ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY

Is polycystic ovarian morphologyrelated to a poor oocyte quality aftercontrolled ovarian hyperstimulationfor intracytoplasmic sperm injection?Results from a prospective,comparative study

Julien Sigala, Pharm.D.,a Christophe Sifer, M.D.,b Didier Dewailly, M.D.,c Geoffroy Robin, M.D.,c

Aude Bruyneel, M.D.,c Nassima Ramdane, B.S.T.,d Val�erie Lefebvre-Khalil, M.D.,a

Val�erie Mitchell, Pharm.D., Ph.D.,a and Christine Decanter, M.D.c

a EA 4308 Gam�etogen�ese et qualit�e du gam�ete, Institut de Biologie de la Reproduction-Spermiologie-CECOS, HopitalJeanne de Flandre, Centre Hospitalier R�egional et Universitaire, Lille; b Service d'Histologie-Embryologie-Cytog�en�etique-CECOS, Hopital Jean Verdier (AP-HP), Centre Hospitalier Universitaire, Bondy; c Service de Gyn�ecologie Endocrinienne etM�edecine de la Reproduction, Hopital Jeanne de Flandre, Centre Hospitalier R�egional et Universitaire, Lille; andd Centre d'Etudes et de Recherche en Informatique M�edicale, Centre Hospitalier R�egional et Universitaire, Lille, France

Objective: To evaluate the relationship between polycystic ovarian morphology (PCOM) and oocyte quality after controlled ovarianstimulation for intracytoplasmic sperm injection (ICSI).Design: Prospective, comparative study with concurrently treated and age-matched controls.Setting: Academic IVF unit of the Lille University Hospital.Patient(s): A total of 194 women were prospectively included before their first IVF-ICSI attempt for exclusive male infertility. Theywere classified into PCOM (n ¼ 97) or control groups (n ¼ 97) according to their follicle number per ovary. The nuclear maturationand morphologic aspects of 1,013 oocytes from PCOM patients were assessed and compared with those of 774 oocytes from controls.Intervention(s): None.Main Outcome Measure(s): Rate of metaphase II (MII) and morphologically abnormal oocytes.Result(s): The mean number of total and MII oocytes retrieved was significantly higher in the PCOM group. The rate of MII andmorphologically abnormal oocytes was equivalent between the two groups. The mean number of embryos was significantly higherin the PCOM group. However, the percentage of top-quality embryos on day 3 was similar between the two groups. The

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implantation and clinical pregnancy rates were significantly higher in the PCOM group.Conclusion(s): Polycystic ovarian morphology does not have a negative impact on the qualityof oocytes and embryos or the outcome of IVF-ICSI. (Fertil Steril� 2014;-:-–-. �2014 byAmerican Society for Reproductive Medicine.)Key Words: PCOS, PCOM, IVF, oocyte quality, oocyte morphology

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Received August 7, 2014; revised and accepted September 26, 2014.J.S. has nothing to disclose. C.S. has nothing to disclose. D.D. has nothing to disclose. G.R. has nothing

to disclose. A.B. has nothing to disclose. N.R. has nothing to disclose. V.L.-K. has nothing todisclose. V.M. has nothing to disclose. C.D. has nothing to disclose.

Reprint requests: Christine Decanter, M.D., Service de Gyn�ecologie Endocrinienne et M�edecine de laReproduction, Hopital Jeanne de Flandre, Avenue Eug�ene Avin�ee, 59037 Lille, France (E-mail:christine.decanter@chru-lille.fr).

Fertility and Sterility® Vol. -, No. -, - 2014 0015-0282/$36.00Copyright ©2014 American Society for Reproductive Medicine, Published by Elsevier Inc.http://dx.doi.org/10.1016/j.fertnstert.2014.09.040

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P olycystic ovarian morphology(PCOM) according to ultrasono-graphic criteria is a very common

finding in an IVF center population. Thisincludes symptomatic patients withpolycystic ovary syndrome (PCOS),identified in 18%–25% of infertile cou-ples (1), and so called ‘‘sonographiconly’’ PCO, the prevalence of which has

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ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY

been estimated as high as 33% in asymptomatic patients (2–4).Polycystic ovarian morphology is characterized by asignificantly enlarged cohort of early-growing and recruitablefollicles. This excessive follicle number is linked todisturbancesin folliculogenesis, which are thought to be the consequence ofintraovarian hyperandrogenism (5–7). The cohort of growingfollicles during controlled ovarian hyperstimulation (COH) isfrequently heterogeneous in size, with mature, intermediate,and small follicles. In addition, the number and quality ofmature oocytes has been proposed as being poor (6, 8, 9); andrecent data suggested that oocyte competence could beimpaired in PCO patients owing to an inadequate dialoguebetween the cumulus cells and oocyte (10, 11).

