PGT-A vs. PGT-M: What’s the difference, and which one do you need?

Preimplantation genetic testing for aneuploidy (PGT-A) and preimplantation genetic testing for monogenetic diseases (PGT-M) both offer crucial insights into an embryo's genetic status during in vitro fertilization, but they do so from entirely different angles.

In this article, we’ll explore PGT-A vs. PGT-M side-by-side, and explain what they test for, how they are performed, and who benefits from them, so you can make informed decisions about your IVF journey and the health of your future child.

What is PGT-A?

PGT-A, previously known as preimplantation genetic screening (PGS), is an embryo screening method used during IVF to assess whether an embryo has the correct number of chromosomes.

Every embryo should ideally have 46 chromosomes — 23 from each parent. But sometimes, an embryo ends up with too many or too few. This condition is called aneuploidy, and it’s one of the most common causes of failed implantation, miscarriage, and genetic conditions, such as: 

• Down syndrome (caused by an extra copy of chromosome 21)

• Edwards syndrome (caused by an extra copy of chromosome 18)

• Patau syndrome (caused by an extra copy of chromosome 13)

• Turner syndrome (caused by the loss or mutation of the X chromosome)

PGT-A has 98% accuracy in detecting chromosomal abnormalities and helps identify embryos more likely to result in a healthy pregnancy.

Source: RDNE Stock project

PGT-SR vs. PGT-A: What’s the difference?

While PGT-A focuses on the number of chromosomes, preimplantation genetic testing for structural rearrangements (PGT-SR) focuses on how chromosomes are arranged.

PGT-A is commonly used when there is no known inherited chromosomal issue but a general concern about aneuploidy. PGT-SR is recommended when one or both partners carry a balanced chromosome rearrangement.

This condition may not affect you, but it can lead to embryos with too much or too little genetic material, often causing miscarriage or developmental issues.

Who should consider PGT-A?

In most cases, PGT-A has become a standard part of care during the IVF journey. It’s especially useful when there's a higher chance of chromosomal abnormalities, such as in advanced maternal age or severe male factor infertility.

You should ask your clinic for a PGT-A test if you:

• Are 35 or older

• Have had multiple miscarriages or recurrent pregnancy loss

• Have experienced repeated IVF failure

• Plan to transfer a single embryo

• Had a previous pregnancy or child with a genetic or chromosomal condition

Source: Nadezhda Moryak

How does PGT-A work?

PGT-A is performed exclusively as part of the IVF process and typically begins about 5 to 7 days after fertilization, once embryos reach the blastocyst stage. At this point, the embryos comprise around 100 cells, some of which will become the baby, and some the placenta. 

PGT-A focuses only on the cells destined to become the placenta, which helps minimize the risk of harming the part of the embryo that could develop into the fetus.

Here’s what the process looks like, step by step:

1. Embryo biopsy: A few cells (usually 5–10) are gently removed from the outer layer of each blastocyst. Almost all embryos continue developing normally after biopsy, but the procedure does carry a slight risk of causing damage that could prevent further development.

2. Embryo freezing: The embryos are frozen using a rapid freezing method called vitrification to store them safely while the biopsy samples are analyzed.

3. Chromosomal analysis: The DNA from the biopsy sample is carefully examined using advanced sequencing technology to count the number of chromosomes and detect any abnormalities. The analysis may also reveal the sex chromosomes of each embryo, though this is usually only reported if medically relevant or requested.

Once the testing lab finishes the analysis, which is typically after one to two weeks, it sends a detailed report back to your fertility clinic, so you can decide which embryo(s) to transfer. Any embryos not chosen can remain frozen for future use.

PGT-A testing results

PGT-A test results offer crucial insight into each embryo's chromosomal health, helping you and your doctor decide which embryo(s) to consider for implantation.

Each tested embryo is typically categorized as:

1. Euploid: All cells sampled from the embryo are chromosomally normal. These embryos are ideal for implantation as they are the most likely to result in a successful pregnancy.

