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. 2020 Oct 20:11:545856.
doi: 10.3389/fgene.2020.545856. eCollection 2020.

Analysis of Chromosomal Copy Number in First-Trimester Pregnancy Loss Using Next-Generation Sequencing

Lei Fan  1 , Jianli Wu  1 , Yuanyuan Wu  1 , Xinwei Shi  1 , Xing Xin  1 , Shufang Li  1 , Wanjiang Zeng  1 , Dongrui Deng  1 , Ling Feng  1 , Suhua Chen  1 , Juan Xiao  1
Affiliations

Analysis of Chromosomal Copy Number in First-Trimester Pregnancy Loss Using Next-Generation Sequencing

Lei Fan et al. Front Genet. .

Abstract

Embryonic chromosomal abnormality is one of the significant causative factors of early pregnancy loss. Our goal was to evaluate the clinical utility of next-generation sequencing (NGS) technology in identifying chromosomal anomalies associated with first-trimester pregnancy loss. In addition, we attempted to provide fertility guidance to couples anticipating a successful pregnancy. A total of 1,010 miscarriage specimens were collected between March 2016 and January 2019 from women who suffered first-trimester pregnancy loss. Total DNA was isolated from products of conception, and NGS analysis was carried out. We detected a total of 634 cases of chromosomal variants. Among the 634 cases, 462 (72.9%) displayed numerical variants including 383 (60.4%) aneuploidies, 44 (6.9%) polyploidies, and 34 (5.5%) mosaicisms. The other 172 (27.1%) cases showed structural variants including 19 (3.0%) benign copy number variations (CNVs), 52 (8.2%) pathogenic CNVs, and 101 (16%) variants of unknown significance (VOUS) CNVs. When maternal age was ≥ 35 years, the sporadic abortion (SA) group showed an increased frequency of chromosomal variants in comparison with the recurrent miscarriage (RM) group (90/121 vs. 64/104). It was evident that the groups with advanced maternal age had a sharply increased frequency of aneuploidy, whatever the frequency of pregnancy loss (71/121 vs. 155/432, 49/104 vs. 108/349). Our data suggest that NGS could be used for the successful detection of genetic anomalies in pregnancy loss. We recommend that fetal chromosome analysis be offered routinely for all pregnancy losses, regardless of their frequency.

Keywords: chorionic villi; copy number variation; fetal chromosomal abnormality; first-trimester pregnancy loss; next generation sequencing.

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Figures

FIGURE 1
FIGURE 1
Flowchart depicting the details of samples analyzed in this study and summary of the characterized chromosomal copy number variations (CNVs). VOUS, variants of unknown significance.
FIGURE 2
FIGURE 2
The type and number of cases of chromosomal anomalies. *, The possible cause of pregnancy loss; #, not the possible cause of pregnency loss.
FIGURE 3
FIGURE 3
The distribution and frequencies of chromosomal aneuploidies. (A) Frequency of aneuploidies in patients with spontaneous and recurrent miscarriage. (B) Frequency of aneuploidy in patients of younger (<35 years) and advanced (≥35 years) maternal age. SA, sporadic abortion; RM, recurrent miscarriage.
FIGURE 4
FIGURE 4
The number and percentage of cases with different sizes of pathogenic deletion/duplication.
See this image and copyright information in PMC

References

    1. Bell K. A., Van Deerlin P. G., Feinberg R. F., du Manoir S., Haddad B. R. (2001). Diagnosis of aneuploidy in archival, paraffin-embedded pregnancy-loss tissues by comparative genomic hybridization. Fertil. Steril. 75 374–379. - PubMed
    1. Carp H., Guetta E., Dorf H., Soriano D., Barkai G., Schiff E. (2006). Embryonic karyotype in recurrent miscarriage with parental karyotypic aberrations. Fertil. Steril. 85 446–450. 10.1016/j.fertnstert.2005.07.1305 - DOI - PubMed
    1. Carp H., Toder V., Aviram A., Daniely M., Mashiach S., Barkai G. (2001). Karyotype of the abortus in recurrent miscarriage. Fertil. Steril. 75 678–682. - PubMed
    1. Choi T. Y., Lee H. M., Park W. K., Jeong S. Y., Moon H. S. (2014). Spontaneous abortion and recurrent miscarriage: a comparison of cytogenetic diagnosis in 250 cases. Obstet. Gynecol. Sci. 57 518–525. 10.5468/ogs.2014.57.6.518 - DOI - PMC - PubMed
    1. Dong Z., Zhang J., Hu P., Chen H., Xu J., Tian Q., et al. (2016). Low-pass whole-genome sequencing in clinical cytogenetics: a validated approach. Genet. Med. 18 940–948. 10.1038/gim.2015.199 - DOI - PubMed

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