{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T17:26:22Z","timestamp":1784395582264,"version":"3.55.0"},"reference-count":297,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Aziza Othmena Hospital and the Tunisian Ministry of Higher Education and Scientific Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2014including 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\u2014encompassing at the primary level, risk reduction; at the secondary level, biomarker-guided intervention; and at the tertiary level, fertility preservation\u2014to anticipate disease progression and personalize reproductive care. By delineating shared pathways between endometriosis and infertility, this work advances precision medicine approaches for affected patients.<\/jats:p>","DOI":"10.3390\/ijms26167706","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T11:02:09Z","timestamp":1754910129000},"page":"7706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Precision Therapeutic and Preventive Molecular Strategies for Endometriosis-Associated Infertility"],"prefix":"10.3390","volume":"26","author":[{"given":"In\u00e8s","family":"Limam","sequence":"first","affiliation":[{"name":"LR99ES11, Faculty of Medicine of Tunis, Tunis El Manar University, Tunis 1006, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0984-6083","authenticated-orcid":false,"given":"Mohamed","family":"Abdelkarim","sequence":"additional","affiliation":[{"name":"Population Health, Environmental Aggressors, Alternative Therapies, Faculty of Medicine of Tunis, Tunis El Manar University, Tunis 1006, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1902-9295","authenticated-orcid":false,"given":"Khadija","family":"Kacem-Berjeb","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medecine, Aziza Othmana University-Hospital, Health Ministry, Tunis 1008, Tunisia"},{"name":"LR16SP01 Procr\u00e9ation-Infertilit\u00e9, Aziza Othmana University-Hospital, Tunis El Manar University, Tunis 1008, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-0171","authenticated-orcid":false,"given":"Mohamed","family":"Khrouf","sequence":"additional","affiliation":[{"name":"LR16SP01 Procr\u00e9ation-Infertilit\u00e9, Aziza Othmana University-Hospital, Tunis El Manar University, Tunis 1008, Tunisia"},{"name":"Centre FERTILLIA de M\u00e9decine de la Reproduction-Clinique la Rose, Tunis 1053, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9817-9445","authenticated-orcid":false,"given":"Anis","family":"Feki","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital of Fribourg, 1708 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-3471","authenticated-orcid":false,"given":"Marouen","family":"Braham","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medecine, Aziza Othmana University-Hospital, Health Ministry, Tunis 1008, Tunisia"},{"name":"LR16SP01 Procr\u00e9ation-Infertilit\u00e9, Aziza Othmana University-Hospital, Tunis El Manar University, Tunis 1008, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7118-6023","authenticated-orcid":false,"given":"Nozha","family":"Chakroun","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medecine, Aziza Othmana University-Hospital, Health Ministry, Tunis 1008, Tunisia"},{"name":"LR16SP01 Procr\u00e9ation-Infertilit\u00e9, Aziza Othmana University-Hospital, Tunis El Manar University, Tunis 1008, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1056\/NEJMcp1000274","article-title":"Endometriosis","volume":"362","author":"Giudice","year":"2010","journal-title":"N. 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