From cell death to embryo arrest: Mathematical models of human preimplantation embryo development

Human preimplantation embryos exhibit high levels of apoptotic cells and hi gh rates of developmental arrest during the first week in vitro. The relati on between the two is unclear and difficult to determine by conventional ex perimental approaches, partly because of limited numbers of embryos. We app ly a mixture of experiment and mathematical modeling to show that observed levels of cell death can be reconciled with the high levels of embryo arres t seen in the human only if the developmental competence of embryos is alre ady established at the zygote stage, and environmental factors merely modul ate this. This suggests that research on improving in vitro fertilization s uccess rates should move from its current concentration on optimizing cultu re media to focus more on the generation of a healthy zygote and on underst anding the mechanisms that cause chromosomal and other abnormalities during early cleavage stages.