Progesterone level in assisted reproductive technology - a Systematic Review and Meta- analysis

Abstract

Abstract Currently, many measure progesterone in ART cycles as part of cycle monitoring. Elevated or inadequate progesterone levels during ART cycle monitoring may lead to cycle cancellations or further progesterone supplementation, but practice varies. It remains controversial if measuring progesterone improves clinical outcomes. This review aims to investigate if progesterone levels at different phases of fresh and frozen ART cycles influence pregnancy outcomes, in particular, that pertaining day 3 versus day 5 embryo transfers. A systematic search of EMBASE, MEDLINE, CINAHL and PubMed identified studies between 2000 and 2022. We included studies with women undergoing fresh and frozen IVF/ICSI cycles; with extractable per woman data on pregnancy outcomes where serum progesterone measurement was performed. We excluded studies with intervention or donor cycles. The primary outcome was LBR and the secondary outcomes were OPR, CPR and MR. Eligible studies were included after the initial screen of the titles and abstracts. PICOS study protocol was used. Analysis was done using RevMan5. The study was registered with PROSPERO (registration ID CRD42022382423). 64 studies (N = 57,988 women) were included. In fresh cycles, there is no evidence that elevated progesterone (EP) impacts live birth rate (LBR) at baseline (OR 0.76, 95% CI 0.39–1.49). EP at ovulation trigger is associated with a lower LBR for D3 (P > 1.0ng/ml, OR 0.46, 95% CI 0.38–0.55; P > 1.5ng/ml, OR 0.68, 95% CI 0.47–0.98) but not D5 embryo transfer (P > 1.5ng/ml, OR 0.96, 95% CI 0.81–1.14). In FET cycles, we were unable to meaningfully meta-analyse studies due to significant study heterogeneity. In controlled ovarian stimulation, EP at baseline did not impact on LBR; EP at ovulation trigger is associated with a lower LBR for D3 but not for D5 embryo transfer. In FET cycles, as the studies were heterogeneous, we were unable to combine the data in a meaningful way.