcinoma specimens may becorrelated with body fat distribution rather than overall adiposity.

P4.06.03CYTOKERATIN EXPRESSION SUGGESTING OCCULTMETASTASES IN REGIONAL LYMPH NODES OFENDOMETRIAL CANCERH. Yabushita , M. Shimazu, K. Hiratake, H. Yamada, H. Narumiya, K.Sawaguchi, M. Noguchi, M. Nakanishi, Dept. OB/GYN, Aichi MedicalUniversity, Aichi, Japan.

Objectives: The clinicopathological significance of cytokeratinexpression in lymph nodes unconfirmed metastasis by hematoxylineosin (H&E) staining was evaluated retrospectively in patients withendometrial carcinoma.Study Methods: We studied 304 pelvic lymph nodes and 46 primarytumors removed from 46 patients with endometrial cancer, consisting of36 stage I and 10 stage IIIc cases. Formalin-fixed paraffin-embeddedtissue sections were stained immunohistochemically using antibodiesagainst cytokeratin, CA125, p53 and macrophage, and also stained withH&E.Results: All of the primary tumors had the cytokeratin expression. In 10stage IIIc cases, the cytokeratin expression in cells other than tumor cellswas found in all 13 lymph nodes with metastasis and in 20 (30.3%) of 66lymph nodes without metastasis. In 36 stage I cases unconfirmedmetastases in any lymph nodes, 37 (16.4%) of 225 lymph nodesexpressed cytokeratin, and 5 of 14 cases with lymph nodes expressingcytokeratin had recurrent disease in pelvic retroperitoneal cavity, whileall 22 cases without those had no recurrence. The cytokeratin wasdetected on macrophages and on the sites observed CA125 or p53expression. In 70 lymph nodes expressed cytokeratin, CA125 wasexpressed in 56 specimens (80%) and p53 was expressed in 25specimens (35.7%) simultaneously. These cytokeratin expressions inregional lymph nodes had a close relationship with a lymph-vascularspace involvement in primary tumor, while they had no relation to thegrade of histological differentiation and depth of myometrial invasion.Conclusions: Even when metastasis was not detected in sections stainedwith H&E, the immunohistochemical expression of cytokeratin inregional lymph nodes suggests the presence of occult metastasis to themand is one of the risk factors for recurrence in endometrial cancer.

P4.06.04CYTOLOGY ASPIRATION STUDY IN ENDOMETRIALCARCINOMA DIAGNOSIS AND HIGH RISK GROUP PATIENTSDETECTION.E.V. Elnogarr, U.U. Tabakman , A.E. Ivanov, Z.M. Vahturova,A.G.Solopova, Department of Obstetrics and Gynecology, Laboratory ofHemostasis Pathology, Sechenov Moscow Medical Academy, BolshayaPirogovskaya St. 2/6, Moscow, 119881, Russia.

Cytology aspiration study is considered the method of first choice inevaluation of pre- and postmenopausal women with anomaly uterinebleeding.We studied 15000 patients with AUB in pre- and postmenopausalperiod. After cytology aspiration as first line diagnosis approach,histology-aspiration (“Pipelle”) or hysteroscopy were performed fordiagnosis verification.Endometrial carcinoma was detected in 1200 cases. Result of cytologyaspiration was positive in 60% of cases, questionable in 18% and falsenegative in 16% of cases. Accuracy of cytology study depended ondegree of histological differentiation. In case of high-grade carcinomapositive results reached 48%, questionable 27% and false negative 25%.In case of low-grade carcinoma 81%, 16% and 6% respectively. In 7%of cases cytology aspiration gave false positive results. Followingpatients in group with false-positive results of cytology aspirationallowed to diagnosed endometrial carcinoma without any clinicalmanifestations in 18% during 1,5-3,5 years after first evaluation.Cytology aspiration is adequate approach as first line method ofendomenrial carcinoma diagnosis. Patients with false-positive results ofcytology aspiration represent high risk group for carcinoma developmentand must be observed carefully.


P4.06.05DIAGNOSTIC HYSTEROSCOPY IN ENDOMETRIALHYPERPLASIASt. Butureanu , R. Socolov, D. Gafitanu, L. Sachelarie, F. Pricop, Dept.OB/GYN, University of Medicine, Iasi, Romania

Objectives: To assess the reproducibility of the hysteroscopic diagnosisin endometrial hyperplasias and to compare different classifications forendometrial hyperplasia from this point of view.Study Methods: 113 endometrial hyperplasias diagnosed in the last 5years with hysteroscopy were all biopsied and had pathological exam.The hysteroscopic images for different types of hyperplasia werecompared. We tried to estimate the value of various classifications forendometrial hyperplasia to the final hysteroscopic diagnosis.Results: The histological diagnosis after hysteroscopy was: simplehyperplasia in 92 patients (81.4%), complex in 12 patients (10.6%),atypical in 5 patients (4.4%) and secretory in 4 patients (3.5%).Indifferent of the type of endometrial hyperplasia classification, theoverall diagnostic accuracy of hysteroscopy was 76% as for the exacttype of hyperplasia. In fact, only 1.6% of the atypias was missed byhysteroscopy.Conclusions: Hysteroscopy cannot replace biopsy but has a goodcorrelation with histologic results. In conjunction with endovaginalultrasound to assess the width of the endometrium, it can be one of themost important tools for the endometrial pathology diagnosis especiallyfor atypical features. Hysteroscopic diagnosis as cystic or polipoidhyperplasia should be avoided.

P4.06.06ENDOGENOUS SEXUAL STEROIDS AND GONADOTROPHINS INWOMEN WITH AND WITHOUT ENDOMETRIAL CARCINOMAV. Tadini (1) , A. Pinto-Neto (2), G. Souza (2), S. Brenna (1), (1)Maternity Hospital Leonor Mendes de Barros, Av. Celso Garcia 2477 –Belém, São Paulo, Brazil, 03015-000, (2) The State University ofCampinas, Barão Geraldo – Campinas, São Paulo, Brazil.

Objectives: The aim of the study was to analyze the levels ofendogenous sexual steroids and gonadotrophins in postmenopausalwomen to emphasize factors associated with genesis of endometrialcarcinoma.Study Methods: This was a cross sectional study that analyzed twogroups of women: the first included 20 postmenopausal women withendometrial adenocarcinoma an the other included 20 postmenopausalwithout carcinoma. Age, menopause interval and index of body masswere used as matching variables. The plasma levels of steroids weremeasured by radioimmunoassay and immunoenzymatic methods.Statistical analysis was performed by Anova or Student t test, acceptingp=0.05.Results: The levels of androstenedione (A), total testosterone (t) and freetestosterone (FT)were higher and luteinic hormone (LH) weresignificantly lower in women who had endometrial carcinoma. It wasalso observed that estrone (E1)/A ratio was lower in women withcarcinoma while estradiol (E2)/E1 ratio was similar between the groups.Conclusions: Sexual steroids and gonadotrophins have been stronglyassociated in genesis of endometrial adenocarcinoma in postmenopausalwomen.

P4.06.07EXPRESSION OF MATRIX METALLOPROTEASE-7 INCARCINOSARCOMA OF THE UTERUSH. Tanimoto (1) , K. Shigemasa (2), I. Kusumi (1), K. Ohama (2), (1)Asada General Hospital, Tsunomori-cho 219, Marugame, Kagawa,Japan, 763-8507, (2) Hiroshima University School of Medicine,Hiroshima, Japan.

Objective: To investigate the expression of matrix metalloprotease-7(MMP-7) in each component of carcinosarcoma of the uterus.Methods: Surgical specimens of uterine carcinosarcomas were obtainedfrom 13 patients. The carcinomatous component consisted ofadenocarcinoma with or without squamous differentiation. Thesarcomatous component consisted of spindle cell sarcoma,chondrosarcoma and rhabdomyosarcoma, either alone or in combination.The immunohistochemical expression of MMP-7 protein was examined

using the avidin-biotin peroxidase complex technique employing theMMP-7 monoclonal antibody.Results: Expression of MMP-7 protein was detected in 9 (69.2 %) of 13adenocarcinoma components, while no staining was observed in any ofthe sarcomatous components examined. In some cases, MMP-7 wasabundantly expressed at the invasive front of adenocarcinomacomponents.Conclusion: MMP-7 was differentially expressed between thecarcinomatous component and the sarcomatous component. Eachcomponent of carcinosarcoma may have its own potential for invasionand metastasis. MMP-7 may contribute to the invasive nature or growthcapacity of the carcinomatous conponent of uterine carcinosarcoma,while it may not have a relation to that of the sarcomatous components.

P4.06.08HORMONE REPLACEMENT THERAPY IN WOMEN WITH AHISTORY OF ENDOMETRIAL CANCERS.Bebar , M.Ursic-Vrscaj, Institute of Oncology, Zaloska 2, Ljubljana,Slovenia, 1000.

Objectives: This overview was carried out with the aim to establish howthe hormone replacement therapy (HRT) influences patients treated forendometrial carcinoma.Study methods: We collected data on 23 patients that were treated at ourinstitute in the period 1988 to 1995.Results: At the time of diagnosis the mean age of the patients was 50years (range 35-66 yrs), and HRT was started 6 months later (range 35-67 yrs). In most cases, HRT was indicated because of acute menopausaldifficulties. Nineteen patients were with stage I (83%), 2 (8%) with stageII, and 2 (8%) with stage III of the disease. Pathohistologicalexamination revealed adenocarcinoma in 22 cases (96%) andadenosquamous carcinoma in one case only. In 52% (12 patients) thetumors were well differentiated, in 31% (7 patients) moderatelydifferentiated and in 17% (4 patients) poorly differentiated. The majorityof patients were treated by surgery and brachyradiotherapy (61%). Allthe patients received non-conjugated estrogens; estrogen alone was usedin 14 patients (61%). The mean duration of HRT was 27 months (range2-49 mos). HRT was discontinued in 6 patients. The average duration offollow up was 53 months (5 - 152).Conclusions: According to the results of our overview, there were nocases of recurrence noted in our group of patients receiving HRT in theappointed period after treatment for endometrial carcinoma. Therefore,we believe that HRT most probably did not influence the prognosis ofour patients. It is noteworthy that at the same time their quality of lifehas been significantly improved.

P4.06.09INSULIN SECRETION IN WOMEN WITH ENDOMETRIALADENOMATOUS HYPERPLASIA AND RESPONSE TO Gn-RhAGONIST THERAPYV. Smetnik , G. Tchernukha, L. Staroseltseva, Research Center ofOB/GYN & Perinatology, Moscow, Russia

Objectives: The aim of the study was to assess carbohydrate metabolismin women of reproductive age with endometrial adenomatoushyperplasia (EAH) and the effect of Goserelin Depot therapy.Study Methods: Thirty-six women (mean age 33.4± 0.92, BMI =28.4±0.86) with histologically verified EAH were included in the study.The Controls were 10 healthy non obese women (mean age 29.9±1.05,BMI = 22.6±0.60). All women underwent standard 75g OGTT and weretreated with Goserelin Depot for 16 weeks. Serum insulin, T, A weremeasured by radioimmune assay before and after the therapy.Results: Fasting i sulin level was elevated in 12 (33.3%) EAH patients.Hyperinsulinemic response to OGTT was noted in 24 (66.7%) cases.Glucose and insulin AUC after glucose intake were significantly higherin EAH group comparing to the controls (AUC insulin 11 910.1 ± 1762.3 vs. 2 759.9 ± 282.1 MU/ml x 120 min, p<0.05; AUC glucose 16451.6 ± 685.9 vs. 13 343.4 ± 529.8 mg/dl x 120 min, p<0.05). Impairedglucose tolerance was revealed in 47.2% of women. Positive correlationwas noted between the insulinemic response to OGTT and BMI, T, andA level. After the Goserelin Depot therapy fasting insulin, glucose levelsand AUC glucose were unchanged but the mean level of insulin AUCwas significantly reduced (11 910.1 ± 1 762.3 vs. 9 277.2 ± 1 238.1,p<0.05).


Conclusion: Hyperinsulinemia and insulin resistance are the commonfeatures found in women with EAH. Gn-Rh agonist therapy leads notonly to reducing of sex steroids but also to the improvement of insulinsensitivity.

P4.06.10LOCALIZATION OF ESTRONE SULFATASE IN ENDOMETRIALHYPERPLASIA AND ENDOMETRIAL CARCINOMAAkihiko Watanabe , Y. Ishizuka, H. Sasaki, T. Tanaka. Jikei UniversitySchool of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo, Japan,105-8461.

Objectives: The tissue localization of Estrone Sulfatase (ES) whichparticipates in the final step of estrogen synthesis in endometrialhyperplasia and endometrial carcinoma has not been determined, nor hasbeen clarified the role of ES in the onset of these lesions. Thus thepresent study was carried out to clarify these issues.Study Methods: Immunostaining was performed using anti-ESmonoclonal antibody (KM1049). Paraffin-embedded sections, obtainedfrom 37 women with endometrial hyperplasia, 20 with normalendometrium, and 11 with carcinoma of the uterine body, wereexamined.Results: In the normal endometrium, the functional layer was negative inall cases, and the basal layer was positive in 30% (6/20). ES wasdetected in all layers in ES-positive cases with endometrial hyperplasia,and the positive rate was 51.4% (19/37) in the endometrial hyperplasiagroup. The positive rate was 66.7% (6/9) in the cases of atypicalhyperplasia and 46.4% (13/28) in the cases of a simple or complex typeof endometrial hyperplasia without atypia. ES was detected in 72.7%(8/11) of women with carcinoma of the uterine body. Stainabilitydiffered between gland ducts, even in the same specimens ofendometrial hyperplasia, and it was found that the severer the atypia ofthe duct, the stronger the stainability.Conclusion: ES was significantly more expressed as atypia andmalignancy became severer. These results suggested that the expressionof estrone sulfatase may involve the onset and growth of endometrialhyperplasia as well as the onset of carcinoma of the uterine body.

P4.06.11MALIGNANT LYMPHOMA OF UTERUS: A CASE REPORT WITHREVIEW OF LITERATUREA.Agrawal (1), G. Ofili (1), T.L. Allan (2), B.S. Mann (3), Law HospitalNHS Trust, Carluke, UK. (1) Dept. of Gynaecology; (2) Dept. ofHaematology; (3) Dept. of Pathology

The female genital tract is rarely the site of initial manifestation ofmalignant lymphomas. Most genital lymphomas arise in the vagina orcervix whilst those of the uterine corpus are extremely rare. Patientsusually present with bleeding, abdominal or pelvic discomfort or backpain but very infrequently the tumors are discovered as a result of aroutine examination. Our patient was a 67-year-old postmenopausal ladypresenting with a haematuria and upper abdominal pain. She had severalinvestigations for haematuria including cystoscopy, IVU as well as renaland pelvic scan. Pelvic scan revealed an enlarged uterus with somecalcification suggestive of a fibroid uterus. An abdominal hysterectomywas performed. Histopathology revealed Non-Hodgkin’s malignantlymphoma of the uterine corpus. She subsequently had post-operativechemotherapy. We present this case of Non-Hodgkin’s malignantlymphoma of the uterine corpus because of its rarity. We reviewed therelevant literature and management options will be discussed.

P4.06.12OCCURRENCE OF METASTATIC LYMPH NODES IN PARAILIACREGION IN ENDOMETRIAL CARCINOMA.Jacek Suzin , Andrzej Bienkiewicz, Leszek GottwaldDept. of Gynecological Oncology, Inst. of Obst. and Gynecol., MedicalUniversity, 37 Wilenska st., 94-029 Lódz, Poland.

Background: Endometrial cancer remains one of the leading cause ofgynecologic malignancy mortality in Poland. Surgical proceduretogether with radiotherapy and hormonotherapy according to staging andgrading are recommended in those cases. Surgical procedure consist of

radical hysterectomy with both adnexa, appendectomy and bilaterallymphadenectomy of parailiac region.Aim of study: We evaluated the efficacy of parailiac lymphadenectomyand occurence of metastatic adenocarcinoma in the removed nodes.Material and methods: We analysed 58 women aged 29-88 yr, withendometrial carcinoma confirmed by endometrial biopsy, whounderwent surgical treatment in our dept. between 1997-1999. In allcases uterus and both adnexa were removed together with trial ofbilateral parailiac lymphadenectomy.Results: In 42 cases bilateral parailiac lymphadenectomy was successful,in 10 cases only unilateral lymphadenectomy succeeded and inremaining 6 cases only fatty tissue was removed from parailiac region.In 5 cases in removed lymph nodes the metastases of endometrialcarcinoma were found. In 2 cases metastases were bilateral. In 2 cases,were metastases were found, the infiltration of myometrium byendometrial carcinoma was only superficial, in 3 cases infiltration wasprofound and in 2 out of those 3 cases the uterine cervix was infiltrated.Among 12 women with profound infiltration of myometrium, and cervixinvolved, in 2 cases adenocarcinoma was found in parailiac lymphnodes.Conclusions: Presented data illustrate the difficulties in parailiac lymphnodes identification and their resection. The occurence ofadenocarcinoma metastases in those nodes in 9% of our patientsincluding those with the superficial infiltration of myometrium supportthe necessity of parailiac lymph nodes removal during surgery inendometrial carcinoma.

P4.06.13PHOTODYNAMIC DETECTION OF ENDOMETRIAL CANCERP. De Jaco (1) , M. Ceccarini (1), M. Giorgio (1), T. Ghi (1), C. DelVecchio (1), D. Santini (2), L. Bovicelli (1), (1) S.Orsola-Malpighi, viaMassarenti, 13, Bologna, Italy, 40100, (2) Istituto di AnatomiaPatologica, Bologna, Italy.

Objectives: Photodynamic procedure is the use of a light beam with aproper wavelength to excite fluorescence in the cells. Some of thesecells, when suitably illuminated, show a spontaneous fluorescence (auto-fluorescence) whereas for other cells prior instillation of aphotosensitizer is requested (induced fluorescence). Amino-levulinicacid is a valid photo-sensitizer since it is selectively picked andconverted in Protoporphirin IX from target cells. Such cells whenilluminated under Argon produce a red light. ALA uptake from tumoralcells seems to be more rapid and selective. Some Authors have used thistechnique for urothelial carcinoma: intravesical instillation of ALAenabled to detect under violet light illumination (l=406.7 nm) 100% ofneoplastic lesions, with a specificity of 68.5% (1). ALA has been alsoproposed to map micromestastasis of ovarian cancer: in mice withovarian malignancies of human origin, fluorescent peritoneal noduleswere detected in all cases (2). Considering selective uptake of ALA fromendometrial cells, some Authors have proposed an endometrial photo-ablation. No study concerning photodynamic detection of endometrialcancer has been published so far in the literature. The aim of our study isto analyse those endometrial areas that, due to the high concentration ofProtoporfirin IX, appear fluorescent under Argon light (D-Light).During hysteroscopy, this procedure is supposed to select normal tissuefrom cancerous one, allowing the operator an accurate topographicdescription and a reliable pre-surgical staging of the tumour.Study Methods: In our Centre seven patients (mean age 64.3 years) wereevaluated. In four of these patients (three with a benign endometriopathyand one with a G1 well-differentiated adenocarcinoma) auto-fluorescence under blue light (Xenon 300 W-D Light- Karl Storz) wasexamined. In the other three patients, two cases of well-differentiated(G1) endometrial adenocarcinoma and one case of well-differentiatedmixed serous-papilliferous endometrioid adenocarcinoma, intrauterineinstillation of ALA, differently among the three patients, was performedbefore surgery. Doses and exposure times to the ALA were stepwiseincreased (concentrations varying from 1.5 to 3 to 4%, during 30 or 40minutes). Topical instillation of the ALA was carried on by ahysterosonography catheter (7 Fr) and then, retracted the catheter, anassessment of the cavity was performed using a 30° angle, 3 mmdiametre hysteroscope (Xenon 300 W, Karl Storz).Results: In the first group of four patients, either in tumoral or in non-tumoral endometrial cells, we were unable to demonstrate any auto-fluorescence. Concerning the use of the ALA and the inducedfluorescence, in our investigation neoplastic areas have never been


detected as selectively fluorescent, while the all endometrium appearedchromatically homogeneous.Conclusions: When illuminated under D blue light, endometrial cellsaffected from neoplastic or non-neoplastic diseases, do not seem to showfluorescence. Moreover, using our protocol for the instillation of ALA,photodynamic evaluation of the endometrium during hysteroscopy doesnot seem to be adequate. In order to map selectively tumoral cells theoptimal schedule of application of ALA must be further investigated.References :1. Kriegmar M, Baumgartner R, Knuechcl R, Steinbach P. Fluorescencephotodetection of neoplastic urothelial lesions following vescicalinstillation of 5-aminolevulinic acid. Urol 44: 836-41, 19942. Hua Z, Gibson S L, Foster T H, Hilf R. Effectiveness of delta-aminolevulinic acid: induced protoporphirin as a photosensitizer forphotodynamic therapy in vivo. Cancer Res 55: 1723-31, 19953. Fehr M K, Wyss P, Tromberg B J, Krasieva T, Di Saia P J. Selectivephosensitizer localization in the human endometrium after intrauterineapplication of 5-aminolevulinic acid. Am J Ob Gyn 175 (5): 1253-59,1996

P4.06.14RELATIONSHIP BETWEEN STROMAL EDEMA ANDLOCALIZATION OF BRADYKIN (BRK) IN UTERINE CANCER.M. Momomrua (1), T. Musha (1), H. Tanaka (1), A. Sugawara (1), I.Abiko (1), Y. Watanabe (1), J. Onodera (1), K. Takahashi (1), M.Iwashita (1), Y. Nakamura (1), Y. Yasuda (2), N. Koyama (3)(1) Dept. OB/GYN, Kyorin University School of Medicine, Tokyo,

Japan(2) Dept. Anatomy, Kinki University School of Medicine, Osaka, Japan(3) Dept. OB/GYN, Koyama Hospital, Ibaraki, Japan

Objectives: Vascular endothelial growth factor (VEGF) contributes totumor angiogenesis and vascular permeability by paracrine mechanismin vivo. Brk is a peptide strongly acts on vasodilation. We examinedimmunohistochemically whether VEGF and Brk are involved inproliferation and metastasis in uterine cancer, and also examined thespatial distribution of angiogenesis and stromal edema in malignanttumors.Results: In normal controls, VEGF and Brk were detected in vascularendothelial cells and macrophage. Brk was also detected in endometrialglandular cells. In cancer tissue there was strong expression of bothVEGF and Brk in cancer cells. Positive reaction to Factor VIIIdemonstrated the location of endothelium so that more branches ofcapillary were distributed in carcinoma than in normal controls.Conclusion: VEGF and Brk in the uterine cancer appear to be producedby the malignant cells themselves and may contribute to theangiogenesis and stromal edema to invade easily into vascular space.

P4.06.16SIGNIFICANCE OF THE EXPRESSION OF VASCULARENDOTHELIAL GROWTH FACTOR (VEGF) AND VEGFRECEPTORS (FLT-1, KDR AND FLT-4) IN ENDOMETRIALCARCINOMAY. Yokoyama , S. Sato, Y. Saito, Dept. OB/GYN, Hirosaki UniversitySchool of Medicine, Hirosaki, Aomori, Japan

Objectives: The relationship between the expression of VEGF and itsreceptors (Flt-1, KDR and Flt-4) in the tissue of endometrial carcinoma(EC) and the clinicopathological prognosis of EC has been examined.Study Methods: Subjects for the research were 86 patients with EC and4 with atypical endometrial hyperplasia (AEH) that underwent surgicaltreatment at the authors’ department after 1988, and 15 with normalendometrium (NE). After consent was obtained from the patients,several procedures were performed. From a block of resected tissuefixed with 10% formalin and embedded in paraffin, 6-mm sections wereprepared and immunohistochemical staining via the LSAB method wasperformed.The expression in the tissue of the tumor was divided into three gradesof negative, weakly positive, and strongly positive for evaluation basedon the proportion of positive cells and the staining intensity.Results:(1) the positive rate for EC was 66% for VEGF, 51% for Flt-1, 38%

for KDR, and 57% for Flt-4. The positive rate for AEH was 28%equally for VEGF, Flt-1 and Flt-4, and 14% for KDR. Only 13%

of NE specimens were weakly positive for VEGF. EC produced asignificantly higher expression of VEGF and VEGF receptors thanAEH and NE.

(2) The 5-year survival rate for groups with strongly positive VEGF,Flt-1, Flt-4 was significantly lower than that in respective weaklypositive and negative groups (p<0.05 respectively).

(3) Multivariate analysis of the prognosis revealed that myometrialinvasion, metastasis to the paraaortic lymph node, and theexpression of Flt-4 were independent factor predicting prognosis.

Conclusion: The results suggest that the expression of Flt-4 in the tissueof endometrial carcinoma may be a strong prognostic indicator.

P4.06.17SITES OF FAILURE IN ENDOMETRIAL CARCINOMA SURGICALSTAGE IBG3 AND IC TREATED WITH POSTOPERATIVEVAGINAL VAULT BRACHYTHERAPYT.Y.Ng , L.Perrin, J.Nicklin, Queensland Centre for GynaecologicalCancer, “E” Floor Clinical Sciences Building, Royal Brisbane Hospital,Queensland 4006, Australia

Objectives: The aim of this study is to examine the patterns of failureafter extended surgical staging and postoperative vaginal vaultbrachytherapy in high-risk surgical Stage I patients.Study Methods: The records of all these patients from January 1989 toDecember 1997 were examined. All patients had extended surgicalstaging and postoperative vaginal vault brachytherapy as their onlyadjuvant treatment. Failures were recorded as in the vagina, pelvis ordistant.Results: Eleven patients had recurrence. Median time to recurrence was15 months (range 6 to 56 months). Recurrences occurred in the vagina in7, pelvis in 1 and distant in 3 patients. Five of 7 vaginal recurrencesoccurred within 2 years. All patients with distant recurrence died fromdisease. One patient with pelvic recurrence is alive with disease. Only 1patient with vaginal recurrence died from disease. Six patients withisolated recurrences in the vagina were successfully treated withradiotherapy with or without local excision. All six have no evidence ofdisease at follow-up (median survival 29 months, range 20 to 71months).Conclusions: The vagina remains the commonest site of recurrence forhigh-risk Surgical Stage I patients treated with postoperative vaginalvault brachytherapy. Close follow-up in the first two years is essential todetect isolated vaginal recurrences. These are amenable to salvagetreatment with good disease-free survival.

P4.06.18SUCCESSFUL SELECTION OF WELL-DIFFERENTIATEDCARCINOMA OF THE ENDOMETRIUM BY HYSTEROSCOPICALEVALUATION FOR CONSERVATIVE MANAGEMENTT. Iha , H. Masamoto, M. Nakayama, K. Kanazawa, Dept. OB/GYN,University of the Ryukyus, Okinawa, Japan.

Objectives: To test the usefulness of hysteroscopy for diagnosing non-invasive well-differentiated carcinoma of the endometrium in an attemptof fertility preservation.Study Methods: 7 patients (27-38 y/0) with a definitive histologicaldiagnosis of endometriod adenocarcinoma G1, who were treated withmedroxyprogesterone acetate (MPA) alone or MPA followed byresectoscopical removal, were included in the study. Hysteroscopy wasperformed prior to treatment for examining a disease status in the uterinecavity, in combination with CT and MRI. Hystero-scopical diagnosticcriteria for non-invasive well-differentiated endometrial carcinomawere: 1) diffuse/localized pedunculated lesions and 2) with no necrotictissue on the tumor surface. Hysteroscopical observation was continuedalso during and after treatment.Results: Of 5 patients with diffuse lesions, the diseases in 4 responded toMPA and disappeared within 8-10 weeks, but in 1 did not and wastherefore removed by hysterectomy. The diseases in 2 patients withlocalized lesions did not respond to MAP and were removedtranscervically using resectoscope. Both of the extirpated diseases wereproven to be histologically non-invasive. All patients have been free ofdisease in the follow-up of 29 to 72 months. Two pregnanciesdeveloped, 1 resulted in abortion and the other is a normal on-goingpregnancy of 12 gestational weeks.


Conclusion: The results show that hysteroscopical evaluation mayprovide useful information in selecting well-differentiated endometrialcarcinoma for conservative management with preservation ofchildbearing potential.

P4.06.19TUMOR MARKERS SERUM TETRANECTIN AND CA125 INENDOMETRIAL ADENOCARCINOMAH. Nyholm , M. Lundstrøm, C. Høgdall*, AL Nielsen**, Dept.OB/GYN, Glostrup and Hvidovre University Hospital, *Dept. OB/GYN,National University Hospital, **Dept. Pathol., Bispebjerg Hospital,Copenhagen, Denmark.

Objectives: Serum tetranectin and CA125 were determinedpreoperatively in patients with primary endometrioid adenocarcinomaand evaluated in relation to tumor grade, stage, and cancer survival.Study Methods: Ninety-nine patients were included. Tetranectin andCA125 were determined by immunobiochemical assays.Results: CA125 levels (median 3,1 (range 1-540) U/ml) correlatedsignificantly with tumor stage (p<0.005), and when dichotomizedaccording to a cut-off level of 35 U/ml, CA125 significantly correlatedwith cancer death in univariately life table analysis. Multivariate Coxanalysis showed that CA125 > 35 U/ml was not an independent factor ofsurvival when stage was introduced. However, we found an insignificanttrend suggesting that the correlation between CA125 and cancer deathdid not merely reflect the relation between CA125 and stage, sincepatients with comparable stages of the cancer had a different outcomeaccording to the CA125 level.Serum tetranectin levels (median 10.56 (range 4.71-16.00) mg/l) in allpatients were within range determined for normal controls and did notshow any association with tumor grade, stage, or survival.Conclusions: Serum tetranectin did not show any capacity as tumormarker in endometrial cancer. One explanation may be that this cancer ischaracterized by rather small tumor volumes compared to ovariancancer, metastatic breast cancer and colorectal cancer, in whichtetranectin has been found to be a significant prognostic marker.On the other hand, the study confirmed the role for CA125 as aprognostic factor in endometrial cancer, and high levels of CA125 maybe of aid in identifying endometrial cancer patients at high risk.

P4.07 ENDOSCOPIC SURGERY

P4.07.01HYPOXEMIA INDUCE BY CO2 OR HELIUMPNEUMOPERITONEUM IS A CO-FACTOR IN ADHESIONFORMATION IN THE RABBIT MODELC.R. Molinas , P.R. Koninckx, Centre for Surgical Technologies,K.V.Leuven, Leuven, Belgium.

Objectives: To test the hypothesis that the increase in adhesionformation following prolonged pneumoperitoneum is mediated byperitoneal hypoxemia.Study Methods: In a prospective andomized trial, laparoscopicstandardized opposing lesions were performed in uterine horns andpelvic side walls by bipolar coagulation and CO2 laser in 6 groups of 8rabbits. 100% of CO2 or helium pneumoperitoneum was used for 10minutes (groups I and IV) or 45 minutes (groups II and V) to evaluatethe effect of duration of pneumoperitoneum. 96% of CO2 or helium with4% of oxygen (groups III and VI) was used for 45 minutes to evaluatethe effect of the addition of oxygen. After 7 days, adhesion formationwas scored by laparoscopy.Results: By two way analysis of variance, total, extent, type and tenacityadhesion scores increased (p=0.0003, p=0.0004, p=0.0004 and p=0.004)with increasing duration of pneumoperitoneum and decreased (p=0.02,p=0.03, p=0.01 and p=0.05) with the addition of oxygen whereas nodifferences were found between CO2 and helium. The same effect wasobserved for laser and bipolar lesions analyzed separately.Conclusions: This study confirmed the effect of duration of CO2

pneumoperitoneum upon adhesion formation and demonstrated the sameeffect using helium, indicating that a gas that does not induce acidosis,such as helium, is a co-factor in adhesion formation. The preventiveeffect of oxygen observed with both gases, strongly suggest that themain cause of adhesion formation is the peritoneal hypoxemia producedby the compression of the capillary flow by the pneumoperitoneum.

These data should be considered for human laparoscopic surgery inorder to reduce postoperative adhesions.

P4.07.02HYSTEROSCOPICAL EVALUATION OF THE MIDSECRETORYPHASE ENDOMETRIUM: A POSSIBLE CORRELATIONBETWEEN UNFAVORABLE APPEARANCE AND EARLYPREGNANCY LOSS AFTER IMPLANTATIONH. Masamoto , T. Iha, K. Kanazawa, Dept. OB/GYN, University of theRyuktus, Okinawa, Japan.

Objectives: The aims were (1) to test whether there was a possiblecorrelation between hysteroscopic findings and early phase pregnancyoutcome after implantation, and (2) to investigate histologic andendocrinologic backgrounds of endoscopical findings.Study Methods: 160 patients who had received hysteroscopicalexamination of the endometrium and then became pregnant wereexcluded. Endoscopical criteria for the ‘Good’ or ‘Poor’ midsecretoryphase endometrium were according to the appearances of both glandularopenings and blood vessels on the endometrial surface.Results: Of 160 patients, 62 (39%) had shown ‘Good’ findings of theendometrium and 98 (61%) ‘Poor’, 1 to 4 cycles prior to the conceptioncycle. 118 pregnancies persisted successfully to get live infants but 42ended in early pregnancy losses. The incidence of early pregnancy losswas significantly higher in ‘Poor’ group (34%) than in ‘Good’ (15%)(p=0.0073). In 20 patients of ‘Poor’ group, the histologically ‘in-phase’endometrium and the ‘out-of phase’ were revealed in 13 (65%) and in 7(35%), respectively. In ‘Good’ group, the ‘in-phase’ endometrium wasdocumented in all 12 patients examined. Thus, the distribution ofhistological findings was significantly different between two groups(p=0.0204). There were no significant differences for serum P4 and E2levels and P4:E2 ratio between two groups.Conclusions: Hysterocscopic evaluation of the midsecretoryendometrium might provide useful information for predicting early-phase pregnancy outcome after implantation.

P4.07.03LAPAROSCOPIC FINDINGS IN SCHISTOSOMIASIS OF THEFEMALE GENITAL TRACT AND PELVIC TUBERCULOSIS: ACOMPARATIVE STUDYA.H. Badawy , Dept. OB/GYN, Cairo University, Cairo, Egypt.

Objective: Objective is to differentiate between pelvic tuberculosis andschistosomiasis of the female genital tract by the help of thelaparoscope.Study Method: Twenty women with pelvic tuberculosis and a similarnumber with schistosomiasis of the female genital tract were included inthe study.Results: The various pathological types of schistosomiasis, such assandy patches, surface granulomata, schistosomal nodules and diffuseinfiltration of the fallopian tubes were found and could be differentiatedfrom tuberculosis which shows more extensive pathology, such as morepelvic adhesions, presence of miliary tubelcles on the surface of thepelvic and general peritoneum and evidence of tubal block withchromotubation. Tubal block is rare in schistosomiasis but common intuberculosis.Conclusion: Laparoscopy helps in the differentiation between pelvictuberculosis and schistosomiasis of the genital tract and together withhysterosalpigography, and examination of the urine and stools forBlharzia ova, a final diagnosis is arrived at.

P4.07.04MYOLYSIS IN PAROUS WOMEN WITH APPLICATION OFNd:YAG LASERSD.Takkar , K.K.Roy , A.Sinha, A. Kriplani and Maya*Dept. of OB/GYN, All India Institute of Medical Sciences, New Delhi,India,110029. * Dept. of Anaesthesia, All India Institute of MedicalSciences, New Delhi, India, 110029.

Objectives: To study the effectiveness of Nd:YAG laser in coagulationof symptomatic myomas.Study Methods: This study comprised of ten women who underwentlaser myolysis with Nd:YAG Laser set at 30-50 watt power and carried


through 600/mm bare fiber through Laparoscope under generalanaesthesia and using three portals for endoscopic procedure.Results: Ten women undergoing Laser myolysis had mean age 40.5years and mean parity 2.8. Commonest symptom was menorrhagia. Onlyfibroids less than 10cm size (range 1.9cm-8cm, mean 5.27cm) weretargeted. Most of the women had single fibroid (70%) while 85.7% hadintramural fibroids, 35% had anterior and 35.7% had fundal fibroids.Preoperative treament with danazol 400mg/day for two months wasgiven. The number of punctures varied from 5-80 (mean 40.5),depending on size of fibroid. Mean operating time was 10.2 minutes andmean blood loss was 99ml. There were no intraoperative orpostoperative complications. At six month follow up 100% symptomaticrelief was found in 1, 75% relief in 2, 50% relief in 4 and no relief in 1.There was significant reduction in size of myoma in all women withoverall improvement of symptoms in 87.5% women.Conclusions:.Nd:YAG Laser myolysis rendered symptomatic relief in87.5% of women thus obviating need for hysterectomy in them in afollow up to six months.

P4.07.05OPEN VERSUS CLASSICAL PERFORMANCE OFPNEUMOPERITONEUM IN GYNECOLOGICAL LAPAROSCOPICSURGERY. COMPARISON OF MORBIDITYM. López-Iglesias , A. Kably-Ambe, J. Barrón-Vallejo. Hospital Angelesde las Lomas. Consultorio # 280. Vialidad de la Barranca s/n. ColoniaValle de las Palmas. Huixquilucan, Estado de México. MEXICO. CP52763.

Objective: The objective of the work was to compare the rates ofcomplications for open and conventional performance ofpneumoperitoneum for patients undergone to gynecological laparoscopy.Study Methods: Were studied the cases of 278 patients divided in twogroups: Group 1 (n=107) patients treated with open creation ofpneumoperitoneum with Origin trocar, and group 2 (n=171) patientsmanaged with blind technique using Veress needle.Results: There were not complications in patients of group 1. On otherhand, in group 2 there were five complications (P less than 0.025), twowere intraabdominal injuries related with blind insertion of sharpinstruments.Conclusions: In this groups of patients, open formation ofpneumoperitoneun seems to have less morbidity than blind procedure;the former modality eilimates life-threatening complications as CO2embolism. However, is mandatory to collect more cases to evaluate theconsequences of techniques to creating pneumoperitoneum ingynecological laparoscopy.

P4.07.06OVARIAN NEOPLASMS ARE AMENABLE TO LAPAROSCOPICMANAGEMENTS. Desai , N. Wadia Maternity Hospital, Mumbai, India.

Objective: An ovarian mass can be managed laparoscopically providedthe lesion is benign.Study Method: 140 patients with benign ovarian cysts (Ca125,transvaginal USG and color Doppler confirmed) were managedlaparoscopically in a private clinic over a 3 year period between January1997 and December 1999.Results: The procedures were performed by a single surgeon andintraoperative and post operative complications were not noted. All thecysts were benign however 25 patients were found to have matureteratomas, 7 of which ruptured during surgery with no untoward effect.Postoperative follow-up up to 3 months was done in most cases.Conclusion: A video clip showing some of the unusual and interestingfeatures noted will be shown.

P4.07.07PATIENTS’ PERCEPTION OF PAIN AT OUT PATIENTHYSTEROSCOPY: A PROSPECTIVE OBSERVATIONAL STUDYS. Jivraj , M. Dass, J. Panikkar, V. Brown, Dept. of Hysteroscopy, JessopHospital for Women, Sheffield, England.

Objectives: To assess the acceptability of out patient hysteroscopy usingpatients’ perception of pain and preference for general anaesthetic.

Study Method: 100 patients attending the out patient hysteroscopy clinicat the Jessop Hospital for Women were included in this study. A rigidAesculapâ 3.5 mm hysteroscope was used and carbon dioxide as thedistension medium. Local anaesthetic was used only if the patientexperienced discomfort or if cervical dilation was required. Six mls of4% Citanestâ (prilocaine hydrochloride 40 mg/ml) was injected directlyat 4 points into the cervix. Patients’ perception of pain (scored on ananalogue scale ranging from 1 to 5) during and immediately afterhysteroscopy and the desire to have the procedure done under generalanaesthetic, were used as outcome measures. Z test was used forstatistical analysis.Results: Significantly more pain (p<0.05) was experienced duringhysteroscopy than afterwards irrespective of the use of Citanestâ. Themean pain score of patients receiving local anaesthetic was higher thanthose who did not receive local anaesthetic. There was a greater desire tohave the procedure done under general anaesthetic when Citanestâ wasused than when it was not used. Pain scores were higher in those patientswho preferred general anaesthetic.Conclusions: Pain is a major factor influencing the acceptance of outpatient hysteroscopy. Our practice of using local anesthetic only whendiscomfort is experienced may be inappropriate. A randomizedcontrolled trial of the elective use of Citanestâ is proposed to establishits effectiveness and acceptability.

P4.07.08RESULTS OF ENDOSURGICAL ELECTRODESTRUCTION OFUTERINE MYOMA AND ADENOMYOSISL.D. Belocerkovceva , A.N. Strizhakov, A.I. Davydov, V.B. Osadchev,2nd Dept. OB/GYN, Sechenov Medical Academy, Moscow, Russia.

Objectives: To define the efficiency of an electrosurgicalelectrodestruction of a uterine myoma and adenomiosis at the patients ofreproductive age. To develop a technique, to determine the indicationsand conditions to application of the given method.Study Methods: 29 women of reproductive period with uterine myomaand adenomiosis are inspected with which the endosurgicalelectrodestruction of a myoma or endometriotic heterotopy is carriedout. To a destruction of nodes of a myoma or adenomiosis applied abipolar laparoscopical needle. At the second stage at the patientsadenomiosis made a hysteroresectoscopy (total ablation ofendometrium). For a control behind efficiency of treatment spenddynamic transvaginal ultrasonic scanning.Results: On data of ultrasound, maximum rate of decrease of size of auterus at the patients adenomiosis marked per the first 60 days, in theconsequent size of a uterus decreased insignificantly or did not vary. Themaximum rate of decrease of size of a uterus at the patients of a myomawas marked by the end of 6 months. For period of observation of arelapse of clinical symptoms, adenomiosis and myoma of a uterus is notfounded.Conclusion: The endosurgical electrodestruction of uterine myoma andadenomiosis is an effective method of treatment.

P4.07.09THE IMPORTANCE OF SURGICAL LAPAROSCOPY IN THECOMPLEX TREATMENT OF PERITONEAL INFERTILITYZ. Sirbu , O. Cernetski, R. Comedant, O. Salari, Dept. OB/GYN, StateMedical and Pharmaceutical University, Nicolae Testemitanu, Chisinau,Republic of Moldova.

This paper contains the results of complex treatment of 386 patients withperitoneal infertility. According to type of resolving and healthimproving therapy patients were divided in to three groups. The firstconsisted of 152 patients who had operative laparoscopy. The secondgroup consisted of 167 patients who had operative laparoscopy followedby adjuvant therapy to prevent postoperative pelvic adhesions. Patientsin the third group had two consecutive surgical laperoscopy withresolving and health improving therapy. The most important role in thisgroup was attributed to the second-look laparoscopy when removing ofnewly formed tubal, ovarian, uterine or peritoneal adhegens wasperformed. Types of procedures performed during surgical laparoscopy:salpingotomy 92 (23, 83%), fimbrioplasty 162 (41.97%),salpingoovareolivis 386 (100%, diatermocoagulations ovarian – 86 (22,28%).


In the second group the adjutant therapy to prevent postoperative pelvicadhegens included: 200 ml of Reopoligliuchine + 10ml of Dioxidineintraabdominal before closure of the peritoneal cavity and for the first 3postoperative days; and gidrotubation with 10 ml Novocain 0.5 + 4 mgDexametasone in patients who had fimbrioplasty of salpingostomyduring laparoscopy and gynaecological manual massage.In the third group with two consecutive laparoscopy the most importantrole was attributed to the second-look laparoscopy while adjuvanttherapy was the same as in the second group.Pregnancy in the first group occurred in 19.73% of cases (30 patients),in second group – in 30.53% (51), in the third – in 52.23% cases (35patients).It is concluded that combination of surgical laperoscopy withmedicaments therapy and, especially, with second-look laparoscopyimproves the results of peritoneal infertility.

P4.07.10TWO METHODS FOR TREATING HIGH GRADE SQUAMOUSLESIONS OF UTERINE CERVIX.C.R.Miranda , J.A.Miranda, M.S.Wanderley, C.N.Resende, A.C.Cunha,University of Brasilia, SQN 206 Bloco A Ap. 401, Brasilia, DF, Brazil,70844010.

Objective: Assess the efficiency for Conic Biopsy Excisor (CBE), a newtool for office uterine cervix conization compared to standard inpatientcold knife conization (CKC) in a University Hospital settings, treatinghigh grade squamous intraepithelial lesions (HG-SIL).Patients And Methods: We are prospectively studying so far, 18 HG-SILpatients randomly set to both CBE and CKC from august 1998 to may1999, comparing surgery duration in minutes, blood loses,hospitalization time, return to day life activities time, and cytologicalevidence of recurrence, three and six months after the proceedings.Results: Twelve patients were submitted to CBE and six to CKC. ToCBE and CKC respectively, surgery duration was 14 and 35 minutes,blood losses were 19.8 and 78.3 ml, hospitalization was zero and 3,25days, and return to day life activities was 2.25 and 4.8 days. Atcytological control by three and six months, no patient recurred in theCBE group and one recurred in the CKC group.Conclusion: This study is planned to encompass 50 patients in CKCgroup and 150 in CBE group. So far this pilot study has shown theevidence of superior results using Cone Biopsy Excisor, which producesgood pathological specimens, is easy to learn and easy to use, and resultsin less morbidity and more confort to patients. In the future we foreseean increasing interest from the medical community in this cost saving,safe and reliable instrument, taking over most of the indications forinpatient proceedings.

P4.07.11URINARY TRACT COMPLICATIONS DURING LAPAROSCOPICSURGERYA. Ostrzenski 1, B. Radolinski2, KM Ostrzenska3 1Medical University of Silesia, Poland; Howard Uni., Washington, DC,USA2Georgetown University School of Medicine, Washington, DC, USA3G. Washington University Medical Center, Washington, DC, USA

Background: Urinary tract (bladder, ureter, and urachus) complications,incidence, location, primary procedure and methods used to repairinjuries incurred during laparoscopic surgery are unknown.Objectives: To present data in reference to urinary tract laparoscopicinjuries based on a review of world literature.Study Methods: MSH terms were used in a search of the Medline,Online ACOG, and Ovidisc computerized database.Results: A high incidence of laparoscopic injury to the urinary tract wasdocumented in certain primary procedures. The study documented that,only in a very few cases was repair performed via laparoscopy.Electrocautery instruments were most commonly involved in injury, andLAVH has the highest rate of complication. Intraoperative diagnosis ofurinary tract injury is not frequently accomplished.Conclusions:.A high prevalence of urinary tract injury incurred duringlaparoscopy was identified.There exists a low standard of intraoperative diagnosis of urinary tractinjuries, leading to a delayed diagnosis of injury.Laparotomy is the primary approach for repair of injury.

Laparoscopic repair is applied in an innovative way departing, in manyinstances, from established surgical principles.

P4.07.12ANALYSIS OF 114 CASES OF TVH AND LAVHY.F. Luo ; N.V. Lau, Dept.OB/GYN, Centro Hospital C.S. J., Macao,P. R. China

ObjectivesWe assessed the advantage, indications, surgical managementand the clinical value of TVH and LAVH for patient without uterineprolapse.MethodsFrom Oct. 1996 to Dec.1999, 114 consecutive womenunderwent TVH (101 cases 88.6%) and LAVH (13 cases 11.4%) forvarious kinds of benign gynecological diseases were included in study.The mean age was 44.5 years (range 32-73). There were 15 patients(13%) with normal uterine size, and 53 patients (47%) with uteri of size12-16 weeks and 46 patients (40%) äT12 weeks. 33 patients (29%) hadhad previous pelvic operation.ResultsThe mean operating time was 55min (range 28-95) for TVH and 117 min (range 85-180) for LAVH. Theamount of operative blood loss was 50-150 ml. Only used one timeCefoxitin 2 g IV before 30 min of operation for prophylactic antibiotic,not to keep urine catheter. Post operation temperature was below38ºC and analgesics were used for 0-3 times. Post-operativehospital stay was averaged 2.9 days.ConclusionsTVH was associatedwith remarkable advantages: shorter operating time, shorterhospitalization, and quicker recovery. Enlargement of uterus to a size>12 gestational weeks, benign adnexa mass and previous operativehistory should not be considered a contraindication to TVH. The keysare performing pelvic examination carefully under anesthesia todetermine condition of pelvic; choosing correct operative methods toreduce size of uterus during operation; applying LAVH if necessary.90% patients who will undergo total abdominal hysterectomy couldprobably undergo TVH or LAVH instead.

P4.07.13SONOHYSTEROSALPINGOGRAPHY (S-HSG) PERFORMED INWOMEN AFTER OVIDUCTS RECONSTRUCTIVE OPERATIONSD. Wojcik , H. Raszcyk, Dept. OB/GYN, Medical University, Gdansk,Poland.

Study Methods: Between 1997-1999, 32 women who have undergoneoviducts reconstructive operations were subjected to medicalexamination. In 24 cases, it was laproscopic, one-sided or two-sidedrecanalisation of the oviducts by perioviducts adhesion separation. In 8cases, it was the plastic surgery of oviducts performed by means oflaparostomy.The USG examination with the use of ECHOVIST contrast medium wascarried out between the 5th and the 12th day of the menstrual cycle, theinflammatory process of the pelvis having been excluded. Contrastmedium was administered via Schultz’s apparatus. 20 ml of contrastmedium was dosed and then the flow of contrast medium through theoviducts to the abdominal cavity was observed by means of transvaginalultrasound.Results: It has been reported than the cases of 15 women from theexamined group, S-HSG image showed the correct anatomy of bothoviducts. In 10 cases, total occlusion of both oviducts stated. In 3 cases,the patency of one oviduct was reported. In 4 cases, the presence of one-sided oviduct hydrocele or one-sided oviduct empyema with itscomplete occlusion was indicated. All 17 women whose S-HSG imagehad proved inappropriate were subjected to laparoscopic examination. In15 cases, the H-SHG came out in accordance with the results of thelaparoscopic examination. 13 women from the examined group weredirected to the IVF impregnation.Conclusion: S-HSG examination enables credible estimation of theanatomical state of the oviducts after the preceeding reconstructiveoperations.


