There are currently over 250,000 survivors of childhood cancer in the U.S. Recent diagnostic and therapeutic advances in pediatric oncology have led to greater survival rates in children with malignancies. However, while cancer therapies improve long-term survival, such treatments can lead to impaired fertility potential and eventual premature ovarian failure. The gonadotoxic effects of chemotherapeutic agents are well documented, particularly for alkylating agents such as cyclophosphamide and appear to be dose dependent. In the infertility setting, several clinical tests, including serum hormone measures and ultrasound measures of the ovaries, have been developed and are routinely used as surrogate markers to evaluate a woman's fertility potential and for counseling regarding treatment options. However, it is not known whether such ovarian function testing can detect diminished fertility potential in young female cancer survivors prior to the onset of ovarian failure. The primary aim of this proposal is to determine whether surrogate measures of fertility potential differ between young female cancer survivors as compared to healthy controls. We shall conduct a prospective cohort study comparing measures of ovarian function between pediatric cancer survivors and comparably aged healthy controls using clinical history, physical examination, ultrasound imaging, and hormonal evaluation. In addition, a secondary aim of this proposal will test the hypothesis that surrogate measures of fertility potential will be dependent on the dose of alkylating agents received. This hypothesis will be tested by comparing measures of ovarian function between three groups of pediatric cancer survivors who have received different doses of alkylating agents. This proposal will assist in establishing a protocol for evaluating ovarian reserve in female pediatric cancer survivors. Specifically, the results of this proposal will serve as preliminary data for the establishment of a long-term cohort study of pediatric cancer survivors to examine the association between these measures and pregnancy rates, pregnancy outcomes and the occurrence of premature menopause. ? ? ?
