Interval required for gonadotropin-releasing hormone-agonist-induced down regulation of the pituitary in cynomolgus monkeys and duration of the refractory state.

OBJECTIVES: To determine the minimal interval of gonadotropin-releasing hormone agonist (GnRH-a) administration required to induce pituitary refractoriness to the positive feedback effects of estradiol (E2) and to determine the duration of the induced refractory state in a nonhuman primate model. SETTING: Research laboratories of The Jones Institute for Reproductive Medicine. SUBJECTS: Cynomolgus monkeys with documented regular menstrual cycles. INTERVENTIONS: Part 1. Groups of four monkeys treated with leuprolide acetate (LA) for increasing intervals (0, 2, 4, 6, and 8 days), then challenged with E2 benzoate to induce a gonadotropin surge. Part 2. Groups of four monkeys treated with LA for the minimal time required to induce pituitary refractoriness (6 days), then challenged with E2 benzoate 2, 4, or 7 days after cessation of LA treatment. MAIN OUTCOME MEASURE(S): Pituitary luteinizing hormone and follicle-stimulating hormone and E2 levels were monitored. RESULTS: A minimum of 5 days of treatment is required for LA to induce pituitary refractoriness to the positive feedback effects of E2 benzoate. Once the down regulated condition is achieved, the refractory state lasts for at least 4 but not more than 6 days. CONCLUSION: The minimal treatment interval required for a GnRH-a to induce pituitary refractoriness to the positive feedback effects of estrogen and the duration of the induced refractory state are determined to be 5 days for these primates.

The gonadotropin-releasing hormone agonist stimulation test--a sensitive predictor of performance in the flare-up in vitro fertilization cycle.

OBJECTIVE: To evaluate the initial versus early pattern of estradiol (E2) change after administration of a gonadotropin-releasing hormone agonist (GnRH-a), i.e., the GnRH-a stimulation test versus E2 pattern, respectively, as predictors of ovarian response and pregnancy in in vitro fertilization (IVF) patients stimulated with a flare-up protocol. DESIGN: Prospective study in a consecutive group of patients. SETTING: Tertiary care, institutional setting. PATIENTS: Two hundred twenty-eight patients entered and completed the study. The only patients excluded from study were those anticipated to have polycystic ovarian disease, those with a single ovary, or those with an ovarian cyst(s). INTERVENTIONS: Patients were stimulated with a GnRH-a flare-up protocol beginning on menstrual day 2. MAIN OUTCOME: Evaluation of the GnRH-a stimulation test and the E2 pattern as predictors of the number of mature oocytes retrieved and pregnancy. RESULTS: The GnRH-a stimulation test but not the E2 pattern was predictive of the number of mature oocytes retrieved (r = 0.53, P less than 1 X 10(-5) and pregnancy (chi 2 = 8.5, P = 0.04). The E2 pattern was predictive of the duration and number of ampules of gonadotropin required for stimulation. CONCLUSION: The GnRH-a stimulation test is a sensitive predictor of performance in the flare-up IVF cycle.