P4.08 GENE THERAPY

P4.08.01AN ATTEMPT FOR GENE DELIVERY OF ATP7B cDNA TOHEPATOCYTES OF YOUNG LEC RAT BY TESTIS-MEDIATEDGENE TRANSFERE. Hashida (1,2), T. Ubagai (2), Y. Sasabe (1), Y. Abe (1), H. Nakagama(2), H. Kubo (1), S. Hirakawa (1)(1) The 1st Dept. OB/GYN, Toho University School of Medicine,

Ohta-ku, Tokyo, Japan(2) Biochem. Div, National Cancer Center Research Institute, Chuo-

ku, Tokyo, Japan

Objectives: Gene transfer to germ cells has been attempted by a varietyof methods including microinjection, virus mediated transfection andsperm mediated transformation. The Testis-Mediated Gene Transfer(TMGT) method is of great interest because of its ease and simplicity.This study was designed to attain foreign gene expression in postpartumprogeny of the Long-Evans Cinnamon (LEC) rat, which has a defect inthe Atp7b gene, by means of direct DNA injection into testes.Study Methods: Cationic liposome-encapsulated plasmid ATP7Bexpression vector pCMV-7B[HA]3 driven by a CMV promoter (30 mg)was directly injected via a needle into the testes of mature male LECrats. Two days after injection, these males were mated with female LECrats. The genomic DNA of day 5 pups (F1) were isolated from the tailtissues, and the ATP7B cording region was amplified by PCR. TheATP7B positive F1 rats were then sacrificed on day 12. The genomicDNAs isolated from several organs were subjected to PCR and ATP7Bexpress was also identified using RT-PCR analysis. Southern blotanalysis was performed to detect ATP7B cDNA fragments. The livertissues of F1 rats were frozen in liquid nitrogen and sections werestained immunohistochemically with anti-HA and antiATP7Bantibodies.Results: On PCR analysis of genomic DNA isolated from the tail tissuesof day 5 pups (F1), ATP7B fragments were detected in all pups (5/5;100%). PCR analysis of genomic DNA isolated from liver of the sameF1 rats was positive for 2 (40%) of 5 pups. However RT-PCR analysisof liver mRNA revealed 5 of 5 F1 rats (100%) to be positive. Southernblot analysis of genomic DNAs revealed the same results as PCRanalysis.Conclusions: In this study, we showed the convenience of using “testis-mediated gene transfer” to integrate ATP7B cDNA into the LEC rathepatocytes genome. In the future, this method may be of value in fetalgene therapy. Because PCR-Southern analysis of genomic DNA isolatedfrom liver suggests either fragmentation and/or gradual disappearance oftransferred ATP7B cDNA, the TMGT method requires furtherimprovement, including the injection route used.

P4.08.02EXPRESSION OF NK4 cDNA IN OVARIAN CANCER CELLSSUPPRESSES INTRAPERITONEAL DISSEMINATION ANDEXTENDS HOST SURVIVALY. Saga (1), M. Suzuki (1), M. Urabe (2), H. Mizukami (2), K. Ozawa(2), T. Nakamura (3), I. Sato (1)(1) Dept. OB/GYN, Jichi Medical School, Kawachi, Japan.(2) Div. Genetic Therapeutics Center for Molecular Medicine, Jichi

Medical School, Kawachi, Japan.(3) Div. Biochemistry Dept. Oncology Biomedical Research Center,

Osaka University Medical School, Suita, Japan.

Objectives: Intraperitoneal issemination is one of the most frequentpathways of progression of ovarian cancer. NK4 is the a-chain ofhepatocyte growth factor (HGF) and inhibits the mitogenic, motogenic,and morphogenic activities of HGF. To further characterize the functionof NK4 and to examine its potential role in gene therapy of ovariancancer, we transfected a NK4 cDNA into ovarian cancer cells andanalyzed the antitumor activities in vitro and in vivo.Study Methods: Cloned NK4 cDNA was inserted into pCMV-IRES-bsr,generating pCMV-NK4-IRES-bsr. The expression vector encoding NK4or the control vector coding luciferase was transfected into ovariancancer HRA cells by calcium phosphate-mediated transfection. Afterselection, the expression of NK4 in each clone was determined bywestern blotting with anti-HGF polyclonal antibody. One NK4-positiveclone (HRA/NK4) and one control clone (HRA/LUC) were furtheranalyzed. Cell migration was measured using an in vitro would healing

assay. HRA/NK4 and HRA/LUC cells were xenografted into nude miceto examine the effect of NK4 on tumor growth and intraperitonealmigration.Results: no differences in cell proliferation between HRA/NK4 andHRA/LUC. In vitro cell migration was markedly decreased inHRA/NK4 cells compared with HRA/LUC cells (p£0.01). All thecontrol mice injected with HRA/LUC cells developed ascites and diedwithin 15 days, whereas HRA/NK4-injected mice showed a delay inascites accumulation and survived significantly longer than control mice(p£0.01).Conclusions: Our data suggest a novel therapeutic approach for ovariancancer by gene therapy using NK4.

P4.08.03METRORRHAGIA IN POSTMENOPAUSIS – TREATMENT ANDHISTOPATHOLOGICAL FINDINGSL. Jovcevska-Ivanovska, G. Adamova, S. Adamoska, Dept. OB/GYN,Hospital in Kumanovo, R. of Macedonia

Objectives: The aim of the study was to investigate which are the mostfrequent hystopatological findings, obtain from material withexploration of cavum uteri in patients with dg.: Metrorrhagia inpostmenopausis.Study Methods: One hundred fifty eight history of the women with dg.Metrorrhagia in postmenopausis, in which Curettage explorativafractionata was performed, were analyzed.Results: Statistical analysis of histopatological investigation demonstratethat the most frequent findings were the following: 27 women (17.1%)were with dg. Regular cylindrical epithelia, 27 (17.1%) with dg.Adenocarcinoma endometrii and 19 (12.0%) with dg. Hyperplasioglandularis endometrii.Conclusions: These results indicate that from the rapid increasing ofmalignant diseases, each case of metrorrhagia in postmenopausis mustbe treated with fractionated explorative curettage.

P4.08.04NEW PRENATAL DIAGNOSIS MEHOD OF STEROID 21-HYDROXYLASE DEFICIENCY AND MUTATIONS IN CYP21BGENE OF JAPANESE PATIENTSZ. Hayashi , A. Yamanaka, S. Suzuki, R. Sawa, Y. Yoneyama, Y.Asakura, T. Araki, Dept. OB/GYN, Nippon Medical School, Tokyo,Japan.

Objectives: The aim of the study was to develop new prenatal diagnosismethod of steroid 21-hydroxylase deficiency. In this study, we appliedthe analysis of polymerase chain reaction-single strand conformationpolymorphism (PCR-SSCP) profiles to DNA-based diagnosis of 21-OHD and attempted to use this technique for prenatal diagnosis. And weanalyzed mutations in CYP21B gene of ten Japanese patients using thismethod.Study Methods & Results: The polymerase chain reaction-single strandconformation polymorphism (PCR-SSCP) profile analysis could beapplied to the prenatal diagnosis of steroid 21-hydroxylase gene,including all the mutations previously reported. PCR-SSCP analysis inten Japanese patients showed at least one polymorphic site in each case.We confirmed that the mobility shifts in SSCP in an affected kindredwere transmitted as a Mendelian trait. As these results indicated thatPCR-SSCP profiles could be used for DNA-based diagnosis, weobtained by chorionic villus sampling of a fetus and PCR-SSCP profileswere analyzed in the PCR-amplified fragments in which the mobilityshifts had been observed in the SSCP of the proband.And we analyzed the presence of several mutant 21-hydroxylase gene inten Japanese patients with steroid21-hydroxylase deficiency. We havefound that allele 655G has a moderately high incidence among Japanesepatients with 21-hydroxylase deficiency.Conclusions: The results suggest that this new application of PCR-SSCPhas advantages over conventional RFLP analysis and is useful in makinga prenatal diagnosis of steroid21-hydroxylase deficiency both rapidlyand accurately.


P4.09 GYN-ONCOLOGY

P4.09.01ANALYSIS OF 38 CASES OF CHORIOCARCINOMAB.K. Chakrabarti , N.R. Mondal, Cancer Welfare Home and ResearchInstitute, Thakurpukur, Calcutta, India.

Objective: A study epidemiology & treatment of choriocarcinoma.Study Methods: Retrospective. 38 cases were analyzed from 1992-98.Predominantly young women, Muslim, between the ages of 20-30 yrs, intheir first or second pregnancy, mostly from a rural population, sufferingfrom the condition. Diagnosis was made by clinical examination,histology report, serum B-HCG, U.S.G., Chest X-ray. 12/38 cases theprecedent event was hydatidiform mole.Result: 9 cases had hysterectomy in other peripheral hospital because ofuncontrolled hemorrhage. All patients received chemotherapy – single ormultiple drug. 4 cases were lost to follow-up. 34 cases were followed upfor one year without any recurrence. 1 case had successful full termpregnancy 4 years after completion of treatment without any fetalabnormality.Conclusion: Chemotherapy should be the first line of treatment inchoriocarcinoma. Most cases respond to methotraxate but in cases withhigh B-HCG in serum, metastsis & recurrence multiple drug has beenuseful. Pregnancy can be successfully undertaken 2-3 yrs. aftercompletion of treatment. Hysterectomy is advised only in cases ofuncontrolled hemorrhage due to uterine perforation by malignancy.

P4.09.02ANALYTIC EPIDEMIOLOGY OF EPITHELIAL OVARIANCANCER WITH A SPECIAL REFERENCE TO DEVELOPINGCOUNTRIES: AN EVIDENCE-BASED ANALYSISM.M.F. Fathalla (1), R. Foy (2)(1) Dept. OB/GYN, Assiut University, Assiut, Egypt.(2) Clinical Effectiveness Network, Edinburgh, UK.

Objective: The review aims to assess studies tackling descriptive andanalytic epidemiology of epithelial ovarian cancer with a particularreference to the picture in developing countries.Study Method Original article of analytic epidemiology of ovariancancer retrieved through Medline, hand searching and reference listchecking was done as well.Results: The reported geographic difference in incidence cannot beaccepted due to difference in data collection and quality. History ofovarian cancer in a 1st degree relative is associated with a RR of 2.8-3.1.Each term pregnancy confers 14-16% risk reduction. Combined oralcontraceptive use is protective (RR 0.46-0.55 for more than five yearsuse). Association of depoprovera, HRT and infertility drugs with risk isuncertain. Perineal talc exposure and high-risk diet such as animal fat,lactose and coffee are associated with a RR of <2. A history of tuballigation or hysterectomy is associated with decreased risk. In thedeveloping world, monitoring the risk factors shows that there isevidence toward an increasing adoption of a high-risk behavior.Conclusion: There is the need for better quality data on ovarian cancer indeveloping countries. Establishing cancer registries will help. With theevidence for a trend to adopt high-risk behavior for ovarian cancer,primary prevention hold the main hope, especially in developingcountries. Achieving tertiary and secondary prevention is difficult andexpensive. Primary prevention holds the main hope for developingcountries. Better understanding of the risk factors can help in thisdirection.

P4.09.03COMPARISON OF CONE MARGINS STATUS IN HIGH GRADECIN TREATED BY SURGICAL CERVICAL AMPUTATION, COLDKNIFE CONIZATION AND LEEP AND THE ROLE OF FROZENSECTION EXAMINATION IN PREDICTING INVOLVEDMARGINSJ.P. Carvalho , F.M. Carvalho, E.A.G. Pereyra, C.I. Parellada, P.LSchivartche, J. Souen, Hospital das Clínicas, Universidade de São Paulo,Brazil.

Objectives: The aim of the study was to investigate the status of the conemargins in patients with high grade CIN treated by three differentprocedures: cervical amputation, cold knife conization and loop

electrosurgical excisional procedure (LEEP) and the role of frozensection examination in predicting the involved margins.Study Methods: One hundred and fifty four women with high grade CINwere included: 41 cervical amputation, 60 cold knife conization and 53LEEP. The cone margins were evaluated. A subgroup of 25 women,older than 40 were submitted to conization, frozen section examinationof the cone followed by hysterectomy.Results: The margins were positive in 8/41 amputation, 28/60 conizationand 24/53 LEEP. Age was the mean factor related to involved margins.Frozen section showed involved margins in 15/25 women. All of themwere confirmed by permanent sections. Residual disease was present inthe uterus in 11/15 women with cone involved margins.Conclusions: Margins involvement occurred in all groups but werehigher in older women. Frozen section examination was accurate in theevaluation of margins status.

P4.09.04CORRELATION BETWEEN SHRINKAGE OF UTERINELEIOMYOMA TREATED WITH GNRH AGONIST ANDESTROGEN RECEPTOR ALPHA GENE POLYMORPHISMA.Tsujimura , N. Kawamura, K. Minakuchi, S. Ogita, Dept. OB/GYN,Osaka City University Medical School, Osaka, Japan.

Objective: To determine the correlation between shrinkage of uterineleiomyoma treated with GnRH agonist and estrogen receptor (ER) alphagene polymorphism of uterine leiomyoma tissue.Study Methods: 35 women with terine leiomyoma who were treatedwith GnRH agonist before surgery were studied. The volume of thelargest myoma nodule was measured by MRI before and 3 months afterthe beginning of GnRH agonist treatment and the percent reduction inmyoma volume was calculated. Genomix DNA was extracted fromleiomyoma tissue and a part of the intron 1 ER alpha gene (1.3kbp) wasamplified by PCR. The PCR products were then digested with arestriction endonuclease, Pvu-II or Xba-I. Genotypic polymorphism wasdefined as XX or PP (Absence of a restriction site on both alleles), xx orpp (presence of a restriction site on both alleles) and Xx or Pp(heterozygous).Results: The distribution of the Pvu-II and Xba-I RFLPs was as follows:five PP’s (14%), 15Pp’s (43%), 15 pp’s (43%), four XX’s (11%), eightXx’s (23%) and 23 xx’s (66%). The mean percent reduction in volumeof the largest myoma was 8±39% for PP; 4±66% for Pp; 41±21% for pp;14±17% for XX; 24±34% for Xx and 18±60% for xx. Uterine myomawith the pp genotype was thus significantly likely to shrink than theother Pvu-II genotypes (p=0.036). There was no significant correlationbetween the shrinkage of uterine leiomyoma and Xba-I genotypes.Conclusion: This study showed that the extent of shrinkage of uterineleiomyoma treated with GnRH agonist was related to ER alpha genepolymorphism of uterine leiomyoma tissue.

P4.09.05CORRELATION BETWEEN SHRINKAGE OF UTERINELEIOMYOMA TREATED WITH GNRH AGONIST ANDINTERSTITIAL DELETION OF CHROMOSOME 7K. Minakuchi , N. Kawamura, A. Tsujimura, S. Ogita, Dept. OB/GYN,Osaka City University Medical School, Osaka, Japan.

Objectives: The purpose of this study was to investigate the correlationbetween shrinkage of uterine leiomyoma treated with GnRH agonist andinterstitial deletion of chromosome 7q, which is one of the mostcommon chromosomal changes associated with uterine leiomyoma.Study Methods: This study covered 31 women with uterine leiomyomawho were treated with GnRH agonist before surgery. The volume of thelargest myoma nodule was measured by means of MRI before and 3months after the beginning of GnRH agonist treatment, and thepercentage of volume reduction was calculated. Genomic DNA wasextracted from leiomyoma tissue and peripheral blood and amplified byPCR using florescently-tagged oligonucleotide primers of 12microsatellite loci on chromosome 7. The PCR products were analyzedfor loss of heterozygosity (LOH) by using an ABI 310 automatedflorescent DNA sequencer.Results: Of the 31 informative tumors, 5 (16%) showed LOH withdeletion of common region D7S419. The mean percent reduction involume of the largest myoma with LOH was 32±13% and without LOHwas 18±58% (not significant). One tumor showed interstitial deletion of


both alleles and a reduction in volume of 19%. Another tumor showedan extra band and an increase in volume of 13%.Conclusions: This study with microsatellite LOH analysis revealed that16% of uterine leiomyomas showed interstitial deletion of chromosome7q. Although the existence of tumor suppressor genes in this region wassuggested, there was no significant correlation between shrinkage ofuterine leiomyoma treated with GnRH agonist and interstitial deletion ofchromosome 7q.

P4.09.06CORRELATION OF DESCRIPTIVE SONOGRAPHIC CRITERIAFOR ADNEXAL TUMORS AND OVARIAN MALIGNANCIESG. Ivanovic, D. Ivanovic, S. Kadija, V. Milenkovic, SV Petkovic,M. Radovic, LJ Mirkovic. Department of Gynecology and Obstetrics,Clinical Center of Serbia, Belgrade, Yugoslavia

Objective: The aim of this study was to determine value of sonographiccriteria in prediction of malignant potential of ovarian tumors.Study Methods: Our study included 112 patients after the surgicalprocedure on our clinic during two years with verified malignant ovariantumor. We analyzed their sonographic findings as a part of routinepreoperative treatment.Results: Among 112 patients 3 of them (3,36%) sonographicaly hadunilocular tumor, 3 (3,36%) unilocular cystic Tu, 15 (16,8%)multilocular Tu, 69 (77,28%) multilocular solid Tu, 23 (64%) solid Tu.Results of our study showed that there is no absolutely specificultrasound pattern which can show us whether the ovarian tumor ismalignant or not, with one exception; malignant ovarian tumors morefrequently have complex sonographic pattern.Conclusions: However as a conclusion we can say that despite inabilityto predict malignancy accurately echographic findings will frequentlyassist the ultrasonographer in making a correct diagnosis and can be ofthe crucial significance in decision making process about furthertherapeutic procedures.

P4.09.07CYTOKERATIN 19 mRNA: A NEW MARKER FOR DETECTIONOF METASTASES IN LYMPH NODES OF GYNECOLOGICALCANCER PATIENTSM. Kagabu , T. Izutu, T. Kagabu, Dept. OB/GYN, Iwate MedicalUniversity, Morioka, Japan.

Objectives: Lymph node metastasis is known as a significant predictorof prognosis in gynecological cancer patients. Recently, reversetranscriptase polymerase chain reaction (RT-PCR) has been applied todetecting micrometastasis. It is reported that cytokeratin 19 (CK-19)mRNA is not expressed in the peripheral blood cells and lymph nodes ofthe healthy subjects. Detection of DNA fragments of CK-19 in thelymph nodes suggests the existence of epithelial malignant tumor cells.We examined whether CK-19 expression can be used as a tumor markerfor lymph nodes metastasis in gynecological cancer patients.Study Methods: We examined 7 gynecological cancer tumors, 3 types ofgynecological cancer cell lines and 59 lymph nodes obtained from 16gynecological cancer patients who underwent curative operation andwere histologically diagnosed, using RT-PCR to amplify mRNAs forCK-19.Results: CK-19 mRNA was detected in 6 gynecological cancer tumors(85.7%). CK-19 mRNA was detected in all of gynecological cancer celllines. CK-19 mRNA was detected in 2 cases of the histologicalmetastasis (66.7%). And CK-19 mRNA was not detected in all of thehistological no metastatic cases (13 cases).Conclusions: Our results indicate that CK-19 is a useful tumor markerfor lymph nodes metastasis in gynecological cancer.

P4.09.08DIAGNOSIS OF THE INVASIVE CERVICAL CARCINOMA AFTERTHE CONISATIONKesic V , Pantovic S, Petkovic S, Argirovic R, Milenkovic V,Mirkovic Lj, Radovic M., Department of Gynecology and Obstetrics,Clinical center of Serbia, Belgrade, Yugoslavia

Objectives: Due to the fact that cervical biopsy don¢t always recognizethe most severe changes on the uterine cervix, it has been suggested that

application of destructive methods in diagnosis of cervical intraepithelialneoplasia (CIN) may result in overlooking of invasive uterinecarcinoma.Study Methods: In order to evaluate diagnostic reliability of targetbiopsy and consequently the incidence of cervical carcinoma in samplesof the cervix obtained by conisation we examined the clinical historiesof 239 patients operated because of CIN lesions: 17 for CIN-I, 48 forCIN-II and 174 for CIN-III.Results: Patohistological examination of the removed tissue evidenced:carcinoma in situ at 42 (15.57%) patients, microinvasive carcinoma in34 (14.22%) and invasive cervical carcinoma in 8 (3.35%). Onemicroinvasive carcinoma was detected in a patient operated for CIN-II,one invasive in a patient operated for CIN-I, while all other cases ofcarcinoma were detected in CIN-III patients. The results of our analysissupport the principle of excising the abnormal transformation zone, ifcytological or colposcopic criteria or biopsy indicate CIN.Conclusions: In spite of introduction of local destructive techniques fortreatment of CIN, conisation of the uterine cervix remains irreplaceablesince it is the most reliable method for identification of the presence orabsence of invasive disease.

P4.09.09DIAGNOSIS OF PLACENTAL INSUFFICIENCY BY A METHODOF LASER CORRELATION SPECTROSCOPY (LCS)V. Nagornaya , V. Marichereda, Dept. OB/GYN, Odessa MedicalUniversity, Odessa, Ukraine.

Objectives: To determine the sensitivity of LCS in diagnosis of placentalinsufficiency at various terms of pregnancy.Study Methods: The LCS of serum, research of homeostasis by definingsub-fractional structure of serum in a range from 0 to 1000 nm by meansof registration of modifications of spectral characteristics of amonochromatic coherent radiation as an outcome of light dispersionwhen passing through serum (plasma). For the qualitative andquantitative analysis of findings, “the semiotic classifier”, distinguishing8 biological conditions has been used.Results: Fifty-seven pregnant women have been examined at the termsof gestation from 9 to 38 weeks – 30 of them had placental insufficiencyand 27 had normal physiological pregnancy.Differentially significant indications have been revealed, defined bydegree of placental insufficiency and pregnancy term. They concern anincrease in the contribution of particles with a low hydrodynamic radiusof 15nm in the women with placental insufficiency, absence of anincrease (according to the term of pregnancy) of the contribution ofmiddle molecular fraction and decrease of very large molecular fraction.The character of modifications of homeostasis in placental insufficiencyusing semiotic classifier is explained as autoimmune processes on thebackground of intoxication in the 1st and 2nd trimesters of pregnancy,increase in catabolic activity in the 3rd trimester.Results: The LCS is capable of reliable diagnosis of the signs ofplacental insufficiency and to conduct monitoring of efficiency ofadministered therapy, that allows it to be suggested for a broad clinicalapplication in obstetrics.

P4.09.10ENDOMETRIAL CHANGES ASSOCIATED WITH TAMOXIFENADJUVANT THERAPY OF POSTMENOPAUSAL WOMEN WITHBREAST CANCER : SONOGRAPHIC AND PATHOLOGICCORRELATIONSM. El-Monayeri , A. Nadim, I. Abdel-Fattah, A. Abbass, Ain ShamsUniversity, Cairo, Egypt

Objective: To assess the endometrial changes in postmenopausal womenwith breast cancer who received Tamoxifen as an adjuvant therapy andto determine the need to periodically check up these patients.Study Methods: A cross sectional study conducted on fiftypostmenopausal women, operated upon for breast cancer, and werereceiving tamoxifen as adjuvant therapy. All were subjected totransvaginal sonography and endometrial sampling using the KarmenKit. Endometrial sampling was hysteroscopically guided in 18 cases andby dilatation and curettage in 3 cases. Results of ultrasound in terms ofendometrial thickness and echo-patterns were correlated tohistopathological findings.


Results: The histopathologic examination revealed proliferativeendometrium in 15 cases (30%), 6 cases simple hyperplasia (12%), 4cases complex hyperplasia (8%), 12 cases hyperplasia and polyps (24%),4 cases solitary polyps (8%) and atrophic endometrium in 9 cases (18%).Associated metaplastic changes were encountered in cases ofhyperplasia and polyps with patchy periglandular condensation ofstroma in many of the polyps.An Endometrial thickness of 8 mm was chosen as a cut off below whichno pathological lesion was encountered. At this cut off the sensitivitywas 100% while the specificity was very low (down to 25%). For thisreason incorporating endometrial echo-pattern was essential. Fivedifferent endometrial echo-patterns were encountered in this study:homogenous endometrium, hyperechoic endometrium with small cysticspaces, hyperplastic endometrium, hyperplasia in association withpolyps and atrophic endometrium. This was associated with a sensitivityof 69.2%, a specificity of 87.5%, a positive predictive value of 85.7%, anegative predictive value of 72.4% and an overall accuracy of 78%.Conclusion: Tamoxifen is associated with a variety of endometriallesions that could progress to endometrial hyperplasia and possiblycarcinoma. Transvaginal sonography may be of help to sort out womenwho are in need of further investigations. An algorithm is suggested tofollow up postmenopausal women under Tamoxifen therapy.

P4.09.11HUMAN PAPILLOMAVIRUS AS A PREDICTOR OF PATIENTSWITH UTERINE CERVICAL CANCERM. Iwasaki , A. Nishikawa, N. Akutagawa, T. Fujimoto and R. Kudo,Dept. OB/GYN, Sapporo Medical University, School of Medicine, S1-W16, Chuo-ku, Sapporo, JAPAN, 060-8543

Objectives: The aim of the study was to elucidate the relationshipbetween human papillomavirus (HPV) and the prognosis of patients withcervical cancer.Study Methods: We analyzed 99 DNAs from Japanese patients withuterine cervical cancer. The presence and type of HPV DNA wasanalyzed by PCR using E6 consensus primers. The disruption of E1/E2regions of HPV 16 was analyzed using specific primers with E1/E2regions of HPV16. Life-table analysis of survival was calculated by theKaplan-Meier method. The difference of survival rate was examined bythe log-rank test.Results: Seventy of 77 squamous cell carcinomas (SCC) (90.2%) and 5of 21 adenocarcinomas (AD) (76.2%) contained HPV DNA. Forty-fourHPV 16-positive samples were eligible for analysis of disruption of theE1/E2 region. Of the analyzed samples, 6.8% showed no amplificationwith E1 primers, 9.1% showed no amplification with E2 primers and25% showed no amplification with both primer sets. There was nocorrelation between the type of HPV, disruption of E1/E2 regions andthe prognosis. However, though there was no strong correlation betweenthe presence of HPV and the prognosis of the patients with SCC, asignificant correlation with the presence of HPV and the prognosis of thepatients with AD was found.Conclusions: Patients with AD showing no HPV DNA had poorersurvival.

P4.09.12IGFBP-3 EXPRESSION IN EPITHELIAL OVARIAN CANCER:FAVORABLE ASSOCIATION WITH CLINICO-PATHOLOGICALPARAMETERS AND PATIENT SURVIVALS.Fracchioli (1) , H.Yu (2), M.Massobrio (1), D.Katsaros (1), (1)University of Turin, via Ventimiglia, 3, Turin, Italy, 10126, (2)Louisiana State University, Shreveport, Louisiana, United States.

Objectives: Insulin-like growth factor binding protein-3 (IGFBP-3) is aglycoprotein with specific binding affinity to peptide hormones insulin-like growth factors (IGFs) which are potent mitogens for a variety ofcells. To study the role of IGFBP-3 in ovarian cancer progression, wemeasured IGFBP-3 levels in ovarian cancer tissues and examined itsassociation with clinical and pathological features of the disease andpatient survival.Methods: Tumor tissue specimens from 147 patients with epithelialovarian carcinoma were collected consecutively at the University ofTurin. The average age of the patients in the study was 55 years and themedian follow-up time was 37 months. IGFBP-3 levels were measuredin the tissue cytosol extracts using a commercial ELISA kit.

Results: High IGFBP-3 levels were significantly associated with some ofthe favorable prognostic features of the disease, including early clinicalstage (p=0.048), small size of residual tumor (p=0.007), and optimaldebulking result (p=0.007). High IGFBP-3 was also associated with asignificantly reduced risk for disease progression (RR=0.52, p=0.034)and an inverse dose-dependent relationship between IGFBP-3 anddisease progression-free survival was evident (p=0.033). However, theassociation with disease progression-free survival was not sustainedwhen other clinical and pathological variables were adjusted in theanalysis. An association between IGFBP-3 and overall survival was notshown.Conclusions: Findings of the study suggest that IGFBP-3 may play arole in the progression of epithelial ovarian cancer, but it has noindependent values in predicting the disease prognosis and the responseof patients to chemotherapy.

P4.09.13INHIBITION OF PROLIFERATION AND INVASION IN CERVICALCANCER CELLS BY GENISTEIN: IMPLICATION FORCHEMOPREVETIONYuh-Cheng Yang (1,2), C. Yang (1), Yun-Ting Hsu (1) & Sung-YuanWang (1)(1) Department of Medical Research Dept. OB/GYN, Mackay

Memorial Hospital, Taipei, Taiwan(2) Division of GYN/Oncology, Taipei Medical College, Taipei,

Taiwan

Objectives: The isoflavone genistein is believed to be the anticanceragent found in soybean, and has been shown to have possiblechemoprevention role in several human cancers. However, there werefew studies about such nutritional factors in cervical cancer. The aim ofthe study is to explore the effect of genistein on cervical cancer cellgrowth.Study Methods: An in vitro model using HeLa, C33A, and ME 180 cellswas employed to explore effects of genistein on cervical cancer cellgrowth, cell cycle distribution, and apototic cell death.Result The IC50 for proliferation inhibition in 48 hours was 36 uM, 60uM, and 105 uM for HeLa, ME-180, and C33A cells, respectively.Twenty-four hours post-treatment, more than 50% of the ME-180 cellsshowed obvious G2 /M arrest while in HeLa and C33A cells there wereno significant G2 /M phase accumulation of cells I the cell cycle.Apoptotic cell death was observed in all 3 cell lines upon addition ofgenistein and was time dependent. Treatment with genistein inducedsignificant nuclear fragmentation in HeLa cell in 24 hours as revealed byDNA laddering, however, oligonucleosomal fragments only becameobvious after 48 hours in C33A and ME180 cells. Moreover, inductionof apoptosis was observed with concomitant increased of pro-apoptoticprotein Bax expression.Conclusions: Genistein exerts different potency on growth inhibition,induction of apoptosis and cell cycle perturbation of different cell typesof cervical cancer and the affects and the sensitivity to the effects ofwere independent of estrogen receptor, p53, pRb, and HPV status of thecell lines. These results suggest the under lying pleiotropic mechanismof cell proliferation in different cell types of cervical cancer might bedifferent.

P4.09.14LIPOIDIC CELLS OVARIAN TUMOR, DOUBLE LOCATED, WITHVIRILIZATION SYNDROM AND SECONDARY POLYGLOBULIAB.Marinescu * , I.Marinescu , L.Tasca *Dept.OB/GYN, Panait SarbuHospital, 5 Calea Giulesti, Bucharest Romania, 77721

Objectives: The aim of the study was to find out the source ofvirilization in a 51 years old women with bilateral , large, subtotalsuprarenalectomy, due to the supposed suprarenal origin. The patienthad also hypertension, diabetes mellitus and severe polyglobulia (Hb-21g/dl , Ht-62% ).Study Methods: Complex hormonal assays were performed: testosteron,E2, FSH, LH, ACTH, cortisol, DHEA-S, 17-alfa hidroxiprogesteron,which revealed huge values of testosteron: 11.12 ng/mg and suppressedvalues of FSH, LH<0.3UI/L. The attemps to discover the source oftestosteron failed . Repeted CT-scans of chest and abdomen, abdominalutero-ovarian echographies and also endovaginal echographies did nothelp to find the source of testosteron.


Results: After all this negative results, a diagnostic an therapeuticlaparoscopy was decided to be practiced. This way, 2 right ovariantumors were found a 2 cm one at the inferior pole and the second one, of1.5 cm, in the hilum. Then, laparoscopic bilateral anexectomy wasperformed. The histopathological and imunohistochemical testsestablished the dagnosis to be a lipoidic cells tumour.The immediatepostoperator evolution and that one a year after were good importantregression of the virilization syndrom, normalization of the testosteronlevel (0.28ng/dl) and also of Hb and Ht (15g/dl , 45%)Conclusions: The diagnosis of the virilization syndrom , in the absenceof an evident source remains a difficult problem in the medical practice.The laparoscopy proved to be a proved to be a preffered method ofdiagnostic and treatment when the ovarian source is prefigured.The particularity of the case is a very low incidence of that kind oftumour and especially the double ovarian localization, the virilizationsyndrom associated to a severe polyglobulia.

P4.09.15OVARIAN PROTECTION IN ADOLESCENT GIRLS TREATEDONCOLOGICALY BY LHRH ANALOGS. LONGITUDINALFOLLOW-UP.L. Teslík , J. Horejsi, J. Radvanska. Dept. OB/GYN and Pediat.Oncology, Charles University Prague, Czech Republic

Objectives: Gonads of pubertal and adolescent girls are much moresensitive and damaged much more seriously by oncotherapy, than thosein prepubertal, nonestrogenized stage. 1995-1997 we tried to protectovaries using LHRH analogs to supress the proliferative processes andhormonal activity of them during whole period of oncological therapy.This study follows up the function of ovaries in such treated adolescents.Study Methods: In 20 postmenarcheal girls with different kind ofmalignancies LHRH analog Zoladex was applied monthly during thewhole period of oncological therapy. After the interval 4 – 5 years afterboth oncological and Zoladex treatment we examined our group fromthe point-of-view of ovarian endocrine function.Results: Five of followed girls died. From 15 healed only one has noperiods and she has to be under HRT. In 14 the menstrual cycle restored,they do not use any hormonal treatment. Four of them asked forcontraception and one delivered healthy child after normal pregnancy.Conclusions: Our results documents good protective effect of LHRHanalogs treatment during oncological treatment in pubertal period,revealing restoration of menstrual and even reproductive functions of theovaries.

P4.09.16PREOPERATIVE DIFFERENTIATION OF OVARIAN TUMORSUSING SUPPORT VECTOR MACHINE AND RISK OFMALIGNANCY INDEXP. Van Trappen , Dept. Gynaecological Oncology, St. Bartholomew'sHospital, London, UK; M. Stitson, Dept. Computer Science, Universityof London, London, UK; R. Woolas, Dept. Gynaecological Oncology,Saint Mary's Hospital, Portsmouth, UK; S. Barnhill, BarnhillBioinformatics, Savannah, Georgia, USA; V. Vapnik, Dept. ComputerScience, University of London, London, UK; A. Gammerman, Dept.Computer Science, University of London, London, UK and I. Jacobs,Dept. Gynaecological Oncology, St. Bartholomew's Hospital, London,UK.

Objectives: This study was designed to compare the usefulness ofSupport Vector Machine (SVM) with the established Risk ofMalignancy Index (RMI) in distinguishing benign from malignantadnexal masses. Support Vector machine could be a reliable test toselect patients for whom minimally invasive surgery or conservativemanagement suffices versus those whom require referral to a specialistcancer centre. The SVM technique is based on the structural riskminimisation principle, which is a well established and proven principle.The main idea of the SVM is to map the original set of input data into ahigh dimensional feature space, and then to construct a linear separatinghyperplane (in the case of pattern recognition), in this feature space.Study Methods: The SVM was trained by supervised learning, based ondata from 140 thoroughly examined patients presenting with ovariantumours of which 98 were benign and 42 malignant. SVM was thenapplied to a different series of 147 patients presenting with adnexalmasses of which 80 were benign lesions, 55 ovarian cancer 12

borderline ovarian tumors. The diagnostic accuracy was then comparedwith the RMI using menopausal status, ultrasound score.Results: The error rate of SVM compared to RMI improves from 20.4%to 11.6%. The RMI method on the same data gives 30 errors, whereasthe SVM gives only 17 errors.Conclusions: In this study of 287 patients our results suggest thatSupport Vector Machine is a useful and reliable statistical model todistinguish benign from malignant adnexal masses and therefore usefulin the appropriate management of patients presenting with ovariantumours.

P4.09.17RISK OF BREAST CANCER IN INFERTILE WOMENH.Sharif 1), S. Krüger Kjaer 1), J. O1sen 1), J. Bock 2)

1) Institute of Cancer Epidemiology, Danish Cancer Society,Copenhagen, Denmark2) Department of Gynaecology, Rigshospitalet, Copenhagen, Denmark

Objectives: The overall aim of the study was to examine the canceroccurrence in a cohort of women who were referred to Danish hospitalsor private clinics for infertility problems with a special focus onhormone-associated and gynaecological cancers. The specific aims wereto determine if there is a higher risk of breast cancer among women whohave been treated with fertility drugs, and if the risk of breast cancer isrelated to the different causes of infertility.Study Methods: A cohort of women referred to Danish Hospitals orprivate fertility clinics with infertility problems in the last 35 years wasestablished. All gynaecological departments and all private fertilityclinics were included. Patients were identified from medical files,microfilms or index cards. In addition, we included patients with aninfertility diagnosis recorded in the National Patient Register, a nation-wide register of all admissions to Danish Hospitals since 1977.Subsequently, the cohort was linked to The Danish Cancer Registry toidentify women with a cancer diagnosis after enrolment. A detailed datacollection including information of type of infertility, treatment, numberof treatment cycles on all relevant cancer cases and 4 times as manycontrols has been conducted.Results: A total of 54.379 patients were included in the cohort ofinfertile women. Approximately 4% of the women were enrolled before1974. In the periods 1975-79, 1980-84, 1985-89, 1990-1994 and 1995-97 respectively 13,6%, 15,3%, 17,7%, 31,8% and 17,7% were included.In the cohort, 716 women developed a hormone-related or gynaecologiccancer after enrolment. Breast cancer was diagnosed in 327 women.Cohort analysis will be performed (SIR), and similar analysescomparing the breast cancer rate in the cohort to that in the generalpopulation after stratification by parity. Finally, a case-cohort analysiswill be presented.Conclusion: Several studies have investigated the association betweeninfertility and risk of breast cancer, but in the majority, the results werebased on a small number of cases (<50 women). We will present theresults from one of the largest cohort studies examining the risk of breastcancer among infertile women.

P4.09.18STRUCTURE MODIFICATIONS OF THE VAGINA WALL INPATIENTS WITH IRRADIATED NEOPLASM OF NECK OF THEWOMB – QUALITATIVE AND QUANTITATIVE EXPERIMENTALRESEARCHF. Pricop , E. Crauciuc, F. Dumitrache, D. Francu, D. Iancu, 3rd Clinic ofOB/GYN, University of Medicine and Pharmacy, Iasi, Romania.

Objectives: Pointing out qualitative and quantitative modifications of thestructure of the vagina wall in patients with irradiated neoplasm of neckof the womb, compared with a control lot, with the aim of applyingmaintenance therapy (experimental research).Material and Method Biopsies were drawn from the residual vaginaportion at two lots of patients: Lot I – patients operated for benigndiseases and Lot II – patients operated for an irradiated neoplasm ofneck of the womb. The pieces obtained were processed through parrafintechnique and then colored with Hematoxilin-Eosin or a Szekellythreechromic solution, with the aim of pointing out the modificationsproduced by irradiation. The research of the slices was performedthrough computer aided qualitative (hystologic) and quantitative(stereologic) methods.


Results: The qualitative histologic research points out: The abundance ofcollagen stroma,, which undergoes a process of hyalinization; theatrophy of muscle fibers; a reduction of elastic fibers of the laminapropria; the blood vessels , especially the arteriolas, show parietalmodifications, with accumulations of hyalin.The quantitative histologic research, performed through stereologicmethods, shows: a reduction of the volume of the muscle tissue from79.34% (lot I) to 60.31% (lot II); an increase of the volume of thecollagen stroma from 14.22% (lot I) to 26.51% (lot II); an increase of theoverall volume of the connective tissue from 21.36% (lot I) to 38.71%(lot II): a reduction of the volume of permeable vessel lumina.Conclusions: The qualitative and quantitative modification pointed outin the structure of the vagina irradiated therapeutically directs thenecessary treatment for preserving its functioning, after radical surgeriesperformed for neoplasm of neck of the womb.

P4.09.19STUDY OF ESTROGEN AND PROGESTERONE RECEPTORS BYIMMUNOHISTOCHEMISTRY IN BREAST TISSUE ADJACENT TOFIBROADENOMA OF PRE-MENOPAUSAL WOMEN TREATEDWITH TAMOXIFEN.L.H. Gebrim , S.L. Leung, M.T. Seixas, G.R. Lima, E.C. Baracat, Dept.GYN (Mastology), Escola Paulista de Medicina – Federal University ofSão Paulo, Brazil.

Objectives: Evaluate the positivity of Estrogen and ProgesteroneReceptors in human breast tissue adjacent to fibroadenoma in pre-menopausal women, treated with tamoxifen in doses of 10 and 20mg/day.Study Methods: Forty-two women between 15 - 43 years old wereincluded in this double-blind placebo-controlled study. They weredivided into 3 groups: A (N=15) placebo; B (N=14) tamoxifen 10mg/day and C (n=13) tamoxifen 20mg/day. Tamoxifen was administeredduring 22 days, starting from the 2nd day of menstrual cycle.Excision of tumor and breast tissue was done with local anesthesia onthe 24th day of cycle. Analysis of estradiol, progesterone, SHBG, LH,FSH and prolactin were done to establish the hormone profile, on the24th day of the cycle before biopsy and on the day of surgery. Receptorswere assessed by immunohistochemistry with monoclonal antibodiesMx Ncl ER-6F11 – Novocastra and Mx Progesterone (1 A 6) – Dako.At least one thousand cells were counted for each patient by the programKS 300 digital system for image analysis and only nucleus with strongbrown color were considered positive.Results: The positivity of Estrogen Receptors, according to statisticalanalysis, was negative. The positivity of Progesterone Receptors (PR)was 15.3% in group A; 7.3% in group B and 2.2% in group C. Using theFisher’s statistical analysis, the group A was higher than B and C, butthere was no difference between group B and C; hence, there were nostatistical differences between the action of tamoxifen in the doses of 10and 20 mg/day.Conclusion: The immunopositivity of ER was low and didn’t allowstatistical analysis. Tamoxifen, either with 10 or with 20 mg/ daysignificantly reduced the expression of the PR.

P4.09.20THE BENIGN EPITHELIAL OVARIAN TUMORS ANDANOVULATION: RESTORATION OF FERTILITY AFTER THEOPERATIONV. Artyomenko , A. Zelynsky, Dept. Perinatal Medicine, Child andAdolescent Gynecology, Odessa State Medical University, Odessa,Ukraine.

Objectives: The aim of our research was the rehabilitation ofreproductive function in women with the benign epithelial ovariantumors (BEOT) and anovulation after the surgical operation for thecorrection of the main regulatory systems of female organisms andhaemodynamics of pelvic organs.Study Methods: The ovarian hormonal function (estradiol, progeteronelevels and their correlation) studied by means of radioimmune assay,system elastase-a1-protease inhibitor means of biochemical technique,the bloodfullness of the internal genitalia by means of rheographicmethod were examined in 36 patients of fertile age with the benignepithelial ovarian tumors and anovulation before and after the surgery aswell as in 16 healthy non-pregnant women of fertile age. The

rehabilitation therapy after the surgery was performed by combinedabdominal and vaginal pulsing vacuum daily for 14 days in a concertwith a hormonal therapy (estrogen-gestogen complexes) during threemenstrual cycles.Results: It has been found that after the operation the examined figuresdon’t normalize in many patients, which demands the second step oftreatment for their correction. After treatment in most of the patients werevealed the normalization of the ovarian hormone producing function,system proteases – proteases inhibitors and rheography figures. Theimprovement and normalization of menstrual (75%) and reproductive(44.44%) function, along with the decrease of the tumor relapses werepointed out.Conclusions: The combined method of local abdominal and vaginaldecompression and hormonal therapy is effective and pathogeneticallygrounded, normalizing ovarian function, local proteolysis and bloodcirculation in pelvic organs. In women with BEOT and anovulation afterthe surgery the restoration of menstrual and reproductive function can beachieved along with the considerable decrease of tumor relapses.

P4.09.21THE INTERNET AND GYNECOLOGIC ONCOLOGY: THE YEAR2000S.A. Farghaly , The Medical College of Cornell University, New York,New York, USA.

The Internet is becoming a third party in the doctor-patient relationship.The Internet has revolutionized the delivery of cancer information byproviding patients and family members access to several sourcespreviously available only to health care professionals. This presentationreviews advantages and disadvantages of the Internet for both cancerpatients and gynecologists and the available web sites for cancerinformation.The role of gynecologic oncologists in respect to the World Wide Webis to:1. Find out what type of gynecologic cancer information is beingdisseminated on the web;2. Use the web material that patients bring to the clinic as a basis forpatient education;3. To become active participants on the Internet.The use of the Internet is expanding and has become an outstanding toolfor providing cancer information for women with cancer, the public,gynecologic oncologists and other health care professionals.

P4.09.22UTERINE SARCOMA – A 16 YEAR PROFILEK.Uma Devi , V.K. Ahuja, U.D. Bafna, E. Vallikad, Dept. GynecologicOncology, KMIO, Bangalore, India.

Objective: To study clinicopathological features of uterine sarcoma inrelation to treatment outcome.Study Methods: A retrospective analysis of case records of patientspresenting for treatment at the Dept. of Gynecologic Oncology, Kidwai,Bangalore, India, revealed 96 cases with uterine sarcoma betweenJanuary 1981 and December 1997. An attempt has been made to studythe age, parity, hormonal status, histology and treatment outcome. Theprimary therapy was surgery along with adjuvant therapy eitherradiotherapy of chemotherapy.Results: Leiomyosarcoma was the most common histology 38/96 (40%)encountered. Malignant mixed mullerian tumor 30/96 (31.8%),endometrial stromal sarcoma (ESS) 13/96 (13%) and rhabdomyosarcoma 15/96 (14.8%) were less frequent. 68% with LMS agedbetween 41 and 60 years with a mean age of 48.5 years. MMMT wereobserved most commonly between 41 and 70 years with a mean age of56.5 years. The usual presentation was either abnormal uterine bleeding(46.7%) or mass per abdomen (24.4%). Most of them presented withpost-hysterectomy status, surgery done elsewhere (56.8%).Conclusion: Uterine sarcoma constitutes a rare entity in genitalmalignancies. Adjuvant therapy like chemotherapy and radiotherapyplan an additive role in the improvement of quality of life.Keywords: Uterine Sarcoma, Clinical Features, Treatment Outcome.

P4.09.23MALIGNANT MONOPHASIC ANGIOMYOLIPOMA OF THEUTERUS


Y. F. Luo, Dep. of Gynecol., Centro Hospitalar Conde de S. Januario,MacauN. L. Wong, Dep. of Pathology, Kiang Wu Hospital, Macau,P. R. China

A 19-year-old Chinese girl was received laparotomy because of a pelvicmass impressed uterine myoma on 29/8/97. A mass on posterior lowersegment of uterus with 5cm diameter without capsule was found. Frozenbiopsy showed malignant sarcoma. The patient underwent TAH,remained both adnexa. Pathologic report was uterine clear cell sarcoma.After one month of operation, pelvic examination and ultrasound foundbilateral pelvic solid mass fixed with pelvic wall. Second laparotomywas performed on 7/10/97. Bilateral adnexa were normal. There weretwo solid gray-brown solid tumors with 6X5X4cm for each size inbilateral inguinal ligament and obturator areas. BSO, pelviclymphadenectomy, paraaotic lymph node biopsy and partialvaginectomy were performed. Post-operation another pathologist reportwas metastatic malignant melanoma of bilateral inguinal-obturatorlymph nodes, residual malignant melanoma in vaginal cuff. Dr. JohnChan of Queen Elizabeth Hospital of Hong Kong and Dr. Bonetti ofItaly reviewed the pathologic slides and did immunohistochemicalstaining . The diagnosis was malignant Monophasic angiomyolipoma ofuterus with pelvic nodal metastases. The patient underwentchemotherapy and radiotherapy. She died from various sites ofmetastases on 20/8/99.Most angiomyolipoma arise in the kidneys ofpatients and the most is a benign lesion. External location and malignantis very rare. This is first case report for malignant angiomyolipoma ofuterus.Malignant angiomyolipoma has a poor prognosis. Most of patientdied of metastatic disease. A successful treatment has not yet beenfound.

P4.10 HEALTH CARE DELIVERY SYSTEMS

P4.10.01”GOING FOR SCALE” – A MEANINGFUL ANTENATALPROCEDURE FOR MOTHERS IN RURAL ZIMBABWEBM Ahlberg, 1T Mathole2, F Majoko3, G Lindmark 4, Dpt of Sociology,Uppsala University2,3 Dpt of Obst/Gyn, University of Zimbabwe, 4 Dptof Women´s and Children´s Health, Uppsala University

Objectives: In a new antenatal package in rural Zimbabwe five-goaloriented visits with only ANC procedures of proven medical benefitwere included and not others, such as weighing. A qualitative study wasalso carried out to explore factors that influence utilisation of ANC andthe meanings women attach to antenatal care.Methods: Data were collected using individual and group interviewswith health providers, mothers, husbands and the traditional birthattendants (TBAs). Data have been transcribed, translated from Shona toEnglish, read, coded and categorised into themes presented in the paper.Results: When mothers wanted more than the stipulated five visits, theyfeared that with too spaced visits complications may develop and not befound during that long period. For others, ANC offered a break from thedaily routines or a chance to discuss with other women. Mothersmoreover wanted to be weighed at all the visits. They expressed the needto know their weight as the major thing they looked forward to in theirANC visit which is commonly referred to as ”going for scale.” Thehealth care providers complied with these expectations by weighingwomen without recording in the cards. Weight gain or loss wassomething women discussed a great deal and compared with each other.Conclusion: It seems the ”scale”, where women themselves participate,has symbolic importance for reassurance and decision making formothers.

