Preimplantation genetic testing for aneuploidy (PGT-A)

Chromosomes and genetic information.

Inside each cell, genetic material (DNA) is organised into structures called chromosomes. Eggs and sperm each contribute 23 chromosomes, 22 non-sex chromosomes and one sex chromosome. When fertilisation occurs, these combine to form 46 chromosomes, creating a unique genetic profile for the embryo.

What is PGT-A?

PGT-A is a test performed on embryos to identify abnormalities in chromosome number. This includes detecting extra or missing chromosomes.

Aneuploidy

An embryo with an abnormal number of chromosomes is described as having aneuploidy.

Most embryos with these abnormalities will either fail to implant or result in miscarriage.

In some cases, however, they may lead to the birth of a child with a chromosomal condition. One example is Down syndrome, where there is an extra copy of chromosome 21.

Limitations of PGT-A

PGT-A focuses on chromosome number. It does not screen for single gene conditions, which are caused by specific gene mutations within chromosomes. An example of a single gene condition is cystic fibrosis.

If there is a known risk of such conditions, separate testing (PGT-M) may be required, usually after genetic carrier screening.

How common is aneuploidy?

The likelihood of chromosomal abnormalities increases with egg age.

For example:

·         At age 35, around 30% of embryos may have abnormal chromosome numbers

·         By age 40, this may rise to approximately 60%

This helps explain why fertility declines and miscarriage rates increase with age.

Embryo biopsy

To perform PGT-A, 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-A 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 actually 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.