Progesterone in frozen embryo transfer cycles: assays, circulating concentrations, metabolites, and molecular action

Programmed or medicated frozen embryo transfer cycles rely on exogenous progesterone (P) administration to prepare the endometrium for implantation and maintain pregnancy. Presently, the optimal route and dose of P replacement for frozen embryo transfer are not known. In addition, there is a paucity of data and insufficient understanding regarding the metabolism and actions of P in implantation and pregnancy maintenance. In the present review, we discuss how different P assay methodologies affect the determination of P thresholds for implantation and pregnancy maintenance. In addition, we discuss the importance of free P and its regulation in the endometrium and show the complexity of molecular signaling that is required for P-dependent endometrial receptivity. We concluded that future studies should focus on defining accurate circulating and endometrial P concentrations, both for total and free P, and how these concentrations correlate with endometrial receptivity and clinical outcomes.