Culture media formulations have advanced significantly over the past 20 years and can now routinely maintain the embryos of several mammalian species (including the human) to the blastocyst stage. Furthermore, access to recombinant albumin and hyaluronan has reduced reliance on blood products as a source of macromolecules, which has made embryo culture safer and more effective. However, in spite of many advances in nutrient composition, embryo culture media do not typically contain cytokines or growth factors, which are present at relatively high levels in uterine fluids. Furthermore, although current culture media may be considered more physiological than their predecessors, there is little that is physiological in the actual manner in which embryos are cultured in the laboratory, i.e. relatively large volumes of media in polystyrene dishes under paraffin oil, and as a static culture in typically outdated tissue culture incubators. Consequently, we inadvertently expose embryos to in vitro-created stresses, which can be detrimental to both embryo development and subsequent fetal & adult health. Of note, should two stresses be present in the same culture system, then one can get a combinatorial effect, further damaging the developing embryo. Significantly, there appears to be a difference between male and female embryos in their physiologies and responses to stress in culture. In order to further improve embryo culture we not only need to consider the role of cytokines and growth factors, but also the physical manner in which we maintain the early embryo.