Increased gonadotropin dosing (375 vs 225 IU/day) does not improve clinical outcomes in poor-prognosis patients undergoing IVF: results of a multi-center randomized controlled trial

Objective Is the use of higher gonadotropin dosing associated with improved clinical pregnancy rate (CPR), live birth rate (LBR) and cumulative live birth rate (cLBR) in expected poor responders undergoing IVF? Design Prospective, randomized, controlled trial of women between the ages of 18-42 years meeting POSEIDON 3 or 4 criteria (low ovarian reserve) in 6 Hungarian IVF centers. Eligible women were randomly assigned to stimulation using a fixed lower (225 IU: 150 IU recombinant follicle stimulating hormone (FSH) + 75 IU human menopausal gonadotropin (hMG)) or higher (375 IU: 225 IU recombinant FSH + 150 IU hMG) dose gonadotropin treatment following an antagonist protocol. Stimulation, embryology and clinical outcomes were compared. Results 190 women were randomized; 185 started treatment (intention-to-treat population) and 133 underwent embryo transfer (as treated population). The groups were well-balanced regarding demographic parameters. Significantly lower dose gonadotropin was used in the low dose arm (2189 IU vs 3550 IU, p<0.001). None of the clinical outcome parameters, including the cLBR (18.1% vs 14.4%, p=0.48) were significantly different. When outcomes based on the different follitropin preparations (FSH-α and FSH-δ) were evaluated, the clinical outcomes appeared superior in the lower dose groups. Still, none of the differences reached statistical significance. Conclusion This exploratory analysis did not observe any benefit from administering higher doses of gonadotropin in poor responder patients, though the study was underpowered to detect small to moderate differences.