Managing fertility in childhood cancer patients.

The scope of potential fertility issues for pediatric cancer patients is broad and difficult to predict. Both genders are susceptible to central dysregulation of the hypothalamic axis. For boys, chemotherapy and radiation can affect production of both sex hormones and sperm. These effects can be reversible or permanent. For girls, the ovary can be similarly affected, with inadequate or absent hormone production and depletion of ovarian follicle reserve. Additionally, even in a young woman with normal puberty and early fertility, premature menopause is a possibility after certain exposures. Finally, the uterus can be affected by radiation and create problems in carrying a normal pregnancy to term, even if hormonal fertility is achieved. Radiation is a clearly established risk to the hormoneand gamete-producing tissues. What is more difficult to predict are the fertility outcomes after chemotherapeutic exposures. The main exposures implicated for pediatric patients are cyclophosphamide and other alkylating agents; large cumulative doses have been shown to irreversibly impair fertility in both male and female patients. However, the variability in gonadal function between different individuals after therapy with an alkylating agent is quite large, making prediction of fertility outcomes after many protocols extremely difficult. Furthermore, evidence suggests that males are more susceptible than females, and spermatogenesis is impaired at lower doses than is testosterone production. Many pediatric patients who are survivors of cancer are never offered fertilitysparing interventions, so it is important for health care personnel to monitor the fertility status of survivors of childhood cancers. Management should focus on assessment of gonadal function via patient history, physical examination, and laboratory screening. Below, I discuss guidelines from the Children’s Oncology Group (COG) that identify high-risk patients who should receive more careful monitoring and counseling regarding long-term issues such as premature menopause and bone density concerns. Future challenges include better definition of patients at risk of infertility pretreatment in order to target fertility preservation schemes accordingly. (For further discussion of fertility risk among pediatric cancer patients, see Garcia and Ginsburg, this volume.)