When There is No Result

Why do some Harmony Prenatal Tests not provide a result?

Our commitment to quality means that we will only provide a result when there is very clear evidence for, or against, the presence of a specific condition. The reason why we cannot report a specific test usually reflects the complex biology of genetics and pregnancy, and is not due to a failing in the laboratory. This section explains some of these biological reasons.

Greater confidence

As part of the testing process, our NIPT includes a precise and accurate measure of the amount of fetal DNA in your blood before proceeding with chromosome analysis. This step is important as it ensures that there is enough of your baby’s DNA available in your blood to provide a reliable result.

Insufficient fetal DNA

During pregnancy, maternal plasma contains fragments of DNA from the mother and from the placenta (referred to as ‘fetal DNA’). In approximately 3% of pregnant women screened by Sonic Genetics, there is insufficient fetal DNA in the mother’s blood (compared to the amount of maternal DNA) to provide an accurate result. We describe this as the ‘fetal fraction’ being too low for reliable analysis.

Low fetal fraction can be due to a lack of fetal DNA or a relative excess of maternal DNA. The level of maternal DNA can vary over time. Low fetal fraction is more likely in women with increased body weight. It may also be more likely in the presence of infection and inflammation, or after exercise.

It is worth repeating the Harmony test because two-thirds of women will get a result on re-testing. There is no additional charge for the re-test with Sonic Genetics.

Insufficient fetal DNA after re-test

This occurs in around one in 100 of all pregnant women screened by Sonic Genetics, i.e. in one third of those whose test could not be reported after the first collection. We do not recommend repeating the Harmony test again or using another form of non-invasive prenatal test, as the underlying cause that made the tests unreportable are likely to persist. In the event that Harmony cannot report a result for disorders of chromosomes 13, 18, 21 or 22q11.2 after two collections, we will, upon request, refund the cost of the test to the credit card holder who ordered the test.

Should other tests be done if there is insufficient fetal DNA after re-test?

This matter should be discussed with your doctor. It may be appropriate for you to have the combined first trimester screening test and/or a detailed ultrasound study of the developing baby. In some situations, it may be appropriate to have an invasive test, i.e. CVS or amniocentesis, to examine the fetal chromosomes. The decision to have such an investigation, and deciding which test is appropriate, will depend on the details of your pregnancy and the questions you want answered.

Fetal sex not reported

In one in 100–200 tests, we can provide a clear result regarding chromosomes 13, 18, 21 and 22q11.2, but are unable to provide a clear answer regarding fetal sex or sex chromosome changes (or both).

The Y chromosome (indicating a male fetus) is much smaller than the chromosomes 13, 18, 21 or 22, and determining the presence or absence of the Y chromosome can be compromised by biological factors which do not limit reporting of the other chromosomes. These factors include the fetal fraction being at the lower end of the acceptable range.

The Harmony test does not report a result unless there is very clear evidence for the presence, or absence, of the fetal Y chromosome. We do not assume that the apparent lack of a Y chromosome means that the fetus is female; we always check to ensure that there is sufficient information to provide a reliable result. There is no evidence to suggest that fetal sex not being reported is associated with an increased chance of any disorder in the developing baby.

If fetal sex cannot be reported, the manufacturer of the testing kit does not recommend that the Harmony test be repeated. The experience of testing hundreds of thousands of women has shown that repeat testing is unlikely to provide a reliable result for fetal sex.

The main purpose of non-invasive prenatal tests such as Harmony is to screen for major chromosomal changes (i.e. trisomy 21, 18 or 13, plus 22q11.2 deletion) which affect the health of the tested baby. We are pleased to offer fetal sex as an additional test at no charge, and are careful to report fetal sex only if the result is clear. As this is a free supplementary test, we do not offer a refund should a result not be available.

Sex chromosome abnormality result not reported

In one in 100–200 tests, we can provide a clear result regarding chromosomes 13, 18, 21 and 22q11.2, but are unable to provide a clear answer regarding fetal sex or sex chromosome changes (or both).

Assessment for fetal sex chromosome abnormality involves counting the number of X and Y chromosomes in the fetus. As noted in the section regarding fetal sex (above), the fetal Y chromosome is small and there are a number of technical and biological challenges in determining the number of Y chromosomes. Similarly, determining the number of fetal X chromosomes is also challenging, as most of the DNA in the sample comes from the mother (two X chromosomes). The Harmony test must count the number of X chromosomes in the smaller component of DNA from the fetus. The potential sex chromosome changes are also more complex than for chromosomes 13, 18, 21 or 22q11.2 deletion because there are multiple possibilities to be evaluated, i.e. fetal X, XX, XY, XXX, XXY, XYY and XXYY.

To complicate matters further, the mother or placenta may have some cells with an abnormal number of X chromosomes. This is relatively common, and need not be associated with any abnormality of cell function. Nonetheless, this variation complicates reliable assessment of fetal X chromosome number.

If fetal sex chromosome number cannot be reported, the manufacturer of the testing kit does not recommend that the Harmony test be repeated. The experience of testing hundreds of thousands of women has shown that repeat testing is unlikely to provide a reliable result for sex chromosome abnormalities.

The main purpose of non-invasive prenatal tests such as Harmony is to screen for major chromosomal changes (i.e. trisomy 13, 18 or 21, and 22q11.2 deletion) which affect the health of the tested baby. We also offer assessment of fetal sex chromosome abnormalities, noting that these are usually less severe than trisomy 13, 18 or 21, or 22q11.2 deletion. We are pleased to provide this additional assessment at no charge, and are careful to provide a report only if the result is clear. As this is a free supplementary test, we do not offer a refund should a result not be available.

Why do some prenatal tests claim to always give a result?

Some non-invasive prenatal tests do not ensure that there is sufficient fetal DNA to provide an accurate report of the fetal chromosomes. For some of these tests, there is limited published information about the performance of the test. The Harmony test has now been provided to more than 1,000,000 women worldwide, and there are published studies of the accuracy of Harmony in more than 23,000 women.

Should other tests be done if fetal sex or sex chromosomes cannot be reported?

This matter should be discussed with your doctor. It may be appropriate for you to have a detailed ultrasound study of the developing baby. In some situations, it may be appropriate to have an invasive test, i.e. CVS or amniocentesis, to examine the fetal chromosomes. The decision to have such an investigation, and deciding which test is appropriate, will depend on the details of your pregnancy and the questions you want answered. We do not recommend having a repeat NIPT from a different provider, as the underlying biological issue responsible for Harmony’s inability to provide a result will be unchanged.

How do I get a refund if the criteria above are met?

Contact our customer service department on 1800 010 447. The refund will be processed in a few business days. If you paid Sonic Genetics by credit card, the refund can only be made to the holder of that card. Note that if you did not pay Sonic Genetics directly for your Harmony prenatal test, your service provider may have a different refund policy that is not related to this information.

Resources

Information for Patients – When Harmony Prenatal Test unable to report on chromosomes examined