LIFE AFTER NEW IVF LEGISLATION IN TURKEY

1. LIFE AFTER NEW IVF LEGISLATION IN TURKEY Hakan Ozornek, MD EUROFERTIL Istanbul

4. LIFE AFTER NEW IVF LEGISLATION • New legislation • Mild stimulation • Antagonist • Letrazol • SET • IVF in Europe • IVF in Turkey

5. New IVF legislation • The new IVF legislation since March 2010 • Patients under 35 the first and second cycles should be transferred single embryo, • All other patients should be transferred maximum double embryo.

6. Mild stimulation • The administration of low doses (fewer days) of exogenous gonadotrophinsin GnRH antagonist co-treated cycles, and/or oral compounds(like anti-estrogens, or aromatase inhibitors) for ovarianstimulation for IVF, aiming to limit the number of oocytes obtained to less than eight.

7. Mild stimulation • Less complex • Less time consuming • Cheaper (making IVF more accessible for a broader patient population) • Reduced chances for complications • Reduced chances for discomfort • Reduced chances for drop-out • Effects on oocyte quality • Effects on endometrial receptivity

8. Mild vs Standart Mild:GnRH antagonist and single embryo transfer. Standard:GnRHagonist long protocol along with the transferof two embryos. A mild treatment strategy for in-vitro fertilisation: a randomised non-inferiority trial randomized trial. Heijnenet al., Lancet, 2007

9. Mild vs Standart Milder ovarian stimulation for in-vitrofertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Baart et al., Human Reprod, 2007

10. antagonist USE

11. Advantages of Antagonists • No initialflareup • Shortertreatmentduration • Lessgonadotrophinconsumption • Lessclinicattendances • Lower risk of OHSS • No hypooestrogenemiceffects • Weightgain, headache, hot flushes, moodchanges, vomiting

12. Agonist Antagonist

13. Antagonist protocols

14. Disadvantages of Antagonists Lowerpregnancyrates ?

15. Clinicalpregnancy rate (PCOS) Grisinger G, RBM Online, 2006

16. Clinicalpregnancy rate (Poor) Grisinger G, RBM Online, 2006

17. Normoresponder-Antagonist Tubalinfertility - DIR Engel, et al., 2006

18. Normoresponder-Antagonist TheEuropeanandMiddle East OrgalutranStudyGroup, 2001

19. Clinicalpregnancy rate Al-Inany HG, RBM Online, 2007

20. LiveBirth Rate

21. Livebirth rate Al-Inany HG, RBM Online, 2007

22. Livebirth rate Al-Inany HG, RBM Online, 2007

23. Livebirth rate Kolibianakis EM, HumanReprodUpdate, 2006

24. Livebirth rate Kolibianakis EM, HumanReprodUpdate, 2006

25. Livebirth rate (Gonadotropintype) Kolibianakis EM, HumanReprodUpdate, 2006

26. Livebirth rate (protocoltype) Kolibianakis EM, HumanReprodUpdate, 2006

27. Livebirth rate (agonisttype) Kolibianakis EM, HumanReprodUpdate, 2006

28. Livebirth rate (antagonist protocol) Kolibianakis EM, HumanReprodUpdate, 2006

29. Livebirth rate (antagonist type) Kolibianakis EM, HumanReprodUpdate, 2006

30. Conclusions • Meta-analysescomparingGnRHagonistsandantagonistshavecalculatedalmostidenticaloddsratios (0.82-0.86) fortheprobability of livebirth, althoughthedifferencewasstatisticallysignificant in oneanalysisand not in another. The difference is unlikely to be of clinical significance. • Ovarian stimulation with antagonists co-treatment can provide live birth rates comparable to those achieved with the standart long agonist protocol and has advantages in terms of tolerability and safety.

31. Analoguse in EUROFERTIL

32. Analoguse in EUROFERTIL 2006-08 * P<0.05

33. CPR in antagonist cycles

34. LETRAZOL stimulation

35. Milder stimulation Letrazol 2.5 mg HCG US/LH test OPU 3 4 5 6 7 8 9 10 11 12 13 14 15 Progesteron Indomethasin 50 mg

36. Indomethacin • Anon-steroidal anti-inflammatorydrug (NSAID), • Anti-prostaglandin effects. • Inhibitionof cyclooxygenase, the enzyme thatcatalysesthe synthesis of prostaglandins, which are essentialmediators of ovulation. • Athanasiouet al., (1996) have shown that indomethacinadministered at the time of a positive urinary LH can delayfollicular rupture. The mechanism of action is probably inhibition of the ‘inflammation’ associated withfollicular rupture. • Unlike GnRH antagonists it does not inhibit theLH surge.

37. RBM online 2008

38. Spontaneous ovulation rate before oocyteretrieval in modified natural cycle IVF with and without indomethacin Kadoch, et al.,RBM online 2008

39. Spontaneous ovulation rate before oocyteretrieval in modified natural cycle IVF with and without indomethacin Kadoch, et al.,RBM online 2008

40. Milder stimulation (2009-2010)

41. Milder stimulation

42. Conclusion • SET is a reality in daily life of IVF centers in Turkey and a shift to milder protocols will be expected in next time. • Letrazol + Indomethasin is a not complex and cheap approach with acceptable pregnancy rate. • Especially powerful to reduce the drop out rates due to the stres during stimulation period. • The mentality should be changed from pregnancy rate per cycle to a cumulative pregnancy rate per patient per year.

44. Modified natural cycle IVF and mild IVF:a 10 year Swedish experience

45. Modified natural cycle IVF and mild IVF:a 10 year Swedish experience 40%

47. Mini IVF • Clomiphene citrate 50 mg, beginningon day 3 and continued untilthe follicles were developed sufficiently for ovulation triggering. • 150 IU hMG every 48 h was begun on day 5 or 8depending on the day-3 FSH concentration. • GnRHa(nasal spray, nafarelin acetate) was administered to trigger an endogenous LHsurge.

48. 54%

50. SET