Did you know that nearly all embryos show some level of mosaicism, even in successful pregnancies? In this conversation with Meaghan Doyle, a Licensed Certified Genetic Counselor specializing in fertility genetics and the founder of DNAide Genetic Counseling, we’re discussing the latest findings on PGT-A testing and what it means for embryo selection and fertility treatment: and this is fascinating!
Meaghan joins me to discuss a fascinating new article titled “New PGT-A Test Shows that Nearly All Blastocysts and Fetal Tissue are Mosaic.” We’ll break down what this means for fertility treatment, embryo selection, and how patients can use this information to make the best decisions for their family-building journey.
In this episode, we cover:
- What PGT-A testing does and how its sensitivity has evolved
- What mosaicism is and why nearly all embryos exhibit it
- How new research is changing the way we interpret mosaic results
- What these findings mean for embryo selection and transfer decisions
- How fertility patients can advocate for themselves and make informed choices
Resources:
Find Meaghan Doyle’s DNAide Genetic Counseling website here
Find Dr. Aimee’s Fertility Essentials & Supplements
Full Transcript:
Dr. Aimee: The title of today’s show is: New PGT-A Test Shows That Nearly All Blastocysts and Fetal Tissue are Mosaic. I’m so glad that we have genetic counselor Meaghan Doyle on today. Did you know that nearly all embryos show some level of mosaicism, even in successful pregnancies? In this interview, we will dive into the latest findings on PGT-A testing and what they mean for embryo selection and fertility treatment. Join us as we explore how these advancements could reshape decision making for patients and providers alike.
I’m so delighted to have Meaghan Doyle back on today. Welcome, Meaghan.
Meaghan Doyle: Thank you for having me back, Aimee.
Dr. Aimee: Meaghan is a licensed certified genetic counsellor, specializing in fertility genetics, and the founder of DNAide Genetic Counselling. With a passion for empowering fertility patients, she provides clear evidence-based guidance to help them navigate complex topics like mosaicism and PGT-A testing. Meaghan began her career in 2018 as an in-house genetic counsellor, where her expertise quickly became essential for interpreting evolving genetic testing results. Today, through DNAide and her educational outreach, she bridges gaps in fertility care, ensuring patients and providers alike are informed and supported in making the best decisions for family building.
The article highlights that nearly all blastocysts and fetal tissue are mosaic to some extent. Meaghan, before we get into what this means for fertility patients, can you explain the PGT-A test and what it does?
Meaghan Doyle: Absolutely. When we do PGT-A in the clinic, we’re usually taking five to ten cells from the area of the embryo that is going to become the placenta. The purpose of PGT-A is to look at the chromosomes. Usually, doctors are using the results from PGT-A to help patients prioritize their embryos for transfer. If the results are normal, those embryos are usually transferred first. Embryos with not-normal results usually get transferred not-first.
Dr. Aimee: Not only not first, but sometimes not at all. That’s what you do for me, you save embryos. You’re literally an embryo rescuer, you are rescuing embryos that people would not have prioritized, and then once you talk to them, they learn more about their results and they can have babies from these embryos that are being described as abnormal when they’re really normal, because PGT-A isn’t perfect. What makes the test more sensitive?
Meaghan Doyle: Usually, when we’re doing PGT-A, we’re testing all of those five to ten cells in one big cluster. This sensitive test that they did in this research study was testing cells one by one and getting the genetic information from each, which isn’t something that we’re able to do in the clinic.
Dr. Aimee: What is mosaicism?
Meaghan Doyle: Mosaicism is when some of those cells have different genetic results from others. Usually, when we get a mosaic result from PGT-A, it would mean that some of the cells are expected to have normal chromosomes, but some of the cells are expected to have abnormal chromosomes.
Dr. Aimee: Why can a mosaic embryo result in a healthy baby, how does that happen?
Meaghan Doyle: The truth is we don’t really know. We do know that it can happen, and for a lot of patients, it does. That’s why it is so heartbreaking, for you and I, a lot of the time when patients don’t get that opportunity. It’s possible that we only tested a small amount of cells, so the part of the embryo that’s going to become the baby wasn’t tested when we did the test. Maybe all of those cells had completely normal chromosomes inside of them, and that might be why completely healthy babies are born.
Dr. Aimee: We never test the part that becomes the baby, because that’s the inner cell mass that’s inside the embryo. What we test is the trophectoderm cells, the cells on the outer shells. Why are the findings in this new study so interesting? When I saw the study, I said “we have to talk about this, people need to know about it.” Why is it such a fascinating and interesting study?
