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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 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 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.
      Firma morfocinética de embriones mosaico: evidencia que apoya su propia identidad genética.

      Objetivo

      proveer de una caracterización morfocinética completa de embriones clasificados con grados de mosaicismo cromosómico diferente.

      Diseño

      Estudio retrospectivo de cohorte.

      Lugar

      Clínica privada de fecundación in vitro afiliada a Universidad

      Pacientes

      Analizamos 1,511 embriones de 424 ciclos de inyección intracitoplasmática de esperma mediante cultivo de embriones en sistema de imagen time lapse y secuenciación de nueva generación. Se evaluaron 106 embriones mosaico.

      Intervenciones

      Ninguna.

      Medidas principales

      Comparación de las características cromosómicas, morfológicas y morfocinéticas de blastocistos clasificados como euploides, aneuploides, mosaico de bajo grado (30% a <50% de células aneuploides en la biopsia de trofectodermo) y mosaico de alto grado (50% a <70% de células aneuploides en biopsia de trofectodermo). El análisis estadístico se realizó utilizando χ2 ,Kruskal-Wallis, o análisis de pruebas de varianza según el tipo y distribución de los datos. Se utilizó un modelo bidireccional de efectos aleatorios para calcular la correlación inter-operador de anotaciones, y se realizó un modelo logístico de efectos mixtos para evaluar el efecto de los factores de confusión sobre el tiempo morfocinético.

      Resultados

      La tasa de mosaicismo fue ∼7% independientemente de la edad de los padres. El mosaicismo y las aneuploidías uniformes no se distribuyeron uniformemente entre los cromosomas. El porcentaje de blastocistos de alta calidad disminuyó significativamente de euploide (66,9%) a mosaico (52,8%) y aneuploide (47,7%). Los blastocistos aneuploides retrasaron significativamente el desarrollo en comparación con los blastocistos euploides en el inicio de la compactación (mediana, 84,72 horas después de la microinyección [hpm], rango intercuartílico [IQR], 13,2; frente a mediana, 82,10 hpm, IQR, 11,5), inicio de blastulación (mediana, 101 hpm; IQR, 11,7; frente a mediana, 98,29 hpm, IQR, 10,5) y momento de aparición de blastocisto (mediana, 108,04 hpm, IQR, 11,50; frente a mediana, 104,71 hpm, IQR, 11,35). Sin embargo, la morfocinética del embrión no se correlacionó con el grado de mosaicismo o con una configuración de mosaicismo que fuera apta para la transferencia de embriones.

      Conclusiones

      El tiempo morfocinético de los embriones mosaico se superpone con el de los embriones euploides y aneuploides, lo que puede reflejar su identidad genética y de desarrollo única. Aunque esto sugiere que los embriones en mosaico no son simplemente un subproducto de un diagnóstico erróneo, se necesitan más estudios para revelar la verdadera identidad de este tipo particular de embrión.

      Keywords

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