Hypocellularity and absence of compaction as criteria for embryonic death

Abstract

Background: A precise definition of death is important for the appropriate application of medical resources and the harvesting of tissues for transplantation. For developed humans, life is considered to end when the criteria for brain death are met, but corresponding criteria are lacking for human embryos, and thus, we undertook a natural history study of embryonic death. Methods: De-identified records of the observations of human embryos in culture were analyzed retrospectively. The embryos were generated by in vitro fertilization for the purpose of reproduction. Cell number and morphology were recorded on embryonic days 2, 3, 5, and 6. Viable embryos (n = 248) were compared to nonviable embryos (n = 444) and the latter were analyzed in subgroups defined by cell number and morphology. Results: Many nonviable embryos (n = 142 out of 444) were hypocellular and lacked compaction on embryonic day 5 (ED5). All of these hypocellular embryos did not progress to compacted morula or normal blastocyst when observed further. No criteria could be discerned for the diagnosis of death on ED3. Conclusions: Arrested development at the multicellular stage on ED5 indicates an irreversible loss of integrated organic function, and hence, the condition of death for the organism. Approximately a fifth of all embryos generated for in vitro fertilization – heretofore misclassified among the ‘nonviable’ – are in fact dead on ED5 by our criteria. We propose that the ethical framework currently used for obtaining essential organs from deceased persons for transplantation could be applied to the harvesting of live cells from dead human embryos for the creation of stem cells.