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Symmetry at the 4-Cell Stage Is Associated with Embryo Aneuploidy

  • Embryology: Original Article
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Abstract

The purpose of this study was to determine if morphometric parameters that can be measured quantitatively using a time-lapse embryo incubator are associated with aneuploidy. Embryos cultured in a time-lapse incubator and assessed with preimplantation genetic testing for aneuploidy (PGT-A) were analyzed retrospectively. Morphokinetic analysis included timing of cell divisions. Quantitative morphometric measurements included the distance between the second and first polar body, zona pellucida thickness at the pronuclear stage and at the 2-cell stage, and blastomere area at the 2- and 4-cell stages. Symmetry at the 2-cell stage was determined by percent difference between blastomeres; symmetry at the 4-cell stage was the percent difference between the smallest and largest blastomeres. Maternal age, blastocyst grade and day of biopsy were recorded. Euploid embryo characteristics were compared to aneuploid embryos. A receiver operating characteristic (ROC) curve was used to evaluate cell symmetry as a predictor of aneuploidy. Embryos (n = 182) from 21 patients (age 22–43; median = 34) were analyzed. Of the 182 embryos, 45% were euploid. Euploid and aneuploid embryos had similar morphokinetics and morphometry across many measures. As expected, age and blastocyst grade were associated with embryo ploidy. It was notable that, additionally, symmetry at the 4-cell stage (27% vs 31%, p = 0.01) was also associated with embryo ploidy. The optimized cutoff from the ROC curve to predict aneuploidy was determined to be 21%. Embryos with > 21% asymmetry at the 4-cell stage had high rates of aneuploidy while morphokinetic parameters were similar. In conclusion, this suggests that embryo selection models using time-lapse parameters would improve if they incorporate cleavage-stage morphometrics.

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Authors and Affiliations

  1. Division of Reproductive Endocrinology and Infertility, Mayo Clinic, Rochester, MN, USA

    Chandra C. Shenoy, Zaraq Khan, Charles C. Coddington, Elizabeth A. Stewart & Dean E. Morbeck

Authors
  1. Chandra C. Shenoy
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  2. Zaraq Khan
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  3. Charles C. Coddington
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  4. Elizabeth A. Stewart
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  5. Dean E. Morbeck
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Chandra Shenoy. The first draft of the manuscript was written by Chandra Shenoy and Dean Morbeck commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Chandra C. Shenoy.

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IRB approved by Mayo Clinic Institutional Review Board 15–007799. Waived by IRB due to retrospective nature. Patients who did not complete Minnesota Research Authorization were excluded.

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Not applicable.

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The authors declare no competing interests.

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Shenoy, C.C., Khan, Z., Coddington, C.C. et al. Symmetry at the 4-Cell Stage Is Associated with Embryo Aneuploidy. Reprod. Sci. 28, 3473–3479 (2021). https://doi.org/10.1007/s43032-021-00758-1

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  • DOI: https://doi.org/10.1007/s43032-021-00758-1

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