Controlled Ovarian Stimulation Outcomes Across Different Malignancies in Women Undergoing Fertility Preservation: The Role of AMH and AFC in Predicting Ovarian Response
Loris Marin, Eleonora Targhetta, Federica Esposito, Guido Ambrosini, Alessandra AndrisaniBackground/Objectives: Fertility preservation is a key component of cancer care in women of reproductive age, and controlled ovarian stimulation (COS) followed by oocyte/embryo cryopreservation is considered the standard strategy. Although COS protocols are generally standardized, systemic effects related to different malignancies may interfere with ovarian reserve assessment and influence stimulation planning and counselling. This study aimed to evaluate COS outcomes across different malignancy types in women undergoing fertility preservation. Methods: This retrospective study included 331 oncological patients who underwent COS for fertility preservation at a single referral center between May 2008 and May 2025. Patients were stratified into three groups according to malignancy type: breast cancer, hematological malignancies, and other cancers. Ovarian reserve was assessed using serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC). COS outcomes, including stimulation duration, total gonadotropin dose, number of retrieved and mature oocytes, follicular output rate (FORT), and follicle-to-oocyte index (FOI), were compared among groups. Results: Patients with hematological malignancies were significantly younger and showed higher AFC values compared with the other groups, whereas AMH levels did not differ significantly. After adjustment for age and AFC, patients with hematological malignancies showed significantly lower AMH levels compared with breast cancer patients (β = −0.94 ng/mL, 95% CI −1.40 to −0.48, p < 0.001), supporting the presence of a relative AMH–AFC discordance. In unadjusted analyses, gonadotropin requirements were higher in breast cancer patients, whereas the number of retrieved and mature oocytes was higher in patients with hematological malignancies. However, after adjustment for age and AFC, malignancy type was not independently associated with retrieved oocytes, mature oocytes, total gonadotropin dose, or stimulation duration. FORT and FOI were comparable among groups. Conclusions: Malignancy type did not appear to independently impair ovarian responsiveness to stimulation. Patients with hematological malignancies showed preserved stimulation outcomes despite AMH values not being proportionally higher than expected based on their younger age and higher AFC. These findings suggest that AMH should be interpreted with caution in systemic malignancies and that AFC may be particularly useful for tailoring fertility preservation counselling and stimulation strategies when AMH and AFC are discordant.