2. Aneuploid: All cells obtained from the biopsy had a chromosomal abnormality, such as missing or extra chromosomes, or irregular shapes. These embryos are not recommended for transfer.

3. Mosaic: Some tested cells are normal, and some are abnormal. The healthy-to-abnormal cells ratio will determine the viability of mosaic embryos.

Sometimes, the results can be inconclusive, which usually happens due to insufficient DNA or poor sample quality. In this case, your fertility doctor may recommend taking the test again.

The report may include information about which chromosome(s) are affected and offer further details about the nature of any abnormalities.

While PGT-A can offer valuable insights, it’s not foolproof. There is a small chance the test may give a false result — missing an abnormality or detecting one that isn’t there. As a result, healthy embryos might be mistakenly discarded.

What is PGT-M?

PGT-M (formerly known as PGD) is a genetic test used to screen embryos before pregnancy for a specific inherited condition caused by a defect in a single gene. 

It can help identify healthy embryos with 98% accuracy, and can test for over 1700 single-gene inherited disorders, including:

• Cystic fibrosis

• Sickle cell disease

• Tay-Sachs disease

• Spinal muscular atrophy (SMA)

• Huntington’s disease

• Duchenne muscular dystrophy

• Hemophilia A and B

• Fragile X syndrome

• Thalassemia

• BRCA1/BRCA2-related hereditary breast and ovarian cancer syndromes

PGT-P vs. PGT-M: What’s the difference?

While PGT-M can detect inherited single-gene disorders, preimplantation genetic testing for polygenic conditions or PGT-P estimates the risk of developing complex, late-onset conditions that depend on the expression of multiple genes.

PGT-P analyzes multiple genetic variants at once to detect the embryo’s risk for developing conditions like diabetes, heart disease, certain cancers, and more. This means parents get a proactive overview of long-term health and have the chance to consider risk reduction for chronic diseases that impact millions every year.

PGT-M, on the other hand, is essential if one or more parents are the carriers of a condition influenced by a single genetic mutation.

Who should consider PGT-M?

You should consider PGT-M if:

• You or your partner carries a known genetic condition (carriers of a known genetic disorder have up to a 50% chance of passing it on to a child)

• There is a family history of a serious inherited condition

• You’ve had a previous pregnancy or child affected by a genetic disorder

• You’re concerned about passing on a condition linked to your ethnic background (e.g., beta-thalassemia in Mediterranean populations, or sickle cell disease in people of African descent)

PGT-M helps you take proactive steps toward building a healthy family and is useful even if you don't have fertility issues.

Because PGT-M is highly targeted, it’s only used when a specific mutation is known to cause a particular condition and the inheritance pattern is understood.

How does PGT-M work?

PGT-M is performed during an IVF cycle, and the cell sampling process is the same as for the PGT-A test. 

A few cells from an embryo's future placenta are tested in a lab to check whether the embryo has inherited a specific genetic mutation from one or both parents. This helps identify which embryos are affected by the condition and which are not, so only the healthy ones are considered for transfer.

Since PGT-M involves genetic testing of the parents and sometimes close relatives, it is custom-designed for your family, and it can be complex, especially for rare conditions.

Source: Artem Podrez

Still, emerging technologies are making PGT-M even more accurate and accessible. For instance, karyomapping is one of the most advanced methods available today.

Karyomapping is like creating a detailed family DNA map. DNA is collected from both parents and, if possible, a close relative who has the condition or is known to be a non-carrier. This helps identify a unique DNA pattern linked to the gene causing the condition in the family, like a family DNA fingerprint.

Scientists then compare each tested embryo’s DNA to the family fingerprint to check whether the embryo inherited the gene mutation or the healthy version.

Bonus read — To gain more insights into available genetic and health tests during IVF, check out these helpful guides:

• Preconception genetic testing

• Quad screen vs. NIPT

• Cystic fibrosis carrier testing

• NIPT vs. amniocentesis

• PGT-P

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PGT-A vs. PGT-M vs. PGT-SR vs. PGT-P: Key differences for better family planning

PGT-A, PGT-M, PGT-SR, and PGT-P all help enhance the chances of a healthy pregnancy for couples undergoing IVF. Each type of PGT focuses on different aspects of genetic health. Depending on your medical history and genetic risks, one or more of these tests may be needed. 

