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Prolonged time to first cytokinesis and the interval between the five cell stage and early cavitation are associated with embryonic mosaicism

      Objective

      The use of time lapse imaging through day 3 of development provides insight into the probability a cleavage stage embryo will blastulate. This raises the question of whether these parameters are correlated with other biologic phenomena occurring during the same time interval. One such parameter is mosaicism. Mosaicism is a particularly problematic abnormality as it may result in misdiagnoses from comprehensive chromosome screening (CCS) and is a potential reason why some embryos designated as euploid fail to deliver. Parameters identifying embryos at increased or decreased risk for mosaicism would, therefore, be useful during embryo selection.

      Design

      Prospective observational study.

      Materials and Methods

      Embryos that tested aneuploid and had undergone time-lapse imaging from the 2PN to the blastocyst stage were studied. The embryos were biopsied 4 times, placed into individual PCR tubes, blinded as to their origin, and submitted for NextGen based CCS. If any of the biopsies yielded different CCS results, the embryo was deemed mosaic. If all biopsies agreed it was deemed non-mosaic. Traditional time lapse parameters shown to predict blastulation and an additional parameter, time from 5-cell stage to the first sign of cavitation, were compared between mosaic and non-mosaic embryos.

      Results

      12 of the 53 (23%) embryos were mosaic. Mosaic embryos took longer to undergo first cytokinesis (P0) (p< 0.02). Other time-lapse parameters evaluated through the cleavage stage of development were equivalent. Interestingly, the time to early cavitation from the 5-cell stage was longer in mosaics (P<0.03).
      Tabled 1Time-lapse parameters in mosaic and non-mosaic embryos
      P0P1P2P3P4Time to Cavitation
      Mosaic24.160.4211.540.7913.7779.47
      Non-Mosaic22.220.3711.161.3012.2574.67
      P Values0.020.810.700.500.150.03

      Conclusion

      These data demonstrate that two time-lapse parameters related to first cytokinesis and time to first cavitation are associated with embryonic mosaicism. The former may reflect abnormalities in formation of the first mitotic spindle. The latter may indicate that cellular processes leading to mosaicism also result in delayed rates of development after genomic activation. With further investigation, such parameters may help avoid the transfer of mosaic embryos.