1. OVARIAN HYPERSTIMULATIONFOR IUIDR. ELMAR BREITBACHDEUTSCHE KLINIKBAD MNDER - HANNOVER

2. STIMULATION FOR IUI: GOALS1. Improvement of Follicular Growth2. Increasing the Number of Follicles3. Treatment of Anovulation (PCOS)4. Better Timing5. Improvement of Luteal Phase 3. Is IUI worthwhile? And when? And how?10%unknown32% 35%both23% 4. Is IUI worthwhile? And when? And how?10%unknown1. Unexplained Infertility32% 35%2. Male subfertilityboth23% 5. IUI AND IDIOPATHIC STERILITYWhat does the holy oracle of EBM say?Cochrane Database Syst Rev. 2012Sep 12;9:CD001838 6. IUI AND IDIOPATHIC STERILITY1. IUI with OH increases the live birth rate compared to IUIalone2. PR increased for treatment with IUI compared to TI instimulated cycles3. No increase of PR with IUI in natural cycles compared toTI in natural cyclesCochrane Database Syst Rev. 2012 Sep 12;9:CD001838 7. IUI AND IDIOPATHIC STERILITY1. IUI helps2. But only when combined with OHCochrane Database Syst Rev. 2012 Sep 12;9:CD001838 8. IUI AND MALE SUBFERTILITYAgain, we look at the Cochrane DatabaseCochrane Database Syst Rev. 2007 Oct17;(4):CD000360 9. IUI AND MALE SUBFERTILITY1. Insufficient evidence for IUI to be superior above TIwith or without OH2. Tendency for IUI plus OH against natural cycle butonly referring to PR not birthrateConclusion: Carefull selection likeasthenozoospermia with normalspermcountCochrane Database Syst Rev. 2007 Oct 17;(4):CD000360 10. IUI OVARIAN HYPERSTIMULATION1. significant higher PR with gonadotrophins compared withclomifen (OR 1.8, 95% CI 1.2 to 2.7)2. Clomifen compared with aromatase inhibitors reportingno significant difference3. No significant difference depending on type ofgonadotrophin4. Adding GnRH agonists increased multiple PR5. High dosage gonadotrophin increases risks, not PRCochrane Database Syst Rev. 2007 Apr 18;(2):CD005356 11. EXPERIENCE BASEDCONCLUSIONS SO FAR1. Choose the patients carefully Age Duration of infertility and reasons Sperm parameters2. Ovarian Hyperstimulation > 30y Clomifen is a cheap good choice with somelimitations (cysts, flat endometrium) Low dose gonadotrophins alone (or combined withCC) is the next step 12. Clomifen1. First day of menstruation: Patient calls theclinic2. Basal hormonal assessment + US on day 3-53. Begin treatment starting 50mg dailyappointment for next examination (d 10-12)4. Ultrasound, E2, LH, Prog, Cervixscore5. Ovulation induction (hCG)6. Insemination 13. WAIT! WHAT ABOUT HCG?1. Insemination should be performed before ovulationoccurs2. hCG could acertain that3. It might induce a better luteal phaseIs it neccessary? 14. IS HCG NECCESSARY AT ALL?1. Timing with spontaneous LH-surge significantly bettercompared with hCGKyrou et al. Reprod Biomed Online. 20122. No difference between the two proceduresZreig et al. Fertil Steril. 1999Kosmas et al. Fertil Steril. 2007Cochrane Database Syst Rev. 2010 15. HCG 24 HOURS OR 36 HOURS?1. In IVF (with supressed endogenous LH) ovulation will notoccur before 40 hours after the injection2. In IUI this might be different, depending on follicle sizeand individual LH-surgeNo difference between the two proceduresRahman et al. Arch Gynecol Obstet. 2011Robb et al. J Natl Med Assoc. 2004 16. HCG AT WHAT SIZE OF FOLLICLE??16 - 17 mm (early) or18 20 mm (late): No differenceda Silva et al. Eur J Obstet Gynecol Reprod Biol. 2012 17. OVULATIONS TRIGGER EBM1. LH-Surge (with test sticks)2. GnRH3. hCGCochrane Database found no significant differences infavour of any these procedures, but:The choice should be based on hospital facilities, convenience for the patient, medicalstaff, costs and drop-out levels. Since different time intervals between hCG and IUI did notresult in different pregnancy rates, a more flexible approach might be allowed.Cochrane