Preimplantation genetic testing for structural rearrangements (PGT-SR)

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-SR?

PGT-SR is a test performed on embryos to identify abnormalities structural chromosomal rearrangements. These are changes where pieces of chromosomes may be rearranged, missing, duplicated or attached to other chromosomes.

PGT-SR is typically recommended for individuals or couples known to carry a structural chromosomal rearrangement, such as a translocation or inversion.

While the person may be healthy, these rearrangements can increase the risk of creating embryos with unbalanced genetic material.

Structural rearrangements and reproduction

Embryos affected by unbalanced structural changes often do not implant or may result in miscarriage. In some cases, they can lead to the birth of a child with a chromosomal condition or developmental problems.

PGT-SR aims to identify embryos that have a normal or balanced chromosome structure, helping to improve the changes of a successful pregnancy.

Limitations of PGT-SR

PGT-SR is designed to detect structural chromosomal changes but does not identify single gene disorders such as cystic fibrosis. If there is a known risk of a specific inherited condition, additional testing (PGT-M) may be required following genetic carrier screening.

PGT-SR may detect some forms of aneuploidy. Aneuploidy is where an embryo has an extra or missing chromosome. A common example is Down Syndrome, where an embryo has an extra chromosome 21. However, PGT-SR is not primarily designed to screen for all aneuploidies, therefore some errors in unrelated chromosomes may be missed, depending on the type of testing required. It is therefore important to have routine testing once pregnant.

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.