Frontiers in Genetics (Jun 2023)

A chromosomal microarray analysis-based laboratory algorithm for the detection of genetic etiology of early pregnancy loss

  • Na Liao,
  • Na Liao,
  • Na Liao,
  • Zhu Zhang,
  • Zhu Zhang,
  • Zhu Zhang,
  • Xijing Liu,
  • Xijing Liu,
  • Xijing Liu,
  • Jiamin Wang,
  • Jiamin Wang,
  • Jiamin Wang,
  • Rui Hu,
  • Rui Hu,
  • Rui Hu,
  • Like Xiao,
  • Like Xiao,
  • Like Xiao,
  • Yunyuan Yang,
  • Yunyuan Yang,
  • Yunyuan Yang,
  • Yi Lai,
  • Yi Lai,
  • Yi Lai,
  • Hongmei Zhu,
  • Hongmei Zhu,
  • Hongmei Zhu,
  • Lingping Li,
  • Lingping Li,
  • Lingping Li,
  • Shanling Liu,
  • Shanling Liu,
  • Shanling Liu,
  • He Wang,
  • He Wang,
  • He Wang,
  • Ting Hu,
  • Ting Hu,
  • Ting Hu

DOI
https://doi.org/10.3389/fgene.2023.1203891
Journal volume & issue
Vol. 14

Abstract

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Background: Chromosomal abnormalities are a major cause of early pregnancy loss. However, models synthesizing existing genetic technologies to improve pregnancy outcomes are lacking. We aim to provide an integrated laboratory algorithm for the genetic etiology of couples who experienced pregnancy loss.Methods: Over a 6-year period, 3,634 products of conception (POCs) following early pregnancy loss were collected. The clinical outcomes from a laboratory algorithm based on single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and parental chromosomal karyotyping assays were comprehensively evaluated.Results: In total, 3,445 of 3,634 (94.8%) POCs had no maternal-cell contamination. Of those POCs, the detection rate of abnormal results was 65.2% (2,247/3,445), of which 91.2% (2,050/2,247) had numerical chromosomal abnormalities, 2.7% (60/2,247) had copy-number variations (CNVs) ≥10 Mb, 2.7% (61/2,247) had CNVs of terminal deletion and duplication, 2.8% (62/2,247) had CNVs <10 Mb, and 0.6% (14/2,247) had uniparental disomy. Furthermore, FISH confirmed 7 of the 60 POCs with mosaic aneuploids below 30% based on the SNP array results as tetraploid. Of the 52 POCs with CNVs of terminal deletion and duplication, 29 couples had balanced rearrangements based on chromosomal karyotyping.Conclusion: The integrated SNP array-based algorithm combined with optional FISH and parental chromosomal karyotyping is an effective laboratory testing strategy, providing a comprehensive and reliable genetic investigation for the etiology of miscarriage, regardless of the number of miscarriages and the method of conception.

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