Prolonged time to first cytokinesis and the interval between the five cell stage and early cavitation are not associataed with embryonic mosiacism

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The application of comprehensive chromosome screening (CCS) has dramatically increased pregnancy rates, but 40% of euploid embryos still fail to progress to delivery. Embryonic mosaicism, the presence of more than one cell line in an embryo, may be the etiology of some of these failures and even explain rare misdiagnoses1. In a pilot study, it was shown that certain time lapse microscopy (TLM) parameters (prolonged time to first cytokinesis (P0) and interval between five cell stage and early cavitation (Tcav)) were associated the ploidy status of embryos2. The goal of the present analysis was to assess whether the previously studied TLM parameters known to be associated with aneuploidy were associated with embryonic mosaicism. Aneuploid cryopreserved embryos that were designated for research and had undergone TLM from the 2PN to the blastocyst stage were included. Embryos were then warmed and biopsied a total of 4 times, blinded as to their origin, and submitted for next generation sequencing based CCS. If any of the biopsies yielded different CCS results, the embryo was deemed mosaic. If all biopsies agreed, the embryo was deemed non-mosaic. The TLM parameters previously associated with aneuploidy (P0 and Tcav) were analyzed and compared between mosaic and non-mosaic embryos. Time points were organized into quartiles and statistical analysis performed via contingency tables and receiver operator characteristic curves utilized. 134 aneuploid embryos met criteria to be included in the analysis. 102 embryos were found to be uniformly aneuploidy (the same karyotype was found in each of the 4 biological replicates). 32 (23.9%) embryos were found to be mosaic and had different karyotypes in each of the 4 biological replicates. No statistical differences were identified in quartile time points for P0 or Tcav to distinguish embryos that were mosaic from those that were uniformly aneuploidy (p=0.37; p=0.21). Similarly, an ROC curve could not distinguish mosaic embryos using these times points. TLM criteria (P0 and Tcav) which are associated with aneuploidy are unable to distinguish between uniform aneuploidy and mosaicism. This may be of importance as more is learned about the reproductive potential of mosaic embryos. Of note, only aneuploid embryos were included in this study, and additional data on embryos designated as euploid will be of interest.