title: Efficient and cost-effective genetic analysis of products of conception and fetal tissues using a QF-PCR/array CGH strategy; five years of data.
abstract: BACKGROUND
  Traditional testing of miscarriage products involved culture of tissue followed by G-banded chromosome analysis; this approach has a high failure rate, is labour intensive and has a resolution of around 10 Mb. G-banded chromosome analysis has been replaced by molecular techniques in some laboratories; we previously introduced a QF-PCR/MLPA testing strategy in 2007. To improve diagnostic yield and efficiency we have now updated our testing strategy to a more comprehensive QF-PCR assay followed by array CGH. Here we describe the results from the last 5 years of service.
  
  
  METHODS
  Fetal tissue samples and products of conception were tested using QF-PCR which will detect aneuploidy for chromosomes 13, 14, 15, 16, 18, 21, 22, X and Y. Samples that were normal were then tested by aCGH and all imbalance >1Mb and fully penetrant clinically significant imbalance <1Mb was reported.
  
  
  RESULTS
  QF-PCR analysis identified aneuploidy/triploidy in 25.6% of samples. aCGH analysis detected imbalance in a further 9.6% of samples; this included 1.8% with submicroscopic imbalance and 0.5% of uncertain clinical significance. This approach has a failure rate of 1.4%, compared to 30% for G-banded chromosome analysis.
  
  
  CONCLUSIONS
  This efficient QF-PCR/aCGH strategy has a lower failure rate and higher diagnostic yield than karyotype or MLPA strategies; both findings are welcome developments for couples with recurrent miscarriage.
authors.affiliation: Genetics Department, Viapath Analytics, Guy's Hospital, London, SE1 9RT UK.
authors.forename: Celia
authors.identifier: 0000-0001-5484-1559
authors.initials: C
authors.lastname: Donaghue
authors.affiliation: Genetics Department, Viapath Analytics, Guy's Hospital, London, SE1 9RT UK.
authors.forename: Nada
authors.initials: N
authors.lastname: Davies
authors.affiliation: Genetics Department, Guys and St Thomas NHS Foundation Trust, London, SE1 9RT UK.
authors.forename: Joo Wook
authors.initials: JW
authors.lastname: Ahn
authors.affiliation: Genetics Department, Viapath Analytics, Guy's Hospital, London, SE1 9RT UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Thomas
authors.affiliation: Genetics Department, Guys and St Thomas NHS Foundation Trust, London, SE1 9RT UK.
authors.forename: Caroline Mackie
authors.initials: CM
authors.lastname: Ogilvie
authors.affiliation: Genetics Department, Viapath Analytics, Guy's Hospital, London, SE1 9RT UK.
authors.forename: Kathy
authors.initials: K
authors.lastname: Mann
keywords: Aneuploidy; Fetal tissue; Miscarriage; Products of conception; QF-PCR; aCGH