Endometriosis and Infertility: A review of the pathogenesis and treatment of endometriosis-associated infertility Original paper

What was reviewed?

This comprehensive review explores the pathogenesis of endometriosis and its impact on infertility, focusing on the mechanisms by which endometriosis impairs fertility and the current and emerging treatment modalities. The article synthesizes evidence on the etiology of endometriosis, including retrograde menstruation, coelomic metaplasia, altered immunity, stem cell involvement, and genetics, and details how these factors culminate in altered pelvic anatomy, inflammatory microenvironments, and molecular changes in reproductive tissues. The review also evaluates the effects of endometriosis on gametes, embryo development, fallopian tube function, and endometrial receptivity, and discusses the effectiveness of treatments such as surgery, medical therapy, superovulation with intrauterine insemination (IUI), and in vitro fertilization (IVF). Future directions, including novel medical therapies, immune modulation, and stem cell-based approaches, are also considered.

Who was reviewed?

The review synthesizes data from a broad range of studies involving women of reproductive age, primarily aged 25–35, affected by endometriosis with and without infertility. It references epidemiologic data showing an increased prevalence of endometriosis among infertile women (up to 50%) and discusses animal models, such as baboons and mice, to elucidate mechanisms relevant to human disease. The populations reviewed include women with varying stages of endometriosis (minimal/mild to advanced), including those participating in surgical, medical, and assisted reproductive intervention trials. Data on genetic and stem cell contributions are drawn from both human and animal research.

Most important findings

Endometriosis is confirmed as a multifactorial, estrogen-dependent inflammatory disease with a robust association with infertility. Mechanistically, infertility arises from both mechanical disruption (e.g., adhesions, distorted pelvic anatomy) and complex molecular interactions involving immune dysregulation, increased inflammatory cytokines, altered gene expression (notably HOXA10 and Wnt signaling), and oxidative stress. These disrupt ovulation, gamete quality, embryo viability, tubal transport, and endometrial receptivity. Aberrant microbiome or microbial signatures are not a primary focus, but the inflammatory milieu, rich in cytokines and altered immune cell populations, could suggest potential secondary impacts on local microbial communities. Treatments are stage-dependent; surgery is most beneficial for minimal-moderate disease, while IVF remains the most effective for advanced cases. There is limited benefit from medical suppression unless used adjunctively before ART. Emerging approaches, such as stem cell therapy and immune modulation, hold promise for restoring endometrial function and correcting epigenetic alterations.

Key implications

For clinicians, this review underscores the need for individualized management in endometriosis-associated infertility, integrating disease stage, patient age, and reproductive goals. The multifactorial pathogenesis, including immune, genetic, and molecular disruptions, highlights the complexity of diagnosis and treatment, and supports the exploration of targeted, non-hormonal therapies and regenerative approaches. Recognizing the altered inflammatory and possibly microbial environment in the pelvis may inform future research and therapeutic strategies, especially for developing microbiome-informed diagnostic or treatment tools.