Genetic testing for monogenic conditions (PGT-M)

Intro to PGT-M-Single gene testing

Some people use PGT-M testing because there is a genetic condition that runs in their family. Others because genetic screening has shown they are carriers. This means they are at high risk of having a baby with a genetic condition. In both cases people choose P GTM testing to reduce the risk of having a child with the genetic condition being tested for.

DNA carries our unique genetic code. This code determines how our body looks and functions. Iin each of our selves DNA is packaged into chromosomes. Chromosomes have distinct regions that we call genes.  These genes control functions in our body.

Our body uses the DNA and genes as an instruction manual informing it on how to grow and repair. At conception, the DNA from both the 23 chromosomes of the egg and the 23 chromosomes of the sperm combine, resulting in a baby with a totally unique genetic code, built upon the DNA of all 46 chromosomes.

During this process, genetic changes or variations can occur in genes. Sometimes these changes do not cause any problems. However, in certain cases these variations can have a serious effect on the way a gene functions. If an important gene function is affected, the child can be born with a serious genetic disease.

What is PGT-M?

PGT-M tests an embryo for the gene variation that causes the genetic disease being tested for. By using genetic testing to identify embryos with a lower chance of gene variation, we can choose to transfer embryos that are less likely to result in a child with a genetic disease.

Aneuploidy and PGT-M testing

Sometimes PGT-M testing can show other problems with an embryo. One of these problems is called aneuploidy. Aneuploidy is where an embryo has the incorrect number of chromosomes.

Although PGT-M testing looks for a specific gene variation located on a chromosome, it can sometimes see extra or missing chromosomes. For example, the embryo receives 23 chromosomes from the egg and 23 from the sperm as well as an extra chromosome number 21, this embryo is known to have trisomy 21 more commonly known as Down syndrome.

However, because the test is specifically looking at genes rather than counting the chromosomes we can't be sure PGT-M has detected all extra and missing chromosomes therefore it is still important have routine testing during pregnancy.

Embryo biopsy

To perform PGT-M, a small number of cells are removed from the embryo in a procedure known as embryo biopsy. This is typically done at the blastocyst stage (day 5 to 7 of development), using cells from the outer layer that will form the placenta.

The sampled cells are sent to a specialised laboratory for analysis. While results are pending, embryos are frozen.

There is a small risk associated with biopsy, about 1% of embryos may be damaged or lost during the process. In some cases, embryos may not be suitable for biopsy, particularly if their structure or quality is not adequate.

Accuracy of testing

PGT-M is a useful tool but is not perfect.

Rarely, results may be incorrect:

•             An embryo may be reported as normal when an abnormality is present

•             An abnormal result may be reported when the embryo is normal

Some very small genetic changes, such as microdeletions, may not be detected with standard testing methods.

Occasionally, results may be inconclusive, or all embryos may be found to have abnormalities. In certain cases, your doctor may discuss the option of re-biopsying an embryo if no result is obtained.

Mosaic Embryos

Some embryos are described as mosaic, meaning they contain a mix of normal and abnormal cells. Many mosaic embryos have resulted in healthy children, but certain patterns may carry risks.

If mosaicism is identified, a detailed discussion with your doctor or a genetic counsellor is recommended to decide whether transfer is appropriate.

Pregnancy after PGT

PGT-A only assesses the specific genetic factors being tested and cannot rule out all possible conditions. For this reason, routine prenatal screening during pregnancy is still recommended to confirm results and check for other conditions.

What happens next?

Embryo biopsy is usually performed 5 to 7 days after egg collection. Results are typically available around two weeks later.

Once results are ready, your doctor or genetic counsellor will review them with you. If no suitable embryos are identified, further IVF treatment may be discussed. If a suitable embryo is available, a frozen embryo transfer cycle will be planned.

During treatment, it is recommended to avoid unprotected intercourse.