Dynamics of the development of multiple follicles during ovarian stimulation for in vitro fertilization using recombinant follicle-stimulating hormone (Puregon) and various doses of the gonadotropin-releasing hormone antagonist ganirelix (Orgalutran/Antagon)

Objective: To investigate relations between dose of GnRH antagonist and follicular phase characteristics. Design: Randomized controlled multicenter trial.Setting: Tertiary referral fertility centers. Patient(s): Three hundred and twenty-nine IVF patients.Intervention(s): Ovarian stimulation for IVF with recombinant FSH starting on cycle day 2. From cycle day 7 onwards, cotreatment was provided with 0.0625, 0.125, 0.25, 0.5, 1.0, or 2.0 mg/d GnRH antagonist. Main Outcome Measure(s): Number of follicles, total follicular surface area, gonadotropin, and serum steroid concentrations. Result(s): In 311 patients, similar follicular growth was observed in all treatment groups. FSH levels increased during the follicular phase. Late follicular phase LH, androstenedione (AD), and E₂ levels showed a GnRH antagonist dose-related decrease (P<0.05). Late follicular phase E₂ levels correlated with total follicular surface area, AD, LH, and FSH (all P<0.001). Increasing GnRH antagonist doses exhibited additional suppressive action on E₂ levels. Conclusion(s): Follicular growth was unaffected by the dose of GnRH antagonist. A rise in follicular phase FSH serum concentrations during the follicular phase, largely related to exogenous FSH, enabled ongoing follicular growth in all treatment groups. The effect of GnRH antagonist on late follicular phase E₂ levels could not be exclusively attributed to suppression of LH.