Cancer Treatment-Related Ovarian Dysfunction in Women of Childbearing Potential: Management and Fertility Preservation Options

Abstract

Purpose: To review the complex concerns of oncofertility created through increased cancer survivorship and the long-term effects of cancer treatment in young adults.

Design: Review chemotherapy-induced ovarian dysfunction, outline how fertility may be addressed before treatment initiation, and discuss barriers to oncofertility treatment and guidelines for oncologists to provide this care to their patients.

Conclusion: In women of childbearing potential, ovarian dysfunction resulting from cancer therapy has profound short- and long-term implications. Ovarian dysfunction can manifest as menstrual abnormalities, hot flashes, night sweats, impaired fertility, and in the long term, increased cardiovascular risk, bone mineral density loss, and cognitive deficits. The risk of ovarian dysfunction varies between drug classes, number of received lines of therapy, chemotherapy dosage, patient age, and baseline fertility status. Currently, there is no standard clinical practice to evaluate patients for their risk of developing ovarian dysfunction with systemic therapy or means to address hormonal fluctuations during treatment. This review provides a clinical guide to obtain a baseline fertility assessment and facilitate fertility preservation discussions.

FIG 1.

Risk of permanent amenorrhea associated with chemotherapeutic agents.^,,- These are general guidelines only. Additional factors such as specific age at time of treatment, baseline ovarian reserve, and specific treatment regimen will determine the individual risk for ovarian toxicity. ^aDose is based on cyclophosphamide equivalent dose. ^bDegree of gonadotoxic potential debated. ^cOn the basis of traditional dosing regimen. Dose-dense administration may be more gonadotoxic. ^dSuspected moderate risk on the basis of limited data. ^eLimited data. Increased malformation risk in offspring noted with female exposure to tyrosine kinase inhibitors during conception/pregnancy. ABVD, doxorubicin, bleomycin, vinblastine, and dacarbazine; AC, doxorubicin and cyclophosphamide; AC-T, doxorubicin, cyclophosphamide, taxol regimen; CAF, cyclophosphamide, doxorubicin, and fluorouracil; CD20, cluster of differentiate 20; CEF, cyclophosphamide, epirubicin, and fluorouracil; CHOEP, CHOP plus etoposide; CHOP, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone; CMF, cyclophosphamide, methotrexate, and fluorouracil; CTLA-4, cytotoxic T-lymphocyte–associated antigen-4; HER2, human epidermal growth factor receptor 2; TBI, total-body irradiation; VEGF, vascular endothelial growth factor.