Pregnancy Loss Testing (CMA)
Patients who have experienced a miscarriage often want to know the reason for their loss. For families seeking answers, Pacific Rim Pathology’s CMA provides an improved alternative to traditional methods.
Chromosomal Microarray (CMA) testing can help patients to:
- Know whether the miscarriage was due to a chromosomal abnormality
- Learn whether there is an increased risk for future pregnancies
- Work through the grieving process by answering the question “Why?”
Indications for use of CMA:
Intrauterine fetal demise or stillbirth
Pregnancy loss or termination in the presence of fetal abnormalities
Recurrent fetal losses of unknown etiology
CMA detects a wide range of chromosome abnormalities
- Whole-chromosome aneuploidy
- Aneuploidy is the presence of an abnormal number of chromosomes in a cell, such as having 45 or 47 chromosomes when 46 is normal. An extra or missing chromosome is a common cause of genetic disorders such as Down Syndrome, and also some human birth defects.
- Molar Pregnancy
- Complete molar pregnancy. An egg with no genetic information is fertilized by a sperm. It does not develop into a fetus but continues to grow as a mass of abnormal tissue that looks a bit like a cluster of grapes and can fill the uterus.
- Partial molar pregnancy. An egg is fertilized by two sperm. The placenta develops abnormally. Any fetal tissue that forms is likely to have severe defects.
- Triploidy means that a baby has three copies of each chromosome in each cell rather than two, making a total of 69 (instead of the normal 46) chromosomes.
- Deletions and Duplications
- DNA segments that are deleted or duplicated can cause abnormalities which might lead to pregnancy loss.
- Parental origin of abnormality
- Abnormal results might be followed up by investigating the parents to see if the abnormality is de novo (occurs in the fetus only) or inherited.
- Consanguinity and Uniparental Disomy (UPD)
- Long contiguous DNA segments of homozygosity can indicate shared ancestry.
- Uniparental disomy refers to the situation in which two copies of a chromosome come from the same parent, instead of one copy coming from the mother, and one copy coming from the father.
- Maternal cell contamination (MCC)
- MCC is bioinformatically detected down to 20%. MCC above 20% will fail the test at the Quality Control step to prevent false negative diagnoses. MCC below 20% does not interfere with the results.
Advantages of Chromsomal Microarray Analysis (CMA) over Karyotyping (Conventional chromosome analysis)
- CMA does not require cell culture
- Microarray analysis provides results in approximately 95% of cases, compared to a 45-75% success rate with conventional karyotyping.
- Culture failure (due to lack of growth of placental or fetal cells) is not a factor
- Between 25-55% of the time, cell culture fails and no result is obtained (Lomax et al., 2000; Bell et al., 1999; Robberect et al., 2009)
- The frustration of waiting for three weeks only to learn of a failed cell culture is upsetting to patients and their families.
- Specimen prep requires less labor
- Decreases time required for testing
5-10 day test result turnaround time allows for faster follow up care.
- CMA involves the use of a standardized computerized analysis.
- In contrast, Karyotyping involves microscopic examination of stained chromosomes, and thus is subject to human error. (ACOG, 2013; Babkina, 2014).
- CMA has a significantly higher resolution than karyotyping (200 kilobase pairs vs. 5 megabase pairs) and is able to identify submicroscopic abnormalities such as microdeletions or gene duplications.
- CMA can determine uniparental or bi-parental origin of the chromosome segments enabling diagnosis of UPD and consanguinity which might be the reason for the pregnancy loss.
- Spontaneous pregnancy loss: CMA uncovered an additional 9.8% abnormal test results with clinical relevance vs karyotyping.
- Stillbirths: CMA uncovered an additional 13% abnormal test results in prior normal or unobtainable karyotypes (Raca, G., A. Artzer, et al. (2009). “Array-based comparative genomic hybridization (aCGH) in the genetic evaluation of stillbirth.” Am J Med Genet A 149A(11): 2437-43)
Types of Test Results
There are typically three types of microarray analysis test results:
Normal: A normal test result means that microarray testing did not detect any chromosomal abnormalities at the 200KB resolution level.
Abnormal: An abnormal test result means that microarray testing did detect extra or missing chromosomal information. If your test result is abnormal, your doctor will provide more specific information about the abnormality detected and whether genetic studies on you and your partner are recommended.
Variant of Uncertain Significance (VOUS ): A VOUS result means that chromosomal microarray testing identified extra or missing genetic information but that this change is not well understood or is very rare. In this situation, it is not possible to determine with certainty whether the change to the chromosomal information was the cause of the miscarriage.
ACOG (American Congress of Obstetricians and Gynecologists) also states that genetic testing should always be preceded and followed by genetic counseling. Genetic counseling typically includes, but is not necessarily limited to, a description of the test methodology; the objective of the test; risks, benefits, and limitations of testing. Post-test counseling for a positive test (a conclusive diagnosis) may include a review of the family history, and a discussion of considering testing of at-risk family members. Genetic counseling may also include a discussion of the potential to identify findings of uncertain significance, consanguinity, and adult-onset disease (ACOG, 2013).
Pregnancy Loss Testing Physician Brochure
POC Specimen Collection and Handling Information Sheet_rev7