Despite the wide utilization of gonadotropin-releasing hormone analogs, progesterone elevation (P 4 E) in the late follicular phase occurs in 5 to 30% of all ovarian stimulation (OS) cycles. Although the detrimental effect of P 4 E on pregnancy rates in fresh in vitro fertilization cycles is valid in all subsets of cases, higher levels of P 4 and a longer duration of P 4 E may be needed in patients with a hyper-ovarian response in order for a negative impact on pregnancy rates to occur. Available preclinical and clinical data suggest that aggressive OS with high doses of follicle-stimulating hormone might increase 3β-hydroxy steroid dehydrogenase and 17β-hydroxy steroid dehydrogenase enzyme activity in human granulosa cells, which leads to high P 4 production and hence a higher amount of leakage to the systemic circulation due to a lack of 17α-hydroxylase enzyme expression in human species. High P 4 concentrations appear to alter gene expression in the endometrium; however, caution is necessary regarding its potential effect on oocyte/embryo quality with respect to the role of inherent follicular disruption in some women. In terms of the mechanism of overproduction in P 4 synthesis, the main preventive strategy should be avoiding aggressive stimulation. Unfortunately, there is lack of large-scale randomized controlled trials for other approaches, including deferred embryo transfer in the thaw cycle. Since there is a significant inter-assay variability for P 4 measurement, it may be wise to recommend that every center should define their own P 4 E and the level needed for harm to occur based on their own assays and datasets before deciding the best approach. [ABSTRACT FROM AUTHOR]