Preimplantation Genetic Testing for Monogenic Disorders (PGT-M)

A Guide for Individuals with an personal or family history of an inherited neurodegenerative condition

This informational site is intended for individuals who are interested in pursuing PGT-M for the genetic variant identified for their personal or family history of an inherited neurodegenerative condition. Individuals will need to have the genetic variant identified in order to pursue this family planning option. If you are interested in other family planning options, please check out this blog post.

PGT-M is a genetic test of embryos in order to identify which embryos have and do not have the genetic variant in question. For embryos without the genetic variant, they are then available to transfer to the person’s uterus to hopefully become a pregnancy.

PGT-M allows for the ability to reduce the possibility of having a child with the inherited neurodegenerative condition. In order to test embryos, the process of in vitro fertilization (IVF) has to ensue. There are many steps involved with both IVF and PGT-M, and it can be a long journey. This informational page goes into more detail about the process of IVF with PGT-M.

The first steps of pursuing PGT-M

2. Identify a fertility clinic

A fertility clinic will have relationships with labs that offer PGT-M. They chose these labs based on logistics, price, and test capabilities. Alternatively, you may have heard of a lab that meet your needs and want to find a clinic that works with this lab. The lab representatives may be able to provide you with a list of clinics they work with already, yet this may be information they can’t reveal. Also, clinics can sometimes set up a relationship with a lab even if they have not worked with them before. FertilityIQ is an organization focused on education and reviewing providers/clinics.

3. Check with your insurance provider

Contact your insurance company to inquire about their coverage for genetic testing and IVF. It is possible they cover genetic testing but not IVF or the other way around. Not all labs work with insurance companies, so it is important to check their billing practices. For individuals without fertility benefits, reduced cost self-pay packages are available at some fertility clinics. RESOLVE offers many resources such as an insurance coverage by state guide.

1. Collect your and your family’s genetic test reports

If you’ve had genetic testing, obtain a copy of those results, so you can send them to your fertility clinic. The fertility clinic will send them to the genetic testing lab along with your test order form. The lab will need this information to review your case. If you haven’t had genetic testing and are not planning to have it done, but one of your relatives (mother, father, aunt, uncle) has, then please obtain a copy of that report. If no one has had genetic testing in the family, then the option of PGT-M is highly unlikely to be available until the testing has been completed.

4. Work with the PGT-M Laboratory

  • Every PGT-M case is reviewed by staff at the genetic testing lab. These individuals are checking to see if the case is clinically indicated, meaning is there a chance that embryos could develop a genetic condition, and if it is technically feasible. As we will review shortly, PGT-M is not like other genetic tests, and requires the lab to create an individualized evaluation for each family pursuing PGT-M. The staff will need to review your situation to make sure it appears that the lab can create a PGT-M test for the family.

    The staff may ask for additional documentation or have questions that need to be addressed. They may ask who in the family has had genetic testing and who is currently living.

    If your test report is in another language, then it is possible the lab asks that you have it translated.

    If a lab accepts your case, then they will move you through their process. At this time, it may not be guaranteed that the lab will be able to design a test for your family. There are other steps in the process to complete.

  • Typically, labs will have a genetic counselor assigned to your case in order to keep up with the necessary documents, as a point of contact for both you and your clinic, and to provide updates as needed. Your genetic counseling consult is primarily used to discuss the PGT-M process and what the lab needs to move forward with your case. You may be asked about your family history. You will be informed of the test’s limitations and possible results. This is where you can ask all of your questions regarding PGT-M. If your clinic hasn’t discussed the option of adding on PGT-A, then this is a good time to discuss the benefits and limitations of this assessment. PGT-A is a genetic test for the embryo to assess for chromosomal conditions. Check out more information here.

  • Once you’ve met with the genetic counselor and all documentation is provided, then the lab will send out kits that you and your family will use to submit DNA samples. The lab is not performing genetic testing for anyone, rather they are identifying unique DNA sequences in order to develop the PGT-M test. The lab may need DNA from other relatives in order to create the specialized PGT-M test. Check out this blog post on Talking with Your Relatives About PGT-M.

    Once everyone’s DNA is submitted, test design usually starts. Test design may take 4-12 weeks, depending on the lab’s turnaround time.

Downloadable checklist

PGT-M requires in vitro fertilization (IVF)

In vitro fertilization (IVF) is the process of creating embryos outside of the uterus. The process involves maturing as many egg cells as possible by having the person with the ovaries take medication. Afterwards, the egg cells are retrieved and fertilized with sperm in a laboratory. Embryos will grow and develop until day 5 or 6 at which point they have about 200 cells and can be biopsied. The biopsied cells are sent to the genetic testing lab for analysis.

It is critical to know that there is something called the “attrition rate”, meaning that at each of these stages there is the potential for eggs retrieved to not be viable, unable to be fertilized, or an embryo that stops developing which is called an “arrested embryo”. Given this, the number of embryos are not equal to the number of eggs originally matured. Some people may start with 20 eggs and end up with 3 embryos for PGT-M testing. Your fertility doctor will be able to further discuss your possible attrition rate.

