Gonadotropin-releasing hormone agonists for ovarian protection during breast cancer chemotherapy: a systematic review and meta-analysis

IMPORTANCE: The increasing trend of delaying childbirth means that more women are being diagnosed with breast cancer before having given birth to their desired number of children. Although chemotherapy can significantly improve the prognosis of this population, it also causes ovarian damage, including premature ovarian insufficiency and infertility. Gonadotropin-releasing hormone agonists (GnRHa) have shown promising fertility protective activity in premenopausal women, but their clinical usage remains controversial. OBJECTIVE: Here, we conducted a meta-analysis to assess the efficacy of GnRHa when administered concurrently with chemotherapy that included cyclophosphamide in the prevention of chemotherapy-induced ovarian damage in premenopausal women. EVIDENCE REVIEW: An extensive literature search was performed using the PubMed, Embase, and Cochrane databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were determined. FINDINGS: Eleven randomized controlled trials with a total of 1,219 participants were included in the analyses. A significantly higher number of women treated with GnRHa experienced the resumption of ovarian function after chemotherapy than those who did not receive this treatment (OR, 3.04; 95% CI, 1.87‐4.94; P < 0.001). Regarding spontaneous pregnancy, a statistically significant difference was observed only in hormone receptor-negative participants (OR, 2.06; 95% CI, 1.03‐4.11; P = 0.04). CONCLUSIONS AND RELEVANCE: When treating premenopausal women with breast cancer, the administration of GnRHa concurrently with chemotherapy appeared to improve the resumption rate of ovarian function; however, the spontaneous pregnancy rate only improved in hormone receptor-negative patients. Thus, the use of GnRHa during chemotherapy may represent a feasible strategy for preserving ovarian function in women with breast cancer.