Impact of adjuvant anti-PD-1 immunotherapy on ovarian function in female patients with resectable melanoma: A prospective observational study

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment and are increasingly used in the adjuvant and neoadjuvant setting for malignancies such as melanoma, which often affect younger adults. With improving survival, concerns about long-term safety, including potential effects on fertility, are growing. METHODS: We conducted a national, multicenter, prospective observational study of female patients < 45 years treated with adjuvant anti-PD-1 therapy for resectable stage III-IV melanoma from 2018 to 2024. Ovarian function was assessed at baseline and at 3, 6, 12, and 18 months after treatment initiation. Each visit included transvaginal ultrasound for antral follicle count (AFC) and serum analysis of anti-Müllerian hormone (AMH), estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and inhibin-B. RESULTS: Seventeen female patients were enrolled (mean age 28.9 years, range 17-38). Median follow-up was 5.1 years. Ovarian morphology and AFC remained normal and stable at all time points. No decline in AMH was observed during or after treatment. FSH, LH, estradiol, progesterone, and inhibin-B levels fluctuated within physiological ranges consistent with normal menstrual cycling. After completing adjuvant therapy, five patients had at least one child, and one was pregnant at data cut-off. Two patients developed endocrine immune-related toxicity (type 1 diabetes and hypophysitis); both conceived post-treatment. DISCUSSION: This prospective evaluation of ovarian function during and after adjuvant anti-PD-1 therapy in melanoma found no evidence of treatment-related ovarian insufficiency, including in patients with endocrine toxicities. These findings are important for counseling young patients receiving adjuvant therapy who may wish to conceive in the future.