Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays

outcomes, benefits, and challenges

Trilochan Sahoo, Natasa Dzidic, Michelle N. Strecker, Sara Commander, Mary K. Travis, Charles Doherty, R. Weslie Tyson, Arturo E. Mendoza, Mary Stephenson, Craig A. Dise, Carlos Benito, Mandolin S. Ziadie, Karine Hovanes

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Purpose:Chromosomal microarray analysis (CMA) is currently considered first-tier testing in pediatric care and prenatal diagnosis owing to its high diagnostic sensitivity for chromosomal imbalances. The aim of this study was to determine the efficacy and diagnostic power of CMA in both fresh and formalin-fixed paraffin-embedded (FFPE) samples of products of conception (POCs).Methods:Over a 44-month period, 8,118 consecutive samples were received by our laboratory for CMA analysis. This included both fresh (76.4%) and FFPE samples (22.4%), most of which were ascertained for recurrent pregnancy loss and/or spontaneous abortion (83%). The majority of samples were evaluated by a whole-genome single-nucleotide polymorphism (SNP)-based array (81.6%); the remaining samples were evaluated by array-comparative genomic hybridization (CGH).Results:A successful result was obtained in 7,396 of 8,118 (91.1%), with 92.4% of fresh tissue samples and 86.4% of FFPE samples successfully analyzed. Clinically significant abnormalities were identified in 53.7% of specimens (3,975 of 7,396), 94% of which were considered causative.Conclusion:Analysis of POC specimens by karyotyping fails in 20-40% of cases. SNP-based CMA is a robust platform, with successful results obtained in >90% of cases. SNP-based CMA can identify aneuploidy, polyploidy, whole-genome homozygosity, segmental genomic imbalances, and maternal cell contamination, thus maximizing sensitivity and decreasing false-negative results. Understanding the etiology of fetal loss enables clarification of recurrence risk and assists in determining appropriate management for future family planning.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalGenetics in Medicine
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2017

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Microarray Analysis
Pregnancy
Paraffin
Formaldehyde
Single Nucleotide Polymorphism
Genome
Karyotyping
Polyploidy
Comparative Genomic Hybridization
Family Planning Services
Aneuploidy
Spontaneous Abortion
Prenatal Diagnosis
Mothers
Pediatrics
Recurrence

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)

Cite this

Sahoo, T., Dzidic, N., Strecker, M. N., Commander, S., Travis, M. K., Doherty, C., ... Hovanes, K. (2017). Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges. Genetics in Medicine, 19(1), 83-89. https://doi.org/10.1038/gim.2016.69
Sahoo, Trilochan ; Dzidic, Natasa ; Strecker, Michelle N. ; Commander, Sara ; Travis, Mary K. ; Doherty, Charles ; Weslie Tyson, R. ; Mendoza, Arturo E. ; Stephenson, Mary ; Dise, Craig A. ; Benito, Carlos ; Ziadie, Mandolin S. ; Hovanes, Karine. / Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays : outcomes, benefits, and challenges. In: Genetics in Medicine. 2017 ; Vol. 19, No. 1. pp. 83-89.
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abstract = "Purpose:Chromosomal microarray analysis (CMA) is currently considered first-tier testing in pediatric care and prenatal diagnosis owing to its high diagnostic sensitivity for chromosomal imbalances. The aim of this study was to determine the efficacy and diagnostic power of CMA in both fresh and formalin-fixed paraffin-embedded (FFPE) samples of products of conception (POCs).Methods:Over a 44-month period, 8,118 consecutive samples were received by our laboratory for CMA analysis. This included both fresh (76.4{\%}) and FFPE samples (22.4{\%}), most of which were ascertained for recurrent pregnancy loss and/or spontaneous abortion (83{\%}). The majority of samples were evaluated by a whole-genome single-nucleotide polymorphism (SNP)-based array (81.6{\%}); the remaining samples were evaluated by array-comparative genomic hybridization (CGH).Results:A successful result was obtained in 7,396 of 8,118 (91.1{\%}), with 92.4{\%} of fresh tissue samples and 86.4{\%} of FFPE samples successfully analyzed. Clinically significant abnormalities were identified in 53.7{\%} of specimens (3,975 of 7,396), 94{\%} of which were considered causative.Conclusion:Analysis of POC specimens by karyotyping fails in 20-40{\%} of cases. SNP-based CMA is a robust platform, with successful results obtained in >90{\%} of cases. SNP-based CMA can identify aneuploidy, polyploidy, whole-genome homozygosity, segmental genomic imbalances, and maternal cell contamination, thus maximizing sensitivity and decreasing false-negative results. Understanding the etiology of fetal loss enables clarification of recurrence risk and assists in determining appropriate management for future family planning.",
author = "Trilochan Sahoo and Natasa Dzidic and Strecker, {Michelle N.} and Sara Commander and Travis, {Mary K.} and Charles Doherty and {Weslie Tyson}, R. and Mendoza, {Arturo E.} and Mary Stephenson and Dise, {Craig A.} and Carlos Benito and Ziadie, {Mandolin S.} and Karine Hovanes",
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Sahoo, T, Dzidic, N, Strecker, MN, Commander, S, Travis, MK, Doherty, C, Weslie Tyson, R, Mendoza, AE, Stephenson, M, Dise, CA, Benito, C, Ziadie, MS & Hovanes, K 2017, 'Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges', Genetics in Medicine, vol. 19, no. 1, pp. 83-89. https://doi.org/10.1038/gim.2016.69

Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays : outcomes, benefits, and challenges. / Sahoo, Trilochan; Dzidic, Natasa; Strecker, Michelle N.; Commander, Sara; Travis, Mary K.; Doherty, Charles; Weslie Tyson, R.; Mendoza, Arturo E.; Stephenson, Mary; Dise, Craig A.; Benito, Carlos; Ziadie, Mandolin S.; Hovanes, Karine.

In: Genetics in Medicine, Vol. 19, No. 1, 01.01.2017, p. 83-89.

Research output: Contribution to journalArticle

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T1 - Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays

T2 - outcomes, benefits, and challenges

AU - Sahoo, Trilochan

AU - Dzidic, Natasa

AU - Strecker, Michelle N.

AU - Commander, Sara

AU - Travis, Mary K.

AU - Doherty, Charles

AU - Weslie Tyson, R.

AU - Mendoza, Arturo E.

AU - Stephenson, Mary

AU - Dise, Craig A.

AU - Benito, Carlos

AU - Ziadie, Mandolin S.

AU - Hovanes, Karine

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Purpose:Chromosomal microarray analysis (CMA) is currently considered first-tier testing in pediatric care and prenatal diagnosis owing to its high diagnostic sensitivity for chromosomal imbalances. The aim of this study was to determine the efficacy and diagnostic power of CMA in both fresh and formalin-fixed paraffin-embedded (FFPE) samples of products of conception (POCs).Methods:Over a 44-month period, 8,118 consecutive samples were received by our laboratory for CMA analysis. This included both fresh (76.4%) and FFPE samples (22.4%), most of which were ascertained for recurrent pregnancy loss and/or spontaneous abortion (83%). The majority of samples were evaluated by a whole-genome single-nucleotide polymorphism (SNP)-based array (81.6%); the remaining samples were evaluated by array-comparative genomic hybridization (CGH).Results:A successful result was obtained in 7,396 of 8,118 (91.1%), with 92.4% of fresh tissue samples and 86.4% of FFPE samples successfully analyzed. Clinically significant abnormalities were identified in 53.7% of specimens (3,975 of 7,396), 94% of which were considered causative.Conclusion:Analysis of POC specimens by karyotyping fails in 20-40% of cases. SNP-based CMA is a robust platform, with successful results obtained in >90% of cases. SNP-based CMA can identify aneuploidy, polyploidy, whole-genome homozygosity, segmental genomic imbalances, and maternal cell contamination, thus maximizing sensitivity and decreasing false-negative results. Understanding the etiology of fetal loss enables clarification of recurrence risk and assists in determining appropriate management for future family planning.

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