DNA methylation and gene expression in IVF

Recently, differences in DNA methylation patterns in placental and umbilical blood samples taken from children born after IVF and children conceived naturally have been reported. Since this may have an effect on gene expression, we highlight some of the biochemical/metabolic pathways in oocytes and embryos that might be relevant to methylation and imprinting during the process of human IVF. First, ovarian stimulation leads to elevated concentrations of follicular homocysteine which may have an effect on methylation. This should be compensated for by the systematic administration of folic acid and other B vitamins to patients. Second, there has been a trend to culture early human embryos in culture medium lacking essential amino acids. Consequently, methionine is not available during the first 3 days of in-vitro culture, a time when methylation is of major importance. We strongly recommend the use of culture medium with essential amino acids in human fertilization and early developmental stages. Finally, although all animals are, to some extent, a model for others, great caution should be exercised in extrapolating data; in particular, data from the mouse should not be assumed to be applicable to human embryology.