1. Prof.Dr.Tayfun BAĞIŞ 15/05/2013 TJOD

3. TerminologyAimMethodology Natural cycle IVFSingle oocyteNo medication No luteal support Modified NC IVFSingle oocyteHCG only, antagonist, and/or FSH/HMG add back (up to 150 IU) Luteal support (HCG or P) Mild IVF2-7 oocytesFixed low dose FSH/HMG (up to 150 IU), oral compounds and antagonist Conventional IVF≥8 oocytesConventional FSH/HMG dose, agonist or antagonist

4. Current ovarian stimulation approachesMild stimulation approaches Time consuming and complex stimulation regimens Less complex Less time consuming High costsCheaper (making IVF more accessible for a broader patient population) Much patient discomfortReduced chances for discomfort Short-term complications—ovarian hysterstimulation syndrome (OHSS) Reduced chances for complications High drop-out ratesReduced chances for drop-out Supraphysiological steroid levels with possible implications Effects on oocyte quality Effects on endometrial receptivity Emphasize additional pregnancy chances from cryopreserved embryos Reduced chances for cryopreserved embryos Emphasize maximizing pregnancy rates per cycleEmphasize maximizing chances for healthy children born per started treatment at reasonable cost, patient discomfort and chances for complications

5. NATURAL CYCLE IVF AND MNC IVF

6. The per cycle costs of NC IVF is 20-23% of stimulated IVF.

8. 4 cycles NC IVF Cumulative PR 46 % LBR 32% (Nargund et al., 2001)

13. 501 cycles In cycles <40 years NC IVFMSP Cycles with oocytes61.3 %77.5 %0.03 PR/cycle9.3 %24.2 %0.01 PR/ET18.4 %36.7 %0.01 No difference in women older than 40 years

16. POR N:136 390 cycles CONTROL N:28 79 cycles P Cycles with oocytes75 %78 %NS Cycles with ET42 %59 %0.011 (+) HCG/cycle4.6 %15.2 %0.0005 LBR/cycle2.6 %8.9 %0.006 (+) HCG/patient12.5 %35.7 %0.003 LBR/patient7.4 %25 %0.005

17. MNC IVF Nonrandomized studies in POR patients Success rates 0- 14% Elizur et al., 2005; Castelo-Branco et al., 2004; Kolibianakis et al., 2004; Weghofer et al., 2004; Hur et al., 2005

20. MNC IVF Pelinck 2006 Cycles started844 Cycles canceled before HCG3 % OR planned90.5 % Planned OR canceled9 % OR performed82.3% OR successful75.3% Fertilization/OR71.9% Embryo transfer37.6 % OPR/cycle8.3% OPR/ET22.1%

21. CLOMIPHENE CITRATE based protocols

27. window threshold recruitment menses selectiondominance atresia FSH level Follicle size Luteo-follicular transitison

52. CONCLUSIONS: Strength: GnRH antagonist advantages Reduced complexity, patient discomfort and risk Reduced cost Beneficial effect on oocyte/embryo quality Weakness: Lower PR/cycle Excessive responses Cost of medications is still high Less margin for suboptimal laboratory performance Fewer embryos for cryopreservation Difficult programming of the cycle