Prof.Dr.Tayfun BAĞIŞ 15/05/2013 TJOD

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

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

NATURAL CYCLE IVF AND MNC IVF

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

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

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

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

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

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%

CLOMIPHENE CITRATE based protocols

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

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