Embryo Preimplantation Genetic Testing (PGT)

Embryo preimplantation genetic testing at a glance

Preimplantation genetic testing (PGT) is a technique used to test the embryos created through in vitro fertilization (IVF) for possible genetic problems, which can result in pregnancy failure or birth defects.
PGT is new terminology for preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS).
This testing identifies problems including single gene disorders (such as sickle cell anemia), extra or missing chromosomes in the embryo (like Down syndrome), or problems in the genes that could cause implantation failure, miscarriage or birth defects in a subsequent child.

What is PGT for embryos?

We can perform up to three types of embryo preimplantation genetic testing during the IVF process. Those include:

PGT-A, which screens for an abnormal number of chromosomes.
PGT–M is the test for individual, or monogenic, diseases.
PGT-SR tests for abnormal chromosomal structural rearrangements, like translocation or inversion.

Are you interested in embryo preimplantation genetic testing?

Through the use of these types of embryo preimplantation genetic testing, fertility specialists can identify embryos with abnormalities that may cause them to not implant or to miscarry after a pregnancy is established. PGT can also determine if any of the embryos carry genetic abnormalities that could cause death or undesirable inheritable conditions and birth defects in the child born from that embryo.

PGT-A, PGT-M and PGT-SR are new terms in the medical community, which replace the terms preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). These three new tests perform the same functions as PGS and PGD.

How is PGT performed on embryos during IVF?

PGT begins with a biopsy of an embryo in the blastocyst stage of development, usually on day 5 or 6 of embryo development. The biopsy removes 3 to 10 cells from the trophectoderm, which is the outer layer of cells that will become the placenta as the embryo develops. The biopsy does not remove any cells from the inner cell mass, which develops into the fetus.

After these cells are removed, the blastocyst is frozen and stored in the lab.

The biopsied cells are sent for laboratory testing. Results are typically returned in a week to 10 days following the biopsy.

Sections below describe how PGT-A, PGT-M and PGT-SR benefit patients using IVF.

Rebecca and Jeff had seven embryos; PGT showed only three were normal.

Their Test for Success

Preimplantation genetic testing for aneuploidy (PGT-A)

This form of PGT examines the number of chromosomes in the embryo cells. Typically, people inherit 23 chromosomes from each parent for a total of 46 chromosomes.

PGT-A identifies if there is a missing or extra chromosome. This is known as aneuploidy. Monosomy is a missing chromosome, while trisomy indicates an extra chromosome.

Common trisomy conditions include Down syndrome, also known as trisomy 21, Patau syndrome and Turner syndrome. According to the Centers for Disease Control and Prevention (CDC), Down syndrome is the most common chromosomal disorder, affecting 1 in 700 babies.

While embryos with the trisomy form of aneuploidy may result in live births, there is only a single form of monosomy that is survivable. This is Turner syndrome, which is the absence of one of the X chromosomes, causing problems with fertility and affecting growth. The National Institutes Health (NIH) states that Turner syndrome occurs in 1 in 2,500 pregnancies.

PGT-A is best for:

Women who have had two or more miscarriages.
Females older than 35 years of age, as age increases genetic defects in eggs.
Women diagnosed with unexplained infertility.
Those who have had previously failed embryo implantation.
Women who have had multiple unsuccessful fertility treatments.
Couples or individuals who have had previous pregnancies with aneuploidy.

Embryo preimplantation genetic testing for monogenic disease (PGT-M)

PGT-M identifies a specific gene mutation that one or both of the parents is known to carry. If there is a family history of genetic disorders, from one or both parents, there is an increased chance for a child to also have that specific genetic mutation that results in a monogenic disease.

Some of these genetic disorders can result in monogenic diseases like sickle cell anemia or cystic fibrosis. A few of the inherited genetic abnormalities, such as the BRCA1 and BRCA2 mutations, can result in an increased risk of cancer.

PGT-M searches for common abnormalities such as:

Fragile-X syndrome.
Muscular dystrophy.
Huntington’s disease.
BRCA1 & BRCA2 mutations.
Cystic fibrosis.
Tay-Sachs disease.
Sickle cell anemia.

PGT for chromosomal structural rearrangement (PGT-SR)

This form of PGT is most useful for patients with a known chromosomal structural rearrangement. This can include inversion or translocation rearrangements.

