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

Martin A, Rodrigo L, Beltran D, Meseguer M, Rubio C, Mercader A, Jose de Los Santos M,
Fertil Steril. Mar. 2021 doi: 10.1016/j.fertnstert.2020.12.031


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 chi(2), 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 effect model was performed to evaluate the effect of confounders on morphokinetic timing. RESULT(S): The mosaicism rate was approximately 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.