A combination of norethindrone acetate and leuprolide acetate blocks the gonadotrophin-releasing hormone agonistic response and minimizes cyst formation during ovarian stimulation

Abstract

A protocol utilizing both leuprolide acetate (LA) and norethindrone acetate (NETA) in subjects undergoing ovarian suppression prior to follicle aspiration proved more effective than LA alone in reducing the incidence of ovarian cyst formation without affecting clinical outcome. Patients (n = 105) undergoing ovarian stimulation followed by follicle aspiration and in-vitro fertilization (IVF) were prospectively randomized and studied, Study measures included ovarian suppression days, days of human menopausal gonadotrophin (HMG) stimulation, serum oestradiol concentrations, number of cycles developing de novo cysts (> 15 mm), number of induced flare responses (day 8 oestradiol ≥ 50 pg/ml), number of office visits, total dose exogenous gonadotrophins, number oocytes retrieved, and clinical pregnancy and delivery rates per retrieval. Patients undergoing IVF received either LA alone (n = 58; controls) or LA and NETA (n = 47; study group) for the first 8 days of their cycle. Results comparing NETA/LA versus LA demonstrated: serum oestradiol 20.7 ± 3.9 versus 57.3 ± 9.4 pg/ml respectively on day 8 of ovarian suppression (P < 0.01); 8.6 ± 2.74 days required for ovarian suppression versus 12.3 ± 6.09 days (P < 0.01); and only three individuals (6.4%) using NETA/LA developed ovarian cysts > 15 mm compared to 15 (25.9%) controls (P < 0.01). No differences were observed for days of stimulation, peak oestradiol attained, total dosage of exogenous gonadotrophins, or number of aspirated oocytes. Neither were there differences in the clinical pregnancy (26.8 versus 22.6%) nor in delivery rates (19.5 versus 20.8%). We conclude that the addition of NETA to LA enhances ovarian suppression and lessens ovarian cyst formation, thereby significantly decreasing the overall cost per cycle.