REPRODUCTIVE-PERFORMANCE OF FEMALE RATS TREATED WITH CYCLOPHOSPHAMIDE AND OR LHRH AGONIST

Previous studies addressing the ovarian protective effects of luteinizing hormone releasing hormone agonists (LHRHa) against adverse effects of chemotherapy have examined histologic and/or hormonal parameters without evaluating reproductive performance. In this report, we initially established a model for chronic treatment of female rats with cyclophosphamide (CTX) that allowed long term survival. In a second experiment, thirty seven female cycling rats (age: 70 days) were divided into 4 treatment groups. They were given either CTX (4 mg/kg/day, 5 days/week) for a total of 76 days (217 mg/kg) and/or the LHRHa leuprolide (Lupron) 5 mug/day by subcutaneous minipump (Alza) for 98 days. LHRHa was started 10 days before CTX and ended 12 days after the last CTX injection. All LHRHa-treated rats entered persistent diestrus. At the end of treatment, most rats treated with CTX only were in persistent estrus. Breeding was started at 218 days of age. A laparotomy to count implantation sites was performed 15 to 16 days after vaginal plug/sperm was demonstrated. All nonpregnant rats were remated. Chi square and ANOVA were used for statistical analysis. The data presented demonstrate that: 1. LHRHa given before and after CTX increased the pregnancy rate/mating (from 4/11 to 9/10; P < 0.05), the number of implantations/mated rat (from 2.5 +/- 1.4 to 13.7 +/- 1.7; P < 0.01), and reduced the need for remating (from 7/11 to 1/10; P < 0.05); 2. LHRHa-treated rats performed better than controls. We conclude that LHRHa protects against chemotherapy-induced fertility reduction in female rats.