Despite these assumptions, the paucity of studies focusingon oocyte quality in women with PCOM does not allow us tomake this conclusion. Most studies are retrospective andcompared PCO patients with a historical control group (12–17). Furthermore, the criteria used to diagnose PCOM wereextremely heterogeneous because of a lack of consensus.The results provided by these studies are thus conflicting,finding either a better oocyte/embryo quality andpregnancy rate or vice versa (18). Moreover, in most ofthese studies, the oocyte quality evaluation was only basedon the evaluation of the nuclear stage (i.e., the meannumber of metaphase II [MII] oocytes) (12, 14, 16). It is nowwell recognized that some specific morphologic oocyteabnormalities, such as the presence of a wide perivitellinespace (PVS) or a granular cytoplasm, must be givenattention because it has been reported that they areassociated with a significant decrease in the chance offertilization (19–21). Likewise, after COH, it is interesting tonote that more than half of oocytes retrieved present one ormore morphologic abnormalities (19, 21). Only oneretrospective study focused on the oocyte morphology inPCOM patients and found no difference with age-matchedcontrols (13). Taking into account the lack of well-designedstudies in this specific topic, we aimed to prospectively inves-tigate the relationship between PCOM and oocyte qualityafter COH by performing a prospective, comparative studywith concurrently treated and age-matched controls.

MATERIALS AND METHODSStudy Design

This was a prospective, comparative study performed in theAcademic IVF Center of Lille University Hospital (France). Itwas approved by the local institutional review board of LilleUniversity Hospital. Written, informed consent was obtainedfrom all subjects before beginning COH.

A total of 194 patients, aged 21–37 years, undergoingtheir first intracytoplasmic sperm injection (ICSI) attemptfor an exclusive male factor indication, were prospectivelyrecruited from January 2008 to December 2011.

The study was designed with 80% power to detect a rela-tive 30% difference between groups (with a significance levelof 5%) for the MII/total oocytes ratio. With the assumption ofa ratio at 70% in the control group, it was calculated that atleast 82 patients had to be included in each group. We there-fore recruited 97 patients with PCOM according to standard-

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ized criteria: we used the revisited threshold for folliclenumber per ovary (FNPO) proposed by Dewailly et al. (22),from our own experience with a new ultrasound machine(i.e.,R19 follicles of 2–9 mm diameter in at least one ovary).This threshold corresponds to the former threshold of 12 withour previous ultrasound machine. Among these 97 PCOMpatients, 51 (52.5%) had PCOS (i.e., ultrasonographic criteriaof PCOM together with either oligoanovulation or hyperan-drogenism or both) and 46 (47.5%) had ‘‘PCOM only’’ (i.e.,ultrasonographic criteria of PCOM, ovulatory cycles, and noclinical or biological hyperandrogenism).

Concomitantly, we recruited 97 age-matched controls.These were ‘‘non-PCOM patients’’ who underwent their firstICSI for exclusively male infertility during the same timeperiod, according to the following criteria: ovulatory cycles,no hyperandrogenism, FNPO between 8 and 18 follicles ineach ovary, and FSH <10 IU/mL. This group was defined asthe control group.

Because it has been suggested in several studies thatobesity could adversely affect oocyte quality, we excludedpatients with a body mass index (BMI) >32 kg/m2, for bothPCOM patients and controls.

Hormonal Assays

All patients had had day-3 baseline hormonal investigationson a blood sample before the ICSI attempt, at least 3 monthsafter any hormonal treatment, including FSH, antim€ullerianhormone, E2, LH, D4-androstenedione, and T.

