“Infertility is a disease. The duration of failure to conceive should be ≥12 months before an investigation is undertaken unless medical history and physical findings dictate earlier evaluation and treatment” *

Monthly fecundity rate in general population is only 15-20%**

*American Society of Reproductive Practice Committee; Hum Reprod 2004;19:1497-501

**Federation CECOS. N Eng J Med 1982;206(7):404-6

Medical Management Surgical Management Artificial Artificial

Insemination (AI)Insemination (AI) IUI Intravaginal Insemination Intracervical Insemination Direct Intraperitoneal

Insemination (DIPI) Fallopian Tube Sperm

Perfusion (FSF) Direct Intrafollicular

Insemination (DIFI)

Assisted Reproductive Techniques (ART)

IVF-ETGIFT, ZIFTICSIPOST

Third Party Reproduction

Adoption

Washed sperm (of the male partner or the donor) is introduced in the uterine cavity in proper time

First used by John Hunter, 1770

Mechanisms Eliminates toxins, bacteria, free radicals present in seminal plasma

Bypasses hostile vaginal acidic pH and cervical mucus

Shortens the distance travelled by the sperms to reach the site of fertilization

Overcomes faulty coital technique

The pregnancy rates per cycle of IUI

The pregnancy rates per couple (undergoing IUI)

Prognostic factors associated with successful IUI

Adverse effects of IUI (if any)

MATERIALS AND METHODSMATERIALS AND METHODS

STUDY AREASTUDY AREADeptt of Obstetrics and Gynaecology, Eden Hospital,Medical College and Hospital, Kolkata STUDYSTUDY PERIODPERIOD 1 year (1st June, 2011- 31st May, 2012)

STUDY DESIGNSTUDY DESIGNObservational Longitudinal Study

STUDY POPULATIONSTUDY POPULATION Infertile couples attending the Infertility clinic, who conform to the inclusion criteria

1. Female partner- 20-40 years

2. Regular frequent unprotected intercourse >1 year but unable to conceive

3. Male factors - Anatomic defects of penis Sexual dysfunction Mild & moderate

oligozoospermia (sperm concentration 5-20 x 106/ml)

Mild asthenozoospermia (<50% sperms showing fast forward and slow progressive motility)

Mild teratozoospermia (morphologically normal sperm 4-15% according to Kruger’s strict criteria)

4. Female factors - Anatomic defects of

vagina or cervix Minimum to mild

endometriosis (AFS score ≤15)

PCOS (defined according to Rotterdam Consensus, 2003- ESHRE and ASRM)

Other causes of anovulation

5. Unexplained infertility

6. All the above factors not responding to conventional medical/ surgical treatment, wherever possible

Exclusion Criteria1.Female factors- Bilateral tubal blockageBilateral tubal blockage Pelvic tuberculosisPelvic tuberculosis Severe pelvic endometriosisSevere pelvic endometriosis

2.Male factors- Azoospermia (No sperm in the ejaculate, confirmed

in three properly collected samples) Severe oligo-astheno-terato-zoospermia(Sperm

density <5 x 106/ml, No motile sperms in the sample, <4% sperm morphologically normal according to Kruger’s strict criteria)

Retrograde ejaculation and anejaculation

RESULTSRESULTS

TOTAL NUMBER OF IUI CYCLESTOTAL NUMBER OF IUI CYCLESNumber Of IUI Cycles

Number Of COUPLES

Total Number Of CYCLES

One 10 10Two 14 28

Three 18 54Four 6 24Five 3 15Six 2 12

TOTAL 53 143

AGE DISTRIBUTION OF THE AGE DISTRIBUTION OF THE COUPLESCOUPLES

0

5

10

15

20

25

30

20-25 26-30 31-35 36-40

6 (11.32% )11(20.75% )

28 (52.83% )

8(15.10% )

Number O

f Wom

en (%

)

Age In Years

AGE O F FEM ALE PARTNERS

n=53

AGE DISTRIBUTION OF THE AGE DISTRIBUTION OF THE COUPLESCOUPLES

05

10

15

20

25

30

35

40

45

50

≤25 26-30 31-35 36-40 >40

2 (3.77% )7 (13.21% )

