title: Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta-analysis.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  MEDLINE (from 1996 to December 2012), EMBASE (from 1974 to December 2012), and CINAHL (from 1996 to December 2012) databases were searched electronically.
  
  
  METHODS
  Studies were selected if CMA was used on products of conception following miscarriage, alongside conventional karyotyping.
  
  
  METHODS
  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).
  
  
  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%).
  
  
  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.
authors.affiliation: Academic Department, Birmingham Women's Foundation Trust, Edgbaston, Birminghmam, UK.
authors.forename: R K
authors.initials: RK
authors.lastname: Dhillon
authors.forename: S C
authors.initials: SC
authors.lastname: Hillman
authors.forename: R K
authors.initials: RK
authors.lastname: Morris
authors.forename: D
authors.initials: D
authors.lastname: McMullan
authors.forename: D
authors.initials: D
authors.lastname: Williams
authors.forename: A
authors.initials: A
authors.lastname: Coomarasamy
authors.forename: M D
authors.initials: MD
authors.lastname: Kilby
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics*; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis*; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D006801:Humans; D007621:Karyotyping / Q000379:methods*; D046228:Microarray Analysis / Q000379:methods*; D011247:Pregnancy
keywords: CMA; arrayCGH; karyotyping; microarray; miscarriage