title: Comparison of cytogenetics and molecular karyotyping for chromosome testing of miscarriage specimens.
abstract: OBJECTIVE
  To compare chromosome testing of miscarriage specimens between traditional cytogenetic analysis and molecular karyotyping using single nucleotide polymorphism microarrays (SNP) and array comparative genomic hybridization (aCGH).
  
  
  METHODS
  Prospective blinded cohort study.
  
  
  METHODS
  University-based practice.
  
  
  METHODS
  Women undergoing dilation and curettage for first-trimester miscarriage between March 2014 and December 2015.
  
  
  METHODS
  None.
  
  
  METHODS
  Chromosome analysis from chorionic villi separated equally and submitted for cytogenetics, SNP microarray, and aCGH testing.
  
  
  RESULTS
  Sixty samples were analyzed, of which 47 (78%) were chromosomally abnormal. A correct call was defined when a result was concordant with at least one other testing platform. The correct call rate was 85%, 93%, and 85% using cytogenetics, SNP array, and aCGH, respectively. We found a 33% overall discordance rate between results. Discordances were due to maternal cell contamination, balanced chromosome rearrangements, polyploidy, and placental mosaicism. Mosaicism was detected in 18% of all samples. Growth failure occurred in four samples sent to cytogenetics, of which three were chromosomally abnormal by molecular testing.
  
  
  CONCLUSIONS
  This study demonstrates the many technical limitations of the three testing modalities. Our rates of maternal cell contamination were low, but it is important to note that this is a commonly reported limitation of cytogenetics. Given the similar overall performance of the three testing modalities, providers may choose a method based on individual availability and consideration of limitations as it applies to each clinical scenario. The unexpected high rate of placental mosaicism warrants further investigation.
authors.affiliation: Stanford University Reproductive Health and Fertility Center, Palo Alto, California. Electronic address: shahm@stanford.edu.
authors.forename: Meera Sridhar
authors.initials: MS
authors.lastname: Shah
authors.affiliation: Ivigen, Inc., Miami, Florida.
authors.forename: Cengiz
authors.initials: C
authors.lastname: Cinnioglu
authors.affiliation: Natera, Inc., San Carlos, California.
authors.forename: Melissa
authors.initials: M
authors.lastname: Maisenbacher
authors.affiliation: Stanford University Reproductive Health and Fertility Center, Palo Alto, California.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Comstock
authors.affiliation: Stanford University Reproductive Health and Fertility Center, Palo Alto, California.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kort
authors.affiliation: Stanford University Reproductive Health and Fertility Center, Palo Alto, California.
authors.forename: Ruth Bunker
authors.initials: RB
authors.lastname: Lathi
mesh_terms: D000022:Abortion, Spontaneous / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D000046:Academic Medical Centers; D000328:Adult; D002869:Chromosome Aberrations; D002877:Chromosomes, Human; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D004107:Dilatation and Curettage; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D059785:Karyotype; D007621:Karyotyping; D008875:Middle Aged; D009030:Mosaicism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies
keywords: Chromosome analysis; cytogenetics; miscarriage; molecular karyotype analysis