Genetics, Mosaic Embryos, and Your Fertility with Meaghan Doyle

Welcome! We’re going to talk about genetics, mosaic embryos, and your fertility. This is something that I’ve wanted to talk about with you for such a long time.

Meaghan Doyle is a genetic counselor specializing in infertility, preimplantation genetic testing, and preconception genetic counseling. After seeing patients who came from other clinics where access to a genetic counselor was not available, she saw the negative impact this had on their care, so she joined Instagram to help provide education on fertility and genetics to help bridge this gap. She’s now launched DNAide Genetic Counseling, her private fertility genetic counseling practice allowing you to see patients Internationally.

Dr. Aimee: I’m so glad that you’re doing that. I swear, when I look at your Instagram posts, I feel like you can read my mind. You’re clearly passionate about genetics and you work so well together with patients so they can feel empowered to make decisions about their fertility treatment, and those decisions are the ones that are best for them. Thank you, Meaghan, for joining us today.

Meaghan Doyle: It’s such a pleasure. Thank you so much for having me.

Dr. Aimee: I want to hear more about you. What made you go into genetics?

Meaghan Doyle: I always knew that I wanted to be in a profession where I was working with people. As soon as I did my first undergrad lecture in genetics, I loved how it was working to understand why we are the way that we are. The more I learned, the more I realized how it wasn’t that straightforward, but really at the basis of everything genetics are the building blocks for why we end up the way we end up and why we are the way that we are.

That’s really what drew me to this field. It’s just such a lovely combination of science and learning and then working with people and individuals to make sure that they’re getting good healthcare and working with a wonderful healthcare team at the same time. It’s just a wonderful experience for me working in the scientific community and still being able to help individuals at the same time.

Dr. Aimee: What are mosaic embryos? How would you describe that term, mosaic embryos, to someone who knows nothing about genetics and might think of mosaics as maybe some tiles in their bathroom?

Meaghan Doyle: That’s right. I like to think of mosaic embryos like a soccer ball. If you think of an embryo, we usually think of it as a bunch of cells, hundreds of cells big. Mosaic embryos, some of the cells are chromosomally normal with normal chromosomes inside of them, and some of the cells have abnormal chromosomes inside of them. So, they’re really like a mixture, some of the embryo is normal, some of it is abnormal. If you think about it like that soccer ball, there’s patches that are different from one another and it’s not all uniform in that way.

Dr. Aimee: How do you find out you have a mosaic embryo, how does that information come to you?

Meaghan Doyle: You can really only find out you have a mosaic embryo if you do an IVF cycle with preimplantation genetic testing. This is a test where we’re able to take a small sample from the embryo, we take between five and ten cells from the area of the embryo that’s around the outside and would eventually develop into the placenta. Since we’re sampling multiple cells, we can get a representation of all of those cells and the chromosomal make up. We learn that there’s a mixture, it’s not completely normal, it’s not completely abnormal, but it’s a mixture of both.

You really need to have PGT-A, that’s preimplantation genetic testing for aneuploidy, in order to find that type of information out about your embryos. It’s also very important that the PGT-A lab that you’re using reports on mosaicism, as this isn’t something that’s always available at every lab, and that it’s requested, because at some clinics it’s not information that they’re requesting, so you need to make sure that it’s something that is being offered as part of your PGT-A test in order to get this information.

Dr. Aimee: Can you give us a very simple sentence that a patient can use to advocate for themselves with their clinic to find out if the clinic is going to reveal mosaic results and the genetic testing company is also going to be able to test for that?

Meaghan Doyle: Yes. I think that most fertility physicians at this point that are using PGT-A are probably familiar with mosaicism as a concept, so you can just simply ask, “Will the PGT-A laboratory that we’re working with going to report mosaicism back to us?”

Dr. Aimee: That was easy. So easy.

Meaghan Doyle: Absolutely.

Dr. Aimee: I have so many questions for you. How are mosaic embryos ranked, are there different kinds of mosaicism?

Meaghan Doyle: There is. This is something we’ve learned a lot about over time. We rank embryos based on the level of mosaicism, so the percentage of cells that we tested that are normal versus abnormal. Embryos that are low level mosaics have a lower percentage of cells that are abnormal compared to high level mosaics, which are more abnormal. Generally, we think of low level mosaics as between 20 to 40% abnormal, high level is 40 to 80%, but those ranges are changing and sometimes we’re thinking maybe a 50% threshold might be a little bit better.

