To compare embryologic and clinical outcomes in terms of preimplantation development, implantation, pregnancy rates, and secretome profile of implanted blastocysts from the preimplantation genetic diagnosis program grown in sequential versus endometrial epithelial cell (EEC) coculture system. Retrospective clinical study and prospective experimental study. In vitro fertilization clinical unit and university research laboratory. Blastomere biopsy, embryo culture, blastocyst transfer, and protein analysis of the media conditioned from implanted embryos obtained from coculture and sequential systems. Clinical study: blastocyst, implantation, and gestation rates in own and donated oocytes. Experimental study: differential protein analysis of implanted embryos grown in coculture system versus sequential system. Of the 12,377 embryos analyzed, the blastocyst rates were 56.0% versus 45.9% in the coculture versus the sequential system, respectively, with own oocytes. With ovum donation, the rates were 70.5% versus 56.4%, respectively. Reproductive outcomes in terms of pregnancy rates (39.1% vs. 27.5%) and implantation rates (33.3% vs. 20.9%,) were statistically higher in EEC coculture versus sequential media. Furthermore, the protein profile of the EEC coculture versus the sequential system was obtained. Interleukin-6 (IL-6) was the most secreted protein by the EEC culture. Further ELISA experiments showed that the IL-6 present in the sequential medium diminished in implanted blastocysts. The coculture system favors blastocyst development and implantation rates, given the contribution of the factors secreted by endometrial epithelial cells, such as IL-6. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.