Gonadotropin-releasing hormone analogs in fertility preservation—lack of biological basis?

Abstract

In this Practice Point commentary, we discuss the results and limitations of a nonrandomized, retrospective–prospective study of gonadotropin-releasing hormone analogs (GnRHa) in women with Hodgkin disease. Blumenfeld et al. concluded that coadministration of GnRHa during chemotherapy preserved cyclic ovarian function but not fertility. As the endocrine and ovulatory functions of the ovary are connected, this conclusion seems implausible. The study did not control for disease severity or the dose of alkylating agents. In addition, GnRHa treatment was not randomized, so patients in the control group were unlikely to have received GnRHa because the severity of their disease resulted in more-aggressive chemotherapy. By contrast, the only randomized study published to date showed no gonadal protection from GnRHa during chemotherapy in either sex. Furthermore, GnRHa did not prevent primordial-follicle loss in a human ovarian xenograft model. Unless a larger prospective study proves otherwise, GnRHa should not be offered as a proven method of fertility preservation.