Gonadotropin Releasing Hormone Agonist (GnRHa) therapy and ovarian preservation in pediateric and adolescent subjects receiving chemoradiation therapy

Advancements in chemoradiation therapies have increased survival rates in cancer subjects. Late effects of therapy, including infertility, become increasingly more important with increased survival. High dose alkylating agents, total body irradiation and radiation to the gonads pose the greatest risk to future fertility. Embryo cryopreservation, gonadal shielding and ovarian transposition are standard fertility preserving therapies. Oocyte and ovarian tissue cryopreservation have been shown to be successful and may be implemented under IRB approved protocols. Hormonal suppression with gonadotropin releasing hormone agonist (GnRHa) therapy has yielded conflicting results in the literature and larger prospective trials are necessary. To date, there are no studies that effectively investigate the effect of GnRHa therapy in pediatric and adolescent subjects receiving chemoradiation therapy. The primary aim of this prospective study is to estimate the impact of GnRHa therapy in preserving ovarian function in pubertal pediatric and adolescent females. Treatment impact will be assessed by measuring follicle stimulating hormone (FSH), estradiol (E2), menstrual function, anti-mullerian hormone (AMH) and antral follicle count (AFC) before and after therapy. The secondary aim will be to assess whether AMH and AFC will be better indicators of ovarian reserve after chemoradiation therapy than FSH, E2 and menstrual function in subjects receiving concomitant GnRHa therapy. The third aim will be to determine whether AMH will be equivalent to AFC as an indicator of ovarian reserve after chemoradiation therapy and GnRHa therapy. The fourth aim will be determine if every 2 month dosing of GnRHa provides better menstrual suppression than every 3 month dosing. The study population will include subjects ages 8 through 19 undergoing chemotherapy who will already receive GnRHa therapy for menstrual suppression and agree to participate in the study. The duration of the study will be 12 months. The study time includes the time necessary for completion of most cancer treatments in this population, which approximates 8-12 months, and time to allow complete excretion of the GnRHa from the systemic circulation with reliable testing of the hypothalamic pituitary ovarian (H-P-O) axis. The results of the study will be used to guide a larger study evaluating the efficacy of GnRHa as ovarian preservation therapy in young subjects receiving chemoradiation.