Meaghan Doyle: I think it’s interesting because they saw that every embryo they looked at had mosaicism, but when we do genetic testing in the clinic, we don’t see mosaic results very often, so it is quite different from what we usually see. It’s hard for patients when they do PGT-A. We’re hoping for normal results. That’s what gets bolded on the report, that is what everyone is hoping for in their hearts. When they get a mosaic result, it’s not what they want to hear. They don’t want to see anything that says anything other than normal. It can take a really long time to come around to the idea of transferring an embryo that has a mosaic result.
I think the idea that maybe mosaicism is a bit more common than we thought, maybe every embryo might have this type of finding, might help patients feel a little bit more comfortable with using embryos that have this type of result.
Dr. Aimee: When I see a mosaic embryo, I tell my patients that’s normal, it’s not an abnormal finding. I prioritize mosaic embryos just like I would an embryo that comes back in bold saying euploid, which means it has a normal set of chromosomes. How should patients interpret mosaic results when they see something like that?
Meaghan Doyle: I think that there are still a lot of different factors that can go into interpreting a mosaic result. Sometimes we use a level of mosaicism, low or high, is it closer to normal or closer to aneuploid or abnormal. We also can look at whether it was just a piece of a chromosome that was abnormal, segmental, or a full copy. All of these different things, including how the embryo looked under the microscope, is creating morphology, how quickly it became a blastocyst, there are so many things that can help a patient prioritize embryos for transfer. Meeting with a genetic counsellor like me can help them decide what they’re comfortable with and how they want to prioritize those embryos. Some embryos with mosaic results might do equally as well as embryos that test normal. Others might have a lower chance of bringing home a baby, possibly higher miscarriage rates, and every patient feels different about those types of things, so it’s important to think about them in detail.
Dr. Aimee: I think what you just mentioned is really important because sometimes patients sign discard forms even before they get their reports back. They’ve already signed a consent form that says, “I want my abnormal embryos discarded.” What they also don’t know is sometimes they’re signing that they want mosaicism masked. It’s really important that you get your official report unmasked and that you meet with someone like Meaghan to talk about your report, so that you’re not discarding potentially normal embryos.
Especially for my patients over 40, you and I – I would say more you than me because you are responsible for counselling my patients – have saved so many embryos from the discard box, so to speak. Thank you for all your work. I can’t say thank you enough.
What are the potential risks? You mentioned maybe a higher risk of miscarriage and potential outcomes of transferring a mosaic compared to euploid. What should patients know?
Meaghan Doyle: I think a lot of the time people are thinking mostly about the health of the child that’s going to be born from an embryo with a mosaic result. There are nuances, depending on the specific chromosome sometimes, that people need to be aware of. The more data we gather, it seems like today at the end of 2024, generally, the risk of having a child with a genetic condition related to the mosaic result is about 1% or less. I think a lot of times people think that number is going to be a lot higher.
Any pregnancy, regardless of whether that embryo tests euploid or not, whether you get pregnant without assistance, there is going to be a risk of a genetic condition or a birth defect. It doesn’t seem like those risks are higher when we use a mosaic result. Again, you can get information to look at your result to make sure that you’re comfortable. But I think that it’s important for people to know, especially with the findings from this study, that it doesn’t seem like the risks for babies born from mosaics are increased when you use a mosaic compared to a euploid.
Dr. Aimee: What would you say to a patient who was starting their IVF journey who, let’s say, doesn’t have options for which clinic they’re going to work with because of where they live, and the doctor won’t prioritize a mosaic embryo? How can they be their own best advocate?
Meaghan Doyle: That’s something that I help patients with a lot. Some doctors are convinced when they hear the research. That’s something that I help them with when I put their consult notes together. I fill it with lots of data from the research so that I can help them be an advocate and show them that for their specific embryo, there may not be that specific risk. Some clinics are willing to change their mind when they hear that information. It might take time, but many of my patients have been the first at their clinic to transfer an embryo with a mosaic result. If it goes well, then they’re usually more willing to do that type of thing. We also have the option of moving to a different clinic if that is something they feel like they have the means to do.
Dr. Aimee: I know that for myself, when I get your consult note and you reassure me, then I feel more assured and confident about transferring the embryos that we’re going to transfer. As a genetic counsellor, does this study change or reinforce the current recommendations for fertility patients undergoing PGT-A? Does this change anything as far as how you counsel patients or are you sharing the same recommendations as before?
