Ovarian Preservation by GnRH Agonists during Chemotherapy: A Meta-Analysis

Purpose: Treatment with cyclophosphamide (CYC) confers up to a 40% risk of ovarian failure in women of reproductive age. The use of GnRH agonists (GnRHa) to preserve ovarian function has been investigated in several small studies. We performed a systematic review of studies examining whether a GnRHa administered during chemotherapy is protective of ovarian function and fertility. Methods: We searched the English-language literature (1966-April 2007) using MEDLINE and meeting abstracts and included studies that reported an association between GnRHa and ovarian preservation in women receiving chemotherapy. Studies without a control group were excluded. Ovarian preservation was defined as the resumption of menstrual cycles and a premenopausal follicle-stimulating hormone (FSH) after chemotherapy. Fertility was determined by a woman's ability to become pregnant. We estimated the summary relative risk (RR) and associated 95% confidence intervals (95% CI) using a random-effects model. Results: Nine studies included 366 women. Three studies included women with autoimmune disease receiving CYC; six included women with hematologic malignancy receiving combination chemotherapy. In total, 178 women were treated with GnRHa during chemotherapy, 93% of whom maintained ovarian function. Of the 188 women not treated with GnRHa, 48% maintained ovarian function. The use of a GnRHa during chemotherapy was associated with a 68% increase in the rate of preserved ovarian function compared with women not receiving a GnRHa (summary RR=1.68, 95% CI 1.34-2.1). Among the GnRHa-treated women, 22% achieved pregnancy following treatment compared with 14% of women without GnRHa therapy (summary RR=1.65, CI 1.03-2.6). Conclusions: Based on the available studies, GnRHa appear to improve ovarian function and the ability to achieve pregnancy following chemotherapy. Several randomized trials are underway to define the role and mechanism of GnRHa in ovarian function preservation. In the meantime, premenopausal women facing chemotherapy should be counseled about ovarian preservation options, including the use of GnRHa therapy.