P4.10.02A COST-EFFECTIVE MODEL FOR PRIMARY WOMEN'S HEALTHCAREV.A. Pavlov1, RI Vaslishin1, K.V. Voronin2, V.I. Bashtovoi1,O.V. Kolobova2, L.P. Gavrish2, R. Goldberg1, M. Gluch 1, B. P. Sachs1

1Harvard Medical School, Boston, MA, USA2Dniepopetrovsk Hospital, Dniepopetrovsk, Ukraine

Objective: To develop a free primary preventative health care programfor women in Dniepropetrovsk, Ukraine.Study design : A gynecology clinic was established in Dniepropetrovskcity hospital #9 by the city government and Harvard Medical School.The program focuses on sexually transmitted diseases, cervical cancerand a very high abortion rate due to lack of birth control options (55 per100 thousand women in 1996) in Ukraine. Due to communication andtransportation difficulties all results are given to the patients at the timeof the visit. The physicians in the women's center received training fromBoston gynecologists.Results: There have been 17,296 patient visits (9,686 patients) since theclinic opened in 1997. Patients with cervical problems constituted 24%of the visits. Of the 10,353 pap smears obtained there were abnormalfindings in 245 women. There were 2341 colposcopies performed,which included women referred from other centers. 24% of the patientswere seen for a diagnosis of a complaint of sexually transmitteddiseases, a positive culture was obtained for chlamydia or gonorrhea in280 cases. There were 7800 months of contraceptives distributed. Theabortion rate for the district served by the clinic fell from 63.2 perthousand women in 1996 to 8 per thousand women in 1999. The cost peryear for the program is approximately $50,000 or $5.00 per visitincluding free pharmaceuticals.Conclusions: This new model program of a primary preventative healthcare for women established in Ukraine improved the health status ofwomen and was cost-effective.

P4.10.03A SURVEY OF DOCTORS’ ATTITUDES TO PREMENSTRUALSYNDROME AND ITS MANAGEMENT.C.Domoney , A.Vashisht, J.Studd, Imperial College of Science,Technology and Medicine, 369 Fulham Road, London, UnitedKingdom, SW10 9NH.

Objective: To investigate attitudes to PMS and compare its managementby primary-care physicians, gynaecologists and psychiatrists.Methods: An anonymous postal questionnaire was sent to all registeredprimary-care physicians in one London health region (n=208), and allmembers and fellows of the Royal Colleges of Obstetricians andGynaecologists (n=270) and Psychiatrists (n=238) in North East Thamesregion.Results: 96% of responders believed PMS exists, 98% of whom agreedit may warrant medical treatment. The majority (83%) of doctors feltboth hormonal and psychological interventions are indicated. Of doctorswho indicated referral for further treatment was appropriate, 85% chosegynaecologists, 4% psychiatrists and 5% psychotherapy.The range of treatments used by gynaecologists was wider than the othertwo groups. Vitamin B6, evening primrose oil and all hormonalpreparations were significantly less likely to be recommended bypsychiatrists than other doctors. One third of primary-care physiciansand gynaecologists use progesterone for the treatment of PMS. Allgroups would recommend SSRIs, although primary-care physiciansmost commonly considered their use (p<0.05). Gynaecologists weremore likely to agree that surgery is ever indicated for the abolition ofthis disorder (p<0.001).62% of doctors felt that media publicity encouraged women to labelthemselves inappropriately as sufferers, yet 75% agreed it encouragedwomen to seek help.Conclusions: Most responders demonstrated awareness of this condition.PMS sufferers present to doctors from different disciplines; this surveyreveals a wide variation in management approaches.


P4.10.04ASSESSING THE IMPLEMENTATION OF THE RISK APPROACHSTRATEGY BY THE PUBLIC HEALTH PERSONNEL INMALAYSIAK. Shamsuddin , Dept of Community Health, Faculty of Medicine,University Kebangsaan Malaysia, Kuala Lumpur, Malaysia

Objectives: The aim of this study was to assess the implementation ofthe risk approach strategy in maternal health care as practiced by thegovernment public health personnel in Malaysia.Study Methods: A cross-sectional survey of antenatal heath cards kept ingovernment health facilities in 16 selected health districts in PeninsularMalaysia was conducted in 1997. Independent assessors abstractedinformation on identified risks, risk assignment and case managementfrom the selected health cards. Comparisons were made betweenrecorded health data and the practice guidelines recommended by theMinistry of Health. Weighted analyses were done to calculate theprevalence of outcomes weighted to the total population served tin the16 health districts.Results: Based on weighted analyses, there were 60 722 health cardsassessed in this study. With regards risk assignment by health personnel,3.6% were not risk coded, 13.3% white-coded (low risk) and 39.3%green-coded (moderately low risk), 39.8% yellow-coded (high risk) and4.3% were red-coded (very high risk) mothers. Only 14.3% of healthcards had risk status fully recorded following the recordingrecommendation of the practice guidelines provided to the health staff.Accuracy of recording of antenatal conditions were only reliable in28.3% of cases while for most cases, intrapartum and postpartumconditions were not recorded at all. Accuracy of risk assignment (color-coding) based on identified and recorded risks was 62.1% and only20.5% of cases were managed appropriate to allocated risk levels orcolor codes as recommended in the practice guidelines.Conclusions: Levels of implementation of the risk approaching maternalcare based on the recommended practice guidelines were found to below. Division of risk levels to 4 categories increased themisclassifications of mothers assessed in this study. A simpler practiceguidelines for risk identification, risk classification, recording andmanagement may improve work practice of health personnel working inthe community.

P4.10.05EMERGENCY MANAGEMENT FOR OPERATING ANDRECOVERY ROOMSK. O’Hanley , AVSC International, New York, New York, USA.

Need and Purpose: Emergency situations occur rarely. Especially inlow-resource settings, providers may occasionally struggle to rememberproper management or drug doses. They do not have the time to consulta lengthy document. A quick-reference guide for use in emergencies hasbeen lacking. Therefore, AVSC International has produced referenceguides designed to hang in operating and procedure rooms for ready-reference.Reference Guides: Emergency Management for Operating and RecoveryRooms (laminated wall chart)Initial steps of response: Management by signs (management of the lifethreatening emergencies: respiratory compromise, low blood pressure,acute asthma and anaphylaxis, slow pulse or no pulse, fast pulse,vomiting, seizure, acute hemorrhage, high blood pressure, restlessnessand disorientation, difficult IV access during emergency, and lockjaw.)Emergency drugs, indications for their use, and protocols foradministrationReference Manual (to hang next to the above wall chart)Introduction Principles for emergency prevention and preparednessEmergency conditions: definitions, causes, clinical findings, treatments(narcotic or sedative overdose, overdose of general anesthetic, ketamineside effects, ketamine reaction, inadequate oxygen, vasovagal response,high level of spinal/epidural anesthesia, acute hemorrhage, acute asthma,anaphylaxis, inadequate anesthesia, vomiting/aspiration, seizure,overdose of atropine, difficult IV access during emergency, laparoscopyside effects)Equipment and supplies for managing emergenciesDrugs: Indications, actions, precautionsCardiopulmonary Resuscitation (laminated wall chart)Basic steps of CPR: airway, breathing, circulation, and drugs in aclinic/hospital setting.

P4.10.06GREEK AEROMEDICAL EVACUATIONS IN PREGNANCYV. Chriskos , P. Georgakopoulos, J. Daglas, Dept. OB/GYN, ElenaVenizelou Maternity Hospital, Holargos, Athens, Greece.

Aeromedical evacuations of pregnants and neonates, are usuallyinterwoven with the urgent need to transport a mother or her newborn toa secondary or tertiary treatment center.The statistical analysis of relevant cases over the years 1982 – 1987 and1994 – 1997 shows the following:a) services provided improved over years 1994 – 1997 in comparison

to 1982 – 1987b) aeromedical evacuations of pregnant women constitute 36.60% of

obstetric-neonate cases (average percentage per year) over 1982 –1987, whereas the percentage is 35.11% during 1994 – 1997

c) aeromedical evacuations of pregnants constitute 14.09% and33.90% respectively

d) premature neonate percentages are 27.68% and 21.62%respectively

e) neonates represent 21.90% and 21.62% respectivelyf) infants account for 5.75% and 24.07% respectivelyg) the Cyclades excel in obstetric aeromedical evacuation with

percentages of 47.49% and 44.15% respectively relating to thetotal obstetric evacuations throughout Greece, in pregnancycomplications with 74.51% and 61.76% for the corresponding timeperiod percentages for each case type, and in confined women with61.07% and 77.25% respectively

h) the Dodecanese islands excel in premature neonate aeromedicalevacuations representing 47.66% and 54.71% neonate casesaccounting for 63.22% and 58.55% and infants with percentages of38.87% and 39.18% respectively.

These percentages with concise indications and complications, allowconclusions to be drawn for the rural areas, epidemiology data forparticular complications and indications for technological, provisionaland educational priorities to improve the National EmergencyAssistance Center (NEAC) aeromedical evacuation system, aiming toreduce perinatal (12.5%) and maternal (1:100 000) mortality in Greece.

P4.10.07KNOWLEDGE, ATTITUDE AND PRACTICE OF PAPANICOLAOUSMEAR AMONG BRAZILIAN WOMENS.Brenna (1) , E.Hardy (2), L.Zeferino (2), I.Namura (1), (1) MaternityHospital Leonor Mendes de Barros, Av. Celso Garcia 2477 – Belém,São Paulo, Brazil, 03015-000, (2) The State University of Campinas,Barão Geraldo – Campinas, São Paulo, Brazil.

Objectives: This aimed to investigate knowledge, attitude and practice ofPap smear among Brazilian women, who had not undergone screeningperiodically.Study Methods: One hundred and thirty-eight women were interviewedin this cross sectional study that analized two groups: 90 with high gradesquamous intraephitelial lesion (SIL) and 48 with invasive cervicalcervical squamous cell carcinoma, all FIGO stages. The statisticalanalysis was performed by Pearson test, accepting p=0.05 and logisticregression.Results: Women with invasive carcinoma had higher inadequateknowledge (p=0.02), attitude (p=0.01)and practice (p=0.04) of Papsmear and they were older, had lived in São Paulo city during feweryears, were homemakers and had personal difficulties as social andeconomic problems to access medical care. The Pap smear, usually,depended on physician's request when the women accessed medical carebecause they had some symptons or felt sick.Conclusions: Social and economic problems could difficult screeningprograms for cervical carcinoma among Brazilian women


P4.10.09MENSTRUAL PROBLEMS IN A RURAL WEST-AFRICANPOPULATIONG. Walraven1, G. Ekpo 1, C. Scherf2, R. Coleman1, L. Morison3, S. Harlow4

1. Medical Research Council Laboratories, P.O. Box 273, Banjul,The Gambia

2. Dept. Medicine, University of Wales, Cardiff CF14 4XN, UK3. London School of Hygiene and Tropical Medicine, Keppel Street,

London WC1E7HT, UK4. Dept. Epidemiology, University of Michigan, 109 Observatory St,

Ann Arbor MI 49109-2029, USA

Objectives..To assess the prevalence and type of menstrual problemsreported by rural West-African women.Study methods As part of the Farafenni reproductive morbidity survey(see abstract Walraven et al.), a questionnaire to assess menstrualproblems was administered by a field worker and then by agynaecologist, who also examined the women. The association betweenmenstrual problems, socio-demographic data and other reproductivemorbidities was examined adjusting for age and parity.Results: Menstrual problems were reported more frequently to thegynaecologist than to the field worker. Of 607 menstruating women notusing hormonal contraceptives, 99 (16%) complained to thegynaecologist of irregular cycles, 85 (14%) of dysmenorrhoea, 48 (8%)of spotting, and 25 (4.1%) of heavy/prolonged bleeding. Irregular cycleswere significantly more common in women aged ³35, married women,and those with a cervical tumour on examination. Dysmenorrhoea wassignificantly more frequent in women aged 15-19, nulliparae, and thosewith clinical depression, infertility, fibroid uterus, or signs of PID.Spotting was significantly increased in women aged ³35, those withinflammation of the cervix, cervical tumour, fibroid uterus, or signs ofPID. Heavy/prolonged bleeding was more common in women aged 30-39, non-educated women, infertile women, and women with signs ofPID.Conclusions: The prevalence and correlates of menstrual problems inthis population, are similar to those in developed countries. Menstrualdisorders constitute an important unaddressed area of reproductivehealth service needs in developing countries, and relatively simple andinexpensive therapies are available to address many menstrualcomplaints.

P4.10.10MIDWIFE-MANAGED CARE - IMPACT ON USE OF HEALTHSERVICES: AN AREA-BASED RANDOMISED CONTROLLEDTRIALA. Berglund , Dept of OB/GYN, Central Hospital, Västerås, SwedenG. Lindmark, Dept of OB/GYN, Uppsala University Hospital, Uppsala,Sweden

Objectives: Risk assessment with planning for individual surveillance isconsidered important in prenatal care and is generally performed byphysicians. In the present study this routine was replaced by a planningconference with midwives reporting new mothers to the doctor. Theimpact on the use of health care during the rest of pregnancy wasassessed.Methods Randomised controlled trial using cluster randomisation of 20antenatal care units to midwife only or standard care (intervention n =835; control n = 716).Results: In the intervention group 23% of the mothers visited the doctorat the ANC-unit after recommendation at the conference. Low-riskmothers requested consultation in 8 %. Extra visits to the antenatal careunit during the first 20 pregnancy weeks were more common in theexperimental group, OR = 1.5 (CI 1.18;1.95). No significant impact onthe proportion of mothers referred to the obstetric outpatient clinic orhaving elective delivery could be demonstrated.Conclusion: Replacing the routine visit to the doctor with a planningconference reduced the proportion of women seen by physician early inpregnancy by 70 % and, although the need for extra contacts during thefirst 20 weeks increased, there was no adverse effect on work load as awhole. Extra doctor´s time could be used for mothers with complicatedpregnancies.

P4.10.11OBSTETRICAL/GYNECOLOGICAL MANAGEMENT SITUATIONIN A SPECIALISED HOSPITAL BANGLADESHC. Roy , Dept.OB/GYN 200 Bed Hospital, Narayangonj, Bangladesh.

Objectives: To evaluate the performance and highlight the quality andquantity of services in a specialised hospital.Study Methods: Review of ten years (1989-1999) hospital records wereincluded in the study.Results: Data based analysis shows the upgrade quality and quantity ofservices in the specialised hospital.Conclusions: With less manpower and resourses large number ofpatients can be manazed in such type of hospital with great satisfaction.So this type of specialised hospital is needed for better services(OB/GYN) at district level in Bangladesh.

P4.10.12PHYSICIAN-PATIENT DIALOGUEM. Fallahian , Dept. OB/GYN, Shaheed Beheshti Medical ScienceUniversity, Tehran, Iran.

Objective: To determine dialogue between physicians and patients.Method2000 patients during discharge of hospitals were interviewed. Thesepatients were admitted in teaching hospitals located in different sites ofTehran.Results: Although the physicians pay attention to details of thecomplaints of their patients, patients believe they are not fully aware ofwhat is going on in their care and decision-making.Conclusion: Still physician-dominated attitude. Physicians pay attentionto patient’s desires but they don’t communicate with them.

P4.10.13PICTURE OF HOSPITAL SERVICES FOR OBSTETRICAL ANDGYNECOLOGICAL PATIENTS IN TWO DISTRICT HOSPITALS INBANGLADESHY. Jahan , Dept. OB/GYN, Sadar Hospital, Rajbari, Bangladesh.

Objective: In our country of Bangladesh, we are now at a turning pointfrom unprotected motherhood to safe motherhood. From the earlynineteen hundred nineties most of the district hospitals have becomestrengthened by obstetricians and gynecologists. A global feeling ofimprovement of womanhood makes women conscious about theirhealth. Needs of obstetrical and gynecological services increaseeveryday. But infrastructure and supportive services will not beincreasing with the demand. In my paper, I want to focus on how thistype of hospital runs with very limited facilities.Study Method Working data of hospital records for one year.Results: A vast majority of people do not come to the hospital. However,proper management for those who attend is very difficult due tolimitation of the facilities.Conclusion: Service data of these hospitals reflect large portion of healthcare delivery system for obstetrical and gynecological patients in adeveloping country like Bangladesh. This will be helpful for makingpolicies for further improvement.

P4.10.14POTENTIALLY AVOIDABLE PERINATAL DEATHS IN THEDONETSK REGION, UKRAINEI. Mogilevkina *, B. Bødker**, J. Langhoff-Roos**, S. Larsen**, G.Lindmark***, A. Orda ****.*Donetsk State Medical University, Donetsk, Ukraine.**Rigshospitalet,University of Copenhagen, Denmark. *** Uppsala University, Sweden.**** Donetsk Health Care Administration, Ukraine.

Objectives: The study was performed within the framework of WHOPerinatal Audit project.The aim of this specific project was to analyse which subgroupscontribute to the high perinatal mortality in the Donetsk Region,Ukraine, in order to make suggestions for priorities in perinatal care.Study Methods: Perinatal mortality in the Donetsk Region, Ukraine1997-98 was studied by application of the Nordic-Baltic perinatal death


classification. Data on all perinatal deaths in the region were retrievedfrom medical records of 1126 cases.Results: The perinatal mortality rate was 16.1/1000 (compared with10.9/1000 in official statistics). Applying the Nordic-Baltic perinataldeath classification, 1/3 of the perinatal deaths were non-malformedantenatal deaths. Single growth-retarded fetuses were responsible for2.7/1000, and normally grown for 2.3/1000.Neonatal death rates of non-malformed fetuses with low Apgar scorewas 7 times higher in infants 28-33 weeks and two times higher ininfants 34 weeks +, compared with those with normal Apgar score atbirth. Intrapartum death occured in 1.2/1000, and perinatal death rate ofpreterm infants below 28 weeks was 1.9/1000.Conclusion: Antenatal diagnosis and monitoring of intrauterine growthretardation, as well as improved intrapartum care to prevent intrapartumdeath and neonatal asphyxia should be priorities for obstetricians inUkraine.

P4.10.15REDEFINING THE ROLE OF TERTIARY CARE PHYSICIANSJogendranath Narone , MD, Rajkumari Narone, MD Patna MedicalCollege and Hospital

Strategies to provide HIV/AIDS medical education to primary carephysicians often translate into prohibitive costs. This study focused onthe role of educating tertiary care academicians and the impact thiswould have on primary care physicians.We analyzed data from January 1998 to January 1999 from the BiharHIV/AIDS Project's database. Tertiary-Care Ob/Gyn faculty attended a4-day Trainer's Training organized by the National AIDS ControlOrganization (NACO). Before the training course, direct physicianinterviews were conducted with 212 tertiary care program faculty(reflecting a response rate of 100 percent) who were drawn from arepresentative random sample of tertiary care physicians in an academicsetting. After the course, 92 percent of all course participants were thensurveyed either by telephone or mailed questionnaire.Before the course, 10 percent of tertiary care providers attending theconference felt they had adequate knowledge about HIV/AIDS,including prevention, epidemiology, pathology, and treatment, while allfelt knowledgeable in the subject after the course. Sixty percent of thetertiary care physicians reported that they had participated in educatingprimary care staff in directly in the rural setting in clinics affiliated withtheir medical colleges while 94 percent indicated that their departmentshad created educational curricula to train primary care physicians onHIV/AIDS.The finding that nearly nine of ten tertiary care providers had developedcurricula to educate primary care physicians affiliated with theiruniversities provides great impetus to develop similar programs.Educating tertiary care providers may provide a cost-effective method ofsocial mobilization for awareness of HIV/AIDS at the primary care levelin rural Bihar.

P4.10.16THE IMPACT OF GROUP MEDICAL VISITS ON THE NUMBER OFDAYS SPENT AFTER GYNECOLOGICAL SURGERYI.L. Ramos , P. Suassuna, M. Andrade, Dept. OB/GYN, InstituteMotherly Infantile of Pernambuco (IMIP), Recife, PE, Brazil.

Objectives: Depression and anxiety can increase the number of daysspent in a hospital after gynecological surgery. Women that receivemore visits from their doctor and his assistants report elevated levels ofrecuperation. The relationship between the doctor and his patient is veryimportant in the recuperation. It is usual these days that theestablishment of a professional relationship between doctor and patientdoes not include the doctor’s emotional involvement. Recent research oncognitive-behavioral approaches suggests the possibility of improvingrecuperation rates as well in all fields of treatment. The efficacy of suchinterventions with increased recuperation rates has not been adequatelyaddressed.Study Methods: The study employed a randomized, controlled,prospective design. Women that had an operation and had more thanthree visits in the first post-operation day from their doctor and hisassistants were randomized to either group with only one visit after oneday of operation. In the visits, the doctor and assistants talk with thepatients about routine when they are at home. The group that received

three visits included relaxation training, nutritional and drug advice,sessions focused on different aspects of surgical experiences, includingthe impact of losing an organ (if that was the case), on self-esteem,marriage, job and family and talk about doubts. All subjects werefollowed for a period of one year.Results: A total of 192 women were recruited and randomized. 52dropped out of the study because of a change of address. 90 womenreceived three visits and 50 received only one visit. When we began thestudy, we divided into two equal groups. The three visits group spent 36hours in the hospital after surgery and made only one ambulatory visitafter this and they report total physical and psychological recuperation.The other group spent 3 days in the hospital and made more ambulatoryvisits to talk about doubts and some abdominal pains. 30% of thembecame depressive.Conclusion: There appears to be a connection between psychologicalsupport and a good rapport establishment and patients’ recuperation.This study supports the complexity of the relationship betweendepression and recuperation post surgery and the indispensible presenceof a patient assistant doctor. If more time is given to a patient, the lessthey look for a hospital and the less money will be spent with areduction of days in a hospital. In ambulatory terms, less consultationswill give more opportunities for other people.

P4.10.17THE IMPORTANCE OF THE IMMUNOHISTOCHEMICAL ANDHISTOPATHOLOGICAL EXAMINATIONS FOR THE DIAGNOSISOF DISFUNCTIONAL UTERINE BLEDDING (DUB)N. Raca , Dept OB/GYN, University of Medicine, Craiova, Romania

Objectives: Evaluation of the importance of the immunohistochemicaland histopathological examinations for the diagnosis of DUB.Study Methods: Endometrial tissue samples from 655 patients withclinical DUB – examination performed in our Laboratory ofAnatomopathology by the hematoxylin and eosin staining method andby immunohistochemical techniques for revealing PCNA and VEGFantigens (normal endometrial tissue from a fertilized woman andendometrial tissue from a 2 years old patient were used for control).Results: The histopathological examination confirmed the diagnosis in50.23% of cases; the others showed endometrial neoplasia, hiperplasia,uterine fibroma. Increased capillary permeability and stromal oedemawere suggestive fore DUB. Disorders in the stroma and in theendometrial glands were also found.The immunohistochemical study found VEGF expressed in theendometrial gland cells while missing in blood vessels. PCNA wasabsent in all endometrial structures during both the proliferative and thesecretary phases.Conclusions: Those two examinations state the diagnosis of DUBspecifying the vascular involvement.

P4.10.18THE REGIONALIZATION: AN OPPORTUNITY FOR THE WOMANIN THE DEVELOPING COUNTRIESN.Y. Aguilar-Jaimes , Hospital La Merced, Ciudad Bolivar, Antioquia,Colombia.

The developing countries have scarce economic and technologicalresources for supply of health services, and they should be distributed inthe best possible way to assist effectively and efficiently the population.In Colombia the attention for complexity levels has allowed to decreasemorbidity, mortality and costs in the woman’s attention. Qualifiedpersonnel with communication and transport systems adapted in lowcomplexity local institutions can evacuate moderate and high riskspatients to hospitals of moderate complexity, endowed with specializedpersonnel and appropriate technology that allow to solve 90-95% of thewoman’s health problems in different stages of their life; leaving 5-10%of patients that will require attention in high complexity institutions andhigher costs.


P4.10.19THE RESULTS OF DYNAMIC INTERACTION BETWEENFAMILIES AND PROVIDERS TO IMPROVE THE QUALITY ANDCOVERAGE OF MATERNAL AND NEWBORN HEALTHSERIVCES IN BOLIVIAG. Seoane , V. Kaune, MotherCare Bolivia Project, La Paz, Bolivia,South America

Objective: The project aim was directed towards the goal to reducematernal and newborn mortality through objectives to increase access toquality services; to promote client-oriented care and institute policy insupport of improved maternal and newborn health. All project objectiveswere met during the duration of the project.Methodology..The results of increased quality and access werecompared in seven MotherCare target districts to one control district.The MotherCare interventions included: provider training to clinical andclient counseling skills; community-based information/communication(IEC) to increase women/families' awareness of pregnancycomplications and appropriate actions to be taken, and policypromotions. The control area introduced only the IEC intervention. Datawere collected from a similar facility monitoring system of keyindicators and community-based surveys. The facility monitoring datawere collected during the first six months of 1996,1997 and 1998.Results (Preliminary)1. Facility deliveries in the MotherCare districts increased by 41%.

Women in the control districts continued to favor home births.2. Percentage increase in met need was slightly higher in the

MotherCare districts than in the control.3. The numbers of women with 4 prenatal visits nearly doubled in the

MotherCare districts.4. The combination of multiple IEC interventions provided a higher

level of effect.5. Women using " Women-Friendly Centers indicated more client

counseling.Final results will be reported in the presentation.Conclusions (Preliminary)1 Significant increase in coverage is dependent upon integrated

community-service approach.2 Obstetric services need to be accessible and acceptable to the

community to increase coverage.3. Facility monitoring systems must be maintained, data analyzed and

used by clinicians.4. Policy is required to sustain quality provider performance.Final conclusions will be available in the presentation.

P4.10.20HEALTH CARE DELIVERY SYSTEMS AND POLICIESHannah Ashwood-Smith , Safe Motherhood Project, Blantyre, Malawi

Objectives: One critical component of the Safe Motherhood Project is tostrengthen obstetric referral systems. A community-based case controlstudy was conducted in Southern Malawi to determine the time-effectiveness, cost-effectiveness and cultural acceptability of bicycleambulances (BAs) and established community transport plans (CTPs).Another aim was to determine whether the presence of CTPs influencehome delivery rates. The study was conducted from July 19th 1999 toJanuary 18th, 2000.Study methods: The study employed qualitative and quantitativemethodologies to collect data from 10 villages located within a fivekilometer radius to three Basic Essential Obstetric Care(BEOCs)facilities. Distance, socio-economic status, topography, culture andethnicity were considered when controlling for sites. Of the four casevillages, two were provided with BAs and two developed transportplans; the six control villages lacked established plans. 30 homogeneousfocus group discussions (FGDs) explored perceptions of modes oftransport with elders, chiefs, women of child-bearing age, and theirpartners. Retrospective interviews with women delivering six monthsprior to the study (n=92) obtained baseline data, whilst prospectively157 deliveries were registered.Results: Home delivery rates in case villages decreased from 37% to18% (P<0.005). The BA mean time to reach the BEOC was 86.48minutes versus a walking time of 106 minutes. Despite the availablityand awareness of BAs, important cultural beliefs deter most pregnantwomen, who believe that publicising onset of labour summons evil

spirits resulting in obstructed labour. General medical cases (80%) usedthe BAs more frequently than obstetric cases (20%).Conclusions: Considering the cultural context of the study population,BAs and CTPs were not effective in strengthening referral systems. Thedearth of international literature coupled with these findings highlightthe need for further detailed studies prior to wide scale adoption oftransport schemes.

P4.10.21WOMEN FRIENDLY HOSPITAL IN BANGLADESHK. Nahar , Dept. OB/GYN, Mymanshingh Medical College,Mymanshingh, Bangladesh.

Bangladesh is committed to reducing the maternal mortality by half bythe year 2000. At the rate of 4.5 women’s deaths per 1000 live births, therate is much too high when compared with a rate of 0.8 in Sri Lanka.Maternal mortality (MMR) of a country is now considered globally as anindicator of the overall status of women. A high MMR represents theend point in a lifetime of discrimination, neglect and also the failure toprovide effective health services. Reducing the maternal mortality ratecalls for a multifaceted strategy. It includes several factors like educationon the care needed for a pregnant woman, provision of services forcomplications of pregnancy, etc. The strategy is not just a health issue; itinvolves the whole of society. However, the hospitals have an importantrole in every part of the strategy.We want to make Mother-Baby Friendly Hospital with the idea of safemotherhood initiative (SMI). While women die of pregnancy-relatedcauses in rural areas, twice as many women die from violence. Bydrawing a parallel between the process of maternal death and that ofdeath by violence, the term Mother-Baby Friendly Hospital is shifted toanother term Women Friendly Hospital where women as persons aretreated with respect, dignity and equality.

P4.11 HIGH-RISK PREGNANCY

P4.11.01AMBULATORY MANAGEMNT OF TOXEMIA. A SERIES OF 117PATIENTSL. Smaïli , M. Yahyaoui, S. Mahjoub, R. Ben Hmid, I. Lebbi, F. Zouari,Dept. GYN/OB, Center of Maternity and Neonates of Tunis, Tunis,Tunisia.

Objectives: The aim of this study was to determine the frequency ofmild and moderate toxemia in our institution, our ambulatorymanagement of these two stages of the illness and the maternal and fetalprognoses.Study Methods: One hundred and seventeen files of patients with mildand moderate toxemia were reviewed retrospectively during a period oftwo years (July 1997- June 1999).Results: Twenty-four patients were at term. Three of these patients hadassociated gestational diabetes. Sixteen were delivered vaginally andeight had a cesarean section. The birth weight average was 3200 g. Anacute abrupto placenta complicated one pregnancy. Two neonatespresented a respiratory distress. Thirty-four patients were between thirty-four and thirty-seven week-gestation. Seventeen had a clements test.This last was positive in four cases indicating fetal extraction. Eighty-nine patients were followed ambulatory. Mothers and their fetuses hadclinical observation daily. Hepatic and renal functions were controlledweekly. All the women had anti-aggregates, corticoids and, if necessary,anti hypertension therapy. 7.7% of the patients developed severetoxemia. 1.1% had abrupto placenta. The average-term of delivery wasthirty-five gestation weeks. The average weight was 26600 g. Deliveryhappened vaginally in 60.5% and by cesarean section in 39.5% of thepatients. The rate of prematurity was 35%. Neonatal death in 1.1% of thecases and 10% of neonates had respiratory distress that evaluatedfavorably.Conclusions: Ambulatory management of mild and moderate toxemiaallowed a shortening in the period of mother-hospitalization and so asignificant reduction in the cost of this frequent pregnancy diseasewithout any augmentation of mother and fetal complications.


P4.11.02DOPPLER BLOOD FLOW VELOCITY WAVEFORMS INHYPERTENSIVE PREGNANT WOMENM.Ivanovski , Dept.OB/GYN, University Hospital, Vodnjanska 17,Skopje 91000, R.Macedonia

Objectives: The aim of the study was to investigate the role of Dopplervelocity waveforms changes in the circulation of a.uterina and a.umbilicalis in hypertensive pregnancies for prediction of fetal outcome.Study Methods: Forty- four hypertensive pregnant women were includedin this study. Doppler velocimetries were performed during thirdtrimester with Pulsed wave Doppler Toshiba, Sonolayer SSa-250A with3,75 transabdominal probe. We recorded the resistance index(RI) ofPourcelot of the umbilcal artery and uterine artery.Results: The hypertensive women were divided into four groups basedof umbilical artery and uterine artery resistance index (RI): 1.(n=9)Normal umbilical and Normal uterine (NuNu); 2.(n=7) Normalumbilical and Abnormal uterine (NuAu); 3.(n=11) Abnormal umbilicaland normal uterine (AuNu); 4.(n=19) Abnormal umbilical and Abnormaluterine (AuAu).Detection of AuAu was connected with higher rate of complications:Gestational age 33+-3,2;Birth weight 1600+-850 g; Cesarean Section forfetal distress 57,9%; SGA 73,6%; NICU>48 h 68,4%; Perinatalmortality 26,3% (p<0,05) than other tree groups separately.Conclusions: Doppler sonography allows better understanding of thehemodinamic changes associated with hypertensive disorders ofpregnancy. Various high risk groups can be classified based on Dopplervelocimetry. Doppler velocimetry can guide us in the treatment of thesepregnancies and the prevention of high mortality and morbidity inhypertensive patients

P4.11.03EFFECT OF NIFEDIPINE ON THE MOTILITY OF THE HUMANUMBILICAL ARTERY IN VITROA. Yassin , F Costa, H. Guimarães, A. Matthes, G. Duarte, S. Cunha.Department of Gynecology and Obstetrics, Faculty of Medicine ofRibeirão Preto, University of São Paulo, 3900 Bandeirantes Ave.,Ribeirão Preto, SP, Brazil, 14049-900.

Objectives: To determine the effect of Nifedipine in an vitro study of thetonus of the human umbilical artery.Study Metohods The action of nifedipine and bradykinin on thecontractility of the human umbilical artery was studied by a perfusionmethod. Forty nine human umbilical segments were studied and avasodilator effect of different nifedipine concentrations was observedcompared to infusion of Tyrode alone.Results: Comparison of the results obtained by infusion of Tyrodesolution and the results obtained by infusion of Tyrode + Nifedipine atdifferent concentrations showed a vasodilator action of nifedipine on theumbilical artery segments.Conclusions: Pregnant women with arterial hypertension usually presenta reduced uterine-placental flow. If in this situation nifedipine had thesame effect as observed here in vitro, this drug could have a beneficialeffect by reducing the vascular resistance of the umbilical artery,probably facilitating maternal-fetal exchange.

P4.11.04FETAL INTRAVASCULAR TRANSFUSION - CLINICAL REPORTD.Filimonovic , Z.Mikovic, A.Cirovic, A.Hajric, OB/GYN ClinicBeograd, Narodni Front Str.62, Belgrade, Serbia, Yugoslavia, 11000.

Objectives: Evaluation of seven-years expirience in fetal intravascularblood transfusions in immunizied fetus.Study Methods: Statistical analysis of data of 93 pregnant woman vithantieritthrocyte antibodies present in circulation. Indication for fetaltransfusions were: absolute:fetal hidrops and decrease of Hct or Hgb lessthan 95 percentiles for gestation age, and relative: fetus inB2 or Czone(Liley), ascites, fetal anemia detected by cordocentesis andexpected decrease of Hct.Results: Acording to accepted criteria, in 14 casses fivt was performed.in general, 26 transfusions,in particular case maximum of 3 transfusionswere performed.From 14 pregnancies, 12 heltlly children were born, 1IFD and 1 terminated pregnancy ( Sy Edvards)

Conclusions: With strice selection and secure tehnical procedure FIVTgives chance to fetuses in cases of confirmed aloimunisation. Althovhigh risks of FIVT are recognised, bat is a acceptibl in most severe casesof aloimunisationes.

P4.11.05FOR EARLY DETECTION OF CONSUMPTION COAGULOPATHYIN PREECLAMPSIA AND ECLAMPSIA – PLATELET COUNTMAY BE A SUITABLE SCREENING TESTN. Khanam , Dept. OB/GYN, Dhaka Medical College, Dhaka,Bangledesh.

Objectives: The aim of this study is to find out whether platelet countcan be used as a suitbale screening test for early detection ofconsumption coagulopathy in preeclampsia and eclampsia.Study Methods: This study was undertaken in Dhaka medical CollegeHospital from February 1997 and October 1998. 130 pregnant womenwere included in this study among them 50 were severe preeclamptic, 50were eclamptic and 30 were normal healthy pregnant women. Normalpregnant women were served as control. All of them were at thirdtrimester of their pregnancy. Prothrombin time (PT), Activated partialthromboplastin time (APTT), Thrombin time (TT), Plasma fibrinogenlevel, D-Dimer and platelet count were determined of all the persons.The data obtained were complied and statistical analysis was done.Result: Mean platelet count was significantly lower in preeclampsia andeclampsia group and 37% were thrombocytopenic. Prolonged PT, APTTand TT were present in 5%, 3% and 2% cases respectively.Hypofibrinogenaemia was present in 18% cases and D-Dimer waselevated in 16% cases. All the people who had any abnormalities in anyof the above test also had thrombocytopenia. One patient developedfrank DIC, her platelet count was very low.Conclusions: It can be concluded that platelet count alone can be used asan effective screening test for early detection of consumptioncoagulopathy in preeclampsia and eclampsia.

P4.11.06HELLP SYNDROME AND POSTPARTUM CORTICOSTEROIDSF.Varol , Trakya University Medical School, Obstetrics and GynecologyDept. , Edirne/Turkey,, T.Aydın, F.Gucer, T.Yardım

Objective: To investigate beneficial effects of postpartum corticosteroidson the labour parameters of HELLP syndrome.Study Method: The study group consisted of 8 postpartum patients withHELLP syndrome.The mean gestational age is 33.5 . A total dose of 30mg dexametasone with 3 doses of 10 mg of intravenous dexametasonewas given 2 hours apart.Only one corticosteroid regimen wasused..Eight patients had laboratory findings of HELLP syndrome beforethe corticosteroid administiration.The HELLP syndrome is characterizedby hemolysis,elevated liver functions,and low platelet counts.The control group consisted of 11 postpartum patients w / HELLPsyndrome who were managed without dexamethason.All patients were postpartum, given intravenous fluids and started onmagnesium sulphate for 24 hours.Management also included nifedipinefor diastotic blood pressure > 105 mm Hg. Mean arterial pressure(MAP) , platelet , liver function tests (serum AST,ALT), lactatedehydrogenase (LDH ) were compared before and after dexametasoneadministiration.Samples for postdexametasone values were evaluatedbetween 6 and 8 hours after corticosteroid regimen.Result: Corticosteroid improve the abnormalities in MAP,mean AST,ALT, LDH and platelet.This shorten the mean hospitalization duration.Conclusion: Consideration should be given to the use of corticosteroid inpostpartum patients with HELLP.

P4.11.07HIGH RISK OR LOW RISK? DO PREGNANT WOMEN CARE?H. Simpson , H. Ashwood-Smith, C. Finye, G. Gondwe, K. Misoya, SafeMotherhood Project, Blantyre, Malawi.

Objectives: Reports from Malawi indicate compliance with obstetricreferral advice is deliberately ignored by women identified to be at ‘highrisk’. This descriptive study was conducted to determine the compliancerate among high-risk pregnant women and to explore the factorssurrounding non-compliance.


Study Methods: Quantitative and qualitative methods were combined toprovide depth and numerical credence to the data. In the qualitativecomponent, a broad spectrum of society, including compliers and non-compliers, were purposively selected. 22 focus group discussions, 7 keyinformants, 8 critical incidents and 6 Venn diagrams provided data andguided questionnaire development. The survey was subsequentlyconducted with 244 recently delivered women attending under 5 clinics.Only women referred during their pregnancy for delivery at the districthospital were included.Results: 54% (CI 47.3 – 60.6%) of high risk women complied withreferral advice. Primagravidas and grand multiparas demonstratedhighest non-compliance. 32% expressed fear of cesarean section, 17%cited distance and transport as problems, and 14% claimed poorprovision of information. Other issues affecting compliance includedfear of pain, altered body image and sexual pleasure followingepisiotomies, and enforced tubal ligation. Husbands played an importantrole and contributed to non-compliance fearing that absence of wiveswould lead to sexual infidelities. Educational status had a strongassociation with non-compliance as did attitude of staff (p=0.001).Women suggested that improved staff attitude and interpersonalcommunication were critical to referral compliance.Conclusions: The accuracy and utility of the high-risk approach hasprovoked much international debate. Unless significant efforts areprimarily directed towards addressing user perspectives of quality,efforts to improve high-risk identification cannot impact upon maternalmortality irrespective of issues of sensitivity and specificity.

P4.11.08INDIRECT EVALUATION OF THE CIRCULATORY VOLUME OFTHE FETO-PLACENTAL UNIT.Lj. Mirkovic (1), D. Plecas(1), N. Radunovic(1), M. Popovic(2), A.Glisic(1), V. Milenkovic(1), M. Radovic(1)(1) Clinical Center of Serbia, Institute of OB/GYN, Belgrade,

Yugoslavia.(2) National Blood Transfusion Institute.

Objectives: Evaluation of feto-placental circulatory volume (FPCV) fora certain gestational age is of utmost importance as a basic physiologicalparameter with practical clinical impact. Therapy of most severe formsof hemolytic diseases of the fetus by intrauterine intravasculartransfusions (IUIVT) enabled the indirect evaluation to changes in thevalues of feta hematocrit as a result of IUIVT blood of known volumeand defined hematocrit.Study Methods: According to the results of pretransfusion andposttransfusion of fetal hematocrit in the course of 193 IUIVT(performed between gestational weeks 18-43) and according to MacGregor’s formula the fetoplacental circulatory volume was calculated:

K x (HctK-Hct1) + VuV=--------------------------------------

Hct 1 – Hct0V-fetoplacental circulatory volume; K-amount of transfused blood;HctK- hematocrit of the transfused blood; Kct1-final fetal hematocrit;Hct0- initial fetal hematocrit; Vu- volumen of the sample for analysis.FPCV value is expressed in relation to the body weight of the fetusevaluated by echographic biometry.Results: The feto-placental circulatory volume was calculated accordingto the large number of IUIVT and amounts to 129.3ml/hk (:13.8) bodyweight.Conclusions: Determination of FPCV value is practically very importantfor evaluation of the about of blood required for IUIVT.

P4.11.09INFLUENCE OF PREGNANCY ON THE OROVALVARBIOPROSTHESIS NATURAL HISTORYMassonetto, Júlio Cesar ; Born, Daniel; Almeida, Pedro A. Marcondesde; Moron, Antonio Fernandes; Buffolo, Enio; Carvalho, AntonioCarlos. UNIFESP-EPM - Obstetrics and Cardiology Division, São Paulo– Brazil. UNILUS – Maternal-Infantile Health Department, Santos -Brazil

Objective: To appreciate if pregnancy influences bioprosthesis naturalhistory.Patients and method: In order to analyze that influence, we haveconducted a longitudinal and retrospective study with 37 female patients

who were submitted to valve replacement. We divided them in twogroups: the group I included 18 patients with bioprosthesis (18 porcinevalves) who had at least one pregnancy during our protocol, with a meanfollow up period of seven years ; the group II included 19 patients withbioprosthesis (19 porcine valves), same age, who did not becomepregnant in the period and who were followed up for an average periodof thirteen years. We analyzed clinical evaluation for both groups andwith regular echocardiographic follow-up and selected calcification,stenosis and bioprosthesis replacement need for statistical analysis. Thiswas performed with the Mann-Whitney test, Pearson c_ analysis andactuarial analysis. A p value less than 0.05 was considered statisticallysignificant.Results: There wasn’t earlier bioprosthesis replacement need in thegroup I - patients with pregnancy. Also there was no significantdifference concerning calcification occurrence in the bioprosthesisbetween the two groups, as well as bioprosthesis stenosis. The averagetime for structural deterioration in the bioprosthesis that failed was sevenyears in the group I and five years in the group II.Conclusion: Our conclusion is that pregnancy has no acute influence onthe bioprosthesis natural history.

P4.11.10INTRACARDIAC OPERATION WITH THE USE OFCARDIOPULMONARY BYPASSJ.Aranyosi , J.Zatik, T.Major, A.Peterffy, University Medical School ofDebrecen, Hungary, P.O.B.37, Debrecen, HBM, Hungary, H-4012.

Open heart operation during pregnancy has got significant maternal andfetal mortality rate. Case reports of two women (27 years old, G:II, P:I,26 weeks of gestation with subaortic ring and a 35 year old, G:III, P:III,21 weeks of gestation with with mitral stenosis) are given whounderwent surgery during pregnancy. The intracardial surgicalintervention, excision of stenotic ring and the mitral commissurotomywas successfully performed in the setting of cardiopulmonary bypass(CPB). The perioperative period was uneventful for both the patients andfetuses. The women normally delivered per vias naturales and thenewborns were progressing well.The therapeutic protocol is proposed to decrease the fetal risk of CPB.The decision to perform the operation during the pregnancy was madeby a team involving cardiologist, obstetrician and neonatologist. Theoperation was timed after organogenesis has been completed. During theoperation the pregnant lied in a left lateral recumbent position.Cardiotocography (CTG) was performed for continuous monitoring ofthe fetal heart rate and uterine activity. CPB provided high flow and highmaternal mean arterial pressure. No hypothermia was used (min. 36degrees centigrade rectal temperature) to avoid uterine contractions,impared placental exchange of respiratory gases and anomalies of fetalmyocardial conduction. The extracorporeal perfusion time was kept to aminimum (45 and 20 minutes). No maternal hypoxaemia, acidosis orhypercapnia occured during the operation.According to the presented protocol open heart surgery with CPB can beperformed safely for the mother and her fetus as well.

P4.11.11MANAGEMENT OF PREGNANCIES WITH IMMUNETHROMBOCYTOPENIC PURPURARecep Has , H. Ermis, A. Yildirim, C. Batukan, L. Ibrahimog, F. Buyru.Dept. of OB/GYN, Istanbul Medical Faculty, Istanbul University,Istanbul, Turkey

Objective: The aim of this study os to evaluate the obstetric managementof hematological problems in pregnancies with idiopathicthrombocytopenic purpura (ITP).Study Design: 31 pregnant women with ITP admitted to our unitbetween 1994 and 1998 were reviewed.Results: Twenty-two of the women were delivered vaginally, and 11with caesarean section. There were no maternal deaths and no stillbirthoccurred. Four of the patients had clinical symptoms ofthrombocytopenia. Two patients had ecchymosis, one had petechiae andone had gingival bleeding and ecchymoses. […] the liveborn infantsdied in neonatal period, mainly due to the complications of prematurity,and six required supportive treatment with corticosteroids and IgG.Conclusion: The rarity of poor neonatal outcome mand majorcomplications in mothers with ITP does not justify obstetric intervention


solely on the basis of […] platelet counts. The management of patientsshould be individualized and carefully […].

P4.11.12MANAGEMENT OF PREGNANCY COMPLICATED BY DIABETESMELLITUS – 4-YEAR EXPERIENCET. Chanturia (1), I. Iashvili (1), N. Asatiani (2), R. Kurasvili (2),M. Hod (3)(1) Maternity Home N2, Tbilisi, Georgia.(2) Georgian Diabetes Center, Tbilisi, Georgia.(3) Rabin Medical Center, Belinson Campus, Israel.

Objectives: In 1996, a Georgian-Israel Twinning Program Diabetes inPregnancy was started. The main aim of the program is outlined in theSVD Declaration: “to achieve pregnancy outcome in diabetic womenthat approximate that of non-diabetic women”.Study Methods: In total, 22 women with Type 1 Diabetes Mellitus gavebirth at the Maternity Home. 11 of them had a bad obstetrical history (6patients had previous stillbirth, 4 had spontaneous abortions, 1 had 7previous pregnancies terminated before the 19th week of gestationbecause of severe diabetes complications).Results: Though all the patients were closely supervised throughout thewhole pregnancy period, 6 of them developed preeclampsia. In one case,due to acute hydramnios, pregnancy was terminated by cesarean sectionat the 35th week of gestation. In another case, pregnancy was terminatedat the 36th week of gestation due to deterioration of renal functions onthe background of diabetic nephropathy. In 4 patients, fetal distresssyndrome developed (in 2 cases during pregnancy and in another 2during labor). In 19 cases (86.4%), cesarean section was performed,vaginal delivery took place in the remaining 3 cases. Mean age ofgestation was 38.1±0.7 weeks; fetal birth weight 2100-4700g; prenatalmortality-0; respiratory distress syndrome-0; neonatal hypoglycemia(mild to moderate) – 4 (18.2%); CNS injury – 8 (36.3%); macrosomia –6 (27.2%); low birth weight –1 (4.5%). In all the cases, there weremultifactoral indications for cesarean section.Conclusion: Data achieved indicate that team approach, education,preconception care and care throughout the pregnancy, and closesupervision of the patient resulted in significant optimization of thediabetic pregnancy outcomes. Our patients showed even better resultsthan that achieved in the general population. The high percentage ofcesarean section is the result of severe somatic and obstetric contingentin our patients.

P4.11.13NAIL-PATELLA SYNDROME IN PREGNANCYL.K. Tan , C.B. Wong, H.K.Tan, A.S.A. Tan, L. Choong* Dept ofOb/Gyn,, Singapore General Hospital, Singapore *Dept of RenalMedicine, Singapore General Hospital, Singapore

Nail-patella syndrome or hereditary onycho-osteodysplasia is anautosomal dominant syndrome comprising nail dystrophy, absent orhypoplastic patella, incomplete elbow extension, conical posterior iliachorns and nephropathy. We present a 29 year old gravida 2 para 1 whowas diagnosed with the condition 3 years ago. She presented withnephrotic syndrome during her first pregnancy 4 years ago which wasnot complicated by pre-eclampsia and resulted in a full term normalvaginal delivery of a 2.3kg baby boy. Following the first pregnancy,investigations revealed persistent nonselective proteinuria , impairedrenal function and focal segmental glomerulosclerosis on renal biopsyand phenotypic features of the syndrome. She booked for joint antenatalcare with the renal physician at 6 weeks. Her blood pressure was normaland urine revealed 4+ proteinuria. Booking renal investigations revealeda creatinine level of 164umol/l, creatinine clearance of 28 ml/h and a 24hour urine protein of 2.65g/dl. Amniocentesis performed for a familyhistory of Down syndrome at 16 weeks revealed a normal femalekaryotype and no structural anomalies noted during a fetal anomalyultrasound scan at 20 weeks gestation. She was on maintenanceprednisolone and methyldopa was added when she developedhypertension (bp 150/120mmHg) at 23 weeks. She did not havesymptoms of fulminant pre-eclampsia. Her renal function had sincesignificantly deteriorated (creatinine 369umol/l, creatinine clearance15ml/h and 24 hour urine protein 10.3g/day) with hypertension needinglarger doses of antihypertensives. She developed preterm labour at 27weeks which was temporarily inhibited to allow the administration of

intramuscular dexamethasone to accelerate fetal lung maturity.Ultrasound scan showed that there was no intrauterine growth restrictionof the fetus with an estimated fetal weight of 740g. A decision was madeto terminate the pregnancy in view of the deteriorating renal functionand poorly controlled hypertension strongly suggestive of superimposedpre-eclampsia. Labour was successfully induced with vaginaldinoprostone with a normal vaginal delivery of a 945g baby girl withApgar scores of 6 and 9 at 1 and 5 minutes of life respectively.Postpartum the mother’s blood pressure improved with marginalimprovement in renal function. This is the only second report in theliterature of nail-patella syndrome in pregnancy and indeed the onlyreport with a livebirth.

