Objective: Successful implantation and placentation depend on the interaction between the endometrium and the embryo. Angiogenesis is crucial at this time. In this article we investigate the direct influence of the human embryo on in vitro endometrial angiogenesis. Design: In vitro study. Setting: Human endometrial microvascular endothelial cells (hEMVEC) grown on an in vitro angiogenesis model. Intervention(s): Conditioned media (CM) of human embryos were used to stimulate in vitro angiogenesis. Main Outcome Measure(s): In vitro angiogenesis of hEMVEC. Result(s): Conditioned media of human embryos, containing significant amounts of vascular endothelial growth factor (VEGF)-A, as determined by enzyme-linked immunosorbent assay (ELISA), caused an increase in hEMVEC tube formation. This effect was prevented by soluble VEGF receptor 1, which quenches VEGF-A activity. Recombinant EGF alone and leukemia inhibitory factor in combination with VEGF-A stimulated hEMVEC tube formation. None of the other tested recombinant mediators, which have been described as produced by the early embryo/trophoblast (interleukin (IL) 10, transforming growth factor (TGF) β, placental growth factor, hCG, colony-stimulating factor 1, interferon-γ, insulin-like growth factor I and II, IL-6, platelet-derived growth factor, and TGFα), had an effect on tube formation by hEMVEC. Conclusion(s): For the first time, it is shown that the human embryo is able to stimulate in vitro endometrial angiogenesis at the time of implantation, a process that is mediated by VEGF-A. © 2006 American Society for Reproductive Medicine.