15 (28.30% )25 (47.17% )

4 (7.55% )

Number O

f Men (%

)

Age In Years

AGE O F M ALE PARTNERS n=53

URBAN/ RURAL DISTRIBUTION OF URBAN/ RURAL DISTRIBUTION OF THE COUPLESTHE COUPLES

Rural, 28

(52.83% )

Urban, 25

(47.17% )

n=53

0

5

10

15

20

25

30

Class I Class II Class III Class IV Class V

0

30(56.60% )

12(22.65% ) 11(20.75% )

0

Number O

f Couples (%

)

Socio-Econom ic Classes (M odified K uppuswam y Scale)

SOCIO-ECONOMIC STATUS OF THE SOCIO-ECONOMIC STATUS OF THE COUPLESCOUPLES

n=53

DURATION OF INFERTILITY OF DURATION OF INFERTILITY OF THE COUPLESTHE COUPLES

0

5

10

15

20

25

30

1-3 yrs 4-5 yrs 6-10 yrs 11-15 yrs >15 yrs

7 (13.21% )

27 (50.94% )

9(16.98% ) 7 (13.21% )3 (5.66% )

Number O

f Couples (%

)

Duration O f Infertility

n=53

Prim ary Infertility,

33 (62.26% )

12

2 13

2

Secondary Infertility,

20(37.74% )

Spontaneous abortion

Induced abortion

Ectopic pregnancy

Pregnancy continued up to 28-37 weeks

Pregnancy continued >37 weeks

n= 53

PAST OBSTETRIC HISTORY OF THE PAST OBSTETRIC HISTORY OF THE WOMENWOMEN

Com bined factors14

(26.42% )

Unexplained12

(22.64% )

17

2432

Single factor27

(50.94% )

M ale subfertility

Endom etriosis

PCOS

Chronic anovulation (without PCOS)Unilateral tubal block

CAUSE OF INFERTILITY OF THE CAUSE OF INFERTILITY OF THE COUPLESCOUPLES

n=53

Seminal Parameters

Number Of Male

Partners(n = 53)

Percentage (%)

Mean ± SD

Sperm density (per ml)

≥20 x 106 36 67.9238.04 ± 24.34

≥10 x 106

<20 x 106 10 18.87≥5 x 106 <10 x 106 7 13.21

Normal sperm

morphology

≥15% 36 67.9222.19 ± 11.72

≥10% <15% 9 16.98≥4% <10% 8 5.10

Sperm motility

≥50% 32 60.38 53.75 ± 9.98<50% 21 39.62

INITIAL SEMINAL PARAMETERS OF INITIAL SEMINAL PARAMETERS OF MALE PARTNERSMALE PARTNERS

0

10

20

30

40

50

60

70

80

90

≥20 ≥10 <20 ≥5 <10

81(56.64% )

42 (29.37% )

21(14.69% )

Number O

f IUI Cycles (%

)

IM SC In m illion/m l

n= 143

INSEMINATING MOTILE SPERM INSEMINATING MOTILE SPERM COUNT (IMSC)COUNT (IMSC)

OVARIAN RESPONSE TO THE DRUGS OVARIAN RESPONSE TO THE DRUGS USED FOR OVULATION-INDUCTIONUSED FOR OVULATION-INDUCTION

18 (12.59% )

46 (32.17% )

25 (17.48% )

32 (22.38% )

19 (13.29% )

3(2.10% )

Num ber And Size O f The Follicles

One, 16-18 m m One, >18 m mTwo, 16-18 m mTwo, >18 m mThree, 16-18 m mThree, >18 m m

n=143

13 (09.09% )

83 (58.04% )

47 (32.87% )

