Programmed cell death and human embryo fragmentation

The quality of embryos produced by in-vitro fertilization (IVF) is variable. Many embryos contain unequal sized blastomeres and multiple cellular fragments. Embryos with excessive fragmentation have limited developmental potential both in vitro and in vivo. Histologically, some blastomeres of fragmented embryos resemble cells undergoing apoptosis as a result of programmed cell death (PCD). The objective of the present study was to determine if the morphological features of apoptosis are observed in fragmented human preimplantation embryos, supporting the possible involvement of PCD in early human embryo arrest and demise. Using combined nuclear and terminal transferase-mediated DNA end labelling (TUNEL) on arrested, fragmented human embryos, we were able to detect extensive condensation and degradation of chromatin, compatible with apoptosis. Electron microscopy confirmed the typical morphological features of apoptosis. No such abnormalities were observed in spare embryos with regular sized blastomeres without fragmentation. The high incidence of condensed chromatin, TUNEL detection of degraded DNA, cell corpses and apoptotic bodies in fragmented human embryos strongly suggest that PCD is triggered in human embryos at a stage prior to blastocyst formation. At such early stages, occurrence of apoptosis seemed to be detrimental, leading to preimplantation embryo death.