Precision Therapeutic and Preventive Molecular Strategies for Endometriosis-Associated Infertility

Abstract

Endometriosis, a chronic estrogen-dependent disorder defined by ectopic endometrial-like tissue growth, causes pelvic pain and infertility in reproductive-age women. Despite its prevalence, the underlying mechanisms driving lesion persistence and reproductive impairment remain unclear. This review synthesizes recent pathophysiological advances, highlighting how hormonal dysregulation, immune dysfunction, epigenetic alterations, and oxidative stress collectively foster lesion persistence and treatment resistance. Critically, these molecular disturbances disrupt critical reproductive functions-including oocyte quality, endometrial receptivity, and embryo implantation. We further explore emerging non-hormonal therapeutic strategies, including MAPK and PI3K/AKT inhibitors as well as epigenetic agents targeting HOXA10 methylation and microRNA modulation, which offer fertility-sparing alternatives to conventional hormonal suppression. To enhance clinical translation, we propose a multi-level prevention framework-encompassing at the primary level, risk reduction; at the secondary level, biomarker-guided intervention; and at the tertiary level, fertility preservation-to anticipate disease progression and personalize reproductive care. By delineating shared pathways between endometriosis and infertility, this work advances precision medicine approaches for affected patients.