Effects of Treatment on Fertility in Long-Term Survivors of Childhood or Adolescent Cancer

In a retrospective cohort study of survivors of cancer and of controls, we estimated the risk of infertility after treatment for cancer during childhood or adolescence. We interviewed 2283 long-term survivors of childhood or adolescent cancer diagnosed in the period from 1945 through 1975, who were identified at five cancer centers in the United States. Requirements for admission to the study were diagnosis before the age of 20, survival for at least five years, and attainment of the age of 21. In addition, 3270 controls selected from among the survivors' siblings were interviewed. Cox regression analysis showed that cancer survivors who married and were presumed to be at risk of pregnancy were less likely than their sibling controls to have ever begun a pregnancy (relative fertility, 0.85; 95 percent confidence interval, 0.78 to 0.92). Radiation therapy directed below the diaphragm depressed fertility in both sexes by about 25 percent. Chemotherapy with alkylating agents, with or without radiation to sites below the diaphragm, was associated with a fertility deficit of about 60 percent in the men. Among the women, there was no apparent effect of alkylating-agent therapy administered alone (relative fertility, 1.02) and only a moderate fertility deficit when alkylating-agent therapy was combined with radiation below the diaphragm (relative fertility, 0.81). Relative fertility in the survivors varied considerably according to sex, site of cancer, and type of treatment; these factors should be taken into consideration in counseling survivors about the long-term consequences of disease. (N Engl J Med 1987; 317:1315–21.), CONTEMPORARY combined radiotherapy and chemotherapy, the double-edged sword that accounts for the increased survival among children and adolescents with cancer,¹ can also cause severe late complications, such as additional neoplasms, major organ dysfunction, and infertility.^{2 3 4} Early menopause, azoospermia, and germ-cell destruction have all been observed after therapy.^{5 6 7} Although the frequency of these events varies with factors such as the type, dose, and duration of treatment^{8 9 10} and the sex and age of the patient,^11,12 there are no firm estimates of the magnitude of the risk involved and little data on the long-term consequences of treatment of childhood cancer. At present, the…