The FSH, LH, and E2 were measured using chemilumines-cent, two-site immunoassays on a multiparameter system(Axsym; Abbott Laboratories). Antim€ullerian hormone wasmeasured using a kit of second immuno-enzymatic genera-tion antim€ullerian hormone–EnzymeImmunoAssays (ref.A16507) provided by Beckman Coulter Immunotech. Delta4-androstenedione wasmeasured in duplicate by radioimmuno-assay using a kit provided by Beckman Coulter Immunotech.Testosterone was measured in duplicate by radioimmuno-assay using the Coat-a-Count kit provided by Siemens DPC.

Ultrasound Examination

The baseline FNPO assessment was performed with a Volu-son E8 Expert (General Electric Systems) with a 5–9 MHztransvaginal transducer by counting all the 2–9 mm diam-eter follicles. During COH, follicles were counted and classi-fied into 3 different size categories: 10–12 mm, 13–15 mm,and >15 mm. All the ultrasonographic examinations wereperformed on the same machine by only two differentoperators.

COH Protocol

Patients received either an agonist or an antagonist protocol.In the agonist protocol daily injections of triptorelin (0.1 mg)were started in themid-luteal phase of the preceding cycle (forwomen with regular menstruations) or on the first day ofbleeding (for women with oligomenorrhea or amenorrhea).Desensitization was checked 12–15 days after initiation ofGnRH agonists (desensitization day). Daily injections of

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recombinant FSH (rFSH) were started only if E2 levels were<50 pg/mL and if there was no functional ovarian cyst.

In the antagonist protocol daily injections of rFSH werestarted on the second day of bleeding. The antagonist wasintroduced on day 6 of the FSH treatment.

The rFSH starting dose varied between 75 and 225 IU/d inthe PCOM group and between 100 and 400 IU/d in the controlgroup, according to age, BMI, and FNPO in both arms. Puri-fied urinary hCG (5,000 IU) was administered as soon as atleast 3 follicles reached a mean diameter R17 mm with aconsistent rise in serum E2 concentration. Oocyte retrievalwas performed 35–36 hours after hCG injection by transvagi-nal ultrasound-guided needle aspiration.

COH Outcomes

Oocyte morphology evaluation. Approximately 2 hours afterthe recovery of oocytes, a decoronization by chemical andmechanical methods was done. Every oocyte was plungedfor 20 seconds into a solution containing hyaluronidase(80 IU/mL hyaluronidase in Flushing, FertiPro), and thedetachment of the cumulus cells and the corona radiata wasdone by successive aspirations and expulsions of oocyteswith a micropipette. This technique allowed the assessmentof oocyte meiotic maturity. Assessment of the morphologyof MII oocytes was done at the time of injection of spermato-zoa, approximately 3 hours after oocyte retrieval, undermagnification �400 with an inverted microscope (LeicaDMIRB) by only two different operators.

Two categories of oocyte abnormalities were defined:extra- and intracytoplasmic. Observed morphologic extracy-toplasmic abnormalities were a fragmented or abnormal firstpolar body (IPB), an abnormal zona pellucida (ZP) (thick, fine,or irregular), presence of an important PVS or material in thePVS, and an abnormal shape of the oocyte. Intracytoplasmicdysmorphologic features were an excessively granular cyto-plasm or presence of one or several vacuoles. Huge oocytesor oocytes containing inclusions of smooth endoplasmicreticulum were systematically ruled out and not injectedaccording to our IVF center policy. The reproducibility ofthe inter-biologist evaluation of oocyte quality was validatedby an internal quality control of our laboratory. Every item(granularity, ZP, IPB, PVS, shape, vacuoles) was blindly esti-mated on 50 consecutive oocytes from our ICSI programaccording the European Society of Human Reproductionand Embryology guidelines: atlas of human embryology(23). There was no significant difference from one biologistto the other. An average oocyte quality index (AOQI) was es-tablished and calculated for the PCOM and the control group.Considering all the MII oocytes retrieved, each morphologicabnormality was scored as 1 if the abnormality was presentand as 0 if it was not. Considering the 7 abnormalities (gran-ularity, ZP, IPB, PVS, presence of material in PVS, shape, vac-uoles), the AOQI score was represented by the ratio betweentotal number of abnormalities and the number of MII oocytes.

