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Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human Embryos.
American Journal of Human Genetics ( IF 9.8 ) Pub Date : 2020-03-26 , DOI: 10.1016/j.ajhg.2020.03.005
Laura Girardi 1 , Munevver Serdarogullari 2 , Cristina Patassini 1 , Maurizio Poli 1 , Marco Fabiani 1 , Silvia Caroselli 1 , Onder Coban 2 , Necati Findikli 3 , Fazilet Kubra Boynukalin 4 , Mustafa Bahceci 4 , Rupali Chopra 5 , Rita Canipari 6 , Danilo Cimadomo 7 , Laura Rienzi 7 , Filippo Ubaldi 7 , Eva Hoffmann 8 , Carmen Rubio 9 , Carlos Simon 10 , Antonio Capalbo 11
Affiliation  

Despite next-generation sequencing, which now allows for the accurate detection of segmental aneuploidies from in vitro fertilization embryo biopsies, the origin and characteristics of these aneuploidies are still relatively unknown. Using a multifocal biopsy approach (four trophectoderms [TEs] and one inner cell mass [ICM] analyzed per blastocyst; n = 390), we determine the origin of the aneuploidy and the diagnostic predictive value of segmental aneuploidy detection in TE biopsies toward the ICM's chromosomal constitution. Contrary to the prevalent meiotic origin of whole-chromosome aneuploidies, we show that sub-chromosomal abnormalities in human blastocysts arise from mitotic errors in around 70% of cases. As a consequence, the positive-predictive value toward ICM configuration was significantly lower for segmental as compared to whole-chromosome aneuploidies (70.8% versus 97.18%, respectively). In order to enhance the clinical utility of reporting segmental findings in clinical TE biopsies, we have developed and clinically verified a risk stratification model based on a second TE biopsy confirmation and segmental length; this model can significantly improve the prediction of aneuploidy risk in the ICM in over 86% of clinical cases enrolled. In conclusion, we provide evidence of the predominant mitotic origin of segmental aneuploidies in preimplantation embryos and develop a risk stratification model that can help post-test genetic counseling and that facilitates the decision-making process on clinical utilization of these embryos.

中文翻译:

人胚节段非整倍性的检测和临床管理的发病率,起源和预测模型。

尽管采用了下一代测序技术,现在可以从体外受精胚胎活组织检查中准确检测节段非整倍体,但这些非整倍体的起源和特征仍然相对未知。使用多焦点活检方法(每个胚泡分析四个滋养外胚层[TEs]和一个内细胞团[ICM]; n = 390),我们确定了非整倍体的起源以及分段性非整倍体检测对ICM的诊断性预测价值。染色体组成。与全染色体非整倍体的普遍减数分裂起源相反,我们表明人胚泡中的亚染色体异常是由约70%的病例中的有丝分裂错误引起的。作为结果,与全染色体非整倍性相比,节段性对ICM构型的阳性预测值要低得多(分别为70.8%和97.18%)。为了增强在临床TE活检中报告节段性检查的临床效用,我们基于第二次TE活检确认和节段长度,开发并临床验证了风险分层模型。在超过86%的临床病例中,该模型可以显着改善ICM中非整倍性风险的预测。总之,我们提供了胚胎植入前节段非整倍体主要有丝分裂来源的证据,并建立了风险分层模型,可以帮助进行遗传测试,并有助于对这些胚胎的临床利用进行决策。分别为8%和97.18%)。为了增强在临床TE活检中报告节段性检查的临床效用,我们基于第二次TE活检确认和节段长度,开发并临床验证了风险分层模型。在超过86%的临床病例中,该模型可以显着改善ICM中非整倍性风险的预测。总之,我们提供了胚胎植入前节段非整倍体主要有丝分裂起源的证据,并建立了风险分层模型,可以帮助进行遗传测试,并有助于对这些胚胎的临床利用进行决策。分别为8%和97.18%)。为了增强在临床TE活检中报告节段性检查的临床效用,我们基于第二次TE活检确认和节段长度,开发并临床验证了风险分层模型。在超过86%的临床病例中,该模型可以显着改善ICM中非整倍性风险的预测。总之,我们提供了胚胎植入前节段非整倍体主要有丝分裂来源的证据,并建立了风险分层模型,可以帮助进行遗传测试,并有助于对这些胚胎的临床利用进行决策。我们基于第二次TE活检确认和节段长度,开发并临床验证了风险分层模型;在超过86%的临床病例中,该模型可以显着改善ICM中非整倍性风险的预测。总之,我们提供了胚胎植入前节段非整倍体主要有丝分裂起源的证据,并建立了风险分层模型,可以帮助进行遗传测试,并有助于对这些胚胎的临床利用进行决策。我们基于第二次TE活检确认和节段长度,开发并临床验证了风险分层模型;在超过86%的临床病例中,该模型可以显着改善ICM中非整倍性风险的预测。总之,我们提供了胚胎植入前节段非整倍体主要有丝分裂来源的证据,并建立了风险分层模型,可以帮助进行遗传测试,并有助于对这些胚胎的临床利用进行决策。
更新日期:2020-04-20
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