M Pauta1, M Grande1, L Rodriguez-Revenga2, E Kolomietz3, A Borrell1. 1. BCNatal Hospital Clínic Barcelona and IDIBAPS, Barcelona, Spain. 2. Biochemistry and Molecular Genetics Department, Hospital Clínic Barcelona and IDIBAPS, Barcelona, Spain. 3. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Abstract
OBJECTIVE: To estimate the increased test success rate and incremental yield of chromosomal microarray analysis (CMA) over conventional karyotyping in detection of pathogenic copy number variants (CNVs) and variants of unknown significance (VOUS) in early pregnancy loss. METHOD: This was a systematic review conducted in accordance with PRISMA criteria. All articles identified in PubMed, Ovid MEDLINE and Web of Science, between January 2000 and April 2017, that described CNVs in early pregnancy losses (up to 20 weeks) were included. Risk differences were pooled to estimate the incremental yield of CMA over karyotyping overall, and after stratification. In addition, test success rate, defined as the proportion of informative results, was compared in series in which CMA and karyotyping were performed concurrently. RESULTS: Twenty-three studies, reporting on 5507 pregnancy losses up to 20 weeks with full data available, met the inclusion criteria for analysis. In the series in which CMA and karyotyping were performed concurrently, CMA showed a significant improvement in success rate, providing informative results in 95% (95% CI, 94-96%) of cases compared with karyotyping in which informative results were provided in 68% (95% CI, 66-70%) of cases. Combined data from reviewed studies revealed that incremental yields of CMA over karyotyping were 2% (95% CI, 1-2%) for pathogenic CNVs and 4% (95% CI, 3-6%) for VOUS. The most common pathogenic CNVs reported were 22q11.21 and 1p36.33 deletion. CONCLUSION: In comparison with conventional karyotyping, CMA provides a significant increase in test success rate and incremental diagnostic yield in early pregnancy loss.
OBJECTIVE: To estimate the increased test success rate and incremental yield of chromosomal microarray analysis (CMA) over conventional karyotyping in detection of pathogenic copy number variants (CNVs) and variants of unknown significance (VOUS) in early pregnancy loss. METHOD: This was a systematic review conducted in accordance with PRISMA criteria. All articles identified in PubMed, Ovid MEDLINE and Web of Science, between January 2000 and April 2017, that described CNVs in early pregnancy losses (up to 20 weeks) were included. Risk differences were pooled to estimate the incremental yield of CMA over karyotyping overall, and after stratification. In addition, test success rate, defined as the proportion of informative results, was compared in series in which CMA and karyotyping were performed concurrently. RESULTS: Twenty-three studies, reporting on 5507 pregnancy losses up to 20 weeks with full data available, met the inclusion criteria for analysis. In the series in which CMA and karyotyping were performed concurrently, CMA showed a significant improvement in success rate, providing informative results in 95% (95% CI, 94-96%) of cases compared with karyotyping in which informative results were provided in 68% (95% CI, 66-70%) of cases. Combined data from reviewed studies revealed that incremental yields of CMA over karyotyping were 2% (95% CI, 1-2%) for pathogenic CNVs and 4% (95% CI, 3-6%) for VOUS. The most common pathogenic CNVs reported were 22q11.21 and 1p36.33 deletion. CONCLUSION: In comparison with conventional karyotyping, CMA provides a significant increase in test success rate and incremental diagnostic yield in early pregnancy loss.