Endometriosis-Associated Infertility: A Review of Pathophysiological Mechanisms and Current Treatment Strategies.

Background

Endometriosis affects 10-15% of reproductive-aged women and is a leading cause of infertility through anatomical, inflammatory, and molecular mechanisms.

Objective

This review synthesizes current evidence on the pathophysiology of endometriosis-associated infertility and evaluates medical, surgical, and ART strategies to guide individualized management.

Methods

We conducted a narrative review (2000-2025; PubMed, Scopus, WoS) synthesizing RCTs, meta-analyses, and observational studies on mechanisms and treatment outcomes.

Results

In rASRM stage III-IV, tubo-ovarian distortion and adhesions mechanically impair oocyte pickup and embryo transport. In superficial disease, animal models demonstrate that peritoneal inflammatory mediators and ROS can impair oocyte maturation, though direct causal evidence in humans is lacking. Epigenetic dysregulation has been identified in the eutopic endometrium and linked to progesterone resistance, though its direct causal role in infertility remains unestablished. Hormonal suppression controls pain but does not improve spontaneous conception rates. Laparoscopic surgery in stage I-II remains debated. Prospective evidence supporting fertility benefit from DIE excision without mechanical obstruction is lacking. Cystectomy consistently reduces AMH, favoring IVF over surgery unless symptoms or retrieval barriers exist. IVF/ICSI live birth rates per cycle in stage I-II are comparable to those without endometriosis; cumulative rates after ≤5 cycles reach 43-46% in treated vs. 28% in untreated stage III-IV patients.

Conclusions

Management requires two sequential decisions: first, whether to perform a diagnostic laparoscopy to identify minimal disease and adhesions, and second, whether to proceed with surgery or transfer directly to ART. Age ≥ 35, infertility > 2 years, or low AMH/AFC favor immediate IVF. Post-surgical EFI guides timing: high EFI supports expectant management or IUI; low EFI should prompt ART referral. When cystectomy is necessary, tissue-sparing techniques should be prioritized and fertility preservation, including oocyte cryopreservation, discussed preoperatively.