Genomic imbalance in products of conception: single-nucleotide polymorphism chromosomal microarray analysis

Area of Science:

• Reproductive genetics
• Cytogenomics
• Prenatal diagnostics

Background:

• Miscarriage is a common pregnancy complication.
• Accurate cytogenomic analysis of products-of-conception is crucial for understanding causes.
• Traditional methods may miss certain genetic abnormalities.

Purpose of the Study:

• To analyze a large cohort of miscarriage samples using high-resolution single-nucleotide polymorphism (SNP) chromosomal microarray.
• To identify all detectable anomalies, including submicroscopic imbalances.
• To assess the utility of SNP arrays in detecting maternal cell contamination, triploidy, and uniparental disomy.

Main Methods:

• Cytogenomic analysis of 2,389 postmiscarriage products-of-conception specimens.
• High-resolution SNP-based chromosomal microarray platform.
• Evaluation for cytogenetic, microscopic (>10 Mb), and submicroscopic (<10 Mb) abnormalities.
• Assessment of maternal cell contamination using SNP data.

Main Results:

• A high success rate (99.9%) was achieved.
• Maternal cell contamination was detected in 22.0% of specimens.
• Of true fetal samples, 59.4% had classical cytogenetic abnormalities (aneuploidy, triploidy, structural anomalies).
• SNP microarray identified clinically significant copy number changes (1.6%) or uniparental disomy (0.4%) in cases normal at the cytogenetic level.

Conclusions:

• Chromosomal microarray analysis provides a high diagnostic yield for miscarriage specimens.
• SNP arrays enhance the detection of genomic abnormalities and confirm true fetal origin.
• SNP chromosomal microarray analysis is recommended for cytogenomic evaluation of miscarriage when clinically indicated.