0 10 20 30 40 50 60 70 80 90

<7 m m

7-9 m m

>9 m m

Num ber O f IUI Cycles

Endometr

ial Thickness

Endom etrial Thickness (O n The Day O f hCG Injection)

n=143

ENDOMETRIAL THICKNESS ENDOMETRIAL THICKNESS

OUTCOMES OF IUI IN TERMS OF OUTCOMES OF IUI IN TERMS OF PREGNANCYPREGNANCY

Total Number of Couples

Total Number of IUI Cycles

Number Of Pregnancy After IUI

Reported Live Birth

53 143 14 8Pregnancy Rate Per Cycle of IUI

Cycle Fecundability

9.79%

Pregnancy Rate Per Couple 26.42%Live Birth Rate Per Cycle of IUI (Reported)

Cycle Fecundity

5.59%

OUTCOMES OF PREGNANCY AFTER OUTCOMES OF PREGNANCY AFTER IUIIUI

RELATIONSHIP BETWEEN RELATIONSHIP BETWEEN PREGNANCY AND NUMBER OF IUI PREGNANCY AND NUMBER OF IUI

CYCLESCYCLES

RELATIONSHIP BETWEEN RELATIONSHIP BETWEEN PREGNANCY AND AGE OF THE PREGNANCY AND AGE OF THE

WOMENWOMEN

RELATIONSHIP BETWEEN RELATIONSHIP BETWEEN PREGNANCY AND AGE OF THE MENPREGNANCY AND AGE OF THE MEN

RELATIONSHIP BETWEEN RELATIONSHIP BETWEEN PREGNANCY AND DURATION OF PREGNANCY AND DURATION OF

INFERTILITYINFERTILITY

RELATIONSHIP BETWEEN PREGNANCY RELATIONSHIP BETWEEN PREGNANCY AND TYPE OF INFERTILITYAND TYPE OF INFERTILITY

RELATIONSHIP BETWEEN RELATIONSHIP BETWEEN PREGNANCY AND INITIAL SEMINAL PREGNANCY AND INITIAL SEMINAL

PARAMETERSPARAMETERS

RELATIONSHIP BETWEEN RELATIONSHIP BETWEEN PREGNANCY AND INITIAL SEMINAL PREGNANCY AND INITIAL SEMINAL

PARAMETERS (Contd.)PARAMETERS (Contd.)

RELATIONSHIP BETWEEN RELATIONSHIP BETWEEN PREGNANCY AND INITIAL SEMINAL PREGNANCY AND INITIAL SEMINAL

PARAMETERS (Contd.)PARAMETERS (Contd.)

RELATIONSHIP BETWEEN RELATIONSHIP BETWEEN PREGNANCY AND IMSCPREGNANCY AND IMSC

RELATIONSHIP BETWEEN RELATIONSHIP BETWEEN PREGNANCY AND OVARIAN PREGNANCY AND OVARIAN

RESPONSERESPONSE

RELATIONSHIP BETWEEN RELATIONSHIP BETWEEN PREGNANCY AND ENDOMETRIAL PREGNANCY AND ENDOMETRIAL

THICKNESSTHICKNESS

POST-IUI COMPLICATIONSPOST-IUI COMPLICATIONS

COMPLICATIONS OF POST-IUI COMPLICATIONS OF POST-IUI PREGNANCIESPREGNANCIES

DISCUSSIONDISCUSSION

Why Six Cycles?Studies showed-

most women conceive after most women conceive after 4-6 cycles 4-6 cycles of IUIof IUIcycle fecundability declines by cycle fecundability declines by ½ to ½ to 22//33 thereafter thereafter 1,2

The NICE fertility guidelines - up to 6 IUI cycles for patients with unexplained infertility, male subfertility, cervical factor and minimum to mild endometriosis 3

In Our Study- Most women conceived after 3rd cycle No pregnancy was reported after 6th cycle

1. Ragni G et al. Fertil Steril. 1999;72(4):619-222. Khalil MR et al.; Acta Obstet Gynaecol Scand. 2001 Jan, 80(1): 74-813. National Institute of Clinical Excellence. Fertility: Clinical

guidelines. No 11. London: Abba Litho Ltd. UK, 2004

• Cycle fecundability- the probability that a cycle will result in pregnancy

• Cycle fecundity- the probability that a cycle will result in a live birth Various studies- IUI cycle fecundity- 3-10% 1-3

