BACKGROUND: Ovarian stimulation is an integral procedure in assisted reproduction treatment. It is achieved by the administration of exogenous gonadotropins to increase follicular recruitment and oocyte yield. Optimization of ovarian stimulation is an essential prerequisite for the success of IVF treatment. AIM: This study aimed to evaluate the effect of a combined stimulation protocol of human FSH and recombinant FSH, simultaneously administered, on oocyte and embryo quality and clinical outcome. PATIENTS AND METHODS: In a prospective randomized study 197 infertile patients with a history of previous IVF failures for at least 3-5 attempts, were enrolled for an in vitro fertilization treatment. All patients had a standard down-regulation with GnRH analog and were then stimulated with FSH. The patients were matched into three groups: group A (no = 66) received human FSH combined with recombinant FSH in equal doses, simultaneously administered; group B (no = 67) received human FSH alone and group C (no = 64) received recombinant FSH alone. RESULTS: There were significantly higher pregnancy (p < 0.04) and implantation rates (p < 0.03) in favor of group A (hFSH/rFSH) compared to groups B (hFSH) and C (rFSH). A significant increase in the proportion of mature metaphase II oocytes (p < 0.002) and grade 1 embryos (p < 0.03) was observed in group A with respect to group B and C. Significantly higher delivery rate (p < 0.01) was achieved in group A compared to groups B and C. No significant differences were observed between groups regarding miscarriage rate and risk of ovarian hyperstimulation syndrome. CONCLUSIONS: The results show that the combination of human and recombinant FSH for ovarian stimulation may produce a positive effect on follicular development as it improve oocyte quality, embryo development, and ultimately clinical outcome.