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

Martin, Angel; Rodrigo, Lorena; Beltrán, Diana; Meseguer, M.; Rubio, Carmen; Mercader, Amparo; Santos, María José de los

doi:10.1016/j.fertnstert.2020.12.031

Cited by 19 publications

(26 citation statements)

References 41 publications

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“…In the group of high-level mosaic embryos, some morphokinetic parameters were delayed (e.g., t5, t8, cc3) and a higher incidence of multinucleations was found [ 37 ]. Another study shows that morphokinetic parameters of embryonic mosaics overlap the timing of cell division of euploid and aneuploid embryos [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Differences in Morphokinetic Parameters and Incidence of Multinucleations in Human Embryos of Genetically Normal, Abnormal and Euploid Embryos Leading to Clinical Pregnancy

Tvrdonova

Bělašková

Rumpíková³

et al. 2021

JCM

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The selection of the best embryo for embryo transfer (ET) is one of the most important steps in IVF (in vitro fertilisation) treatment. Preimplantation genetic testing (PGT) is an invasive method that can greatly facilitate the decision about the best embryo. An alternative way to select the embryo with the greatest implantation potential is by cultivation in a time-lapse system, which can offer several predictive factors. Non-invasive time-lapse monitoring can be used to select quality embryos with high implantation potential under stable culture conditions. The embryo for ET can then be selected based on the determined morphokinetic parameters and morphological features, which according to our results predict a higher implantation potential. This study included a total of 1027 morphologically high-quality embryos (552 normal and 475 abnormal PGT-tested embryos) from 296 patients (01/2016–06/2021). All embryos were cultivated in a time-lapse incubator and PGT biopsy of trophectoderm cells on D5 or D6 was performed. Significant differences were found in the morphological parameters cc2, t5 and tSB and the occurrence of multinucleations in the stage of two-cell and four-cell embryos between the group of genetically normal embryos and abnormal embryos. At the same time, significant differences in the morphological parameters cc2, t5 and tSB and the occurrence of multinucleations in the two-cell and four-cell embryo stage were found between the group of genetically normal embryos that led to clinical pregnancy after ET and the group of abnormal embryos. From the morphokinetic data found in the PGT-A group of normal embryos leading to clinical pregnancy, time intervals were determined based on statistical analysis, which should predict embryos with high implantation potential. Out of a total of 218 euploid embryos, which were transferred into the uterus after thawing (single frozen embryo transfer), clinical pregnancy was confirmed in 119 embryos (54.6%). Our results show that according to the morphokinetic parameters (cc2, t5, tSB) and the occurrence of multinucleations during the first two cell divisions, the best euploid embryo for ET can be selected with high probability.

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Section: Discussionmentioning

confidence: 99%

Differences in Morphokinetic Parameters and Incidence of Multinucleations in Human Embryos of Genetically Normal, Abnormal and Euploid Embryos Leading to Clinical Pregnancy

Tvrdonova

Bělašková

Rumpíková³

et al. 2021

JCM

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“…Considering confounding variables from nonembryonic factors, that is, maternal age, mature oocyte numbers, and oocyte sources, the present study revealed that delayed blastocyst formation was positively associated with increased mosaic levels ( Table 3 ). Two studies, which applied TL monitoring and hr-NGS simultaneously for PGT-A cycles, observed that aneuploid blastocysts exhibited a significant delay in tSB or tB as compared with euploid blastocysts ( Lee et al, 2019 ; Martin et al, 2021 ). Multivariate GEE analysis in this study further demonstrated a meaningful correlation of tSB and tB with mosaic levels when the threshold was set at 50%.…”

Section: Discussionmentioning

confidence: 99%

Blastocyst Morphology Based on Uniform Time-Point Assessments is Correlated With Mosaic Levels in Embryos

Chen¹,

Lee

Huang³

et al. 2021

Front. Genet.

