The impact of unilateral endometriomas on ovarian response to stimulation: a systematic review and meta-analysis

STUDY QUESTION: How do unoperated ovarian endometriomas affect ovarian response during ovarian stimulation cycles? SUMMARY ANSWER: Ovaries affected by unoperated ovarian endometriomas show similar outcomes to unaffected ovaries following controlled ovarian stimulation. WHAT IS KNOWN ALREADY: Ovarian endometriomas are estimated to affect between 17% and 44% of women with endometriosis. The heterogeneity of the published literature from IVF/ICSI cycles aggregated in meta-analyses has shown both lower and similar reproductive outcomes in women with ovarian endometriomas compared with control women. To overcome these problems in studying reproductive outcomes in presence of ovarian endometriomas, some observational studies have been performed, comparing the affected unoperated ovary with the unaffected contralateral ovary in women with unilateral disease. This approach allows to investigate both the quantitative and qualitative aspects of the ovarian response in presence of a unilateral ovarian cyst. STUDY DESIGN, SIZE, DURATION: A systematic search for all eligible studies in the PubMed and Cochrane databases until 1 May 2025 was conducted. Eligible studies met the following criteria: (i) original studies comparing unoperated unilateral endometriomas with contralateral healthy ovaries in the same patients, (ii) clear description of diagnostic methods for ovarian endometriosis, and (iii) available data on ovarian response, oocyte collection, and reproductive outcomes following ART from each ovary. PARTICIPANTS/MATERIALS, SETTING, METHODS: Studies were screened, data were extracted, and the risk of bias was assessed independently by two investigators. The main outcome was the number of oocytes retrieved per ovary. Secondary outcomes included the number of MII oocytes, fertilization rate, the number of embryos formed, the number of good-quality embryos, and implantation rates. MAIN RESULTS AND THE ROLE OF CHANCE: Two thousand nine hundred and three studies were identified and 13 observational studies met the inclusion criteria and were included in this systematic review and meta-analysis. The meta-analysis of the number of oocytes retrieved showed comparable results between affected and unaffected ovaries in women with unilateral ovarian endometrioma (MD -0.72, 95% CI -1.45 to 0.02; I² = 97%; 11 studies, 560 patients). Similarly, the number of MII oocytes and good-quality embryos were comparable between affected and unaffected ovaries (MD -0.60, 95% CI -1.86 to 0.66; I² = 81%; 6 studies, 149 patients and MD -0.18, 95% CI -0.53 to 0.18; I² = 0%; 3 studies, 74 affected vs 74 unaffected ovaries, respectively). Conversely, the number of embryos formed was significantly lower in affected ovaries (MD -0.72, 95% CI -1.39 to -0.05; I² = 68%; 4 studies, 192 affected vs 193 unaffected ovaries, respectively). LIMITATIONS, REASONS FOR CAUTION: Most of the included studies were observational, with eight being retrospective, which increases susceptibility to bias. In addition, the outcome reporting was inconsistent, and none of the studies was preregistered, raising the risk of selective reporting. WIDER IMPLICATIONS OF THE FINDINGS: Unoperated ovarian endometriomas appear to have little or no impact on ovarian stimulation outcomes, however, the impact of larger endometriomas remains uncertain. These findings suggest that gynecologists should carefully consider whether to recommend surgery prior to IVF/ICSI, particularly for small endometriomas, which may not adversely impact ovarian stimulation outcomes. FUNDING: No funding was used to conduct this study. DISCLOSURES: D.R.K. received research grants from Gottfried und Julia Bangerter-Rhyner and Bouriez foundations. E.S. declares speakers' fees from IPSEN and Gedeon Richter, fees from consultations from Ferring and grants for research from IBSA and Ferring. P.V. has received honoraria as Co-Editor-in-Chief of the Journal of Endometriosis and Uterine Disorders. M.C. has nothing to disclose. C.B. reports grants and personal fees from MSD, Ferring, Abbott, and Gedeon Richter. The remaining authors have nothing to disclose. REGISTRATION NUMBER: CRD42024507807 (https://www.crd.york.ac.uk/PROSPERO/view/CRD42024507807).