Recent advances in the production of viable human embryos in vitro.

The introduction of stress to embryonic blastomeres through inappropriate culture conditions results ultimately in the loss of viability. Retention of normal metabolic function in human preimplantation embryos, as well as those of other mammalian species, has been improved by the use of stage-appropriate culture media wherein energy substrates and amino acids are provided in a temporally evolving sequence. While the time dependence of nutrient exposure to embryos has received wide attention, spatial considerations in the embryonic microenvironment have received none. The manner in which media are presented to embryos, the rate at which media are changed, the rate at which cell products are removed and the macromolecular influences upon embryonic microenvironments have received far less attention in the experimental literature. Recent advances in micro-scale engineering allows for the rapid production of matrices containing culture channels slightly larger than the dimensions of preimplantation embryos. Microfluidic systems hold great promise for providing physical configurations yielding significantly reduced volumes but simultaneously providing control over the dynamics of media change and waste removal via fluid flow with time. Additionally, macromolecules may be presented from fixed sites in a minimum volume of solvent thus allowing us to test the importance of space and geometry in facilitating the physical and chemical effectiveness of the embryonic milieu.