Ovulation induction in premature ovarian failure: a placebo-controlled randomized trial combining pituitary suppression with gonadotropin stimulation.

OBJECTIVES

To determine the effect of pituitary suppression with a GnRH agonist (GnRH-a) on the success of ovulation induction with exogenous gonadotropins in patients with premature ovarian failure (POF).

DESIGN

Placebo-controlled, randomized, double-blind study. The data were analyzed with a Fisher exact test.

SETTING

A tertiary care academic center for Reproductive Endocrinology and Fertility.

PATIENTS

Thirty patients with POF, 15 in each group.

INTERVENTIONS

The study consisted of four phases: phase 1, no interventions; phase 2, a 4-week period in which the patients received either 1,000 micrograms intranasal buserelin acetate daily or placebo; phase 3, a 3-week period during which the patients additionally received hMG in weekly augmented doses, two, four, and six ampules daily in the first, second, and third weeks, respectively. Ovulation was induced whenever the follicular diameter reached 18 mm and/or total 24-hour estrogen excretion > 140 micrograms (500 nmol). Luteal support was 5,000 IU hCG every 72 hours; phase 4, no interventions.

RESULTS

Follicular growth was seen in five patients of the agonist group and in four patients of the placebo group. Three of 15 patients in the agonist group ovulated versus none in the placebo group. The difference was not statistically significant.

CONCLUSIONS

The fact that 3 of 15 cycles cotreated with a GnRH-a were ovulatory versus none in the placebo-treated group appeared not to be enough evidence to demonstrate that pituitary suppression with a GnRH-a improves the success of ovulation induction with exogenous gonadotropins in patients with POF.