Chemotherapy and radiotherapy can both cause ovarian failure, and radiotherapy can also damage the uterus increasing the risk of miscarriage and premature delivery. Alkylating agents are recognised to be the most gonadotoxic class of chemotherapeutic agents, but treatment regimens often involve multiple drugs complicating assessment of effect and risk. The prepubertal reproductive system is also sensitive to these effects, although age, with treatment regimen, are important determinants of the degree of effect. Many of the larger studies use amenorrhoea as the key outcome of cancer treatment, with fertility less frequently assessed although there are now data from larger studies after childhood cancer. Premature ovarian insufficiency is also an important outcome, highlighting issues related to the loss of estrogen production as well as shortening of reproductive lifespan.
The explosion in clinical activity surround fertility preservation highlights the need for better individual assessment of risk of loss of post-treatment ovarian function. This involves identification of patient-specific issues, such as the potential impact of her pre-existing ovarian reserve, and extrinsic factors, particularly the treatment she will be receiving, and what fertility preservation techniques are in reality available to her. Pre-chemotherapy ovarian reserve biomarkers such as AMH are predictive of post-chemo ovarian activity in women with breast cancer. The evidence for the efficacy of GnRH analogues to protect ovarian function in early breast cancer is also growing, although the amount of ovarian function saved is likely to be small. Other approaches are also in development to protect ovarian function after chemotherapy, but are largely preclinical at present.