Juno Genetics offers a test that sheds light on the cause of miscarriage. The test examines chromosomes in cells from the embryo/fetus or associated tissues, called products of conception (POC).
Miscarriage can affect 10-40% of pregnancies, depending on female age. An incorrect number of chromosomes, known as ‘aneuploidy’, is the most common cause of miscarriage and may explain two-thirds to three quarters of all pregnancy losses.
In order to help clarify whether aneuploidy is likely to have contributed to a miscarriage, Juno Genetics offers a test that assesses cells from the embryo/fetus or associated extraembryonic tissues (e.g. placenta). This material is collectively referred to as products of conception (POC).
Testing of POC potentially provides useful information for any couples who have experienced a pregnancy loss, but may be particularly valuable for those with any of the following: a history of several miscarriages; an abnormal ultrasound prior to a lost pregnancy; a fetus affected by intrauterine growth retardation; an abnormal prenatal test result; a pregnancy loss after IVF.
Traditional methods for examining chromosomes in POC samples have several problems. Cells have to be grown in the lab, which takes time, delaying results. Additionally, a significant number of POC samples fail to grow and therefore no result can be obtained. On other occasions, cells from the mother are present in the POC sample and outgrow the embryo/fetal cells, so that the final result obtained reflects the cells of the mother (normal female) rather than the cells of the embryo/fetus. This leads to unreliable results in about 20% of traditional POC tests.
The method of analysing POC samples used by Juno Genetics does not suffer from these problems because it avoids the need to grow cells in the lab. Furthermore, Juno Genetics carries out an extra genetic test to confirm that the cells tested are from the embryo/fetus and not from the mother.
A POC sample and a maternal blood sample are collected using the kit supplied by Juno Genetics.
Genetic material (DNA) is extracted from each of these samples and subjected to a technique known as Next Generation Sequencing (NGS). NGS allows hundreds of thousands of pieces of DNA to be examined in each sample. Reading the sequence of each of these DNA fragments reveals the chromosome that the piece came from and, by counting the number of DNA fragments from each chromosome, it is possible to deduce the number of chromosomes with very high accuracy.
The presence of an extra chromosome in a POC sample, leading to a condition known as trisomy, is seen as an increase in the number of DNA fragments derived from the affected chromosome
On the other hand, having a chromosome missing, a condition known as a monosomy, is associated with fewer pieces of DNA from the affected chromosome.
The unique NGS method used for the analysis of POC by Juno Genetics is one of the most advanced available. Combining next-generation sequencing, to measure the amount of DNA from each chromosome, and DNA fingerprint analysis, to rule out maternal contamination, results in accuracy exceeding 95%. Not only are abnormalities affecting single chromosomes detected, but also conditions affecting the entire chromosome set, such as triploidy which affects 2-3% of pregnancies and is responsible for 15-18% of miscarriages. Losses and duplications of pieces of chromosome (>18Mb) are also detectable.
POC analysis using NGS is not able to detect all chromosome abnormalities. For example, the method may not detect deletion or duplication involving pieces of chromosome less than approximately 18 Mb in size, microdeletion syndromes, some forms of tetraploidy, or balanced structural chromosome rearrangements (such as translocations and inversions). Low levels of mosaicism (<30% of cells affected by aneuploidy) may also go undetected. If an aneuploidy is found, it is likely to have been the cause of the miscarriage, although it should be recognised that some pregnancy losses might have other contributory factors.
POC results are typically available 6 days after Juno receives the maternal blood and POC samples (although up to 10 days may be required).