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Avoiding aneuploid embryo transfers has been shown to improve pregnancy outcomes in patients with implantation failure and pregnancy loss. This retrospective cohort study aims to analyze the correlation of time-lapse (TL)-based variables and numeric blastocyst morphological scores (TLBMSs) with different mosaic levels. In total, 918 biopsied blastocysts with time-lapse assessments at a uniform time-point were subjected to next-generation sequencing–based preimplantation genetic testing for aneuploidy. In consideration of patient- and cycle-related confounding factors, all redefined blastocyst morphology components of low-grade blastocysts, that is, expansion levels (odds ratio [OR] = 0.388, 95% confidence interval [CI] = 0.217–0.695; OR = 0.328, 95% CI = 0.181–0.596; OR = 0.343, 95% CI = 0.179–0.657), inner cell mass grades (OR = 0.563, 95% CI = 0.333–0.962; OR = 0.35, 95% CI = 0.211–0.58; OR = 0.497, 95% CI = 0.274–0.9), and trophectoderm grades (OR = 0.29, 95% CI = 0.178–0.473; OR = 0.242, 95% CI = 0.143–0.411; OR = 0.3, 95% CI = 0.162–0.554), were less correlated with mosaic levels ≤20%, <50%, and ≤80% as compared with those of top-grade blastocysts (p < 0.05). After converting blastocyst morphology grades into scores, high TLBMSs were associated with greater probabilities of mosaic levels ≤20% (OR = 1.326, 95% CI = 1.187–1.481), <50% (OR = 1.425, 95% CI = 1.262–1.608), and ≤80% (OR = 1.351, 95% CI = 1.186–1.539) (p < 0.001). The prediction abilities of TLBMSs were similar for mosaic levels ≤20% (AUC = 0.604, 95% CI = 0.565–0.642), <50% (AUC = 0.634, 95% CI = 0.598–0.671), and ≤80% (AUC = 0.617, 95% CI = 0.576–0.658). In conclusion, detailed evaluation with TL monitoring at the specific time window reveals that redefined blastocyst morphology components and converted numeric TLBMSs are significantly correlated with all of the threshold levels of mosaicism. However, the performance of TLBMSs to differentiate blastocysts with aberrant ploidy risk remains perfectible.

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“…However, the ine ciency of PGT-A has been shown in recent studies considering the mosaicism of embryos and the heterogeneity of biopsy techniques among clinics [12][13][14] . Additionally, embryo morphokinetics cannot accurately re ect the degree of chromosomal mosaicism 15 . Even diploid embryos with normal morphological parameters may result in miscarriages 16 .…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic signatures in trophectoderm and inner cell mass of human blastocysts with different expectations of pregnancy

Kai

Mei

Kawano

et al. 2022

Preprint

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Selection of high-quality embryos is important to achieve successful pregnancy in assisted reproductive technology (ART). Recently, it has been debated whether RNA-sequencing (RNA-seq) should be applied to ART to predict embryo quality. However, the information on which genes can serve as markers for pregnant expectancy is limited. Furthermore, there is no information on which transcriptome of trophectoderm (TE) or inner cell mass (ICM) is more highly correlated with pregnant expectancy. Here we performed RNA-seq analysis for TE and ICM, respectively, in human blastocysts of which the expectation of pregnancy was retrospectively determined by the clinical outcomes of 1,890 cases of frozen-thawed blastocyst transfer. We identified dozens of genes that were correlated with the expected pregnancy rate in ICM and TE, respectively, with a larger number of genes identified in TE. Importantly, downregulated genes in TE of blastocysts that were estimated to have lower expectation of pregnancy included tight junction-related genes, such as CXADR, CLDN10, and ATP1B1, which were implicated in peri-implantation development. Additionally, we showed that aneuploidy estimation by RNA-seq datasets does not correlate with pregnancy expectation. Our study thus provides an expanded list of candidate genes for prediction of pregnancy in human blastocyst embryos.

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

Cited by 19 publications

References 41 publications

Differences in Morphokinetic Parameters and Incidence of Multinucleations in Human Embryos of Genetically Normal, Abnormal and Euploid Embryos Leading to Clinical Pregnancy

Differences in Morphokinetic Parameters and Incidence of Multinucleations in Human Embryos of Genetically Normal, Abnormal and Euploid Embryos Leading to Clinical Pregnancy

Blastocyst Morphology Based on Uniform Time-Point Assessments is Correlated With Mosaic Levels in Embryos

Transcriptomic signatures in trophectoderm and inner cell mass of human blastocysts with different expectations of pregnancy

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