P4.11.14NIMODIPIN IN THE MANAGEMENT OF PREGNANCY INDUCEDHYPERTENSION (P.I.H.)S. Dasgupta , Dept. OB/GYN, Jamshedpur, India

Serotonin released following platelet aggregation and endothelialdamage aggravates vasospasm and hepato renal damage in PIH. Thisstudy has been undertaken to assess the effect of antiserotonin drug likeNimodipin as a therapy of PIH.Study Design: Straight trial carefully controlled.Setting: four Medical Schools (Collaborative)Drug Schedule: The drug was administered 30 mgBD on the first andsecond day followed by 30 mgBD TDS for next two days. If the controlwas not satisfactory dosage was increased to Nimodipin 30mg fourtimes a day.Subjects: 119 patients were recruited. The criteria of selection for trialwas patients after 20 weeks. The criteria of hypertension was140/90mmHg confirmed by two observers.Results: Mean MAP at entry of trial was 112.30. A good response wasnoted in 81 patients out of a total of 116 patients (69.83%). The meanbirth weight was 2.7kg. There was no neonatal death.Conclusions: This is the first trial of oral Nimodipin in PIH indicating aneffective role. The special advantage of this drug therapy was the safetyin domiciliary use, which may be difficult with anti-hypertensive drugs.

P4.11.15OBSTETRICAL AND PERINATAL OUTCOME IN MULTIPAROUSADOLESCENTSJ.L. Pinto E Silva , M. Chinaglia, N. Oliveira, University ofCampinas/UNICAMP, Alexander Flemming, 101, Campinas, São Paulo,Brazil, 13083-970.

Objective: To compare the obstetrical and perinatal outcome ofmultiparous adolescents to two groups: nulliparous adolescents andmultiparous adults. Study design: A retrospective cohort study. Setting:A tertiary university care center Patients and methods: A total of 199multiparous adolescents were compared to 398 nulliparous adolescentsand 398 multiparous adults. Exclusion criteria included patients withchronic diseases, stillborn, twins, and fetal malformation. Statisticalanalysis was performed using Chi-squared test, Student's t test forindependent samples, and multiple logistic regression.Results: Small-for-gestational age newborns (SGA) were significantlyhigher in the group of multiparous adolescents (7.3%) than inmultiparous adults (3.6%). Maternal age =19 years was significantlyassociated with an increase risk for SGA newborns (p=0.53, OR=2.119).Conclusions: Multiparous adolescents presented a higher percentage ofSGA newborns when compared to multiparous adults. Lower maternalage (=19 years) showed to be an isolated factor that doubled the risk forSGA newborns.

P4.11.16PREGNANCY AFTER LIVER TRANSPLANT: 3 CASESREPORTEDN. S. Carvalho , R. S. Schwarz, L. A. Thereza, Dept. OB/GYN, ClinicHospital, Federal University of Parana, Parana, Brazil.

Objectives: The purpose of the study was to relate three cases ofpregnancy and liver transplant in the clinic Hospital of Parana FederalUniversity in the period 1997 and 1998.


Study Methods: Prospectively was studied 3 patients with livertransplant in the liver transplant service and obstetric and gynecologydepartment of the clinic hospital. Was analyzed the evolution of thepregnancy and liver function of the patients.Results: All were attendanted during all pregnancy case with normalevolution, but at end pregnancy one patient developed toxemia, andamniotic fluid, another with premature rupture of membranes andmeconius amniotic fluid to and last with abruption placenta and fetaldistress. All the cases were submitted to cesarean section because theobstetrics intercorrences and the 3 newborns were without diversed. Theliver function was normal through the pregnancy and after the delivery.ConclusionsAll three patients with liver transplants and pregnancy showed normalpregnancy cases evolution but obstetrics intercorrences happens duringthe end of the pregnancy and the delivery. Than liver transplant andpregnancy will be evaluated as high-risk pregnancy.

P4.11.17PREGNANCY AFTER LIVER TRANSPLANTATIONR. Winograd , D. Spaccevento, O. Imventarza, S. Grimoldi, M. Celotto,O. Parada, Hospital C. Argerich, Buenos Aires, Argentina.

Objectives: Analyzing the course and outcome of pregnancies in livertransplanted patients.Study Methods: Since 1992, 133 women have been transplanted in theArgerich and in the Garraham Hospitals, Buenos Aires, Argentina.Eleven patients have gotten pregnant 13 times after transplantation.These pregnancies were managed by a team of liver transplantationspecialists, physicians, psychologists, and kidney specialists.Hypertensive disorders, fetal growth, liver function tests and infectivedisorders were specially monitored. Standard immunosuppressiveregimen during pregnancy consisted of cyclosporine A (CyA),tacrolimus (FK) and low-dose steroid therapy. One patient received ahigh-dose steroid therapy and 5 ASA because suffered a reacuteulcerative cholitis. AyA and FK whole blood through levels weremonitored on a routine basis to keep therapeutic range (CyA 80-150ng/mL;FK 4-8 ng/mL).Results: Mean interval from liver transplantation to pregnancy was 37.1months. No patient had a graft loss and there were no lethal mother’scomplications. The incidence of complications was the same as that inpublished series. Six cases of preeclampsia occurred and 2 pregnanciesbegan (in the same patient) with chronic hypertension. Infections haveoccurred 7 times and anemia and kidney disorders with hiperuricemia 3times. Terms of gestation had a mean of 36.8 weeks, deliveries inducedwere 2 and we have performed 10 cesarean section. Three pregnancieswere preterm (less than 37 wk) and 3 babies were under weight (lessthan 2500g). There was one stillbirth and one neonatal mortality. Onewoman had a miscarriage at 12 weeks of pregnancy due to uterinetuberculosis. The worst results occurred when the patients with the riskfactors published for other authors (interval from transplantation lessthan one year, chronic hypertension, graft rejection and kidneydisorders). Neither congenital malformation nor unusual infection wereseen in the children. Postnatal follow-up revealed appropriate physicalgrowth to date.Conclusion: Our data indicate that successful pregnancies after livertransplantation under careful management by a multidisciplinary teamhave a good outcome.

P4.11.18PREGNANCY OUTCOMES IN WOMEN AGED 35 AND OLDER INA TERTIARY LEVEL HOSPITAL OF BANGLADESH.M.R. Begum , Dept. OB/GYN, Dhaka Medical College and Hospital.Bangladesh; N. Nasrin, Dept. OB/GYN, Dhaka Medical College andHospital. Bangladesh; A.Begum, Dept. OB/GYN, Dhaka MedicalCollege and Hospital. Bangladesh; S..Nahar, Dept, National Institute ofPreventive and Social Medicine. Bangladesh

Objective: The purpose of this study was to identify the effect of age of35 years and above on pregnancy outcome in comparison to the youngergroup.Study method: A retrospective review of patients admitted in ObstetricsDepartment of DhakaMedical College and Hospital for pregnancy related causes and deliveryfor the year 1997 and 1998.

Results: Out of 25030 patients 1010 (4.03%) were ³35 years of age.Most of them (92.77%) were multiparous and 7.22% were primiparous.Seven hundred and eighty five (77.72%) patients had obstetric andmedical complications and 66.53% had abnormal labour. The mostfrequent complications were Spontaneous abortion 31.09% vs 9.27%(R.R-3.5, 95% CI 3.04 -3.71, p=0000), Induced abortion 4.06% vs1.28% (R.R-3.2, 95% CI 2.30-4.36, p=0000), Obstructed labour 4.45%vs 3.63% (R.R-1.23, 95% CI 0.92-1.65, p=0.031), Ruptureduterus1.09% vs 0.59% (R.R -1.9, 95% CI 1.01-3.42, p=0.0001) forwomen ³35 years vs 34 years or younger . Primary caeserean sectionrate was 41.60% vs 33.82% (R.R-1.5, 95% CI 0.95-2.94, p=0.0000).Perinatal outcome was also poor in older group. Perinatal death was14.41% vs 8.92% (R.R-1.7, 95% CI 1.33-1.95, p=0.0000) andCongenital anomalies were 1.20% vs 0.19% ( R.R-6.2, 95% CI 2.87-13.21, p=0.0000).Conclusions: Women of ³35 years of age are at higher risk ofdeveloping various complications during pregnacy and labour than thoseof younger group. As 93% patients of this series were multiparous, soage alone may not appear to be an important risk factor for all pregnantwomen.

P4.11.19SUBDORAL HEMORRAGE, ACUTE FATTY LIVER, TRIPLETGESTATION IN A PATIENT WITH HYPOTHALAMICAMENORRHEAM. Ghaffarnejad , Mehr and Mirza Kuchakkhan Hospital, TehranUniversity of Medical Science, Tehran, Iran.

BackgroundAcute fatty liver of pregnancy (AFLP) is reported to be more common inmultiple than in singleton pregnancy. We report a case of hypothalamicamenorrhea with previous history of successful singleton pregnancy thatin second trial of induction with HMG, HCG she became pregnant(triplet). She was hospitalized due to subicter, mild hypertension,sustained nausea, vomiting, malaise and contractions at 34 weeks ofgestation. After liver function tests and others the babies were deliveredpromptly by C/S. All fetuses survived. After transfer of patient to wardshe had severe post partum hemorrhage that stopped with aggressivesupportive care.The AFLP was diagnosed on the third hospital day after laboratoryresults. One week after C/S she discharged and liver function testsimproved. Despite normalization of blood pressure and coagulopathy.The patient came back with sustained headache. CT scan was carried outand showed subdural hematoma. The emergent drainage of hematomawas performed. Finally the patient recovered.Conclusion: AFLP must be suspected in all pregnant patients with pre-eclampsia, multiple gestation and symptoms of gastritis. Clinicians mustbe alert of diagnosis and prompt delivery of this rare and severecondition and careful follow up. This patient is the first report of AFLP,triplet gestation, subdural hematoma in the patient with hypothalamicamenorrhea.

P4.11.20THE LIPID PROFILE OF WOMEN IN PROLONGED PREGNANCYP.Piech, R.Adamowicz , B.Waksma_ski. Silesian University School ofUniversity, Chair and Clinic of Gynaecology, 41-800 Zabrze, Pl.Traugutta 6 – Poland

The study is an attempt to investigate the changing levels of lipids in theblood plasma of women in prolonged pregnancy and after induction oflabour with Prepidil prostoglandin preparation.Study was performed for three groups of pregnant women.A-15 women which gave birth spontaneously after prolongedpregnancy,B-15 women after prolonged pregnancy in which labour was inducedwith Prepidil,C-15 control group – women with normal pregnancy course and birthon time.The following lipid parameters of the blood plasma were analysed: totalcholesterol concentration, cholesterol concentration in LDL and HDLfractions, triglyceride concentration – TG, concentration ofphospholipids – PL.This study has shown that the mean values of the concentration of totalcholesterol and its LDL fraction has increased while the concentration of


phospholipids and HDL cholesterol fraction was lower in the test groupin prolonged pregnancy (the same applies to the groups A and B) incomparison with the control group (group C).There was no difference in the lipid profile of the group of womenwhich gave birth spontaneously after prolonged pregnancy and in thegroup in which labour was induced with Prepidil.Conclusion: The identification of the changing levels of lipid in theblood plasma may be of significant help in diagnosis of prolongedpregnancy.

P4.11.21TOXEMIA OF PREGNANCY – HEMATOLOGICAL &BIOCHEMICAL CHANGESK. Begum , Dept. OB/GYN, Sir Salimullah Medical College & MitfordHospital, Dhaka, Bangladesh.

Objectives:(1) To estimate the coagulation defects in out toxemic patients.(2) To estimate the hematological abnormalities and early institution of

symptomatic therapy to improve maternal and fetal outcome.(3) To detect the effects of toxemia on major organ function.Study Methods: Prospective case controlled study of 100 cases – 51toxemic, 26 normal pregnancy and 23 non-pregnant as control. Done inDhaka Medical College Hospital from April 1997 to December 1997.Investigations performed included Hb%, Platelet count, TLC, serumelectrolytes, AST, LDH, APTT, ATIII activity, Fibrinogen, FDP, Urea,Creatimine and urine analysis. Data analysis by SPSS program andexpressed as frequency or %. Comparison between the groups were doneby Chi Square or student t-test as appropriate.Results: Antenatal care was significantly less in toxemic group (p-0.001). Hb% platelet count. TLC increase significantly in toxemicgroup. Serum sodium and potassium shows significant decrease (0.000and 0.002 respectively). Regarding LFT, only LDH shows significantincrease in toxemic group (p-0.003). But coagulation factors like FDP,APTT, AT III activity show marked changes. Renal function tests showsno significant change.Conclusions: PET can not be prevented absolutely but the incidence ofeclampsia, its complications and effects to the mother and fetus can bereduced by close patient monitoring, timely intervention by drugs andinvestigations which predict some ominous signs, so that valuable livescan be saved.

P4.11.22UMBILICAL CORD AROUND FETAL PARTS: PREVALENCE,RISK FACTORS, MATERNAL AND PERINATALCOMPLICATIONST. Silberstein , M. Hallak, S. Eyal, G. Holcberg, M. Katz, M. Mazor,Dept. OB/GYN, Soroka University Medical Center Faculty of HealthSciences, Ben Gurion University of the Negev, Beer Sheva, Israel.

Objectives: To determine the rate, risk factors, maternal and fetalcomplications associated with deliveries of neonates born with cordaround body parts.Study Methods: During the years 1989-1997, 89,872 deliveries occurredin our institution. The study group consisted of 13,948 fetuses in whomthe umbilical cord was detected around fetal parts such as: neck, body,legs or hands. The control group consisted of remaining 75,924 patients.Several associated risk factors, complications, and perinatal outcomeswere analyzed. Statistical analyses were performed using multivariateanalysis on independent significant variables.Results: The prevalence of umbilical cord around fetal body parts was15.5% (13,948/89,872).

OR CI pNon progressive labor –1st stage 1.23 1.09-1.39 <0.01MSAF 1.3 1.25-1.37 <0.01Ripening of cervix by PG 1.15 1.06-1.24 <0.01Induction of labor by oxytocin 1.25 1.1-1.41 <0.01Fetal distress 1.57 1.45-1.71 <0.01Male gender 1.15 1.09-1.2 <0.01

There were no significant differences between groups in the rates ofIUGR, abnormal presentations, stillbirth, postpartum death, Apgarscores in 1’ and 5’, abruptio placenta, non progressive 2nd stage andcesarean sections.

Conclusions: Cord around fetal parts was associated with a higher rate ofperipartum complications. In contrast no significant difference wasnoted in the perinatal morbidity and mortality between the groups.

P4.11.23VALUE OF ENHANCED MRI IN THE DIAGNOSIS OF PLACENTAPERCRETAJM Palacios Jaraquemada 1, C Bruno2, M Pesaresi3, S Hermosid4 C, Departamento de Tocoginecología, Hospital Durand1-3-4. Av. Díaz Vélez5044 (1405) Capital Federal, Argentina. Resonancia MagnéticaLomas1,2, Hipólito Irigoyen 8680, (1832) Lomas de Zamora, Pcia. DeBuenos Aires, Argentina.

Objective: To demonstrate the utility of Enhanced Magnetic ResonanceImaging in the differential diagnosis of placenta percreta.Methods We studied 35 patients with multiple cesarean sections andclinical or ultrasound suspicion of placental adherent disorder. Patientswere between 30 and 34 weeks of gestation. All patients consented toboth magnetic resonance imaging (MRI) and contrast administration.They underwent an enhanced MRI with gadolinium (0.1 mmol/kp)through Resonator 1.5 Tesla, technique Spin echo, breath hold. Imageswere obtained from the three planes, at 60 and 90 sec following contrastadministration.Results: The following results were obtained: 11 diagnoses of placentapercreta, 3 of placenta increta, and 13 of placenta accreta. In 6 patientsof the latter group, MRI modified the extension of the adherent disorderdiagnosed by ultrasound.Conclusions ..Enhanced MRI has proved to be useful for the differentialdiagnosis of placenta percreta. Its use is recommended for patients athigh risk for placental adherent disorder, when ultrasound diagnosis isnot conclusive.

P4.12 INFECTIONS IN OBSTETRICS AND GYNECOLOGY-HIV

P4.12.01CAN ISOLATED POSTPARTUM ZIDOVUDINE PROPHYLAXISREDUCES PERINATAL HIV TRANSMISSION?G.Duarte , M.M.Mussi-Pinhata, M.C.Cervi, C.M.Kato, M.C.Paschoini,S.M.Quintana, School of Medicine of Ribeirão Preto of São PauloUniversity, Avenida Bandeirantes 3900, Ribeirao Preto, Sao Paulo,Brazil,14049-900.

Objectives: The objectives of this study were to examine whether onlyneonatal zidovudine (ZDV) prophylaxis could reduce HIV verticaltransmission (VT), considering the presence of breastfeeding (BF).Methods A cohort of 38 infants born at the University Hospital of theSchool of Medicine of Ribeirão Preto, whose HIV-infected mothers hadnot received ZDV during pregnancy or at delivery was selected toreceive oral ZDV (2 mg/kg, 6/6h) for at least 30 days. HIV infectionstatus of these children was determined by 2 HIV DNA-PCR tests at age>3 mo. and/or confirmed HIV serology at age of 18 mo. Comparisongroup of no ZDV prophylaxis was composed of 150 infants born toHIV-infected mothers at the same hospital when ZDV was not availablefor prophylaxis against vertical transmission of HIV in Brazil.Results: Studied groups were comparable regarding to maternal HIV-related symptoms, associated infections, IVDU during pregnancy, typeof delivery, membranes rupture interval, gestational age and BF.Overall, the VT rates were 19.4% (CI 95% 13.2-26.9) in no ZDV groupand 5.4% (CI 95% 0.9-6.7) in ZDV group (p=0.042). After adjustmentfor BF with similar duration, the comparison of VT rates showed areduction of 64% in perinatal transmission when ZDV was used (15.0%to 5.4%). Although this difference was impressive, it does not reachstatistical significance (p=0.237; RR=0.36; CI 95% 0.08-1.53), probablybecause of the limited number of cases.Conclusions: These results have shown that postpartum ZDVprophylaxis might reduce HIV perinatal transmission and this reductionseems to be impaired in presence of breastfeeding. These informationare very important mainly for less developed countries, where themajority of the HIV-infected mothers are diagnosed during their deliveryadmission.


P4.12.02CAUSES AND TREATMENT OF OB/GYN ORIGIN DIFFUSEPERITONITISV. Milenkovic , M. Petronijevic, S. Vrzic, S.Petkovic, M.Berisavac,V.Boskovic, Lj.Mirkovic, S.Kadija, M.Radovic.

Objectives: The aim of this study was to investigate causes and besttherapeutic methods for treatment of diffuse peritonitis at our clinic.Study Methods: During two year period in Intesive care unit of ourdepartment were treated 17 cases of diffuse peritonitis of differentorigin. Most of them were caused by pre-existing tuboovarian abscess 11(64,7%), while other cases included tuboovarian abscess andappendicitis 2 (11,7%), tuboovarian abscessand paralytic ileus, statusafter cesarean section, status after subtotal abdominal hysterectomy formyomatose uterus and status after vaginal hysterectomy. Average age ofour patients was 44 year varying from 18-68. Vital signs of all patientswere closely monitored.Results: Surgical treatment was performed when indicated and in total22 operative procedures were done. Most frequently performed weretotal abdominal hysterectomy with bilateral adnexectomy in 8 patients(47%), and adnexectomy in 3 patients (17,6%). Other surgicalprocedures included appendectomy, intestinal resection, hysterectomywith conservation of the ovaries, salpingectomy, resection of the ovariesand extirpation of capsule. In all cases was performed extensiveadhesiolysis and drainage. After various time spent in intesive care unitand presenting minor complications, except in one case of pulmonaryembolism and deep vein thrombosis, all our patients were dismissedfrom the hospital.Conclusions: Diffuse peritonitis is relatively rare, but severe condition inobstetric and gynecological practice. Female genital tract is like no otherpotential inflammatory seat suitable for surgical managing. Withremoval of infectious seat accompanied with adequate antibiotic therapymost cases of severe inflammatory diseases with this location can byconsidered cured.

P4.12.03COMPARATIVE STUDY OF THE PATHOLOGICAL FLORA INVAGINA AND CERVIX OF PREGNANT PATIENTS FROM THREEDIFFERENT ETHNIC GROUPS IN SKOPJEAleksandar Blazevski , M. Petrovska, N. Panovski, V. Stoiceva, S.Pangovska, L. Nacevska, N. Dimitrovska. Department of Gynecologyand Obstetrics-Health center Skopje, Institute of Microbiology MedicalUniversity of Skopje, Partizanska 64a I/7, Skopje, Macedonia, 91000.

The aim of the study was to compare the vaginal and cervicalpathological flora in Macedonian, Albanian and Gypsy pregnant woman,tree different ethnic groups by their way of living, traditions andbehavior.Vaginal and cervical swabs were taken from 84 patients on their firstvisit for control of the pregnancy. First group were 26 gypsy patients,second 27 albanian and third group 31macedonian patients. We take onevaginal and tree cervical swabs from each patient and the swabs andmedia sand in the laboratory. After the examination therapies wereapplied and control.Results: The results of the first group show 14(54%) patients- candidaalbicans(ca); 2(0,08%) -escherichia coli hemolytica(ec); 2(0,08)-enterococus(en); 4(0,15%) - gardnerella vaginalis(gv); 5 (0,19%)-chlamidia trachomatis(ct); and 3(0,11%)-ureaplasmaurealiticum(ur).Tbl-1 Second -17(63%)-ca; 1(0,04%)- staphylococcusaureus mrs.; 3(0,11%)-ec; 2(0,07%)-bacterioides species; 2(o,o7%)-en;4(0,15%)-gv; 7(0,26%)- ct; 9(0,33%)- ur.Tbl-2 Third group show 25(80%)- ca;2(o,o6%)- streptococcus; 3(0,01%)- ec; 4(0,12%) gv;9(0,29%) ct;and 10(o,32%) ur-Tabl 3Conclusion: Third group show bigger percentage of candida andclamidia trachomatis, second with ureaplazma urealiticum andgardnerela vaginalis, and first group show bigger percentage of otherpathological bacterial flora and less with candida albicans. Gonorhoeawas not fond. Bigger analyses might give interesting results.

P4.12.04FORECASTING OF THE HEAVY FORMS INTRAUTERINEINFECTION BY ESTIMATION OF FEATURES HORMONALFUNCTION FETO-PLACENTAL COMPLEXT. Tareeva , I, Antipova, L. Kuzmenko, T. Budikina, N. Bashakin,Dept. OB/GYN, Moscow Regional Scientific Research Institute,Moscow, Russia

Objectives: The aim of the study was the forecasting of the heavy formsof intrauterine infection by estimation of features hormonal functionfeto-placental complex (FPC).Study Methods: Was included hormonal function FPC and level a-fetoprotein (aFP) at 344 pregnant women with infectious diseases.Results: At performance of the specified conditions it is possible offorecasting of the heavy forms intrauterine infections when one of thefollowing situations is present: (1) The level aFP on the moment ofresearch is within the limits of normal date: as well as three weeks back.(2) The level placental laktogen (PL) is within the limits of normal date:as well as three weeks back. (3) The concentration aFP on the momentinvestigation is within the limits of normal conditional borders as well asconcentration estriol from 2 about 5 weeks back. (4) The concentrationaFP is within the limits of normal conditional borders and concentrationestriol from 2 about 5 weeks back was below normal level. (5) Theconcentration cortisol is within the limits of normal date and parametersestriol and aFP from 1 about 5 weeks back were below normal date.Conclusions: Use of the forecast the heavy forms intrauterine infectionallows to optimize therapy during pregnancy and to lower riskrealization of infection in early neonatal period.

P4.12.05INFLAMMATORY OVARIAN LESIONS VERIFIED BYHYSTEROSALPINGOGRAPHYNikolov B ., Sazdanovic P., Nikolov M., Ob/Gyn Clinic, Clinical-Hospital Center Kragujevac, Kragujevac, Yugoslavia

Background: Our aim was to confirm the value ofhysterosalpingography in detection of chronic inflammatory processes ofovaries, i.e. their incidence, type, degree, with topographic distributionof ovarian injuries.Material and methods: We analyzed hysterosalpingographic images in368 patients treated for tubal sterility.Results: In total of 620 oviducts (36 were previously removed) weconfirmed chronic inflammatory processes and oviduct impairment:Proximal part lesions in 176 oviducts;Distal part impairments in 382 oviductsLesions alongside 348 oviductsInjuries of the whole oviduct wall and deformities like smaller or greatersactosalpinx in 118 oviducts.Conclusions: Chronic inflammatory process is due to prolonged phase ofdestruction, i.e. its reparation and restitution. Chronic oviductinflammation, as time elapses, induces smaller or greater damages,especially with exacerbation. Due to scant clinical picture, it issometimes difficult to be confirmed with routine laboratory analyses;therefore, all available methods should be used. Even now,hysteresalpingography represents a procedure that can indicate chronicoviduct inflammation and its damage with great certainty.

P4.12.06INTRA-UTERUS INFECTIONSO. L. Antonova, V. K. Chaika, B. A. Iotenko, Donetsk State RegionalCenter of Motherhood and Childhood Protection, Donetsk, Ukraine

Objectives: The aim of the study was to estimate the rate of infectionsamong the 140 pregnants, to estimate original tactics of pregnants'management depending on pregnancy outcomes, conditions of fetus,newborn.Study Methods: One hundred and forty pregnants with symptoms ofpregnancy terminated threat with pathological obstetrical andgynaecological anamnesis were examined in pH-measuring of vaginalsmears, bacteriological and bacterioscopic tests of vaginal smears, IgM,IgG in serum to Chlamydia trachomatis, Cytomegalovirus (CMV),Herpes virus II (HSV), Toxoplasma, alpha FP in serum, ultrasoundexamination of fetus in 17 weeks of pregnancy, cardiotocography in 32weeks of pregnancy. Pregnants with acute infection got ethiotropical


treatment, immunotherapy, and treatment of fetus-placentalinsufficiency. Pregnants with chronic infection were treated byethiological remedies.Results: CMV was observed in 12% of cases, HSV II in 16%,Chlamydia in 19%, Toxoplasma in 18%, Bacterial vaginosis in 25%.Three quarters of all pregnants had mixed infections. Pregnancyoutcomes: preterm delivery in 4% cases (6/140), deliver in time in 96%(134/140).There are not cases of intra-uterus infection of fetus and newborn.Conclusions: Proposed original tactics of pregnants' management helpsto indicate the cause of pregnancy terminated threat, to avoid intra-uterous infections of fetus/newborns.

P4.12.07IS C-REACTIVE PROTEIN AN ACCURATE PREDICTOR OFINFECTION? (PRELIMINARY REPORT)A. K. Syamsuri , A Abadi, M. Marwansyah, ZulkarnainDept. OB/GYN, Sriwijaya University, Palembang, Indonesia

Objectives: The aim of the study was to know whether or not C-reactiveproteins really accurate predictor of infection?Study Methods: One hundred patients were included in this “crosssectional study” with including criteria as follows: patients withpremature rupture of membrane (PROM) at 28-40 weeks gestation andno medical complication, C-reactive protein was measured frommaternal and umbilical cord blood serum. 44 patients were measuredtheir amniotic fluid culture an 46 patients was asked for histologicconfirmation and biophysical profile scoring examinationResults: Maternal with CRP ³ 6 mg% has mean temperature 37.24oC,SD=0.623 higher than maternal with CRP < 6 mg % has meantemperature 37.16oC, SD= 0.434, p=0.001. But both figure of thematernal CRP above didn’t have significantly difference to infected andnon infected infant, p=0.1117, infant morbidity has mean temperature38.00oC, SD=0.389. Higher than healthy infant who has meantemperature 37.12oC, SD=0.389, p=0.003. 79.5% amniotic fluid haspositive bacterial culture. Mean maternal CRP who has bacterialchorioamnionitis = 54 mg/l, SD=97.944 mg/l, higher than meanmaternal CRP who has negative bacterial chorioamnionitis. (mean-39.923 mg/l. SD=83.016 m/l), but no significant, p=0.0981. Meanmaternal CRP who has clinical chorioamnlonitis=108.00 mg/l,SD=119.331 mg/l, higher than mean maternal CRP that didn’t haveclinical chorioamnionitis. (mean=27.375 mg/l, SD=69.427 mg/l),p=0.0037. There were no correlation between maternal CRP andbiophysical profile scoring. Also there were no significantl relationshipsbetween histologic chorioamnionitis with mother and infant CRP.Conclusion: Maternal CRP was not really accurate predictor for bothmother and infant infection regarding to gold standard examinationbacterial culture and histologic confirmation. Otherwise, regarding toclinical chorioamnionitis mother CRP may be useful as a predictor ofinfection. It’s still needed other continuing study to prove the accuracyof CRP as a predictor of both mother and infant infection.

P4.12.08PECULIARITIES OF THE COURSE OF UROGENITALINFECTIONS IN WOMEN OF PRE AND POSTMENOPAUSEV.K. Chaika, V.G. Changli , B. A. Iotenko, Donetsk State RegionalCentre of Maternity and Child Protection, Donetsk, Ukraine

The most significant clinical manifestation developing in period ofpostmenopause are vegetoneurological manifestations (climactericsyndrome – CS), urogenital impairments, dystrophic changes of the skin,a high risk of the development of atherosclerosis and ischemic disease ofthe heart, osteoporosis, psychic disturbances.78 patients at the age of 45-69 years of age were under the observation.The women were divided into 3 groups: group I (28 persons) receivedonly etiotropic antibacterial treatment. They applied mentronidazol 0.5 x2 t/d during 7 days. Group II (25 persons) received both etiotropicantibacterial and local treatment with estriol-ovule 0.5 mg during 14days. Group III (25 persons) received the same therapy as the women ofgroup II + replacing therapy with one of combined oral hormonalpreparations used at climacteric period.On the background of the replacing combined hormonotherapy thenormalization of the flora and pH of the vagina was observed in 92% of

cases in group III, in group II - 80%, in group I the cure occurred only in64.2% of cases.Conclusions: To establish the disturbances in this or that link of thepathogenisis. And their correction it is important to carry out thecomplex of necessary examinations and adequate medical measures. Inthe period of the extinction of the estrogenic function of the ovaries inthe women with the urogenital disturbances it is expedient torecommend applying the antibacterial therapy in the combination withthe replacing hormonotherapy. According to the results received duringour examination, it is right to use the preparations containing naturalhormones for the etiotropic hormonotherapy.

P4.12.09PERITONEAL BILHARZIASIS AND CHRONIC PELVIC PAINV Freitas , JM Soares Jr, EC Baracat, CE Lang, E Schor, SN Mancini,WJ Gonçalves. Department of Gynecology - Escola Paulista deMedicina, Federal University of São Paulo, Brazil.

Objective: The aim of this work was to describe a case of peritonealbilharziasis by S. mansoni associated a choronic pelvic pain.Study Methods: A 20 year old white multipara woman, attended theoutpatient clinic of the Department of Pelvic Pain and Endometriosis ofthe Gynecology Department of the Escola Paulista de Medicina –Universidade Federal de São Paulo in 04/09/97. She complained of asix-month pain in her flanks and in the left iliac fosse. We usedultrasonography, videolaparoscopy and biopsy to evaluate the case.Results: The Ultrasonography showed a cystic formation with clear andregular limits, a homogeneous aspect, and dimensions of 110x96x71 mmat the retrouterine region, which was projected into the left iliac fosse.Videolaparoscopy evidenced multiple loose adherences between thehepatic capsule and the abdominal wall and also in the vesicouterine pit.The retrouterine pit was blocked by a pseudo-cyst – a neoformed tissuecapsule of a whitish color – similar to fibrin, which involved the uterinewall, the tube and the left ovary. The cyst has punctured, and it wasfound to contain a fluid of greenish color. The histopathologic examevidenced a chronic inflammatory process with fibrosis, eosinophilia,and numerous S. mansoni eggs.Conclusion: Our study aims at warning gynecologists of a possibleoccurrence of this association in women complaining of pelvic pain,especially in those coming from the endemic zone of this disease.

P4.12.10REPRODUCTIVE TRACT INFECTIONS AMONG MARRIEDWOMEN IN UPPER EGYPTM.M. El Said (1), S. A. Sallam (2), A.A. Mahfouz (2), N.I. Dabbous (2),M El-Barrawy (2), A. El-Ghamry (2), A. Malatawy (3)(1) Dept. OB/GYN, College of Medicine, Heliopolis, Cairo, Egypt(2) High Institute of Public Health, Alexandria, Egypt(3) Unicef, Cairo, Egypt

Objectives: To study magnitude, determinants of RTIs among marriedwomen in Upper Egypt and to investigate their knowledge, attitude andbehaviors towards RTIs.Study Methods: The survey targeted three governorates of Upper Egyptnamely El-Minia (a population of 3.3 million in 99 districts), Assiut (apopulation of 2.9 million in 11 districts) and Sohag ( a population of 3.1million in 11 districts). The present study used Focus Group Discussions(FGDs) and community based survey designs. Using cluster-samplingtechnique, 30 clusters were selected from urban and rural areas of eachgovernorate. From each cluster, 15 women were selected, interviewedand examined. Endocervical swabs and blood samples were taken forlaboratory investigations.Results: The survey included 1344 women (387 women from urbanareas and 957 women from rural areas). The overall prevalence of RTIsamounted to 52.8%. The most prevalent forms were Candida albicans(28%), trichomonas vaginalis (8.7%), Asperigillus (7.4%), Streptococci(4.6%), Chlamydia trachomatis (4.2%), and Gardnella (2.8%).Cytomegalo virus was found in 24.1%, Herpes simplex type II in 11.9%and Mycoplasma in 24.8% of the examined samples. All samples werefree from Neissera gonorrhea, HIV and Treponema pallidum. FGDsshowed lack of awareness regarding RTIs. Women regarded havingexcessive vaginal secretions as a normal process. Multivariate analysisshowed that certain groups of women were a high risk of developingRTIs. They included women currently using IUDs (OR-1.89, 95% CI:


1.08-265), with unhygienic practices during daily personal hygiene(OR=1.83, 95% CI: 1.04-2.94), or during personal hygiene after sexualintercourse (OR=1.62, 95% CI: 1.11-2.85), women who did not seekmedical advice (OR=1.64, 95% CI: 1.06-2.49), women using sharedtoilet facilities (OR=2.07, 95% CI: 1.31-5.65) and women lacking anymass media facilities in the dwelling (OR=1.75, 95% CI: 1.08-2.74).Discriminant analysis showed that symptoms were of low discriminatingvalue in detecting RTIs. On the other hand, certain signs were of a gooddiscriminating value in detecting RTIs.Conclusions: RTIs among married women in Upper Egypt is a Publichealth problem with a widespread magnitude. There is a great need toupgrade knowledge of the community especially women in the area ofRTIs focussing on proper hygienic practices.

P4.12.11SCREENING SEXUAL TRANSMITTED DISEASES ON SINGLEWOMEN CANDIDATES TO ABORTION IN A TUNISIANHOSPITALH. Chelli , D. Chelli, D. Zeghal, A. Souki, M.B. Chennoffi , B. Tanfous,E. Sfar

Objectives: The aim of this prospective study is the screening of sexualtransmitted diseases (STD) on single women candidates to voluntaryabortion in a tunisian hospital.Study Methods: Prospective study of 174 single women pregnant in thefirst 3 months for which systematic blood sampling was made withdetermination of :- AgHbs- TPHA- HIVResults: B Viral hepatitis Is the most commun STD for women havingmultiple partenaires in our context. In this study, risk factors, frequenceof STD in Tunisia and prevention methods were analysed.Conclusion: The epidemiological supervision of STD in this groupallows the screening and prevention of these deseases in the wholepopulation.

P4.12.12SIMPLIFIED DISPOSABLE ABDOMINAL AND VULVAR DRAPESFOR CAESAREAN SECTION IN MATERNAL HIV-1 INFECTIONW. Phuapradit , P. Panburana, J. Buamuenvai, Dept. OB/GYN,Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 10400

Objectives: To develop simplified disposable abdominal and vulvardrapes preventing surgical soiling during Cesarean section in maternalHIV-1 infectionStudy Methods: The drapes are designed for efficient collection anddisposal of amniotic fluid and blood via abdominal incision and vaginalcanal, thereby reduce the risk of exposure to the surgeons and nurses.The are made of ordinary polyethylene plastic bags, transparentpolyethylene acrylate glued sticker with paper backing and water-repellant, non-woven cloths. Before using both drapes are sterilized byethylene oxide.Results: Elective C esarean sections were performed in 21 HIV-1infected pregnant women at 38 weeks gestation. Mean operative timewas 61 min. The procedures were tolerated well by all of the patients.Both drapes effectively prevented surgical soiling during the operations.Postoperatively, the prepped abdominal surface surrounding the incisionsite appeared no allergic reaction and there were no febrile morbidites.The average length of stay after surgery was 4.2 days.Conclusions: This hospital made simplified disposable abdominal andvulvar drapes offer safe, convenient and inexpensive draping method forelective Caesarean section in term of cost-benefit for the reduction ofperinatal HIV-1 transmission especially in developing countries.

P4.12.13STUDY OF TOXOPLASMA INFECTION IN PREGNANCY INDURGAPUR, INDIADr. Sabuj Sengupta , Bidham Nagar, India

The actual clinical history of toxoplasmosis began in 1923 when the firstcase report of a congenitally infected human baby was published. thedangers of acquired toxoplasma infection during pregnancy and itsclinical implication on the new born came to light since 1980.The author has come across twenty cases of toxoplasma infection duringpregnancy in last two years. All were seropositive (high titre of of lgg)during early pregnancy and all of these were having bad obstetricalhistory. they were all given spiramycin 2 tabs twice daily for 3 weeksand 2 weeks interval till parturition. all of them went to term anddelivered healthly babies who were all seronegative.Hence all cases with bad obstetrical history should have this serologicaltest to exclude toxoplasmosis and if detected-it should be adequatelytreated. Details will be discussed in actual presentation.

P4.12.14THE PREVALENCE OF RECTAL AND GENITAL GROUP BSTREPTOCOCCUS COLONIZATION SCREENED FORREPRODUCTIVE AGE TURKISH WOMENZ.N. Kavak (1), A. Uzener (2), G. Söyletir (3), A. Basgül (1)(1) Dept. OB/GYN, Marmara University Hospital, Istanbul, Turkey.(2) Ümraniye Public Hospital, Istanbul, Turkey.(3) Dept. Microbiology, Marmara University Hospital, Istanbul,

Turkey.

Objectives: Women who are colonized with group B streptococcus(GBS) are prone to develop certain complications during labor. So, weinvestigated to determine the frequency of GBS carriage in genital andrectal cultures in reproductive age Turkish women and to see if there is arelation between being a GBS carrier and a socioeconomic level,educational level, parity, miscarriage number and intrauterine deviceusage.Study Methods: We formed two groups according to their annualincome. In the first group, we evaluated 166 women with lowsocioeconomic status. In the second group, of the 287 women enrolled,there were 121 women with high socioeconomic status.Both of the groups were screened with a rectal and genital culture placeddirectly in a selective media.Age, parity, miscarriage number, curettage number, intrauterine deviceusage, and educational level of the women were noted.We compared the results of the two groups for group B streptococcuscolonization. Statistical analyses were performed with the use of chisquare test, correlational analyses, Kruncall Wallis variant analysis.Results: In the first group, the rate of GBS colonization was 13.9% (23patients). In the second group, there were 12 patients (19.9%) with theGBS colonization. No significant difference was found between thesetwo groups (p>0.05).Conclusions: We decided that group B streptococcus is a frequentfinding in the reproductive age Turkish women population unrelated toeconomic or educational level.

P4.12.15THE ROLE OF UROGENITAL CHLAMIDIOSIS IN WOMEN TOINFECT THE NEWBORNSN. Japarashvili , V. Sandandelidze, Zhordania Institute of HumanReproduction, Tbilisi, Georgia.

Objectives: The aim of the work was to study the chlamidiosis infectionin pregnant women and the frequency of transmission of newborns.Study Methods: We have investigated 235 women with urogenitalchlamidiosis, aged 20-35, and they were divided into 2 groups. In thefirst group were 120 women and in the second, 115 pregnant women.After the specification of etiological factor, all women were treatedetiopathogenetically stage by stage.After due examination, the women of both groups underwent stage bystage treatment of etiopathogenetical individual therapy with antibiotics(aminoglycosides, macrolides, cephalosporins, quinodix, rifampycingroup) with two 10-day courses. As a result of the said treatment, 98(81.7%) out of 120 women of the first group were cured fromchamidiosis, 62 (63.3%) of them became pregnant and only one of the


62 newborns had chlamidic conjunctivitis, the remaining 61 newbornshave been under the control during a one-year period and no signs ofchlamidiosis infection were revealed.After the treatment, 22 patients of the same group (18%) were stillsuffering from chlamidiosis, 10 (45%) of them became pregnant, 4newborns out of the 10 were taken ill with chlamidic pneumonia, while6 of them developed chlamidic conjunctivitis.59 (51.3%) of 115 pregnant women of the second group showed gotresults after the treatment; 15 (25.4%) newborns in this group werehealthy while the remaining 44 (75.6%) newborns developedchlamidiosis (20-uropieticsexual organs, 11-pneumonia, 13-conjunctivitis).As to 56 (48.7%) of pregnant women of the second group recoveredfrom chlamidiosis, all (100%) of newborns developed the disease ofchlamidiosis.Conclusion: As a result of our investigation, it is advisable torecommend in women’s consultations of all women before thepregnancy for revealing chlamidiosis and specific treatment before thepregnancy with the aim to prevent pyoinflammatory processes ofchlamidiosis etiology in newborns because the etiopathogenic treatmentduring the pregnancy has no effect.

P4.12.16TREATMENT OF BACTERIAL VAGINOSIS IN PREGNANCY: ARETROSPECTIVE COHORT STUDY IN A BRAZILIANUNIVERSITY HOSPITALR.P.S. Camargo , J.A. Simoes, J.G. Cecatti, Dept. OB/GYN, School ofMedical Sciences, University of Campinas, Campinas, Brazil.

Objectives: To compare perinatal complications in women with a treatedbacterial vaginosis during prenatal care and women without bacterialvaginosis in a low risk pregnancy.Study Methods: 714 women were included in this retrospective cohortstudy developed at the university of Campinas, Brazil, from January1997 to March 1999 and divided in two groups: 134 women withdiagnosis and treatment of bacterial vaginosis during last pregnancy and580 women with Qui square, Fisher and variance tests. Risk ratios with95% confidence interval were calculated for the main dependentvariables.Results: There was no difference between the groups except for themean age that was lower and smoking habit which was higher in thebacterial vaginosis group. The risk ratios were not significantly higher,1.34, 1.07, 0.71 and 0.64 for a treated bacterial vaginosis regardingpreterm premature rupture of the membranes, preterm labor, prematurityand low birth weight, respectively. Prematurity occurred in 3.7% of thegroup of bacterial vaginosis and in 5.5% in the group without bacterialvaginosis. There were no significant differences in puerperal infectionand neonatal outcomes rates between the groups.Conclusions: Perinatal complications among women with a treatedbacterial vaginosis are similar to those of women without bacterialvaginosis in a low risk pregnancy.

P4.12.17WHO SHOULD BE SCREENED FOR BACTERIAL VAGINOSIS INPREGNANCY?T.S. Siw , M.S. Othman, N.M. Zaki, Dept. OB/GYN, PPSP, HospitalUSM, Kelantan, Malaysia.

Objective: To study the risk factors for bacterial vaginosis (BV) inpregnancy.Study Methods: A convenient sample of pregnant women attending theirfirst antenatal visit in Hospital USM from January to December 1998were recruited. Patients’ demographic data, prior pregnancy history,sexual history, douching behavior, education level, income per capitaand contraception practice were noted. Speculum examination andlateral vaginal wall swabs were taken for examination. BV wasdiagnosed if presence of any 3 of the following features a) grayishhomogenous discharge, b) vaginal pH>4.5, c) positive amine test, or d)presence of clue cell from gram stain. Multiple logistic regression wasused for analysis.Results: The proportion of women with BV was 60 (17.9%) in 336women enrolled. Women who had multiple sexual partners were 3.9 foldmore likely to have BV after adjustment of other variables (p=0.04).There was no significant association between BV with race, younger age

(<20 year), prior pregnancy history (including preterm delivery andmiscarriage), practice of douching, contraception practice, low educationlevel and low income per capita group.Conclusion: BV is a common infection in pregnancy and screeningshould be offered in pregnant women who have had multiple sexualpartners.

P4.13 INFERTILITY/ASSISTED REPRODUCTIVETECHNOLOGY

P4.13.01CHROMOSOME ANALYSIS OF EMBRYOS RESULTING FROMASSISTED REPRODUCTIVE TECHNOLOGYY. Sasabe , T. Nishimura, Y. Shibui, K. Ito, Y. Abe, H. Kubo,S. Hirakawa, 1st Dept. OB/GYN, School of Medicine, Toho University,Tokyo, Japan.

Objectives: The purpose of this study was to reveal the distribution ofchromosomal abnormalities on embryos resulting from assistedreproductive technology (ART), such as conventional in vitrofertilization (IVF), and intracytoplasmic sperm injection (ICSI) withejaculated or testicular sperms.Study Methods: 59 embryos were donated from 18 infertile couplesundergoing IVF, 71 from 33 infertile couples undergoing ICSI withejaculate or testicular with their consent. The difference of maternal ageswas not significant. There were no significant differences in theproportion of developmental and morphological good, fair, or poorembryos. They were confirmed to be 2 pronucleus zygotes on day 1.They were fixed on the slides on day 3 and blastomeres were analyzedby fluorescence in situ hybridization (FISH) using chromosome-specificprobes 18, X and Y.Results: The embryos were analyzed on the basis of their ploidy. Theproportion of 2n embryos (including embryos which were not exactlydiploid) was 63% of ICSI and 63% of IVF. In 2n embryos, theproportion of aneuploid was 7% of ICSI and 3% of IVF and theproportion of mosaic was 22% of ICSI and 16% of IVF. The differenceswere not significant.Conclusions: The distribution of chromosomal abnormalities on ICSIembryos was the same as those on IVF embryos on day 3. However theembryos resulting from ART include high proportion of chromosomeabnormal embryos. Careful genetic tests, such as cytogenetic analysisprior to ART, and chorionic villi sampling or amniocentesis afterestablishment of conception by ART, would be necessary.

P4.13.02CHROMOSOME ANALYSIS OF INFERTILE COUPLES ANDAMNIOCENTESIS OF PREGNANCIES IN ART PROGRAMY. Shibui , Y. Sasabe, T. Nishimura, K. Ito, M. Shiokawa, Y. Nakano, H.Ikenaga, K. Masaki, Y. Abe, H. Kubo, S. Hirakawa, K. Miura, 1st Dept.OB/GYN, School of Medicine, Toho University, Tokyo, Japan.

Objectives: Genetic counseling has come to be the essential process inART program. The aim of this retrospective study was to investigate therole of genetic tests, such as the chromosome analysis of infertilecouples prior to ART, and the amniocentesis of pregnancies resultingfrom ART, in the genetic counseling for ART.Study Methods. The chromosome analysis of 31 couples prior to ART (7couples before conventional IVF and 24 before ICSI) and theamniocentesis of 26 pregnancies resulting from ART were carried outwith their consents at Toho University, Tokyo, Japan.Results: One balanced reciprocal translocation (A) and 1 Robertsoniantranslocation (B) were recognized in males and 1 pericentric inversion(C) and 1 sex chromosome mosaicism at low level (D) in females by thechromosome analysis of couples. Case A and C were a couple and FISHanalysis revealed that their arrested embryo was unbalanced reciprocaltranslocation. Case B and D established their pregnancies and endedmiscarriages. The chromosome analysis of abotus revealed trisomy 16and balanced reciprocal translocation in case B and trisomy 15 in caseD. One trisomy 18 and 1 balanced reciprocal translocation wererecognized in 2 pregnancies by the amniocentesis. No abnormal resultswas obtained from the chromosome analysis of these couples.Conclusions: The genetic tests give us useful information for the geneticcounseling to infertile couples in ART program. The genetic informationmight reveal the influence of ART to the next generation.


