We read with great interest the article by Valenti et al investigating the association between preoperative antimüllerian hormone (AMH) levels and surgically confirmed endometriosis, including its staging and typology. The authors are to be commended for their robust study design, which effectively isolates the effect of endometriotic lesions themselves from the confounding effects of surgical intervention. The findings that ovarian endometriomas and moderate-to-severe (stages III and IV) diseases are substantially associated with lower AMH levels provide valuable evidence supporting a direct pathophysiological relationship between endometriosis and diminished ovarian reserve.
Although the study conclusively demonstrated the association, we believe that it opens a crucial avenue for discussing the underlying mechanisms and clinical translation. The authors appropriately hypothesize that inflammation and anatomic distortions may be key drivers. Building on this, we suggest that future research could significantly benefit from integrating specific inflammatory mediators (eg, interleukin 6 and tumor necrosis factor alpha) or markers of oxidative stress measured in serum or peritoneal fluid with AMH levels. Such an approach could help delineate whether the observed AMH reduction is mediated by a generalized inflammatory state or a more localized, follicle-toxic microenvironment created by the lesions, particularly endometriomas.
Furthermore, the study’s use of the revised American Society for Reproductive Medicine staging and a mutually inclusive typology classification, although pragmatic, presents a challenge in pinpointing the exact lesion characteristic most detrimental to ovarian reserve. As the authors noted, the strong signal from ovarian endometriomas likely drives the association seen in other subtypes. Future studies might consider using more granular classification systems, such as the #Enzian classification, which separately documents peritoneal, deep, and ovarian diseases, to disentangle their individual contributions and better predict fertility outcomes.
From a clinical perspective, the findings reinforce the importance of assessing ovarian reserve in women with suspected moderate-to-severe diseases or ovarian endometrioses, especially those presenting with infertility. This prompts the question, “Could serial AMH monitoring in these patients serve as a useful tool to gauge disease progression or response to medical therapy aimed at suppressing inflammation?” The pronounced effect observed in women with infertility (−72.6% lower AMH with ovarian endometriomas) underscores a subgroup that may warrant particularly vigilant fertility counseling and perhaps earlier consideration of fertility preservation strategies.
Finally, given the cross-sectional nature of the analysis, the crucial next step is longitudinal research. Prospective cohort studies tracking AMH trajectories from diagnosis through various treatments and across the natural history of endometriosis are essential to establish causality and understand the dynamics of ovarian reserve depletion.
We thank Valenti et al for their important contribution, which not only confirms previous observations but also provides a clearer presurgical benchmark. Their work compellingly directs the scientific community toward deeper mechanistic inquiries and more personalized clinical management for women with endometriosis.
CRediT authorship contribution statement
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