Endometriosis

Endometriosis impairs fertility through multiple, often simultaneous mechanisms. Peritoneal disease (Stage I–II) creates an inflammatory pelvic environment that is hostile to sperm, eggs, and embryos — elevated peritoneal fluid cytokines, macrophage activation, and reactive oxygen species all impair sperm–egg interaction and early embryo development. Tubal disease (Stage III) can distort or occlude the fallopian tubes, preventing natural conception. Ovarian endometriomas (Stage III–IV) cause direct mechanical damage to the ovarian cortex, reducing the primordial follicle pool and measurable markers of ovarian reserve — AMH and antral follicle count are typically lower in women with bilateral endometriomas (Streuli et al., J Assist Reprod Genet 2014).

Deep infiltrating endometriosis (Stage IV) and adenomyosis (endometriosis within the uterine muscle wall, which frequently co-exists) can impair endometrial receptivity and implantation. Abnormal uterine peristalsis, altered integrin expression, and immune dysregulation within the endometrium have all been implicated. This explains why, even with apparently normal ovaries and tubes, women with moderate-to-severe endometriosis may have lower per-cycle pregnancy rates than women without the disease.

The relationship between Stage I–II endometriosis and infertility is more nuanced — the peritoneal inflammatory environment appears to be sufficient to impair fertility even in the absence of anatomical distortion. A landmark RCT (Marcoux et al., NEJM 1997) found that laparoscopic excision of minimal-to-mild endometriosis increased cumulative pregnancy rates from 17% to 31% over 36 weeks versus diagnostic laparoscopy alone. Subsequent meta-analyses have confirmed a modest but real benefit of surgery for Stage I–II disease (Duffy et al., Cochrane 2014).