P4.13.03CLINICAL EVALUATION OF ONE-WAY AND ROUND-TRIPTRANSPORT SYSTEM FOR ARTA. So (1), Y. Abe (1), Y. Sasabe (1), M. Shiokawa (1), Y. Shibui (1), E.Hashida (1), K. Ito (1), Y. Nakano (1), H. Nakano (1), H. Ikenaga (1), K.Masaki (1), M. Suga (1), H. Kubo (1), S. Hirakawa (1), M. Maeda (2)1st Dept. OB/GYN, School of Medicine, Toho University, Tokyo, Japan.Dept. OB/GYN, Tokyo Metropolitan Ebara Hospital, Tokyo, Japan.

Objectives: To reduce the burden of infertile couples, who live far awayfrom ART institutes, two different types of transport system for ARThave been developed. The aim of the study was to evaluate the clinicaloutcomes of ART.Study Methods: Controlled ovarian hyperstimulation and oocyteretrieval was carried out at the satellite institute. The oocytes in thefollicular fluid were transported to ART institute by the male partner.The procedures in the laboratory were carried out at the ART institute.The embryos were transferred at the ART institute (one-way transportART) or at the satellite institute (round-trip transport ART). Smallincubator was used for the transport to warm up the oocytes or embryosat 37°C. The clinical outcomes of both one-way and round-trip transportART were evaluated.Results: In case of conventional IVF, 10 pregnancies out of 51 cycles(20%), 41 cases (24%) by one-way transport and 3 out of 13 cycles(23%), 9 cases (33%) by round-trip transport were established. In case ofICSI, 10 pregnancies out of 56 cycles (18%), 46 cases (22%) by one-way transport and 7 out of 54 cycles (13%), 32 cases (22%) by round-trip transport were established. No significant differences were admitted.Conclusions: The clinical outcomes of round-trip transport ART standcomparison with those of one-way transport ART. The transport systemsdescribed here could reduce infertile couple’s burden without decline ofthe clinical outcomes.

P4.13.04DOES GROWTH HORMONE AUGMENTATION AND A HIGHLYPURIFIED FSH SUPEROVULATION STIMULATION REGIMENIMPROVE PREGNANCY RATES IN IVF?L.K. Tan , S.L. Yu, Dept of Ob/Gyn, Singapore General Hospital,Singapore

Objectives: To review retrospectively the efficacy of using a highlypurified FSH superovulation stimulation regimen and GH augmentationfor women undergoing IVF who failed to conceive earlier on a highlypurified FSH and Menogon® combination superovulation regimen.Methodology The study group comprised women undergoing IVF whofailed to get pregnant using a superovulation regimen combining highlypurified FSH (FSH-HP) and Menogon®. The subsequent superovulationstimulation regimen used only highly purified FSH and GHaugmentation was given to women found to be deficient in GH. Acomparision group comprising all women in 1998 undergoing their firstIVF cycle (using the FSH-HP and Menogon® combination) served as acontrol group. The following parameters were obtained: number ofoocytes retrieved, fertilisation rate, implantation rate per embryotransferred and pregnancy rates in each of the groups.Results: There were thirty-two women identified for the study group. Ofthese, 13 were found to be deficient for GH. There were ninety-sevenwomen in the control group. There were no statisticially significantdifferences in the number of oocytes retrieved between the study andcontrol groups and between the first and second stimulation cycleswithin the study group. There was however a statistically significantincreased implantation rate per embryo transferred for the secondstimulation cycle using only highly purified FSH (13.42% versus 3.52%;OR 4.23 95%CI 1.03-17.11). There were 7 pregnancies in the 13(53.8%) GH deficient women and 4 in the 19 (21.1%) remainingwomen. This difference is also statistically significant (P= 0.026). Therewere nineteen pregnancies in the control group (19.6%).Conclusion: A FSH-HP only superovulation regimen improves theimplantation rate per embryo transferred for women who failed to getpregnant using the FSH-HP/Menogon® combination regimen. Suchwomen who are deficient for GH in particular have a significantlyimproved pregnancy rate with this regimen. This regimen however didnot improve pregnancy rate results for the rest who were not deficientfor GH. Screening for GH deficiency in women may identify thesubgroup of women who may obtain superior pregnancy rates using a

FSH-HP only superovulation regimen. A randomised controlled trial iswarranted to validate this observation.

P4.13.05HISTORICAL REVIEW OF INFERTILITYB.Dhorepatil , Shree Maternity Home, Siddharth Mansion, Nagar Road,Pune 411 006, Maharashtra, India, 411006.

Objective :To study the scientific development in the field of infertility.Study Methods: Infertility concept in ancient civilization:Scientificdevelopment till middle agesDevelopment in 17-18-19th century.Development in early 20th century.Development in late 20th century.Future.Conclusion: In near future there should be a complete answer to theproblem of infertility.

P4.13.06HUMAN EMBRYO IS A HUMAN EMBRYO, NOT A PRE-EMBRYOS. Avanzini (1), R. Colombo (1), A. Bompiani (2), A. Ferrari (3), S.Mancuso (4), A.G. Spagnolo (1), E. Sgreccia (1), M. Vignali (5)Center for Bioethics, Catholic University of the Sacred Heart, Rome,Italy.Pediatric Hospital “Bambino Gesù”, Rome, Italy.VI Dept. OB/GYN, University of Milan, Milan, Italy.Dept. OB/GYN, Catholic University of the Sacred Heart, Rome, Italy.II Dept. OB/GYN, University of Milan, Milan, Italy.

Objectives: The aim of the study was to investigate the scientificevidence underlying the progressive introduction of the new term “pre-embryo” in the literature concerning in vitro fertilization and appliedpreimplantation genetics.Study Methods: Four approaches to the study of the developing humanembryo were considered: genomics, DNA expression,cytology/cytogenetics, and cell differentiation. The relevant recentbiomedical literature (1985-1999) was collected and critically examinedfor the presence of molecular, cytological or hystological datasuggesting a documented discontinuity in the development’s process or asignificant biological novelty concerning the identity of the newlygenerated organism. A comparative approach (non-human mammaliandevelopment) was also adopted to fill the gap in some investigationsconcerning the human embryo.Results: No relevant data were found supporting the hypothesis of agenomical or cytological discontinuity between the embryo’s organismat any stage of preimplantation development and the same embryo’sorganism during or after the implantation process. Unless theexceptional case of monozygotic twinning, in which a new organism isgenerated from an existing one, any single formed human embryonicorganism is genomically and cytologically related to the same organismthrough the cell cycle events. Since the fusion of the two gametes, thezygote is no more cytogenetically working as a maternal cell, even issome time is required before the full expression of the new genometakes place. This temporal condition appears to be the genetic rule of anydevelopment during the life of the human organism, and does notrepresent a characteristic of the early embryo.Conclusions: The distinction between a stage of human developmentcalled “pre-embryo” and a stage called “embryo” (proper) issurreptitious since it does not rest on solid scientific evidence of anykind. Therefore it should be dropped out.

P4.13.07HYPERPROLACTINEMIA AND INFERTILITYV. Organdziski , L. Jovcevska, P. Kokormanov, G. Mirkovska,Specialistic health organization for OB/GYN "Dr. Vanco Organdziski"Stip, Republic of Macedonia

Objectives: The aim of this paper is to show the hyperprolactinemia(HiPRL) as one of the many reasons for infertility. It is presented in ourmaterial and through the results of the treatment of the same.Study Methods: This paper includes 25 infertile woman (17-38 yearsold) with hyperprolactinemia (HiPRL) out of which 22(88%) had


primary and 3(12%) secondary sterility. 4(16%) of them had primary,13(52%) secondary amenorea and 8(32%) of them had neatmenstrual cycle.With the help of the radioimunity method, we have determined thehormonic values and the corelation between PRL, FSH and LH. At thesame time we discovered that out of 25 women with HiPRL, 8(32%) hadlower FSH values and 10(40%) lower LH values.Galactorea was present in 12(48%) cases and a pathologicaltomographic finding of the heat in 3(12%) cases. According to theophtalmologic finding only 2 women had slight pathological changes inthe widerness of the eye field and the eye bottom.Results: After the applied therapy with Bromcriptin in the case of22(88%) women we have found lower values of PRL, in 11(64,78%)cases the women restored their normal menstrual cycle and in the case of10(40%) women it resulted with pregnancy.Conclusion: The low HiPRL results in shortened luteal phase and thehigh HiPRL inhibites the ovulation.

P4.13.08IDENTIFICATION OF THE HUMAN SPERM PROTEININTERACTING WITH ANTISPERM ANTIBODY IN SERA OFINFERTILE WOMENM. Kamada 1, S. Yamamoto1, M. Takikawa1, K. Kunimi1, M. Maegawa1, S. Futaki2, Y. Ohmoto3, T. Aono1, S. S. Koide4, 1Dept. OB/GYN,2Pharmacol., Univ. of Tokushima; 1Otsuka Pharmacol., Tokushima.Japan; 4Pop. Council, New York, USA

Objectives: To identify the target antigen of naturally occurringantisperm antibodies present in the circulation of infertile women.Study Methods: Twenty-nine infertile women with sperm immobilizingantibodies, 22 infertile women with other etiologies and 20 fertilewomen. Titers of antibodies to rSMP-B were determined by ELISAusing as substrate the synthetic peptide segment (rSMP-230)corresponding to the hydrophilic domain of rSMP-B. Polyclonalantibody to rSMP-230 was assessed for the same biological activities assperm immobilizing antibodies. Namely, tests for sperm immobilizationand zona penetration were performed using the in vitro humanfertilization system.Results: Anti-rSMP-230 antibodies were detected in 10 out of 29 (34%)sera obtained from immunologic infertile women; whereas only oneserum sample (2%) among women whose sera contain no spermimmobilizing activity had a low titer of anti-rSMP-230 antibody.Polyclonal anti-rSMP-230 antibody completely immobilized humansperm in the presence of complement and blocked sperm penetrationacross human zona pellucida.Conclusions: The human sperm protein, rSMP-B, is probably the targetantigen of sperm immobilizing antibodies.

P4.13.09INDUCTION OF OVULAT1ON BY EXTENDED CLOMIPHENECITRATE AND (PREDNISONE OR BROMOCRIPTINE) INCLOMIPHENE CITRATE NONRESPONDERS.A. Beigi , F Zarrinkoub, Dept. OB/GYN, Arash Maternity Hospital,Tehran University of Medical Sciences, Tehran, Iran.

Objectives: To evaluate effectiveness of these alternative therapies forclomiphene citrate resistant patients.Study Methods: In a retrospective study in Arash maternity hospital,Tehran University of medical sciences from Mar 1997 to Jul 1999. 46anovulatory patients who failed to ovulate after clomiphene cirtate150mg daily for 5 days were identified. Treatment consist of clomiphenecitrate given on cycle days through 9 at a dose of 150mg daily but 34patients of this group addition ally were given prednisone 5mg orallyeach night throughout the cycle, and 12 rest patients were givenbromocriptine 2.5mg daily.Results: A total of 34 patients who received cloimiphene citrate plusprednisone completed 88 cycles of treatment. 26 (76%) of 34 patientsbecame ovulatory and 62 (70%) of 88 treatment cycles resulted inovulation, 15 of 34 patients (44%) conceived with this therapy. A totalof 12 patients who received clomiphene citrate plus bromocriptinecompleted 32 cycles of treatment, 8 (66%) of 12 patients becameovulatory and 21 (65%) of 32 treatment cycles resulted in ovulation. 5 of12 patients (41%) conceived.

Conclusions: Administration of extended clomiphene citrate plusprednisone or bromocriptine in clomiphene resistant patients isassociated with high rate of ovulation and pregnancy and is a goodalternative therapy before gonadotropin stimulation or surgery.

P4.13.10INFERTILITY IN THE CASES WITH ENDOMETRIOSISV. Organdziski , L. Jovcevska, P. Kokormanov, G. Mirkovska,Specialistic health organization for OB/GYN "Dr. Vanco Organdziski"Stip, Republic of Macedonia

Objectives: The aim of this study is to evaluate the cases withendometriosis treated for infertility, in our society in the last 10 years(1990-1999). We were mostly interested in the relationship between theminor asymtomatic endometrial implant in unexplained infertility andthe comparative results gained by conservative surgery and the hormonaltherapy in different stages of this illness.Study Methods: 86 cases were analysed; 32 (37,2%) in weak form, 41(47,7%) in medium form and 13 (15,1%) in advanced form ofendometriosis. In all cases histerosalpingographical (HSG) examinationwere performed for indirect radiological evaluation of tubal ovarial orperitoneal endometriosis, Ultrasound examination, by what the selectionof patients was allowed for early laparoscopy and treatment forinfertility. The diagnosis was confirmed by laparoscopy andhistopsthological method.Our experience, as well the experience of the other authors, assert thatthe therapy with Danazol amp. Zoladex and progestagene before theconservative surgical treatment improved the state of endometricalimplant and allowed using less radical operation. In the cases wherethere were only andometrical cistae, the success of the treatment wastwice bigger than in the cases of athesia.Results: Out of all patients treated with hormonal therapy, 18(20,9%)got pregnant. These are the patients with asymptomatic weakendometriosis. By conservative surgery 18(20,9%) patients were treatedand 5(5,8%) got pregnant. On the whole, 25(29,1%) women gotpregnant. According to the literature 6-15% of the infertile women hadendometriosis as the only cause for infertility.Conclusion: The way in which the endometriosis affects the fertility isunknown yet. Most probably it works through the ovarial disfunction orworstenes the transport of the ovulum because of the disturbed tubalmobility.Most of the pregnancies appeared one year after the diagnosis wasgiven, and treatment was undertaken. Our practise has shown Danazolamp. Zolodex and Progestagenes to be a very effective mean insupression of endometriosis.

P4.13.11INFLAMATORY DISEASES OF THE CERVIX AS A CAUSE OFINFERTILITYG. Mirkovska, V. Organdziski, L. Jovcevska, P. Kokormanov, SpecialistHealth Organization for OB/GYN "Dr. Vanco Organdziski" Stip,Republic of Macedonia

Objectives: This work has its emphasis on the inflammatory type ofcervical secretion, as a reason of infertility in the cases of organichealthy woman with normal hormonal status.Study methods: A group of 40 female patients, in the cases of whichthere was a reasonable doubt that the cause of infertility was in thecervix, were submitted to various investigation processes.Through the tests we have found out that all of the patients have regularovulations and HSG picture, and the male patients, that their husbandsare all fertile.In the series order all of them were submitted to an endocervical smearin, to examin the bacteriological research and the antibiogram. The chart1 shows the kind and number of the bacteriological research andantibiogram.

kind

of bac.

Esch.

coll.

Str.

fec.

Ent.

coc.

Str.

Bhe.

Dif.ba

c.

Sta.

Alb.

Tri.

Vag.

Can.

Alb.

Mic.

Pla.

Chl.

Tra.

Urea.

Ura.CMV

Number 16 5 9 8 3 5 4 11 10 4 11 3

The patients were from 19 to 42 years old. Twenty four (24) of them hada primar sterility and sixteen (16) had a secondary one. Their treatmenthas consisted of use of antibiotics, hemotherapies and local antiseptictherapy.


Results: During the first year of treatment of the cervix 28 (70%) of thepatients had become pregnant. Three (3) of them (10,7%) had anspontaneous abortion, two (2) of them (7,14%) gave a premature birth,and the rest of them 23 (82,1%) gave a birth of a healthy and livechildren. The remaining number of patients that didn't become pregnant12 (30%) are qualified as one with the unknown etiology which requiresadditional researches and treatment.Conclusion: There are two major groups of inflammatory type: Specific,and non-specific. Their relationship has a relevant influence on thequality of the cervical mucus and the fertility of spermatozoa, which gothrough it. On their way they get infected and cause infertility or spreadthe infection to the embryo membranes and can cause miscarriage.

P4.13.12INTRACYTOPLASMIC INJECTION USING SPERM ASPIRATEDBY PERCUTANEOUS EPIDIDYMIS IN TREATMENT FOROBSTRUCTIVE AZOOSPERMIAMeng Xiangge , Li Yuan Qiu Yi Fan Yun-jing Zhang Mei-xinShandong Insititute for Family Planning, Jinan, Shandong P.R. China250002

Percutaneous epididymal sperm aspiration (PESA) and intracytoplasmicsperm injection (ICSI) were used in patients with congenital bilateralabsence of the vas deferens (CBAVD, n=16) and failing vasovasotomy(n=7). ICSI was carried out in 23 cycles. Sperm retrieved by PESA was2-82_106/mL with 1-80% motility and 20-95% abnormal forms. A totalof 179 eggs were collected and 199 subsequently were microinjected.Normal fertilization occurred in 145 oocytes, fertilization rate was81.0% (145/179). 23 subjects underwent ET in which tenconceived(pregnancy rate 56.52% per transfer). Six of them gave birthto normal babies. Our result reveals that PESA-ICSI is an effectivemethod for infertile patients with obstructive azoospermia.

P4.13.13IUI WITH SHORT-LIVED SPERMATOZOA1. Geeta Shroff , OB/GYN, Nutech Mediworld (Ferti.Clinic), G-15/1,Malviya Nagar, New Delhi-110017, India. 2. Vera Hingorani, Retiredfrom AIIMS & Batra Hospital MRC, New Delhi, India

Objectives: To improve upon the seccess rate of Intra UterineInsemination (IUI), especially when the male partner has very short-lived or too few spermatozoa.Twenty five women, one cycle each, undertook IUI procedure withejaculates containing very short-lived spermatozoa some times it was aslow as about half an hour. The IUI was performed with 0.5 ml. of theejaculates within 10 minutes of taking the sample. It was used in:i) Unwashed condition ; ii) but was timed with the availability of theovum in the Ampulla of the Fallopian Tube i.e. about 18 hours after therupture of the foilicle seen by Ultrasound scan.Results: Out of the 25 women who had undergone the IUI procedure, 16became pregnant and nine did not conceive in the first cycle. Thus itraised the success ratae of IUI of 64% from 10-15% world wide.Conclusions: Infertility caused by very short-lived/Low count sperms, incouples with otherwise normal fertility parameters, IUI could overcomeit to a great extent by fast use of unwashed ejaculates and synchronizingthe procedure with the availability of the ovum in the Ampulla of theFallopian tube.

P4.13.14PEPTIDE-M INDUCED EFFECTS ON THE CHANGE OF HUMANSPERM QUALITYM Radovic 1, S Arsenijevic2, A Zivanovic2, S Petkovic1, Lj. Mirkovic1, S.Kadija1, S. Pantovic1, V. Milenkovic1.Institute for Gynecology and Obstetrics, Clinical Center of Serbia,Belgrade, YugoslaviaClinic for Gynecology and Obstetrics, KBC Kragujevac, Yugoslavia

Objectives: The motility of spermatozoa is of crucial importance for thepenetration through the cervical mucus as well as zone free hamster eggpenetration test in vitro. It is possibly decisive for the penetrationthrough the envelope of the oocyte in vivo, too. The aim of this studywas to evaluate the efects of met-enkephalin Peptid-M on function ofhyman spermatosoa.

Study Methods: Twenty two asthenozoospermic men, volunteers frominfertile couples, served us as study group. These patients were dailyi.m. administered 5 mg Peptide-M during 7 days. Normal parameters forthe evaluation of the sperm quality were measured.Results: Data obtained in this study indicate that the thymic preparationPeptide-M excerts a significant influence on the progressive motility(PM%), motility (M%), and agglutination of the spermatozoa.Progressive motility has been significantly increased after the therapy(P=0.003; P<0.05). The motility of spermatozoa (M%) inasthenozoospermic men has been also significantly increased after thetreatment with Peptide-M (P=0.005; P<0.05). And agglutination of thespermatozoa showed a significant decrease after the therapy (P=0.008;P<0.05). The volume, total number of spermatozoa, number ofleukocytes, and number of spermatozoa with normal morphologyhowever, did not significantly change during the therapy.Conclusions: I.M. administered thymic peptides, probably pass to someextent into the seminal plasma, thus positively influencing the motility,progressive motility and agglutination of spermatozoa. Thesepreliminary results suggest that PEPTIDE-M can be useful in thetreatment of male infertility, especially in immunologic infertility as anadjuvant therapy to corticosteroid treatment for idiopathicasthenospermia and for the preparation of male patients for reproductiveprocedures (IUI, IVF, GIFT, and ZIFT).

P4.13.15PROSPECTIVE, BLINDED EVALUATION OF THE UTERINECAVITY AND THE FALLOPIAN TUBES USING THREEDIMENSIONAL CONTRAST SONOGRAPHYR.S. Sankpal (1), E. Confino (2)(1) Dept. Post Partum, Nowrosjee Wadia Maternity Hospital, Parel,India.(2) Section of Reproductive Endocrinology, Northwestern UniversityMedical School, Chicago, Illinois, USA.

Hysterosalpingography is routinely performed on all infertility patients.This procedure provides anatomical information on the uterine cavityand the fallopian tubes. Since hysterosalpingogram results in a minimalamount of radiation delivered to the patient, there is a need to develop acomparable procedure that does not require radiation. Previous attemptsto perform contrast sonography of the uterus and fallopian tubesdemonstrated that this procedure provides valuable information aboutthe uterine cavity. Contrast sonography of the fallopian tube hasprovided limited information on tubal anatomy and limited informationon unilateral or bilateral tubal spillage of contrast material into theabdominal cavity. The introduction of three dimensional ultrasound mayresult in better resolution and imaging of the fallopian tubes. Thisequipment is currently available for clinical use. The purpose of thisstudy is to compare patients’ hysterosalpingogram to contrastsonography of the uterus and fallopian tubes performed with threedimensional ultrasound. The performer of the ultrasound will be blindedto the results of the previously performed hysterosalpingogram.

P4.13.16RELATIONSHIP BETWEEN PLASMA LEVELS OF INSULIN ANDLEPTIN, AND SYMPATHETIC ACTIVITY IN WOMEN WITHPOLYCYSTIC OVARY SYNDROMEElsy Velazquez , G. Arata de Bellabarba, V. Villarroel, Z. Molina.Universidad de Los Andes, ULA, Apartado 42, Merida 5101,Venezuela.

Objectives: This study was planned to evaluate the relationship betweeninsulin and leptin plasma levels with sympathetic activity in women withpolycystic ovary syndrome (PCOS).Study Methods: d 19 non-obese women with PCOS were studied.Twelve healthy non-obese women served as controls. An oral glucosetolerance test (OGTT) was performed and blood samples were takenbefore and at 30, 60, and 120 min. after glucose load. Glucose, insulin,leptin, and Ä4androstenedione were measured before the OGTT. Supineblood pressure and plasma norepinephrine (NE), and response to uprightposture was performed.Results: Basal and post-glucose insulin levels and Ä4androstenedionewere higher in PCOS patients. There were not significant differences insupine NE levels between groups but the response to upright posture wassignificantly (p< 0.05) higher only in obese women. In this group,


systolic blood pressure (SBP) was higher both in supine as in uprightposture. Leptin levels were significantly (p< 0.001) higher only in obesewomen. A significant positive correlation (r = 0.355; p = 0.01) betweenleptin and NE response was observed.Conclusions: Our results show that obese women with PCOS havehigher insulin and leptin levels associated to a higher SBP and anincreased sympathetic activity. The high levels of leptin might increasethe sympathetic activity in obese women with PCOS and make them athigh risk for hypertension.

P4.13.17SUCCESSFUL PREGNANCY AFTER TREATMENT OFHODGKIN’S DISEASEM. Rocha , A. Sarto, M. Geller, C Quintans, RS. Pasqualini.Halitus Instituto Médico, M T Alvear 2084 (1122), Buenos Aires,Argentina.

Introduction: Advances in antimitotic treatments have improved theprognosis of young women suffering Hodgkin disease. The resultingincrease in life expectancy raises the question of the subject’s futurefetility, a question that should be posed before starting any anticancertherapy which could lead to a gonadal failure. Otherwise, oocytedonation remains the alternative indication proposed for these patientsdesiring a child.Objective: To describe a case of pregnancy occurred after an assistedreproductive technique in a patient with infertility due to anoncohaematologic treatment.Case: A 33-year-old woman with Hodgkin Lymphoma treated withradiotherapy and chemotherapy, experienced amenorrhea and problemswith conception. Two procedures of assisted reproductive techniques(ART) were done with oocyte donation. A biochemical pregnancy wasachieved in the second cycle. She was diagnosed an hypofibrinolysis andlupus anticoagulant. Thus, she received aspirin 100 md/day and LowMolecular Weight Heparin (LMWH) when the third ART was done.Pregnancy of triplets was acheived. Heparin was suspended at 20 weeksof gestation. At 25 weeks of gestation, an ultrasound was made and onefetus was dead. LMWH was reinitiated. Cesarean section was done at 30weeks of gestation and two live births were conceived with adecuateweight for their gestational age.Conclusions: Successful pregnancy is possible in selected women withcytotoxic therapy through ovum donation

P4.13.18THE EFFECT OF MECHANICAL ASSISTED HATCHING USING AMICRO-HOOKS. Takahashi , M. Sakai, E. Saitoh, I. Tachibana, M. Suzuki, Dept. IVFLaboratory, M. Suzuki’s Memorial Hospital, Miyagi, Japan.

Objectives: We have experiences of patients who had repeatedly failedto conceive by IVF-ET in spite of transfer with good quality embryos.High pregnancy rate by these procedures has not yet been established.However, assisted hatching of embryos to increase the implantation rateand pregnancy rate has been reported by several methods of authors.Study Methods: Technique of assisted hatching was used to 262 cyclesof patients in IVF-ET at M. Suzuki’s Memorial Hospital from January1998 to December 1999. Those cycles are classified into two groups.Group A: repeated IVF in younger (less than 38 years old). Group B:repeated IVF in older (more than 38 years old). The control group isalso defined as those with same conditions but had ART treatmentbefore 1997. Assisted hatching was performed on two to six cell stageembryos using the micro-hook. This technique uses two micro-hooks asa set, which are made to the level under 25 mm and formed by us. Thistechnique is called “Suzuki’s Assisted hatching Method (SAM)”.Results: 674 embryos were processed by the assisted hatching using amicro-hook

Group A Group BAssisted Hatching + - + -Number of cycles 168 170 94 84Mean age 33.6±2.7 33.6±2.4 39.8±1.7 39.5±1.6Implantation Rate (%) 12.3 7.0 *1 4.5 4.3Pregnancy Rate (%) 30.2 18.2*2 11.7 13.1

*1: P<0.005 *2: 0.01<P<0.025

Conclusions: These results demonstrate that assisted hatching methodusing the micro-hook is quick and safe. Furthermore, implantation rateand pregnancy rate of the women with the repeated unsuccessful cycleof IVF patients under 38 years old became significantly higher.

P4.13.19THE STUDY ON THE EFFECT OF PSYCHOTHERAPY ANDINSTRUCTION FOR PREGNANCYMeng Xiangge , lun Yulan, Shandong Institute for Family Planning, 69Yuhan Rd. Jinan 250002, Shandong, P.R.China

Objective: The aim of the study was to investigate the effect ofpsychotherapy and instruction for infertility couples due to severeoligospermia.Study Methods: 38 infertility couples due to the men suffering formsevere oligospermia, infertility time for 3-12 years. They asked medicalhelp with intracytoplasmic sperm injection (ICSI). First we taught themto understand the requirements for pregnancy, and monitor the ovulationthemselves and have intercourse during periovulation. The men tookherb finely we told that they can become pregnancy.Results: 13 of them,34%(13/38) become pregnant in natural cycle after3-6 monthsConclusion: Psychotherap and instruction were important for infertilitycouples due to severe oligospermia

P4.13.20VALUE OF THE CLINICAL EXAMINATION “SPERM FERTILITYINDEX” IN MALE STERILITYI. Tachibana , S. Takahashi, M. Ishikawa, M. Suzuki, Dept. of IVFLaboratory, M. Suzuki Memorial Hospital, Miyagi, Japan.

Objectives: We crave to know previously the possibility of fertilizationby analysis of sperm data because of a plan to carry out the treatment ofmale sterility. Furthermore, it is required many years of clinicalexperiences to select the best procedure among a lot of diagnostictechniques of male sterility. We have made “Sperm Fertility Index(SFI)” in order to classify the ability of fertility of the patient’s sperm.Study Methods: SFIs calculation expression is the following:SFI = Sperm concentration1 x sperm activity2 x semen volume3

*1. No. of spermatozoa in 1 ml/million, *2. Sperm activity – Goodsperm + _ Fair sperm + 1/10 Poor sperm (Good sperm: percentage of themoving actively and straightly sperms without abnormal morphology.Fair sperm: percentage of the moving not straightly sperms withoutabnormal morphology. Poor sperm: percentage of the moving howevernot progressing sperms and/or with abnormal morphology). *3. Themaximum semen value adopted is 2 ml.The criteria of SFI value were established into four groups: normal,slight, fair and severe damages. We made a comparison cases ofartificial insemination with husband (AIH) (n=484), in vitro fertilization(IVF) (n=384) and micro fertilization (MF )(n=109).Results: We fixed a data of criteria of SFI value, severe damage was SFI£ 3.3, fair damage was 3.3 < SFI £ 11.6, slight damage was 11.6 < SFI £30.0, normal was 30.0 < SFI.Conclusions: We have found effectiveness for the SFI to be one of thebest indicators to select procedures of the therapy in male sterility. Forour theme in the future, we expect to make the better SFI calculationexpression than this one.

P4.14 MEDICAL AND SURGICAL COMPLICATIONSOF PREGNANCY

P4.14.01CHANGES IN ANTITHROMBIN III (AT-III) ACTIVITY IN WOMENWITH SINGLETON PREGNANCIESH. Minakami , A. Ohkuchi, T. Koike, A. Izumi, S. Matsubara, I. Sato,Dept. OB/GYN, Jichi Medical School, Tochigi, Japan.

Objectives: AT-III activity and platelet count gradually decrease in thelast month of twin pregnancies. It is suggested that both the decreasedAT-III activity and the decreased platelet count are risk factors for theHELLP syndrome. It is not extensively studied whether AT-III activitydecreases in late singleton pregnancies.


Study Methods: AT-III activity and the platelet count were determinedtwice at 28.6±1.0 weeks of gestation (second trimester) and at 37.0±0.8weeks of gestation (third trimester) in 851 women with singletonpregnancies.Results: The AT-III activity of 111±9% of normal (mean±SD) at thesecond trimester slightly decreased to 106±12% of normal at the thirdtrimester. Tenth percentile AT-III value changed from 99% at the secondtrimester to 90% at the third trimester. During the period, 29% ofwomen exhibited a decrease in AT-III activity of >10% of normalwhereas 5% of women exhibited an increase in AT-III activity of >10%of normal. The platelet count of 236±58 x 109/L (mean±SD) at thesecond trimester slightly decreased to 230±60 x109/L at the thirdtrimester. Tenth percentile value changed from 161 x 109/L at the secondtrimester to 152 x 109/L at the third trimester. During the period, 23% ofwomen exhibited a decrease in the platelet count of >30 x 109/L whereas12% of women exhibited an increase in the platelet count of >30 x109/L.Conclusions: There existed a small number of women who showed asignificant decrease in the AT-III activity and/or platelet count.However, because there were a small number of women who showed asignificant increase in these variables, the mean AT-III activity and themean platelet count changed a little during the period.

P4.14.02DISORDER ASSOCIATED RISKS (PARTICULARLYPREECLAMPSIA) IN WOMEN WITH HETEROZYGOUS SICKLECELL ANEMIAR. Tantanassis , P. Tampakoudis, A. Papagianni, E. Alexopoulos, E.Vlachaki, S. Mantalenakis, 1st Dept. OB/GYN, Aristotelian Universityof Thessaloniki, Greece.

Objectives: The aim of the study was to investigate the disorderassociated risks in women with heterozygous sickle cell anemia, andespecially the risk for preeclampsia.Study Methods: Out of a total of 11,523 pregnant women who deliveredin our department between 1988-1997 there were 121 women sufferingfrom the afore-mentioned disorder (Group A). As controls 215 healthypregnant women were enrolled in the study.Results: In 31 subjects of Group A pregnancy was complicated bypreeclampsia as compared to Group B, where only 22 subjects wereaffected (25.6%, vs 9.8%, respectively, p<0.0001). There was nosignificant difference observed in what the chronic hypertension anddiabetes mellitus incidence rates are concerning the two study groups. InGroup A the gestational age at delivery as well as the newborn weightwere both significantly different compared to the values of Group B(35.8±2.2W vs 37.1±2.8W and 2.918±601g vs 3.165±620g respectively;p<0.05 and p<0.05 respectively) what cesarean rates are concerningGroup A - there were 28 cases (23.1%) and in Group B 38 cases(17.6%), (p<0.001) registered. Puerperal endometritis was morefrequently encountered in Group A (10.7%) as compared to Group B(4.6%) [p<0.001].Conclusions: Pregnant women with heterozygous sickle cell anemia areexposed to increased risk for developing perinatal complications;intensive perinatal care and interdisciplinary commitment is absolutelynecessary in order to achieve better perinatal outcome.

P4.14.03MANAGEMENT OF SEVERE POSTPARTUM HEMORRHAGEWITH A PROSTAGLANDIN E1 ANAOGUE (MISOPROSTOL): ADESCRIPTIVE STUDYH. Adbel-Aleem , I. El-Nashar, A. Shaheen, A. Abdel-Aleem, Dept.OB/GYN, Faculty of Medicine, Assiut University, Assiut, Egypt.

Objective: To evaluate the use of misoprostol, adminstered rectally, inthe treatment of severe atonic postpartum hemorrhage, unresponsive tooxytocin and methylergometrine.Setting..Assiut University Hospital.Study Methods: The study included 18 women with severe postpartumhemorrhage unresponsive to intravenous oxytocin, methylergometrineand/or Intramyometrial prostaglandin F2alpha. Misoprostol administeredvia the rectal route was used in all cases after failure to respond to theseagents and prior to surgical intervention. The dosage used in this studyranged from 600 to 1000 mcg misoprostol.

Results: 16 cases responded promptly to misoprostol (88.8%). 6 casesexperienced minor side effects in the form of fever, vomiting, diarrheaand shivering.Conclusion: These preliminary data indicate that misoprostol can beeffective in treatment of severe postpartum hemorrhage not respondingto oxytocin and methylergometrine. Using misoprostol this was has theadvantages of potency and simplicity. Further work is needed to confirmthese results in a randomized trial.

P4.14.04PREGNANCY AND LABOR IN PATIENTS WITH VONWILLEBRAND’S DISEASE COMPLICATED BY DISSEMINATEDINTRAVASCULAR COAGULATIONS.G. Braginskaya , A.D. Makatsaria, Dept. OB/GYN, Laboratory ofHemostasis Pathology, Sechenov Moscow Medical Academy, Moscow,Russia.

Objective: The aim of the study was to confirm that patients with vonWillibrand’s disease who have more prominent hereditary hemostasisdefect in non-pregnant state demonstrate less effective compensatoryadaptation during pregnancy.Study Methods: Over a period of 5 years (from 1994 to 1999) under ourobservation were 31 women with von Willebrand’s disease. Diseasecourse, laboratory findings and characteristics of hemorrhagic syndromewere carefully reviewed in this group and demonstrated that patientswith higher degree hemostasis defect in non-pregnant state had worsecompensation during pregnancy. What is more, obstetrical complicationswere seen more often in patients with higher degree of hemostasisdefect.Results: Threatened abortion was diagnosed 1.3 times more often inpregnant with marked hemostasis defects, pre-eclampsia, 1.9 times moreoften. Placenta abruption and hemorrhage in early postpartum periodoccurred in 7 patients. Hemostasis dysadaptation with acute DIC, despitefresh frozen plasma infusion developed in 4 cases of pre-eclampsia, 1case of chronic endometritis and in 1 case of placenta remnants. Pretermlabor induction was recommended in cases of complicated pregnancy toprevent excessive hemorrhage.Conclusion: Complicated pregnancy course (including pre-eclampsia)obviously upset hemostasis adaptation to the time of delivery. Wesuggest that multiple blood product tranfutions, post-hemorrhagicanemia that lead to prostanoids dysbalance induce endothelium damageand aggravate course of pre-eclampsia. High incidence of hemorrhagiccomplications during labor are caused by rapidly developing pre-acutestage if DIC based on pre-existing hemostasis system defects.

P4.14.05SUCCESSFUL ENUCLEATION OF A NECROTIZING FIBROIDCAUSING OLIGOHYDRAMINIOS AND FETAL POSTURALDEFORMITY IN THE 25TH WEEK OF GESTATIONJ. G. Joo , J. Inovay, M. Silhavy, Z Papp, 1st Dept. OB/GYN,Semmelweis University Medical School, Budapest, Hungary.

Objectives: On the occasion of a case, the authors review the potentialcomplication of the fibroids during pregnancy and the possibilities ofmanagement thereof.Study Methods: This is a case of a 32 year old patient in the 25th week ofgestation, with a fibroid cause oligohydramnios and fetal posturaldeformity. A laparotomy and myomectomy were performed with thehope of preserving the pregnancy. Ultrasound examinations performedpostoperatively showed that the fetal postural deformity had ceased andthe pace of the intrauterine development of the fetus had returned tonormal. A living, healthy male newborn weighing 3600 g, was deliveredin the 40th week of gestation via cesarean section.Conclusion: The scientific literature generally agrees upon conservativetherapy (analgesy, infusion-therapy), however there are indication forlaparotomy during the course of pregnancy. In order to make theappropriate decision, knowledge of the possible risk and compilationsare necessary. The risks can be estimated on the basis of the number andlocalization of fibroids.


P4.14.06SUCCESSFUL TREATMENT OF SPONTANEOUS RUPTURE OFILIAC ARTERY ANEURYSM IN PUERPERIUMF. Pietropaolo , G. Cormio, AG. Del Bianco, S. Bragho, G. PutiganoDept. OB/GYN, University of Foggia, Foggia Italy

Aneurysms of the iliac artery are very rare during pregnancy andperperium. They are usually asymptotic until they rupture.We report the case of a 30-year-old white woman, gravida 1 para 1,submitted to cesarean delivery at the 38th week of gestation. On the thirdpost-operative day, the patient suddenly complained of violent pain inthe right hypocondrium followed by hypertension nausea, vomiting andhaemorrhagic shock. CT scans of the abdomen and pelvis demonstratedthe presence of a retroperitoneal hematoma extending from the rightkidney to the uterus.At emergency laparotomy, the hematoma was drained and smallaneurysm of the right common iliac artery was note. The hypogastricartery was ligated and an aorto-iliac by-pass, using autologousomolateral inverted saphevous vein was performed. Post-operativecourse was uneventful and the patients were discharged on the 1 dayfollowing surgery.In cases of deep pain without profuse bleeding in a pregnant or puerperalwoman, the suspicion of iliac, uterine or ovarian aneurysmal ruptureshould be considered. The prompt use of ultrasound, cardiovascularmonitoring and CT scan can help of ultrasound, cardiovascularmonitoring and CT scan can help to recognize this rare condition andtreat it immediately.

P4.14.07ULTRAVIOLET INTRAVASCULAR LASER IN COMPLEXTREATMENT OF LUNG PATHOLOGY IN NEWBORNSA. Zelynsky, M. Korsakova, T. Shestakova , V. Artyomenko. Dept. ofPerinatal Medicine, Child and Adolescent Gynecology, Odessa StateMedical University, Odessa, Ukraine.

Objectives: The aim of our research was to study the effectiveness ofultraviolet laser therapy in newborns suffering from lung pathologies.During 1996-1998, intravascular laser therapy was performed on 122newborns (81 with pneumopathy and 41 with congenital pneumonia).Study Methods: Clinical, paraclinical, biochemical, radioimmune,rentgenological and instrumental methods were used to determine theroutine blood and urine data, partial O2 and CO2 blood pressure and itsoxygenation, lungs RÖ-graphy in 122 newborns of the main group (laser+ traditional therapy) in comparison with 102 newborns of the controlgroup (traditional therapy only). Laser irradiation was performedintravascularly daily (exposure 30 sec.) by means of «ALOU-2» laser(wave length 0,63 mcm, continuous beam, up to 2 mVt capacity) during7 days.Results: In newborns with pneumopathy, the laser therapy leads tosignificant decrease of oxygen-dependent days quantity (4,5±0,34 days)in comparison with newborns of the control group (8,4±0,75 days) andsignificant increase of blood oxygen saturation (P<0,001 and P<0,005respectively). After the intravascular laser application in newborns withcongenital penumonia the significant clinical condition improvementwas observed along with blood and urine data normalization which wasquicker in comparison with the same parameters in newborns of thecontrol group.Conclusions: The ultraviolet intravascular laser therapy in newbornswith pneumopathy and congenital pneumonia is very effective, leadingto mortality and morbidity decrease and good far-reaching results.

P4.14.08TYPE, FREQUENCY AND COMPLICATIONS OF ABORTIONV. Elizalde , Hospital de Ginecología y Obstetricia, DIFEM, Toluca,México., Arceo M, Universidad Autónoma del Estado de México,Toluca, México, Rodriguez F, Hospital de Ginecología y Obstetricia,DIFEM, Toluca, México, Linares A. Hospital de Ginecología yObstetricia, DIFEM, Toluca, México.

Objective: To identify type, frequency and complications of theabortion.Study methods: We performed a retrospective, descriptive andtransverse study in 27 801 clinical files.

Results: Of all the files, 3405 had tne diagnosis of abortion. Thecharacteristics of the group in study were as follows: the more affectedgroup of age was that of 20 to 24 years, and the majority of patientswere married ( (63.5 %), the degree of education that was of secondaryschool, 18.1 % of the patients had previous history of abortion, the ageof pregnancy at which the abortion appeared most frequently was of 8 to12 weeks. The type of abortion presented more frequently was theincomplete abortion (67.7 %).Conclusions: The abortion rate was of 12 for each 100 patients and thesepsis was the first cause of complication (3.3 %), producing one death(due to this cause) in a patient with provoked abortion.

P4.14.09UTERINE RUPTURE IN SOUTH SUMATRAPangemanan WT . Dept. OB/GYN, Sriwijaya University, 1528 BaasukiTahmat Street, Palembang, Suoth Sumatera, Indonesia.

Objectives: The aim of study to investigate the incidence rate of uterinerupture in South of Sumatra, who was referred to Mohammad HoesinHospital.Study Methods: By retrospective were collected data form hospitalmedical record, that was found 77 cases of uterine rupture sinceDecember 1998. The number of labor as the same period 11.468 cases.All data were presented within tabulation and analyzed its related withrisk factor.Result The highest incidence to women about 26-30 years old (30.67%).Based on original referred, most of them came from the rural area(77.67%) and about 42.67% had parity 2-4.Conclusions: The high level incidence of uterine rupture still have beena problem for perinatal/maternal morbidity and mortality.Kewwords: Uterine rupture, perinatal mortality, maternal mortality,incidence.

P4.15 MENOPAUSE

P4.15.01A ONE YEAR TRIAL OF TRISEQUENS ON PERIMENOPAUSALCHINESE WOMEN WITH DYSFUNCTIONAL UTERINEBLEEDINGR.K.H. Chin, P.W.Y. Lam , A Wong. Department of Obstetrics andGynaecology, Caritas Medical Centre, 111 Wing Hong Street, Kowloon,Hong Kong, China.

Objectives: To assess the effects of Trisequens in Chineseperimenopausal women on menstrual cycle control, lipid profile andmenopausal symptomsStudy Methods: Irregular period is a common feature in the years beforemenopause. After ruling out organic diseases, many women needhormonal treatment. Oral contraceptives or progestogens alone havebeen used. They can frequently control excessive or irregular bleedingbut are only intended for short-term regulation of menstruation. Thepresent study is designed to assess whether Trisequens, a drug normallygiven as hormonal replacement therapy (HRT) to patients withclimacteric symptoms, is able to regulate menstruation in womensuffering from menstrual disorders.Twenty-eight patients above age 45 who sought medical treatmentbecause of irregular menstruation were studied. Hysteroscopy andcurettage (H & C) were done in all patients to exclude organic diseases.Trisequens was started on the fifth day of the menstrual cycle thatfollows the H & C. The bleeding pattern, symptoms and side effectswere assessed.Results: Sixteen patients completed the 6-month treatment. The cyclecontrol in these patients was satisfactory and the haemoglobin level atthe end of treatment was significantly higher than the pre-treatmentlevel. Menopausal scores were also improved. The other patients did notcomplete treatment because of drug intolerance, failure to controlmenstruation, development of asthma and screening fault.The types of menstrual disorder, uterine histology, menopausal scores,lipid profile in the group of patients completing treatment compared tothe group aborting treatment are presented.Conclusions: Trisequens achieved good cycle control in over half ofperi-menopausal patients presented with irregular menstruation.


P4.15.02A RANDOMIZED DOUBLE-BLIND, PLACEBO-CONTROLLEDSTUDY OF COMBINATION ESTRADIOL/NORETHISTERONEACETATE TRANSDERMAL HORMONE REPLACEMENTTHERAPY (ESTALISÒ SEQUI) IN A SEQUENTIAL REGIMEN ONMENOPAUSAL VASOMOTOR SYMPTOMSM. Notelovitz , Women’s Research Center Inc. America, Gainsville,Florida, USA.

Objectives: To evaluate the efficacy and tolerability of a sequentialestradiol/norethisterone acetate (E2/NETA) transdermal patch (EstalisÒ

Sequi) versus placebo in reducing post-menopausal vasomotorsymptoms.Study Methods: In a 12-week randomized, double-blind, multicentertrial a total of 220 healthy postmenopausal women (age 40-70 years)with a history of moderate-to-severe vasomotor symptoms and with anintact uterus, were assigned to placebo or one of three doses ofcontinuous sequential therapy consisting of a patch releasing 17 b-estradiol 50 mg/day alone for days 1-14 of each cycle and a combinationpatch releasing 17 b-estradiol 50 mg/day plus norethisterone acetate(E2/NETA) 140, 250 or 400 mg/day for days 15-28 of each cycle.Vasomotor symptoms (number and intensity of hot flushes and intensityof sweating) as well as patch tolerance adhesivity were rated andrecorded by patients and quality of life was evaluated from aquestionnaire.Results: The mean number of hot flushes per day and the mean intensityof hot flushing and sweating were significantly reduced (p<0.001) witheach of the E2/NETA treatments compared to placebo. Sexual arousaland sexual satisfaction scores were significantly better with the 50/250and 50/400 E2/NETA treatments groups. The majority of women(~80%) reported that the E2/NETA patch never fell off throughouttreatment.Conclusions: A combination of E2/NETA transdermal hormonereplacement therapy administered in a sequential regimen withtransdermal E2 if effective in treating moderate to severe vasomotorsymptoms and urogenital atrophy and thus improves the quality of life ofpostmenopausal women. Furthermore, the patch was well tolerated anddemonstrated excellent adhesive properties.

P4.15.03A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLEDSTUDY OF TRANSDERMAL COMBINATIONESTRADIOL/NORETHISTERONE ACETATE THERAPY(ESTALISÒ) USING A CONTINUOUS COMBINED REGIMEN ONMENOPAUSAL SYMPTOMSS. Shumaker , The Bowman Gray School of Medicine, Wake ForestUniversity, Winston-Salem, North Carolina, USA.

Objectives: To evaluate the efficacy and tolerability of continuouscombined transdermal estradiol/norethisterone acetate (E2/NETA) HET(EstalisÒ) in reducing moderate-to-severe postmenopausal vasomotorsymptoms compared to placebo.Study Methods: In a 12-week randomized, double-blind, placebocontrolled, multicenter trial, a total of 226 healthy postmenopausalwomen (age 40-70 years) with an intact uterus and with a history ofmoderate-to-severe vasomotor symptoms of at least eight hot flushes perday were randomly assigned to one of four treatment groups: E2/NETA50/140, 50/250 or 50/400 (mg/day hormone delivery) combination patchtherapy or placebo, applied every 3.5 days. Vasomotor symptoms(number and intensity of hot flushes and intensity of sweating) as well aspatch tolerance and adhesivity were rated and recorded by patients andquality of life was evaluated from a questionnaire.Results: This study showed that each of the E2/NETA transdermaltherapies significantly reduced the number and intensity of hot flushesand sweating compared to placebo (p<0.001). Sleep disturbances werereduced and sexual function improved in the three treatment groups.Compared to placebo, the 50/140 E2/NETA treatment group hadsignificantly better sexual arousal scores and sleep index and the 50/250E2/NETA treatment group had significantly better cognitive functionand sleep index (p<0.001). The E2/NETA patch was very well toleratedand demonstrated excellent adhesive properties (>90% adhered in ~80%of patients).Conclusions: It is concluded that a combination of E2/NETAtransdermal therapy administered in a continuous regimen is effective intreating moderate to severe vasomotor symptoms and urogenital atrophy

and thus improves the quality of life and the psychological well-being ofpostmenopausal women.

P4.15.04ACUTE CHANGES IN SERUM CALCIUM AND PARATHYROIDHORMONE CIRCULATING LEVELS INDUCED BY THE ORALINTAKE OF CALCIUM CITRATE AND CALCIUM CARBONATEIN MENOPAUSAL WOMENH-T.Chao , P-H.Wang, C-S.Chen, J.Fang, Vetrans General Hospital-Taipei, Yang-Ming Medical University, 201, Section 2, Shih-Pai Road,Taipei, Taiwan, 11217.

