Large studies have shown that modern chemotherapy typically has less impact on the fertility of female survivors who experienced cancer in childhood, with most survivors having a greater chance of becoming pregnant; in contrast, male survivors have poorer fertility, especially when receiving chemotherapy regimens with high doses of alkylating agents and platinum compounds. I. Comparison of Fertility in Male Cancer Survivors Currently, approximately 80% of pediatric cancer patients survive to adulthood, and fertility becomes a major problem for them. There is a growing recognition of the side effects of highly intensive chemotherapy regimens in pediatric cancer patients. Previous studies have shown that many types of chemotherapy, including alkylating agents, pose hazards to fertility, yet little is known about the effects of newer agents such as isocyclophosphamide on the fertility of childhood cancer survivors. The study followed pediatric cancer patients under the age of 21 at 27 institutions in the U.S. and Canada between 1970 and 1999, and these survivors 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 radiation to the pelvis or brain. Compared to 80 percent of their compatriots, 70 percent of the female survivors were pregnant at age 45, and for the male survivors, that number dropped to 50 percent. For male survivors, fertility decreased with increased exposure to alkylating agents, and high cumulative doses of several alkylating agents (cyclophosphamide, isocyclophosphamide, and methylbenzylhydrazine) with platinum compounds were significantly associated with reduced fertility. This study is consistent with previous findings of reduced sperm counts and reduced testicular volume in men treated with these drugs. The dose threshold for isocyclophosphorylamide that reduced fertility in male survivors was much lower than the dose threshold that triggered 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 even more pronounced, possibly due to accelerated oocyte attrition and accelerated menopause associated with chemotherapy exposure. Second, further research on less common drug risks The study relied on self-reports of pregnancy and live births, and one-quarter of the pregnant women were not aware of being 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 research is needed to assess the risks associated with some less common medications. It is believed that these results will be encouraging for the majority of females undergoing chemotherapy in childhood, however, fertility and fertility preservation options still need to be better explored before chemotherapy is administered, particularly diagnosed males should be encouraged to store sperm for future reproductive options after puberty, and the current options for fertility preservation in females are a little more complex and include egg and embryo cryopreservation. Semen cryopreservation is simple, but there are significant shortcomings in terms and accessibility, and appropriate technologies need to be developed to help achieve fertility preservation for males unable to freeze sperm before and during puberty, and the results of this study are more encouraging for girls and young women, but there is a need to accurately identify high-risk populations in order to avoid unnecessary treatments for low-risk populations.