My PGT-M case was declined
Preimplantation genetic testing for monogenic conditions (PGT-M) is a genetic test that can be performed on embryos. It is specifically designed to identify hereditary conditions with an increased likelihood of being passed on to children. Individuals who have a personal genetic diagnosis or a reproductive pair that are identified as carriers may consider PGT-M as they know there is an increased chance to pass on the hereditary condition.
Despite significant scientific advancements, one might assume that PGT-M, which has been available for over a decade, would have all the answers. However, there are instances where PGT-M cannot be utilized for certain families. In this blog post, we will explore these situations and delve into the reasons why PGT-M is not universally accessible.
How is PGT-M performed?
In our Preimplantation Genetic Testing Information Page, we talked about the basics of PGT. However, PGT-M is a bit more complex compared to other types of PGT tests. It still involves taking a few cells from embryos made through in vitro fertilization (IVF). But, unlike other PGT tests, PGT-M requires more information from the family and the laboratory doing the assessment.
Each PGT-M test is designed specifically to the family’s genetic information. For example, if two families need PGT-M for cystic fibrosis, they won't use the same test. Even though cystic fibrosis is caused by the same nonworking gene, the reasons behind the gene not working may differ between the families as well as the families have other unique genetic factors. So, each family gets their own unique PGT-M test based on their genetics.
That means, even if a lab has made a PGT-M test for cystic fibrosis before, they haven't created a test for your family's genetics specifically.
Because each test is designed specifically to a family’s genetics, the laboratory needs to first determine if PGT-M is feasible
Before having a detailed conversation of how PGT-M works and the logistics of proceeding with the assessment, the laboratory must evaluate its feasibility based on a few important factors.
Firstly, the lab needs to determine if there is a valid reason for conducting the PGT-M test. Sometimes, families may have genetic variations that don't pose health risks, or only one member of a couple may be a carrier of a genetic condition, which means there isn't an increased chance for their child to inherit the condition. By assessing the clinical indication for the test, it ensures that pursuing PGT-M is a reasonable choice. Since PGT-M is costly and requires significant time and effort, it's crucial that the test is used in appropriate cases.
Next, the lab needs to evaluate if they have the technical capability to perform the test. They examine the genetic reports provided by the family to determine if the specific genetic variations can be targeted and tested.
It's important to note that this initial step doesn't guarantee the lab's ability to design a test. Rather, it helps prioritize cases so that those who genuinely require the test can proceed with further discussions about expectations and requirements.
What information does a lab need?
The required information for the lab to make a determination may vary. In all cases, it is necessary to provide genetic test reports of the individuals who have or are carriers of the requested condition. These reports are essential for the assessment process. It is preferable to provide the lab with genetic reports of other family members, who are willing to participate in the test design. Having any documentation from a medical provider that explains the test results is valuable and sometimes necessary. If you have received genetic counseling, if possible, include the genetic counseling letter as it contains much of the necessary information.
Cases can either be declined or accepted after the lab receives the needed information.
A case can be rejected for either clinical reasons or technical limitations related to PGT-M.
Here are some examples of clinical reasons:
When only one member of the reproductive pair is a carrier of a genetic condition, and the other member has had negative testing, reducing the risk for future children.
When both members of the reproductive pair are carriers of the same condition, but the condition is expected to be “mild” with limited to no symptoms
When a condition seems to be present in only one child of a couple, known as "de novo." This means the genetic change occurred for the first time in that individual, not inherited from either parent, so the chances of it occurring again in another child are not expected to be increased.
Some of these clinical reasons may involve subjective judgments, or even if the risk seems low, families may still have concerns about the condition. If someone's PGT-M case is declined for a clinical reason, it is reasonable to ask for further clarification. Labs often have policies to help manage the large number of cases they receive, but it's important to remember that a policy is not a person.
However, when cases are rejected for technical reasons, the determination is less subjective and more based on specific requirements.
Here are some examples of technical reasons:
When there are no available family members to participate in the test design. In certain situations, the lab may need DNA samples from other family members, aside from the reproductive pair, to assist in designing the PGT-M test.
When one member of the reproductive pair is unable to provide a DNA sample. Both the egg and sperm contributors must provide a DNA sample, typically through a saliva sample or, in the case of sperm donors, a vial of sperm, in order to facilitate the design of a PGT-M test.
Many labs have genetic counselors as part of their team to explain why a case is declined and to address any anticipated challenges. Genetic counselors are assigned to each case to gather all the necessary information required by the lab and to provide detailed explanations about the complexities involved.
In some cases, a person's case may initially be accepted, but challenges may arise during the test design stage due to the customized nature of the test based on the family's genetics. Although rare, unforeseen difficulties can occur during the creation of the test.
Despite when someone’s case gets declined, it can be disheartening, especially if this was their reproductive plan. At the very least, it can be helpful to know why a case is declined, and the genetic counselors at the lab can assist in discussing the reasons.
For individuals planning to utilize PGT-M, it can be helpful to initiate the process as early as possible to assess feasibility and develop a suitable plan.
Resources:
https://www.fertstert.org/action/showPdf?pii=S0015-0282%2823%2900210-8
* 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.