Objective: The aim of the present study was to evaluate and compare theacute changes in serum calcium (Ca) and parathyroid hormone (PTH)levels following the oral administration of Calcium citrate and calciumcarbonate in postmenopausal women.Study Methods: Forty postmenopausal women were included in thisdouble-blind randomized cross-over study.Results: Both calcium salts induced significant increases in serum Caand decreases in serum PTH compared to baseline values. The serum Cafollowing the oral administration of Calcium citrate and calciumcarbonate were1.165„b0.053¡F1.159„b0.059¡F1.196„b0.040¡F1.208„b0.049 mM/DLand 1.172„b0.050; 1.168„b0.051; 1.201„b0.046; 1.208„b0.054 mM/DL¡]mean„bSD¡^ at t-30, t60, t120, t240. Serum calcium (Ca) is increasedbetween t120 and t240 for calcium citrate and calcium carbonate.However, no statistically significant differences were observed betweenCalcium citrate and calcium carbonate for serum Ca increments. Thedecrease in serum PTH observed after administration of Calcium citrateand calcium carbonate. The serum PTH following the oraladministration of Calcium citrate and calcium carbonate were30.795„b9.411¡F20.494„b7.957¡F 18.326„b5.629¡F18.894„b8.137pg/ml and 29.324„b8.420; 20.767„b9.428; 18.810„b6.569;20.825„b8.118 pg/ml¡]mean„bSD¡^at t-30, t60, t120, t240. Whenassessing the area under the curve (AUC) of PTH values, we observedthat calcium citrate induce a significantly greater decrease in serum PTHthan calcium carbonate.Conclusions: In conclusion, compared to baseline values, both Calciumcitrate and calcium carbonate significantly increase serum calcium anddecrease serum parathormone in postmenopausal women. However,significant suppression of parathormone are observed following the oraladministration of Calcium citrate and calcium carbonate and might be ofimportance for their clinical use.

P4.15.05ASSOCIATION BETWEEN HYSTERECTOMY AND BONEDENSITY IN POSTMENOPAUSAL WOMENA.O. Pedro , J.D.Obeika, A.M.Pinto-Neto, L.C.Paiva, State University ofCampinas, Rua Alexander Fleming,101, Campinas, São Paulo, Brazil,13083-370.

Objectives: The aim of this study was to evaluate the effect ofhysterectomy on bone mineral density of postmenopausal women.Methods Data from a cross-sectional study among 30 premenopausehysterectomized women evaluated in the postmenopause was comparedwith 102 non-hysterectomized postmenopausal women. The patientswere selected from the Menopause Clinic of State University ofCampinas. All women answered a questionnaire and underwent to bonedensitometry (LUNAR DPX) to measure the bone mineral density(BMD) of the lumbar spine and femur.Results: The statistic analysis showed that the mean age, BMI, color ofthe skin, smoke habits, educational level, menarche and parity weresimilar in the studied groups. The multiple comparison of the BMDaverage and t-score of the three sites of the femur and lumbar spine didnot show statistical differences. Multiple regression analysis showed thatthe BMI is directly associated and age is indirectly associated with BMDof the lumbar spine and femur. The variables educational level, browskin and parity were associated only to BMI of the lumbar spine. Theprevious hysterectomy did not show any association with BMD.Followed this analysis, the 30 hysterectomized women were joined byage and BMI to 30 non-hysterectomized women and this analysis alsodid not show any differences.Conclusions: These findings suggest that premenopause hysterectomywith bilateral ovarian conservation does not seem to cause an additional


reduction on bone mineral density when evaluated in thepostmenopause.

P4.15.06BIOCHEMICAL MARKERS OF BONE TURNOVERMODIFICATIONS IN CLIMATERIC WOMEN.G. Morgante , A. Ditto, A. la Marca, D. Lanzetta, V. De LeoDepartment of Obstetrics & Gynecology, University of Siena (Italy)

Objective: Bone mineral density (BMD) measured by densitometry isthe elective parameter for the diagnosis of osteopenia and osteoporosis.Biochemical markers have been proposed as sensitive indicators of highbone turnover and for monitoring response to anti-resorptive treatment.Study Methods: We conducted a retrospective study to investigate thevalues of biochemical markers of bone metabolism with a view to earlydiagnosis of osteoporosis and monitoring of hormone replacement andcalcitonin therapy. The subjects were 415 women with a mean age of51±8 years (43-62 years) in peri- and post-menopause, recruited at theMenopause Center of Obstetrics and Gynecology Department of SienaUniversity and divided in 5 groups. In all subjects was performed bonedensitometry and taken a blood sample for assayed biochemical markers[Osteocalcin (OC), Parathyroid hormone (PTH), type 1 procollagen(PICP), Calcitonin (CT)].Results: Three groups of women were divided into two subgroups: thosewith normal and those with low BMD (<1 SD). Basal concentrations ofPCP1, OC, PTH and CT were compared in the various groups. Twogroups of postmenopausal women with BMD below the normal weretreated with estrogen replacement therapy and with unmodified eelcalcitonin.We evaluated whether some of these biochemical markers of boneturnover could enable the identification of women with low BMD andwhether could be useful for monitoring the results of antiresorptivetherapies.Conclusions: Markers of bone formation (PICP and OC) make itpossible to distinguish women with high turnover who are therefore atrisk for osteoporosis from women with low turnover in menopause. Agood correlation was also found between changes in levels of thesemarkers and changes in BMD during treatments, which suggests that thePICP and OC would be useful for monitoring response to anti-resorptivetherapy.

P4.15.07BLEEDING - SIDE EFFECT OF CONTINUOUS ESTROGEN-PROGESTAGEN REPLACEMENT THERAPYT.Moskovic , N. Antic, A. Knezevic, V. Pazin, M. Pantic, UniversityHospital of OB/GYN Narodni Front, 11000 Belgrade, N. fronta 62,Yugoslavia

Objectives: The aim of the study is to analyze onset, frequency andduration of bleeding in postmenopausal women receiving continuos E-Ptherapy.Study Methods: A total of 57 postmenopausal women (45-67 age),requiring HRT for the treatment of menopausal symptoms were enrolledin a prospective study lasting 12 months, and 397 cycles were analyzed.All women received orally 2mg estradiol + 1mg norethisterone acetatedaily continuously. Patients were asked to complete questionnaire aboutbleeding onset for each of 12 months. Endometrial thickens wasevaluated by ultrasound, between 3-6 months of therapy. In seven casesD&C and histological examination of endometrium was performed.Results: Bleeding onset was found in 25,67% of cycles. 77.19% ofwomen had bleeding episodes. Percentage of patients with bleedingepisodes declined from 61% in 1st cycle, to 37.7% in 2nd cycle and14.2% in 11th cycle. Bleeding episodes were more often in earlypostmenopause independently of women`s age. Bleeding lasted 1-3 daysin 66.6% of cycles and more than 10 days in 13.72%. Haevy bleedingepisodes were found in 11.8% of bleeding cycles, and regular bleedingepisodes were found in 22,7% of cycles. D&C was performed in 7 casesdue to long lasting bleeding episodes. Only in one case proliferativeendometrium was found.19.29% of women discontinued therapy due toirregular bleeding.Conclusion: Majority of women receiving continuos E-Ptherapyexperience bleeding episodes more often in first three months of therapy.Even irregular bleeding is mostly light and short duration but it is reason

for discontinuation of therapy in about 20% of women. Bleeding ismostly due to endometrium atrophy.

P4.15.08CARBOHYDRATE METABOLISM IN POSTMENOPAUSALPATIENTS TREATED WITH TRANSDERMAL ESTRADIOL ANDNORETHISTERONE ACETATEE. Vladescu (1), I. Munteanu (1), A.O. Mueck (2), B. Salbach (3), T.von Holst (3), T. Rabe (3)(1) University Women’s Hospital “Bega”, Timisoara, Romania.(2) University Women’s Hospital, Tuebingen, Germany.(3) University Women’s Hospital, Heidelberg, Germany.

Objectives: In this study the effect of transdermal estradiol combinedwith oral norethisterone acetate on carbohydrate metabolism in non-diabetic postmenopausal women has been investigated. Twoestrogen/progestin regimens were tested: sequential vs. continuousprogestin addition.Study Methods: Carbohydrates were analyzed in 33 postmenopausalpatients undergoing a prospective, open, randomized, 12 monthcomparison trial with transdermal estradiol, ESTRADERM TTS (ETTS;0.05 mg) plus norethisterone acetate (NETA; 1 mg orally) in a cyclic(n=17) versus continuous (n=16) regimen. Measurements were doneduring the estrogen phase.Results: There we..e no negative or only minor side effects on fastingglucose and on oral glucose tolerance test (oGGT) 2 hours after oralglucose loading (100 g) in both regimens. One hour after oGGT therewas a steady increase in glucose up to 22% above pretreatment valuesduring continuous progestin treatment but only +8% in the sequentialtreated group. A mild fasting functional hyperinsulinemia was found inboth groups. HbA1c values indicate no preclinical diabetes mellitus, andno deterioration during HRT was found.Conclusion: Transdermal estradiol sequentially or continuouslycombined with oral norethisterone acetate, does not cause undesireddeterioration of carbohydrate metabolism which might have a clinicalrelevance.

P4.15.09CHARACTERISTIC CHANGE WITH QUANTITATIVECOMPUTED TOMOGRAPHY (QCT) METHOD CONCERNINGBONE MINERAL DENSITY (BMD) UNDER HORMONEREPLACEMENT THERAPY (HRT)K.Hayashi , S.Tsuyama, Dept. OB/ GYN, National ShimonosekiHospital, 1-1-1Ushiroda-cho Shimonoseki , Yamaguchi,Japan,751?8501, J.Nobutani Shimonosek Public Health Office, 1-1Nabe-cho, Shimonoseki, Yamaguchi, Japan, 751?0006

Objectives: The aim of the study was to investigate characteristicchanges of BMD with QCT method under HRT during five yearcompared with Dual energy X-ray (DEX) method.Study Methods: Fifty-three women (average age : sixty-two years) underHRT were included in this investigation. The BMD was measured on thethird lumbar vertebra (L3) with HITCHI- CW2000 and checked everyyear during five years. Conjugated estrogens (0.625mg) andmedroxyprogesterone acetate ( 2.5mg ) were prescribed for HRT.Result..The average rate of change of BMD in every year was 9.3%,11.5%, 8.7%,- 3.2%,- 7.5% during five years. The BMD was for the firstthree years increased, but decrease of BMD was recognized after thefourth year even if HRT was performed.Conclusion: Generally, the BMD increased continuously with DEXmethod under HRT, but through our investigation it became clear thatQCT method had a different alteration form of BMD from DEX method.

P4.15.10ECHOGRAPHIC TRANSVAGINAL EVALUATION: OVARIANCYSTS AND REPLACING HORMONAL THERAPY (HRT)S. Staiano, A. Nucci, C. Lampariello, G. De Placido. ClinicalDepartment of Obstetric and Gynecological Emergency and Medicine ofReproduction – “Federico II” University – Naples – 87100 ITALY

Objectives: The purpose of this study is to determine the predominanceof simple ovarian cysts in healthy post-menopausal women and theinfluence of HRT on this pathology.


Study Methods: 987 women during post-menopause were examined forour study and they underwent a screening ecographic examination.Subsequently we identified all the patients who suffered from ovariancystic proliferation (?) and they were examined by eco-doppler andhemodynamical determination of CA-125.The cut-off of resistance index has been fixed (LO.50) according tointernational literature.We divided the patients into two study groups: in the first group patients(37.7%) receiving substitutive treatment (HRT) were examined; thesecond group included patients (64.3%) not receiving HRT treatment.Every three months the patients of both groups underwent a transvaginalecographical follow-up.We identified some patients (11.8%) out of 987 women, sufferin fromunilocular cysts: 29% of these patients received HRT treatment and theremaining 71% did not.Both serum CA-125 and the resistance index were normal in everypatient.Results: During our monitoring we observed:in the first group 29.4% of cysts had disappeared; 8.8% were reduced indimension; 26.4& had increased their dimension; 35.4% had remainedinchanged; in the second group : 30% of cysts had disappeared; 3.6%were riduced in dimension; 25.3 had increased their dimension; 41% hadremained unchanged.There was non evidence of any remarkable statistical correlatio, so thatour results concluded that the predominance of ovarian cysts in the twogroups amount to 9.6% in the first one and 13% in the second one.Conclusions: The reduced dimensions of a lot of cysts or theirprogressive disappearing, together with the high index of resistance toDoppler-echo and the regular serum CA-125 levels, led us to a diagnosisof begin cysts.Our results could suggest us a conservative management about simplecysts occurring in post-menopausal women, based on a limited follow-up by transvaginal echo serum monitoring.Neverthless further studies are necessary in order to evaluate theinfluence of HRT on ovarian cysts.

P4.15.11EFFECT OF FOLIC ACID SUPPLEMENTATION ON THECARDIOVASCULAR RISK FACTOR HOMOCYSTEINE INPOSTMENOPAUSAL WOMEN.V. De Leo , A. la Marca, G. Morgante, D. Lanzetta, S. Palazzi, N.Caparelli. Department of Obstetrics & Gynecology, University of Siena(Italy)

Objective: There are indications that plasma Hcy is related to oestrogenstatus. Premenopausal women have lower plasma Hcy than men andpostmenopausal women and plasma Hcy decreases in menopausalwomen on oestrogen replacement therapy. Blood levels of Hcy areinversely related to blood levels of folate. Several randomized controlledtrials have showed that dietary supplements of folic acid lowered Hcylevels. The aim of our randomized controlled trial is to verify the effectof folic acid supplementation on homocysteine plasma levels inpostmenopausal women.Study design: Thirty-six women were divided randomly into two groups:placebo (n=18) and 500 mcg folic acid/day for 4 weeks (n=18). Toassess concentrations of plasma Hcy, venous blood samples were takenon enrollment and after 4 weeks of treatment.Results : Mean plasma Hcy levels were 10.9 ± 2.7 in the placebo groupand 7.8 ± 2.35 mmol/L (p<0.01) in the group receiving 500 mcg folicacid/day for 4 weeks. The tertiles of the women with the highest baselineHcy plasma levels showed the greatest reduction in Hcy, with a meandecreases of 4.35 mmol/L (32%; p<0.01), as compared to a decrease of3.35 mmol/L (29%; p<0.01) in the middle tertile and 1.3 mmol/L(22.4%; p=0.09) in the lower tertile.Conclusions: The results show that low doses of folic acid are associatedwith a significant reduction in plasma concentrations of Hcy. Thehighest initial levels of Hcy showed the most important reduction aftertherapy. The data that low doses of folic acid reduce plasmaconcentrations of Hcy paves the way for fortification of foods with lowdoses of folic acid so as to reduce plasma levels of this aminoacid.

P4.15.12EFFECT OF MENOPAUSE ON CEREBRAL AND CEREBELLARBLOOD FLOW IN WOMENT. Ohkura , K. Hoshimoto, Y. Ohta, M. Hayashi, Dept. OB/GYN,Koshigaya Hospital, Dokkyo University School of Medicine,Koshigaya, Japan.

Objectives: The aim of this study was to investigate the effect ofmenopause on cerebral and cerebellar blood flow (CBF and Cb1BF) inwomen.Study Methods: 48 women aged 43-50 years were included in this study.24 were premenopausal women with a mean age of 47.1 ± 2.5 (SD)years and the remaining 24 were postmenopausal women with a meanage of 47.1 ± 2.4 years. The CBF and Cb1BF were measured using 99mTc-ethyl cysteinate dimer (ECD) and SPECT. Statistical analyses werecarried out using unpaired t-test.Results: The mean CBF of 47.6 ± 2.7 ml/100g/min in the premenopausalwomen was significantly higher that that of 43.7 ± 4.0 ml/100g/min inthe postmenopausal women (p<0.001). The Cb1BF of 54.8 ± 4.8ml/100g/min in the premenopausal women was also significantly higherthan that of 47.5 ± 4.5 ml/100g/min in the postmenopausal women(p<0.0001). Mean serum estradiol (E2) levels in the premenopausalwomen was 108 ± 65 pg/ml and all E2 levels in the postmenopausalwomen were less than 10 pg/ml. There were no significant differencesbetween premenopausal and postmenopausal women in any of the meanvalues of blood pressure, hemoglobin and hematocrit.Conclusions: It is inferred from these results that the CBF and Cb1BFdecrease after menopause and ovarian estrogen affects the CBF andCb1BF in women.

P4.15.13EFFECT OF TRANSDERMAL CONTINUOUS COMBINEDDELIVERY OF ESTRADIOL AND NORETHISTERONE ACETATE(ESTALISÒ) VS. ESTRADIOL ALONE FOR ENDOMETRIALPROTECTION IN MENOPAUSAL WOMEND.F. Archer , Dept. OB/GYN, The Jones Institute for ReproductiveMedicine, Eastern Virginia Medical School, Norfolk, Virginia, USA.

Objectives..To determine whether a continuous combinedestradiol/norethisterone acetate (E2/NETA) transdermal delivery system(EstalisÒ) reduces the incidence of endometrial hyperplasia inpostmenopausal women more than transdermal E2 alone. The incidenceof urogenital bleeding/spotting and vasomotor symptoms were alsoassessed.Study Methods: A total of 625 healthy postmenopausal women with anintact uterus were assigned to one of four transdermal treatments, E2 50mg/day, or E2/NETA with 50 mg E2 and 140, 250 or 400 mg/day NETA.Results: Endometrial samples from 413 (66%) women were available foranalysis. Endometrial hyperplasia was found in 38% (39 of 103) in theE2 alone group versus 0.8% (1 of 123), 1% (1 of 98) and 1.1% (1 of 89)in the E2/NETA 50/140, 50/250 and 50/400 groups, respectively(p<0.001). The rate of amenorrhea was stable throughout the study forthe E2/NETA 50/140 group (60% at cycle 1, 61% at cycle 11) andincreased steadily over 12 months with the 50/250 group (37% at cycle 1and 55% at cycle 11). The mean number of days per episode was alsolowest in the 50/140 and highest in the E2 50 group. The mean numberof hot flushes per day decreased to less than one in each treatment groupat endpoint. The E2/NETA combination patch was well tolerated andcomparable to the E2 patch alone (the most common adverse eventsreported in each treatment group were breast pain, dysmenorrhea andheadache).Conclusions: Continuous combined transdermal HRT with E2/NETA(EstalisÒ) dramatically reduces the incidence of endometrial hyperplasiathat occurs with transdermal E2 alone. The EstalisÒ transdermalcontinuous combined delivery system provides increased dose flexibilityand may therefore improve compliance with HRT.


P4.15.14EFFECTS OF PROGESTOGENS ON THE EXPRESSION OFENDOTHELIAL CELL ADHESION MOLECULES (ICAM-1 ANDVCAM-1) INDUCED WITH INTERLEUKIN 1-bH. Tatsumi , K. Tanaka, T. Tamura, H. Honjo, Dept. OB/GYN, KyotoPrefectural University of Medicine, Kyoto, Japan.

Objectives: The most important initial event in atherosclerosis is theadhesion and transmigration of monocytes to endothelium. This studywas designed to examine whether progestogens prevent this process byinhibiting the expression of adhesion molecules in it as reported aboutestrogen.Study Methods: Human umbilical venous endothelial cells (HUVEC)were stimulated by IL-1b (1.0ng/ml), and simultaneously mediated withmedroxyporgesterone acetate (MPA), noresthisterone (NET) orlevonorgestrel (LNG) [10-10 – 10-8M each] for 8 hours. 1) Thenquantitative analysis of OCAM-1 and VCAM-1 was done using enzyme-linked immunosorbent assay; 2) Examined the expression ofprogesterone receptor (PR) in HUVEC by RT-PCR method; 3) we alsoinvestigated whether the PR antagonist, mifepristone, could block theactions.Results: Each progesterone (10-9M and 10-8M) significantly stimulatedthe expression of ICAM-1 and VCAM-1 (p<0.01). The effect was thestrongest with LNG and weakest with MPA. The expression of PR inHUVEC was recognized on mRNA level by RT-PCR and those effectswere blocked by mifepristone respectively.Conclusions: It is suggested that progestogens exacerbate atherosclerosisvia PR, but relative binding affinity to receptor of MPA, NET, LNG arevery different, so we had better be more careful about the kind andquantity progestogens combined with estrogen HRT.

P5.15.15ESTROGEN REDUCES THE ELEVATION OF INTRACELLULARCALCIUM CONCENTRATION AND CELLULAR PEROXIDATIONINDUCED BY AMYLOID b PROTEINT. Hosoda , K. Kariya, H. Tatsumi, H. Kojima, C. Katou, T. Okuda, K.Tanaka, T. Tamura, M. Urabe, H. Honjo, Dept. OB/GYN, KyotoPrefectural University of Medicine, Kyoto, Japan.

Objectives: In past studies, we reported the efficacy of estrogenreplacement therapy (ERT) on Alzheimer’s disease (AD). In AD,apoptosis of neuronal cells is the cause of disease. We further reportedthat estrogen inhibits apoptosis of cultured neuronal cells induced byamyloid b protein ( Ab). Ab is supposed to cause apoptosis byincreasing cellular calcium influx or cellular peroxidation. In the presentstudy, we investigated whether estrogen influences intracellular calciumconcentration and cellular peroxidation.Study Methods: 100 mM of Ab was added to differentiated PC-12 cells,and they were labeled with Fluo-3 and DCFH-DA to quantifyintracellular calcium concentration and cellular peroxidation byflowcytometry. The effect of pretreatment with various concentrations(10-8 ~ 10-12 M) of 17 b-estradiol (E2) and E2+ICI 182780 (estrogenreceptor antagonist) were examined.Results: The addition of Ab increased both intracellular calciumconcentration and cellular peroxidation and these increases wereinhibited by E2. The inhibition of E2 was attenuated by ICI 182780.Conclusions: It is suggested that estrogen inhibits neuronal apoptosis bysuppressing the cellular calcium influx and cellular peroxidationincreased by Ab, and these effects are mediated by estrogen receptor.

P4.15.16EVALUATION OF HYPERLIPIDEMIA, OSTEOPOROSIS ANDOBESITY IN PRE- AND POSTMENOPAUSAL ASYMPTOMATICJAPANESE WOMENK. Takeuchi , M. Ohta, A. Sakao, M. Terasawa, Tottori Red CrossHospital, 117, Shotoku-cho, Tottori, Japan, 680-8517.

Objectives: The aim of this study was to investigate the prevalence ofhyperlipidemia, osteoporosis and obesity in pre-and postmenopausalasymptomatic japanese women.Study Methods:1) Lipid profiles including total cholesteroL (TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol (HDL-C) and baseline characteristics

such as age, weight, height were examined in 1322 healthy women aged40-86 years (mean_}SD:53.4_}9.2 years). They were divided intofollowing 4 groups according to their age (GroupI:40-49 years, II:50-59,III:60-69, IV:over 70.)2) Lumbar spine bone mineral density(BMD) were measured by dual-energy X-ray absorptiometry(DEXA) in 325 women aged 40-87 years(mean_}SD:64.8_}9.6years).Results:1)The incidence of hyperlipidemia (TC_†220mg/dl and/orTG_†150mg/dl) in 4 groups were 25.6%,48.6%,59.0% and 52.5%,respectively. Statistically significant differences were noted in the levelsof TC, TG, LDL-C and BMI values between 4 groups, respectively(Kruskal-Wallis'test, p_ƒ0.01).2) Normal, osteopenic and osteoporotic BMD values according to WHOcriteria were 20.9%, 22.5% and 56.6%, respectively. BMD valuesshowed a negative correlation with age (R=0.566,p_ƒ0.0001).3) Obesity(BMI_†26.4)were only in 8.8% of total patients. BMI had nosignificant correlations with lipid profiles and BMD.Conclusions: High rates of hyperlipidemia and osteoporosis especially inthe postmenopausal women suggest the large influence of estrogen on th

P4.15.18INFLUENCE OF RISK FACTORS AND REPRODUCTIVE HISTORYON BONE DENSITY OF POSTMENOPAUSAL WOMENL.C.Paiva , S.Filardi, J.F.Marques-Neto, A.M. Pinto-Neto, A.O.Pedro,State University of Campinas, Rua Alexander Fleming, 101, Campinas,São Paulo, Brazil, 13083-370.

Objectives: The aim of this study was to analyze the influence of riskfactors and reproductive history on bone mineral density (BMD). Aretrospective study was carried out with 268 menopausal women withosteoporosis, who were attended at the Osteoporosis Clinic of StateUniversity of Campinas.Study Methods: Data were obtained by clinical examination and by aquestionnaire with information about family history of osteoporosis,physical activity, body mass index, smoke habits, calcium intake, age atmenarche, parity, duration of breastfeeding, time since menopause andhormone replacement therapy. BMD of lumbar spine and femoral neckwere evaluated by bone densitometry – DEXA (DPX-LUNAR).Results: Patient’s mean age was 63.6 years (SD=8.8) and time sincemenopause was 16.8 years (SD=8.8). Only 21% of patients had usedhormone replacement therapy during a mean period of 5.4 years(SD=6.3). The mean value of lumbar spine BMD(L2-L4) was0.821g/cm2 (SD=0.127) and at femoral neck was 0.720 g/cm2(SD=0.116). Multiple linear regression analysis showed that the factorsassociated with lumbar spine BMD were body mass index (p<0.001) andsedentariness (p<0.001). The associated factors to femoral neck’s BMDwere body mass index (p<0.01) and time since menopause (p<0.001).Others risk factors and reproductive history did not show any associationto BMD.Conclusions: It is concluded that a higher body mass index and fewyears since menopause are protective factors while sedentariness is arisk factor to osteoporosis in this population.

P4.15.19LOCAL TREATMENT OF POSTMENOPAUSALVAGINAL ATROPHY WITH PROMESTRIENE.C. Quevedo, C. Sanchez, A. Villanueva, M. de Gomez, R . Pizzi, P.Lopez Herrera. Dept. OB/GYN. University Hospital. Caracas.Venezuela.

Objectives: The aim of the study was investigate the effect ofPromestriene treatment of postmenopausal vaginal atrophy, theimprovement of symptoms and hystological changes.We studied the systemic and side effects of Promestriene.Study and methods Forty one women were incluided in the study.Complete medical record and physical with enphasis in vaginalsymptoms ( dryness, itching, pain, dispareunia ) was made before andafter treatment.Promestriene, 10 mg. vaginal capsules per day for 20 days, was given toeach patient.Hystopatological studies were made ( hormonal vaginal citology andbiopsy) pre and post treatment.


FSH, LH and Estradiol levels and transvaginal ultrasound ( endometrialthickness ) were made to evaluate the systemic effect of treatment.Results: The medium of menopausal age was 57 years; 100% of patientshad improvement of disuria and vaginal itching, and 50 % women hadrelief of vaginal dryness.The hormonal citology showed improvement in Kariopicnotic index in80,5%, and 56 % of the vaginal biopsies.No changes in the endometrial thickness, FSH, LH and Estradiol levelswere found.Conclusions: Promestriene vaginal treatment was found to have asignificant effect to improve the postmenopausal vaginal symptoms andthe atrophyc changes, without systemics and side effects.Promestriene is a safety vaginal therapy in postmenopausal women withsystemc estrogen contraindication use.

P4.15.20LOW INCIDENCE OF ENDOMETRIAL PATHOLOGY INPOSTMENOPAUSAL WOMEN ON HORMONAL REPLACEMENTTHERAPY WITH ABNORMAL UTERINE BLEEDINGM. Bianchi (1), A. Santini (1), A. Manzur (1), C. Nien (1), P. Villaseca(2), E. Arteaga(2)(1) Dept. OB/GYN(2) Dept. EndocrinologyFacultad de Medicina, P. Universidad Católica de Chile, Santiago, Chile.

Objective: The aim of this study was to screen for endometrial pathologyin 76 postmenopausal women with abnormal uterine bleeding receivinghormone replacement therapy.Study Methods: Endometrial biopsy specimens were obtained with a Zsampler aspiration curette, processed by standard methods, and stainedby hematoxylin and eosin and special methods to reveal subtle featuresof the edometrium. The aspirative endometrial biopsies were performedby one of the gynecologist of the Menopausal Clinic at the UniversidadCatólica Clinic Hospital.Results: The results of the endometrial biopsies were as follows: 30.3%secretory, 19.7% proliferative, 10.5% atrophic, 6.6% hyperplasticwithout atypia, 3.9% benign endometrial polyps, 23.7% endometrialtissue benign, inactive or fragment of epithelium insufficient fordiagnosis and 5.3% of no endometrium identified. We did not findspecimens with adenocarcinoma and hyperplasia with atypia.Conclusions: Office endometrial biopsy is a less expensive and well-tolerated procedure. The best results are obtained in diffuse endometrialpathology. In our experience, the aspirative biopsy permits to know theactual condition of the endometrium in these patients. The absence ofpremalignant pathology in our study confirms that these diseases have alow incidence in patients with adequate regime of hormone replacementtherapy.

P4.15.21MENOPAUSE, MELLITO DIABETES AS PROTECTIVE FACTORIN THE VAGYNITES OF THE WOMAN IN MENOPAUSEM.G. Mazza , D. Galea, Dept. OB/GYN, General Hospital A.S.S.L.5,Crotone, Italy

Objectives: The high prevalence of the positiviness of Schiller’s test isthe previsions work of ours in the diabetic in menopause has suggestedus to check the incidence of the aspecific vagynites in the same samplecontrasting it with a same sample of non-diabetic people.Study Methods: For this reason, the vaginal secretion of 150 diabeticwomen of type II, not insulin-dependent, not fat, with post-menopausalperiod not less to 5 years and with parity not more to 3 years, has beenundertaken to a cultural exam with antibiogramm.Results: The result of such an exam has been compared with thatobtained by the similar study conducted on a control sample that didn’tpresent the diabetic aspect. Contrary to what we thought, knowing theprotective effect of the mellito diabetes, the group of the diabetic womenhas put in evidence only 2 cases of aspecific vaginites (1.44%), while inthe group of the not diabetic women did not occur as related to themetabolic balance since the half of the whole sample presented differentgrades of metabolic imbalance.Conclusions: The explanation of such an observation could be seen inthe fact that the high glicoistachia remarkable in the mellito diabetescould determine an optimal substratum to the action of the lattobacillawith consequent iperproduction of lactic acid and a drop of the

vaginal pH, these last conditions typical of the vaginal ecosystem of thefertile woman.

P4.15.22STUDIES ON THE SAFETY OF TREATMENT WITHTRANSDERMAL PATCHES CONTAINING ESTRADIOL ANDNORETHISTERONE (ESTALISÒ)D.F. Archer (1), E.G. Luftkin (2), M-P Dain (3)(1) Dept. OB/GYN, The Jones Institute for Reproductive Medicine,Eastern Virginia Medical School, Norfolk, Virginia, USA.(2) Dept. of Endocrinology, Mayo Clinic, Rochester, Minnesota, USA.(3) Rhône-Poulenc Rorer, Antony, France.

Objectives: To confirm the safety and tolerability of the estradiol andnorethisterone (E2/NETA) transdermal delivery system used as hormonereplacement therapy.Study Methods: Several studies of the E2/NETA patch delivery system(EstalisÒ) have included assessments of safety. Three studies involvedtreatment with transdermal E2/NETA patches delivering either 50/150,50/250 and 50/400 mg E2 and NETA respectively. In two of thesestudies an E2 only patch (MenorestÒ) was also given in either acontinuous or sequential regimen in each cycle. Another study involvedassessing two E2/NETA patches (50/140 and 50/250) with oralE2/NETA (KliogestÒ) as a comparator. Safety, tolerability and incidenceof adverse events were assessed in all studies.Results: In all E2/NETA groups, treatment was well tolerated with a lowincidence of adverse events. The majority of adverse events were mild tomoderate; the most common being breast pain, application site reaction,dysmenorrhea and headache. Mean endometrial thickness increasedslightly in all groups but was significantly less in the E2/NETA groupscompared to the E2 group alone (p=0.001). The incidence of amenorrheadecreased in the E2 50 group compared to the oral E2/NETA group(52.5%) and E2/NETA patches: 50/250: 39%, 50/140: 53% and 50/400:44%. The incidence of withdrawal of bleeding/spotting was similar in allE2/NETA groups and cycles occurring overall in about two thirds ofpatients.Conclusions: Administration of the E2/NETA transdermal deliverysystem is generally well tolerated. Endometrial hyperplasia is less thanwith estradiol alone; E2/NETA was better tolerated than oral NETA andcaused fewer occurrences of mild erythema than E2 alone.

P4.15.23THE EFFECT OF ISOFLAVONE IN THE SYMPTOMS OFPOSTMENOPAUSAL WOMENK.K Han (1) , C. Hayashi (1), M.B.C. Girão (1), E.C. Baracat (1), D.K.Yim (2), M.C. Panizzi (3), (1) Federal University of São Paulo, RuaNapoleão de Barros, 715.7oF, São Paulo, Brasil, 04023-900, (2)Department of Microbiology of the State University of Campinas,Campinas, Brazil, (3) EMBRAPA (Empresa Brasileira de PesquisaAgropecuária), Londrina, Parana, Brazil.

Objectives: The proposition of this work is to evaluate the beneficialeffects of isoflavone in the postmenopausal women with relationship tothe symptoms and prevention of the chronic disease, using 100g/day.Patients and Method: The group was constituted by the patients attendedin the Discipline of Gynecology in the Section of Postmenopausal of theFederal University of São Paulo – Escola Paulista de Medicina(UNIFESP-EPM).We will study 80 patients, through the Randomized Double-blind Study,and we will divide in two groups of 30. The duration of the study will beof 16 weeks. The first group received 100mg of isoflavone daily in thecapsule form, besides the orientation of appropriate diet for notmodifying the initial levels of cholesterol and glicose, supervised by theDepartment of the Nutrition. The second group will receive placebo.Initially, our attention will be returned to the accomplishment of themenopause diagnosis, that is to say, the patients that present symptomsof clinical and laboratorials. The approaches of inclusion of this workwill be: To agree in participating in the study, by means of consentwriting in formulated document and approved by the of Medical ÉticCommission of UNIFESP-EPM.Patient that are in the menopause phase, that is to say, period of largeramenorrhoea than 12 months.To present frequent clinical symptoms in the menopause period as “hotflushes”, palpitations, sudorese, isônia, irritation, emotional lability, etc.


Laboratorial menopause, that is to say the values of FSH above thenormality and the estradiol values below the normality.The patients will be accompanied for 16 weeks and they will besubmitted it you control newspapers of exams laboratorials andradiologics.Our research protocol will the following item:The patients to the they submit to the study, all the routine exams will beaccomplished for prevention of gynecological cancer and they will beappraised the initial levels of plasmatic cholesterol, glicemia,triglicerides and bone densitometry.Whole answer a questionary detailed to characterize the alimentaryhabits and of life.The clinical accompaniment will be to every 2 weeks and thelaboratorial of 4 weeks.We will accomplish the transvaginal ultra-sonography for themensuration of the thickness of the endometry in the beginning and inthe end of our work.Thus, we can study with details the effect of the isoflavone, afitoestrogen of easy access in what refers to the price and distribution, toimprove the symptoms and organic degeneration cause by themenopause. This way we will be minimizing the collateral effects causeby the use of steroid hormone. The chronic use of isoflavone will alsohelp in the prevention of some cancer types and coronary diseases.3-Results : The climateric sintoms evaluated by Kupperman’s indexshowed that 32 (80%) of patients of group G1 was decrease , while thegroup G2 only 5 patients(12,5%) showed the change. This difference isestatistically significant.The sintoms like “hot flushes” is decrease in 19 patients ( 46%) in thegroup G1 and 2 patients ( 5%) in the group G2.The FSH and Estradiol also showed modifications with the decrease of42 % and the increase of 37% repectivally. In the group G2 didn’tshowed estatistically significant.The cholesterol level showed decrease in 35 ( 87.5%) patients in thegroup G1 . In the group G2 the decrease was only in 13 patients(32,5%). This values had estatistically significant.The control transvaginal ultra-sound showed endometrial proliferation in4 patients of group G1 and 2 patients of group G2, this values didn’thave estatistically significant.In 18 patients ( 45%) of group G1 showed reduction of corporal weightand 3 increase. In the group G2 only two patients showed the reductionof corporal weight and 12 increase.Four patients of group 4 related the diminuition of libido with thetreatment and the group G2 this sintoms was related by 6 patients.The vaginal citology of the group G1 showed that 9 (22.5%) paientshave proliferation of the superficial cells ( estrogen activity). The groupG2 the same change was observed in 3 patients(7.5%).Conclusions: We concluded that the isoflavone can de used for treatmentof climateric sintoms with safety in the women that can’t use naturalestradiol and the women who wants use natural estrogen (Phytoestrogen).

P4.15.24THE EFFECT OF RALOXIFENE ON THE INCIDENCE OFOVARIAN CANCER IN POSTMENOPAUSAL WOMENP. Neven (1), S.L. Silfen (2), A.V. Ciacci (2), R. Akers (2), B. Bekele(2), S. Eckert (2)Dept. OB/GYN, Algemene Kliniek St., Brussels, Belgium.Lilly Research Laboratories, Indianapolis, Indiana, USA.

Objectives: In the USA, the incidence of invasive ovarian carcinoma isin the range of 29-65/100,000 person years for 50 to 85 year-oldCaucasian women, as reported in the SEER database. The aim of thisanalysis is to determine the incidence of ovarian cancer inpostmenopausal women treated with raloxifene, as compared withplacebo, in 15 long-term placebo-controlled clinical trials.Study Methods: Up to October 1, 1999, a total of 15 long-term (³ 6months) raloxifene studies involving 11,681 postmenopausal womenhave been conducted. The total raloxifene exposure was 21,864 personyears as compared with 10,374 for placebo. Ovarian cancer cases wereidentified from the clinical trial safety database.Results: Mean age of women in pooled studies was 63.1 years (SD =8.3). A total of 16 cases of ovarian cancer have been reported; 8 women(77.1/100,000 patient years) on placebo and 8 women (36.6/100,000patient years) on pooled raloxifene doses. Relative risk of ovarian cancerin this database is 0.50 (CI 0.19, 1.34).

Conclusions: The rate of ovarian cancer in long-term placebo-controlledraloxifene studies was consistent with the rates reported for Caucasianwomen of similar age groups in the general population in the USA.Raloxifene use was not associated with an increased rate of ovariancancer.

P4.15.25THE MALAYSIAN GYNECOLOGIST’S OPINION ON USE OFHORMONE REPLACEMENT THERAPY IN PATIENTS WITHTREATED GENITAL TRACT CANCERA. Mohamed , Z. Akhtar, H. Dali, N. Nasri, Malaysia.

Method: A mail questionnaire was sent to all gynecologists registeredunder the Malaysian Medical Association.Results: A total of 67 gynecologists responded out of 198 questionnairessent (33.8% response). AL the gynecologists agree that HRT isbeneficial for menopausal symptoms and almost all prescribed itregularly for their patients with menopausal symptoms. In patients whohad been treated for gynecological cancer, 15 out of 67 do not prescribeHRT to all their patients. For patients presenting with menopausalsymptoms after treatment, HRT/ERT is the most popular choice oftreatment followed by use of herbal treatment. 34 out of 67 respondentsonly prescribe HRT for early stage disease and 14 prescribed it only forlate stage disease. Most common reason for not starting HRT is cited asits use being controversial in patients with previous genital tract cancers.Most gynecologists felt most comfortable in prescribing HRT forcervical carcinoma and felt least comfortable in prescribing HRT forendometrial carcinoma. Those who do not prescribe for endometrialcancers believe it would cause a relapse in the disease. Gynecologistsvary in the timing to start HRT with most starting after 3 to 6 months oftreatment and some waited for menopausal symptoms to occur beforeprescribing.Conclusion: Although HRT is being prescribed freely by the MalaysianGynecologists for menopausal symptoms, opinions vary when thepatients are rendered menopausal by treatment for genital tract cancers.A total of 15 out of 67 (23%) respondents actually do not prescribe HRTat all, although most respondents noted that their patients do havemenopausal symptoms post treatment. The use of HRT beingcontroversial and fear of relapse of disease is the most commonly citedreasons and this can be seen in the use of herbal medications as analternative to the use of hormones. As expected, endometrial cancer,which is hormone dependent, is the least prescribed for fear of relapse ofthe disease.As more and more women become aware of their health, hopefully morewomen would be diagnosed at an earlier stage of disease which wouldmean better survival and these women would certainly have betterquality of life with HRT. Therefore, the problem of whether HRT is safeor not in patients with previous genital tract cancers should be addressedas aggressively, in Malaysia at least, as in other menopausal women withosteoporosis who do not have cancers. Gynecologists should be made tofeel comfortable prescribing hormones without fear or worry of relapse.

P4.15.26TREATMENT OF THE CLIMACTERIC SYNDROMET.Rogovskaya , Kharkov Medical University, 4 Malinovskiy Street,Kharkov, UkrainE, 61052.

Objectives: The aim of the study was to create and to investigate theeffect of the method for regulation of hormonal interactions during theclimacteric without any drugs.Study Methods : The new method have been created and named as themethod of the psychosomatic regulation /PSR/. The method is based onthe concentration of the attention on ovaries and a successive movingthrough all glands of the internal secretion to the cerebral cortex forbuilding a uniform power ring.Results: These women used the PSR method after special studies fortreatment CS.In group A, 35w.(70%) the first result has received aftertwo-week usage of the method (15 women, 40.3%). The rest of patientshave received results after one month of treatment. In group B 15w.(30%) were suffering from severe CS the significant effect has receivedafter five weeks of the treatment. The normal interactions between FSH,LH and estradiol have found (see table)Before treatment After treatmentEstradiol mg/ml 35.8 ± 2.1 88 ± 7.73


FSH mlu/ml 28.1 ± 0.5 9.1 ± 0.89LH mlu/ml 11.1 ± 0.1 9.2 ± 0.21Index LH/FSH 0.4 1.5Conclusions: The new PSR method for treatment the CS is accessible,harmless and high-effected. This treatment may be recommended forrepairing the hormonal interactions; it gives a real possibility for womanto avoid the beginning of climacteric for a long time.

P4.16 MOLECULAR GENETICS

P4.16.01APOPTOSIS IN ENDOMETRIOSIS AND ADENOMYOSISI. Matalliotakis (1), A. Goumenou (1), I. Panayotides (2), M. Tzardi (2),E. Koumantakis (1), University of Crete, Greece.(1) Dept. OB/GYN(2) Dept. of Pathology

Objectives: The aim of the study was to investigate the Bcl-2 and Baxexpression in endometriotic and adenomyotic tissues.Study Methods: 56 tissue samples were collected during gynecologicalsurgery and confirmed by histology to have 25 endometriosis and 31adenomyosis. The Bcl-2 and Bax expression were investigated byimmunochemical staining and electron microscopy.Results: The difference of Bcl-2 positive protein between endometriosisand adenomyosis was not significant. No significant difference wasfound between Bcl-2 expression and the proliferative and secretoryphase of the cycle in women with endometriosis. The difference of Baxpositive protein between endometriosis and adenomyosis was notsignificant. In addition, no significant differences were found betweenthe various phases of the cycle. We have found strong inversecorrelation between the expression of Bcl-2 and Bax in endometriosisthan in adenomyosis.Conclusion: Our results suggest that the pathogenesis of ovariaendometriosis is different from this of adenomyosis and the persistentBcl-2 and Bax expression during both phases of the cycle in ovarianendometriotic tissues may have important implications for the survivaland proliferation of the ectopic endometrial tissue.

P4.16.02ATTEMPT OF FORECASTING FETO-PLACENTALINSUFFICIENCY AND GESTOSIS BY MOLECULAR-GENETICANALYSISG. Y. Khotait , T. V. Galina, V. E. Radzinskiy, E. V. Karpova, A. V.Itkes, Dept. OB/GYN, Dept. Biol. & General Genetics, MaternityHospital N 25, Russian Peoples’ Friendship University, Moscow,Russia.

The problem of EPH-gestosis, as well as restriction of intrauterinegrowth (IUGR), remains a “white patch” in work up theories of etiologyand pathogenesis, in therapy and prognostication. Taking into accountthat one of the main reasons leading to development of gestosis isalterations in the wall of blood vessel, we provided a study of alleleglycoprotein GP IIIa in pregnant women with IPH-gestosis and withproved IUGR. This gene controls synthesis of cell receptors- integrines.In the population the frequency of this allele is near 14%. DNA in bloodwas studied with polymerize chain reaction with using of oligonucleotidprimers. Analyses of fragments was made by electrophoresis inpolyacrilyc gel. Results were fixed by silver painting. We examined 66women: 30 patients were with proved fetal hypotrophy, 32 patients withgestosis (15 – with combined gestosis). We found that 10 (30%) womenfrom the 30 with IUGR were carriers of allele GP IIIa and one of themwas homozygous, 3 (17.65%) women from 17 with gestosis also werecarriers of this allele, and there were no one carrier in the group withcombined gestosis. It’s interesting to note: there were indication in theircase histories on failures in the previous pregnancies: miscarriages,IUGR, placenta adherens. Study is in progress.Conclusion: Carriers of allele GP IIIa are in group of high risk of IUGR.Pregnancies in this group should be managed with more care. Wesuggest this method for prognosing IUGR in patients from group of risk.Development EPH-gestosis does not depend on glycoprotien GP IIIa, itmore depends from predisposing extragenital factors.

P4.16.03CLONING, EXPRESSION AND GENE REGULATION OF AHUMAN OXYTOCIN RECEPTOR IN PREGNANT UTERUST.Kimura , M.Takemura, T.Nobunaga, K.Ogita, Y.Matsumura, C.Kusui,H.Nakamura, M.Koyama, C.Azuma, Y.Murata, Dept.OB/GYN, Facultyof Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 5650871,Japan.

Objectives: Oxytocin receptor (OTR) expression should play a crucialrole for initiation and regulation of labour in the pregnant uterus. Toelucidate the molecular mechanism of the OTR regulation, we attemptedto clone the human OTR cDNA, the gene for OTR and transcriptionfactor for this gene. Study Methods: Term uterine myometrium wasobtained from uterine rupture under informed consent, mRNA wasextracted and cDNA library was constructed. OTR cDNA was clonedfrom the library using Xenopus oocyte expression system. OTR genewas cloned from human genomic library. Chromosomal localization wasdetermined by FISH. Nuclear proteins to bind the OTR gene werecharacterized by gel shift assay and methylation interferencefootprinting. To clone the binding protein, yeast one hybrid system wasapplied.Results: Human OTR cDNA was 4.1kb, encoding 389 aminoacidspolypeptide belongs to the 7 transmembrane receptor family. OTRmRNA was highly upregulated (~300-fold) in term myometriumcompared with non-pregnant myometrium. OTR gene spans 17kb,locates on the chromosome 3 (3p26.2) and contains 3 introns and 4exons. Computer analysis indicated several consensus transcriptionfactor-binding DNA sequences, such as for SP-1, NF-IL6 and Stat 3. Gelshift assay revealed term myometrium contains at least 2 apparentnuclear proteins which upregulated in term uteri. One protein, US-1binding protein, was partially purified by batch method and themolecular weight is 70kDa. Another protein, cloned by yeast one hybridsystem, is a human homologue of Maf F and no transactivation activityto the OTR gene. Conclusions: We have clarified the molecular structureand mechanism of OTR expression in human pregnant uterus.

P4.16.04EFFECT OF FOLATES (LEVOFOLINIC ACID) TREATMENT ONHOMOCYSTEINE PLASMA LEVELS IN A GROUP OF HEALTHYYOUNG WOMEN DISTRIBUTED BY C677T GENOTYPES OF THEMTHFR POLYMORPHISM.M. Gallo * , E. Fabre**, MJ. Gaitan***, E. Muñoz***, R. Gonzalez deAgüero**, P. Muñoz-Rodríquez***, M. Ruiz***.and A. Reyes-Engel***,(*) Dept, OB-GYN. University Hospital “Carlos Haya”. Malaga. Spain(**) Dept. OB-GYN. University Hospital “Lozano Blesa”. Zaragoza.Spain(***) Dept. Molecular Biology. School of Medicine. Malaga. Spain.

Introduction: High plasma homocysteine levels have been associatedwith Neural Tube Defects (NTD), recurrent early fetal loss, placentalabruption and the C677T polymorphism in themethylenetetrahydrofolate reductase (MTHFR) gene. PericoncepcionalFolates treatment is recommended worldwide to prevent NTD.Objectives: To evaluate the homocysteine response in function of thegenotypes (CC,CT and TT) in healthy women treated with Levofolinicacid.Study Methods… 26 healthy women with a mean age of 22 years wereincluded in this descriptive study. All cases following no special diet, noprevious pregnancy and no previous treatment with folates, B12 vitaminand anti-folic drugs. Allsubjects received 5 mg/day orally administeredLevofolinic acid during 4 weeks Homocysteine levels at –2 days, +2, +5,+10, and +28 days, were analyzed by HPLC with electrochemicaldetection. C677T genotypes were determined by PCR and restrictionenzyme analysis.Results: There is a dramatic decrease in homocysteine levels betweendays –2 and +2 (p<0.001) and remains until day +28. The threegenotypes CC, CT and TT showed a significant decrease inhomocysteine levels (p<0.003, p<0.001 and p<0.05 respectively,although the most significant difference was observed among TTwomenbetween days –2 and +28. This could be due to higher homocysteinelevels at –2 day related to T allele.Conclusions: Levofolinic acid produces a decrease in homocysteinelevels irrespective of the studied genotypes. The drug showed highestefficacy at day 2 after treatment. Related factors such as homocysteine


levels before treatment and C677T genotypes could have influence onthe results.

P4.16.05EFFECT OF TAXIMOFEN ON THE EXPRESSION OFPROLIFERATIVE CELL NUCLEAR ANTIGEN (PCNA) IN THEEPITHLIUM AND STROMA OF FIBROADENOMAS IN WOMENDURING MENACMEJ.R.M. Bernardes Jr ., M.T. Seixas, L.C. Marinho, G. Rodrigues de Lima,E.C. Baracat, L.H. Gebrim, Dept. of Gynecology, Federal University ofSão Paulo, São Paulo, Brazil.

