How does Preimplantation Genetic Screening (PGS) work and what are the risks associated with it?

PGS testing also referred to as PGT-A, is a medical procedure used to select the best embryo to transfer during IVF. During PGS, a few cells are removed from the embryo, and the DNA of the sample is examined for chromosomal abnormalities to increase the success rate of IVF.

But despite the many possible benefits of this procedure, it has its own risks. In the following piece, we will look at what PGS means, how it works, and whether the test can cause harm to the embryo.

What is preimplantation genetic screening (PGS)?

Preimplantation genetic testing (or embryo biopsy) is a genetic testing technique that helps identify chromosomal or genetic abnormalities in embryos created through IVF before they are transferred. There are two tests that can be done to evaluate embryos: preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD).

PGS evaluates embryos for multiple genetic issues or chromosomal disorders (which affect up to 28% of embryos, depending on the woman’s age). Apart from playing a key role in various diseases, research shows that chromosomal abnormalities may also raise the odds of miscarriage and failed fertility treatments. 

Genetic testing can be especially beneficial for individuals or couples who have heritable disorders, as it may help reduce the risk of transferring those diseases to their babies. It can also increase the likelihood of a healthy pregnancy by checking for possible genetic problems that can affect pregnancy and delivery. 

Some facts about the risks of PGS testing 

Preimplantation genetic screening is a testing procedure in which embryos created using IVF are checked for net loss or gain of genetic materials.  Basically, PGS can detect chromosomal abnormalities like Down Syndrome,  Turner Syndrome, etc.

•  PGT helps doctors to choose the most viable, healthiest embryos for transfer.
• Embryos that have the correct number of chromosomes are referred to as euploid embryos and may be more likely to result in a pregnancy, although the evidence behind this is controversial. 
• Research shows that an embryo can become damaged during PGS testing, but this remains unclear. 
• It may be difficult to produce a euploid embryo during IVF: not all embryos grow to become blastocysts, and not all blastocysts will have the right number of chromosomes.
• While there is a higher chance of achieving a pregnancy with a euploid embryo, there is no guarantee that it will work. 
• The results of PGS testing may be flawed, and sometimes, a seemingly abnormal embryo may not be abnormal after all. 
• Aneuploidy or an incorrect number of chromosomes – aneuploidy refers to the presence of an abnormal number of chromosomes in the cell, e.g, having 45 or 47 chromosomes instead of 46.
  • Edward syndrome – there is an extra copy of chromosome 18
  • Down’s Syndrome – there is an extra copy of chromosome 21
• Re-arrangement or translocation of a segment of one chromosome onto another chromosome.
• Deletion or omission of one segment of a chromosome or
• Sex-chromosome abnormalities, such as deletion or duplication of X or Y. Examples of disorders associated with sex chromosomes include:
  • Klinefelter Syndrome with three copies of sex chromosomes – two X and one Y.
  • Turner Syndrome with a single copy of sex chromosome – one X.

Who is a good candidate for PGS?

PGS checks for abnormalities in an embryo’s chromosome, so it is more accurate at identifying embryos with correct genetic makeup than visual microscopic observation often used during IVF. Therefore, PGS enables the doctor to choose a normal embryo to be transferred into the mother’s womb, raising the odds of delivering a healthy baby. 

Couples or individuals who are at great risk of having embryos with abnormal chromosomes should consider PGS. These include people with :

1. Advanced reproductive age
2. Recurrent pregnancy losses
3. Failed IVF cycles 

Other people who may consider PGS testing are individuals or couples who wish to have an elective single embryo transfer to prevent conceiving multiples in order to:

(i) increase the chances of a healthy baby through IVF  or  (ii) balance their family.

How preimplantation genetic screening (PGS) works

There are several methods to check all the 24 chromosomes, otherwise known as comprehensive chromosomal screening (CCS):

• Next-generation sequencing (NGS) and 
• Array comparative genomic hybridization (aCGH) 

These techniques are performed using a few cells from a day 5 or day 6 embryo or one or two cells biopsied from a day 3 embryo. 

What are the steps involved in PGS?

A lot of steps are involved in the PGS process, with each step carried out by different experts and fertility laboratories. 

1. The first step is in vitro fertilization (IVF), through which embryos are formed using the traditional IVF technique or intracytoplasmic sperm injection (ICSI). Fertilized eggs (embryos) are grown in a culture medium for 3 to 5 days. 
2. The next step is embryo biopsy, which is typically done on day 3 or day 5 of embryo development.
   • On day 3 of embryo biopsy, one or two cells are taken from the embryo for testing.
   • On day 5 or 6 of embryo biopsy, around 3 to 6 cells are removed for testing. 

