Endometriosis-associated infertility: Multi-omics insights into pathogenesis and precision therapeutics

Yuyi Ou, Hao Wang, Cankun Zhou, Yonglian Chen, Jun Lyu, Minqing Feng, Xiaobin Huang
Frontiers in endocrinology · 2025 · vol. 16 , pp. 1613334 · doi:10.3389/fendo.2025.1613334 · PMID:41113721 · PMC12527851 · W4414741682
review OA: gold CC0 ⤵ 5 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This review synthesizes multi-omics data to explain how endometriosis-associated infertility arises from hormonal, immune, oxidative stress, genetic, and microbiome factors, and appraises current and emerging precision therapeutics.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This systematic review synthesizes multi-omics and clinical evidence on mechanisms driving endometriosis-associated infertility, integrating hormonal/endocrine dysregulation, immune-inflammatory dysfunction, oxidative stress/ferroptosis, genetic and epigenetic alterations, and microbiome/metabolic changes to map potential targets and biomarkers. It reports that infertility is linked to local estrogen dominance with progesterone resistance, pervasive immune dysregulation, and iron-driven oxidative injury/ferroptosis that can particularly harm granulosa cells, alongside genetic/epigenetic regulators and gut/reproductive tract dysbiosis; clinically, endometriosis is described as reducing ovarian reserve and oocyte quality, disrupting endometrial receptivity/decidualization, and remodeling pelvic anatomy via adhesions and fibrosis, with variable outcomes from surgery, hormonal suppression, and ART. A stated limitation is that adjunctive antioxidant and immune-modulating approaches and biomarker-driven personalization require robust clinical validation. This paper is centrally about endometriosis-associated infertility — providing a multi-omics synthesis of pathogenesis and precision-therapeutics strategies.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

INTRODUCTION: Endometriosis is a prevalent, estrogen-dependent, inflammatory disease that impairs fertility via hormonal dysregulation, immune dysfunction, oxidative stress/ferroptosis, genetic and epigenetic alterations, and microbiome imbalance. We summarize multi-omics insights and clinical implications for endometriosis-associated infertility. METHODS: This article is a Systematic Review that synthesizes recent multi-omics and clinical evidence on mechanisms (hormonal, immune-inflammatory, oxidative stress/ferroptosis, genetic/epigenetic, microbiome/metabolic) and appraises therapeutic strategies spanning surgery, hormonal suppression, assisted reproductive technologies (ART), and emerging adjuncts. Mechanistic and clinical findings are integrated to map targets, biomarkers, and precision-care opportunities across disease phenotypes. RESULTS: Evidence indicates local estrogen dominance with progesterone resistance, pervasive immune dysregulation, and oxidative stress with iron-driven ferroptosis that particularly injures granulosa cells, alongside disease-relevant genetic/epigenetic regulators and reproductive-tract/gut microbiome dysbiosis. Clinically, endometriosis detrimentally affects ovarian reserve and oocyte competence, disrupts endometrial receptivity/decidualization, and remodels pelvic anatomy through adhesions and fibrosis, cumulatively reducing fecundity. Current management includes laparoscopic excision/ablation, hormonal suppression (e.g., progestins, GnRH analogs/antagonists), and ART tailored to goals and disease severity. Adjunctive antioxidant and immune-modulating approaches show promise but require robust clinical validation. Biomarker discovery-including epigenetic regulators and microbiome-derived signals-may enable earlier diagnosis and personalization. Innovative avenues include immunotherapy targeting nociceptor-immune crosstalk, ferroptosis modulation, microbiota manipulation, and diet-based metabolic strategies. DISCUSSION: The pathogenesis of endometriosis-associated infertility is multifactorial and interconnected. While current treatments offer benefits, their efficacy is variable. The integration of multi-omics data is unveiling novel diagnostic biomarkers and therapeutic targets. Future management requires a patient-centered, multidisciplinary precision medicine approach that combines mechanistic insights with individualized treatment strategies to improve reproductive outcomes across the disease spectrum.

My notes (saved in your browser only)

Condition tags

endometriosisinfertility

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (73)

Cited by (6)

Source provenance

europepmc
last seen: 2026-06-13T17:20:28.795615+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pmc
last seen: 2026-05-13T20:22:03.195721+00:00
pubmed
last seen: 2026-06-13T21:04:57.466334+00:00
License: CC0 · commercial use OK