What is PGT-M? Understanding Pre-implantation Genetic Testing for Monogenic Disorders
An interview with Diane Myles Reid, Genetic Counsellor at Markham Fertility Centre
On EP36 of My Fertility Podcast we welcome back for a third interview, Diane Myles Reid, the lead genetic counsellor at Markham Fertility Centre and the former President of the Canadian Association of Genetic Counsellors. In this episode, she shares her expertise on preimplantation genetic testing for monogenic conditions (PGT-M). As a powerful tool in reproductive genetics, PGT-M allows families to reduce the risk of passing on serious genetic conditions to their children. Diane explains the process, benefits, and considerations for PGT-M, providing invaluable insight for those navigating this specialized area of fertility treatment.
What is PGT-M and Who is it For?
Diane, welcome back! Can you explain to our listeners what PGT-M is and who might benefit from it?
Diane: Thank you for having me back! PGT-M stands for preimplantation genetic testing for monogenic conditions. “Monogenic” refers to conditions caused by a specific genetic variant in a single gene. This test is designed for families who already know they have an increased risk of passing on a specific genetic condition.
This might include individuals diagnosed with a genetic condition themselves, those with a family history of such conditions, or couples identified as carriers of the same autosomal recessive condition. PGT-M is not for everyone—it’s a specialized test for specific circumstances where there is a clearly identified genetic risk.
How Do You Know If You’re at Risk?
How would someone know if they’re at risk of passing on a genetic condition?
Diane: Great question. Risk is typically identified in three main ways:
- Personal Diagnosis: An individual may already have a diagnosed genetic condition.
- Family History: A person might learn of a genetic condition in their family, prompting further investigation.
- Carrier Screening: Couples may discover through genetic testing that they are carriers of the same autosomal recessive condition. This combination increases the likelihood of having an affected child.
For autosomal recessive conditions, each parent must pass on the altered gene for the child to be affected. If only one parent is a carrier, the child is unlikely to inherit the condition, but may still become a carrier.
Understanding Carriers and Genetic Inheritance
You mentioned the term “carrier.” What does it mean to be a carrier, and how does that relate to genetic inheritance?
Diane: A carrier has one copy of a gene that functions as it should and one copy with a genetic variant. Most carriers are healthy because the functioning copy compensates for the faulty one. However, if both parents are carriers of the same condition, there’s a 25% chance their child will inherit two faulty copies of the gene, leading to the condition.
For autosomal recessive conditions, the genetic risk is calculated as:
- 25% chance of an affected child
- 50% chance of a carrier child
- 25% chance of a child unaffected and not a carrier
In autosomal dominant conditions, only one copy of the gene needs to be altered to cause the condition. Here, each embryo has a 50% chance of being affected.
What PGT-M Can and Cannot Test For
Can PGT-M detect all genetic conditions, or are there limitations?
Diane: PGT-M is very specific. It can only test for a condition if the genetic cause is clearly identified. The test is tailored to the specific genetic variant present in the family. This means families must first undergo genetic testing to confirm the exact cause of their condition before PGT-M can be offered.
What about conditions like ADHD or autism?
Diane: Most cases of ADHD or autism are not caused by single-gene changes. These are complex traits influenced by multiple genes and environmental factors. PGT-M is typically unsuitable for such conditions unless a specific genetic variant linked to autism or ADHD has been identified in the family.
Common Conditions Tested with PGT-M
What are some examples of conditions commonly tested for using PGT-M?
Diane: PGT-M has been used to test for hundreds of conditions. Some of the most common include:
- Cystic fibrosis
- Spinal muscular atrophy
- Fragile X syndrome
- Huntington’s disease
- Inherited cardiomyopathies
- Inherited cancer syndromes, such as BRCA mutations
These conditions are often severe or life-limiting, making PGT-M an invaluable tool for families who wish to minimize these risks.
The Role of Carrier Screening
What about families without a known history of genetic conditions? How can they determine their risk?
