Endometriosis-Associated Infertility: Molecular Mechanisms and Evidence-Based Clinical Management

Kai-Jung Chang, Tsung‐Hsuan Lai
In: International Journal of Molecular Sciences · 2026 · vol. 27(20) , pp. 9040 · doi:10.3390/ijms27209040 · W7221545922
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This narrative review integrates molecular mechanisms of endometriosis-associated infertility with evidence-based clinical management strategies, including diagnostic phenotyping and assisted reproduction protocols.

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Abstract

Endometriosis is a chronic, estrogen-dependent inflammatory disease and a major contributor to female infertility. Endometriosis-associated infertility arises from interacting anatomical and biological mechanisms, including pelvic adhesions and tubal dysfunction, reduced ovarian reserve, altered follicular and oocyte competence, oxidative stress, immune dysregulation, and impaired endometrial function. This narrative review integrates current concepts of disease pathogenesis with evidence-based fertility management. It first examines the molecular, cellular, and immune processes that support ectopic lesion establishment and may impair reproduction. It then discusses diagnostic phenotyping, infertility evaluation, prognostic tools, medical suppression, fertility-preserving surgery, intrauterine insemination, and in vitro fertilization. Particular attention is given to the strength and clinical relevance of current evidence, including surgery for ovarian endometrioma before assisted reproduction, prolonged gonadotropin-releasing hormone agonist pretreatment, fresh versus frozen embryo transfer, and the use of intracytoplasmic sperm injection without male-factor infertility. Emerging anti-angiogenic, immunomodulatory, antioxidant, stem-cell, and gene- or epigenetic-based interventions remain investigational. Because neither a single treatment nor a single assisted-reproduction protocol is optimal for all patients, management should integrate age, ovarian reserve, symptom burden, disease phenotype, prior surgery, coexisting infertility factors, and reproductive priorities. Mechanistically informed clinical trials using live birth and patient-centered outcomes are needed to advance precision fertility care.

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