Ep 14: Genetic Testing with Teresa Cacchione, Certified Genetics Counselor
Fertility Forward Episode 14:
Teresa Cacchione is a board-certified genetic counselor at RMA of New York who guides patients on several genetics-related concerns such as cytogenetic anomalies, carrier screening, family history concerns, and preimplantation genetic testing (PGT) of embryos, including single-gene disorders, aneuploidy, and structural rearrangements. In this episode, we take a deep dive into the topic of genetic testing, including the rapid evolution of the field over the last decade, and as you will hear from Tereasa, science has truly come a long way to help individuals optimize their chances of conceiving. She explains to listeners what PGT broadly involves and then gets into the different variations – PGT-A and PGT-M. She also discusses the advantages and disadvantages of 23andMe home testing, why eggs and sperm are near impossible to test for viability, the conditions that are typically screened for, the new research around mosaicism, and how testing science is impacting the world population.
Rena: Hi everyone! We are Rena and Dara and welcome to Fertility Forward. We are part of the wellness team at RMA of New York, a fertility clinic affiliated with Mount Sinai Hospital in New York City. Our Fertility Forward podcast brings together advice for medical professionals, mental health specialists, wellness experts, and patients because knowledge is power and you are your own best advocate.
Dara: Teresa Cacchione is a board certified genetic counselor here at RMA of New York, where she provides guidance to patients on a number of genetics related concerns, such as cytogenic anomalies, carrier screening, family history concerns and preimplantation genetic testing of embryos, including single gene disorders, aneuploidy, and structural rearrangements. We are so happy to have Theresa Cacchione today in the house, just a couple doors down from us. She is our genetic counselor here at RMA and I've known personally Teresa here for probably 5 or 6 years. You didn't start in genetics. Where did you start?
Teresa: I started as an IVF coordinator at RMA back in 2011. So, almost a decade ago, which is crazy to think about.
Rena: And I only know you as a genetics counselor.
Teresa: Yeah, I was an IVF coordinator for Dr Copperman for five years so from 2011 to almost 2016. And during my time here, that was when I realized I wanted to go back to school to be a genetic counselor. And so I did that 2015 to 2017. And when I graduated, just so happens that RMA was ready to start having someone in house. So they approached me, and I was super excited to come back and sort of consider RMA to be my home. It's where I sort of grew up in my first job outside of college. So I was really excited to come back and love putting all of my previous fertility knowledge to use now in this sort of setting instead.
Dara: And you already probably felt comfortable at RMA?
Teresa: Yes, I consider it my home.
Rena: We’re so lucky to have you here. Such a great asset. You’re a source, um, of so much knowledge. I’m always so impressed by how much you know
Dara: So was the impetus of going back to school for genetics was just out of interest? You felt like there was something lacking in the world of fertility or was it just genetics in general?
Teresa: Genetics in general and then I think, actually, as I sort of went through the program, realized that there, even now there are not very many genetic counselors in this particular area of medicine. It's just starting to grow. I think most genetic counselors work either in prenatal where someone's individuals are already pregnant or in cancer, some cardiac and neurogenetics is starting to be more common. But there were not very many genetic counselors in the fertility setting at all. I would find that as you know, we would go through classes and talk about topics in my program, I would be the only person that sort of knew this area of specialty and was realizing that there was maybe a need to have that more representative. So I was excited when this possibility came up, and sort of being what there are a couple of other fertility counselors in New York City and a few on the West Coast, but that's about it. So I was excited to sort of join the small population and maybe start to grow it a little bit
Dara: And in house too which I think it's great.
Teresa: Yeah, because you know, I think every fertility clinic operates a little differently. Every clinic has their own sort of groove and their own philosophy so being able to tailor all of the genetic principles that are obviously the same across the board to that particular clinic’s way of practicing medicine is really important.
Rena: That is so wild. I didn't realize it was such a small field because just because of my own personal experience, then of course, being here where we have such amazing genetics resources I kind of thought it came with the territory and I don't really understand, you know, how you go through this process without a genetics person?
