Chromosomal microarray analysis in pregnancy loss: Is it time for a consensus approach?

Abstract

OBJECTIVE: To investigate the efficacy and outcomes of chromosomal microarray (CMA) in the cytogenomic evaluation of products of conception (POC). METHOD: Over a 42-month period, 323 POC samples were tested by CMA. Results were assessed using variables including phenotype, gestational age, results from orthogonal testing, and follow-up parental analysis. RESULTS: CMA identified cytogenetic abnormalities in 47.4% of first trimester losses and 10.9% of second and third trimester losses. Chromosomal microarray results specifically from 5 to 7-week losses showed similar rates of abnormalities (45.6%) compared to those of all first trimester losses combined. CMA and karyotype results were discordant in 20.0% of cases, most likely due to maternal cell overgrowth in culture. The most prevalent abnormalities identified in all losses were autosomal trisomies, followed by triploidy. In 43/323 cases, the observed abnormality suggested a parental aberration that prompted follow-up studies; two of these cases indeed identified an inherited aberration. CONCLUSION: Our findings of specific types of genetic abnormalities and the respective frequencies by gestational age closely align with those of published karyotype studies, supporting the use of routine CMA testing for POCs. CMA outperforms karyotype analysis because it does not require viable, sterile cultures free of maternal admixture or admixture due to multiple gestations. Finally, CMA results can play an important role in identifying increased recurrence risks for some couples.