Understanding PGT-M

Preimplantation Genetic Diagnosis

Preimplantation Genetic Testing for Monogenic/Single Gene Defects (PGT-M) is a technique used by specialized medical laboratories to select embryos not found to carry specific genetic disorders prior to their transfer into a woman’s womb. It is also known as Preimplantation Genetic Diagnosis (PGD).

Why is PGT-M used?

PGT-M is normally used in an attempt to eliminate the risk of passing a specific genetic disorder from the parents to their child. For example, a parent carrier of inherited pancreatic disease may appear to be normal but would have a greater chance of conceiving a child with the disease.

Image credit: New Hope Fertility

PGT-M should not be confused with Preimplantation Genetic Screening (PGS). Couples who seek PGT-M with IVF treatment don’t necessarily suffer from infertility. In fact, many PGT-M candidates are perfectly fertile. PGS, unlike PGT-M, is a genetic screening approach used to rule out the routine chromosome abnormalities that reduce pregnancy rates and increase miscarriage rates in infertile couples.

How many types of PGT-M are there?

Single gene mutations

Nucleic acids (DNA) are the building blocks of our genetic material. They are represented in four different types of molecules (A, T, G, and C). Single gene mutations include substitution, for example, the replacement of an A for a G or a C for a T, deletions, and insertions of at least one nucleotide. These genetic alterations can happen by chance, or they may be inherited by children from their parents. Although PGD can identify either type of mutation, it is normally used to identify those an embryo would receive from parents who are carriers of a particular genetic abnormality.

Not all genetic alterations are fatal and not all mutations cause disease. Sometime mutations are in a non-coding chromosomal region leading to no apparent clinical effect. Other mutations may be in a area of coding DNA but are not translated into an amino acid change or do not result in any negative effect. These are silent mutations.

When mutations occur in a coding region they are usually translated into a amino acid change and thus a change in the structure of a protein. The mutation may have an impact on health. When the mutation alters a biological process, a protein function, or regulatory pathway, it can lead to a clinic effect, e.g., cancer, inherited disorders, etc.


Translocations are common chromosomal alterations that often impact health. Translocations are generally divided into two types: balanced or unbalanced. Balanced translocations consist of an exchange of large chromosomal regions between two chromosomes, with no net loss or gain of DNA. These events are difficult to detect using PCR-based techniques. An unbalanced translocation, however, is generally detectable, especially when the chromosomal gain or loss is large (over 10MB).

How is PGD conducted?

The most common way to perform PGT-M for a single mutation is Realtime PCR (RT-PCR), a technique that relies on two fluorescent probes to detect a single mutation, one probe for the mutant allele (gene) and a second probe for the non-mutated allele (gene). RT-PCR has a considerable rate of non-conclusive results and is prone to contamination.

For the first time in the field of IVF, Progenesis brings Next Generation Sequencing (NGS) as a viable alternative to RT-PCR. NGS can read the mutation of interest directly with a coverage and sensitivity that is unmatched by RT-PCR because NGS quantifies the representation of each allele present.

To learn more about PGT-M at Progenesis, click here.