The addition of GnRH antagonists in intrauterine insemination cycles with mild ovarian hyperstimulation does not increase live birth rates—a randomized, double-blinded, placebo-controlled trial

BACKGROUND: This multicenter, double-blinded RCT investigated the efficacy of GnRH antagonists in cycles with mild ovarian hyperstimulation (MOH) followed by IUI in subfertile women. METHODS: Couples diagnosed with unexplained, male factor subfertility or associated with the presence of minimal or mild endometriosis were randomized with a computer-generated list of numbers by a third party in a double-blinded setting to receive either a GnRH antagonists or a placebo in 12 institutional or academic hospitals. All women were treated with recombinant FSH in a low-dose step-up regimen starting on Day 2-4 of the cycle. A GnRH antagonist was added when one or more follicles of 14 mm diameter or more were visualized. When at least one follicle reached a size of >= 18 mm, ovulation was induced by hCG injection. A single IUI was performed 38-40 h later. Couples were offered a maximum of three consecutive cycles. The primary outcome of the trial was live births. Secondary outcomes were pregnancy rates, multiple pregnancy rates, miscarriages and ovarian hyperstimulation syndrome rate. RESULTS: A total of 233 couples were included from January 2006 to February 2009, starting 572 treatment cycles. Live birth rates were not significantly different between the group treated with GnRH antagonist (8.4%; 23/275) and the placebo group (12%; 36/297) (P = 0.30). Three twin pregnancies occurred in the GnRH antagonist group and two twin pregnancies in the placebo group. CONCLUSIONS: Adding a GnRH antagonist in cycles with MOH in an IUI program does not increase live birth rates. Dutch Trial Register no: NTR497.