What should I expect with PGT-M?
Preimplantation genetic testing is performed on embryos created through in-vitro fertilization (IVF). An embryo is created after an egg is fertilized by a sperm. After fertilization, embryos develop from a single cell into a cluster of around 200 cells. In order to perform the genetic analysis, a few cells are biopsied from the embryo and sent to a genetic testing laboratory. The laboratory will run the PGT-M analysis to generate a report for each sample sent in. The report will help guide which embryos are expected to have the condition and which are not.
The main purpose of PGT-M is to carefully select and implant embryos that do not carry the specific genetic condition of concern. This helps increase the chances of the birth of a baby without the genetic condition.
PGT-M is a genetic test that can check for one or a few specific conditions if there is a known chance of passing them on. However, it is important to know that PGT-M does not assess for all possible genetic conditions. It is a specialized test focused on specific conditions of concern.
Even though PGT-M is a helpful tool, it is not foolproof. There is a small possibility of getting false results, both negative (missing a condition) or positive (indicating a condition that is not present). That's why it's still important to consider other testing options during pregnancy or after a baby is born.
To test embryos with PGT-M, several steps need to be followed. This includes going through the IVF process and developing the specific PGT-M test for your family's genetic situation. The development of the PGT-M test can take some time, usually between 4 to 12 weeks. Additional appointments and testing may also be necessary throughout the process.
Why is PGT-M different from other genetic tests?
PGT-M stands out from other genetic tests for two primary reasons.
PGT-M is a highly specialized assessment that is tailored specifically to each family's genetics. Unlike other genetic tests, in which everyone uses the same assessment, PGT-M creates a unique test for every family. Even if a PGT-M test has been developed for a particular condition in the past, it doesn't necessarily apply to your family's genetic makeup.
Therefore, it's important to note that PGT-M may not be suitable or feasible for every family's situation and certain requirements must be met. The initial step in the PGT-M process involves a comprehensive case review, where genetic test reports and family information are carefully examined to determine if PGT-M is a viable option.
PGT-M differs from other genetic tests in that it focuses on tracking a specific variant that may be passed on from a couple or individual to their embryos. This is achieved through a method called linkage analysis. In contrast, many other genetic tests, such as carrier screening tests, involve sequencing a person's DNA to identify any changes or variations in the genes that could impact their function. It's akin to reading through the instruction manual of a person's body to identify errors or missing information whereas linkage analysis is like comparing two editions of the manual to see if there are any special markings or changes that help us tell them apart.
By utilizing linkage analysis, PGT-M enables the identification and tracking of specific variants within a family's genetic makeup.
What is Linkage Analysis?
For most of our genes, we all have two copies. One we inherited from our mom or egg donor and the other from our dad or sperm donor. Linkage analysis is the ability to distinguish between the two gene copies. By distinguishing between the two gene copies, linkage analysis will be able to discern which gene copy is the one with the variant and the gene copy without the variant.
Linkage analysis involves examining the DNA sequence of a person to identify distinctive qualities or markers that help distinguish between the two gene copies. These markers can be specific changes in the genes that do not cause harm to the gene's function but aid in differentiating the gene copies. Multiple markers are identified to create a "marker profile" for each gene copy. Then, during embryo evaluation, these marker profiles are analyzed to determine which gene copy was inherited.
It's important to note that performing linkage analysis requires the involvement of a second generation. For instance, if a person has a known genetic condition and their father is also impacted by the same condition, the DNA of the person's parents can be compared to their own DNA. This comparison helps identify the specific gene copy responsible for the condition and the corresponding marker profiles.
Below is a visual example of how linkage analysis is used.
The above diagram is called a pedigree. It illustrates the relationships between the patient, her parents, her partner, and his parents. The squares represent genetic males, while the circles represent genetic females. In this diagram, the patient is a genetic female, and her partner is also shown.
The partner's father has marker profiles A and B, while his mother has marker profiles C and D. When the partner was conceived, he inherited his father's B marker profile and his mother's C marker profile. The partner and his father have both been diagnosed with the genetic condition. Given both the partner and father have the genetic condition, the B marker profile is considered to be linked to the variant that causes the condition.
Now, the couple wants to test their embryos for this genetic condition. There are two possible options for the inheritance of marker profiles in the embryos from the partner. 50% of the embryos will inherit the partner's B marker profile, while the other 50% will inherit the C marker profile. You'll notice that the potential embryo results will also have a 50% chance to inherit the E or F marker profile that has been established for the patient. Neither the E or F marker profile have a variant of concern.
It is presumed that the embryos inheriting the B marker profile will have the genetic condition because this marker profile has been linked to the disease variant.
Please note that this is a simplified explanation for illustrative purposes. In some cases, there will be egg or sperm donors or other family structures not shown. The actual process and analysis of PGT-M involve more detailed genetic assessments.
Below is a checklist of the major steps before and during PGT-M. Genetic counselors at the lab or clinic can further discuss what to expect.
* This blog constitutes general information about genetic testing and medical screening. This blog does not offer or provide medical advice or diagnosis, and nothing in this blog should be construed as medical advice or diagnosis. Do not rely on the information in this blog/article to make medical management decisions. Please consult with a medical professional before making those decisions. Do not delay in seeking professional medical advice if you think you have a medical concern. Do not disregard professional medical advice based on any information received in this blog.
