Protecting Ovaries During Chemotherapy Through Gonad Suppression A Systematic Review and Meta-analysis

OBJECTIVE: To estimate whether gonadotropin-releasing hormone (GnRH) analog administration during chemotherapy can protect against development of ovarian toxicity. DATA SOURCES: MEDLINE (1966 to present), EMBASE (1980 to present), Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched through March 2015 using the phrases: gonadotropin-releasing hormone, chemotherapy, and premature ovarian failure. Hand-search on conference abstracts, SCOPUS, and ISI Web of Science were also searched. METHODS OF STUDY SELECTION: Published English-language randomized controlled trials comparing resumption of ovarian function between GnRH analogs plus chemotherapy with chemotherapy without GnRH analogs were included. Studies including women with pelvic metastases or recent history of receiving chemotherapy were excluded. Accordingly, 10 eligible trials (907 women) were analyzed. TABULATION, INTEGRATION, AND RESULTS: Our primary outcome was the proportion of women with resumed ovarian function (defined as resumption of menstruation, prevention of chemotherapy-induced ovarian failure, or both) at the longest follow-up after the end of chemotherapy. Secondary outcomes were evaluating ovarian reserve parameters and pregnancy. Risk ratio was used to integrate qualitative results and mean difference was used for quantitative data. Gonadotropin-releasing hormone analog cotreatment did not significantly increase ovarian function resumption (320/468 [68.4%] in GnRH analog arm and 263/439 [59.9%] in the chemotherapy alone arm; risk ratio 1.12, 95% confidence interval [CI] 0.99-1.27). No protective effect existed after subgroup analyses (type of malignancy [P=.31], age [P=.14], and GnRH analog type [P=.44]). Gonadotropin-releasing hormone analogs did not protect any of ovarian reserve parameters, whether follicle-stimulating hormone (mean difference 22.63, 95% CI 27.33 to 2.07), antral follicle count (mean difference 1.66, 95% CI 20.69 to 4.01), or anti-Mullerian hormone (mean difference 0.31, 95% CI 20.41 to 1.03). Spontaneous pregnancy was also comparable (risk ratio 1.63, 95% CI 0.94-2.82). CONCLUSION: Gonadotropin-releasing hormone analog administration during chemotherapy does not appear to protect the ovaries from gonadal toxicity. It is not a reliable method for fertility preservation.