A randomized, double-blind, multicentre clinical trial comparing starting doses of 150 and 200 IU of recombinant FSH in women treated with the GnRH antagonist ganirelix for assisted reproduction.

BACKGROUND: Studies with the GnRH antagonist ganirelix in assisted reproduction have indicated that compared with traditional GnRH agonist downregulation protocols, slightly fewer oocytes are retrieved. In this study it was investigated whether an increase in the starting dose of recombinant FSH (rFSH) could compensate for this loss. METHODS: A randomized, double-blind, multicentre clinical trial comparing a starting dose of 150 and 200 IU of rFSH (follitropin beta), in women undergoing treatment with the GnRH antagonist ganirelix. RESULTS: In total, 257 women were treated with rFSH, of whom 131 received 150 IU and 126 women 200 IU. Overall, 10.3 oocytes were retrieved in the 150 IU group and 11.9 in the 200 IU group (P=0.051). This difference became significant when women with cycle cancellation before HCG administration were excluded. Nearly 500 IU of additional rFSH was given in the high-dose group (2014 versus 1541 IU). In the low-dose group, 4.6 high-quality embryos were obtained compared with 4.5 in the high-dose group. Vital pregnancy rates were similar (31 and 25% in the 150 and 200 IU-treated women, respectively). Serum concentrations of FSH, estradiol and progesterone were significantly higher in the high-dose group at day 6 of rFSH treatment and on the day of HCG administration. In the high-dose group, serum LH concentrations were higher at day 6 of rFSH treatment but lower at the day of HCG administration. CONCLUSION: By increasing the starting dose from 150 to 200 IU of rFSH, slightly more oocytes can be retrieved in GnRH antagonist protocols for assisted reproduction. However, because this did not translate into a higher number of high quality embryos, the clinical relevance of such a dose increase may be questioned.

Use of gonadotrophin-releasing hormone agonists to trigger ovulation.

The introduction of gonadotrophin-releasing hormone (GnRH) agonists combined with gonadotrophins is considered to be one of the most significant advances in the development of in vitro fertilization (IVF) treatment. However, ovarian hyperstimulation syndrome (OHSS) remains a significant complication of controlled ovarian hyperstimulation. One possible strategy to reduce the risk of this complication would be the use of GnRH agonists instead of human chorionic gonadotrophin (hCG) to trigger the final stages of oocyte maturation. GnRH agonists are able to induce an endogenous surge of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and the effect may be more physiological than that of exogenous hCG. Several uncontrolled and controlled clinical studies have confirmed the efficacy of GnRH agonists for triggering ovulation, and pregnancy rates are comparable to those achieved with hCG. The incidence of OHSS appears to be decreased, but larger controlled studies are required to confirm this observation. The recent introduction of GnRH antagonists has led to renewed interest in the use of GnRH agonists to induce final oocyte maturation. An international multicentre randomized controlled trial has been completed recently comparing the efficacy of GnRH agonist with hCG for triggering ovulation in women undergoing controlled ovarian hyperstimulation using the GnRH antagonist ganirelix for pituitary suppression. The aim of the study was to determine the efficacy of the novel protocol for ovarian stimulation before IVF, in terms of pregnancy outcomes and the prevention of OHSS.