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

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Authors:

Ángel Martín, M.Sc., Lorena Rodrigo, Ph.D., Diana Beltrán, M.Sc., Marcos Meseguer, Ph.D., Carmen Rubio, Ph.D., Amparo Mercader, Ph.D., María José de los Santos, Ph.D. 

Abstract:

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 χ2, 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 ∼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.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.