Here’s a breakdown of the purpose, ideal candidates, and limitations of each test to help you understand how they can support you in building a healthy family:

Benefits and risks of PGT-M vs. PGT-A

Weighing the benefits and risks of PGT isn’t only about understanding the facts but about deciding what is right for your family. These choices often rely on personal values, from how you define health and quality of life to how you envision the future for your child.

It may help to look at the potential benefits and risks side by side:

Consider what matters most to you regarding your child’s health and future, and what decisions you would or wouldn’t feel comfortable making based on genetic results. For instance, think about what you would do if none of our embryos came back as chromosomally normal.

Source: Fayette Reynolds M.S.

What happens when PGT tests don’t give a clear answer?

An embryo biopsy sent for PGT testing can come back without clear answers because the laboratory could not confidently determine the embryo’s chromosomal status or genetic makeup. It occurs in around 5% of tested embryos at many fertility clinics.

An inconclusive PGT report doesn’t necessarily mean something is wrong with the embryo. It usually happens due to:

• Not enough DNA in the sample

• Degraded or poor-quality DNA

• DNA amplification failure

• Technical limitations during testing

• Poor embryo quality that wasn’t detectable before the biopsy

These embryos can still be eligible for transfer, and many view them similarly to untested embryos in natural conception.

You may store or retest the embryo, but a new biopsy involves thawing, retesting, and freezing again, which may not be possible in every case.

If you want more clarity during your IVF journey, you can also consider genetic optimization tools like Nucleus Embryo for support.

Source: Cottonbro studio

Nucleus Embryo offers a unique software for post-PGT decision-making that helps you compare your embryos based on dozens of genetic insights. It builds on the PGT-P data of your embryos and helps you analyze and sort them based on their risk for common conditions such as Type 2 diabetes, breast cancer, prostate cancer, heart disease, Alzheimer’s disease, and more. The result is a refined, data-driven method to help you make decisions beyond immediate viability but with a long-term view of your family’s health.

How Nucleus Embryo provides more clarity

Even after a successful PGT-A or PGT-M, choosing the right embryo can be challenging. That’s where Nucleus Embryo can provide next-step support for families seeking deeper insight.

Nucleus offers clinical-grade analyses that expand on the PGT-P embryo data your clinic provides. You can upload the data for up to 20 embryos and get access to: 

• Risk scores for common diseases like Type 2 diabetes, heart disease, multiple sclerosis, OCD, Parkinson’s disease, and more

• Physical trait predictions, including height, eye color, intelligence, and muscle strength

If you’re yet to get your PGT-P testing done, you can reach out Lifeview for support.

Additionally, if your clinic offers whole-genome embryo files, Nucleus can also screen for rare variants for inherited conditions not covered by standard IVF testing panels.

The best part is that Nucleus Embryo is designed for parents. In an interactive, visual dashboard, you will be able to compare embryos side-by-side using clear graphics and straightforward explanations.

In addition to embryo analysis, you can opt for multigenerational analysis. By adding your and your partner’s DNA, you can get more personalized insights, helping you understand how certain risks or traits may be passed on and what the chances are of them showing up in your child. You can get the Nucleus Family all-in-one health screening for you and your partner together for a discounted price.

How to get started with Nucleus Embryo

Nucleus Embryo is the next step after you’ve done PGT-P embryo testing, so make sure to ask for the test early on. Here’s what the process can look like:

1. Ask your clinic for PGT-P testing with LifeView by Genomic Prediction

2. Sign up for Nucleus Embryo during or after your IVF cycle

3. Request your embryos’ PGT-P DNA data from your clinic

4. Upload the data to Nucleus Embryo and analyze the embryo analysis report

If you got any questions or curiosities around the process, fill out the Nucleus Embryo form and have an expert reach out to you.

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Featured image source: Nataliya Vaitkevich