Genetic disorders are a major cause of fetal abnormality and miscarriage, as well as IVF failure. It is often possible, however, to detect abnormalities through pre-implantation genetic testing (PGT), whereby an individual embryo, formed during IVF treatment, is screened for such disorders. This process involves removing a number of cells from the embryo which are then analysed to detect genetic abnormalities so that only normal embryos are then replaced into the uterus. A number of terms are used to describe this process but, essentially, there are two categories of tests:

• PGT-A: testing for aneuploidy, or an abnormal number of chromosomes (for example, Down Syndrome). This was previously known as PGS or preimplantation genetic screening.
• PGT-M: testing for a specific (or monogenetic) disorder, such as thalassemia or cystic fibrosis. This used to be called PGD or preimplantation genetic diagnosis.

In both cases, using a laser, a number of cells are removed from the edge of the embryo once it has developed to the blastocyst stage, usually five days after fertilisation. The cells that are removed are from the area that will later form the placenta, not the baby itself, so there is no risk of damaging the baby by the process itself. Nonetheless, it is a highly skilled and precise technique that should only be conducted by a trained and experienced embryologist.
It is possible to remove a single cell when the embryo is less developed, three days after fertilization, but this technique is less reliable and best avoided.

Over the years, different techniques have been used to analyse the cells obtained and currently, the most common, and accurate, the method is by Next Generation Sequencing (NGS). Older techniques include array-CGH and FISH, which are rarely used now as they are less reliable.

PGT has the major advantage that abnormalities are detected before pregnancy and thus avoids the distress of detecting a problem through prenatal testing, which is then more difficult to manage.

Who Might Benefit from PGT?

• Couples with a known family history, or who are carriers, of single-gene disorders such as thalassaemia, or cystic fibrosis
• Couples with known genetic problems such as a translocation
• Couples who have had abnormalities detected on comprehensive genetic testing (CGT) and whole exome screening (WES). This is especially useful for consanguineous marriages.

Currently, more than 2000 disorders can be detected through PGT-M and the list if growing all the time. Each test, however, is tailored specifically to the couple, as there are often genetic variations, so there is an initial preparation stage involving blood tests for both partners, which takes time, often more than one month.

PGT-A may be of benefit to couples:

• Who have experienced repeated miscarriage
• Who have undergone repeated failed cycles of IVF
• Where the woman is aged over 35 years
• With severe male factor infertility
• Who have a consanguineous marriage, and are related to each other
• Who desire gender selection

Genetic testing can be of great value in helping couples to achieve a successful pregnancy, but it is important to understand that it cannot detect every abnormality, so it is not a guarantee of a completely healthy child. Unfortunately, there are disorders that can arise that do not have a genetic basis.
It is strongly recommended that couples who are considering genetic testing discuss the implications with a trained genetic counsellor, as well as their physician.