People utilize IVF for many reasons. Some reasons can include a same sex couple with a need for donor sperm or egg, a couple who have an infertility diagnosis, a person planning for single parenthood, an individual who has a cancer diagnosis and preserved their egg/sperm cells, and individuals who are pursuing PGT-M for a personal genetic condition or a couple who are carriers of a condition. While there are many people coming to IVF for their own reasons, it can still feel isolating to pursue IVF for PGT-M for an inherited neurodegenerative condition. It may require you to advocate for your needs and explain the need for clear and quickened timelines. Everyone will feel the impending time to pregnancy, but it is reasonable to express your unique relationship to time given the realities of a neurodegenerative condition.

Another point that is not always discussed is for couples who pursue IVF for the purpose of PGT-M and otherwise have not yet tried to conceive spontaneously, unexpected fertility issues may arise during the process. This experience can add another layer of complexity, particularly if only discovered in the middle of their IVF process.

The PGT-M Process

After the genetic testing lab completes the test design, they will be able to test embryos. 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. At this stage of an embryo’s development, we call it a blastocyst. In order to perform the genetic analysis, a few cells are biopsied from the embryo and sent to the genetic testing laboratory. Specifically, 5-10 cells from the outside layer of the embryo, called the trophectoderm, are biopsied. The cells of the trophectoderm will become the future placenta and supporting structures of the pregnancy whereas the cells of the inner cell mass on the inside will become the future baby.

The laboratory will run the PGT-M analysis to generate a report for each sample sent in which may take a few weeks. The report will help guide which embryos are expected to have the genetic variant and which are not. PGT-M is a genetic test that can evaluate for one or a few conditions, but it is not a comprehensive assessment. PGT-M does not assess for all possible genetic conditions.

Even though PGT-M is a helpful tool, its accuracy is not 100%. There is a possibility of getting false positive or negative results. The lab you work with should have statistics on their accuracy rates. Testing in pregnancy or after birth can still be considered because PGT-M is not considered diagnostic. The way to view the testing is as something that can substantially reduce the chance of passing on the genetic variant, but it does not eliminate the chance completely.

The final steps of pursuing PGT-M

5. Start the IVF process

If you are pursuing IVF only for the purposes of PGT-M, then it is ideal to wait for the lab to confirm the test design was successful. In most cases it is, but there are times it is not.

6. Send embryos for PGT-M testing

Depending on the lab, it may take 2 or so weeks to receive the results. Check in with the lab and your clinic to get the appropriate turnaround time for results.

7. Select which embryo to transfer, if any are available

Your physician and a genetic counselor at the lab or at a clinic can review the results in more detail. It is possible the results are not straightforward and some uncertainty may persist.

8. Potentially restart the IVF process to obtain more embryos or transfer an embryo

It is possible that it takes more than 1 round of IVF to identify an embryo negative for the genetic variant. Once the embryo is identified, then it is transferred. It is possible that an embryo transferred may result in a pregnancy or miscarriage. Your provider can discuss what those chances are. There are multiple appointments after transferring to assess the health of the pregnancy.

“PGT-M can be difficult and filled with uncertainty. Give yourself grace.”

“Start the process as soon as you’ve become even slightly interested. You can back out, if needed.”

Important topics

  • PGT-A

    Preimplantation genetic testing for aneuploidy (PGT-A) is another assessment that often is included with PGT-M. PGT-A counts the number of chromosomes present with the intention to implant embryos with the typical number of chromosomes to increase implantation and reduce the risk of miscarriage. Check this page out for more details of this testing and its limitations.

    Click Here

  • Exclusion or Nondislosure PGT-M

    An individual may know they have a family history of ALS and the gene that causes the condition; however, they may not be ready to learn their status and forgo predictive testing. There may still be the option to pursue PGT-M testing through “exclusion or nondisclosure” testing. This page explores the option further and requirements.

    Click Here

  • Research Results

    Genetic testing through a research program is one way individuals have discovered their status. Some PGT-M labs may accept the report for the development of the PGT-M test, yet other labs may ask for clinical testing with a lab that has been CLIA and CAP approved.

    Click Here

  • Talking with your family

    Some people may have relatives that are not supportive in their decision to pursue PGT-M or they have relatives that are unsure of why they need to provide their genetic testing reports and DNA to the lab. This page discusses these points and ways to discuss PGT-M with relatives.

    Click Here

  • Why is PGT-M so different from other genetic tests?

    PGT-M requires DNA from families and genetic test reports whereas other genetic testing is not as demanding. The reason for this is because PGT-M is performed via linkage analysis and is the process of developing a specialized test designed only for your family.

    Click Here

  • Egg Cryopreservation/ Freezing

    You may not be ready to have a child or haven’t met your significant other yet. However, you want to increase your odds to have as many embryos as possible for when you do pursue PGT-M. Egg freezing is a way to preserve your fertility given after a woman turns 35, there is reduced fertility and number of eggs available to retrieve for embryo creation.

    Click Here

  • Other Family Planning Options

    PGT-M with IVF is one of many options someone can pursue. Some individuals may utilize multiple options to complete their family. These options are highly personal

    Click Here

  • DNA Banking - Obtain your relative's DNA

    In many cases, in order to create the PGT-M test, your relative, who was diagnosed with ALS and the genetic variant, will need to provide a DNA sample. Even if you are not yet ready to pursue PGT-M, DNA banking can be an option to prepare for when you are.

    Click Here

  • What to do with embryos you aren’t transferring?

    In the world of In Vitro Fertilization (IVF), the main goal is to obtain embryos that are eligible for transfer. However, what do you do with the embryos you aren’t planning to transfer whether they are eligible or not.

    Click Here

To talk to a genetic counselor, click here.