The morphokinetic signature of mosaic embryos: evidence in support of their own genetic identity

Objective: To provide full morphokinetic characterization of embryos ranked with different degrees of chromosomal mosaicism. Design: Retrospective cohort study. Setting: University-affiliated private in vitro fertilization clinic. Patient(s): We analyzed 1,511 embryos from 424 intracytoplasmic sperm injection cycles by culturing embryos in a time-lapse imaging system and performing next-generation sequencing. We assessed 106 mosaic embryos. Intervention(s): None. Main Outcome Measure(s): Comparison of chromosomal, morphological, and morphokinetic characteristics of blastocysts classified as euploid, aneuploid, low-degree mosaic (30% to <50% aneuploid cells in trophectoderm biopsy), and high-degree mosaic (50% to <70% aneuploid cells in trophectoderm biopsy). Statistical analysis was performed using c2, Kruskal-Wallis, or analysis of variance tests according to data type and distribution. A two-way random effects model was used to calculate interoperator correlation of annotations, and a logistic mixed effects model was performed to evaluate the effect of confounders on morphokinetic timing. Result(s): The mosaicism rate was -7% regardless of parental age. Mosaicism and uniform aneuploidies were not evenly distributed across chromosomes. The percentage of high-quality blastocysts significantly decreased from euploid (66.9%) to mosaic (52.8%) and aneuploid (47.7%). Aneuploid blastocysts significantly delayed development compared with euploid blastocysts in start of compaction (median, 84.72 hours postmicroinjection [hpm], interquartile range [IQR], 13.2; vs. median, 82.10 hpm, IQR, 11.5), start of blastulation (median, 101 hpm; IQR, 11.7; vs. median, 98.29 hpm, IQR, 10.5), and timing of blastocyst (median, 108.04 hpm, IQR, 11.50; vs. median, 104.71 hpm, IQR, 11.35). However, embryo morphokinetics were not correlated to the degree of mosaicism or to a mosaicism configuration that was apt for embryo transfer. Conclusion(s): Morphokinetic timing of mosaic embryos overlaps with that of euploid and aneuploid embryos, which may reflect their unique genetic and developmental identity. Although this suggests mosaic embryos are not simply a misdiagnosis by-product, further studies are needed to reveal the true identity of this particular type of embryo. (Fertil Sterile 2021;116:165-73. (c) 2020 by American Society for Reproductive Medicine.) El resumen est & aacute; disponible en Espa & ntilde;ol al final del art & iacute;culo.

Automated summary

This study provided a full morphokinetic characterization of embryos with different degrees of chromosomal mosaicism. It was found that the percentage of high-quality blastocysts decreased from euploid to mosaic and aneuploid embryos. Aneuploid blastocysts showed delayed development compared to euploid blastocysts, but embryo morphokinetics were not correlated to the degree of mosaicism or a mosaicism configuration apt for embryo transfer.