The effect of a GnRH antagonist on follicle maturation in normal women

Research question: Ganirelix is a gonadotrophin-releasing hormone (GnRH) antagonist used for the prevention of premature LH surge during ovarian stimulation. What is the impact of ganirelix on follicle maturation in normal women? Design: Ten normally cycling women were investigated during two menstrual cycles, i.e. cycle 1 (control) and cycle 2 (ganirelix). During both cycles, daily blood samples were taken from day 2, while transvaginal ultrasound scans were performed on cycle days 8 and 10 and daily thereafter. During cycle 2, all women were given 0.25 mg/day subcutaneous injections of the GnRH antagonist ganirelix from day 2 until the day of the endogenous LH surge onset in cycle 1. Results: During treatment with ganirelix, serum FSH and oestradiol concentrations remained stable, while those of LH decreased significantly on days 3, 4, 7 and 9 (P < 0.05) compared with controls. Nevertheless, there was no significant within-cycle variation in LH concentrations. From day 10 onwards, no follicle maturation was observed in cycle 2, in contrast to cycle 1. Ovulation occurred in 9 of 10 women in cycle 1. In cycle 2, ovulation was delayed by at least 1 week in eight women. Follicle growth and ovulation occurred in only one woman while on ganirelix treatment. Conclusions: This study demonstrates for the first time that in normal women dominant follicle selection failed during treatment with ganirelix. As there was a similar gonadotrophin profile in the two cycles, it is suggested that ganirelix interferes with the process of follicle selection by acting in the ovary.