ASSESSING OVARIAN RESERVE AFTER FOLLICULAR PROTECTION PRIOR TO X-IRRADIATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ovarian failure is a common side-effect of radiation or chemotherapy treatment in girls and young women. In view of increasing survival rates, especially in breast cancer patients, long-term consequences of cancer treatments with respect to fertility are important considerations for quality of life after cancer. Novel strategies for protecting the ovaries from adverse effects of cancer therapies are currently under development. For example, direct ovarian exposure to sphingosine-1-phosphate (S1P) prior to radio-or chemotherapy in mice maintains the health and function of follicles and their enclosed oocytes from damage such that fertilization and birth of live offspring are possible. These studies have been extended to nonhuman primates wherein intraovarian infusion of S1P or S1P agonist prior to X-irradiation protects a cohort of follicles that leads to normal ovarian/menstrual cyclicity and production of mature oocytes capable of preimplantation embryonic development. Although antral follicles can be observed using ultrasound, the number of growing preantral follicles remaining after cancer treatment, that represent ovarian reserve, cannot be quantified directly in vivo. Therefore, a non-invasive method for predicting ovarian reserve in cancer patients after ovarian protection is needed. Anti-mullerian hormone (AMH), produced by granulosa cells of preantral follicles, and inhibin B (INHB), produced by granulosa cells of antral follicles, are being used to assess ovarian reserve in women desiring assisted reproductive technologies for pregnancy. We are investigating the utility of these hormones to measure ovarian reserve after cancer treatment with longitudinal comparisons of circulating levels pre- and post-X-irradiation in rhesus monkeys receiving S1P-based ovarian protection.