Embryo morphology evaluation. The technique of ICSI wasperformed routinely on each MII oocyte as previouslydescribed (24). Normal diploid fertilization was estimated16–18 hours after injection. Only oocytes with 2 visible

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pronuclei were considered as normal and were consequentlyestimated. Early cleavage was observed 27 hours afterinjection. Embryo quality was estimated 44–46 hours after in-jection. The system of embryo classification in our center wasbased on the number and the size of blastomeres, the degree offragmentation, and the presence of multinucleated blasto-meres according to the Van Royen classification, confirmedwith the recent new Istanbul consensus scoring system (25,26). On day 2, an embryo was considered as good quality ifit had 4 or 5 adequate-sized blastomeres, exhibiting no multi-nucleation with <10% of cytoplasmic fragmentation. If thetransfer took place on day 3, to be considered as good qualitythe embryos had to have 7 or 8 adequate-sized blastomereswith <10% of cytoplasmic fragmentation and no multinu-cleation. In this study good embryos were called ‘‘top-quality’’embryos. The reproducibility of the inter-biologist evaluationof embryo qualitywas validated by an external quality controlof our laboratory (Evaluation externe de qualit�e, embryologieClinique, Biologie prospective). Embryo transfers were per-formed with a soft catheter 2 or 3 days after oocyte retrieval.Luteal-phase support consisted of 600 mg vaginal micronizedP per day and 6mg oral E2 per day, both initiated from the dayof oocyte retrieval. If a pregnancy occurred, P and estrogenadministration were maintained up to the evidence of a fetalheart activity at ultrasound. Clinical pregnancy rate wasdefined as the number of pregnancies with at least 1 gesta-tional sac exhibiting fetal heart activity. Implantation ratewas defined by the ratio between the number of gestationalsacs with fetal heart activity and the number of embryostransferred. All pregnancies were followed up until delivery.

Statistical Analysis

Continuous variables were expressed as mean, minimum, andmaximum. Categorical data were expressed as frequency andpercentage. The assumption of normality was tested forcontinuous data using the Shapiro-Wilk test. The Mann-Whitney U test or Student test were used to compare 2 groupsaccording to distribution of the variable. The comparison offrequencies was performed by the c2 test or the Fisher exacttest. P values of< .05 were considered statistically significant.Statistical analysis was performed with SAS software, version9.3 (SAS Institute).

RESULTSClinical and hormonal characteristics of all patients areshown in Table 1. The PCOM and control groups did not differin terms of age and BMI. Antim€ullerian hormone levels andFNPO were significantly higher in PCOM patients.

The characteristics and the outcomes of COH are pre-sented in Table 2. The repartition of the 2 protocols was asfollow: 37.1% of antagonist protocol and 62.9% of agonistprotocol in the PCOM group vs. 23.7% of antagonist protocoland 76.3% of agonist protocol in the control group (nonsig-nificant [NS]). There was no statistical difference betweenthe 2 protocols regarding the primary and secondary end-points in both groups.

The rFSH starting dose in the PCOM group varied between75 IU and 225 IU. The total dose of gonadotropin was

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TABLE 1

Baseline clinical, hormonal, and ultrasonographic characteristics ofthe study population.

CharacteristicPCOM group(n [ 97)

Control group(n [ 97) P value

Age (y) 28.7 (21–37) 28.7 (21–37) NSBMI (kg/m2) 23.5 (17.6–32) 22.4 (16.5–29) NSFSH (IU/L) 5.6 (1.3–8.9) 6.1 (3.6–9.6) NSE2 (IU/L) 34.8 (13–69) 38.7 (12–88) NSLH (IU/L) 4.8 (1.3–12.9) 4.7 (0.9–12) NSD4 (ng/mL) 1.7 (0.5–4.1) 1,4 (0.5–3) NST (ng/mL) 0.3 (0.1–0.6) 0.2 (0.1–0.5) NSAMH (pmol/mL) 59.5 (28.9–158.9) 24.5 (14.3–31) < .0001FNPO (n) 23 (15–55) 11 (8–18) < .0001PCOM-only (%) 47.5 –

PCOS (%) 52.5 –

Note: Values are expressed as mean (range). PCOM-only ¼ ultrasonographic criteria ofPCOM, ovulatory cycles, and no clinical or biological hyperandrogenism; PCOS ¼ ultrasono-graphic criteria of PCOM plus either oligoanovulation or hyperandrogenism or both; D4 ¼D4-androstenedione.

