Endometrium en Infertiliteit

1. Endometrium en Infertiliteit P Devroey MD PhD Centre for Reproductive Medicine Dutch-speaking Brussels Free University Brussels - Belgium

2. Natural cycle • FSH • LH • E2 • Prog Noyes criteria proliferatie secretie

3. Is there any influence on endometrial histology during the follicular phase in gonadotrophin stimulated cycles before the injection of hCG ? YES or NO

4. Is there any influence on endometrial histology during the follicular phase in gonadotrophin stimulated cycles before the injection of hCG ? YES or NO Answer : Yes 100 % secretory advancement in preovulatory endometria ( pre - hCG ) during ovarian stimulation ( Marchini FS 1991 )

5. Is there any influence on endometrial histology in agonist / gonadotrophin stimulated cycles 36 hours after hCG administration ? YES or NO

6. Is there any influence on endometrial histology in agonist / gonadotrophin stimulated cycles 36 hours after hCG administration ? YES or NO Answer : Yes 100 % ( n = 40 patients ) 2 - 5 days advancement ( Ubaldi FS 1997 )

7. Is there any influence on endometrial histology in antagonist / gonadotrophin stimulated cycles ? YES or NO

8. Is there any influence on endometrial histology in antagonist / gonadotrophin stimulated cycles ? YES or NO Answer : Yes 100 % ( n = 55 patients ) 2 - 4 days advancement ( Kolibianakis FS 2002 )

9. Endometrial biopsy on the day of ovulation , natural cycle No secretory features

10. Endometrial biopsy on the day of oocyte retrieval , GnRH agonist and gonadotrophin stimulation cycle Clear secretory features

11. Is there any relation between endometrial advancement and ongoing pregnancy rates ? YES or NO

12. Is there any relation between endometrial advancement and ongoing pregnancy rates ? YES or NO Answer : Yes Endometrial advancement Kolibianakis FS 2002

13. Endometrial advancement persists in the midluteal phase YES or NO

14. Histological regression of endometrium from oocyte retrieval to the midluteal phase Kolibianakis, Bourgain, Platteau, Albano, Van Steirteghem, Devroey F S 80 2003

15. Describe the LH concentration during the luteal phase ( post hCG ) in agonist gonadotrophin stimulated cycles LOW or HIGH

16. Describe the LH concentration during the luteal phase ( post hCG ) in agonist gonadotrophin stimulated cycles LOW or HIGH Answer : Low Smitz HR 1988

17. Are the LH concentrations during the luteal phase ( post hCG ) in agonist - gonadotrophin stimulated cycles similar to the LH concentrations in the follicular phase ? YES or NO

18. Are the LH concentrations during the luteal phase ( post hCG ) in agonist - gonadotrophin stimulated cycles similar to the LH concentrations in the follicular phase ? Answer : No Demoulin FS 1991 WHY ?

19. Is the luteal phase LH concentration ( post hCG ) in antagonist - gonadotrophin cycles normal or decreased ?

20. Is the luteal phase LH concentration ( post hCG ) in antagonist - gonadotrophin cycles normal or decreased ? Answer : decreased

21. Are the luteal phase concentrations ( post hCG ) similar in gonadotrophin alone versus antagonist gonadotrophin stimulated cycles ? YES or NO

22. Are the luteal phase concentrations ( post hCG ) similar in gonadotrophin alone versus antagonist gonadotrophin stimulated cycles ? YES or NO Answer : Yes Tavaniotou HR 2001

23. Luteinizing hormone serum concentrations in Clomid gonadotrophin antagonist or gonadotrophin antagonist cycles Tavaniotou F S 77 2002

24. Is the luteal phase length normal after gonadotrophin stimulation in non IVF ? YES or NO

25. Is the luteal phase length normal after gonadotrophin stimulation in non IVF ? YES or NO Answer : No Olson FS 1983

26. Statement :GnRH antagonist can be safely administered in gonadotrophin stimulated IUI cycles without luteal phase supplementation Ragni HR 2001

27. Is the statement in contradiction with the lecture ? YES or NO Answer : No Ragni HR 2001

28. Steroid serum concentrations Tavaniotou Master Thesis Brussels 2000

30. hCG versus prog IM + E2V (RCT) Smitz unpublished

31. Progesterone IM + E2V versus vaginal progesterone + E2V (RCT) Smitz HR 1992

32. Vaginal progesterone versus vaginal progesterone + E2V (RCT) Smitz HR 1993

33. Is luteal support necessary in GnRH antagonist cycles? Fixed dose of rec FSH 150 IU, daily antagonist by a follicle of 14mm By a follicle of 18mm patients were randomized to receive rec hCG, rec LH, GnRH agonist No luteal support When 40 patients had been included, the study was canceled prematurely because of observed premature luteal phase bleeding and extremely low pregnancy rates. Beckers et al 2004 JCEM

34. Support of corpus luteum function remains mandatory after ovarian stimulation for IVF with GnRH antagonist cotreatment. Is luteal support necessary in GnRH antagonist cycles? Beckers et al 2004 JCEM

35. Ovarian stimulation • Day 2 • Puregon 200 U (unchanged) • Orgalutran 0.25 mg from day 6 stimulation onwards • Final egg maturation as soon as ≥ 3 follicles of 17 mm of diameter at ultrasound • Computer generated list • either 10.000 U hCG • either 0.2 mg Triptorelin (the decision was only made on ultrasound)

36. Stimulation characteristics

37. Cycle outcome Odds ratio (95% CI) 0.11 (0.02 - 0.52) P level = 0.005

38. Westergaard 0.5 mg Busereline Discontinuation of luteal support at pregnancy Progesterone Our study (Kolibianakis) 0.2 mg Triptorelin No discontinuation of luteal support Progesterone + Progynova

39. GnRH agonist to induce oocyte maturation Engmann FS 2008

40. Advanced endometrial maturation correlates with altered gene expression • Endometrial maturation advancement of > 3 days never resulted in an ongoing delivery (at ovum pick-up) • Comparing pregnant and non pregnant patients (23 genes differentially expressed) • SERPINB6 • SOX17 • FOX03A • CDC42 (P < 0.001) Van Vaerenbergh ... Devroey Bourgain HR 2008

42. Conclusions • Ovarian superovulation (IVF) destroys luteal phase function • Endocrinology • Endometrium behaviour • Luteal phase supplementation is mandatory • The degree of luteal steroid production is the key factor