Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta-analysis

Background Approximately 50% of spontaneous miscarriages are associated with chromosome abnormalities. Identification of these karyotypic abnormalities helps to estimate recurrence risks in future pregnancies. Chromosomal microarray analysis (CMA) is transforming clinical cytogenetic practice with its ability to examine the human genome at increasingly high resolution. Objectives The aim of this study was to determine whether CMA testing on the products of conception following miscarriage provides better diagnostic information compared with conventional karyotyping. Search strategy MEDLINE (from 1996 to December 2012), EMBASE (from 1974 to December 2012), and CINAHL (from 1996 to December 2012) databases were searched electronically. Selection criteria Studies were selected if CMA was used on products of conception following miscarriage, alongside conventional karyotyping. Data collection and analysis Nine papers were included in the systematic review and meta-analysis. All statistical analyses were performed using stata 11.0 (Stata Corp., College Station, TX, USA). Main results There was agreement between CMA and karyotyping in 86.0% of cases (95% CI 77.0–96.0%). CMA detected 13% (95% CI 8.0–21.0) additional chromosome abnormalities over conventional full karyotyping. In addition, traditional, full karyotyping detected 3% (95% CI 1.0–10.0%) additional abnormalities over CMA. The incidence of a variant of unknown significance (VOUS) being detected was 2% (95% CI 1.0–10.0%). Author's conclusions Compared with karyotyping, there appears to be an increased detection rate of chromosomal abnormalities when CMA is used to analyse the products of conception; however, some of these abnormalities are VOUS, and this information should be provided when counselling women following miscarriage and when taking consent for the analysis of miscarriage products by CMA.