Teresa: A lot of the time, I know a lot of other places will refer out to genetics clinics, which is fabulous. You know, that's what I believe we used to do before I was on staff. We would refer out to the genetics clinic at Mount Sinai, which is great. But, you know, I would say usually those clinics are a little bit more focused on the prenatal setting, and there are some things that are pretty special and specific to this particular field of medicine that unless you're in it, you may be may not be able to appreciate quite as much or know as many details about, so I feel like being in-house I can give patients that particular view instead of being looked over otherwise,
Dara: Even like I know Rena could attest to this. I think it's great to have an integrative approach, looking at the big picture and looking at the different parts and how it all connects. You know, the importance of wellness so meeting with Rena, meeting with myself, meeting with you, I think it's it's nice to have the big picture all in one house so we can all better understand that patient or each individual.
Teresa: And that's something I integrate into my sessions. I'll look at the notes of sort of what the doc, what was discussed with the patient, the doctor, all the fertility testing they have done. You know, when we're making decisions about how to proceed and sort of what the patient wants to do in terms of preconception and prenatal testing options, I usually take into account. What treatment are you already talking about doing with the doctor? What have your results shown? What is your prognosis? What makes sense for you? to really try to help individualize it. Which is something that if you're not familiar with fertility testing and prognosis and what we're doing in-house, you might not be able to do so...
Rena: Right. And I think it's so much easier too and you know the team, right? And the people.. Much easier.
Dara: And they know you too. You know, how you operate, how you work. I think it's also great collaboratively. I see you often go to the meetings.
Teresa: Oh, yeah, I love to try to and honestly a lot of the times I’ll go to the meetings just even if it's not a topic that I'm actively involved in just to sort of cross train and find out what's going on in other areas of the practice. What are our patients experiencing, what's going on in the field in general to try to make sure that when I talk to them, I can have, like you said, that holistic approache and sort of know what’s going on in their treatment in general, and integrate that into our discussions.
Rena: I think it's wonderful. So I think so let's jump right into it. I think the big questions everyone always wants to know is let's talk about PGT, PGD, labs and all the nuances that you know, go into those things.
Dara: And also how, you know, it's come a long way. And I'm sure you came at the perfect time. What was it like way back when? Was genetic testing...to be honest with you, I always thought it was, if you're Jewish, you need to get genetic screening. And I thought that was only for a small group of people, and it's not.
Teresa: So there have been big changes in the last decade, you know, in terms of both genetic testing, which you're referring to, Dara, in terms of carrier screening, and in terms of embryo testing, the P G. T. So we can talk about them both. You know, both, very, a lot of changes. The thing about the carrier screening first...so I would say back in the day when she was 10 years ago, just really isn't that long of a time. But in terms of genetics, that's actually a very long time things change really quickly. We really, each condition that we tested for was, it was expensive to do testing because it took a lot of resources, and each test was an individual test in the laboratory. So if you were testing five conditions, those were five separate tests with five separate processes for that individual person. So doing DNA testing was a lot of work. So what we would have to do back then as we would have to tailor it to okay, Based on what you know, to be your ethnicity, based on your family history, What are the most common things in that ethnicity that we see pop up? What diseases do you want to be testing for? And so we would tailor it that way. So people of Jewish ancestry do have a lot of conditions for a number of reasons. But they're also specific conditions that individuals who are Caucasian in general are at risk for people of African American and Mediterranean descent have other conditions. So we used to do it that way.
Dara: That’s a lot of work.
Teresa: And what we will be looking for, just to clarify for anyone listening who's not in this world and doesn’t automatically know what we're looking for are recessive conditions. So going back to high school bio, taking everyone back for a second. If you remember as humans, we have two copies of every gene, one that we inherit from Mom, one that we have heard from Dad and genes are basically the instructions that make our bodies work properly. Every gene is a different job, and there are genes that you know, help our heart to beat and tell us how to digest food and tell our bodies how to carry oxygen. Every gene has a job, And recessive genetic conditions are conditions where both copies of that gene so the one inherited from Mom and the one and heard from Dad have to both not be working properly anymore or be broken or mutated in order for someone to actually show symptoms of that disease. Okay, carriers are people who have one working copy of the gene, one non-working copy of the gene and that remaining working copy gives their body everything that it needs, so they would never know that they’re a carrier, they don't show any symptoms, and they're usually is no family history of the disease. So a lot of people will walk in and say, Oh, why do I need genetic testing? I don't have any family history of the disease. For recessive conditions we wouldn't expect there to be. There usually isn’t.
Rena: Well and for a lot of people they say that this is a big surprise, right? They have no idea. They’ve been walking around living their life and they could be a carrier for something.