Objectives: The aim of the study was to investigate the effect ofTamoxifen on the proliferative activity of both the epithelium and thestroma of fibroadenomas in women during menacme following theadministration of 10 and 20 mg/day during 22 days.Study Methods: 41 females with fibroadenoma were selected for arandomized double-blind trial. They presented regular menstrual cyclesand had neither received hormones nor become pregnant 12 monthsprior to this study. Patients were divided in three groups: A (n=15;placebo), B (n=13; 10 mg/day) and C (n=13; 20 mg/day). The treatmentwas initiated on the 1st day of their menstrual cycle, and the surgerieswere performed on the 22nd day. Estradiol, progesterone and steroidhormone binding globulin (SHBG) were measured twice. The firstmeasurement was performed on the 22nd day of the previous menstrualcycle and the second one on the occasion of the surgery. The mammarytissue was fixed in 10% formaldehyde solution and stained with HE andthen processed through immunohistochemical reaction (PC-10 DAKOcode number M879 Denmark A/S). The immunoexpression of theproliferative cell nuclear antigen (PCNA) of at least 500 epithelial and500 stromal cells was evaluated. Such cells were interactively countedusing Kontron Imaging System KS-300 computerized analysis system,with 400X magnification.Results: As to the PCNA expression in the epithelium of fibroadenomas,the average percentage of stained nuclei in groups A, B and C was 25.2(standard error = 3.0), 19.3 (standard error = 2.9) and 18.0 (standarderror = 2.5), respectively. However, no significant difference was foundin the variance analysis of these data (p=0.168). Upon the study of thestroma of fibroadenomas, the average percentage of stained nuclei foundin groups A, B and C was 32.4 (standard error = 3.3), 23.2 (standarderror = 4.6) and 18.4 (standard error = 3.0), respectively. The varianceanalysis (p=0.031) and Fisher’s multiple comparison test (1.39; 26.67confidence interval) confirmed that the number of PCNA expressingnuclei in the stroma was significantly lower in group C (20 mg/day)when compared to group A (control). However, there was no significantdifference between groups (10 mg/day) and C (20 mg/day).Conclusion: Thus, it was concluded that the administration of 10 mg/dayand 20 mg/day of tamoxifen reduced the PCNA expression in the stromaof fibroadenoma after 22 days of treatment; however, its effect wasstatistically significant only in the stroma when doses of 20 mg/day wereadministered.

P4.16.06EXPRESSION OF APOPTOSIS REGULATORY PROTEIN BCL-2AND BAX IN HUMAN FOLLICLES OF POLYCYSTIC OVARYSYNDROMELiang Xiaoyan , Zhuang Guanglun,Zhou can quan, Dept. OB/GYN, IVFcenter, First Affiliated Hospital of Sun Yat-sen University of MedicalSciences, Guangzhou , P. R. China.

Objectives: The increased follicular atresia and anovulation are featuresof polycystic ovary syndrome (PCOS).Apoptosis-related genes appear tohave a role in follicular atresia. There is some animal evidence tosuggest that dysregulation of these genes may result in an attenuatedatresia resulting in polycystic ovaries. The arm of the study was toinvestigate the expression and implication of the apoptosis regulatoryprotein bcl-2 and bax in every classes of primary follicles of PCOS.Study Methods: The study group consisted of 18 PCOS and 13 normalsubjects collected from March 1997-May 1998, Total numbers offollicles from their ovaries were 240,which were divided into fourgroups based on diameter of the follicles. Measurement of the apoptosisregulatory protein bcl-2 and bax were taken in usingimmunohistochemical method and determining the Grey value by

Germany Konton Ibas Software. Analysis of variance was used toperform SPSS Package.Results: A total of 240 follicles were evaluated. There were theapoptosis regulatory protein bcl-2 and bax in all primary follicles. Thebcl-2 and bax protein expression in every classes of primary folliclesfrom PCOS groups was not significantly different. When the diameter ofthe follicle reach to 60-120mm,Bcl-2 expression was higher in PCOSthan that in control group (p<0.05).Bax expression was increasedmarkedly following by primary follicles growth in PCOS, it presenteddecreasing when the diameter of follicle>120mm, resemble as the controlgroup. Bcl-2/Bax Grey ratio was smallest in the diameter of the follicle>=120mm.Conclusions: The bcl-2 and bax protein expression in every classes ofprimary follicles had presented. There were significantly higher inPCOS than that in normal ovary (60-120mm). The bcl-2 and bax proteinexpression was increased following follicle growth in PCOS and controlgroups. When the diameter of follicle >= 120mm, the apoptosis wereweakened, the follicle growth accelerated. This study suggests thatbefore primary follicles, the expression of apoptosis regulatory proteinbcl-2 and bax were normal in PCOS.

P4.16.07EXPRESSION OF ARYLHYDROCARBON RECEPTORMESSENGER RNA IN THE HUMAN ENDOMETRIUMD. Nakayama , S. Sugita, N. Hamaguchi, T. Samejima, H. Masuzaki, T.Ishimaru, Dept. OB/GY, Nagasaki Univ. Sch. Med., Nagasaki, Japan

Objectives: Animal studies have demonstrated that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with the developmentof endometriosis. Many of the biochemical and toxic effects of dioxinand dioxin-like substances appear to be mediated by means of thearylhydrocarbon receptor (AhR), which has a high affinity for dioxin.We studied the expression of AhR mRNA in the human endometrium.Study Methods: We collected 12 urerine specimens by hysterectomy inpatients treated for uterine myoma, adenomyosis, dermoid cyst of ovaryor cervical intraepithelial neoplasia. The age of the patients ranged from38 to 56 years. Eleven patients had regular menstirial cycles and apatiens was postmenopausal. We extracted total RNA from theendometial tissue and analyzed expression of AhR mRNA by northern-blot hybridization.Results: The AhR mRNA of 5.5 kb was detected in endometirium of allthe 11 patients with regular menstrual cycles. The level of expressionwas low in early proliferative phase, gradually increased in mid to postproliferateve phase and was maximum at mid secretory phase. Low levelexpression of AhR mRNA was also detected in the endometirum of postmenopausal woman.Conclusion: Our results showed that AhR mRNA was expressed inhuman endometrium and the level of expression seemed to be associatedwith menstrual cycle.

P4.16.08EXPRESSION OF CRF AND CRF-R TYPE I MESSENGER RNA INTHE RAT FETAL BRAIN AND ITS RESPONSIVENESS TO LPSCHALLENGEA. Yamanaka , S. Akira, T. Ishihara, M. Seto, T. Takeshita, T. Araki, J.Imaki, Dept. OB/GYN, Dept. Anatomy, Nippon Medical School, Tokyo,Japan

Objectives: In this study, we investigated the expression ofcorticotropin-releasing factor (CRF), CRF receptor type I (CrF-RI)mRNA in the brain of fetal rats and their response to lipopolysaccharide(LPS) stress compared to that in controls using in situ hybridization.Study Methods: Pregnant rats on day 20 of gestation were injected withLPS intraperitoneally. After 3 hours they were deeply anesthetized withpentobarbital and perfused with ice-cold 4% paraformaldehyde. Thebrains were placed for 2 days at 4°C in the same fixative containing 10%sucrose. Frozen sections were cut with a sliding microtome, CRF andCRF-RI mRNA in the paraventricular nucleus (PVN) weresemiquantified after in situ hybridization.Results: CRF mRNA expression was localized in the PVN of thematernal and the fetal brains, and it was increased by LPSadministration. CRF-RI mRNA expression was widely distributed in thecortex of the maternal and the fetal brains, however, it was not detectedin the PVN of them. By LPS administration, CRF-RI mRNA was


increased in the PVN of the maternal brain, but was not changedsignificantly in the PVN of the fetal brain. In conclusion, CRF and CRF-RI mRNA were already expressed in the rat fetal brain by day 2- ofgestation. In the rat fetal brain, LPS challenge increased CRF mRNAexpression but didn’t change CRF-RI mRNA expression in the PVN.Conclusion: It is suggested that CRF upregulates its own receptormRNA in the PVN of maternal brain, but the fetal brain doesn’t yet havethis mechanism.

P4.16.09FACTOR V LEIDEN IN PATIENTS WITH RECURRENT FETALLOSSM. Drabkova 1, M. Vojtiskova2, A. Vasku3, T. Burnog1, P. Janku1, K.Kankova3 1Dept. of Obstet. Gynecol., 2Dept. of Genetic, 3Institute ofPathological Physiology, Medical Faculty, Masaryk University, Brno,Czech Republic, Europe.

Objectives: To determine the association of Factor V Leiden mutation(FVL) frequency and recurrent fetal loss.Study Methods: A total of 445 women 17 to 45 years old were includedin this case-control study. We examined the prevalence of the pointmutation in the factor V gene (R 506 Q or Leiden). 138 unselectedwomen with a history of one or more (mean 2.5, range 1 to 5)spontaneous abortion or stillbirth of unexplained etiology. Mutationanalysis was performed by polymerase chain reaction and restrictionanalysis with Mln I. The control group were 307 unselected women whogave birth at our department . The significance of the difference in bothgroup was tested by the chi-square test.Results: The frequency of the FVL in the case group was 14.5 %(20/138), in the control group 7.0 % (22/307) (p>0.005). There were nodifferences in the group of the women with one abortion and controlgroup (p= 0.121). The frequency of FVL in the group with two abortionswas 14.0 % (10/72) (p>0.005), in the group with three and moreabortions 18.0 % (8/45) (p>0.005). Significant increase of homozygousgenotyp was found in the case group, especially in the group of womenwith repeated loss.Conclusions: population Czech women, a statistically significantassociation of the Leiden mutation with recurrent fetal losses was found.The risk for recurrence of fetal loss tended to be greater in homozygouscarriers.

P4.16.10FLUORESCENCE IN SITU HYBRIDIZATION ON UNCULTUREDAMNIOCYTESO.Torok (a), I. Zsupan (a), Zs. Buezico (a), R. Adany (b), M.Balazs (b)(a) Dept. OB/GYN(b) Dept. of Hygiene(c) University of Debrecen, Hungary.

Objectives: To demonstrate the advantages of FISH in prenatal diagnosisof aneuploidiesStudy Methods: In an initial study the results of FISH on unculturedamniocytes were compared with standard karyotyping in 178 secondtrimester cases. Subsequently FISH was applied in cases undergoingamniocentesis for abnormal ultrasound finding or if the amniocentesishad to be repeated for the suspicion of low-level true mosaicism inculture of amniocytes. The results were controlled by standardkaryotyping,Results: The hybridization was successful in 98% of cases and a goodcorrelation was found in between FISH and the standard cytogeneticmethod. In 7 fetuses with major structural anomalies and in 4 cases withsevere IUGR the correct diagnosis could be set up by FISH two daysafter the ammocentesis. In 5 samples with the suspicion of truemosaicism at least 200 interphase ammocytes could be scored usingFISH. In 2 cases mosaicism of "trisomy 20" and "21" could be ruled outwith high probability. In 2 cases FISH supported the presence of lowlevel mosaic "trisomy 21" and "X" monosomy. Conventionalcytogenetic analysis in the second amniotic fluid specimen confirmedthe FISH findings. In one case contrary to FISH standard karyotypingfrom the second amniotic fluid sample did not reveal mosaicism.Conclusion: Our results suggest that in case of severe IUGR andstructural anomalies detected by ultrasound the rapid result of FISH canbe considered for further management decisions. In the diagnosis ofchromosomal mosaicisms the role of FISH needs further examinations.

P4.16.11MOLECULAR BIOLOGICAL CHARACTERIZATION OF SOLUBLEPLACENTAL TISSUE PROTEINS: PP13/GALECTIN,PP17b/MANNOSE-6-PHOSPHATE RECEPTOR TRANSPORTERAND PP18/BRANCHED-CHAIN AMINO ACIDAMINOTRANSFERASEN.G. Than , Dept. Biochemistry, University of Pécs, Pécs, HungaryH. Bohn, Behringwerke AG, Marburg/Lahn, GermanyG.N. Than, Dept. OB/GYN, University of Pécs, Pécs, HungaryB. Sümegi, Dept. Biochemistry, University of Pécs, Pécs, Hungary

Objectives: S o lu ble pl a c e nt a l ti s s u e pr o te i ns (P P s ) ar e syn the s i z e d in in c r e a s e d am oun ts du r in g pr e gna nc y and pla y an im p or ta n t rol e in the de ve lop m e n t of the fe tu s and pl a c e nt a or in the ma in te n a nc e of pr e gn a nc y.F r om th e 26 dif f e r e n t PP s fo ur ha v e be e n re c e nt ly cl one d and ch a r a c t e r i z e d by our re s e a r c h te a m .Study Methods: cDNAs encoding for PPs were isolated from a placentalcDNA library with monospecific antisera and sequence analyzed. RNAexpression in different tissues were examined by Northern-blot analyses.PP contents in human sera and in different human healthy and tumoroustissues were detected by chemiluminescence Western-blot analysis.Structural and functional characteristics of PPs were also investigated.Results: We ha ve cl on e d and se qu e nc e d cD N A s enc o din g for PP 13 , PP 18 a n d tw o me m b e r s of the PP 1 7 pr o te i n fa m ily (P P 1 7a , PP 17 b) . By our r e s u lts PP 13 is a ne w me m b e r of th e _- g a la c t os i de bi ndi ng S- typ e ani m a l le c t in (ga le c ti n) fa m il y, PP 17b tu r n e d out to be a ma nn os e - 6 - ph os p ha te r e c e pto r (M P R) ca r go pr ote in wh ile PP 18 is a br a nc he d- c ha i n am i no ac idtr a n s a m ina s e (BCA T ) . Be s id e s fu nc t io na l st ud ie s , se c ond a r y and te r ti a r y s t r u c tu r a l cha r a c t e r is t ic s of the pr ote ins ha ve be e n co m pu te d. Spe c i f ic e x pr e s s ion pa tt e r n s of the PP s in di f f e r e n t he a lth y and tu m o r ou s tis s ue s ha v e be e n de te c te d, as we ll as th e pos s ib ili ty of se r om on ito r iz a t ion of ce r v ic a lc a r c ino m a pa tie nts with PP 17 - a s s a y ha s tur ne d up.Conclusions: Seemingly PPs have oncodevelopmental functions:PP13/galectin may be involved in cell-cell and cell-matrix interactions;PP17b/MPR transporter may function in HSV-2 infection and cervicalcancer genesis; PP18/BCAT may a c t in the cell cycle r e g ul a t e d by th e c - m y c proto-oncogene.

P4.16.12PATERNITY IN PRENATAL PERIODJ. Jovanovic-Privrodski (1) , S. Romac (2), Z. Belopavlovic (3), M.Bogavac (3), A. Krstic (1), V. Manasijevic (2)Institute of Child and Youth Health Care, Novi Sad, Yugoslavia.Institute for Biology, Belgrade, Yugoslavia.University Clinic of Obstetrics and Gynecology, Novi Sad, Yugoslavia.

The problem of paternity can exist in prenatal period like in other partsof life. This problem can be solved successfully using the mostfrequently used genetic marker – DNA probe. Most frequently the bloodtest is used for analyzing DNA, but sometimes the other genetic markerslike chorion villi and amnion in prenatal period or (post-mortem) haircan be used as well.In this paper we describe prenatal exclusion of paternity using DNA. Apregnant women (20 weeks of pregnancy) came to visit geneticcounseling. She wanted to solve the problem of paternity of her fetus(she had two partners but the blood could be gotten only from one ofthem). The fetal blood was gotten by cordocenthesis. Six gene locuseswere determined using AmpliType PM+DQAI kit for humanidentification DNA. In this case paternity for the presumed father wasexcluded because the fetus had two gene locuses, but the presumedfather did not.

P4.16.13PHOSPHORYLATED INSULIN-LIKE GROWTH FACTOR (IGF)–BINDING PROTEIN-1 (IGFBP-1) INHIBITS WHILENONPHOSPHORYLATED IGFBP-1 STIMULATES IGF-I-INDUCEDAMINO ACID UPTAKE BY CULTURED TROPHOBLAST CELLSM. Momoi , K. Tsuchiya, M. Iwashita, Y. Nakamura, Dept. OB/GYN,Kyorin University, School of Medicine, Tokyo, Japan

Objectives: IGFBP-1 has been found to be phosphorylated and four tofive phosphorylated forms (pIGFBP-1) and one nonphosphorylated form


(npIGFBP-1) have been identified in various biological fluids. Toelucidate the biological effects of these phosphoisoforms, we studiedeffects of pIGFBP-1 and npIGFBP-1 on amino acid uptake induced byIG-I using cultured trophoblast cells.Study Methods: IGFBP-1 was purified from mid term amniotic fluidusing ammonium sulfate precipitation followed by phenyl-Sepharosecolumn. Purified IGFBP-1 was further purified by DEAE-cellulosecolumn in which pIGFBP-1 and npIGFBP-1 were separated.Trophoblast cells obtained from term pregnancy were incubated withindicated concentration of pIGFBP-1 or npIGFBP-1 for 24 hr andfurther incubated with 10 nM IGF-I for 3 hr. Cells were then incubatedwith 3H-a-amino isobutyric acid (3H-AIB) for 30 min. Cells weresolubilized and the radioactivity in cells was counted by a scintillationcounter.Results: Both pIGFBP-1 and npIGFBP-1 alone had no effect on 3H-AIBuptake, however, pIGFBP-1 inhibited IGF-I stimulated 3H-AIB uptakewith ED 50 of 0.26 nM while npIGFBP-1 potentiated 3H-AIB uptakewith ED50 of 0.27 nM. Maternal IGF-I promotes fetal growth bystimulating nutrients transport in the placenta.Conclusions: As shown in this study, pIGFBP-1 inhibits whilenpIGFBP-1 stimulates this IGF-I action in the placenta. Thus, it issuggested that IGFBP-1 phosphoisoforms are also involved in fetalgrowth by modulating IGF-I action in the placenta.

P4.16.14PRENATAL DETERMINATION OF FETAL SEX AND RH DSTATUS BY DNA ANALYSIS OF MATERNAL PLASMAK. Hiraki , H. Masuzaki, D. Nakayama, T. Ishimaru, Dept. OB/GYN,Nagasaki Univ Sch Med, Nagasaki, Japan

Objectives: The recent demonstration of fetal DNA in maternal plasmaraises the possibility that fetal DNA analysis may be possible with theuse of maternal plasma, without cell separating techniques. We reportuse of PCR to detect fetal Y chromosome and Rh D gene from maternalplasma.Study Methods: We used QIAamp DNA Blood Mini Kit to extract DNAfrom maternal plasma. We used conventional PCR to amplify a Y-specific DNA sequence in plasma DNA samples from 26 pregnantwomen who had a gestational age of 14 to 41 weeks, and a Rh Dsequence from three Rh D-negative pregnant women of 14 to 34 weeks.Results: Y sequences were detected in all of the 11 maternal plasmasamples from women bearing male fetuses. None of the 15 womenbearing female fetuses had positive results. The plasma samplesobtained from three Rh D-negative women were positive for Rh D PCRanalysis, which were concordant with the results of serologic analysis ofthe neonates.Conclusions: Prenatal determination of fetal sex and Rh D status withthe use of maternal plasma can be performed rapidly and reliably. FetalDNA in maternal plasma may be a valuable source of material fornonivasive prenatal diagnosis.

P4.16.15PRELIMINARY RESULTS ON THE REGULATION OF THEHUMAN FSH RECEPTOR PROMOTER ACTIVITY BY SELECTEDE2F FAMILY MEMBERSL. Jakowicki (1), L. Putowski (1), C. Lee (2), W. Schillings (3),P. Reddy (2)(1) Dept. Surgical Gynecology, University School of Medicine, Lublin,Poland.(2) Fels Institute for Cancer Research and Molecular Biology,Philadelphia, PA, USA.(3) Women’s Health Care Associates Newton, NJ, USA.

Objective: Since E2F’s transcriptional factors regulate expression ofseveral proteins involved in cell cycle regulation we underwent studiesconcerning the influence of this factor on he FSH receptor promoteractivity.Study Methods: DNA fragment containing FSH receptor promoter wassublcloned into pGL3 vector. Construct alone or together withexpression vectors for E2F factor was transfected into cultured CHOcells. Additionally pRL-CMV vector was co-transfected in order tonormalize transfection efficiency. Promoter activity was estimated bythe measurement of firefly luciferase activity in cell lyzate. Obtained

results were normalized to the renilla activity driven by co-transfectedpRL-CMV vector.Results: E2F1 decreased promoter activity (0,43±0,001). E2F4 andE2F5 increased promoter activity (1.29±0.04 and 1.66±0.20).Conclusions: Surprisingly increase (1.66 fold) in the activity caused byE2F5 is not so dramatic as it was noted previously for rat FSH-Rpromoter under the same condition. Lack of the E2F binding site in thehuman FSH-R receptor promoter, whereas it is present in rat gene, ispossible explanation of these differences. E2F1 decreases the FSH-Rpromoter activity. It is more likely, the influence of E2F familymembers on human FSH-R promoter seems to be an indirect effect ofthis proteins.

P4.16.16RELATION BETWEEN BIRTH WEIGHT AND GENETICPOLYMORPHISM OF THE INSULIN GENE REGION INJAPANESEY. Iitsuka , H. Osada, H. Sekimoto, K. Masuda, K. Seki, S. Sekiya,Dept. OB/GYN, Chiba University School of Medicine, Chiba, Japan.

Objective: Fetal development depends not only on the intrauterineenvironment provided by the mother, but is closely associated withgenetic factors from both parents. We examined the relation betweenbirth weight and gene polymorphism in the IDDM2 region including theinsulin gene in Japanese.Study Methods: We enrolled 211 neonates delivered to Japanesemothers after 36 weeks of normal pregnancy. DNA was extracted fromthe umbilical blood and also maternal peripheral blood cells.Polymorphic regions in the insulin-like growth factor II (IGF2) andtyrosine hydroxylase (TH) genes adjacent to the insulin gene wereamplified by PCR. Birth weights were converted into standard deviationunit (SDU) based on gestational week, sex and para status.Results: For IGF2 polymorphism, SDU of birth weight were notsignificantly different among the 3 genotypes (-/-,+/-,+/+). For THpolymorphism the frequencies of neonates with alleles 6 to 11 were25.9, 24.9. 4.7, 39.8, 4.5 and 0.3%, respectively. Allele 10 has beenreported to have strong linkage with class III allele that is a repeatingsequence upstream of the insulin gene. The SDU was significantlyhigher in individuals with allele 10 than other alleles (p=0.016). SDUwere significantly different between neonates with and those withoutallele 10 in the genotype (p=0.0007). When classified further by parentalorigin of allele 10, a significant difference in SDU was observed onlybetween paternal derived allele 10 (+) and allele 10 (-) groups(p=0.0027).Conclusion: This study showed that gene expression of the insulin generegion is one of the factors that regulate development in fetal stage.

P4.16.17RELATIONSHIP BETWEEN GESTATIONAL AGE ANDFREQUENCY OF FETAL TROPHOBLASTS AND NUCLEATEDERYTHROCYTES IN MATERNAL PERIPHERAL BLOODA. Tan (1) , T-H. Lim (1), V.H.H. Goh (2), (1) Singapore GeneralHospital, Outram Road, Singapore, 169608, (2) National UniversityHospital, Singapore.

The relationship between gestational age and frequency of fetal cells inthe maternal blood was studied in order to determine the optimal timefor cell recovery. Immunomagnetic colloid system was used to enrichnucleated erythrocytes (NRBCs) and trophoblasts from 20ml of maternalblood obtained between 9 and 35 weeks gestation (N=41). Nestedpolymerase chain reaction (PCR) for the Y chromosome of enrichedNRBCs and trophoblasts showed decreasing negative predictive valueswith increasing gestational age. The sensitivity and th overall frequencyfor correct fetal gender diagnosis were the lowest in the third trimester.Fluorescence in situ hybridisation (FISH) using XY DNA-specificprobes was used to determine the fetal gender of trophoblasts-enrichedfraction. The fetal origin of enriched NRBCs was determined usingsimultaneous immunophenotyping for fetal hemoglobin and FISH withXY probes. The mean number and mean percentage purity for both fetaltrophoblasts and NRBCs showed decreasing values with increasinggestational age. However, statistical analysis showed no relationshipbetween gestational age and frequency of fetal cells even though morefetal cells tend to exist during the first trimester. Nevertheless, the first


trimester appears to offer the most optimal time for fetal cell recoveryfrom maternal blood for the purpose of prenatal diagnosis.

P4.16.18SOMATIC MUTATIONS AND GENETIC POLYMORPHISMS OFTHE PPPR1R3 GENE IN PATIENTS WITH SEVERAL TYPES OFCANCERSS. Takakura (1) , A. Okamoto (2), J. Yokota (1), T. Tanaka (2), T. Kohno(1), T. Yamada (1), K. Shimizu (1), S. Ohwada (1), (1)National CancerCenter Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo, Japan,1040045, (2) Jikei University School of Medicine, Tokyo, Japan.

Objective: Recent studies on PTEN and PPP2R1B (a regulatory subunitof PP2A) mutations in human cancer indicate that aberrations ofintracellular signaling pathways via protein phosphatases (PP) areinvolved in human carcinogenesis. We examined genetic alterations ofthe PPP1R3 gene located at chromosome 7q31, which encodes theregulatory subunit 3 of PP1, in various types of human cancers to assesthe role of this gene in human carcinogenesis.Study Methods: All of coding exons of PPP1R3 were examined formutations and polymorphisms in 104 cancer cell lines and 192 primarytumors by PCR-SSCP and direct sequencing.Results: Sixteen mutations of the PPP1R3 gene were detected in 9 of104 cancer cell lines and 5 of 192 primary tumors, and they occurred ina subset of ovarian cancer, lung cancer, colorectal cancer, and gastriccancer. Sixteen mutations detected consisted of 3 nonsense mutations,10 missense mutations, 2 silent mutations and a mutation in intronsequence. Seven novel single nucleotide polymorphisms (SNPs)associated with the substitution of amino acids were also identified incancer patients, in addition to three known nonsynonymous SNPs,including three previously reported ones as having an impact on thesusceptibility to insulin resistant disorders.Conclusions: Differences in the activities and properties of multiplePPP1R3 proteins, which are produced in human cells due to variablesomatic mutations and genetic polymorphisms in the PPP1R3 gene, canbe involved in human carcinogenes

P4.16.19b2-GLYCOPROTEIN AND IMMUNE COMPLEXES LOCATION INPLACENTAL TISSUES OF WOMEN WITH REPEATEDPREGNANCY LOSSG.L.Gromiko, L.B.Zubjitskya, I.P.Pavlov Medical Univercity,D.O.Ott Institute of Obstetrics and Gynecology, St.Petersburg, Russia

Objectives: To study the consequence of antiphospholipid antibodies(aPL) on pregnancy complications we investigate localization of b2-glycoprotein I (b2-GP I) in placental tissues of women with recurrentpregnancy loss. Having a regulatory role in blood coagulation, b2-GP Iappear significantly related to most frequent complications (thrombosisand fetal loss) in patients with aPL.Study Methods: 46 samples of placentae and blood sera of women withrepeated pregnancy losses were investigated. Method of fluorescentantibodies in indirect modification with sera of women that were testedon the presence of anti-cardiolipin antibodies on bovine heart was used.For elimination of cross-reacted antibodies to bovine cardiolipin andsave antibodies to b2-GP I tested sera were adsorbed by standartcardiolipin antigen. Placentae cryostat sections of women were treatedfor detecting complement-fixing immune complexes (IC). In parallelafter washing, placentae sections were treated by adsorbede seracontaining b2-GP I.Results: Specific luminescence of IC was detected in 91% of women,aPL in 78%. Luminescence was detected on membrans ofsyncytiotrophoblast and on endothelium of chorion vessels. Thetopographical identity of a luminescence of complement-fixing IC isestablished with sites of a luminescences, obtained at handling washingplacentae sections by adsorbede sera.Conclusions: We assume presence of the b2-GP I in a structure of IClocalized in a placental tissue. Being an antigenic target of aPL, b2-GP Ican be immediately connected to development of placental thrombosis

P4.16.20THE APPLICATION GENNO-ENGINEERING a2b- INTERFERON INTHE TREATMENT NONSPECIFIC INFLAMMATORY DISEASESOF WOMEN’S REPRODUCTION ORGANST.V. Bannycova (1), T.N. Dyomina (2), G.D. Mysuna (2),(1) Donetsk State Regional Centre Gruarding Maternity and

Childhood, Donetsk, Panfilova, Ukraine.(2) Donetsk State Medical University, Donetsk, Illycha, Ukraine.

Objectives: The aim of given research was the study of the effect genno-engineering a2b - interferon during treatment nonspecific inflammatorydiseases of women’s internal genitals.Study Methods: It was conducted clinic-immunology investigation 108women with nonspecific inflammatory diseases of ovaries and of uterineappendages. The 70 patients had immunocorrection therapy by“Laferon” (preparation a2b - interferon), the 40 patients –had thetraditional antibacterial treatment.Results: The suppresion cell and humoral links of the immunity (thedeficit T-cell, the dysimmunoglobulynemia), the factors of thenonspecific stability (the reduction of metabolic potence leukocytes) theinterferon-deficit state (the higher level serum interferon’s, the reductionof the production the direct a and g - interferon) was revealed in patientsof two groups. It was marked the normalization of functions theimmunocompetents system’s in the group, who was treated by the“Laferon.” The convalescence was coming in 97.1% of the patients, itwas marked improvement of state considerable 2.9% of patients. Thepositive dynamics of the index immunity wasn’t marked in the patient,who had antibacterial therapy: 72.5% women has convalescence; thestate has improved in 20%; the therapy was not effective for 7.5% of thepatients.Conclusions: The using a preparation a2b - interferon to allow back tonormalcy the functions of the immunocompetent systems’ and to raisethe effectiveness therapy nonspecific inflammatory diseases of internalgenitals females.

P4.16.21THE CORRECTION OF THE HORMONAL INSUFFICIENCY OFTHE OVARIES WITH THE TRANSPLANTATION OF THEOVARIAN TISSUEL. Matitsina , Dept. PED/AD GYN, Donetsk regional center of Maternityand Child Protection, Donetsk, Ukraine.

Objective: The task of our invention is the correction of the hormonalinsufficiency of the ovaries by the transplantation of the culture of theovarian tissue cells.Study Methods: A new thing of this method is that the culture of thecells of the ovarian tissue is used as a transplant. The safety and thefunctional ability of the transplant is a main condition of the successfulhormonal correction of the sufficient function of the ovaries.Results: The cells of the fetus ovarian tissue, which do not have anantigen activity, have not undergone the rejection, function on beingintroduced into the organism, producing estradiol and progesterone, inconnection with this it appeared a possibility with the help ofallotransplantation to correct the insufficiency of the ovarian function.Effective functioning transplanted culture of the ovarian tissue andabsorption of estrogens, produced by it, is possible due to the increasedadequate and sufficient permeability through the walls newly formedcapsule.Conclusions: Thus, the quality of the introduced material was improved,the permeability throng the formed capsule was increased, the durationof the functioning of the transplant cells was increased, the culture in theform of suspension was introduced and activation of blood supply roundthe formed capsule, contributing to the formation and appearance ofestrogens, lead to the start of the mechanisms of H-H-O regulation andinitiation of extragonadal synthesis of estrogens and progesterone.

P4.16.22THE ROLE OF AMNIOTIC FLUID INTERPHASE FISH ANALYSISIN PATIENT MANAGEMENTW.C. Leung (1,2), E.J.T. Winsor (1), G. Seaward (1), R. Windrim (1),D. Chitayaat (1), G. Ryan (1)(1) University of Toronto Perinatal Complex, Toronto, Ontario,

Canada.(2) Dept. OB/GYN, University of Hong Kong, Hong Kong, China.


Objectives: To determine the value of amniotic fluid FISH analysis inthe management of patients at increased risk for fetal aneuploidies.Study Methods: Results of 306 amniotic fluid interphase FISH analysesperformed (Oct. 1995 to April 1999) were retrospectively reviewed.Commercially available chromosome-specific DNA probes forchromosomes 13, 18, 21, X and Y were used. The results of FISH werecompared to standard karyotype analysis in all cases. Indications foramniocentesis, gestational age at amniocentesis, clinical interventionsafter FISH results as well as interventions after final culture reports wereanalyzed.Results: There were 244 (80%) normal FISH results, 52 (17%) abnormalresults (T21=25, T18=11, T13=4, sex chromosome aneuploidy=6,triploidy=4, others=2) and 10 (3%) were inconclusive. There were nofalse positive or false negative results. The presence e of multipleultrasound abnormalities gave the highest yield of abnormal FISHresults. Of the 52 abnormal FISH results, 33 women (63%) elected toterminate the pregnancy based on the FISH result, and 30 of whom(91%) also had ultrasound abnormalities: 22 of which were majorabnormalities. 3 of the 33 had amniocentese performed close to 24 wksgestation, the accepted upper limit for abortion of non-lethal anomaliesin Canada. The final culture reports revealed an additional 14 structuralchromosomal abnormalities that were not detectable by the FISH probesused, and provided results in the 10 inconclusive cases.Conclusions: In the presence of ultrasound abnormalities, patientmanagement decision, including pregnancy termination, may reliably bebased on abnormal FISH results without waiting for the final culturereports. However, this approach does not replace standard karyotypeanalysis, which detects a significant number of structural chromosomalabnormalities not detected by interphase FISH.

P4.16.23THYROID HORMONE RECEPTOR GENE EXPRESSION IN FIRSTTRIMESTER HUMAN FETAL BRAIN: COMPARISONBETWEENBRAIN MEDULLA AND SPINAL CORDJ.Iskaros (1) , M. Pickard (2), I.Evans (2), A. Sinha (2), (1) UCLH,Huntley Street, London, United Kingdom, WC1E 6AU, (2) Division ofMolecular Endocrinology, UCL Medical School, London, UK.

Objective: To investigate the presence of thyroid hormone receptorsisoforms in the medulla and compare the ontogenesis of gene expressionof c-erbAa and -b isoforms in different regions of the human fetal CNSby RT-PCR in first trimester human fetuses.Methods: Intact fetuses were obtained from surgical first trimestervoluntary termination of pregnancy (range 8-13 weeks post menstrual)under ultrasound guide. Samples were dissected immediately and storedon dry ice. This was approved by the local ethical committee. Braintissues without medulla (n=9), medulla oblongata (n=8) and spinal cords(n=13) samples were collected in good condition for analysis. TotalRNA was isolated, DNase-treated and reverse transcribed. PCR wasperformed using primer sets specific for c-erbAa1, -a2, -b1 and -b2isoforms, as well as 18S rRNA. Products were electrophoresed,visualized by ethidium bromide staining and captured by digital camera.Images were analysed using INH-6 soft ware for Apple Macintoshcomputer. Ontogenecity was assessed for the different isoforms inrelation to 18S rRNA.Results: Ontogenic increases were apparent for a1 and a2 isoforms in thebrain , the medulla and the spinal cord. Apart from the expectedproducts, a minor band was apparent in all samples amplified using thec-erbAa2 primer set. b1 on the other hand showed a different ontogenicpattern, with a an initial decrease in expression until 11 weeks followedby an increase until 13 weeks, whereas the spinal cord continued toshow a similar pattern to the a1 and a2 isoforms.Conclusion: Transcripts for a1,a2 and b1 TH nuclear receptors and non-TH binding variants are expressed in both the human fetal brain andmedulla as early as 8 weeks. If translation occurs, these proteins mayprovide a mechanism by which maternal TH can regulate genetranscription during first trimester brain development.

P4.16.24VEGF PRODUCTION IN LUTEINIZED HUMAN GRANULOSACELLS IN VITRO: IMPORTANCE OF EXTRACELLULAR CA2+

J. Neulen 1, H. Weich2, E. Wünsch1 1Univ. Clinic of Gyn.Endo./Reprod.Med., RWTH Aachen,Pauwelsstrasse 30, 52074 Aachen, Germany; 2GBF, Mascheroder Weg1,38124 Braunschweig, Germany

Introduction: Cytosolic and extracellular calcium (Ca2+) is expected toaffect VEGF mRNA expression and protein secretion in granulosa cells(Endocrinology, 139, 3606-3612, 1998). This study was designed toinvestigate effects of intracellular and extracellular Ca2+ and magnesium(Mg2+) on basal and hCG-stimulated VEGF synthesis.Materials and Methods: Human luteinized granulosa cells (GCs) wereobtained from follicular fluids of patients undergoing in vitrofertilization. After 24 h preincubation in M199 culture procedures werecontinued until day 3 or day 7 conventionally or in M199 supplementedwith or without physiological Ca2+ or Mg2+ concentrations. The cellcount of viable GCs remained constant irrespectively of the incubationregime. VEGF slot blot detection and protein qunatification aredescribed elsewhere (Mol. Hum. Reprod. 4, 203-206, 1998)Results: After 48 hrs of culture, there was no significant differencedetectable between the treatment regimes with or without any Ca2+

and/or Mg2+ concentrations for basal and hCG stimulated VEGF mRNAexpression and protein secretion. After 144 hrs without extracellularCa2+ and Mg2+ hCG-stimulated VEGF mRNA expression was reduced byabout 40%, whereas basal expression was not affected and VEGFprotein secretion declined by about 75% compared with physiologicalcontrol. For media supplemented with 100% Ca2+ exclusively, hCG-stimulated VEGF mRNA expression and protein secretion werecomparable with GCs grown in media containing 100% of both bivalentkations. If M199 was supplemented with 150% magnesium and 0%Ca2+, hCG-stimulated mRNA expression was decreased about 20%, andVEGF secretion was reduced about 45% compared to media withphysiological Ca2+ and Mg2+ content.Discussion: Prolonged incubation under Ca2+-free conditions resulted indepletion of intracellular Ca2+ stores which have to be refilled bytransmembrane Ca2+ influx in order to maintain LH receptor-mediatedeffects on VEGF production in GCs. Mg2+ cannot banish Ca2+ deficiencycompletely.

P4.16.25X CHROMOSOME DEFECTS AS A CAUSE OF IDIOPATHICFAMILIAL PREMATURE OVARIAN FAILUREMr Colin J Davis 1, Dr Rina M Davison2, Professor Charles H Rodeck1,Dr Gerard S Conway2

Depts. of Obstetrics and Gynaecology1 and Endocrinology2, UniversityCollege Hospital, London.

Objectives: The aim of the study was to characterise the patterns ofinheritance of familial premature ovarian failure (POF) and comparethem to published pedigrees. We hypothesised that, if X chromosomedefects were responsible for the inheritance of familial POF then maleoffspring might not be viable leading to a preponderance of females inaffected pedigrees.Study Methods: We characterised the pattern of inheritance of 41 casesof familial POF and compared them to published pedigrees. In 11families a clear genetic association of POF could be identified. Theremaining 30 families were classified as idiopathic. We calculated thefemale to male sex sibling ratio for each family.Results: The mode of inheritance included autosomal recessive,dominant and X-linked dominant patterns. We found a female/male sexratio of 2:1 in our idiopathic group of 30 families which was statisticallysignificant on Chi squared analysis. This was mirrored in the publishedseries of 13 families with idiopathic POF. There was no significantfemale sex ratio in the autosomal causes of POF.Conclusions: Familial idiopathic ovarian failure has a femalepreponderance compared to known syndromes causing POF and may bean indication of an occult X chromosome defect. The screening for Xchromosome gene mutations should be available as a form of geneticscreening for affected families in the near future.


P4.17 PHYSIOLOGY OF REPRODUCTION

P4.17.01BIOLOGICAL ROLES OF ANGIOTENSIN II VIA ITS TYPE 2RECEPTOR DURING RAT FOLLICLE ATRESIAE. Kotani (1), K. Kondo (1), M Saitoh (1), S. Usuki (1), T. Kubo (1), K.Song (2), M. Miyazaki (2), H. Miyazaki (3)(1) Dept OB/GYN, institute of Clinical Medicine, University of

Tsukuba, Tsukuba-shi, Ibaraki, Japan(2) Dept of Pharmacology, Osaka Medical College, Takatuki-shi,

Osaka, Japan(3) Gene Experiment Center, University of Tsukuba, Tsukuba-shi,

Ibaraki, Japan

Objectives: Type 1 angiotensin II (Ang II) receptors play crucial roles inthe regulation of blood pressure and fluid osmolarity, whereas thephysiological roles of type 2 Ang II receptors (AT2) remain unclear.Because AT2 is expressed in atretic follicles where granulosa cellsundergo apoptosis, we examined the space and time relationshipbetween AT2 expression and follicle atresia in vivo, and the effect ofAT2 on FSH actions in vitro.Study Methods: For in vivo experiments, immature female rats weresubcutaveouls infected with eCG, and the ovaries were remove on eashof days 3-6 after injection for autoradiographic studies and in situ 3’-endlabeling analysis. Granulosa cells were prepared for low molecularweight DNA analysis, quantitative RT-PCR analysis and bindingstudies. For in vitro experiments, granulosa cells were cultured for 48hwith or without various additives for low molecular weight DNAanalysis, binding assay of 125I-hCG and measurememt of estradiol-17b.In subsequent experiments of mitogen-acticated protein (MAP) kinaseactivity, the granulosa cell cultures were plated for 48h in 10% fetal calfserum and cultured for an additional day in serum-free media. Then,cells were incubated with or without various additives for 2 min.Results: Binding studies, autoradiography, and RT-PCR of AT2revealed that the AT2 content in granulosa cells was time dependentlyincreased at both protein and mRNA levels in eCG-treated immaturefemale rats. This increase paralleled the progression of atresia. And IIsuppressed FSH-caused prevention of DNA fragmentation, increases inthe LH receptor content, and estrogen production through AT2 incultured granulosa cells. Moreover, FSH-induced stimulation ofextracellular signal-regulated kinase activity, critical for cell survival,was inhibited by AT2 stimulation.Conclusion: These results suggest that AT2 mediatesteh progression offollicle atresia through granulosa cell apoptosis by inhibiting the FSHactions.

P4.17.02EGF MODULATES LEPTIN EFFECT ON STEROIDOGENESIS INFSH-INDUCED HUMAN GRANULOSA CELLSE.M. Tsai (1), S.S. Yuan (1), H.R. Lin (1), P.S. Li (2), J.N. Lee (1)(1) Dept. OB/GYN, Kaohsiung Medical University Hospital,

Kaohsiung, Taiwan.(2) Dept. of Physiology, National Cheng Kung University, Taiwan.

Objectives: The aim of the study was to investigate whether epidermalgrowth factor has an interaction with leptin effect on the steroidogenesisof human ovarian granulosa cells (GCs).Study Methods: Human GCs were obtained from IVF program viatransvaginal aspiration of follicular fluid. After appropriate treatment,GCs were cultured and reagent such as FSH, leptin, and EGF wereadded according to the study protocols. The supernatant media wereharvested after 2-day incubation and subjected to radioimmunoassaysfor estradiol and progesterone measurements.Results: FSH and EGF stimulate GCs to produce estradiol andprogesterone in a dose-dependent manner. Leptin inhibitssteroidogenesis in GCs culture. At the presence of FSH, leptinsuppresses estradiol production, but this action disappears by co-incubation with EGF. However, the stimulating progesterone productionshows unalternation.Conclusion: EGF modulates leptin effect in the regulation of ovariansteroidogenesis in luteinized granulosa cells of human ovary.

P4.17.03EMBRYO CHROMOSOME STATUS AFTER OOCYTECRYOPRESERVATIONA. Cobo 1, C. Rubio1, A. Pellicer1,2 and J. Remohi 1,2 1. Instituto Valenciano de Infertilidad. 2. Department of Paediatric,Obstetric and Gynaecology, University of Valencia, España

Objectives: To test our oocyte freezing method and to analyse embryochromosomal abnormalities by in situ hybridisation FISH.Study Methods: Group I included 143 oocytes obtained from donors(24.5 ± 3.6 years) and collected after ovarian stimulation. They werepartially decumulated, cryopreserved after 4-6 hours of ovum pick-upusing PROH and sucrose cryoprotectants. Survival was checkedimmediately after thawing and after two hours. Then oocytes wereenzimatically decumulated and metaphase II ones were microinjected.Embryo biopsy was performed for FISH analysis of chromosomes13,18,21, X and Y on day 3. Results were compared with those of 124embryos (group II), from patients who underwent preimplantationdiagnosis for sex-linked diseases ( < 36 years old).Results: The overall survival rate for cryopreserved oocytes was 62.9%and 59.4% after two hours. The differences were not significant betweenthe two groups in fertilisation rates (76.5 vs. 90.5%) or blastocyst rates(29.6 vs. 35%). Moreover, no difference in chromosome status wasfound (66.6 vs. 74.0% of normal embryos). In group I, abnormalitieswere aneuploidies related to chromosomes 13 and 21. Group Ichromosomal normal embryos reaching blastocyst stage (62.5%) werecryopreserved.Conclusions: Cryopreserved oocytes achieved acceptable fertilisationand cleavage rates. FISH analysis results suggest that oocyte freezingcould be employed as a reliable technique in assisted reproduction.

P4.17.04EXPERIMENTAL HYPERPROLACTINEMIA. MORPHOLOGICALEFFECTS ON ADULT MOUSE ENDOMETRIUM.AGZ Rossi , EC Baracat, JM Soares Jr, CE Lang, AF Parlow, MJSimões, MG Nunes, ELA Motta, MA HaidarDepartment of Gynecology - Escola Paulista de Medicina, FederalUniversity of São Paulo, Brazil.

Objective: The aim of this work was to analyze the effects ofexperimental hyperprolactinemia on the mouse endometrial morphologyduring the diestrous phase.Study Methods: Forty virgin adult mice were divided into four groups:CGI - control group I (0.2 ml of saline solution); CGII – control group II(0.2 ml of saline solution); EGI – Experimental Group I (200 mg ofmetoclopramide); EGII – Experimental Group II (200 mg ofmetoclopramide). All animals received subcutaneous injections of salinesolution or drug during 50 days and vaginal smears were taken daily.After that, the animals were sacrificed during diestrous phase, theirblood collected and the uteri removed.Results: We observed the following percentages on the animals that didor did not have estrous cycles: CGI, 87,5% and 12,5%; EGI, 70% and30%; CGII, 90% and 10%; EGII, 80% and 20%. The averages of thePRL serum values (ng/ml) were: CGI (69.3±14.7); EGI (236.6±28.8);CGII (39.2±4.6); EGII (331±44.9). Morphologically, experimentalanimals with estrous cycles showed much more well developedendometrium than controls, columnar epithelium with many figures ofmitoses, thicker stroma with much intercellular substance, manyfibroblasts and glands with secretion in its interior. The experimentalanimals, under persistent diestrus, appeared similar to the controlgroups.Conclusion: The female mice with hyperprolactinemia that had estrouscycles, and the endometrium appeared more developed during thediestrus phase in relation to their controls; in those that did not cycle, theendometrium appeared less developed.


P4.17.05FLUOXETINE’S EFFECT ON FOOD CRAVING DURING THELUTEAL PHASE IN WOMEN WITH PREMENSTRUALDYSPHORIC DISORDER (PMDD)M. Steiner (1), R. Judge (2), E. Brown (3), and J. Dillon (2).

(1) McMaster university, St. Joseph’s Hospital, Hamilton, Ontario,Canada(2) Eli Lilly and Company, Lilly Corporate Center, Indianapolis,Indiana, USA(3) Eli Lilly and Company, Nederland, CO, USA

Objective: A previously reported, placebo-controlled, multi-site trialfound fluoxetine effective in mediating PMDD mood symptoms; thesedata are now used to determine fluoxetine’s effectiveness on eatinghabits during the luteal phase in women with PMDD. Though cyclicalmood, disturbance is the pathognomonic feature of PMDD, a markedchange in appetite, overeating or specific food craving is one of the 11DSM-IV diagnostic criteria for PMDD.Study Methods: Eating habits were assessed in 320 PMDD patients whowere randomized to fluoxetine 20mg/day, fluoxetine 60mg/day, orplacebo. Symptoms were measured by 2 questions on the self-rated and1 question on the observer-rated Premenstrual Tension Syndrome Scale(PMTS-SR, PMTS-O). Both scales assessed increase in food intake andspecific food cravings. Outcome measure for each woman was herfrequency of increased food intake/craving during the luteal phase of the6 months of treatment.Results: Fluoxetine..treatment (20 and 60 mg/day) statisticallysignificantly reduced the frequency of increased food intake/cravingcompared with placebo treatment when measured on the PMTS-SR(p<0.01). A statistically significant reduction was detected for fluoxetine20mg/day versus placebo using PMTS-O (P<0.01).Conclusion: Fluoxetine treatment was statistically significantly superiorto placebo in reducing the frequency of reported food cravings in womensuffering from PMDD as measured by the PMTS-SR and PMTS-O.

P4.17.06FUNCTION OF ARG-GLY-ASP (RGD)-BINDING SITES ON b 1INTEGRIN IN HUMAN DECIDUAL CELLSH. Hanashi (1), S. Shiokawa (1), K. Sakai (1), N. Suzuki (1) , K.Noguchi (1), M. Higashi (1), M. Hashimoto (1), M. Iwashita (1), Y.Nakamura (1), Y. Kasuga (2)(1) Dept. OB/GYN, Kyorin University School of Medicine, Tokyo,Japan(2) Dept. OB/GYN, Ashikaga Red Cross Hospital, Tochigi, Japan

Objectives: Amino acid residues 140-164 of integrin b1 comprise onArg-Gly-Asp (RGD) cross-linking region. The present study wasundertaken to study the role of the RGD cross-linking region of integrinb1 submit in embryo implantation.Study Methods: A synthetic peptide used in this study was derived fromthe long arm of the integrin b1 chain, residue numbers 140-164 (DDL,DYPIDLYYLMDLSYSMKDDLENVKS). A variant peptide (AAL,DYPIDLYYLMDLSYSMKAALENVKS), in which both Asp 157 andAsp 158 were replaced by Ala, was also used. Embryo attachment andspreading assays were performed using cultured human decidual cells.Mouse blastocysts obtained at 96h after hCG injection were cultured ondecidual cells. Decidual cells were cultured without or with syntheticpeptides, at concentrations of 1 to 100nM. Measurements of embryohatching and attachment were made at 12h and 24h of incubation. Thearea of embryo outgrowth was measured using a color image analyzingsystem (sp500) between 48h and 96h of incubation.Results: Treatment of decidual cells with synthetic peptides did notaffect the rates of hatching and attachment of blastocysts. The outgrowthof embryos on decidual cells was inhibited by DDL peptide in a dose-dependent manner, but not by AAL peptide.Conclusions: The present data demonstrated that integrin b1 [140-164]in decidual cells may be important in embryonic development anddifferentiation following attachment.

