Use of the GnRH Agonist Leuprolide Acetate (Lupron(Registered Trademark)) to Preserve Ovarian Function in Women Undergoing Chemotherapy

As a result of the inability of female germ cells to regenerate after injury, a number of chemotherapeutic agents induce premature ovarian failure in the majority of reproductive age women who receive them. The long-term survival for these women has increased with more effective chemotherapies, making iatrogenic ovarian failure and infertility an increasingly significant issue. Currently the choices for maintaining fertility include in vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and the use of GnRH agonist and antagonist to preserve ovarian function.

Much of the evidence for the use of GnRH agonist to prevent premature ovarian failure is found in the systemic lupus erythematosus literature. Blumenfeld and colleagues have published a report that demonstrates preservation of ovarian function in 100% of patients treated with leuprolide acetate prior to cyclophosphamide therapy, compared to a 50% ovarian failure rate in patients not receiving leuprolide acetate. Although the results of animal studies and human studies are encouraging, adequately controlled trials are needed. Future trials will need to have sufficient numbers of patients, receiving multiple types of chemotherapeutic agents to adequately document the utility of medical prophylaxis. The experience with ovulation induction suggests GnRH antagonists may have similar efficacy to GnRH agonists. GnRH antagonists compete directly with GnRH in receptor binding, and as a result antagonists rapidly inhibit secretion of gonadotropin and sex steroids. Unlike GnRH agonists, GnRH antagonists have an immediate effect and antagonists can be given independent of menstrual cycle day. These differences represent several practical benefits offered by an antagonist. In a recent case series by Sauer et al, cetrorelix acetate, a GnRH antagonist, was given in doses of 3mg at four day intervals to four patients ages 21-30. Menses was preserved in all four patients and there was one spontaneous conception. Because of the potential advantages of the use of a GnRH antagonist when compared to an agonist, cetrorelix acetate will be studied against placebo in this investigation.

Our specific aim is to compare the rates of ovarian preservation in reproductive age women receiving chemotherapeutic agents known to affect ovarian function who receive Cetrorelix acetate co treatment with women who receive these agents and do not receive Cetrorelix acetate. A second aim is to evaluate the ability of the Cetrorelix acetate co treatment to induce therapeutic amenorrhea in a study population at risk for thrombocytopenia and associated heavy vaginal bleeding.