Addition of GnRH antagonist in cycles of poor responders undergoing IVF

Abstract

Concern about the use of gonadotrophin-releasing hormone (GnRH) agonists in ovarian stimulation of poor responder IVF patients has arisen from the claim that GnRH agonists might have a direct deleterious effect through their receptors on the ovary. In this study, we compared two ovarian stimulation protocols in which no GnRH agonists were used. In all, 40 patients with a poor response in previous treatment cycles were included. They were divided into two groups: group I (n = 20) received ovarian stimulation for 20 cycles, without the addition of either GnRH agonist or antagonist; while group II (n = 20) patients received ovarian stimulation for 20 cycles, including the administration of a GnRH antagonist (Cetrorelix, 0.25 mg daily) during the late follicular phase. There was no statistically significant difference between the groups for mean age, duration of infertility, baseline FSH concentration, cancellation rate, number of ampoules of gonadotrophin used, number of mature oocytes retrieved, oestradiol concentrations on the day of injection of human chorionic gonadotrophin (HCG), fertilization rate and number of embryos transferred. The clinical pregnancy and implantation rates in group II appeared higher than in group I, but were not significantly different (20 and 13.33% compared with 6.25 and 3.44% respectively). The addition of GnRH antagonists to ovarian stimulation protocols might be a new hope for poor responder IVF patients, but this report is preliminary and further controlled randomized prospective studies with larger sample sizes are required.

Gonadotropin-Releasing Hormone (GnRH)-Antagonist Versus GnRH-Agonist in Ovarian Stimulation of Poor Responders Undergoing IVF

“…It was demonstrated that the use of GnRHantagonists resulted in significantly less ampoules of gonadotropins and a shorter duration of stimulation (15). In addition, since a deleterious effect of agonists directly on the ovary might be the reason for the failure in those with a limited ovarian reserve, Akman et al compared ovarian stimulation in 20 low responders following the use of GnRH-antagonists to that without the addition of an agonist, and reported higher, though not statistically significant, clinical pregnancy and implantation rates in the antagonist group than in the group without an agonist (20 and 13.33% compared to 6.25 and 3.44%, respectively) (16). Contrary to these preliminary encouraging results, a recent prospective randomized trial comparing the efficacy of the flare-up protocol to the antagonistic multiple dose protocol in ovarian stimulation of 24 poor responders reported that of the parameters evaluated, only the estradiol concentrations on the day of hCG were higher in the GnRH-agonist group, whereas the clinical pregnancy and implantation rates among the groups did not show any significant difference, concluding that the impact of these two regimens in ovarian stimulation of poor responders seems to be the same (17).…”

A prospective randomised study comparing a GnRH-antagonist versus a GnRH-agonist short protocol for ovarian stimulation in patients referred for IVF

“…Although initially the antagonist protocol was used in poor responders hoping for a better ovarian response, these studies mostly compared an antagonist protocol to an agonist long protocol (Akman et al, 2000;Marci et al, 2005;Franco et al, 2006). We observed in our study a higher cancellation rate of 8% in the antagonist treated group due to low ovarian reaction versus 1 % in the agonist protocol, this despite a slightly higher mean age in the agonist group.…”

Is there an ideal stimulation regimen for IVF for poor responders and does it change with age?

“…Other variations to the stimulation regimen that have been examined, in randomised trials, include DR/FSH versus stop agonist long protocol once DR has been achieved [28,29], Ant/FSH versus no down regulation [30] and, Boost versus natural cycle IVF [31]. As with the other studies described there was no significant difference in pregnancy rates between groups and no consistent definition of a 'poor' responder.…”