We aimed to investigate the value of fourth day serum estradiol levels in predicting cycle outcome in poor responders. The medical records of 426 patients with low oocyte yield following controlled ovarian hyperstimulation (CON) treatment for a procedure in our institution's center for ART between 2008 and 2013 were evaluated. Eighty-eight patients exhibiting poor ovarian response (POR) were included in the study. The clinical outcomes of IVF/ICSI were compared based on the basal hormone profile, clinical, and laboratory parameters. Cycle day 4 E2 levels below 110 pg/ml had an odds ratio of 6.05 (95% CI 2.33-15.7; p < 0.001) for embryo transfer. The early follicular response to ovarian stimulation can be anticipated with the cycle day 4 estradiol levels during COH. When a low day 4 serum estradiol level is encountered, abandoning the current CON and proceeding with agents that increase ovarian response to ovarian stimulation before the next treatment cycle can be a realistic approach.