Endometriosis Uncovered: From Chronic Inflammation to Reproductive Dysfunction and Impaired ART Outcomes.

Background and

Objectives

Endometriosis is a chronic, estrogen-dependent disorder characterized by the presence of functional endometrial tissue, comprising both glandular and stromal components, located outside the uterine cavity, affecting approximately 6-10% of women of reproductive age and up to 30-50% of those with infertility. Increasing evidence indicates that endometriosis is not solely a localized gynecological condition but rather a systemic inflammatory and immune-mediated disease. Chronic inflammation and immune dysregulation contribute to disease progression and may impair reproductive function. This review aims to analyze the current evidence regarding the inflammatory and immunological mechanisms underlying endometriosis and to evaluate their impact on reproductive dysfunction and assisted reproductive technology (ART) outcomes. Materials and

Methods

A comprehensive narrative review was conducted using major scientific databases, including PubMed, Scopus, and Web of Science. Relevant articles published in the last decade were selected using keywords such as "endometriosis", "inflammation", "immune response", "cytokines", and "ART outcomes". Both clinical and experimental studies were included to assess the relationship between inflammatory markers, immune alterations, and reproductive performance.

Results

Endometriosis is associated with elevated levels of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), as well as increased oxidative stress and altered peritoneal microenvironment. Immune dysfunction is characterized by activated macrophages, decreased natural killer (NK) cell cytotoxicity, and an imbalance in T-cell populations. These alterations negatively affect oocyte quality, fertilization, embryo development, and endometrial receptivity. Emerging biomarkers such as IL-6, TNF-α, and CA-125 show potential in predicting disease severity and ART outcomes, although their clinical utility remains under investigation.

Conclusions

Endometriosis should be regarded as a systemic immuno-inflammatory disorder with significant implications for reproductive health. The interaction between chronic inflammation and immune dysregulation plays a central role in infertility and suboptimal ART outcomes. Further research is required to validate reliable biomarkers and develop targeted therapeutic strategies to improve reproductive success in affected patients.