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Early times to cavitation are associated with a reduced prevalence of aneuploidy in embryos cultured to the blastocyst stage: a prospective blinded morphokinetic study

      Objective

      Temporal and morphologic markers of embryo development typically direct selection. Novel “in-incubator” systems provide frequent imaging of early embryo development. Early cleavage rates are correlated with blastulation rates and clinical outcome. There are limited data relating these new parameters and other factors influencing embryonic reproductive competence such as aneuploidy. This study evaluates those relationships.

      Design

      Prospective.

      Materials and Methods

      Entire cohorts of embryos were imaged using the Eeva™ system (Auxogyn, Menlo Park, CA). Those becoming blastocysts underwent biopsy and qPCR based aneuploidy screening. Imaging parameters including the time from ICSI to start of 1st cytokinesis, duration of 1st cytokinesis, duration of the 2, 3 and 4 cell stages and times from 1st cytokinesis or 5 cells to cavitation were determined. Results were grouped by parameter distribution quartiles and compared with ploidy status.

      Results

      307 embryos from 24 patients were imaged. 135 blastulated and were analyzed. 121 had imaging and aneuploidy assessments completed. When assessing the predictive values of these parameters, two measures were found to be correlated with aneuploidy: the times from either the 1st cytokinesis (P=0.02) or the 5 cell stage (P=0.01) to the onset of cavitation. Other comparisons were non-informative for ploidy.

      Conclusion

      Time to early cavitation from 1st cytokinesis and from the 5 cell stage provide some discrimination of aneuploid risk in their outer quartiles. Extended culture to the blastocyst stage is necessary to identify these parameters. Their middle quartiles and all quartiles of the other parameters were non-discriminatory. The magnitudes of the changes were modest. The predictive value to exclude aneuploidy is more than an order of magnitude less precise than other screening platforms. Still, these differences may provide meaningful selection value and explain some of the mechanism of the enhanced outcomes observed when using these techniques.