Guide to Preimplantation Genetic Testing (PGT)

There have been many great strides and innovations made in reproductive medicine. Among them is preimplantation genetic testing (PGT). The ability to assess your embryos’ genetic health is one of the primary advantages of undergoing in vitro fertilization (IVF) rather than other fertility treatment options. Below, you’ll find an explanation of PGT and its different types, what it is screening for, and why it can be important to opt for this elective procedure. 

What is preimplantation genetic testing (PGT)? 

Preimplantation genetic testing (PGT) is a procedure used to screen the genetic health of embryos created with in vitro fertilization (IVF). This procedure is performed by embryologists once your embryos reach the blastocyst stage of development and the embryos have been frozen. 

The purpose of preimplantation genetic testing is to screen for specific genetic conditions or certain types of chromosome abnormalities. Doing this will significantly reduce the chances of transferring an embryo with concerning genetic differences. However, it should be noted that while PGT is highly accurate, it is considered a screening test and it is still recommended that you confirm your results during your pregnancy with diagnostic prenatal testing. 

Preimplantation genetic testing for aneuploidy (PGT-A) 

Preimplantation genetic testing for aneuploidy (PGT-A), as the name suggests, is designed to screen for aneuploidy. This is a genetic disorder where the total number of chromosomes doesn’t equal 46. This most commonly happens when the number of chromosomes a child acquires from their biological parents doesn’t equal 46 due to an error in the creation of egg or sperm. The two types of aneuploidy are trisomy, where there is an extra chromosome, and monosomy, where there is a missing chromosome. 

Aneuploidy is particularly important to screen for because it commonly results in miscarriage. In fact, chromosomal abnormalities cause about 50% of first-term miscarriages. As you get older, your chance of aneuploidy occurring increases. By age 40, the risk of aneuploidy is estimated at 1 out of every 65 pregnancies. It is for this reason that PGT-A testing can help reduce the likelihood of miscarrying during your IVF treatment. 

PGT-A versus PGS 

In recent years, the naming convention for the three types of preimplantation genetic testing has changed. This is quite common in the scientific community, but it can take several years or longer for the new names to be universally adopted. This is why your clinic might still be using the old name for PGT-A, which used to be called preimplantation genetic screening, or PGS. Some places also call it comprehensive chromosome screening, or CCS. 

Preimplantation genetic testing for monogenic/single-gene diseases 

Preimplantation genetic testing for monogenic/single-gene diseases is a type of genetic screening that looks for the presence of specific disease-causing genes. PGT-M is ideal for parents who are concerned about being carriers of specific genes that cause disease. Additionally, parents using donated eggs, sperm, or embryos who don’t know the donor’s medical history may wish to do PGT-M before the embryo transfer process. 

There are many diseases caused by defects in single genes: hemophilia, spinal muscular atrophy, Tay Sachs Disease, Huntington’s Disease, cystic fibrosis, and sickle cell anemia are all examples. 

PGT-M versus PGD 

As mentioned previously, the naming convention for preimplantation genetic testing has changed. PGT has become the umbrella term for all preimplantation genetic testing. What is now called PGT-M used to be called preimplantation genetic diagnosis, or PGD. Some clinics still use the old name. 

Preimplantation genetic testing for structural chromosomal rearrangements (PGT-SR) 

One of the first applications of preimplantation genetic testing, PGT-SR is used to screen for structural chromosomal rearrangements (SRs). Structural chromosomal rearrangements can contribute to infertility, repeated implantation failure, pregnancy loss, and congenitally affected children. SRs occur when genetic segments have been deleted, duplicated, or inverted. 

While it’s possible for children born with balanced SRs to be perfectly healthy, there can be serious issues if the SR is unbalanced. It is recommended that parents with known balanced SRs have PGT-SR done before the embryo transfer process. 

PGT-SR versus Chromosomal PGD 

As with the other types of preimplantation genetic testing, PGT-SR used to be known by another name. Some clinics may still refer to it as chromosomal PGD. 

How is preimplantation genetic testing performed? 

When it is time to test your embryos, one or more cells are taken and sent to a lab for analysis. As each type of preimplantation genetic testing is screening for something specific, there are different testing methods used. Below you’ll find an overview of the most commonly used procedures. It should be noted that in order to have your embryos tested, they have to reach the blastocyst stage and then be frozen. Some embryos may not develop into blastocysts or may not be suitable for biopsy. 

Fluorescent in situ hybridization (FISH) 

Fluorescent in situ hybridization, or FISH, is a laboratory technique used to detect and locate a specific DNA sequence on a chromosome. This technique involves affixing an individual’s full set of chromosomes on a glass slide, and then uses purified DNA tagged with a fluorescent dye. The tagged DNA segment will then find and bind to its matching segment. 

This allows scientists to identify specific DNA sequences in the genome. It is used in both diagnosing genetic diseases and identifying genetic abnormalities. 

