Preimplantation Genetic Testing
for MONOGENIC DISORDERS
WHAT IS IT?
Preimplantation genetic testing for monogenic disorders (PGT-M), previously referred to as single gene preimplantation genetic diagnosis (PGD), is a genetic test that, using an embryo biopsy sample, assesses an embryo’s DNA to determine if it is predicted to be affected with a specific single gene disorder. By doing this, embryos predicted to be unaffected can be prioritized for transfer to drastically reduce the risk of having a child with a genetic disease due to a known inherited risk.
WHO IS IT FOR?
PGT-M is meant for all individuals or couples who have a known high risk of having a child with a single gene disorder. Examples include:
1. Individuals who have a personal and/or family history of genetic disease, such as hereditary breast and ovarian cancer (BRCA1/2) or Huntington’s disease
2. Couples who are both known carriers of a recessive condition, such as cystic fibrosis or sickle cell anemia
3. Individuals who are carriers of or affected with an X-linked genetic condition, such as Fragile X syndrome or Duchenne/Becker muscular dystrophy
Whether or not an inherited mutation will cause disease in an individual depends on the type of inheritance pattern that that particular gene follows. For example, some conditions follow an autosomal dominant pattern, wherein having a mutation on just one copy of the gene is sufficient to cause disease. In these cases, an individual carrying a dominant mutation is affected with the particular disease and thus has a 50% chance of passing it on to his or her child.
On the other hand, diseases that follow an autosomal recessive pattern require a mutation on both copies of a gene in order to cause disease. In that case, typically both parents are healthy carriers of a mutation in the same gene and would have a 25% chance of having a child who inherits both mutations and is thus affected with the disease.
Additional patterns of inheritance, such as X-linked or Y-linked, also exist. With PGT-M, individuals or couples at high risk of having a child with a single gene disorder can substantially reduce their risks of having an affected child.
HOW DOES IT WORK?
If you decide to undergo IVF with PGT-M due to a single gene mutation carried by you and/or your partner, the process is simple.
Your doctor’s office will send a test requisition form and your genetic testing records to our laboratory before you begin your IVF cycle. We will review these records and ensure that the single gene mutation(s) you carry can be tested for in your embryos. We will notify your doctor’s office regarding whether or not we can accept your case for testing within a few days.*
If the case is accepted, you will be contacted by a genetic counselor to review the PGT-M process. You will need to provide saliva samples for proper test preparation; additional relatives’ samples may also be necessary and this will be reviewed in detail with the genetic counselor.
Once test preparation is complete, your doctor’s office will be notified so that you can begin your cycle. IVF will be performed at your doctor’s laboratory to produce embryos.
Once your embryos reach the blastocyst stage (typically at Day 5 or Day 6 of development), an embryologist will biopsy a few cells from each embryo’s trophectoderm, the part of the embryo that goes on to form the placenta. Your embryos will be cryopreserved and stored safely at your doctor’s laboratory.
The embryo biopsy samples are sent to our partner Genomic Prediction’s genetic testing laboratory, where they will analyze the DNA for the specific single gene mutation(s) of interest (as well as sporadic aneuploidies if you opted to also have PGT-A performed).
Once testing is complete --typically within 2 weeks --a report is sent to your doctor’s office detailing the results of each embryo biopsy. Your doctor can then use those results to determine which embryos are suitable for transfer.
*While the vast majority of diseases and mutations can be tested for in embryos, some cannot, so the initial case review is very important to ensure PGT-M is possible before you begin the IVF process.
WHAT RESULTS CAN I EXPECT?
Though it can slightly vary depending on the specific disease or gene, there are generally three types of results you can receive: 1) affected, 2) unaffected, or 3) carrier.
“Affected” embryos are those which are predicted to be affected with the single gene disease that was tested for. The transfer of these embryos is not recommended.
“Unaffected” embryos are those which are predicted to not be affected with the single gene disease that was tested for. These embryos are the ones prioritized for transfer.
“Carrier” embryos are those which are predicted to carry a disease-causing mutation but are not expected to be affected. This can vary based on the specific disease, as some carrier states can be associated with symptoms. The transfer of “carrier” embryos is generally acceptable, unless there is scientific literature recommending against it for specific conditions.
If you opted to have PGT-A in addition to PGT-M, there are two types of results you can receive: 1) euploid or 2) aneuploid.
“Euploid” indicates that no chromosome abnormalities were identified in the biopsy sample. Euploid embryos have the highest chance of leading to a successful pregnancy and healthy baby. Thus, euploid embryos are the ones prioritized for transfer.
“Aneuploid” indicates that one or more chromosome abnormalities was identified throughout the biopsy sample. Aneuploid embryos are unlikely to result in a successful pregnancy or can lead to miscarriage or the birth of a child with a serious genetic disorder. Thus, the transfer of aneuploid embryos is not recommended.
Though rare, the results of PGT can sometimes be inconclusive. At Genomic Prediction, this risk is <1% for PGT-M and <5% for PGT-A. Inconclusive results can occur due to a variety of reasons, including poor embryo or cell quality, degraded DNA, or technical failure. When this occurs, a re-biopsy of the embryo can be considered, as a second sample returns a conclusive result the vast majority of the time. However, the option of re-biopsy should be discussed in detail with your doctor and/or the IVF lab’s embryologist(s) to determine if it is a recommended procedure.
It is important to note that PGT is not meant to replace standard prenatal care. Should a transfer be successful, you are encouraged to consider any prenatal genetic testing options presented to you by your OB/GYN.