Does Endometrioma Diameter Impact Serum anti-Müllerian Hormone Levels? A Systematic Review and Meta-analysis

Abstract STUDY QUESTION Is endometrioma diameter associated with ovarian reserve, as reflected by serum anti-Müllerian hormone (AMH) levels, in women of reproductive age with no history of ovarian surgery? SUMMARY ANSWER Across 30 independent cohorts, endometrioma diameter showed no independent association with serum AMH levels when modeled either continuously or categorically, indicating that cyst size is unlikely to be a principal determinant of diminished ovarian reserve in non-operated endometrioma. WHAT IS KNOWN ALREADY The extent to which endometrioma diameter contributes to ovarian reserve impairment remains uncertain and has historically informed size-based thresholds for surgical intervention. Whether larger cysts exert a greater deleterious effect on ovarian reserve remains debated. Observational studies in women without prior ovarian surgery have reported inconsistent and often contradictory findings. STUDY DESIGN, SIZE, DURATION Systematic review and meta-analysis of studies published in English between 1 January 2000 and 30 June 2025. Searches were conducted in PubMed, ClinicalTrials.gov, the Cochrane Library, Web of Science, and EBSCOhost. PARTICIPANTS/MATERIALS, SETTING, METHODS Eligible studies compared serum AMH across different endometrioma diameters within the same population and setting in reproductive-age women with non-operated endometrioma. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-I. The primary inferential analysis was a cohort-level multivariable random-effects meta-regression based on 30 independent, non-overlapping cohorts derived from 16 studies, adjusting for age. Diameter was modeled both as a continuous predictor and as prespecified strata (<4 cm, 4–5 cm, 5–6 cm, >6 cm). Supportive exploratory threshold and subgroup analyses (predefined cut-offs 3 to 8 cm) were interpreted with multiplicity control using the Holm–Bonferroni sequentially rejective procedure. MAIN RESULTS AND THE ROLE OF CHANCE Sixteen studies, including 1,484 women, met the inclusion criteria, and 30 independent cohorts were used in the primary analysis. Endometrioma diameter was not a significant predictor of serum AMH when modeled continuously (β = 0.122, SE = 0.128, P = 0.35) or categorically across diameter strata (β = 0.245, SE = 0.220, P = 0.28). In contrast, age accounted for most of the between-cohort heterogeneity (R2 = 58.2%). Supportive subgroup and threshold analyses did not materially alter the primary inference after multiplicity adjustment. Of the 16 eligible studies, two were judged to be at low risk and 14 at moderate risk of bias, suggesting overall moderate certainty of the evidence. LIMITATIONS, REASONS FOR CAUTION The analysis was restricted to non-operated endometriomas; therefore, the relationship between preoperative diameter and post-surgical AMH decline could not be assessed. Residual confounding is possible given the observational nature of the included studies and variation in measurement and laboratory methods. WIDER IMPLICATIONS OF THE FINDINGS In women with non-operated endometrioma, ovarian reserve impairment, when present, appears largely independent of cyst diameter, arguing against a predominant “mass effect” as the principal mechanism. These findings support clinical counselling and management strategies that do not rely on cyst size alone when considering infertility care, delayed childbearing, and fertility preservation. STUDY FUNDING/COMPETING INTEREST(S) No funding was received for the conduct of this study. The authors declare no competing interests. REGISTRATION NUMBER Prospectively registered at PROSPERO under number CRD42025632149 on 28 December 2024