Ovarian estradiol production in vivo. Inhibitory effect of leuprolide acetate.

Objective

To determine the impact of reducing the dose of gonadotropin-releasing hormone agonist (GnRH-a) for controlled ovarian stimulation in in vitro fertilization (IVF) on subsequent response to stimulation and cycle outcome.

Study design

An IVF database was searched to identify patients who underwent at least two cycles of ovarian stimulation at a university-based medical center, and a retrospective chart review was performed. Fifty-one patients whose IVF stimulation protocols during the two cycles were identical except for the leuprolide dosage utilized for luteal pituitary suppression were included in the study. Two leuprolide dosages were utilized for suppression: a low dose, 0.5 mg daily, and a high dose, 1 mg daily. The leuprolide dose was uniformly halved upon initiation of gonadotropin stimulation; the gonadotropin dose and preparation were identical in the two protocols. Day 3 follicle-stimulating hormone levels, duration of stimulation, amount of gonadotropins required, midcycle and peak estradiol levels, oocyte yield and implantation rates were compared.

Results

Lowering the dose of GnRH-a while maintaining the same stimulation protocol resulted in a faster estradiol rise and higher mean peak estradiol level. The higher estradiol levels were obtained with a lower total gonadotropin dose. The oocyte yield was not affected by the stimulation protocol utilized.

Conclusion

Lowering the dosage of leuprolide allows higher estradiol levels in those patients. This suggests an inhibitory in vivo effect of leuprolide acetate on ovarian steroidogenesis.