In Our Study- at least 5.59%

1. Miller D et al. Urology 2002;60:4972. Van der W LA et al. J Asst Reprod Gen 1998;15:359-643. Ford WC et al. Baillieres Clin Obstet Gynaecol 1997;11:691

Studies Fecundability Per CYCLE

Fecundability Per COUPLE

Steven R B et al (2008)

4-18%

Haebe J et al (2002)

4-15%

Guzick et al (1999)

18%

Nulsen et al (1993)

19.3%

Martinez AR (1990)

11.9% 20%

Our Study 9.79% 26.42%

DETERMINANTS OF IUI OUTCOME Age of the Women

Steven R B et al (2008) - Maximum success, if <25 years

Marviel et al (2010) – Maximum conception, if <30 years

Badawy et al (2009)- Little success, if >35 yearsIn our study-

Maximum success- 20-25 years (22.22%) Declines progressively with increased age

Age of the Men Mathieu C et al (1995)- Increased age adversely affects outcome

In our study- Maximum success 26-30 years (33.33%)

DETERMINANTS OF IUI OUTCOME (Contd.)

Duration of InfertilityMathieu C et al (1995)- Highest rate when <3 years

Nuojua-H S et al (1999)- Duration <6 years- conception rate 20%Duration >6 years- conception rate 10%

In our study- Highest success rate if ≤3 years Then declines rapidly

DETERMINANTS OF IUI OUTCOME (Contd.) Type of Infertility

Dickey et al (2002)- maximum success for ovulatory dysfunction, followed by male subfertility

Khalil MR et al (2001)- Best results in anovulation and unexplained infertility

In our study- The best result in PCOS (25%)Followed by unexplained infertility (20%) And male subfertility (10.81%)

DETERMINANTS OF IUI OUTCOME (Contd.) Initial Seminal Parameters

Haebe J et al (2002)- Higher success with total motile sperm count >2 million post wash motility >40% normal sperm morphology >4%

Montanaro GM et al (2001)- Pregnancy rates 18.2% when normal sperm morphology >10% Pregnancy rates 4.3% when normal morphology <10%

Lee RK et al (2002)- Best results with normal morphology >14% Poor when fewer than 4% sperms were normal.

Shulman et al (1998)- Higher success with motility>30%

In our study- The best results were obtained when sperm density- 10-20 x 106/ml 10-15% sperms had normal morphology >50% sperms had normal motility

DETERMINANTS OF IUI OUTCOME (Contd.) Ovarian Response

Endometrial Thickness Various Studies-

Contradictory results 1-3 In our Study- Best results when thickness is 7-9 mm

1. Abdalla HI et al. Hum Reprod 1994;9:363-52. Basil S. Ultrasound Obstet Gynecol 2001;18:258-63. Seddigheh E et al. Fertil Steril 2006;88:432-37

Number of Follicles

Pregnancy ratesIberico et al (2004)

Our Study

One 6.2% 5.55-8.70%Two 12.9% 8.00-12.50%Three 30.0% 10.53-33.33%

COMPLICATIONS OF IUIImportant complications- Important complications- Mild OHSS and multiple pregnancy were observed in 22.30% and 0.70% of total cycles respectively

Wang JX et al (2002)- higher incidence of preterm birth associated with IUI pregnancies

In our study- preterm birth rate at least 21.43%

Nuoja HS et al (1999)- No increased congenital anomaly of the offspring

In our study- no congenital anomaly was reported

CONCLUSIONCONCLUSION

IUI can make many infertile couples feel the taste of parenthood

Proper case selection is important before useless wastage of money, time, energy and resources

If there is no conception after 6 cycles, the investigations should be reviewed and alternatives should be considered

The prognostic factors should be kept in mind before IUI and should be discussed with the couples

Can safely be conducted in hospitals with relatively low resources

THANK YOUTHANK YOU