Teresa: Exactly. And so the problem is if two people, so two gamete sources, egg and sperm, are both carriers for the same condition, that's when we can see the disease show up. And, like I said, they would never know usually. They’d be healthy. They'd be walking around, they have no family history. Everybody carries something. There are thousands of recessive conditions out there.
Dara: Wow I didn’t realize everyone carries them. But that makes sense. And there's also I'm sure if you even are a carrier... so if you're a carrier, that doesn't mean it's gonna be expressed unless you have both mother-father.
Dara: But if you have both mother-father that also doesn't necessarily guarantee it.
Teresa: Yes. It's a 25% chance
Dara: That it will, that it will basically be turned on.
Teresa: Exactly, so, basically, if both parents biological parents are a carrier for the disease, the same disease, then there's a each time they have a child a 25% chance the child will have the disease. So that child inherits the non-working copy from each parent, so one from each of them. A 50% chance the child's going to be a carrier and not show any symptoms, just like the parents. So get a working copy from one parent, a non-working copy from the other. And then a 25% chance being completely negative. So getting a fully working copy from each parent. So again, some ways there are probably carrier couples out there who rolled the dice luckily, and when they had children and it just never showed up. But you know, when we're thinking about, you know, fertility treatments because, you know, in this setting, there are which we'll talk about are options to intervene, you know, the average couple may in many cases, this is changing luckily, but in many cases may not think about that carrier screening before they’re, you know, sort of trying naturally. But when we're already talking about options and we have a way to intervene, which is PGT which we'll talk about more in a little bit in the fertility setting we need to know up front whether or not there are those risks because if we know about them, there are things we can do.
Dara: Carrier screen is done across the board at this fertility clinic?
Teresa: Yes, it is recommended for everyone. Of course, it’s always optional. You know, not everyone wants that information. Not everyone wants to sort of dig into genetics, and that's fine. It's always optional, but it is highly recommended. We find that usually nationwide, approximately 1 to 2% of couples are carriers for the same thing which doesn't sound like a lot. But when you think about the many millions of people in this country, that's actually quite a large number of people, and we see in our patient population at RMA about 3% of couples are carriers for the same thing, well, likely because we have a couple of large populations that are at increased risk for genetic conditions. So it is... that is a significant number of people when you think about how many patients RMA has so we do recommend that everyone do that screening before, as part of their initial fertility workup before they decide what treatment do.
Dara: I think all gynecologists should be recommending You know, you go see your gynecologist before you're thinking of starting a family. It should be, in my opinion, it should be one of those things right on the back of a checklist.
Teresa: We're seeing that to be more common, like I have to say, you know, personally that my OBGYN, you know, recommended it, but they recommended it. A lot of the OBGYNs in the Sinai system that are familiar with RMA and that have a lot of genetic counselors sort of giving them little pushes. You know, we're seeing that happen more frequently in major metropolitan areas in general. I think it's becoming more common, hopefully it will filter down to other areas of the country as well soon and the reason why I think just to sort of circle back to what we were initially talking about. The reason it’s become more common now is like I said, back in the day. each genetic test was a separate test in the laboratory. Now, a couple of years ago, a new technology called the Next Generation sequencing came out, where we can run multiple conditions at the same time as part of the same test on the same blood sample.
Dara: So it’s streamlined?
Teresa: It's streamlined. So basically before each test was a separate test and each one was about $1000 and now we can run as part we can run at this point 283 conditions at the same time as one test.
Rena: And is it a simple blood test?
Teresa: Yes, simple blood test. Or you can even in some cases, do saliva. So, for example, we have some patients who have partners or spouses who travel a lot, who aren’t always around...we can always give a saliva kit if they’re away or something like that.
Rena: So it makes it a lot more accessible and affordable.
Teresa: Affordable, yes, so usually it varies person to person in terms of insurance. But these days, you know we’re seeing it down to a couple hundred dollars instead of $1000 per condition. So it became a lot more accessible, and now that it is much more accessible and easy to run and easy to interpret and sort of running it on a larger mass scale, we are, at this point, you know, recommending it more for everyone instead of just based on high risk scenarios. And we're seeing that a lot of the conditions that we thought were maybe isolated to certain ethnicities are actually may be a little more common across or more panna than we thought they were. The other factor that is, that it's also possible that, you know, we're not always each of us 100% certain about our ethnic backgrounds. And sometimes there's more crossover than we knew their was. So it actually adds up that we're, I think, in the future will be sort of thinking about more of panethnic approach or screening for the same things across all ethnicities instead of, you know, sort of segmenting it into different conditions of different ethnicities.
