Association Between Progesterone Elevation on the Day of Human Chronic Gonadotropin Trigger and Pregnancy Outcomes After Fresh Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles

Progesterone elevation (PE) during the late follicular phase of controlled ovarian stimulation in fresh embryo transfer in vitro fertilization/intracytoplasmic sperm injection cycles has been claimed to be associated with decreased pregnancy rates. However, the evidence is not unequivocal, and clinicians still have questions about the clinical validity of measuring P levels during the follicular phase of stimulated cycles. We reviewed the existing literature aimed at answering four relevant clinical questions, namely, (i) Is gonadotropin type associated with PE during the follicular phase of stimulated cycles? (ii) Is PE on the day of human chorionic gonadotropin (hCG) associated with negative fresh embryo transfer in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles outcomes in all patient subgroups?; (iii) Which P thresholds are best to identify patients at risk of implantation failure due to PE in a fresh embryo transfer?, and (iv) Should a freeze all policy be adopted in all the cycles with PE on the day of hCG? The existing evidence indicates that late follicular phase progesterone rise in gonadotropin releasing analogue cycles is mainly caused by the supraphysiological stimulation of granulosa cells with exogenous follicle-stimulating hormone. Yet, the type of gonadotropin used for stimulation seems to play no significant role on progesterone levels at the end of stimulation. Furthermore, PE is not a universal phenomenon with evidence indicating that its detrimental consequences on pregnancy outcomes do not affect all patient populations equally. While patients with high ovarian response to control ovarian stimulation are more prone to exhibit progesterone elevation at the late follicular phase, the potential adverse effect of progesterone elevation on fresh embryo transfer pregnancy outcomes seem to be offset by the increased probability of obtaining high-quality embryos for transfer in this patient subset. Given the limitations of the currently available assays to measure progesterone at low ranges, caution should be applied to adopt specific cut-off values above which the effect of progesterone rise could be considered detrimental and to recommend ‘freeze-all’ based solely on pre-defined cutoff points.