PGT-M, or Preimplantation Genetic Testing for Monogenic/Single Gene Disorders, is a specialized genetic test performed on embryos during an in vitro fertilization (IVF) cycle. Its primary purpose is to identify embryos that may have inherited a known single-gene disorder from their biological parents. This process provides prospective parents with information to help them make informed decisions regarding embryo selection for transfer.
What PGT-M Is
PGT-M is a diagnostic tool used alongside in vitro fertilization (IVF) to screen embryos for specific genetic conditions. This testing focuses on monogenic disorders, which are caused by mutations in a single gene. Examples include cystic fibrosis, Huntington’s disease, sickle cell anemia, certain forms of muscular dystrophy, and inherited cancer syndromes like those related to BRCA1 and BRCA2 mutations.
PGT-M helps identify whether an embryo carries a genetic mutation known to exist in the family. It is distinct from other embryo screening methods that check for chromosome number abnormalities, such as aneuploidy. While sometimes referred to by its older name, Preimplantation Genetic Diagnosis (PGD), the updated terminology of PGT-M clarifies its specific focus on single-gene disorders. The technique has been in use for over twenty-five years.
The PGT-M Process Explained
The PGT-M process begins with genetic counseling and preparation, which involves developing a specific test tailored to the family’s known genetic condition. This custom test development involves examining DNA samples from prospective parents and potentially other family members to identify the genetic markers associated with the gene mutation. This preparatory phase can take several weeks or even months to complete before the IVF cycle can begin.
Once the custom test is ready, an IVF cycle begins. This includes ovarian stimulation to produce multiple eggs, followed by egg retrieval. These eggs are then fertilized with sperm in a laboratory setting to create embryos. The embryos grow for approximately five to six days until they reach the blastocyst stage. At this stage, the embryo consists of two main cell types: the inner cell mass, which will form the baby, and the trophectoderm, which will develop into the placenta.
A small number of cells are carefully removed from the trophectoderm layer of each blastocyst-stage embryo in a procedure called an embryo biopsy. This biopsy is performed by an embryologist. The removal of these cells from the future placental tissue is generally considered safe for the embryo. After the biopsy, the embryos are cryopreserved while the biopsied cells are sent to a specialized genetics laboratory for analysis.
In the laboratory, the DNA from the biopsied cells is analyzed to determine if the specific genetic mutation is present. This analysis helps identify embryos that are unaffected, affected, or carriers of the condition. Based on these results, unaffected embryos are selected for transfer into the uterus in a subsequent frozen embryo transfer cycle.
Who PGT-M Can Help
PGT-M is typically considered for individuals or couples who face an increased risk of passing on a single-gene disorder to their offspring. This includes prospective parents who are known carriers of a specific genetic mutation, even if they do not exhibit symptoms themselves. For instance, if both partners carry the gene for a recessive condition like cystic fibrosis, PGT-M can help identify embryos that have not inherited the condition.
The test is also relevant for couples who already have a child affected by a monogenic disorder and wish to prevent future children from inheriting the same condition. PGT-M can also be an option when one parent is affected by an autosomal dominant disorder, such as Huntington’s disease, where there is a 50% chance of passing the condition to each child. PGT-M can be performed for a wide range of serious genetic conditions, provided the specific gene mutation within the family has been identified.
Considering the Results and Broader Picture
The results of PGT-M classify embryos as unaffected, affected, or, in some cases, carriers of the genetic condition. Unaffected embryos are those that do not carry the specific genetic mutation being tested for. Embryos identified as affected carry the mutation and are typically not chosen for transfer. An embryo may also be identified as a carrier, meaning it possesses one copy of a recessive gene mutation but is not expected to develop the disease itself.
The accuracy of PGT-M is generally high, often exceeding 97%. However, no genetic test is 100% accurate, and there is a small possibility of misdiagnosis or inconclusive results. Factors such as mosaicism or issues with DNA quality from the biopsy can sometimes lead to unclear outcomes. For this reason, post-transfer prenatal diagnostic testing, such as amniocentesis, may be recommended to confirm the PGT-M results during an established pregnancy.
PGT-M specifically screens for the single-gene disorder for which it was designed and does not test for all genetic conditions or birth defects. It also does not guarantee a completely healthy baby, as other genetic or developmental issues unrelated to the targeted gene are not assessed. The process of embryo selection itself raises ethical considerations regarding the choice to select or not select embryos based on their genetic status. Ultimately, PGT-M offers a pathway for families at risk of passing on specific inherited conditions to make informed reproductive choices.