1. IVF TROUBLESHOOTING ( Clinical Perspective) Malvin Emeraldi M. Luky, Dianing ASR,Muchsin J Family Fertility Center, RSIA Family Fatmawaty Hospital Jakarta, INDONESIA HIFERI JAYA ROAD SHOW 2014

2. Outline Background IVF Troubleshooting Low Success Rate ?? Risk of Complication Expensive ?? Take Home Messages Objective Method Result Discussion Conclusion

3. Assisted Reproductive Technology Background Objective Method Result Discussion Conclusion IUI ( Inseminasi Intra Uterine ) GIFT ZIFT IVF ( In Vitro Fertilization ) – Ovarian stimulation – Endometrial preparation – Ovum Pick Up – Embryo Transfer – Cryopreservation – ICSI ( Intra Cytoplasmic Sperm Injection ) – IVM ( In Vitro Maturation ) – Sperm Retrieval Technique – Oocyte and Embryo Donation – Donor oosit/ sperma/ embryo/ Ovarium PGD ( Pre Implantation Genetic Diagnosis )

4. IVF Background Objective Method Result Discussion Conclusion 1978 : England 1980 : Australia 1981 : USA 1982 : Sweden & France 30 tahun Robert Edwards & Patrick Steptoe Louise Brown

5. IVF Background Objective Method Result Discussion Conclusion 1988: Indonesia TIM MELATI Nugroho Karyanto

6. IVF TROUBLESHOOTING LOW SUCCESS RATE ?? COMPLICATION ?? EXPENSIVE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

7. Regular intercourse Zinaman et al. Fertil Steril 1996 Background Objective Method Result Discussion Conclusion

8. Speroff L, Glass R, Kase N. Clinical gynecologic endocrinology and infertility, 7 th edition, 2005 IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion Natural Female Fertility Decline with Age

9. Natural way is the best way !! ( Cummulative Pregnancy ) 84 % within one year 92 % after 2 years 93% after 3 years Normal, young women (< 30 yrs) For those not normal: IUI/IVF LOW SUCCESS RATE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

11. LOW SUCCESS RATE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

12. LOW SUCCESS RATE ?? Chance of pregnancy per cycle: Intra Uterine Insemination In Vitro Fertilization IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

13. Overall IVF success rate 30 – 40 %/ cycle LOW SUCCESS RATE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

14. IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

17. Total Quality Management. Pre Congress Course ESHRE 2013 IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion COMPLICATION ?? 1.84 %

18. COMPLICATION ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

19. Ovarian Hyperstimulation Syndrome (OHSS) 19 Incidence of OHSS – Varies from center to center 1-10% (serour et al, 1998) – Serious life threatening 0.1-2% (Blinder et al,2007) INA – IVF* PCO/PCOS  Greatest risk for OHSS – Odds ratio 6.8 for severe OHSS ( Tummon et al, 2003) YearOHSSCYCLEPercentage 20094415852.7% 20106616923.9% 20113026271.1% 20125232971.5% 20136934881.9% * Severity of OHSS were not defined IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion 2.22%

20. 20 Prevention: Coasting Cryopreservation of oocytes and embryos Antagonis protocols In Vitro Maturation GnRH agonis trigger in antagonis protocol Ovarian Hyperstimulation Syndrome (OHSS) IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

21. day 1 2 3 ----//---- 8 9 10 11 12 13 14 15 16 ultrasound and hormone level FSHr 100 - 150 IU IVM FSH + HCG hCG 10.000 IU OPUICSIET IVM (24 h) Embryo culture Menses Progynova Crinone

22. day 1 2 3 ----//---- 8 9 10 11 12 13 14 15 16 ultrasound and hormone level FSHr 150 - 225 IU GnRH agonist trigger + HCG Buserelin 0.5 OPU and ICSI ET Embryo culture Menses Progynova Crinone GnRH antagonis HCG 1500 iu 1 – 2 hrs after OPU

23. COMPLICATION ?? PCO/PCOS IVM FSH+HCG GnRH Agonist trigger + HCG 1500 iu Clinical pregnancies per cycle 20.4% (9/44)31.5% (6/19) Implantation rate 8.5% (9/105)16% (9/54) No. of miscarriages 5/91/6 No. of live birth babies 4/95/6 OHSS 02 ( Mild) First 4 IVM babies in INDONESIA Family Fertility Clinic 2009 -2012 IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion Malvin E. Oral Presentation, Malaysia Reproductive Medicine Congress 2013

24. IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion COMPLICATION ?? Total Quality Management. Pre Congress Course ESHRE 2013

25. IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion COMPLICATION ?? Total Quality Management. Pre Congress Course ESHRE 2013

26. IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion COMPLICATION ?? Total Quality Management. Pre Congress Course ESHRE 2013

27. EXPENSIVE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

28. day 1 2 3 ----//---- 8 9 10 11 12 13 14 15 16 ultrasound and hormone level FSHr 150 - 225 IU IVF STANDARD PROTOCOL HCG 10000 OPU and ICSI ET Embryo culture Menses Crinone GnRH antagonis STIMULATION CLINICAL AND LAB. PROCEDURES

29. EXPENSIVE ?? PROTOCOLS – NATURAL – NATURAL MODIFIED – MILD – IVM – LONG AGONIST – ANTAGONIS – ANTAGONIST + LH PRICE VARIES* – MIN. Rp 20 million – MAX. Rp 60 million IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion *Family Fertility Center 2014

30. EXPENSIVE ?? Most important Pregnancy rate !! IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

32. IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

33. EXPENSIVE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion 44 % 27 % Family Fertility Center IVF Registry 2014 135 cycles

34. IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

35. Optimal number of oocytes needed to Maximize the pregnancy rate after IVF – Ranges between 8 – 15 oocytes – Higher chance to have embryos stored – Between 15 – 20 oocytes no further increase in pregnancy rates – Above 20 oocytes – drop in pregnancy rates caused by cancellation and freeze all (OHSS) EXPENSIVE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion P. Humaidan. LIFE Congress, 2014

36. EXPENSIVE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion Family Fertility Center IVF Registry 2014 135 cycles

37. EXPENSIVE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion 50% FROZEN EMBRYO TRANSFER Family Fertility Center IVF Registry 2014 12 cycles15 cycles

38. To reduce cost of IVF Milder stimulation without harming pregnancy rate Best Candidate: – Women Age < 35 Ovarian Reserved 8 – 15 EXPENSIVE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion Many options for IVF Stimulation Protocols

40. LOW SUCCESS RATE ?? – Early IVF for: Women – Age > 38 yrs – Poor Ovarian Reserved (AMH, AFC) Men – Poor Sperm Parameter COMPLICATION ?? – IVM or GnRH agonis trigger for PCO/S – Proper training and prevention EXPENSIVE ?? – Good candidate for lesser stimulation Women with Age < 30 yrs Women with predicted oocyte retrieved between 8 – 15 Take Home Messages

41. Cycle Optimization To make it easier To make it safer To make it more cost effective To make more babies Take Home Massages Objective Method Result Discussion Conclusion

42. Dr. Malvin Emeraldi Dr. Luki Satria Dr. Yuli Dr. Muchsin Jaffar Dr. Dianing Amalia Inne Hendarmani Anggun Esti Zr. Astina Zr. Hanifah Koparina Zr. Dian Indriani Zr. SriGuswanti Helijah Syafrudin THANK YOU www.bayitabung-rsiafamily.com