Sigala. Oocyte quality after COH in PCOM patients. Fertil Steril 2014.

ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY

significantly lower into the PCOM group. There were signifi-cantly more intermediate follicles (i.e., 10–15 mm) duringCOH in the PCOM group. The ratio between MII oocytes andeach size category of follicles did not differ between the 2groups. A higher number of total and MII oocytes wasretrieved in the PCOMgroup. There was no difference betweenthe 2 groups regarding the number of immature and atretic oo-cytes. We obtained significantly more embryos in the PCOMgroup. The fertilization rate did not differ in patients withPCOM compared with controls. However, the mean numberof top-quality embryos was significantly higher in thePCOM group. Implantation, ongoing pregnancy, and deliveryrates were significantly higher in the PCOM group (Table 2).

Analysis of the oocyte cohort showed that the number ofMII oocytes exhibiting a normal morphology was equivalentbetween the PCOM and control groups (Table 3). No signifi-cant difference was observed regarding extracytoplasmicabnormalities (i.e., percentage of abnormally shaped oocytes,fragmented IPB, abnormal ZP, large PVS, or presence of ma-terial in PVS). Incidence of cytoplasmic abnormalities such aspresence of vacuoles or an abnormal granularity was similarbetween the 2 groups. The AOQI score was comparable inPCOM and control groups (0.8 vs. 0.9, respectively).

No difference was found between PCOS and PCOM-onlyregarding all these characteristics. From total embryos scoredin each group, 34.5% were top embryos in the PCOS subgroupand 38.6% in the PCOM-only subgroup (P¼NS). The rate ofmorphologically normal oocytes was equivalent betweenthese 2 subgroups (31%vs. 35.7%, respectively), andno signif-icant difference was noted concerning all of the morphologicabnormalities. The AOQI was also similar (0.79 vs. 0.86,respectively; P¼NS). No differences in clinical pregnancy, im-plantation, or birth rates were observed between PCOS andPCOM-only patients.

DISCUSSIONFrom the results of the present study, it seems that PCOM isnot associated with poor oocyte/embryo quality or with an

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unfavorable outcome of ICSI. Data from the literature in thefield of polycystic ovaries and IVF are scarce. Nevertheless,it has been frequently argued that the disordered folliculogen-esis of this syndrome could have detrimental effects on thedevelopmental competence of the oocyte (5, 6, 8, 9, 27). Inaddition, recent data have suggested that MII oocytes frompatients with PCOS had an altered gene expression profile,especially for genes implicated in chromosome alignmentand segregation during meiosis and mitosis, cell-cycle check-points, genes containing androgen receptor binding sites, andgenes of primary follicle recruitment (10, 11, 28, 29). Whetherthese abnormalities could interfere with the reproductivecompetence of oocytes remains to be elucidated. Indeed,despite these interesting results, a meta-analysis found thatpatients with PCOS had the same pregnancy rate as other pa-tients undergoing IVF, suggesting that polycystic ovaries arecapable of producing at least enough competent oocytes afterCOH (30). Not surprisingly, we found a higher number of totaland MII oocytes in the PCOM group, with no differenceregarding the number of immature or atretic oocytes. The ac-curate study of the dynamics of follicular growth in bothgroups during COH revealed that this high number of MIIoocytes is directly related to the higher number of matureand intermediate follicles. Our results are in accordancewith those of authors who have found higher numbers butthe same rate of MII oocytes between PCO patients andcontrols (12–14), and a higher number but the same rate oftop-quality embryos (13, 14). The prospective design of thepresent study allowed a comparison of age-matched controlstreated concurrently. In addition, the use of standardized andconsensual diagnosis criteria for PCOM significantlyenhanced the statistical power of these results.