Next, we look at the type of abnormality in the mosaic embryo. If you think about each chromosome as one big instruction book for the embryo, you might have an entire copy of that instruction book that’s present in a cell that’s extra or missing, or there might just be a few chapters from that instruction book that are missing or extra. It’s something that we look at. We call those segmental mosaics if it’s just a segment of a chromosome that is missing or extra, or whole chromosome mosaics if there is an entire copy of a chromosome missing or extra.

Number of abnormalities in a mosaic. Is there one, two, three, four, or more? Then the specific chromosomes involved that are abnormal as well.

Dr. Aimee: We’re here talking about mosaic embryos because obviously I’m passionate about this, you’re passionate about this, but the reason why I’m so passionate about this is I’m worried that people don’t know this information and they’re discarding embryos that could turn into perfectly healthy babies.

Meaghan Doyle: Right.

Dr. Aimee: How can that happen, how does that happen? Tell us more.

Meaghan Doyle: That’s one of my favorite questions. I love it when people ask me if mosaic embryos can become healthy babies, because they absolutely can. It’s so important to know that.

What happens is that the embryos actually are correcting themselves. That’s the leading theory for how they are becoming healthy babies. We think about the embryo as a whole, it’s a mixture of normal and abnormal. For the embryo to become a healthy baby, the abnormal cells are actually dying off. They’re not as healthy as the normal ones, so the abnormal cells will slowly die.

As long as there’s enough normal cells in the embryo to fill in those gaps, you think about the soccer ball that has some holes in it, normal cells come in and patch it up, then that embryo is now completely normal, and it goes on and becomes a completely healthy baby. That’s really how these embryos are correcting and becoming completely healthy babies. The abnormal cells are just going away very early on in the pregnancy.

Dr. Aimee: Is there any testing in pregnancy for someone to do to find out if their mosaic embryo is now a normal baby?

Meaghan Doyle: Yes, absolutely. It’s something that’s completely optional because it is something that does come with some risk. The best test for pregnancy that has resulted from a mosaic embryo is what we call an amniocentesis.

This is a test that we do in the second trimester of pregnancy, usually after the 15 thweek. It’s a needle that goes through the abdomen of the person carrying the pregnancy, and under ultrasound guidance we remove some of the amniotic fluid. In that fluid are cells that come from the baby- skin cells, bladder cells- and so we can directly test the genetic material that is coming from the baby and see if there is any mosaicism present or if everything looks great.

That’s really the best test when we have a pregnancy from a mosaic embryo, because all of the other tests that we usually consider for average risk pregnancies- blood tests, ultrasounds, even something called a chorionic villus sampling that’s done a little bit earlier in pregnancy- all of those tests are looking at placental DNA. Sometimes, but especially when we think about mosaicism, the placenta and the baby can have different genetics.

The placenta is actually a little bit more likely to harbor those abnormal chromosomes to protect the baby. We really need to make sure that if you want reassurance of the health of your baby after a mosaic embryo transfer that we’re doing an amniocentesis and directly testing cells from the baby and not the placenta.

Dr. Aimee: Just one quick question along those lines. If you’re doing an amniocentesis, everything comes back normal, you have a normal baby, should you still be worried once your child is born that that baby started as a mosaic embryo?

Meaghan Doyle: Really, if everything is corrected, there’s not a lot of need to worry. It’s a lot easier for me to feel reassured because I have a great understanding of the biology at the early embryo stages, but really if all of those abnormal cells are dying off and we truly have an embryo that has fully corrected and there are only normal cells, then there really shouldn’t be an impact on the health of the baby afterwards, everything should be completely normal. That’s what we’re seeing from the literature so far as well.

Dr. Aimee: I love that what you’re sharing is based on science, based on the evidence, based on your experience. It’s very comforting for me to hear someone with your background say the same thing that I’ve been saying for years now. At last, we’re here. We could not have had this conversation five or six years ago.

Meaghan Doyle: No. I probably wouldn’t have been having this conversation 10 months ago.

Dr. Aimee: Yes. For people who are trying to conceive, are there some indicators they should be aware of that might mean they should consider genetic testing?

Meaghan Doyle: It really depends on what type of genetic testing you’re thinking of, because there are so many different genetic tests. A lot of the time, I think about there are genetic tests you can do on the people who are planning to conceive and there are genetic tests that you can do on embryos.

Genetic tests we do on people who are planning to conceive… You can consider genetic tests on yourself if you are having trouble conceiving because of azoospermia, so if there is no sperm or very low sperm count, it’s a good idea to do some genetic tests on the sperm provider. As well if there is any family history of genetic disease, then it’s important to speak with a genetics professional to see if there may be a risk of that genetic disease being passed on to your future children.

