Reliability of 46,XX results on miscarriage specimens: a review of 1,222 first-trimester miscarriage specimens.

OBJECTIVE: To examine the rate of maternal contamination in miscarriage specimens. DESIGN: Retrospective review of 1,222 miscarriage specimens submitted for chromosome testing with detection of maternal cell contamination (MCC). SETTING: Referral centers requesting genetic testing of miscarriage specimens at a single reference laboratory. PATIENT(S): Women with pregnancy loss who desire complete chromosome analysis of the pregnancy tissue. INTERVENTION(S): Analysis of miscarriage specimens using single-nucleotide polymorphism (SNP) microarray technology with bioinformatics program to detect maternal cell contamination. MAIN OUTCOME MEASURE(S): Chromosome content of miscarriages and incidence of 46,XX results due to MCC. RESULT(S): Of the 1,222 samples analyzed, 592 had numeric chromosomal abnormalities, and 630 were normal 46,XX or 46,XY (456 and 187, respectively). In 269 of the 46,XX specimens, MCC with no embryonic component was found. With the exclusion of maternal 46,XX results, the chromosomal abnormality rate increased from 48% to 62%, and the ratio for XX to XY results dropped from 2.6 to 1.0. CONCLUSION(S): Over half of the normal 46,XX results in miscarriage specimens were due to MCC. The use of SNPs in MCC testing allows for precise identification of chromosomal abnormalities in miscarriage as well as MCC, improving the accuracy of products of conception testing.

Genomic imbalance in products of conception: single-nucleotide polymorphism chromosomal microarray analysis.

OBJECTIVE: To report the full cohort of identifiable anomalies, regardless of known clinical significance, in a large-scale cohort of postmiscarriage products-of-conception samples analyzed using a high-resolution single-nucleotide polymorphism (SNP)-based microarray platform. High-resolution chromosomal microarray analysis allows for the identification of visible and submicroscopic cytogenomic imbalances; the specific use of SNPs permits detection of maternal cell contamination, triploidy, and uniparental disomy. METHODS: Miscarriage specimens were sent to a single laboratory for cytogenomic analysis. Chromosomal microarray analysis was performed using a SNP-based genotyping microarray platform. Results were evaluated at the cytogenetic and microscopic (greater than 10 Mb) and submicroscopic (less than 10 Mb) levels. Maternal cell contamination was assessed using information derived from fetal and maternal SNPs. RESULTS: Results were obtained on 2,389 of 2,392 specimens (99.9%) that were less than 20 weeks of gestation. Maternal cell contamination was identified in 528 (22.0%) specimens. The remaining 1,861 specimens were considered to be of true fetal origin. Of these, 1,106 (59.4%) showed classical cytogenetic abnormalities: aneuploidy accounted for 945 (85.4%), triploidy for 114 (10.3%), and structural anomalies or tetraploidy for the remaining 47 (4.2%). Of the 755 (40.6%) cases considered normal at the cytogenetic level, SNP chromosomal microarray analysis revealed a clinically significant copy number change or whole-genome uniparental disomy in 12 (1.6%) and three (0.4%) cases, respectively. CONCLUSION: Chromosomal microarray analysis of products-of-conception specimens yields a high diagnostic return. Using SNPs extends the scope of detectable genomic abnormalities and facilitates reporting "true" fetal results. This supports the use of SNP chromosomal microarray analysis for cytogenomic evaluation of miscarriage specimens when clinically indicated. LEVEL OF EVIDENCE: III.