Meaghan Doyle: My recommendations are the same, to be honest. I think that what matters to me is seeing what happens when we use embryos. Right now, when we’re doing testing on embryos, we are still testing five to ten cells, we’re not testing them one at a time, and all the different PGT labs do things so differently. What really matters is what happens when we use embryos with these results. Do they implant? Do they miscarry? How healthy are the babies? That’s what we have years of data on.
I’m not sure that one study at this point is necessarily going to change all of our recommendations. That’s why it’s important to look at the broader data that we have, and that is becoming more and more reassuring for a lot of people.
Dr. Aimee: When patients go to a fertility clinic, they’re not usually given an option or a choice as far as which PGT company the clinic is going to use. As a patient, are there any questions the patient could ask so that they’re more informed about what the limitations could be before they start an IVF cycle with that particular company?
Meaghan Doyle: You can ask things like whether mosaicism will be reported back to you or not, if you feel like that’s information that you want. If not, you can ask how mosaic results are categorized. Sometimes embryos with mosaic results are split into high and low. Low-level mosaics typically do better than high-level mosaics, so sometimes those are called euploid or normal, but sometimes those are called aneuploid or abnormal. An embryo that has a really good chance of leading to a healthy baby when mosaic results are masked is put into an abnormal category, and you might be losing an embryo with a great chance of success.
Sometimes these nuances can play a role in whether a patient chooses to do PGT-A or not, because it could impact the number of embryos they have available for transfer based on lab reporting and clinic policies.
Dr. Aimee: I’m glad you brought that up, because it can influence whether someone wants to do PGT-A testing or not. I counsel patients from all over the world. I feel like if you’re working with a clinic and you don’t have any options, and they won’t allow you to transfer low mosaic segmentals, then you might be better off not doing PGT-A at all, if you’re not going to be able to use every single embryo you possibly have. I wish that patients would have more autonomy over what they could transfer. If a patient is well-informed, has informed consent, they should be able to transfer any embryo that they would like to transfer.
Are there specific scenarios where the information from this study might be particularly more relevant than other scenarios?
Meaghan Doyle: I think that this is mostly relevant for the low-level mosaic results. Those are the ones where we’re expecting less of the tested cells to have had genetic differences and where we see the better outcomes. This is where I think this is relevant. If we’re thinking from the study all embryos showed mosaic findings, maybe that makes sense, maybe these are the ones that fit with that and why the outcomes are so good for embryos like that. If all embryos do have this, maybe that’s why we are seeing that these do so well, because it isn’t that unique.
Dr. Aimee: Do you think the lab environment might have had something to do with these results?
Meaghan Doyle: I think that there is a lot that we need to take into account with this study. It is possible that some of these could be false positives when we’re testing a single cell. I talked to some of my colleagues who know a lot more about the lab side of things than I do, and there is sometimes concern for a higher rate of false positives when we’re testing cell by cell. That’s why we don’t do it in the clinic at this point in time. We certainly need to take these results with a grain of salt. They tested the whole embryo, which really means doing things to embryos that we wouldn’t be doing in the clinic itself, so it’s hard to know exactly how this would correlate with an actual embryo that somebody uses. It is important to keep in mind those limitations.
Dr. Aimee: Is there anything else that we should keep in mind when looking at this study and its findings?
Meaghan Doyle: I’d like to see it repeated as well, just other people doing this type of research, and seeing if we see the same things or not. I think that’s important to do with all research, and see how things evolve.
Dr. Aimee: To make sure that it’s reproduceable. That makes sense. Meaghan, where can people find you? If it were up to me, every single patient going through IVF would have you to work with. How can they work with you if they’re looking for a specialized genetic counsellor in fertility genetics?
Meaghan Doyle: You can go to my website at DNAide.com. I have my online calendar there, where you can pick a time that works for you and meet with me through Zoom. You can also find me on Instagram @DNAideGC. I post lots of information there about research studies like this, other information about PGT, other infertility genetic information, and our collaborations as well.
Dr. Aimee: Awesome. Is there anything else that you’d like to add today?
Meaghan Doyle: Just keep in mind that “abnormal” is not a genetic result. Like you said, that could mean anything. If you know your embryos are abnormal on PGT-A, ask more questions, get more information. They’re your embryos, you deserve that much before you make these crucial decisions.
Dr. Aimee: Excellent point. Thank you again, Meaghan, for joining us. Thank you for all the work that you’re doing in this field, you’re saving embryos one pregnancy at a time.
Meaghan Doyle: Thanks for having me again.