DNA microarray 

DNA microarray is a laboratory tool that helps to identify whether the DNA from a particular individual contains a mutation in a specific gene. There are many diseases known to result from specific gene mutations. With DNA microarray technology, scientists are now able to identify whether an individual is a carrier of any of these mutations. 

Single-nucleotide polymorphism (SNP) analysis 

Single-nucleotide polymorphisms (SNP) are the most common form of genetic variation. Each SNP represents a difference in a single DNA building block, called a nucleotide. SNPs occur normally throughout a person’s DNA at an average of 1 in 1,000 nucleotides. 

While most SNPs have no effect on health or development, they can help predict an individual’s risk of developing disease. Additionally, SNPs can also be used to track the inheritance of disease-associated genetic variants within families. 

Can preimplantation genetic testing harm my embryos? 

It should be noted that preimplantation genetic testing involves the biopsy of potential embryos. This is an additional service in IVF treatment that is considered invasive in nature. It’s for this reason that there have been concerns that PGT could cause an increased risk of birth defects or adverse outcomes. 

However, the research doesn’t support this claim. A review published in 2018 has concluded that PGT independently is not a risk factor for birth defects or adverse outcomes. That said, if there is any indication that your embryo might not survive the biopsy, your embryologist will deem it unsuitable for preimplantation genetic testing. 

How long does preimplantation genetic testing take? 

When you opt for preimplantation genetic testing, your embryos will be cryopreserved (frozen) in order to prevent them from developing further while the lab processes their samples. Results can take two weeks at a minimum to come back, so you should expect to schedule your embryo transfer procedure one or more menstrual cycles after your egg retrieval. 

It is possible that your PGT results may take longer than two weeks to come back. Depending on the demand for the service, and the number of embryologists available to do the lab testing, there could be a wait list. Your fertility specialist will likely have a more precise timeline of when to expect results. 

How much does preimplantation genetic testing cost? 

Rates for preimplantation genetic testing costs vary by clinic. This is an add-on service, so it won’t be included in the cost of IVF treatment. Some clinics charge a flat rate fee for the biopsy, and then another fee for each embryo you’re having tested. Others charge a lump sum for the first six or so embryos, and then a fee for each additional embryo you have tested. Additionally, each type of PGT you opt for will likely be charged separately. It’s for these reasons that PGT ranges from $1,800 to $6,000. 

During your consultation, you can ask your clinic for an itemized breakdown of what each of their services cost. This will give you an idea of how much you should expect to spend if you decide to do any genetic screening. 

Who should opt for preimplantation genetic testing? 

Preimplantation genetic testing is recommended for parents with known genetic conditions in their family history, such as Huntington’s Disease or cystic fibrosis, and for parents with known structural chromosomal rearrangements. 

Additionally, the risk of aneuploidy goes up as you get older. As aneuploidy can frequently result in miscarriage, parents who are nearing their 40s will likely be counselled to opt for PGT-A testing to ensure they don’t transfer embryos with aneuploidy. 

Finally, chromosomal abnormalities are known to contribute to repeated implantation failures. Parents who’ve experienced multiple implantation failures may use PGT to find out if there is a genetic factor causing it. 

Does preimplantation genetic testing improve IVF success rates? 

The short answer is that yes, preimplantation genetic testing can improve IVF success rates. In fact, it can increase pregnancy rates by 15-20%. This is because it allows you to make sure that you don’t transfer embryos that have any of the chromosomal abnormalities that result in implantation failure or miscarriage. By eliminating those embryos from your pool of viable embryos, you increase the odds of successful embryo implantation and live birth. 

However, it is important to remember that there are no guarantees. There are many factors that impact the ability to get pregnant and carry to term. While chromosomal abnormalities are one element that affects pregnancy rates, factors like age, infertility, or pre-existing health conditions cannot be overcome with PGT alone. 

Why is preimplantation genetic testing important? 

The genetic health of your embryos can have an impact on successful embryo implantation and pregnancy. Preimplantation genetic testing screens for three things that can affect the viability of your embryos: PGT-A screens for aneuploidy, which can cause conditions like Down Syndrome or Turner Syndrome, or, more commonly, miscarriage. The risk of aneuploidy goes up with age. PGT-M tests for disease-causing genes that may be present. This is especially important for parents who may be carriers of these genes, or if the family history of a donated embryo is unknown. Lastly, PGT-SR tests for unbalanced structural chromosomal rearrangements, which can have serious ramifications on your child’s ability to have children of their own. 

Assessing the genetic health of your embryos can ensure that you are only transferring the most viable ones. Researchers have identified numerous chromosomal abnormalities that result in implantation failure or miscarriage. Therefore, knowing in advance whether any of these chromosomal abnormalities are present in your embryos can improve your chances of a successful IVF treatment cycle.