Diane: For these families, expanded carrier screening is an excellent option. This test checks for hundreds of genetic conditions, many of which a person might not realize they carry. Carrier screening is especially useful in cases involving donor sperm or eggs, allowing intended parents to ensure compatibility and reduce genetic risks.
Personalizing PGT-M for Dominant and Recessive Conditions
Can you elaborate on the difference between autosomal dominant and recessive conditions in the context of PGT-M?
Diane: Certainly. For autosomal recessive conditions, both parents must be carriers of the same variant for there to be a risk of an affected child. This scenario is less common but important to identify.
For autosomal dominant conditions, only one parent needs to carry the altered gene. Every embryo then has a 50% chance of inheriting the condition. PGT-M allows families to determine which embryos are unaffected and can be safely transferred.
The Emotional Power of PGT-M
Do you have any personal stories that illustrate the impact of PGT-M?
Diane: Absolutely. I worked with a patient who carried a gene linked to a hereditary cancer syndrome that had plagued his family for generations. After undergoing PGT-M, he had a healthy baby without the genetic variant. I’ll never forget his words: “It ends with me.” Knowing he could change the trajectory of his family’s health was profoundly moving.
Accuracy and Limitations of PGT-M
How accurate is PGT-M, and are there limitations families should know about?
Diane: PGT-M is highly accurate—above 98% in most cases. However, no test is perfect. We often recommend follow-up prenatal testing, like amniocentesis or chorionic villus sampling (CVS), to confirm the results once a pregnancy is established. While the chances of an error are low, this additional testing provides reassurance.
The PGT-M Process
What does the process of undergoing PGT-M look like?
Diane: Here’s an overview of the PGT-M process:
- Genetic Testing: Identify the specific genetic variant in the family or individual.
- Fertility Consultation: Patients meet with a fertility specialist to plan for IVF.
- Genetic Counseling: A genetic counselor reviews family history and prior test results, ensuring all necessary samples are collected.
- IVF and Embryo Biopsy: Embryos are created via IVF and grown to the blastocyst stage (5-6 days). A small sample of cells is biopsied and sent to the PGT lab for analysis.
- Results: Results typically take 3-4 weeks, and patients can opt to combine PGT-M with PGT-A (chromosomal screening) for additional insights.
The Difference Between PGT-A and PGT-M
How do you distinguish between PGT-A and PGT-M for patients?
Diane: PGT-A, or preimplantation genetic testing for aneuploidy, is broader. It screens for chromosomal abnormalities in all IVF patients, assessing embryo viability and reducing miscarriage risks. PGT-M, on the other hand, is targeted. It focuses on specific genetic conditions for families with a known risk.
Costs and Financial Considerations
What are the costs of PGT-M, and is it covered by insurance?
Diane: Unfortunately, PGT-M is not covered under Ontario’s OHIP-funded fertility program. Costs typically range from $6,000 to $10,000 per cycle, depending on the number of embryos and lab requirements. Sequential testing (PGT-A first, then PGT-M) can sometimes reduce costs by avoiding unnecessary testing on abnormal embryos.
For Families Without Fertility Challenges
What options exist for families who don’t face infertility but still want to minimize genetic risks?
Diane: For naturally conceiving couples, prenatal diagnostic testing like CVS or amniocentesis can provide information during pregnancy. However, only PGT-M ensures embryos are unaffected before transfer, eliminating the potential for difficult decisions later in pregnancy.
The Importance of Genetic Counselling
How important is access to genetic counseling for families considering PGT-M?
Diane: It’s crucial. Genetic counseling helps families understand their risks, the testing process, and their options. At Markham Fertility Centre, we’re fortunate to have an in-house team of genetic counselors who work closely with patients, ensuring they receive comprehensive care tailored to their needs.
Closing Thoughts
PGT-M is a groundbreaking technology that empowers families to reduce the risk of serious genetic conditions. While it’s not for everyone, it offers a lifeline for those with known risks, enabling them to build healthier futures. By combining PGT-M with expert genetic counseling and fertility care, patients can navigate this complex journey with confidence and clarity.