Preservation of gonadal function in women undergoing chemotherapy: a systematic review and meta-analysis of the potential role for gonadotropin-releasing hormone agonists

To evaluate the available randomized controlled trials (RCTs) in the literature investigating the use of gonadotropin-releasing hormone agonist (GnRHa) co-treatment for ovarian preservation in women receiving chemotherapy. A systematic review of the literature was performed from 1960 through 2017 to identify relevant RCTs. Included patients had lymphoma, ovarian cancer, or breast cancer. The primary outcome was the proportion of women who retained ovarian function after chemotherapy. Extracted data points included study design, patient characteristics, and proportion of women who developed premature ovarian failure (POF). A risk of bias assessment was performed according to the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The pooled odds ratio was calculated, and outcomes of individual studies were compared using the random-effects model with the inverse-variance method and the DerSimonian-Laird estimator. Twenty-nine RCTs were identified, and 10 met criteria for inclusion in the meta-analysis. An analysis of patients who did not develop POF after chemotherapy revealed eight studies supporting the use of GnRHa (OR 1.83; 95% CI 1.34-2.49). The duration of benefit of GnRHa is unclear. An analysis of three studies with outcome data at 2 years revealed a non-significant OR of 0.53 (95% CI 0.22-1.30) for the preservation of ovarian function with GnRHa treatment. GnRHa may have a protective effect against the development of POF after gonadotoxic chemotherapy; however, the duration of benefit is unclear and requires further study.