Jonathan Van Blerkom1,2,3 and Patrick Davis1,2 and
Samuel Alexander2
1Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309 and 2Colorado Reproductive Endocrinology, Rose Medical Center, Denver, CO 80220, USA
3To whom correspondence should be addressed at: Department of Molecular, Cellular and Developmental Biology University of Colorado, Boulder, CO 80309, USA. E-mail:
The occurrence of a pleiomorphic population of cytoplasmic fragments is a common characteristic of early human embryos fertilized in vitro.
Here, temporal, spatial, fine structural, and biochemical aspects of fragmentation were examined in fragmented monospermic and dispermic pronuclear to early cleavage stages human embryos classified as stage-appropriate during the first 3.5 days of culture.
The morphodynamics of certain common patterns of fragmentation and the movement and composition of fragments were analyzed by time-lapse video, mitochondrial fluorescent probes, and transmission electron microscopy.
Plasma membrane and nuclear DNA integrity were assessed by annexin V staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) and single-cell alkaline gel electrophoresis ('comet') assays respectively.
Developmental competence for affected embryos was related to outcome after embryo transfer.
The results demonstrate that certain common forms of spontaneous fragmentation affecting early human embryos are not lethal, and that clusters of apparent fragments are often transient structures, which disappear by resorption or lysis.
The findings suggest that the occurrence and fate of fragments characteristic of these phenotypes may be related to oncosis-like processes associated with transient and focal ATP deficiencies in blastomeres and mitochondrial deficiencies or absence in extracellular fragments.
Abstract, Human Reproduction Vol.16, No.4 pp. 719-729, 2001
