# Potential Changes in the Eutopic Endometrium in Endometriosis: A Narrative Review

## TL;DR

This review explores how endometriosis may alter the normal endometrium, affecting fertility through inflammation, immune changes, and progesterone resistance.

## Contribution

The paper provides a narrative review of novel mechanisms linking endometriosis to eutopic endometrial dysfunction, focusing on immune profiles and hypoxia.

## Key findings

- Endometriosis is associated with pro-inflammatory macrophage and Th17 immune profiles in the eutopic endometrium.
- Hypoxia in endometriosis may alter angiogenesis and epigenetic regulation, affecting endometrial cell metabolism.
- Progesterone resistance is a potential contributor to impaired endometrial cell homeostasis in endometriosis.

## Abstract

Endometriosis is a disease characterized by the presence of ectopic endometrium, mainly within the peritoneal cavity, and is associated with the development of inflammation due to cyclic endometrial alterations. The end result of endometriosis is usually infertility, often leading couples to assisted reproduction techniques (ARTs). In the context of infertility, several approaches have been made, aiming to highlight potential pathophysiological mechanisms; it is now accepted that endometriosis may affect both ovarian and endometrial function.

The current review aims to summarize the main alterations reported on potential eutopic endometrium changes in cases of endometriosis, focusing mainly, but not exclusively, on local inflammatory pathways, angiogenesis, and immune alterations that may affect implantation. New evidence implies that, in cases of endometriosis, macrophage and T helper 17 (Th17) immune profiles are rather pro-inflammatory - a finding possibly explaining reduced endometrial receptivity. Concurrently, the hypoxic stress noted in endometriosis has been considered the cause of alterations in angiogenesis, as well as in epigenetic regulation. This, in turn, may lead to changes in endometrial cells’ metabolism. In the same direction, progesterone resistance has been shown as a potential factor of impaired endometrial cell homeostasis. The proposed mechanisms of eutopic endometrial cell alterations may be set as research targets for therapeutic interventions via designing proper clinical trials.