Ovarian cortex cryopreservation in pediatric and adolescent medicine

Abstract

Background: Increased pediatric/adolescent cancer survivor rates have enhanced awareness of long-term effects of therapy, specifically gonadal failure. Ovarian cortex cryopreservation may hold the promise of fertility for those at risk for ovarian failure due to medical therapy. The object of this study was to determine if an ovarian cryopreservation program is feasible and to define suitable candidates.Method: A MEDLINE search supplemented by bibliographies. The review was limited to English articles on ovarian failure rates following radiation and/or chemotherapy and on ovarian cryopreservation. Investigators in the field were consulted to identify other sources.Results: Approximately one third of postpubertal females exposed to chemotherapy or radiotherapy develop ovarian failure. The risk is mostly significant for patients exposed to pelvic radiotherapy (up to 32% decrease in fertility) and alkylating agent based chemotherapy (infertility in 22%). A ninefold increase in premature ovarian failure results from exposure to combined pelvic radiotherapy and alkylator based chemotherapy. Practically all patients exposed to multiple agent chemotherapy combined with pelvic radiotherapy at doses used in preparation for bone marrow transplant will undergo irreversible loss of ovarian function. Currently human ovarian cortex can be cryopreserved, thawed and stimulated with gonadotrophins to produce follicles when transplanted into immunosuppressed mice, however there has yet to be any human pregnancies. The immunosupressed mouse model could also serve as a test to determine whether the tissue carries metastatic risk prior to reimplantation into the donor.Conclusion: Based on the literature we propose ovarian cortex cryopreservation and banking for postpubertal females prior to chemotherapy and/or radiation therapy that holds a high risk of ovarian failure. In the future this may provide oocytes for reproductive purposes. A protocol is currently under approval by the Hospital for Sick Children's ethics committee.