Early administration of gonadotropin-releasing hormone antagonist versus flexible antagonist ovarian stimulation protocol in poor responders: a randomized clinical trial

Abstract Background Determining the initiation day of antagonist administration is an important and challenging issue and different results have been reported in the previous studies. The present study was designed to compare the controlled ovarian hyperstimulation (COH) cycles outcomes of early-onset gonadotropin-releasing hormone antagonist (GnRH-ant) protocol with conventional flexible GnRH-ant protocol in patients with poor ovarian response (POR) diagnosis. This randomized clinical trial was performed on infertile women who were diagnosed as poor responders in in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycles at Arash Women’s Hospital affiliated to Tehran University of Medical Sciences. POR was defined according to the Bologna criteria and the eligible women were randomly allocated into an experimental (early-onset GnRH-ant) and control (conventional flexible GnRH-ant) groups. The women in the experimental group received recombinant gonadotropins (150–225 IU) and GnRH-ant (0.25 mg) simultaneously on the second day of the cycle. In the control group, the starting and the dose of gonadotropins were similar but daily administration of GnRH-ant was initiated when the leading follicle diameter was ≥ 13 mm. The COH outcomes were compared between groups (n=58 in each group). Results The analysis showed that the two groups did not have statistically significant differences in terms of the ovarian stimulation duration and the total dose of used gonadotropins. The total number of metaphase II (MII) oocytes in the experimental group was significantly higher than that of in control group (P = 0.04). Moreover, clinical and ongoing pregnancy rates per embryo transfer (ET) in the experimental group were significantly higher than those in the control group (P = 0.02 and P = 0.03, respectively); however, the implantation and miscarriage rates were similar between groups. Conclusions The early-onset GnRH-ant protocol can improve the number of retrieved and MII oocytes and probably the pregnancy outcomes after fresh embryo transfer in POR patients. However, larger randomized clinical trials are required to compare the pregnancy outcomes after this approach with other COH protocols with considering cost-effectiveness issue. Trial registration IRCT20110731007165N9. The name of the registry: Ladan Kashani. The date of trial registration: 8.02.2020.