What is PGT-A? Understanding Preimplantation Genetic Testing for Aneuploidy

An interview with Diane Myles Reid, Genetic Counsellor at Markham Fertility Centre

On EP30 of My Fertility Podcast, we welcome back Diane Myles Reid, genetic counseling lead at Markham Fertility Centre and the former President of the Canadian Association of Genetic Counselors.  She walks us through the intricate details of pre-implantation genetic testing for aneuploidy (PGT-A) on this episode. This conversation highlights the science, benefits, risks, and nuances of this advanced fertility treatment tool, answering common patient questions and shedding light on controversies within the field.

What is PGT-A?

Diane, let’s start at the very beginning. What exactly is PGT-A?

Diane: PGT-A, short for pre-implantation genetic testing for aneuploidy, is a genetic test performed on embryos created through in-vitro fertilization (IVF). It analyzes the chromosomes in the embryo’s cells to determine whether the correct number is present. Chromosomal abnormalities—extra, missing, or structurally altered chromosomes—can significantly impact an embryo’s viability. These abnormalities are the primary reason for implantation failure or early miscarriage. By identifying embryos that are chromosomally normal, we can improve the chances of a successful pregnancy.

The Basics: Genetics 101

Can we take a step back and cover some basic genetics for listeners who might be unfamiliar with terms like DNA, genes, and chromosomes?

Diane: Of course! Each of us is made up of millions of cells. Within these cells are chromosomes—structures that carry our DNA. Our DNA is a molecule that contains genes, the “instructions” that tell our bodies how to grow, develop, and function. In humans, chromosomes come in pairs. Typically, we have 23 pairs, or 46 chromosomes in total—half from the egg and half from the sperm.

When an embryo forms, the egg contributes 23 chromosomes, and the sperm contributes the other 23, forming a complete set of 46 chromosomes. PGT-A looks at this chromosomal DNA to ensure the correct number and structure of chromosomes in the embryo.

What is the Goal of PGT-A?

What is the ultimate purpose of PGT-A?

Diane: The primary goal is to identify chromosomally normal embryos, which we call “euploid.” These embryos have the highest chance of implantation, pregnancy, and live birth. With PGT-A results, doctors can prioritize transferring the best-quality embryo, increasing the likelihood of success.

The Procedure: How Embryos are Tested

How exactly are embryos tested for PGT-A?

Diane: After fertilization, embryos grow in the lab for five to six days until they reach the blastocyst stage. At this point, they consist of 100 to 200 cells divided into two main parts:

• The trophectoderm, the outer layer of cells that will form the placenta and supporting pregnancy structures.
• The inner cell mass, which will develop into the fetus.

The embryologist carefully removes four to six cells from the trophectoderm. These cells are then sent to a specialized lab for genetic analysis, while the embryo itself is frozen and remains safely stored at the fertility center.

Why do we biopsy the trophectoderm and not the inner cell mass?

Diane: The inner cell mass is what will eventually form the baby. Removing cells from it could harm the embryo’s development. By taking cells from the trophectoderm, we minimize risks and ensure safety.

Why Do Chromosomal Abnormalities Occur?

What causes chromosomal abnormalities in embryos?

Diane: Chromosomal abnormalities often occur by chance due to errors during egg or sperm formation. However, the likelihood of abnormalities increases with the age of the person providing the egg. Individuals are born with all their eggs, and as they age, so do their eggs. This natural aging process can lead to a higher rate of errors during cell division.

Can you provide specific statistics on how age impacts chromosomal abnormalities?

Diane: Absolutely. For those in their early thirties, about 30% of embryos may be chromosomally abnormal. By age 35, approximately 50% of embryos may be abnormal. By age 38, this rises to 65-70%, and by age 40, only about 10-15% of embryos are chromosomally normal.

Understanding the Benefits of PGT-A

What are the main benefits of PGT-A?