Individuals with these types of structural rearrangements have a higher risk of producing embryos with an incorrect amount of chromosomal material. These embryos are less likely to result in a live birth, and patients with this type of problem often have recurrent miscarriages.

PGT-SR examines for disorders including:

Non-reciprocal translocations.
Reciprocal translocations.
Robertsonian translocations.

Mosaic embryos

Mosaicism occurs when an embryo has two groups of cells, some of which are genetically normal and some are abnormal. Mosaic embryos are identified through PGT as is the extent of the mosaicism.

There are classifications of mosaicism depending on the extent of the genetically abnormal cells in an embryo.

Normal: Fewer than 20% abnormal cells.
Low level mosaicism: 20%-40% abnormal cells.
High level mosaicism: 40%-70% abnormal cells.
Abnormal: 80% or more abnormal cells.

Transferring to the womb embryos with mosaicism may have a lower rate of implantation, a higher rate of miscarriage, and result in preterm delivery or more severe problems.

However, not all embryos with mosaicism should be discounted. Embryos with low level mosaicism can result in a successful, healthy pregnancy. More research on mosaic embryos is necessary.

Considerations with embryo preimplantation genetic testing

Embryo quality

Some patients generate multiple embryos, yet none of them are euploid (have the normal number of chromosomes). If a woman generates seven embryos and does not know they are all abnormal because they have not been evaluated by PGT, then she may go through multiple embryo transfer failures and multiple miscarriages. What she really needed all along was to have PGT performed first, which may have revealed that she really needed to get a new batch of eggs.

This is an example of where PGT is very cost effective. The cost of an embryo transfer and the costs associated with many miscarriages will exceed the cost of PGT.

PGT is particularly helpful as women get into their later 30s, since fewer and fewer of their embryos are genetically normal. It can be particularly useful for these women to know if they should go through IVF again to get a new batch of eggs.

Just because a person does not have any normal embryos in one batch, does not mean she won’t have any normal ones from a second attempt.

Family planning

If a person would like two or three children, it would be nice to know if her batch of embryos has that many normal ones so she can freeze normal embryos for future pregnancy. If not, she might consider another IVF stimulation to increase the number of normal embryos. The younger a woman is when she stimulates, the greater her chances of having a normal embryo.

Conversely, if a person already has two children and has four embryos she has not used, it might be very helpful to know which, if any of them, are genetically normal. People are more likely to abandon their embryos if they have a large number of them.

However, if they did PGT, they might learn that only one or two of those embryos are normal. Knowing only one or two more pregnancies could result from their batch of embryos will often give couples the courage to use all their embryos.

Risks of PGT

The estimate is that 1 in 100 embryos will be lost or damaged by doing PGT. PGT also requires freezing of the embryos, and not all embryos survive the freeze/thaw processes. Fewer than 5% of embryos will have some damage from the freezing or thawing. So PGT is not risk free to the embryo; however, the vast majority do well.

It is possible that embryos could be damaged by the PGT biopsy. If the embryos stop growing, it’s difficult to know how they may have fared if no biopsy had been performed.

In some cases, embryos can be misdiagnosed. Specifically, when testing for certain gene disorders, the chance of transferring an affected embryo that was mistakenly identified as normal is between 2% and 11%, depending on the disorder being tested for.

Performing PGT on an embryo does not improve the embryo’s quality or its ability to result in a pregnancy. If there is only one embryo, for example, doing PGT will not help someone get pregnant. By doing PGT, we know more about the embryo and learn only if it is one that can result in a healthy live birth.

The goal of PGT is the birth of an unaffected, healthy child. The PGT procedure itself has not been linked to any birth defects. While the data so far is reassuring, we don’t have extensive long-term data to know if there are small increased risks due to the biopsy.

How much does PGT cost?

PGT adds an additional cost to the IVF procedure, averaging $4,500 per cycle. Other incidental costs for embryo shipping may be incurred.

Trends in PGT

More and more couples are opting for PGT, as it helps them confidently select a single embryo for transfer with a very high rate of success and low chance of miscarriage. Couples are also choosing to do PGT more because it means they will need fewer frozen embryo transfers in the future in order to utilize all of their embryos.

For patients with many embryos, this can be cost effective. For older women, it can be critical to let them know if none of their embryos will work and instead of doing any transfers, they need a new batch of embryos.