Monitoring ovarian reserve dynamics via a high-sensitivity anti-Müllerian hormone assay in premenopausal breast cancer patients undergoing chemotherapy.

STUDY QUESTION: Does an ultra-sensitive anti-Müllerian hormone (UD-AMH) assay enhance the accuracy of ovarian dysfunction assessment in premenopausal women with breast cancer (PBC) during and after chemotherapy? SUMMARY ANSWER: Low AMH levels at pre-treatment and end-of-chemotherapy, measured by the UD-AMH assay, are strong predictors for the development of premature ovarian insufficiency (POI) at 12 months post-chemotherapy. WHAT IS KNOWN ALREADY: Anti-Müllerian hormone (AMH) is a recognized biomarker for assessing ovarian reserve and serves as an early indicator of ovarian dysfunction in female cancer patients. However, post-chemotherapy AMH levels frequently fall below detectable limits of conventional assays, hindering rapid and accurate evaluation of residual ovarian reserve. STUDY DESIGN, SIZE, DURATION: Prospective cohort study; 145 total subjects enrolled; follow-up conducted from pre-treatment through 12 months post-chemotherapy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Premenopausal women (aged 18-46 years) with breast cancer recruited at diagnosis; 83 scheduled to receive chemotherapy and 62 who did not. Serum samples were collected pre-treatment (T0), after each chemotherapy cycle, at end-of-chemotherapy (T1), 3 (T2), 6 (T3), and 12 (T4) months post-chemotherapy. AMH levels were quantified using the UD-AMH assay (detection limit 0.13 pg/ml, offering 100-fold higher sensitivity than conventional methods). POI was defined as oligo/amenorrhea with follicle-stimulating hormone (FSH) levels >25 mIU/ml. MAIN RESULTS AND THE ROLE OF CHANCE: AMH was quantifiable in all samples by using the UD-AMH assay. At T4, 30% of PBC exhibited POI. AMH levels at T0 were significantly higher in the non-POI group compared to the POI group (median 5425 pg/ml vs 1103 pg/ml, P < 0.001), as were levels at T1 (median 127 pg/ml vs 10 pg/ml, P < 0.001). T0 AMH predicted POI with an AUC of 0.86 (sensitivity 67%, specificity 95%), while T1 AMH showed superior predictive value with an AUC of 0.89 (sensitivity 81%, specificity 93%). LIMITATIONS, REASONS FOR CAUTION: This trial was a single-center study with sample size attrition due to the COVID-19 pandemic. Additionally, the study focused on hormonal dynamics up to 1 months post-chemotherapy, lacking long-term data on clinical fertility outcomes in the identified risk groups. WIDER IMPLICATIONS OF THE FINDINGS: The application of the UD-AMH assay enables early prediction of POI and offers a valuable tool to guide personalized treatment decisions and fertility preservation strategies in young female cancer patients. FUNDING: This work was supported by the National Key Research and Development Program of China (2023YFB3210301), National Natural Science Foundation of China (82271664), Shanghai Municipal Council for Science and Technology (20JC1412100), the Shanghai Municipal Health Commission (202240345), the interdisciplinary program of Shanghai Jiao Tong University (YG2022ZD028), and the Shanghai Key Laboratory of Embryo Original Diseases (Shelab2022ZD01). DISCLOSURES: R.A.A. has received research support from Roche Diagnostics; all other authors declare no competing interests. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04767607.