The future of fertility preservation for women treated with chemotherapy

Cytotoxic chemotherapies have been a mainstay of cancer treatment but are associated with numerous systemic adverse effects, including impacts on fertility and endocrine health. Irreversible ovarian damage and follicle depletion are the side effects of chemotherapy that can lead to infertility and premature menopause, both being major concerns of young cancer patients. Notably, many women will proceed with fertility preservation, but unfortunately existing strategies do not entirely solve the problem. Most significantly, oocyte and embryo freezing do not prevent cancer treatment-induced ovarian damage from occurring, which may result in the impairment of long-term hormone production. Unfortunately, loss of endogenous endocrine function is not fully restored by hormone replacement therapy. Additionally, while GnRH agonists are standard care for patients receiving alkylating chemotherapy to lessen the risk of premature menopause, their efficacy is incomplete. The lack of more broadly effective options stems, in part, from our poor understanding of how different treatments damage the ovary. Here, we summarise the impacts of two commonly utilised chemotherapies – cyclophosphamide and cis-diamminedichloroplatinum(II) (cisplatin) – on ovarian function and fertility and discuss the mechanisms underpinning this damage. Additionally, we critically analyse current research avenues in the development of novel fertility preservation strategies, with a focus on ferto-protective agents. LAY SUMMARY: Over the past few decades, advances in the detection and treatment of cancer have dramatically improved survival rates in young women. This means that ensuring patients have a high quality of life after cancer treatment has become a new priority. Therefore, it is important to understand and prevent any long-term negative side effects of cancer treatments, with infertility and early-onset menopause being major concerns for women receiving chemotherapy. The current fertility preservation options available to young women have significant limitations. Therefore, the identification of new approaches to protect fertility has been an intense topic of research in recent years. In this review, we provide information on the negative side effects of two commonly used chemotherapy drugs – cyclophosphamide and cis-diamminedichloroplatinum(II) (cisplatin) – on fertility, and discuss how they cause damage to the ovaries. We also critically analyse recent preclinical studies related to the development of new fertility preservation techniques.