As advancements in anti-cancer treatments improve survival rates, understanding the potential long term side effects of these treatments become increasingly important. Treatment related ovarian toxicity can potentially lead to infertility and early menopause, and is an important consideration for premenopausal women when making treatment decisions.
Although it is well established that alkylating chemotherapy can negatively impact ovarian function, little is known about the effects of other systemic anti-cancer agents on the human ovary. In recent years, many new classes of anti-cancer agents have received regulatory approval and are now routinely used in clinical practice, such as immunotherapy, targeted therapies, monoclonal antibodies and antibody-drug conjugates. The targets of some of these drugs have fundamental roles in normal ovarian physiology, and preclinical studies have suggested that PARP inhibitors, PDL1 inhibitors and CTLA4 inhibitors can significantly reduce primordial follicle counts (i.e., the ovarian reserve) in mice.
Yet, ovarian toxicity is currently inadequately assessed in cancer clinical trials. Indeed, only 24% of phase 3 breast cancer clinical trials which enrolled premenopausal women collected data regarding ovarian function measures. Interviews with clinical trialists found that the main barrier to ovarian toxicity assessment in clinical trials enrolling young women was that the issue was rarely considered during trial design.
Information regarding the impact of anti-cancer agents on ovarian function is urgently needed to facilitate fully informed decision-making regarding cancer treatment and family planning. This is a major gap in knowledge that needs to be addressed.