P4.17.07HISTOMORPHOMETRIC OVARIAN ASPECTS OF ADULTPINEALECTOMIZED RATS.JM Soares Jr , EC Baracat, CE Lang; MA Haidar, MJ Simões, EL Dair,G Rodrigues de Lima. Department of Gynecology - Escola Paulista deMedicina, Federal University of São Paulo, Brazil.

Objective: The aim of this work was to evaluate the histomorphology ofinterstitial cells of ovarian stroma in pinealectomized rats.Study Methods: Twenty-six rats were divided in three groups after threenormal cycles: GI - Control group (n=9); GII - Sham pinealectomizedrats (n=6); GIII - Pinealectomized rats (n=11). After two months, allanimals in estrous phase were sacrificed and the ovary was removed andfixed in 10% formaldehyde. The material was processed by H.E. andMasson Trichrome. . Besides analyzing of the morphology of theovarian stroma, we calculated the maximum diameter of the interstitialcell nuclei.Results: The pinealectomized animals presented larger concentration ofinterstitial cells in the ovarian stroma. The histomorphometrical analysesrevealed that the maximum diameter of the nuclei of the interstitial cellswas much larger in pinealectomized rats than in the other groups.Conclusion: Our data suggest that larger metabolic activity and possiblylarger hormonal production too could be taking place in these cells.

P4.17.08IDENTIFICATION AND CHARACTERIZATION OF HUMAN 20a-HYDROXYSTEROID DEHYDROGENASET. Nakajima (1), M. Nishizawa (2), K. Yasuda (1), S. Ito (2), H. Kanzaki(1) Dept OB/GYN, Kansai Medical University, Osaka, Japan(2) Dept Medical Chemistry, Kansai Medical University, Osaka, Japan

Objective: 20a-hydroxysteroid dehydrogenase (HSD) belongs to aldo-keto reductase (AKR) superfamily and catalyzes the reaction ofprogesterone to 20a-Hydroxyprogesterone, which is biological inactiveform. Rat 20&-HSD gene was cloned and analyzed by human 20&-HSDwas not. The aim of this study was to investigate human 20&-HSD tounderstand progesterone metabolism.Study Methods: genomic library by hybridization with rat 20&-HSD[AKR1C8] cDNA and performed high-stringency polymerase chainreaction (PCR) for hybridization positive clones with gene-specificprimers. Four genes were isolated. We examined the expression of thesegenes by reverse transcription PCR in various human tissues and thesubstrate specificity using recombinant enzymes.Results: We isolated four aldo-keto reductase genes which shared highhomology; human 20&-HSD [AKR1C1], bile acid-binding protein(BABP) {AKR1C2], prostaglandin F synthase (PGFS)[AKR1C3], anddihydrodiol dehydrogenase (DD) 4 [AKR1C4] genes. Human 20&-HSD, BABP, and PGFS mRNAs were expressed ubiquitously, whileDD4 mRNA was restricted in the liver. The four recombinant enzymesshowed distinct substrate specificity.Conclusion: Human gene coding for the progesterone-metabolizingenzymes 20&-HSD was cloned. BABP, PGFS, and DD4 genes, whichwere highly homologous to 20&-HSD gene, were also cloned. Theexpression and the substrate specificity of these genes were elucidated.

P4.17.09IMMUNOMORPHOLOGIC INVESTIGATION OF PUNCTUREBIOPSY SPECIMENS FROM WOMEN WITH PREVIOUSGESTOSISL.E. Mourashko , J.G. Moisuk, I.M. Ilinsky, I.V. Sergeyko, F Baranova.Research Centre for Obstetrics, Gynecology & Perinatology, Moscow,Russia

Objective: Gestosis is known to be a serious pregnancy complicationwith negative influence on maternal and perinatal outcomes. Also,chronic renal impairment is known as one of the causes of gestosis. Weattempted to study immunomorphologic renal changes in women withprevious gestosis.Metods: 20 women (mean age 32,0 + 0,4 years) who had had completedpregnancies ( 25% had one and 75% had two or more pregnancies)complicated by severe gestosis underwent renal biopsy performed 8 days- 1,5 years later pregnancy completion. Immunomorphologicinvestigation of these specimens was done.


Results: Clinical and morpholocical data revealed chronic renal diseasesin 6 (35,3%) patients (3 women had chronic pyelonephritis and 3 -chronic glomerulonephritis ( membranous, proliferous andmembranoproliferous forms). Immunologic valuation of biopsyspecimens detected IgG in 88,2% cases, IgM - in 52..9%, IgA - 35,3%,C3 - 82,4% cases, which could be a confirmation of immunologic theoryof gestosis.Conclusion: Renal puncture biopsy is needed in patients with a historyof previous gestosis and I-st and II-nd trimester pregnancy women tosolve the problem of treatment chronic renal disease and /or gestosis.

P4.17.10MECHANISM OF RAT OVARIAN PGS-2 EXPRESSIONREGULATED BY IL-1Y. Sano (1), M. Ando (1), M. Sato (1), M. Iwashita (1), Y. Nakamura(1), K. Sugawara (2)(1) Dept. OB/GYN, Kyorin University School of Medicine, Tokyo,Japan(2) Sugawara Clinic, Saitama, Japan

Objectives: It was the purpose of this presentation to provide an initialcharacterization of the potential role of the sphingomyeline-ceramide (S-C) pathway in the ability of interleukin-1b (IL-1b) to upregulate ovarianprostaglandin endoperoxide synthase-2 (PGS-2) expression.Study Methods: Whole ovarian dispersates (1.5X1.06 viable cell/dish)from immature SD rats were cultured for 48h with or without variousexperimental agents. To examine the early response, cells were initiallycultured for 24h in the absence of treatment. Total RNA from culturedcells was extracted and subjected to RNase protection assay usingantisense riboprobes corresponding to rat PGS-2 and hormonally-independent ribosomal protein L19 (RPL19), that normalize PGS-2signals. The intensity of the signals was quantified using a digitizingphosphoimager.Results: Treatment with sphingomyelinase (SMase, 0.3U/ml),sphingosin (Sph, 10mM), C6- and C8-ceramide (100mM) for 48hculture were without significant effect of PGS-2 transcripts. To study theearly response of the S-C pathway, SMase and Sph had transientlyeffects on 1.5h (774 times increments vs. initial value) and 2h (840 timesincrement vs. initial value), respectively. In contrast, treatment with IL-1b increased PGS-2 transcript time-dependent until 48h. The addition ofSMase produced dose-dependent manner (0.001-0.3 U/ml) on 1htreatment.Conclusions: These findings suggested that IL-1 may rapidly inducesphingomyeline turnover, producing ceramides, which may act as asecond messenger molecule in intraovarian signal cascade.

P4.17.11THE RELATIONSHIP BETWEEN THE HORMONE LEVELS ANDOVARIAN SIZE IN POLYCYSTIC OVARY SYNDROMEB. Kastratovic Kotlica , S. Petkovic, S. Kotlica, J. Opalic, G. Ivanovic,D. Ivanovic, O. Kontic, Inst. of OB/GYN, Clinical Center of Serbia,Beograd, Yugoslavia

Objectives: The aim of the study was to evaluate hormonalconcentrations in the relation with the degree of ovarian enlargement inPolycystic Ovary Syndrome (PCOS).Study Methods: Ninety-six women with PCOS were divided into threegroups according to ultrasound criteria for ovarian size: I group –patients with normal ovaries, II group – with moderately enlarged andIII group – very enlarged ovaries. We analyzed at least two sets ofandrogens from the plasma: testosterone (T), androstenedione (A),dehydroepiandrosterone-sulfate (DHEAS) as well as sex hormone-binding globulin (SHBG0, FSH and LSH. Hormone analysis were doneby RIA and statistics by descriptive methods, Student’s t-test and 1- wayANOVA.Results: LH levels increased from 14.27 to 20.83 U/l with highlystatistical difference among groups (p<0.01). FSH was at the lowernormal level, but there was significant difference between groups II andIII. T levels were always above the normal limits, the highest in IIIgroup and with highly statistical significant difference among groups(p<0.01). Concentrations increased from 12.47 to 17.45 nmol/l and therewas no statistical difference. DHEAS levels were within normal limitsand there was no significant difference among groups. SHBG was 32.03,

24.24, 18.92, respectively, and there was statistical difference among Iand III group.Conclusion: Our best results have shown that the ovarian size in PCOScorrelates with : LH, FSH, T and SHBG levels.

P4.17.12USEFULNESS OF ERYTHROCYTE PROTOPORPHYRIN AS ASCREENING TOOL FOR IRON DEFICIENCY, AT DELIVERYC.R. Ortega Soler (1), L. López (1), S.H. Langini (2), S. Fleischman(2),M.L. de Portela (2)(1) D. Paroissien Hospital, Buenos Aires, Argentina(2) School of Pharmacy & Biochemistry, University of Buenos Aires,Buenos Aires, Argentina

Objectives: Sensitivity, specificity and predictive value of ErythrocyteProtoporphyrin (EP) as an index of iron (Fe) nutritional status, werestudied in a group of women at delivery, in relation to classicalhematological parameters.Materials and Methods: Venous fasting blood samples were collectedwith EDTA in 306 women assisted at delivery, in a suburban Hospital ofGreater Buenos Aires, between July 98 and January 99. Hematocrit(Hct), Red Blood Cell count (RBC), White Blood Cell count (WBC),Hemoglobin (Hb), Mean Corpuscular Volume (MCV) and MeanCorpuscular Hemoglobin (MCH) were determined by an electroniccounter; EP by Piomelli’s method. Sensitivity (Se), specificity (Sp) andpositive and negative predictive values (V+ and V-, respectively), werecalculated for EP and Hb, in relation to MCH.Results: Mean values, standard deviations and ranges (between brackets)were: RBC (x106/ml): 3.74±0.52 (5.3-2.2); Hct (%): 34.5±5.4 (52-21);MCV (fL): 92±7 (115-71); Hb (g/dL): 11.2±1.9 (16.9-6.4); MCH (pg):30.0±2.9 (38.0-19.1); EP (mg/dL RBC): 50±25 (9-207); WBC/mm3 :9540±2690 (19700-3000). EP and Hb values as a diagnostic tool were,respectively: Se 39% & 88%, Sp 85% & 65%, V+: 60% & 28%; V-:90%&97%. An EP/Hb (mg/g Hb) cutoff point of 2.44 corresponded tothe accepted cutoff value of 70mg EP/dL RBC.Conclusions: These results show the usefulness of EP as a specificindicator of Fe screening deficiency a delivery. Therefore, EP would beadvisable as an easy determination with an hematofluorometer in orderto carry out the prenatal and postnatal maternal care avoiding theconsequences of Fe deficiency anemia, mainly in this target group.Supported by University of Buenos Aires (Argentina), Grant TA 060

P4.18 ULTRASOUND

P4.18.01A CRITICAL EVALUATION OF TRANSPERINEALSONOGRAPHY (TPS) IN THE DIAGNOSIS OF PLACENTAPREVIAG. Patel , Dept. OB/GYN, Sharda Hospital, Visnagar, Gujarat, India.

Objectives: The aim was to evaluate TPS in the diagnosis of placentaprevia.Study Methods: Fifty gravid women in second and third trimester ofpregnancy underwent transabdominal (TAS) and TPS for diagnosis ofplacenta previa.Results: Using TAS, placenta previa was excluded in 41 cases. In theremaining 9, lower limit of placenta could not be seen. With TPS lowerlimit of placenta was visualized in 9 cases and diagnosis of placentaprevia was confirmed in 4 cases.Conclusion: TPS should be considered when TAS is inconclusive forplacenta previa due to poor visualization of the lower margin ofplacenta.

P4.18.02ACARDIAC TWINS: SONOGRAPHIC EVALUATION INPERINATAL MANAGEMENTK.G. Wang , C.L. Chang, C.J. Jeng, C.P. Chen, Dept. OB/GYN, MackayMemorial Hospital, Taipei, Taiwan.

Objectives: The clinical outcomes of acardiac twin pregnancies managedat our hospital are analyzed for reference.Study Methods: The computer database of our hospital is serched andthe cases of acardiac twins are retrieved for analysis.


Results: Four cases of acardiac twins are recruited from our database.All of them were diagnosed prenatally and intensive fetal surveillance ofthe pump twin was instituted soon after diagnosis. All were prematurelive births and growth retarded. There was one neonatal death,complicated by congenital heart disease and bilateral hydronephrosis.The mean gestational age at delivery was 34.3±2.6 weeks, and the meanbirth weight of pump twins was 1461±476 grams.Conclusions: Early prenatal diagnosis allows the management option ofpregnancy termination, based on the fact that the surviving twin carries ahigh risk of severe preterm birth and long term morbidity. There is alsoan increased risk of major structural abnormalities. Expertise anatomicalultrasound scan, fetal Dopplers, and fetal echocardiography aresuggested.

P4.18.03CLINICAL VERSUS ULTRASOUND ESTIMATION OF FOETALWEIGHT AT TERMS.N. Bhuiyan , R. Begum. Dept. OB/GYN, Chittagong Medical CollegeHospital, Chittagong, Bangladesh.

Objective: To compare the accuracy of routine ultrasonic and clinicalbirth weight estimation.Methods: This prospective study was done in Department of OB/GYNof Chittagong Medical College Hospital, Bangledesh from January 1998to July 1999. The study was designed specifically to compare withactual birth weight. A total 100 women with singleton pregnancy withcepalic presentation a 30-40 weeks gestation was studied. The studycases were included those delivered within 72 hours of estimation ofweight. Actual birth weight was obtained within hours of delivery.Accuracy was determined by mean absolute error (actual minusestimated weight) mean standardized absolute error (absolute error ingm/girth weight) and error of estimate within ±10% of actual birthweight.Results: Actual birth weight in study sample averaged 2941±452.54 gm(Mean±SD) and ranged between 2647-3235 gm. In the 2500-3500 gmbirth weight ultrasonographic estimation was significantly higher thancinical estimation (p<0.001). In birth weight less than 2500 gm, error forclinical estimation was also more than ultrasonographic estimation(p<0.05). But birth weight more than 3500 gm, estimation by bothmethods was not significantly different. When we consider as a wholethe mean error of clinical was 395.77 gm, 140.52 gm/kg, for a 14%error. The error of ultrasound is same population was 184.01 gm, 60.87gm/kg, for a 6% error statistical analysis show ultrasound estimationsignificantly higher than those of clinical estimation.Conclusion: Clinical estimation of fetal weight is not as accurate asultrasonographic estimation of making obstetric decision. Routineultrasonographic estimation of fetal weight is necessary, where it isindicated; though this is costly and not easily accessible in our country.

P4.18.04EARLY DETECTION OF REVERSED UMBILICAL VEIN FLOW INA CASE OF TRISOMY 9C.Murta (1) , A.Moron (1), M.Ávila (2), L.França (3), (1) FederalUniversity of São Paulo, Av. César Hilal - 1181/401, Vitória, ES, Brazil,29052-231, (2) Federal University of Rio de Janeiro, Rio de Janeiro, RJ,Brazil, (3) Federal University of Espírito Santo, Vitória, ES, Brazil.

Background: During the last 2 years, few prenatal ultrasonographicstudies have documented a strong association between abnormal fetalvenous return and chromosomal abnormalities. Articles in the English-language medical literature were identified through MEDLINE. There isonly one report of reverse flow pattern in the umbilical vein in severeintrauterine growth restriction at 29 weeks’ gestation. The present case isthe earliest documentation of this alteration in fetal venous return.Case report: A 30-year-old primigravida was referred to ourultrasonography clinic at 12 weeks of gestation. The fetal crown-rumplength (57mm) was not compatible with menstrual dates. The ultrasoundexamination showed an increased nuchal translucency (9.1mm), bilateralpyelectasis, hiperechoic bowel, echogenic intracardic focus andventricular septal cardiac defect. The fetal heart rate was 147 beats/min.The Doppler examination revealed high retrograde flow in the inferiorvena cava, reverse flow in the ductus venosus during atrial contractionand reverse flow in the umbilical vein. Cytogenetic analysis by chorionicvillus sampling diagnosed trisomy 9. Ten days later, fetal demise was

observed. A nonmosaic trisomy of chromosome 9 was confirmed onfetal cells’ analysis. At autopsy, the characteristics findings were ofcomplete trissomy 9 and the multiple abnormalities detected byultrasonography were confirmed.Conclusion: Doppler blood evaluation of the venous return to the heartmight provide relevant information on cardiac function. The reverseblood flow in umbilical vein may indicate an impending fetal death. Wespeculate that the association of abnormal nuchal translucency thicknesswith alterations of the fetus venous return might be a complementarytool to assess the risk for fetal aneuploidy in the first trimester ofpregnancy. In addition, these Doppler velocimetry alterations can be analarm sign for investigating cardiac abnormalities.

P4.18.05EARLY SONOGRAPHIC MARKERS OF POOR PREGNANCYOUTCOMEL. Sichinava , O. Panina, G. Savelieva, M. Kourtser, Russian StateMedical University, 24a Sevastopolsky prosp., Moscow, Russia,113209.

Objectives: This study was undertaken to evaluate the prognosticsignificance of abnormal yolk sac and uteroplacental circulation at earlygestation.Study Methods: We have investigated 1035 pregnants at 7-13 gestationweeks (cohort study) and assessed their follow-up. During thetransvaginal echography not only have we measured the yolk sacdiameter, but assessed its shape, internal echogenity and the signs of itsfailure as well. Perfusion characteristics were studied by color Dopplerimaging in uterine and spiral arteries using S/D, PI and IR indices.Results: The increased or decreased diameter, the internal spacehyperechogenisity, the imperfect shape of the yolk sac and its pretermfailure (9-10 weeks) were revealed in 15 % cases. The positiveprognostic value of abnormal yolk sac was no more than 12 %, howeveramong 25 pregnants with IUGR 20 turned to have abnormal yolk sac.The prognostic value for the perinatal outcome has increased (up to 74%) while taking into account the diminished gestational sac volume. Theincreased indices in uterine and spiral arteries were obtained in 140pregnants. The main quantity (124) of these patients was those withpreeclampsia at late gestation. The history of these 124 patients showedthat 40 of them had chronic hypertension, the rest 84 had no signs ofpreimposed extragenital diseases. In cases with chronic hypertension in92,5 % patients pathological dopplerometric indices in uterine arterytook place at early gestation. The increased S/D and PI in spiral arterieswere observed more frequently in patients with preeclampsia withoutpreimposed hypertensionConclusions: Thus we believe that isolated ultrasonographic yolk sacimage studies done between 7 and 13 weeks gestation have littleprognostic significance for the fetal integrity and outcome. In patientswith preeclampsia with preimposed hypertension in late pregnancy thepathological changes touch first of all the uterine arteries. The primaryinvolvement of spiral arteries is associated with preeclampsia withoutpreimposed hypertension.

P4.18.06INFLUENCE OF VAGINAL DANAZOL ON UTERINE AND BRAINPERFUSION DURING HORMONAL REPLACEMENT THERAPY(HRT).Guerriero S , Paoletti AM, Ajossa S, Orru’ M, Lai MP, Vacca AMB, BoiM, Angiolucci M, Melis GB and *Perrone, G. Departments of Obstetricsand Gynecology- University of Cagliari and *Rome Italy

Objectives: to evaluate the effectiveness of vaginal danazol as progestinsupplementation to estrogen replacement therapy and its interference onuterine and carotid arteries in a prospective, controlled study andcompared with medroxyprogesterone-acetate (MPA) or estrogen alone.Study Methods: Forty postmenopausal women (PMW) were randomlyincluded in 4 different treatments for a period of 6 months: transdermalestradiol (50 _g/day, in continuous way) (TE) plus a monthly 10-daycourse of MPA (10 mg/day) (Group 1, N=10); TE with a monthly 10-day course of vaginal danazol (200 mg/day) (Group 2, N=10); TEwithout progestin supplementation (Group 3, n=10); placebo (patchesindistinguishable by TE) (Group 4, n=10). Carotid and uterine pulsatilityindex (PIs) were assessed by color Doppler at baseline and during the


1st, 2nd, 3rd and 6th month of treatment. At the same time-intervalsendometrial thickness was measured using transvaginal ultrasonography.Results: In the PMW of the Groups 1, 2 and 3 the values of carotid anduterine PIs were significantly (P<0.05) and similarly decreased duringthe treatment, whereas in women of group 4 they did not change. Onlyin Group 3 endometrial thickness was significantly higher during thetreatment period than before (P<0.05). No endometrial iperplasia waspresent in the four groups at the end of treatment.Conclusions: These findings suggest that, similarly to MPA, vaginaldanazol is able of counteracting mitogenic effect of estrogens on theendometrium. In addition, we demonstrate that both MPA and vaginaldanazol do not reduce the effectiveness of estrogens in improvingcarotid and uterine arterial perfusion.

P4.18.07INTRACARDIAC ECHOGENIC FOCUS : NO APPARENTASSOCIATION WITH STRUCTURAL CARDIAC ABNORMALITYI. Wolman 1, S. Diamant2, R.I. Gull1, J. Hartoov1, R. Amster1,JB. Lessing3, AJ Jaffa1 Ultrasound Unit1 and Department of Obstetricsand Gynecology3 Lis Maternity Hospital, and the Echocardiographiclaboratory, Dana Hospital for Children2, Tel-Aviv Sourasky MedicalCenter, Tel-Aviv University, Tel-Aviv, Israel

Objective: The purpose of this prospective study was to evaluatewhether intracardiac echogenic foci (ICEF) are related to impairment ofventricular performance.Study Methods: 3744 low risk patients were prospectively evaluated bythe same ultrasonographer. A 4-chamber view of the heart and thecardiac outlet of the great vessels were demonstrated in all fetuses. ICEFwere defined as an hyperechogenicity located on the chordae tendinae.Fetuses with ICEF underwent further full echocardiographic evaluation.These fetuses were compared to a control group of 167 fetuses withoutany apparent cardiac pathology who underwent a full echocardiographicevaluation due to the mother request. Neonates were clinicallyexamined, and referred for an additional echocardiographic evaluationonly if a clinical suspicion of cardiac impairment arose.Results: Of the 3744 patients in the study group, 138 fetuses (3.7%)presented with ICEF. The majority of the ICEF (78%) were located inthe left ventricle, 18% were located in the right ventricle and 4% werebilateral. Of the 138 fetuses in this group, there was one case (0.7%) ofpulmonic stenosis in a twin gestation. The co-twin did not demonstrateany ICEF. There was no other cardiac malformation or dysfunction inthe other fetuses. Of the 167 fetuses in the control group, there was onecase of fetal bicuspid aortic valve. There was no statistical significancebetween the 2 groups.Conclusions: We conclude that the finding of ICEF is not correlatedwith cardiac dysfunction. However, these lesions should be carefullydifferentiated from rhabdomyoma or teratoma .

P4.18.08MEASUREMENTS OF OBSTETRICS CONJUGATE, THESHORTEST ANTEROPOSTERIOR DIAMETER OF THE PELVICINLET, AND PELVIC APERTURE ANGLE BYULTRASONOGRAPHIC TOMOGRAPHYMitsuhiro Yoshinaga 1, M. Katanozaka1, K. Fuchiwaki 2, Y. Nagata1.Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima,Japan; 2Fuchiwaki Ladies Clinic, Miyakonojou City, Japan.

Objectives: To determine the usefulness of the measurements ofultrasonographic obstetrics conjugate (UOC), the shortestanteroposterior diameter of the pelvic inlet(UAPD), and pelvic apertureangle(UPA) for the assessment of dystocia.Study Methods: Subjects were 165 primigravida women, who haddelivered at the Dept of OB/GYN, Kagoshima University Hospital,between January 1997 and August 1999. At 36 to 40 weeks ofgestational age, fetal biparietal diameter (BPD), maternal UOC, UAPD,and UPA were measured by transabdominal ultrasonographictomography. Relationship between these variables and dystocia wasinvestigated retrospectively.Results: Mean value of UAPD was 13.1 ¥} 0.9 (range, 11.1¥\15.1 cm).Mean difference in UAPD and BPD (UAPD¥\BPD) was 3.8 ¥} 0.8(range, 1.8¥\5.9 cm). Of 21 women with UAPD¥\BPD (_ 3.0 cm), 13women (61.9%) underwent cesarean deliveries because of cephalopelvicdisproportion (CPD). Mean value of UPA was 88.3 ¥} 8.8¥‹ (range, 65

to 115¥‹). Of 24 women with UPA (_80¥‹), 9 women (37.5%)underwent cesarean deliveries because of CPD. One hundred twenty-three women with both UAPD¥\BPD (> 3.0 cm) and UPA (> 80¥‹),only two women (1.6%) underwent cesarean deliveries. Cesarean rate inthese women was significantly lower than that in women withUAPD¥\BPD (_ 3.0 cm) or UPA (_ 80¥‹) (P < 0.001).Conclusions: Based on these results, we conclude that ultrasonographicmeasurements of UOC, UAPD, and UPA are useful to predict thedystocia.

P4.18.09OBSTRUCTIVE UROPATHIESA. Patil , H. Divakar, P. Chitra, Divakars Hospital, BTM Layout,Bannerghatta Road, Bangalore, Karnataka, India, 560076.

Objectives: To determine the incidence of urinary tract abnormalitiesdetected in the presence of mild to moderate fetal renal pelvis dilatation.Study Materials: 1200 routine prenatal mid trimester ultrasoundexaminations were performed over 2 years (January 1998 to December1999).Results: 48 (4%) cases showed mild renal pelvis dilatation (greater thanor equal to 4 mm). Of these 29 cases showed regressive patterns, 11cases showed a stable pattern and 8 cases showed an evolutive patternon follow up scans. In the presence of an evolutive pattern 6 casesshowed presence of urinary tract obstruction (2 cases of unilateral PUJobstruction , 1 case of bilateral PUJ obstruction , 2 cases of posteriorurethral valve, 1 case of multicystic kidney). Obstetric managementdecisions were mainly based on routine fetal surveillance and AFImeasurements, the liquor volume being used as indirect evidence of fetalrenal function. Neonatal follow up and definitive management of caseswill be presented.Conclusion: Measurements of the anteroposterior diameter of the fetalrenal pelvis and assessment of the degree of caliectasis does provideimportant Clinical information that permits early and effective postnatalmanagement.

P4.18.10PREDICTING RISK OF PRE-ECLAMPSIA BY QUANTITATIVEASSESSMENT OF DIASTOLIC NOTCH IN UTERINE ARTERYFLOW VELOCITY WAVEFORMA. Ohkuchi (1), H. Minakami (1), H. Mori (2), T. Nakano (2), M.Tateno (3), I. Sato (1)(1) Dept. OB/GYN, Jichi Medical School, Tochigi, Japan.(2) Dept. OB/GYN, Toyama Prefectural Central Hospital, Toyama,

Japan.(3) Dept. OB/GYN, Toyama Red Cross Hospital, Toyama, Japan.

Objectives: We have developed a new quantitative index, the notchdepth index (NDI). We evaluated the association of the NDI with therisk of pre-eclampsia, and compared its clinical utility with that of otherindices, the uterine artery resistance index (RI) and the AC ratio.Study Methods: Uterine artery color Doppler ultrasound was performedin 288 consecutive healthy pregnant women at 20.2±2.0 (range, 16.0 to23.9) weeks of gestation. The NDI represents the depth of the earlydiastolic notch divided by the maximal diastolic velocity.Results: Nine (3.1%) of the 288 women developed pre-eclampsia. TheNDI was associated with subsequent onset of pre-eclampsia. Theoptimal cutoff value for the NDI in predicting pre-eclampsia was 0.14,which gave a sensitivity, specificity, and a positive predictive value(PPV) of 67%, 93%, and 22%, respectively. The PPV of the NDI, 22%,was the largest of the three indices evaluated (12% for he RI and 16%for the AC ratio). The relative risk for pre-eclampsia in women with ³the optimal cutoff value of the RI, AC ratio and the NDI was 9.7 [95%CI, 2.5-3.7], 19.2 [4.2-91], and 19.2 [5.1-71], respectively. The NDI of0.14 improved the PPV of 18% determined by the presence of notches inbilateral uterine arteries.Conclusions: The NDI value in the second trimester was associated withthe onset of pre-eclampsia, and was more useful clinically in predictingpre-eclampsia than were two conventional indices.


P4.18.11SUCCESSFUL INTRAUTERINE TREATMENT OF A HYDROPICFETUS WITH MACROCSYTIC CCAM WITH SERIALTHORACOCENTESES AND THORACOAMNIOTIC SHUNTPLACEMENTA.M. Barth , Dept. OB/Gyn, Städtische Kliniken Frankfurt/Main-Höchst,P.J. Czygan, Dept. OB/Gyn, Städtische Kliniken Frankfurt/Main-Höchst, F. Bahlmann, Dept. Prenat. Diagnosis OB/Gyn,Universitätsklinik Mainz, Germany

Objectives: A severily compromised 24+6 weeks fetus affected withunilateral macro-cystic CCAM with signs of fetal distress was treatedsucessfully with serial fetal thoracocenteses and thoracoamniotic shuntplacement). The pregnancy was carried near term and the newborn wasoperated successfully.Study Subject: A 34 -year gravida 2, para 1, presented at 24+6 weeks´gestation The ultrasound scan showed a hydropic fetus with a largecystic mass in the right lung with displacement and rotation of the fetalheart. CTG was ominous, an absent end-diastolic bloodflow in theumbilical artery was present. After counseling the couple both opted fortreatment despite of the outcome.Results: Four thoracocenteses were performed (24+6, 26+3, 28+5, 29+4)with 50-70 ml of fluid removed each time. Immediatly after the firstprocedure the doppler studies showed a marked improvement in the end-diastolic bloodflow. The anasarca disappeard within one week. The fetalcondition was good despite a gradual increase of ascites and amnioticfluid. At 30+5 weeks` a thoraco-amniotic shunt placement wasperformed. The ascites dis-appeared, the amniotic fluid stayed withinnormal range. At 37+2 weeks´ a cesarion section was performed due toan abnormal CTG pattern and a FBS of ph 7,20. (male infant 3215 g,Apgar scores 6/8/8 , pha 7,23). Assisted ventilation was necessaryshortly after birth. Surgery was done on the third day of life. The childmade a full recovery and left the hospital three weeks later.Conclusion: The thoracocenteses where sucessful in resolving the lifethreatening situation for the fetus. The shunt with continuousdecompression of the chest organs resulted in a normal range ofamniotic fluid volume and absorption of the ascites. In contrast to fetalsurgery with the implications for the ongoing and any further pregnancythe inconvenience for the mother was minor.

P4.18.12THREE DIMENSIONAL VOLUMETRY – A CLINCALLYCONTROLLABLE AND ACCURATE MEASURING METHOD ANDITS PRATICAL BENEFITA. Pal , G. Vajda, A. Babinszki, L. Thurzo, Dept. OB/GYN, Universityof Szeged, Szeged, Hungary

Objectives: The authors intended to create a simple and easilyreproducable method for evaluating the volumes of bio targets in 3dimension and compare them with those in vivo, and tested its practicalusefulness.Study Methods: The authors examined 35 women, age between the 38-53, before hysterectomy using COMBISON 530, and three-dimensionalultrasound equipment. In each case, the volume of the uterus wasmeasured by three-dimensional volumetric methods. The calculatedvolumes were subsequent compared with the exact uterine volumes afterhysterectomy which were determined by the water-displacement. On thebasis of volumetric measurements, 20 ovarian tumors were measuredbefore, during and after the cytostatic treatments.Results: The statistical comparison of the measured and calculatedvolumes didn’t show significant differences, and the efficacy of infusiontreatment was well detectable in cases ovarian tumors.Conclusions: The change in the volume of an object could be animportant sign of the progression of regression of a process, e.g. amalignant tumor. On the basis of this study, it seems that the three-dimensional ultrasound technique has got the advantage of providing aneasily and satisfactory reproducible method for the evaluation ofquantitative values and exact volumetric measurements of severalorgans. This technique can be a sensitive marker of the tumor treatmentprocedure.

P4.18.13TREATMENT OF OVARIAN CYSTS WITH ALCOHOL SCLEROSISV. Kukura , S. Ciglar, Z. Duic, G. Zovko, Dept. OB/GYN, MerkurUniversity Hospital, Zagreb, Croatia.

Objectives: The purpose of this study is a technique of punction andconservative treatment of cystic ovarian tumors.Study Methods: For this procedure the cyst must be unilocular,sonulucent, with smooth inner wall of the capsule, without septa andwithout neovascularisation on transvaginal color Doppler. Serum CA-125 levels were lower than 35 U/ml. This offers the possibility of moreconservative management of ovarian cysts that have a low risk ofmalignancy. Cysts capsule was punctured by 18 gauge needle under thecontrol of 5 MHz transvaginal probe. If the cytologic findings werenegative, after complete evacuation of cyst we injected sterile 96%alcohol in the 50% of the evacuated liquor amount. Alcohol remains insitu for 5 minutes and then it was completely evacuated.Results: During the period of 12 years we punctured 140 patients withovarian cyst volume between 40 and 140 ml in the age from 20 to 60.For the local anestheisa we injected 2% Xylocain into posterior vaginalfornix. Five of the patients had very intensive pelvic pain but we treatedthem conservatively with analgetics. Relapse after three monthsappeared in 7 patients (5.00%) where the volume of cysts were biggerthan 100ml. No menstrual disturbance was noticed in any patient.Conclusions: Technique of punction is simple and easy performed.Method of treating by 96% alcohol showed good results. Cyst volumebigger than 100 ml is better to treat surgically, by laparoscopy orlaparotomy.

P4.18.14ULTRASONIC FETAL AND PLACENTAL TISSUECHARACTERISATION AND THE ROLE OF DOPPLERULTRASOUND IN LUNG MATURITYM. Podgajski , M. Podobnik, S. Ciglar, B. Gebauer, Dept. OB/GYN,University Hospital Merkur, Zagreb, Croatia

Objectives: The aim of this study is to known the relationship betweenthe gestational age and quantitative assessment of ultrasonic signs ofplacental tissue, fetal lungs and liver tissue and to correlate Dopplerparameters from main stems of the pulmonary arteries for determiningfetal lung maturity in normal pregnancy and pregnancy withpreeclampsia and diabetes.Study Methods: The placenta, fetal lungs and fetal liver in 300 normalpregnancies, 100 preeclamptic pregnancies and 100 diabetic pregnancywere examined by ultrasound at 30-41 weeks of gestation. Thecoefficients of variation (the standard deviation divided by the meanvalue) were used to characterise the tissue in different groups duringpregnancy. Doppler velocimetry was performed in the main stems ofpulmonary arteries in normal pregnancies and pregnancies withpreeclampsia and diabetes.Results: The coefficients of variation in mature foetuses were greaterthan 29% for placentas in-vivo, greater than 34% for placentas in-vitro,greater than 28% for liver tissue and greater than 30% for lung tissue.Placental, lung and liver tissue of diabetic pregnancy tended to havelower coefficients of variation throughout their pregnancies. We foundin mature foetuses mean peak systolic velocity higher than 40 cm/sec.and PI lower than 3,00. In mature foetuses with preeclampsia we foundhigher mean peak systolic velocity in comparing with normotensivepatients.Conclusions: The coefficient of variation values for placentas in-vivoand in-vitro, and fetal lungs and liver increase during pregnancy innormal and preeclamptic patients with increasing gestational age anddecrease in diabetic patients.


P4.18.15ULTRASONOGRAPHIC & SONO-SALPINGOGRAPHICPARAMETERS SUGGESTIVE OF GENITAL TUBERCULOSIS –BASIS FOR THERAPEUTIC TRIAL OF ANTI-TUBERCULARTREATMENT (ATT) IN FEMALE INFERTILITYS. Gupta (1), P.P. Gupta (2)(1) Dept. OB/GYN & Sonology, Jeevan Jyoti Medicare, Gorakhpur,

UP, India.(2) Dept. Pharmacology, BRD Medical College, Gorakhpur, UP,

India.

Objectives: The study was done to frame ultrasonographic & sono-salpingographic guidelines for therapeutic trial of ATT in femaleinfertility.Study Methods: This open, prospective & non-comparative study wasdone with150 infertile women. After routine clinical exam, they weresubjected to thorough abdominal, vaginal sonographic and sono-salpingographic (SSG) examinations on 10th day of menstruation. On thebasis of positive findings, 9 parameters were laid out. 50 patients having4 or >4 positive parameters were selected for therapeutic trial of ATT.For an initial 12 weeks (base line phase) patients were treated forinfertility on the lines of individual merits. For the next 12 weeks,antitubercular therapy was added to these patients (study period).Results: The efficacy parameters evaluated during the study periodcompared to baseline included improvement in menstrual function(cycle & flow); pelvic pain & vag. discharge; ovulation and conceptionrate. Efficacy parameters were analyzed and compared. Improvement inall the parameters in study period (after adding ATT) was significantcompared to baseline phase (p<0.001, Wilcoxon Rank Sum Test).Conclusion: Sono- and sono-salpingographic parameters laid down inthis study may form a promising, valuable and basic tool to screen andtreat genital tuberculosis in female infertility.

P4.18.16UTERINE ARTERY DOPPLER VELOCIMETRY IN PATIENTSWITH SYMPTOMS OF PRETERM LABORG. Daskalakis , A. Antsaklis, N. Papantoniou, S. Kitmirides, A.Dimitreli, S. Michalas, 1st Dept. OB/GYN, Alexandra MaternityHospital, Athens University, Athens, Greece.

Objectives: The aim of the study was to investigate if spontaneouspreterm delivery is associated with abnormal uterine artery Doppler.Study Methods: The study population consisted of 127 women withsingleton pregnancies who admitted for symptoms of preterm laborbetween 24 and 36 weeks’ gestation. All women had a fetalultrasonographic scan and color Doppler ultrasound of both uterinearteries before initiation of tocolytic treatment. Both uterine arterieswere examined at their crossing with the external iliac artery.Gestational age was calculated from the last menstrual period, or from afirst trimester ultrasound if there was a discrepancy of more than a week.Pregnancies complicated by renal disease, hypertension, pre-eclampsia,or fetal growth retardation were excluded from the study. The resistanceindex (RI) was computed for the uterine arteries and the outcomes ofpregnancies with preterm and term deliveries were compared.Results: 82 of 127 (64.5%) women with symptoms of preterm laborgave birth preterm. Uterine artery Doppler RI was significantly higher inthe patients delivered preterm (RI: 0.61), compared to those delivered atterm (RI:0.43). Abnormal values of uterine artery RI (>0.58) weredetected in 43 patients of the preterm group (52.4%).Conclusions: Preterm delivery is associated with increased resistance inthe uterine arteries. This is more evidence that poor placental perfusion,attributable to abnormal implantation, may play a role in thepathogenesis of preterm delivery.

P4.18.17VERIFYING THE EFFECTIVENESS OF MEDICAL ABORTION -ULTRASOUND VS. HCG TESTINGC. Fiala , P. Safar, Dept. OB/GYN, General Public Hospital,Korneuburg, Austria

Objectives: Medical abortion with Mifepristone and Misoprostol iseffective in 95-98.6% of cases. We compared ultrasound examinationand HCG testing to determine the effectiveness of the treatment.

Study Methods: 217 women with an unwanted pregnancy up to 49 daysof amenorrhea were treated between 26 April and 10 November 1999.They received 600mg Mifepristone and 400mg Misoprostol 48 hourslater. Expulsion was not verified routinely. An ultrasound examinationand HCG test was performed on day one and between days 6-18.Results: The treatment was successful in 98.6 % of cases. A total ofthree curettages had to be performed; one for continued pregnancy,missed abortion and haemorrhage respectively. One patient had a missedabortion but expelled after hormone withdrawal. Expulsion of the sacwas verified in six patients.HCG levels at the control visit dropped to 3 % in average (SD 3) rangingfrom 1-17 % in all cases of successful abortion, with three exeptions of27%, 32% and 44%. The two missed abortions and the persistentpregnancy led to an HCG rate of 91%, 159 % and 7900% respectively.Endometrium measured 10 mm on average (SD 4) at the control visit inthe cases of successful abortion, ranging from 1-24 mm. Diagnosis ofsuccessful treatment could be based on ultrasound examination in only66% of cases, owing to the early stage of the pregnancy in the remainingcases.Conclusion: Measuring HCG level before and after treatment gave areliable result in 98.5% of successful abortions, compared to 66% withultrasound examination.

P4.19 VULVA

P4.19.01PROGNOSTIC INDICATORS AND THERAPEUTIC STRATEGIESIN MELANOMA OF THE VULVAA. Ditto , F. Raspagliesi, R. Fontanelli, Dept. of Gynecologic SurgicalOncology, Istituto Nazionale Tumori, Milan, Italy.

Objectives: The aim of this retrospective study was to evaluateprognostic significance of lymph nodal variables in melanoma of thevulva.Study Methods: From 1979 through 1991, 39 women with a diagnosis ofvulvar melanoma underwent radical surgery. Age, size and location ofthe tumor, histologic type, ulceration, depth of invasion, tumorthickness, lymph node status, and number of positive nodes wereassessed for prognostic significance by univariate and multivariateanalysis.Results: Level and tumor thickness were significant predictors of lymphnode involvement but not of overall survival. The most powerfulpredictor of survival by multivariate analysis was the number of positivenodes (P<0.00003), followed by lymph node status (P<0.0001).Conclusions: On the basis of the data, the number of positive lymphnodes represents the strongest, independent prognostic factor inmelanoma of the vulva. Owing to the lack of effective adjuvanttherapies, such prognostic indicators might be used to define the extentand timing of the primary surgical approach to this tumor.

P4.19.02SIGNIFICANCE OF VULVOSCOPY IN PATIENTS WITH VULVALSYMPTOMSD. Goswami (1), A. Batra (2), S.K. Das (2), M. Chandra (3)(1) Dept. OB/GYN, All India Institute of Medical Sciences, New Delhi,India.(2) Dept. OB/GYN, Safdarjang Hospital, New Delhi, India.(3) Institute of Pathology, Safdarjang Hospital Campus, New Delhi,India.

Objectives: To evaluate the accuracy of naked eye examination andvulvoscopy as compared to histopathology for diagnosing vulval lesions.Study Methods: Subjects included 34 women with vulval symptomspresenting to the gynae outpatient clinic. In each case, naked eyeexamination of the vulva was performed followed by vulval colposcopy(Carl Zeiss, 0.4x and 1x) after application of (a) normal saline, (b) 5%acetic acid, and (c) Collin’s test. Lesions detected were biopsied.Results: 24 of 34 (7 %) women had vulval lesions on colposcopy, 18 ofwhich were also evident on naked eye examination. Histopathologicaldiagnosis for the 24 lesions were humanpapillomaviral (HPV) lesion(n=12), nonneoplastic epithelial disease (NNED)of vulva (n=5), NNEPwith HPV changes (n=2), well differentiated squamous cell carcinomaand HPV lesion (n=1), nonspecific inflammation of dermis (n=1) and


nonspecific vulval ulcer (n=3). For HPV lesions, naked eye examinationwas 53% sensitive and 88% specific while colposcopy was 86%sensitive and 100% specific. For inflammatory vulval lesions, naked eyeexamination was 50% sensitive and 75% specific while colposcopy was75% sensitive and 100% specific. For NNED of vulva, both naked eyeexamination and colposcpy were 100% accurate. Single case of vulvalmalignancy was not diagnosed on naked eye examination but wasstrongly suspected on vulvoscopy and Collin’s test.Conclusion: Vulvoscopy had a higher sensitivity and specificity thannaked eye examination for the HPV, inflammatory and malignant vulvallesions. Hence vulvoscopy should be routinely used for examining andtaking targeted biopsies in patients with vulval symptoms.

P4.19.03SQUAMOUS VULVAR CARCINOMA: OUR EXPERIENCE IN THELAST TEN YEARSJ. Lombardía-Prieto , M.L. Fernández-Pérez, M. A. Garcia-Largo, M. V.Peral, M. Sánchez-Dehesa, A. Sanchez-Dehesa, Gynecology OncologyUnit, Dept. OB.GYN, Hospital, Virgen de la Salud, Toledo, Spain.

Our experience with 22 cases of squamous vulvar carcinoma with aretrospective study (1987 – 1998).Vulva cancer accounts for about 4% of all gynecological cancer, in ourstudy 6%, being the 88% squamous vulvar cancer.The mean age at presentation was 69.4 years (range 51-87); there werefamiliar history about oncological pathology in 22.7%; we have found asrisk factors associated: inflammatory or non-neoplasic lesion (18.2%),dystrophic lesion (VIN) (22.7%) and hypertension (59%).Labia majora was the most common site (86.3%); the most commonmacroscopic histological type was the ulcerous one (54.5%) and the firstsymptom was in the 77.2%, the itching. Range time first symptom-consulting was 32.6 months (1-120), and range time diagnosis-treatmentwas 27.6 days (10-58).The diagnosis was in all of them with a biopsy and the surgery was:radical vulvectomy with inguinofemoral lymphadenectomy (81.8%),simple vulvectomy (9.1%) and hemivulvectomy with node ipsilateraldiseccion (9.1%).The FIGO stage at diagnosis was I (36%), II (52%), III (12%).There were positive nodes in 8% (we used radiotherapy).There wasn’t mortality because of the surgery. The following meantimehas been 55.5 months (4-228). In 22.7% were a recidivity in mean timeof 17 months after the surgery (6-36); 7 women death, 2 are living withthe pathology and 13 of them are free of illness. The principal mortalitywas cardiovascularin, 50% of these 8 cases.

P4.19.04TRICHILEMMAL CARCINOMA OF THE VULVAT.Shimada , H. Nakajima, T. yamabe, T. Ishimaru, Dept. OB/GYN,University Hospital, Nagasaki, JapanM.Fuse, Dept.OB/GYN, R.Hirose, DermatologyNational Nagasaki Central Hospital, Nagasaki, Japan

Introduction: Trichilemmal carcinoma is a malignant neoplasm of hairfollicles which is derived from the outer root sheath. It usually developsas a simple tumor on the face, but rarely appears on the vulva. We reporta case of trichilemmal carcinoma on the vulva and discuss thehistological findings.Case Report: The patient was 42 years old Japanese woman. She noticeda painful, small and reddish tumor on the anterior right labia majora twomonths ago and transferred to National Nagasaki Central Hospital atMarch 8 1999. On examination, a brown, hard tumor 10_~10mm in sizewas seen on the anterior right labia majora. External groin node was notpalpable. Because the tumor seemed to be benign, it was removedsurgically under local anesthesia.Histologicaly, the H-E stained section of the specimen showed lobularproliferation centered on the pilar apparatus. Tumor cell was PAS-positive, large in size and irregular, and had the pleomorphic nuclei. Thehistological diagnosis was trichilemmal carcinoma. Because one part ofthe section showed the tumor invasion to the derma, we enforced theexpanded excision of the remains.Since the specimen obtained from the remains didn't show tumorinvasion, neither radiation nor chemotherapy was carried out.Conclusion: Trichilemmal carcinoma is usually derived from the faceand leg. The frequency of trichilemmal carcinoma on the vulva is about

4.3%. Almost prognosis of this tumor is thought to be good, but onereport has described one case of died patient after the excision of thetumor. We think that we must be careful to the tumor on the vulva evenif it seem to be benign tumor.

P4.19.05VULVAR CANCER: EXPERIENCE AT UNIVERSITY OF THERYUKYUSY. Teruya , H. Masamoto, M. Takashiki, K. Kanazawa, Dept. OB/GYN,University of the Ryukyus, Okinawa, Japan.

Objectives: The aim was to retrospectively analyze patients with vulvarcancer who were managed at the Ryukryu University Hospital.Study Methods: Medical records of 42 patients with histologicallyconfirmed primary vulvar cancer, treated between 1986 and 1999 werereviewed in reference to histology, stage, treatment and survival.Results: Mean age at diagnosis was 68.9 years with a range of 28 to 90years. The definitive histological diagnoses were squamous cellcarcinoma in 37 cases (88%), adenocarcinoma in 2, Paget disease in 1and malignant melanoma in 2. The 37 patients with squamous cellcarcinoma were classified in FIGO Stage 0; 6 cases, Stage I: 5; Stage II:10; Stage III: 13 and Stage IV:3. In 29 (78%) of the 37 cases, theprimary treatment was surgical and 1 additionally received radiotherapy.In the other 8 patients, the primary treatment was radiotherapy. In recentyears, not radical vulvectomy but radical local excision withlymphadenectomy via separate grion incisions was applied to patientswith Stage I disease. 1 young patient with Stage 0 was successfullytreated by ablation using CO2 laser vaporization and thereafter delivered3 healthy babies. Recurrences developed in 11 patients, locally in 7cases and distantly in 4. Five-year survival rates (Kaplan-Meier) were100% in Stage 0, 100% in Stage I, 83% in Stage II, 48% in Stage III and0% in Stage IV.Conclusions: Our experience appeared to support the recent therapeuticaspect that management of patients with Stage 0 and I squamous cellcarcinoma of the vulva should be individualized in consideration ofconservative treatment.

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