If you or your partner are considering in vitro fertilization (IVF), you may have heard of preimplantation genetic testing (PGT). PGT is a new reproductive technology that can help doctors identify genetic abnormalities in embryos before implantation. It is not always necessary, but it can be a valuable tool for couples at risk of passing genetic disorders to their children.
Learn more about preimplantation genetic testing, who it’s for, and how it works.
What is preimplantation genetic testing (PGT)?
Preimplantation genetic testing (PGT) involves testing embryos for genetic abnormalities before the embryo is transferred into the uterus.
PGT can be used to screen for a variety of genetic abnormalities, including:
- Aneuploidy: This is a condition with extra or missing chromosomes.
- Single-gene disorders: This condition is caused by a single gene mutation resulting in a genetic disorder.
- Structural rearrangements: This is a condition in which a piece of chromosome is missing or duplicated.
PGT can help to increase the chances of a successful pregnancy and to reduce the risk of miscarriage. It can also be used to select embryos that are less likely to have a genetic disorder.
What are the different types of PGT?
There are three types of PGT:
- PGT-Aneuploidy (PGT-A)
- PGT-Monogenic Conditions (PGT-M)
- PGT-Structural Rearrangements (PGT-SR)
Preimplantation genetic testing for aneuploidy (PGT-A)
PGT-A, or preimplantation genetic testing for aneuploidy, is a type of genetic testing used to screen embryos for chromosomal abnormalities. This is the most common type of PGT.
Most human cells have 23 pairs of chromosomes, for a total of 46 chromosomes. However, in aneuploidy, there are extra or missing chromosomes. One extra chromosome is termed trisomy. A missing chromosome is referred to as monosomy. Most cases of aneuploidy result in miscarriage. However, some aneuploidies can result in a live birth. The most common aneuploidy that infants can survive is Down syndrome, Turner syndrome, and Klinefelter syndrome.
Examples of aneuploid chromosomes include:
- Trisomy 21: Trisomy 21 (Down syndrome) is the most common type of aneuploidy and occurs when there’s an extra copy of chromosome 21.
- Trisomy 18: Trisomy 18 (Edwards syndrome) is a rare but serious genetic disorder with three copies of chromosome 18 instead of two. Trisomy 18 is often fatal within the first few weeks of life.
- Trisomy 13: Trisomy 13 (Patau syndrome) is another severe genetic disorder caused by an extra copy of chromosome 13. Trisomy 13 is often fatal within the first few weeks of life.
- Monosomy X: This genetic disorder is caused by the absence of one X chromosome in females. Monosomy X is also known as Turner syndrome.
- 47, XXY: This genetic disorder is caused by an extra X chromosome in males. 47, XXY is also known as Klinefelter syndrome.
Candidates for PGT-A Include:
Here are some factors that may make a couple good candidates for PGT-A:
- Advanced maternal age: Women 35 and older are at increased risk of having a child with a chromosomal abnormality.
- Recurrent pregnancy loss: Chromosomal abnormalities affect 2%–8% of couples with recurrent pregnancy loss.
- Couples who have had multiple failed IVF attempts
Preimplantation genetic testing for a monogenic disease (PGT-M)
PGT-M, or preimplantation genetic testing for monogenic diseases, is a type of genetic testing that screens embryos for single-gene disorders.
Examples of monogenic diseases include:
- Autosomal recessive disorders: These disorders are caused by two copies of a mutated gene. Some examples of autosomal recessive disorders include cystic fibrosis, sickle cell anemia, and Tay-Sachs disease.
- Autosomal dominant disorders: These disorders are caused by a single copy of a mutated gene. Some examples of autosomal dominant disorders include Huntington’s disease, polycystic kidney disease, and Marfan syndrome.
- X-linked disorders: These disorders are caused by a mutated gene on the X chromosome. Some examples of X-linked disorders include hemophilia, Duchenne muscular dystrophy, and Fragile X syndrome.
Monogenic diseases can range in severity from mild to severe. Some monogenic diseases are fatal, while others can be managed with treatment.
Candidates for PGT-M Include:
PGT-M can be a valuable tool for couples who risk passing on a genetic disease to their children.
Here are some of the factors that may make a couple good candidates for PGT-M:
- Family history of genetic disorders: Couples with a family history of genetic disorders may be at increased risk of passing on the disorder to their child. PGT-M can be performed if the specific familial mutation has been identified and appropriate family members are available for test preparation.
- Carrier status: The risk of an affected child depends on the inheritance pattern of the disorder: 50% for autosomal dominant disorders, 25% for autosomal recessive disorders, and 25% for female carriers of X-linked disorders.
PGT for chromosome structural rearrangement (PGT-SR)
PGT-SR stands for preimplantation genetic testing for structural rearrangements. PGT-SR screens embryos for chromosomal structural rearrangements (CSRs).
Chromosomal structural rearrangements can happen when a piece of a chromosome breaks off and attaches to another chromosome, when a piece of a chromosome flips over, or when a piece of a chromosome is duplicated (extra copies) or missing.
Candidates for PGT-SR Include:
PGT-SR, or preimplantation genetic testing for structural rearrangements, is an option for couples where one partner has a chromosome rearrangement such as translocation or inversion.
Here are some factors that may make a couple good candidates for PGT-SR:
- History of chromosomal structural rearrangements: A couple with a history of CSRs has a higher risk of passing them on to their children.
- Recurrent pregnancy loss: About 3% of couples with recurrent pregnancy losses have chromosomal rearrangements.
What is an embryo biopsy?
