Comparison of cytogenetics and molecular karyotyping for chromosome testing of miscarriage specimens.

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).

DESIGN

Prospective blinded cohort study.

SETTING

University-based practice.

PATIENT(S): Women undergoing dilation and curettage for first-trimester miscarriage between March 2014 and December 2015.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Chromosome analysis from chorionic villi separated equally and submitted for cytogenetics, SNP microarray, and aCGH testing.

RESULT(S): 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.

CONCLUSION(S): 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.