What is PGT-M?

PGT-M (preimplantation genetic testing for monogenic diseases) is a specialised form of preimplantation genetic testing that targets specific gene mutations responsible for monogenic (single-gene) disorders. A monogenic disorder is caused by a single-gene mutation and can lead to severe health problems or life-long conditions.

PGT-M is performed on embryos during the process of in vitro fertilisation (IVF) to identify those without the targeted genetic mutation, allowing only unaffected embryos to be selected for transfer to the uterus for implantation. The procedure is a key tool in reproductive health, helping families who are carriers of genetic mutations reduce the risk of passing on hereditary conditions.

When is PGT-M recommended?

PGT-M is recommended in cases where there is a high risk of passing on a known genetic mutation. This includes:

• People who are carriers of the same autosomal recessive condition.
• People who are carriers of an autosomal dominant condition, where one parent has a mutation.
• People who have X-linked conditions that primarily affect male offspring.
• People who have experienced previous pregnancies or births affected by a genetic condition.

Some examples of the conditions that PGT-M can detect include:

• Cystic fibrosis: A genetic disorder that poses a life-threatening risk and impacts the lungs and digestive system.
• Sickle cell disease: A genetic disorder that causes abnormally-shaped red blood cells, leading to pain and organ damage.
• Tay-Sachs disease: A neurological genetic disorder occurring in infancy that poses a life-threatening risk.
• Huntington’s disease: A progressive neurological genetic disorder.
• BRCA1 and BRCA2 mutations: Genetic changes linked to a higher risk of inherited breast and ovarian cancer.

Is PGT-M different from PGT-A?

Yes, PGT-M is different from PGT-A (preimplantation genetic testing for aneuploidy).

PGT-M is designed to test for single-gene mutations that cause monogenic disorders by identifying whether an embryo carries a particular gene mutation. This test is a targeted approach developed based on the parents’ known genetic risks, aimed at preventing specific gene disorders being passed down through family lines.

PGT-A, on the other hand, is designed to evaluate embryos for chromosomal abnormalities, such as missing or extra chromosomes. This includes conditions like Down's syndrome (caused by an extra chromosome 21) and Turner syndrome (caused by the absence of one X chromosome). 

Both tests can be combined if necessary, especially in cases where the parents face both chromosomal and single-gene risks.

What does the PGT-M testing process involve?

The process first requires IVF, where eggs are retrieved from the ovaries and fertilised with sperm in a laboratory. Once fertilisation occurs, the embryos are cultured until they reach the blastocyst stage, which is typically around 5-7 days after fertilisation.

At this stage, a small number of cells are removed from the outer layer of the blastocyst for PGT-M analysis. This procedure, called a biopsy, doesn’t harm the inner cells, which will form the baby.

The DNA from the biopsied cells undergoes advanced genetic analysis to detect the specific mutation associated with the targeted monogenic disease. This analysis will require the development of a custom testing protocol, which is based on genetic material from the parents (and sometimes other family members).

The genetic analysis typically takes 1 to 2 weeks. However, the preparation to create a customised test for the family’s specific genetic mutation may take several weeks before IVF begins.

Once the test results are ready, only embryos that are unaffected by the genetic mutation are prioritised for transfer into the uterus for implantation. The remaining embryos are frozen, discarded, or donated, depending on the patients’ preferences.

What is the success rate of PGT-M in reducing genetic risks?

PGT-M is highly effective in identifying embryos that don’t carry the targeted genetic mutation, reducing the risk of passing on genetic disorders. The success rate of preventing genetic conditions with PGT-M is approximately 98-99%, depending on the accuracy of the test and the specific mutation being analysed.

However, it’s important to know that PGT-M doesn’t ensure the overall health of the baby. Other factors, such as chromosomal abnormalities or environmental influences, can still impact pregnancy outcomes.

Couples with questions about PGT-M should seek guidance from a qualified fertility specialist and a genetic counsellor for further information and support. This will ensure that professionals can guide them through the process, address any concerns, and tailor the testing to their specific needs.