Embryo biopsy is when a fertility specialist or embryologist removes embryo cells for genetic testing. Couples at risk of passing genetic disorders on to their children can use embryo biopsy as a valuable tool during an IVF cycle.
The biopsy is usually performed on day 5 or 6 of the embryo’s development. The embryologist gently removes about five to 10 cells from a part of the embryo that will go on to make the placenta. Embryo biopsy has been shown to be a safe procedure that does not harm the embryo or the baby that develops from it. The cells are then sent to a laboratory for genetic testing, and the results are usually available within a few days.
An embryo biopsy is necessary for all types of PGT.
How PGT Works
PGT, or preimplantation genetic testing, is a two-step process that includes embryo biopsy and genetic testing.
Here’s how PGT works:
- IVF cycle: First, the couple must undergo an IVF cycle, in which the woman’s ovaries are stimulated to produce multiple eggs. These eggs are retrieved from the ovaries and are then fertilized with sperm in the laboratory to become embryos.
- Embryo biopsy: Once the embryos reach the blastocyst stage, day 5 or 6 of development, five to 10 cells are removed from each embryo. An embryologist does this using a biopsy needle or a laser.
- Genetic testing: The cells are sent to a laboratory for genetic testing (PGT).
- Embryo selection: The genetic testing results are then used to select embryos for transfer. Embryos free of genetic abnormalities are more likely to result in a successful pregnancy.
How is genetic testing performed?
The following methods are used for genetic testing in PGT:
- Polymerase chain reaction (PCR): This technique amplifies DNA, creating millions to billions of copies of a specific DNA sample for analysis.
- Next-generation sequencing (NGS): This technique determines the sequence of DNA, which can be used to identify genetic disorders caused by changes in the DNA sequence.
What is preimplantation genetic diagnosis (PGD)?
Preimplantation genetic diagnosis (PGD) is a type of PGT that tests for a known, specific genetic disorder.
The recently modified terminology is preimplantation genetic testing for monogenic disorders (PGT-M), as above.
What is preimplantation genetic screening (PGS)?
Preimplantation genetic screening (PGS) is a type of PGT that screens embryos for chromosomal abnormalities.
The recently modified terminology is preimplantation genetic testing for aneuploidy screening (PGT-A), as above.
PGT vs. PGD vs. PGS
PGT, PGD, and PGS all involve genetic testing of embryos before uterine implantation. However, there are some differences between these procedures.
- PGT (preimplantation genetic testing) is a general term encompassing all types of genetic testing performed on embryos before they are implanted in the uterus. This includes PGD (PGT-M) and other types of testing, such as PGS (PGT-A).
- PGD (preimplantation genetic diagnosis) tests embryos for a specific genetic disorder. This is termed PGT-M.
- PGS (preimplantation genetic screening) tests for chromosomal abnormality. This is termed PGT-A.
In other words, all PGD is PGT, but not all PGT is PGD. All PGS is PGT, but not all PGT is PGS.
Risks and Advantages of PGT Testing
Like any medical procedure, preimplantation genetic testing has risks and advantages.
- Damage to the embryo: There’s a small risk that the embryo biopsy could damage the embryo. This could lead to a miscarriage or other complications.
- Limitations: Despite advances in genetic testing and increasing accuracy and efficiency, false-positive and false-negative results are possible. There are challenges in detecting microdeletions and microduplications, de novo variants, and imprinting disorders. Another issue is the detection of mosaicism during PGT-A. While the clinical utility of PGT-M and PGT-SR are established, the best use of PGT-A in IVF is not as clear.
- Cost: PGT testing is a relatively expensive procedure. The cost can vary depending on the test and the clinic.
- Increased chances of a successful pregnancy: PGT can help to increase the chances of a successful pregnancy by selecting embryos that are more likely to implant in the uterus and result in a healthy pregnancy.
- Reduced risk of miscarriage: PGT-A can help to reduce the risk of miscarriage by selecting embryos less likely to have chromosomal abnormalities.
- Peace of mind: PGT can provide couples peace of mind by knowing they are selecting embryos less likely to have a genetic disorder.
Success Rates for PGT
The success rate of PGT depends on many factors, including maternal age, embryo quality, and the type of PGT performed. The success rate of PGT is also affected by the clinic that performs the procedure.
In general, PGT-A increases clinical and sustained implantation rates.
Frequently Asked Questions
Below are some answers to common questions about PGT.
How long does PGT take?
The time it takes to complete PGT varies depending on the type of PGT and the clinic performing the procedure. However, generally, PGT can take 1-2 weeks to complete.
Does PGT-A test for Down syndrome?
Yes, PGT-A can test for Down syndrome. Down syndrome is a chromosomal disorder caused by an extra copy of chromosome 21. PGT-A can identify embryos with an extra copy of chromosome 21.
How much is PGT?
The cost of PGT can vary depending on the PGT type, the laboratory performing the testing, and the number of embryos that need to be tested.
Does PGT test for autism?
No, PGT cannot test for autism (ASD). Autism is a complex disorder caused by genetic and environmental factors. No single gene has been identified as causing autism, so PGT cannot be used to screen for autism.
However, some research is being done on using PGT to detect ASD susceptibility genes. This research is still in its early stages, and it is unclear how effective PGT would be in identifying embryos at risk for ASD.
A Word from RMA Network
Deciding whether to undergo preimplantation genetic testing is a personal and important decision for couples. It is essential to consider the risks and advantages of PGT before making a final decision. A fertility specialist or genetic counselor can help couples navigate this decision-making process and provide guidance based on their circumstances.
RMA Network offers a full range of fertility services and financial options to help you start or extend your family. We can also help you navigate the decision-making process for PGT.