Database Syst Rev. 2010 18. OVULATIONS TRIGGER EXPERIENCEBASED1. Timing of IUI ist easier with hCG2. More convenience for patients3. Easier planning of schedules in the clinic4. Safer, when planning the IUI prior to ovulation 19. Clomifen1. First day of menstruation: Patient calls theclinic2. Basal hormonal assessment + US on day 3-53. Begin treatment starting 50mg dailyappointment for next examination (d 10-12)4. Ultrasound, E2, LH, Prog, Cervixscore5. Ovulation induction (hCG)6. Insemination 20. LUTEAL PHASE SUPPORT1. micronized progesterone vaginal/oral administration2. synthetic progesteron3. hCGRCT IUI with gonadotrophins: Significant improvement withvaginal applicationErdem et al. Fertil Steril. 2009 21. Patient flow chart.Kyrou D et al. Hum. Reprod. 2010;25:2501-2506 The Author 2010. Published by Oxford University Press on behalf of the European Society ofHuman Reproduction and Embryology. All rights reserved. For Permissions, please email:journals.permissions@oxfordjournals.org 22. LUTEAL PHASE SUPPORTNo improvement of pregnancy rates in normo-ovulatorywomen stimulated with clomiphene citrate for IUIKyrou et al. Hum Reprod. 2010 23. LUTEAL PHASE EBM1. Significant improvement with progesterone2. Favouring synthetic progesterone over micronizedprogesterone3. hCG increases risk for OHSS4. Estradiol is of no use5. GnRH increases live birth rateCochrane Database Conclusion:For now, progesterone seems to be the best option as luteal phase support, with betterpregnancy results when synthetic progesterone is used.Cochrane Database Syst Rev. 2011 24. LUTEAL PHASE SUPPORT EXPERIENCEBASED1. In normoovulatory women not neccessary2. hCG is sufficent in those cases (with no risk for OHSS)3. Age > 35 hormonal disturbances or irregular cyclus orspotting: Progesteron vaginally4. Independant of pretreatment 25. CLOMIFEN: SIDE EFFECTS1. Unsolved: Induction of neoplasia if used more than 6x?2. Insler-Score often reduced3. Reduction of endometrial growth4. Long term effects (half-life-time)5. Rising LH-Levels (confuses the doctor, lowers the Quality of oocytes)Adititional E2 or gonadotrophins. 26. Clomifen + hMG1. Start on day three2. Basal hormonal assessment + US3. Begin treatment starting 50mg daily + hMGevery second day4. Ultrasound, E2, LH, Prog, Cervixscore5. Ovulation induction (hCG)6. Insemination 27. CLOMIFEN + HMG1. CC helps reduce the use of expensive gonadotropins2. hMG reduces Clomifen side effects (flat endometrium,cervixscore etc.)3. In cases of clomifen resistance worth a try 28. Gonadotrophins1. Start on day three2. Basal hormonal assessment + US3. Begin treatment starting 1 Inj. daily + hMGevery second day4. Ultrasound, E2, LH, Prog, Cervixscore5. Ovulation trigger (hCG)6. Insemination 29. SUCCESS? 30. OHSS1. Only in rare cases2. PCOS patients are at risk3. hCG triggers OHSS 31. BEST DOSAGE?1. Depends on various factors2. High age or low sperm count lowers the risk of multiples,therefore even 3 or 4 follicles could be reasonable3. low age, high AMH or signs of PCOS should lead tolower dosage.4. Better start too low rather than too high. 50 mg ofclomifen, 1 amp. hMG or 75 IU FSH are a good startingdosage in most cases. 32. HOW OFTEN?% 504030201001. 2. 3. 4. 5.pro ZyklusKumulativ2 4cycle 33. CONCLUSIONS1. Indications: Unexplained infertility, carefully chosencases of male factor cases2. Stimulation helps, gonadotrophins significantly betterthan CC. Combine CC with hMG (reduce costs)3. HCG for better planning/convenience, timing does notmatter (follicle size, time till IUI)4. Luteal phase support: Progesteron first choice. HCGmore convenient, sufficient in young women with nohomonal problems.5. IUI just for 3-4 times. After that, statistics works againstyou (& your patient) 34. Thank You