We intentionally chose the sole PCOM criteria to establishour study group because it is now well recognized that there isno difference in the IVF outcome between PCOM-only andPCOS (3, 13, 14, 31, 32). Nowadays there is an almostuniversal consensus on the choice of follicular excess as themain criteria to define PCOM. However, establishing theright threshold for distinguishing polycystic from normalovaries remains a source of debate. Recently, from acomprehensive analysis of the recent literature, theAndrogen Excess and Polycystic Ovary Syndrome Societyreported a consensual definition of PCOM with a thresholdof 25 follicles of 2–9 mm per ovary, but to be used onlywith new ultrasound machines whose maximal frequencyprobe is >8 MHz (33). However, this consensus recognizesthat asymptomatic PCOM (so-called ‘‘PCOM only’’) mighthave FNPO below this threshold. Therefore, for the presentstudy we used our ‘‘in-house’’ threshold (i.e., 19 follicles perovary), based on cluster analysis that permits exclusion ofall asymptomatic PCOM from a control population (22).With this definition, we did not find any difference betweenPCOS and ‘‘PCOM only’’ during COH.

Regarding oocyte morphology, we failed to observe anydifference between patients with PCOM and controls. To ourknowledge, this is the first report of the systematic prospec-tive evaluation of oocyte morphology in this specificsubgroup of women with polycystic ovaries. Furthermore,we standardized in our study the oocyte and embryo

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TABLE 2

COH outcome.

Parameter PCOM group (n [ 97) Control group (n [ 97) P value

Agonist protocol (n) 61 74Antagonist protocol (n) 36 23rFSH starting dose (IU) 136.5 (75–225) 185.2 (100–400) < .0001rFSH total dose (IU) 1,586 (750–3,425) 2,014 (850–4,800) < .0001Duration of stimulation (d) 11.6 (8–28) 10.8 (7–24) NS>15 mm follicles (n) 9.1 (3–19) 8.2 (3–20) .0213–15 mm follicles (n) 7.3 (1–17) 5.1 (0–13) < .000110–12 mm follicles (n) 6.2 (0–18) 2.8 (0–11) < .0001Total oocytes (n) 14.4 (4–27) 11.3 (3–23) < .0001MI þ VG oocytes (n) 1.9 (0–11) 1.3 (0–6) NSAtretic oocytes (n) 1.9 (0–6) 1.9 (0–8) NSMII oocytes (n) 10.4 (2–21) 8 (2–17) .001Ratio MII oocytes/total oocytes 0.7 (0.1–1) 0.7 (0.2–1) NSRatio MII oocytes/>15 mm follicles 1.3 (0.2–3.8) 1.1 (0.2–3.7) NSRatio MII oocytes/R13 mm follicles 0.7 (0.1–2) 0.6 (0.1–2.1) NSRatio MII oocytes/R 10 mm follicles 0.5 (0.1–1.1) 0.5 (0.1–2.1) NS2PN fertilization rate (%) 63.7 (12.5–100) 64.5 (20–100) NSEarly cleavage rate (%) 33.7 (0–100) 39.9 (0–100) NSEmbryos (n) 6.3 (1–17) 4.7 (1–13) < .0001Top-quality embryos (%) 36.5 (0–100) 37.3 (0–100) NSTop-quality embryos/MII oocytes (%) 24 (0–86) 24.6 (0–100) NSFrozen embryos (n) 2.8 (0–12) 1.2 (0–7) .001Embryos transferred (n) 1.6 (1–2) 1.7 (1–2) NSeSET (%) 29.9 (0–100) 22.7 (0–100) NSImplantation rate with fresh embryos (%) 37.4 (0–100) 22 (0–100) .005Ongoing clinical pregnancy rate per transfer with fresh embryos (%) 46.4 (0–100) 33.7 (0–100) .04Delivery rate per transfer with fresh embryos (%) 44.3 (0–100) 31.2 (0–100) .04Note: Values are expressed as means (range). 2PN ¼ two pronuclei; eSET ¼ elective single embryo transfer; MI ¼ metaphase I oocyte; VG ¼ germinative vesicle.

Sigala. Oocyte quality after COH in PCOM patients. Fertil Steril 2014.