On day five or day six of embryo development,  the cells within an embryo would have separated into two types: those that will form the baby and those that will form the placenta (trophectoderm). Many cells can be extracted at this stage without affecting the embryo’s viability, which allows you to get a more accurate result. 

Biopsy of a day 5 embryo

3. After the cells are removed, they are placed in test tubes are transferred to an IVF for analysis.
4. Usually, the cells are analyzed by an external laboratory. 
5. It takes more than a day for the results of the test to come out. Hence,  it is essential to freeze the embryos using a fast-freezing technique called vitrification. The embryo is frozen at Coastal Fertility.
6. The last step – that is, the thawing of the frozen embryo and its subsequent transfer into the uterus – is done at our fertility center. 

What are the risks associated with PGS? 

The risks of PGS testing are not different from those of traditional IVF. 

But with PGS, it is also possible that:

• Some embryos will become damaged due to the biopsy 
• No or unclear result because of a technical issue 
• Incorrect result due to chromosomal mosaicism in the embryo (Mosaicism is when a person has two or more cells with different chromosomal composition in their body).

To conduct PGS testing on a cleavage-stage embryo, one or two cells are removed and sent to the lab for testing. But with only a few cells, to begin with, this may cause severe damage to the embryo. 

It’s obvious how this could damage the embryo – what if the cell or cells biopsied are necessary for the development of the embryo? Considering that there are a handful of cells at this stage, PGS testing may pose serious harm to the embryo. But with blastocysts, there are a lot of cells.

Does biopsying a blastocyst-stage embryo cause any harm to the embryo?

Blastocyst culture has become more common nowadays, and biopsy performed on a blastocyst-stage embryo is believed to be superior to cleavage-stage biopsy. 

As you can see above, a biopsy of a cleavage stage embryo can damage the embryo. The reason is that there are only a few cells, to begin with. But with blastocyst stage embryos, there are several cells in the trophectoderm (that form the placenta), so removing a small piece should not cause much damage, right? Well,  it is not clear. 

A 2013 research showed that embryo biopsy did not cause any damage and that biopsied embryos had the same chances of success as non-biopsied embryos. However, there are also studies that suggested the opposite.

5 to 6 cells are removed during an embryo biopsy, but what if it is the larger piece that was biopsied?

In a 2014 study,  researchers found that ongoing pregnancy rates decreased when a large piece was removed from an embryo,  perhaps because the embryo could not recover. 

The development phase of the embryo during PGS

Another thing that can also have a huge impact is the development stage of the embryo at the time of biopsy.

According to a 2019 study, embryos had better implantation chances if their cells are removed when they expanded and were hatching out of the zona pellucida. On the contrary, embryos biopsied very early had significantly lower success chances, and the researchers suggest that this may be due to damage resulting from the biopsy itself. 

A 2020 paper also precluded that about 17 to 39% of embryos may be lost during the embryo biopsy process. The authors arrived at this figure by checking the data of a large study where preimplantation genetic testing failed to perform as expected. 

Therefore, PGS testing may pose harm to a blastocyst-stage embryo, affecting its success chances. Although removing the right-sized piece at the right development stage can help lower the potential damage, it is possible that there are other factors involved we don’t know about. 

Does PGS testing improve success rates?

The chances of having a positive outcome with PGS testing and IVF depend on the number of the produced embryos that have a positive result in the test. Existing data show that the live birth rate is between 60-80% when a single frozen embryo is transferred in a second cycle. 

These data are promising since most of the women who undergo PGS in conjunction with IVF treatment are more likely to produce chromosomally abnormal embryos. This may be due to advanced reproductive age, unsuccessful IVF attempts, or repeated pregnancy losses.

A 2015 review of studies comparing PGS testing with no testing found that it is indeed beneficial, but these studies involved only a few participants and used good prognosis women ( below 35 years)  who may have had a better chance even without the test.

Plus, a 2019 research found that there’s no difference when PGS testing is used for women aged between 25 and 40. But further analysis indicated that the ongoing pregnancy rates improved in women aged 35 to 40. 

At times, none of the embryos will be suitable for transfer because: 

• Only a few eggs are collected or fertilized 
• The cells got damaged  during the biopsy 
• All the embryos have an incorrect number of chromosome

Does PGS testing lower the chances of miscarriage?

A 2018 report contains data suggesting that PGS testing lowers the rates of miscarriage.

Bottom line

Overall, PGS testing may be a good option for women above 35. The reason is that egg quality decreases with age, and there is an increased chance of producing chromosomally abnormal embryos when you are old. However, you need euploid embryos to achieve success with PGS testing.

Coastal Fertility Medical Center offers complete PGS and PGD testing along with specialized IVF procedures to increase your chances of success. Schedule a consultation to learn how we can realize your dream of parenthood.