Ovarian reserve after chemotherapy in premenopausal women with breast cancer undergoing fertility preservation counselling with and without unilateral ovarian tissue cryopreservation.
Yde Anna Mathilde AM, Colmorn Lotte Berdiin LB, Pinborg Anja A, Forman Julie Lyng JL et al.
What is the impact of chemotherapy on the ovarian reserve in premenopausal women diagnosed with breast cancer, and how is this impacted by fertility preservation (FP) strategy and age at diagnosis? Chemotherapy reduces ovarian reserve in women with breast cancer, with the greatest reductions observed among women who underwent ovarian tissue cryopreservation (OTC) and those of advanced reproductive age (≥35 years). Breast cancer is the most prevalent cancer among women of reproductive age, and in recent decades increasing emphasis has been placed on FP, including ovarian tissue, embryo, and oocyte cryopreservation. However, few large prospective studies have evaluated the effect of chemotherapy on ovarian reserve in patients with breast cancer using both anti-Müllerian hormone (AMH) and antral follicle count (AFC), and no large studies have assessed the impact by choice of FP. In this combined retro and prospective cohort study, we included 152 premenopausal women diagnosed with breast cancer who received FP counselling at Rigshospitalet, Copenhagen University Hospital, between 1 January 2018 and 31 August 2023. Women aged 18-42 years scheduled for FP counselling before chemotherapy were included. Exclusion criteria were previous chemotherapy, oophorectomy, and death or emigration within 2 years of inclusion. Medical and gynecological history, and oncological treatment plans were recorded. Ovarian reserve was assessed using AMH and AFC at baseline and at 6, 12, and 24 months after chemotherapy. Changes over time were analyzed using linear mixed models adjusted for age at baseline and hormonal contraceptive use. Of 152 women, 57 underwent OTC, while 41 underwent oocyte/embryo cryopreservation and 54 had no FP. Baseline median AMH was 13.9 [95% CI: 10.7, 18.1] pmol/l among women who did not undergo OTC and 13.3 [10.9, 16.3] pmol/l among those who did. A marked reduction in both AMH and AFC was observed after chemotherapy, with partial recovery within 2 years after treatment. The reduction was more pronounced, and recovery more limited, in women with OTC and in those of advanced reproductive age (≥35 years). Compared to baseline, the adjusted reduction in median AMH was 90% [95% CI: 85%, 93%] at 6 months and 75% [95% CI: 63%, 83%] at 24 months in women without OTC and 93% [95% CI: 85%, 95%] and 85% [95% CI: 78%, 90%] in women with OTC, respectively. Similar patterns, however, not as profound, were seen for AFC. Not all women completed assessments at all three follow-up visits, likely reflecting emotional exhaustion, hospital fatigue, reluctance to attend additional appointments, or changes in reproductive intentions. Furthermore, the observed reduction in ovarian reserve may, to some extent, also reflect the natural age-related decline in ovarian reserve. These findings may support counselling women with breast cancer about chemotherapy-related ovarian damage and thus the need for FP. The study is funded by the Independent Research Fund Denmark (Grant ID 10.46540/4308-00130B). A.P. has received grants (paid to the institution) and consulting fees from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S, and Cryos; honoraria from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S, and Organon; and support for meeting attendance and/or travel (paid to the institution) from Gedeon Richter. A.T.P. received speaker fees from Astellas, Gedeon-Richter, and Novo Nordisk. These companies had no role in the study. The other authors have no conflicts or interests to declare. N/A.