Large studies have shown that modern chemotherapy typically has less impact on the fertility of female survivors who experience cancer in childhood, with most survivors having a better chance of becoming pregnant; in contrast, male survivors are less fertile, especially when receiving chemotherapy regimens with high doses of alkylating agents and platinum compounds. Comparative fertility of male cancer survivors Currently, approximately 80% of childhood cancer patients survive into adulthood, with fertility becoming a big issue for them. There is a growing recognition of the side effects of highly intensive chemotherapy regimens for pediatric cancer patients. Previous studies have shown that many types of chemotherapy, including alkylating agents, pose a risk to fertility, yet little is known about the effects of newer agents such as isocyclophosphamide on fertility in childhood cancer survivors. The study tracked pediatric cancer patients under the age of 21 at 27 institutions in the United States and Canada between 1970 and 1999 who survived for at least five years after diagnosis. In the current study, researchers examined the effects of different doses of 14 common chemotherapy drugs on pregnancy and live birth in 10,938 male and female survivors, with 3,949 siblings as controls. The study focused specifically on survivors who received chemotherapy and those who did not receive any radiotherapy to the pelvis or brain. Compared to 80% of their siblings, 70% of female survivors became pregnant at age 45, and for male survivors, this number dropped to 50%. For male survivors, fertility decreased with increased exposure to alkylating drugs, and high cumulative doses of several alkylating drugs (cyclophosphamide, isocyclophosphamide, methylbenzylhydrazine) with platinum compounds were significantly associated with reduced fertility. This study is consistent with previous findings of reduced sperm counts and reduced testicular volumes in men treated with these drugs. The isocyclophosphamide dose threshold for reducing fertility in male survivors was well below the dose threshold that would trigger a high risk (25,000
mg/m2 vs. 60,000 mg/m2). For female survivors, only leucovorin and high doses of cyclohexylnitrosourea were directly associated with reduced fertility. Overall, female survivors were less likely to become pregnant compared to their siblings, and male survivors were even less likely to have children. However, for women who delayed pregnancy until age 30 and beyond, this difference was more pronounced, possibly because chemotherapy exposure accelerates egg loss and accelerates menopause. Further study of less common drug risks The study relied on self-reported pregnancies and live births, and a quarter of pregnant women were unaware of having become pregnant. Although the study was consistent with the results of similar studies, it did not take into account other factors such as marriage or cohabitation, intended pregnancy, or prolonged intended pregnancy. The number of survivors in this study was large and responses to medications varied, however more studies are needed to assess the risks associated with some of the less common medications. It is believed that these results will be encouraging for most women who receive chemotherapy in childhood, however, fertility and fertility preservation options still need to be better explored before proceeding with chemotherapy, especially since diagnosed males should be encouraged to store sperm for future reproductive options after puberty and current options for female fertility preservation are relatively more complex and include egg and embryo freezing. Semen cryopreservation is simple, but the terms and accessibility have significant shortcomings, and appropriate technologies need to be developed to help achieve fertility preservation in prepubertal and adolescent males who are unable to freeze their sperm.