Diane: One of the key benefits is identifying chromosomally normal embryos, which helps doctors prioritize which embryo to transfer first. This can save time and emotional energy by reducing the number of unsuccessful transfers or miscarriages. Additionally, it helps patients avoid transferring embryos with abnormalities that might lead to complex pregnancies or chromosomal conditions in a live birth.

For older patients, where the likelihood of abnormalities is higher, PGT-A can be even more valuable. With fewer embryos available in these cases, PGT-A ensures the best use of these precious embryos.

Risks and Limitations of PGT-A

What risks should patients consider before opting for PGT-A?

Diane: While the biopsy procedure is generally safe, there’s a minimal risk that it could harm the embryo and stop its development. Another consideration is the possibility that all tested embryos may be chromosomally abnormal, leaving no viable options for transfer.

Additionally, PGT-A isn’t 100% accurate. Although the results are over 97% reliable, there’s still a very small chance that an embryo deemed abnormal could actually be viable.

Mosaicism and Its Implications

What is mosaicism, and how does it affect PGT-A results?

Diane: Mosaicism occurs when some cells in an embryo are chromosomally normal, while others are abnormal. These embryos fall into a gray area—mosaic embryos are less likely to implant and more likely to result in miscarriage, but they can still lead to healthy pregnancies.

With advancements in data, we now know that transferring mosaic embryos can result in healthy babies. However, the decision to transfer a mosaic embryo requires thorough counseling and careful consideration of the specific chromosomal abnormalities and the level of mosaicism.

The Accuracy and Scope of PGT-A

Can PGT-A guarantee a healthy pregnancy or baby?

Diane: Unfortunately, no. PGT-A is highly accurate for detecting chromosomal abnormalities, but it doesn’t test for single-gene disorders, intellectual disabilities, or complex traits like autism. While it increases the chances of a successful pregnancy, it doesn’t eliminate all risks.

What is the success rate of transferring a chromosomally normal embryo?

Diane: At Markham Fertility Centre, the success rate is about 65-70% per transfer for euploid embryos. This is significantly higher than untested embryos but still not a guarantee.

Criticism and Controversy Surrounding PGT-A

Why do some people criticize PGT-A?

Diane: One critique is that PGT-A relies on just five or six biopsied cells, which may not represent the entire embryo. In rare cases, an embryo categorized as abnormal could have resulted in a healthy pregnancy. Some patients and practitioners worry about discarding embryos that might have had potential.

PGT-A as an Embryo Selection Tool

How does PGT-A serve as an embryo selection tool?

Diane: PGT-A helps prioritize which embryos to transfer, reducing time, financial costs, and emotional strain. It’s particularly helpful in cases where patients have multiple embryos frozen. Knowing which ones are chromosomally normal allows for better long-term planning, especially for families hoping to have multiple children from one IVF cycle.

Financial and Emotional Considerations

What should patients know about the financial side of PGT-A?

Diane: At Markham Fertility Centre, the cost of PGT-A is based on the number of embryos tested. While there’s an upfront cost, it may save money in the long run by reducing the need for repeated transfers or cycles.

And emotionally?

Diane: PGT-A can provide peace of mind by offering clarity about an embryo’s potential. It reduces the emotional toll of failed transfers, miscarriages, and the uncertainty of not knowing whether frozen embryos will result in successful pregnancies.

Mosaic Embryos: From Fear to Understanding

How has the understanding of mosaic embryos evolved?

Diane: Initially, mosaic embryos were avoided due to fears about poor outcomes. However, studies and real-world data have shown that many mosaic embryos can lead to healthy pregnancies. Counseling patients about the specific mosaicism details—like the type of chromosomal abnormality and the level of affected cells—helps them make informed decisions.

Who Should Consider PGT-A?

According to clinical guidelines, who is PGT-A recommended for?

Diane: PGT-A is especially beneficial for:

• Patients over 35, due to higher rates of chromosomal abnormalities.
• Those with recurrent miscarriages.
• Patients who’ve had multiple failed IVF transfers.

However, decisions about PGT-A should be personalized, considering factors like the number of embryos available and the patient’s family-building goals.