Ovarian Stimulation in IUI- Overview Sr. Jyoti Bhaskar

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  • Ovarian Stimulation in IUI- Overview Sr. Jyoti Bhaskar

    1. 1. Ovarian Stimulation in IUIOverview Dr. Jyoti Bhaskar MD MRCOG Director Lifecare IVF
    2. 2. Rationale for COH in IUI • Increasing the number of eggs available for fertilisation • Overcoming subtle defects in ovulatory function and luteal phase. #
    3. 3. Aim of COH 1. 2. 3. 4. 5. Recruiting multiple follicles Control timing of ovulation Prevention of premature LH surge To time the insemination Increase the pregnancy rate #
    4. 4. Optimum Ovarian Stimulation for IUI  2 – 3 follicles with Ø 18 – 19 mm.  Endometrium ≥ 9 mm thick & trilaminar.  IUI between Cycle D13 and D16, 36-40 hrs. from HCG inj. #
    5. 5. Classification WHO • I - Hypothalamic pituitary failure (Hypogonadotrophic hypogonadism) Kallman’s, Sheehan’s, anorexia • II - Hypothalamic pituitary dysfunction (PCOS) • III – Ovulatory Failure – Hypergonadotrophic hypogonadism, Turner’s, autoimmune, mumps, RT, CT #
    6. 6. Drugs for Ovarian Stimulation • Clomiphene Citrate, • Gonadotrophins: • HMG • highly purified ur FSH • Rec. FSH • GnRH antagonist #
    7. 7. CLOMIPHENE CITRATE • Most widely • Simple to use,  Minimal side effects,  Cost effective #
    8. 8. CLOMIPHENE CITRATE ( SERM) Binds HYPOTHALAMUS ER GnRH Blocks ER Pituitary FSH Cervix Vagina OVARY Folliculogenesis Endometrium #
    9. 9. DOSAGE Starting Dose 100mg day 2 onwards for 5 days • Single dose -- together • Monitor Cycle with USG • If ovulation confirmed – maintain same dose • Max to 150 mg #
    10. 10. CC FAILURE ( 40%) No Pregnancy 2 CYCLES OF CC WITH OVULATION AND TIMED INTERCOURSE 2 CYCLES OF CC WITH IUI #
    11. 11. CC RESISTANCE (20%) 2 CYCLES OF CC NO OVULATION COST , PT’S CHOICE COUNSELLING CC + GONADOTROPHINS GONADOTROPHINS #
    12. 12. Antioestrogenic Effect • Thin Endometrium • Poor cervical Mucus Start early in cycle – Day 2 or Day 1 Add oestradiol valearate from day 8/9 Use all gonadotrophin cycle #
    13. 13. Gonadotrophins - Indications CC Resistance CC Failure #
    14. 14. Choice of Gonadotrophins • HMG • Highly purified Urinary HMG/FSH • Recombinant. FSH Day 2 LH/FSH FSH LH FSH PCOS WHO group1 HMG #
    15. 15. DOSE • • • • • BMI Ovarian reserve Age Cause of Infertility Dose needed in previous cycle #
    16. 16. Complications  Multifetal pregnancy • OHSS - Life threatening Monitoring Experience Strict protocols #
    17. 17. Protocols 1. CC only with TI or IUI 2. CC ± FSH or ± HMG with IUI 3. Gonadotrophin only n Conventional regime n Gn. Low dose step-up protocol n Gn. step-down protocol 4. Gonadotrophin with GnRH antag #
    18. 18. DAYS OF CYCLE 2 3 4 5 6 7 8 9 10 11 12 13 14 15 CC ONLY PROTOCOL -- +/- IUI B LONG F ONCE DAILY ALL THROUGH OUT THE CYCLE TVS – ET AND AFC CC 100 MG DAILY Day 2-6 TVS – FOLLICLE SIZE, ET IF ET< 5MM OV 2MG BD DAILY TVS – FOLLICLE , ET , CERVICAL MUCUS STUDY, POST COITAL TEST FOLLICLE >20MM -- LH SURGE + VE stat -VE Inj HCG 5000 U i/m 8pm Timed Intercourse 24hrs later at 8am 36 hrs later at 8am at Lifecare IUI Sexual relation at same night and for 2 days 21 Luteal support – ETV ES/ Susten vaginally at night # Serum Progesterone 7 days after IUI/Ovulation UPT 18 days after IUI/Ovulation
    19. 19. Unripe follicle Ripening follicle Ovulation Corpus luteum Regression of Corpus luteum Oocyte mature 38 hrs Clomiphene 100 mg day2 for 5 days Gonadotrophin stimulation HCG Leading follicle > 18mm #
    20. 20. Gonadotrophin Regimens Chronic Low dose Step up regimen Days 7 14 hCG 150 IU 112.5 IU 75 IU 37.5 IU 21 28 Step down IU 112.5 IU 150 IU 75 hCG Foll. ≥ 10 mm Conventional Regime 75-150 U daily 6 hCG 12 Foll. ≥ 16mm #
    21. 21. Gonadotrophins with Antagonists • Lubek Protocol • French Protocol 15-20% cycles with Gonadotrophins have premature LH surge #
    22. 22. Advantages of Antagonist Protocol • Helps avoid IUI at weekends • Compared to agonist – simple and inexpensive • Lower rates of OHSS #
    23. 23. Anti-oestrogens Cost effective but less effective when compared to gonadotrophins. Do not prevent multiple pregnancies Have anti-oestrogenic effect on the endometrium Gonadotrophins Most effective drugs for IUI Low dose protocols (50 to 75 IU per day) are advised Pregnancy rates do not seem to differ significantly from pregnancy rates with high dose regimens (> 75 IU per day) whereas the changes to encounter negative effects from ovarian stimulation, such as the risk of multiples and the risk of OHSS might be higher with high dose protocols. The Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ # 23
    24. 24. GnRH-agonists There seems to be no role in IUI programs Increase costs Increase multiples without increasing the probability of conception Urinary gonadotrophins versus Recombinant products There is no significant difference GnRH-antagonists Whether or not are going to play a role in mild ovarian hyperstimulation/IUI programs needs to be determined in future trials. Letrozole There is no convincing evidence that Letrozole is superior to clomiphene citrate and therefore the cost should be taken into account when using anti-oestrogens. The Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ #
    25. 25. Ovarian stimulation protocols (anti-oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility (Review) The Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ Gonadotrophins might be the most effective drugs with IUI Low dose protocols are advised No studies using CC + gonadotrophins # 25
    26. 26. • There is evidence that IUI with OH increases the live birth rate compared to IUI alone. • The likelihood of pregnancy was also increased for treatment with IUI compared to TI both in stimulated cycles. • There is insufficient data on multiple pregnancies and other adverse events for treatment with OH. • Therefore, couples should be fully informed about the risks of IUI and OH as well as alternative treatment options. # 26
    27. 27. Conclusion • Choice depends on doctors expertise and patients condition, choice • Gonadotrophin only protocol offers the best success rate TIME TO MOVE ON TO TOTAL GONADOTROPHIN CYCLE #
    28. 28. Ovarian Stimulation protocol • Simple • Cost Effective • Minimal side effects • Best success rates #
    29. 29. Thank you #

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