Fertility and Sterility®

observations using internal and external quality controlsvalidating the reproducibility of these parameters in our lab-oratory. Sahu et al. (13) reported similar oocyte morphologyin isolated PCO, PCOS, and age-matched controls, but thisstudy was retrospective, making the findings of this workto be considered with caution. The predictive value of oocytemorphology in human IVF remains controversial. A recentsystematic review about predictive value of oocytemorphology highlighted conflicting results, due to theextreme variability of the methodology (20). Rienzi et al.(19) performed a retrospective study analyzing the matureoocyte morphologic scoring system to evaluate the signifi-

TABLE 3

Oocyte morphology.

Parameter PCOM group Control group P value

Total MII oocytes (n) 1,013 774Normal (%) 31.6 (0–100) 31 (0–100) NSFragmented IPB (%) 48.3 (0–100) 48.3 (0–100) NSAbnormal ZP (%) 3.6 (0–50) 6.1 (0–66.7) NSLarge PVS (%) 2.5 (0–40) 7.8 (0–40) NSMaterial in PVS (%) 11.2 (0–85) 9.3 (0–66.7) NSAbnormal shape (%) 1.9 (0–25) 1.6 (0–33.3) NSGranular cytoplasm (%) 7.8 (0–50) 9.2 (0–60) NSVacuoles (%) 5.7 (0–47) 6 (0–60) NSAOQI 0.8 (0–2.4) 0.9 (0–2) NSNote: Values are expressed as mean (range). AOQI ¼ (total number of abnormalities for alloocytes of an attempt)/(number of MII oocytes).

Sigala. Oocyte quality after COH in PCOM patients. Fertil Steril 2014.

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cance of human oocyte morphology on ICSI outcome. Theyfound that only the presence of specific oocyte peculiarities(i.e., abnormal IPB, large PVS, increased cytoplasmic granu-larity, and presence of a centrally located granular area) isassociated with a significantly reduced fertilization rate.They also highlighted relationships between mature oocytemorphologic scoring and female age, basal FSH, and clinicaloutcome, but the ovarian morphology was not taken into ac-count in this study. Another recent meta-analysis, including14 studies, showed that the probability of an oocytebecoming fertilized is significantly reduced by the presenceof large IPB, large PVS, refractile bodies, or vacuoles (21).Because its value is still debated, the morphologic assess-ment of the oocyte cannot be considered as a gold standardfor quality; but because it is noninvasive and easily appli-cable in routine practice, it still deserves to be considered(19, 21).

We did not find any difference regarding the rate oftop-quality embryos between our 2 groups, but the absolutenumber of top-quality embryos was higher in the PCOMgroup. The implantation and clinical pregnancy rates weresignificantly higher in the PCOM group. Even if this studywas not designed to assess the pregnancy rates, these resultsare noteworthy. They could be explained by the fact weexcluded from our study group the obese patients, who arewell known to be at high risk of low implantation and highmiscarriage rates. Furthermore, it has been shown that obesityand hyperinsulinemia associated with PCOM could be detri-mental for oocyte quality, early embryo development, and

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endometrial receptivity (6, 34, 35). Furthermore, our deliveryrate in the present study is close to our pregnancy rate,confirming that pregnancies in patients with PCOM withoutmetabolic disorders have the same prognosis as in controls.In addition, it has to be noted that we did not exclude low-responder patients from our control group, which canpartially explain the significant difference between preg-nancy and delivery rates in the 2 groups. Polycystic ovarianmorphology–only patients presented the same dynamics offollicular growth and COH outcome as PCOS patients, con-firming that the therapeutic management should be thesame in these 2 subgroups.

In conclusion, from the results of this prospective,comparative study, it seems that PCOM is not related toadverse oocyte quality, at least regarding the rate of nuclearmaturation and the rate of morphologic abnormalities.Furthermore, it seems that PCOM does not negatively affectthe outcome of ICSI in terms of implantation and clinical preg-nancy rates.

Acknowledgments: The authors thank Prof. Alain Duhameland Prof. Patrick Devos for assistancewith statistical analysis;Prof. Pascal Pigny of the Laboratoire de Biochimie et Hormo-nologie (Centre de Biologie Pathologie, Centre HospitalierR�egional et Universitaire, Lille, France) for performing hor-monal measurements; and Prof. Adam Balen and Mr. PhilipJones for their corrections and contributions to the Englishtranslation.

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