We also think about doing genetic tests before conceiving in individuals who are experiencing recurrent pregnancy loss. Both to see if there is a cause we can identify and to see if there might be any risk to the health of any children that are conceived as well. It can help with determining treatment.

Anybody who is in a relationship with a blood relative and they’re conceiving together, so if individuals are cousins and they’re having a child together, which is common in certain cultures, they could consider genetic tests before conceiving to see if there is a higher genetic risk for them.

Sometimes we consider genetic tests on individuals with premature ovarian insufficiency as well. Again, to identify causes and have answers for them.

Then I also think about personal interest. Especially for PGT-A when we think about testing on embryos, there have been various guidelines and studies done about which populations it’s most beneficial for. But I really am a believer that it should be offered to most individuals, unless there is a contraindication where it may be harmful for you and your fertility treatment. I think that as long as you are educated as to the reasons it can be helpful, what it can do and what it can’t do, and what the risks are, I think it’s something that people should consider or should be offered.

Dr. Aimee: I agree. I think it’s important for everyone to be offered PGT-A and then it’s up to you to decline it. I feel like sometimes people make decisions for their patients that they wouldn’t have made had they been given all of the information upfront. That’s why we’re here talking about this stuff. So, thank you.

Meaghan Doyle: That’s right.

Dr. Aimee: What are the myths and misconceptions about mosaics that you’d like to set straight before we finish today?

Meaghan Doyle: I probably have so many. I think the first one that actually came to mind was high level versus low level mosaics. Usually, in my experience, sometimes people see high level mosaics and they assume that the embryo is bad or is going to have a poor success rate.

But really when I’m assessing mosaic embryos, the first thing that I look at, is it a segmental mosaic or is it a whole chromosome mosaic, because in our clinic’s experience and in the literature, I think this is one of the first things we learned about mosaic embryos is that segmental mosaics have the best outcomes. They have the highest pregnancy rates, the highest chance of leading to an ongoing pregnancy and a live birth.

Whether it’s a high level segmental mosaic or a low level segmental mosaic, being segmental automatically puts you up into the best category of mosaic embryo with the most likelihood of success. I think the level of mosaicism being the most important is one of the biggest myths out there with patients and providers sometimes.

Dr. Aimee: Let me just ask you one question about that. You’re saying segmental. For our listeners who don’t know what segmental means, tell us how you would look at your report to see if you had a segmental.

Meaghan Doyle: Absolutely. It depends on your laboratory. You might see things that say dup or del, for deletion or duplication. You might see the letters p and q, which talk about the different arms of the chromosomes that might be deleted. Lots of the segmental results look a lot longer. If they’re whole chromosomes, you just see a plus, a minus, and then a number. Whereas the segmentals look a lot more complicated than they actually are.

Dr. Aimee: Great. Keep going with your myths and misconceptions. I didn’t mean to interrupt you. I want to hear more.

Meaghan Doyle: No. That’s totally fine. One other thing that people think a lot about is we think about embryos that are totally abnormal, and that’s completely related to the age of the egg provider. Mosaicism, on the other hand, is not. Mosaic embryos, the risk of those does not increase with age.

We don’t actually have a great understanding of why mosaicism happens, which is very frustrating for a lot of people, especially individuals who seem to have a large number of mosaic embryos. There’s early data that we’re kind of trying to figure out why mosaicism happens and if certain people are more prone to it, but age is not a factor for mosaic embryos, so I like to reassure individuals that they’re not at risk for two different types of potentially abnormal embryos just because of age. So, that’s something that we like to think about, too.

Dr. Aimee: Meaghan, I’ve learned so much from you today. Thank you for joining us. I really appreciate your time. For people who are listening thinking, “Where can I find Meaghan Doyle,” tell us where we can find you.

Meaghan Doyle: My website www.DNAide.com and right now, I’m on Instagram @ MeaghanDoyleGC and @DNAideGC. I’m just there, so we just finished a big series on mosaic embryos. I have a feeling it’s not over. I can’t get away from them, they’re my favorite thing to talk about. You can definitely find me on Instagram and learn more.

Dr. Aimee: Awesome. For those of you who don’t know, I did a documentary for NOVA called Fighting for Fertility. At minute 38, we talk all about one family’s journey from mosaic embryo to healthy baby. Check it out if you guys haven’t watched it yet.

Thank you, Meaghan, for joining us. I hope you’ll come back again and tell us all about your series. Everyone, have a great day. Bye.

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Originally published at https://draimee.org.