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

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

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 )

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

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

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

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

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

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

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

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

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

IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

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

COMPLICATION ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

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 % % % % % * Severity of OHSS were not defined IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion 2.22%

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

day // ultrasound and hormone level FSHr IU IVM FSH + HCG hCG IU OPUICSIET IVM (24 h) Embryo culture Menses Progynova Crinone

day // ultrasound and hormone level FSHr 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

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 IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion Malvin E. Oral Presentation, Malaysia Reproductive Medicine Congress 2013

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

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

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

EXPENSIVE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

day // ultrasound and hormone level FSHr IU IVF STANDARD PROTOCOL HCG OPU and ICSI ET Embryo culture Menses Crinone GnRH antagonis STIMULATION CLINICAL AND LAB. PROCEDURES

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

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

IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

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

IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion

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

EXPENSIVE ?? IVF TROUBLESHOOTING Objective Method Result Discussion Conclusion Family Fertility Center IVF Registry cycles

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

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

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

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

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