Infertility affects one-in-six couples, often necessitating in vitro fertilization treatment (IVF). IVF generates complex data, which can challenge the utilization of the full richness of data during decision-making, leading to reliance on simple ‘rules-of-thumb’. Machine learning techniques are well-suited to analyzing complex data to provide data-driven recommendations to improve decision-making. In this multi-center study (n = 19,082 treatment-naive female patients), including 11 European IVF centers, we harnessed explainable artificial intelligence to identify follicle sizes that contribute most to relevant downstream clinical outcomes. We found that intermediately-sized follicles were most important to the number of mature oocytes subsequently retrieved. Maximizing this proportion of follicles by the end of ovarian stimulation was associated with improved live birth rates. Our data suggests that larger mean follicle sizes, especially those >18 mm, were associated with premature progesterone elevation by the end of ovarian stimulation and a negative impact on live birth rates with fresh embryo transfer. These data highlight the potential of computer technologies to aid in the personalization of IVF to optimize clinical outcomes pending future prospective validation.