PREVENTION OF MULTIPLES FROM A CLINICIAN’S STANDPOINT

1. PREVENTION OF MULTIPLES FROM A CLINICIAN’S STANDPOINT Bulent Urman M.D. American Hospital of Istanbul

2. TRENDS IN EMBRYO TRANSFER PRACTICE EARLY 1980s 1985-1995 1995-2000 2000-TODAY FROM SINGLE TO MULTIPLE EMBRYO TRANSFERS NO LEGAL OR ETHICAL RESTRICTIONS IN THE NUMBER OF TRANSFERRED EMBRYOS PREVENTION OF TRIPLETS AND HOMP PREVENTION OF TWINS PREGNANCY========HEALTHY BABIES========HEALTHY SINGLE BABY

3. Current Turkish Legislation • A maximum of 3 embryos are allowed to be transferred • The number can be increased if the clinician feels that it is indicated under special circumstances

4. How many embryos do we actually transfer?

6. Is there a need to change the current policy?Should we decrease the number of transferred embryos?

7. If yes: Questions! • Why should we reduce the number of transferred embryos? • How is the success of ART affected? • SET vs DET • Are we ready to do it in Turkey? • A proposed national model

8. Factors affecting embryo transfer policy • Pressure to be successful • Insurance non coverage • Pressure form patients-twins are the ideal outcome • Implantation rates of the individual center • Cryopreservation • Availability • Uptake

10. The couple’s decision-making in IVF: one or two embryos at transfer? From Blennborn et al. Hum Reprod 2005

11. Probabilities for singleton and multiple pregnancies after in vitro fertilization Peter M. Martin, M.D.,*† and H. Gilbert Welch M.D., M.P.H.†‡ FERTILITY AND STERILITYt VOL. 70, NO. 3, SEPTEMBER 1998

12. Probabilities for singleton and multiple pregnancies after in vitro fertilization Peter M. Martin, M.D.,*† and H. Gilbert Welch M.D., M.P.H.†‡ FERTILITY AND STERILITYt VOL. 70, NO. 3, SEPTEMBER 1998

13. Probabilities for singleton and multiple pregnancies after in vitro fertilization Peter M. Martin, M.D.,*† and H. Gilbert Welch M.D., M.P.H.†‡ FERTILITY AND STERILITYt VOL. 70, NO. 3, SEPTEMBER 1998

14. Probabilities for singleton and multiple pregnancies after in vitro fertilization Peter M. Martin, M.D.,*† and H. Gilbert Welch M.D., M.P.H.†‡ FERTILITY AND STERILITYt VOL. 70, NO. 3, SEPTEMBER 1998

15. Pregnancy and live birth rates after the transfer of 2-3 embryos From Brinsden RBM Online 2003

16. Factors affecting success in IVF • Age • Tubal infertility • Previous IVF outcome • Gonadotropin dose • Initial • Total • Good quality embryos • Available • Transferred • Cryopreserved From Strandell et al. 2000

17. Is there a subset of couples who would benefit from (no compromise in PR and no twins) from single embryo transfer?

18. Pregnancy rate according to the number of embryos transferred From Zhang et al. 2008

19. Multiple pregnancy rate according to the number of embryos transferred From Zhang et al. 2008

20. Results of SET and DET according to embryo morphology From Saldeen and Sundstom Hum Reprod 2005

21. Optimal number of embryos to be transferred based on quality From Hu et al. Fertil Steril 1998

22. From Roberts et al. Hum Reprod 2009

23. Cohort studies of SET vs DET From Gerris et al. Hum Reprod Update 2005

24. Prospective evaluation of elective single-embryo transfer versus double-embryo transfer following in vitro fertilization: a two-year French hospital experience From Leniaud et al. Gynecol Obstet Fertil. 2008 Feb;36(2):159-65

25. Randomized trials of SET vs DET From Gerris et al. Hum Reprod Update 2005

26. Single versus double embryo transfer: cost-effectiveness analysis alongside a randomized clinical trial From Fiddelers et al. Hum Reprod 2006

27. In unselected patients, elective single embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared with double embryo transfer: a randomized controlled trial From van Monfoort et al. Hum Reprod 2006

28. From van Monfoort et al. Hum Reprod 2006

29. Better embryo selection? • Blastocyst transfer • PGS

30. Single vs double blastocyst transfer: randomized trial

31. Papanikolaou, E. et al. N Engl J Med 2006;354:1139-1146

32. A prospective randomized controlled trial of preimplantation genetic screening in the "good prognosis" patient From Meyer et al. Fertil Steril 2008

33. Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis From Kjellberg et al. Hum Reprod 2006

34. Transfer policy in the American Hospital • Prior to August 2000 • Up to 3-4 embryos until the age of 39 • 5-6 embryos after 40 • After August 2000 • Maximum 2 good quality fresh or frozen thawed embryos up to 37 • If embryo quality is suboptimal 3 is allowed • Maximum 3 good quality fresh or frozen thawed embryos after 37 • If embryo quality is suboptimal 4 is allowed after 40

35. Transfer edilen ortalama embryo sayısı

36. 7300 D3 embryo transferinde klinik gebelik oranları

37. 1100 D5 embryo transferinde klinik gebelik oranları

38. Incidence of singletons, twins, and HOMPs in the American Hospital

39. Number of embryos transferred in view of • Efficacy • Implantation and pregnancy rates • Side effects • Multiple pregnancies • Cost effectiveness • Society resources • Can the system handle increasing multiples?

40. TRANSFER EDİLEBİLİR EMBRYO SAYISI İLE İLGİLİ TÜRKİYE MODELİ ÖNERİSİ

41. İyi prognoz kriterleri İyi yanıt veren kadında ilk ART siklusu Kryoprezervasyon için uygun olan embryoların varlığında selektif embryo transferi yapma olasılığı Doğum ile sonuçlanan ART gebeliği öyküsü 2 veya 3. günde 4 veya 8 hücreli G1 veya G2 embryoların varlığı 5. günde G1 veya G2 blastokistlerin varlığı

42. Kötü prognoz kriterleri 3. veya sonraki ART siklusları Over stimülasyonuna kötü yanıt (3 veya daha az oositin toplandığı durumlar) Kötü kaliteli embryoların varlığı

43. Is the Scandinavian model of SET valid in Turkey • Pregnancy and implantation rates in Turkish IVF centers are largely unknown • In unselected patients, single embryo transfer decreases twin pregnancy rate but also decreases the pregnancy rate • Pregnancy rate is dependent on embryo quality, women's age, rank of IVF attempt and also other variables • That is the reason why a flexible policy of transfer adapted to each couple is preferable • Each couple and each IVF team must keep the freedom to choose how many embryos must be transferred to obtain healthy babies, and to avoid twin pregnancies

44. CONCLUSIONS Q: Should we prevent multiples? A: Yes Q: Should we decrease the number of embryos we transfer? A: Yes Q: Is IVF the only problem? A: No

45. Conclusions • Infertile couples with good prognosis should be encouraged to wait • Life style changes improving fertility should be promoted • IUI should be considered in the natural cycle. If COH is instituted nor more than 2 follicles should be the aim • Mild stimulation protocols for IVF should be adopted • Elective SET should be considered in good prognosis couples • Transfer policy according to prognostic factors should be adopted

48. Ülkelerde IVF merkezi başına düşen nüfus (x 1000)

49. IVF VE TURKİYE • Sektörel sorunlar • Etik sorunlar • Standardizasyon • Denetim • Yönetmelikler • Başarı • Çoğul gebelikler • Veri toplama