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CC BY 4.0 · Glob Med Genet 2024; 11(01): 123-131
DOI: 10.1055/s-0044-1785227
Original Article

Patterns of Cytogenomic Findings from a Case Series of Recurrent Pregnancy Loss Provide Insight into the Extent of Genetic Defects Causing Miscarriages

Authors

  • Autumn DiAdamo

    1   Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States

  • Hongyan Chai

    1   Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States

  • Mei Ling Chong

    1   Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States

  • Guilin Wang

    1   Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States
    2   Yale Center for Genome Analysis, New Haven, Connecticut, United States

  • Jiadi Wen

    1   Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States

  • Yong-Hui Jiang

    1   Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States
    3   Yale Center for Genomic Health, Yale University School of Medicine, New Haven, Connecticut, United States

  • Peining Li 

    1   Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States
    3   Yale Center for Genomic Health, Yale University School of Medicine, New Haven, Connecticut, United States

Funding This study was partly supported by NIH grant R01 HD105267-01 to Y.-H. J.
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Abstract

Background A retrospective study was performed to evaluate the patterns of cytogenomic findings detected from a case series of products of conception (POC) in recurrent pregnancy loss (RPL) over a 16-year period from 2007 to 2023.

Results This case series of RPL was divided into a single analysis (SA) group of 266 women and a consecutive analysis (CA) group of 225 women with two to three miscarriages analyzed. Of the 269 POC from the SA group and the 469 POC from the CA group, a spectrum of cytogenomic abnormalities of simple aneuploidies, compound aneuploidies, polyploidies, and structural rearrangements/pathogenic copy number variants (pCNVs) were detected in 109 (41%) and 160 cases (34%), five (2%) and 11 cases (2%), 35 (13%) and 36 cases (8%), and 10 (4%) and 19 cases (4%), respectively. Patterns with recurrent normal karyotypes, alternating normal and abnormal karyotypes, and recurrent abnormal karyotypes were detected in 74 (33%), 71 (32%), and 80 (35%) of consecutive miscarriages, respectively. Repeat aneuploidies of monosomy X and trisomy 16, triploidy, and tetraploidy were detected in nine women.

Conclusions A comparable spectrum of cytogenomic abnormalities was noted in the SA and CA groups of RPL. A skewed likelihood of 2/3 for recurrent normal and abnormal karyotypes and 1/3 for alternating normal and abnormal karyotypes in consecutive miscarriages was observed. Routine cytogenetic analysis should be performed for consecutive miscarriages. Further genomic sequencing to search for detrimental and embryonic lethal variants causing miscarriages and pathogenic variants inducing aneuploidies and polyploidies should be considered for RPL with recurrent normal and abnormal karyotypes.

Keywords

recurrent pregnancy loss - products of conception - chromosomal abnormalities - pathogenic copy number variants

Ethics Approval and Informed Consent Statement

This project was categorized as a chart review retrospective case study and deemed exempt from Institutional Review Board (IRB) approval and granted waiver of consent based on the policy of the Yale University IRB.


Data Availability Statement

Data and materials are available from the corresponding author upon request.


Authors' Contribution

P.L. organized this retrospective study and wrote the manuscript. A. D. A. compiled cases from the laboratory database. H.C., M.C., and G.W. performed CMA on POC specimens and reviewed cytogenomic results. J.W. and Y.-H.J. provided scientific insight and reviewed the manuscript.




Publication History

Article published online:
29 March 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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