Pregnancy Loss Microarray

Clinical Information

Pregnancy loss occurs in up to 15% of all recognized pregnancies. In approximately half of these cases, the loss can be attributed to the presence of one or more chromosome abnormalities. The pregnancy loss microarray is performed using the Illumina Diversity Array + Cytogenetics (GDA+Cyto) Microarray system. This analysis can detect the following abnormalities:

• Aneuploidy
• Mosaicism as low as 20%
• Common microdeletion and microduplication syndromes
• Interstitial and terminal chromosome deletions and duplications greater than 300 kb
• Loss of heterozygosity and suspected uniparental disomy (UPD)

If a maternal sample is also sent to the laboratory, maternal cell contamination can be detected, and the parent of origin for uniparental isodisomy can be determined.

Technical Information

Isolated DNA is analyzed using the Illumina Diversity Array + cytogenetic (GDA+Cyto) Microarray system. This diagnostic assay identifies genomic copy number variations and loss of heterozygosity regions. VIA software (BioNano Genomics) is utilized in data analysis. SNP genotyping on this platform has the enhanced ability to identify long contiguous stretches of homozygosity (LCSH) and uniparental disomy; however, this assay cannot detect polyploidy, balanced rearrangements, point mutations, and most mosaic conditions. All copy number changes are determined using the human genome build 38 (hg38/GRCh38).

Copy number variants are reported according to the most recent International System for Human Cytogenetic Nomenclature (ISCN) guidelines. CNV classification is based on the guidelines recommended by the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resources (ClinGen). Reportable variants include pathogenic variants, likely pathogenic variants, and variants of uncertain significance. Likely benign and benign variants are not routinely reported.

Specimen Requirements

Products of Conception: Using a sterile technique, obtain POC and place in a sterile transport container with tissue transport media or a sterile solution such as a balanced salt solution. DO NOT allow the specimen to come into contact with formalin or other fixatives if chromosome analysis is ordered as fixed tissue not grow for chromosome analysis. Chromosome analysis cannot be performed on FFPE samples.

Fresh tissue: Using sterile technique, obtain a 5 mm biopsy of unmacerated fetal tissue and place in tube containing transport media. If tissue culture media is not available, sterile solutions such as balanced salt solution may be used. The preferred placental tissues are fetal membranes or chorionic villi. If fetal samples are obtained at autopsy, lung, gonad or thymus are preferred for chromosome study.

Cultured tissue: 2-T25 confluent flasks can be sent for analysis.

A maternal sample is recommended to accompany the prenatal specimen for maternal cell contamination (MCC) studies. The preferred maternal sample type for MCC is 3-4ml of peripheral blood collected in an EDTA (purple top) tube. Additional accepted maternal sample types include extracted DNA or saliva.
Send approximately 5µg of extracted DNA at requested concentration of 90-130ng/µl.
Saliva samples must be submitted in an approved saliva kit.
Blood and saliva kits are available by request.

Transport Instructions

POC: The specimen should kept at room temperature if transported immediately. If the specimen is not being immediately transported to the laboratory, it may be refrigerated. Do no freeze. The sample should be sent by courier or overnight shipping to arrive at the laboratory within 24 hours.

Fresh tissue: The specimen should kept at room temperature if transported immediately. If the specimen is not being immediately transported to the laboratory, it may be refrigerated. Do no freeze. The sample should be sent by courier or overnight shipping to arrive at the laboratory within 24 hours.

Cultured tissue: The specimen should kept at room temperature if transported immediately. If the specimen is not being immediately transported to the laboratory, it may be refrigerated. Do no freeze. The sample should be sent by courier or overnight shipping to arrive at the laboratory within 24 hours.

Blood specimens should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

Extracted DNA can be sent at room temperature via overnight delivery.

Saliva is stable at room temperature and can be delivered overnight or ground shipping.