Obesity and PCOS: the effect of metabolic derangements on endometrial receptivity at the time of implantation

Abstract

Successful embryonic implantation is the result of a receptive endometrium, a functional embryo at the blastocyst stage and a synchronized dialog between maternal and embryonic tissues. Successful implantation requires the endometrium to undergo steroid-dependent change during each menstrual cycle, exhibiting a short period of embryonic receptivity known as the window of implantation. The term "endometrial receptivity" was introduced to define the state of the endometrium during the window of implantation. It refers to the ability of the endometrium to undergo changes that will allow the blastocyst to attach, penetrate, and induce localized changes in the endometrial stroma. These changes are metabolically demanding, and glucose metabolism has been proven to be important for the preparation of the endometrium for embryo implantation. Obesity and polycystic ovary syndrome (PCOS) represent 2 common metabolic disorders that are associated with subfertility. The aim of this review is to summarize the effect of obesity and PCOS on endometrial receptivity at the time of implantation. Focus will be on metabolic alterations that regulate decidualization, including glucose metabolism, hyperinsulinemia, and hyperandrogenism.

Keywords: PCOS; endometrial receptivity; implantation; metabolism; obesity.

Figure 1.

The effect of hyperinsulinemia on the endometrium in polycystic ovary syndrome (PCOS) and obesity. Obesity and PCOS lead to a compensatory hyperinsulinemic state, which affects endometrial homeostasis, leading to decreased insulin receptors and decreased production of decidualization biomarkers.

Figure 2.

Effect of hyperandrogenism on endometrium in polycystic ovary syndrome (PCOS) and obesity. Polycystic ovary syndrome and obesity are hyperinsulinemic states which contribute to hyperandrogenism by enhancing luteinizing hormone (LH)-stimulated androgen production in the ovary and adrenal expression of dehydroepiandrosterone. This hyperandrogenism affects the window of implantation by decreasing gene expression of HOXA10 and WT1 and by affecting endometrial decidualization.