Protective effect of a gonadotropin-releasing hormone analogue on chemotherapeutic agent-induced ovarian gonadotoxicity: A mouse model

Objective: To demonstrate the protective effect of triptorelin, a GnRH analogue, on chemotherapy-induced ovarian gonadotoxicity. Study design: Twenty-four sexually mature, virgin, female FVB/NJNarl mice were divided into four groups: busulfan (B); low-dose triptorelin plus busulfan (T-L + B); high-dose triptorelin plus busulfan (T-H + B); and control. Mice in the T-L + B and T-H + B groups were injected with 3.8 and 38 mg/kg of triptorelin subcutaneously, respectively. Four weeks later, mice in the B, T-L + B. and T-H + B groups were injected with busulfan intraperitoneally at a dose of 36 mg/kg. Histologic examinations were performed 4 weeks later. Results: Obvious destruction of ovarian structure and significant depletion of primordial, primary, and secondary follicles were demonstrated in the B group compared with the control group, affirming the gonadotoxicity of busulfan. In the T-L + B group, a greater number of larger primordial and primary follicles were enumerated compared with the B group; however, statistical significance was not achieved. In the T-H + B group, the number of primordial and primary follicles was significantly greater than in the B group, and the ovarian tissue in the T-H + B group was spared, demonstrating the effect of triptorelin pre-treatment on ovarian protection. Conclusion: Our results have demonstrated a dose-dependent protective effect against gonadotoxic chemotherapy of a GnRH analogue on ovarian reserve, thus suggesting a novel application of GnRH analogues in fertility preservation. Crown Copyright (C) 2009 Published by Elsevier Ireland Ltd. All rights reserved.