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二细胞胚胎中的核异常表型与辅助生殖后的囊胚形成率相关。

Nuclear error phenotypes in the two-cell embryo are correlated to blastocyst formation rate after assisted reproduction.

作者信息

Stenberg Amanda, Baumgart Juliane, Adolfsson Emma

机构信息

Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro, Sweden.

Department of Obstetrics and Gynecology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.

出版信息

J Assist Reprod Genet. 2025 Jan;42(1):115-124. doi: 10.1007/s10815-024-03354-9. Epub 2024 Dec 27.

DOI:10.1007/s10815-024-03354-9
PMID:39730945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11805727/
Abstract

PURPOSE

Map the nuclear error phenotypes in the two-cell embryo after assisted reproduction using time lapse images and the effect on good quality blastocyst formation.

METHODS

Retrospective cohort study using time lapse images, categorizing 2331 two-cell embryos from 392 patient couples and 504 ART cycles categorizing each embryo as mononucleated, multinucleated, micronucleated, binucleated, split nucleation or mixed error. Correlating nuclear error phenotype with good quality blastocyst formation rate (BFR) using contingency tables and unadjusted odds ratio.

RESULTS

An overall nuclear error rate of 47.1% was observed in two-cell embryos. The most frequent error was multi-nucleation (14.2%) followed by mixed error (11%), micro-nucleation (8.6%), bi-nucleation (7.4%) and split nucleation (5.8%). Blastocyst formation rate (BFR) was reduced in embryos with nuclear errors, 46.2% for embryos with one cell affected, 27.6% for embryos with both cells affected, compared to 58.6% for mononucleated cells, p < 0.001 for both. Binucleated embryos were as likely as mononucleated embryos to become clinically useful blastocysts (56.8% vs 58.6%, n.s., unadjusted OR 0.94), whereas all the other phenotypes were less likely to develop into good quality blastocysts. The worst outcome was noted for embryos with split nucleation, with just 12.4% BFR, OR 0.12 (0-08-0.21), p < 0.001.

CONCLUSION

Nuclear errors are common at the two-cell stage. Overall, presence of nuclear errors reduces the likelihood of becoming good quality blastocysts. Both the number of affected cells and the different nuclear error phenotypes have impact on blastocyst formation rate, except binucleated embryos.

摘要

目的

利用延时图像绘制辅助生殖后二细胞胚胎中的核错误表型,以及其对优质囊胚形成的影响。

方法

采用延时图像进行回顾性队列研究,对来自392对患者夫妇的2331个二细胞胚胎和504个辅助生殖周期进行分类,将每个胚胎分类为单核、多核、微核、双核、分裂核或混合错误。使用列联表和未调整的优势比将核错误表型与优质囊胚形成率(BFR)相关联。

结果

在二细胞胚胎中观察到总体核错误率为47.1%。最常见的错误是多核化(14.2%),其次是混合错误(11%)、微核化(8.6%)、双核化(7.4%)和分裂核化(5.8%)。有核错误的胚胎的囊胚形成率(BFR)降低,一个细胞受影响的胚胎为46.2%,两个细胞都受影响的胚胎为27.6%,而单核细胞的囊胚形成率为58.6%,两者相比均p<0.001。双核胚胎成为临床可用囊胚的可能性与单核胚胎相同(56.8%对58.6%,无显著性差异,未调整的优势比为0.94),而所有其他表型发育成优质囊胚的可能性较小。分裂核化的胚胎结果最差,囊胚形成率仅为12.4%,优势比为0.12(0.08 - 0.21),p<0.001。

结论

核错误在二细胞阶段很常见。总体而言,核错误的存在降低了发育成优质囊胚的可能性。除双核胚胎外,受影响细胞的数量和不同的核错误表型均对囊胚形成率有影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1758/11805727/b282aaeae93a/10815_2024_3354_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1758/11805727/e617f21900b7/10815_2024_3354_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1758/11805727/19953759a71a/10815_2024_3354_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1758/11805727/b282aaeae93a/10815_2024_3354_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1758/11805727/e617f21900b7/10815_2024_3354_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1758/11805727/19953759a71a/10815_2024_3354_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1758/11805727/b282aaeae93a/10815_2024_3354_Fig3_HTML.jpg

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本文引用的文献

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Embryo multinucleation: detection, possible origins, and implications for treatment.胚胎多核:检测、可能的起源及对治疗的影响。
Hum Reprod. 2024 Nov 1;39(11):2392-2399. doi: 10.1093/humrep/deae186.
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Shape of the first mitotic spindles impacts multinucleation in human embryos.第一次有丝分裂纺锤体的形状影响人类胚胎的多核化。
Nat Commun. 2024 Jun 25;15(1):5381. doi: 10.1038/s41467-024-49815-8.
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The first two blastomeres contribute unequally to the human embryo.最初的两个卵裂球对人类胚胎的贡献是不均等的。
Cell. 2024 May 23;187(11):2838-2854.e17. doi: 10.1016/j.cell.2024.04.029. Epub 2024 May 13.
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Chromosomal Aberrations As a Biological Phenomenon in Human Embryonic Development.染色体畸变作为人类胚胎发育中的一种生物学现象。
Acta Naturae. 2023 Jul-Sep;15(3):27-36. doi: 10.32607/actanaturae.25255.
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The first mitotic division: a perilous bridge connecting the zygote and the early embryo.第一次有丝分裂:连接受精卵和早期胚胎的危险桥梁。
Hum Reprod. 2023 Jun 1;38(6):1019-1027. doi: 10.1093/humrep/dead067.
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Binucleated embryos at the two-cell stage show higher blastocyst formation rates and higher pregnancy and live birth rates compared to non-multinucleated embryos.与非多核胚胎相比,二细胞期的双核胚胎显示出更高的囊胚形成率、更高的妊娠率和活产率。
Hum Reprod Open. 2022 Nov 24;2022(4):hoac049. doi: 10.1093/hropen/hoac049. eCollection 2022.
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The first mitotic division of human embryos is highly error prone.人类胚胎的第一次有丝分裂高度易错。
Nat Commun. 2022 Nov 8;13(1):6755. doi: 10.1038/s41467-022-34294-6.
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Nucleation status of Day 2 pre-implantation embryos, acquired by time-lapse imaging during IVF, is associated with live birth.通过体外受精过程中的延时成像获得的第 2 天胚胎的核化状态与活产有关。
PLoS One. 2022 Sep 22;17(9):e0274502. doi: 10.1371/journal.pone.0274502. eCollection 2022.
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Nuclear Envelope Integrity in Health and Disease: Consequences on Genome Instability and Inflammation.核膜完整性在健康与疾病中的作用:对基因组不稳定性和炎症的影响。
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The impact of embryo binucleation depends upon its origin.胚胎双核化的影响取决于其起源。
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