Dara: Do you think that’s come to light because of 23 and me and ancestry.com?
Teresa: Maybe. I think, honestly, the biggest factor was just being able to run this screening at this large of a scale on more people. You know, like I said before, we were doing just a handful of conditions. And as I said earlier, there are thousands of recessive conditions. But most of them are so rare that it would be astronomically unlikely for two individuals, unless they're being related was, really unlikely for them to both be carriers of the same thing. But there are a couple hundred conditions, which are the ones that are currently screened for that are seen at a common enough frequency for us to want to be screening the general public.
Teresa: Yes, so right now the panel is 283 conditions that we’re able to screen for. We use a lab called Sema4 for that. But the most of the genetic carrier screening labs are between 200 and 300 diseases right now, and that will expand over time as the technology gets better and as we can screen for more and more conditions.
Rena: And now is this something, say you so many people are now using those at home kits we just talked about. Is it something that that screens for or it’s totally separate?
Teresa: So ancestry, I believe, only looks for obviously your ancestral markers, and you know that’s super fun. I tell people you know, enjoy go for it because I think it’s always fun to find out what's going on there. 23 and Me does also have a health component that includes carrier screening, but I would say it does not replace doing a medical, a clinical carrier screening through an OBGYN or through a genetics department for a couple different reasons. First reason is it only looks for, I believe, 20 conditions the last time I checked whereas now with the panethnic screening we’re doing, like I said, between 200 and 300 depending on what genetics lab your OBGYN or fertility clinic uses. 23 and Me is designed to really only look for a couple of mutations at each gene. So when it looks for the most common ways the gene could change or brake. Whereas the clinical version of the testing that we do here looks at the entire gene, so it is much has a much higher detection rate. In addition, 23 and Me, the reason why it is allowed to be done at home is that it doesn't take the final step that we do clinically, which is if we find an abnormality we do a second type of testing to confirm it and they do not do that, which is why it's so cheap and accessible. So we do see a rate of both false positives and false negatives that is much higher than what would be acceptable clinically. So I think it's super fun for learning more about yourself and learning more about your health markers and ancestry and all of that. But we typically say not to use that to replace clinical testing. We've had a lot of people get false reassurances through that, and we want them to make sure they've sort of done thorough testing clinically if we're thinking about planning for, you know, conception, all of that.
Rena: Still do the screening at a doctor.
Dara: 23 and Me is for fun but go see a genetic counselor.
Rena: So okay, so say they come and they okay, so now talk about sort of PGT and PGD. So first let's talk about maybe what is PGT and PGD and then who would do both of those testing.
Dara: And when did it even start because I know the names even changed over the years when I was a patient in 2010 it was called something else and now it’s evolved.
Teresa: Yes, the terminology is constantly changing just cause we like to keep everyone on their toes, keep everyone very confused. So the last couple of years, I believe, it was 2017, the terminology was updated to PGT, T as in Tom, Preimplantation genetic testing. So that is sort of an umbrella term for multiple different types or indications to test embryos. So just back up for a second. For anyone who doesn't know who is listening when we talk about preimplantation genetic testing, we're talking about testing on embryos that have been created through IVF. So an individual, a patient or a couple would go through IVF, where the female would take injections to make her body produce more eggs than usual. Those eggs are retrieved and then fertilized using the sperm source. The fertilized eggs are what we refer to as embryos. And then we grow them in the lab for 5 to 7 days so that they reach a particular stage of development where it's safe for us to take a small biopsy of a couple of cells from the embryo. Freeze all of the embryos right after we take that biopsy because we don't want them to keep growing in the laboratory much past that day 5 to 7 point which is called the blastocyst stage. And then we send those biopsies that we took from each embryo off to a genetics lab for testing to find out some more information about each embryo before deciding which ones to use to attempt pregnancy and which ones to avoid and not use. Because we can't tell just by looking at the embryos anything about their genetics, their chromosomes, which we'll talk more about in a second. You know, a lot of people will see or have read that we can grade embryos, and they get sort of quality ratings, which they do.
Dara: Yeah, I thought that.
Teresa: And you’ve had Donna on here, right? I’m sure she’s talked about that a little bit.Grading is important in helping us assess the metabolic potential or the overall health of an embryo and its ability to implant in the uterus but it doesn't tell us much about its ability in terms of genetics or chromosomes to become a healthy, viable pregnancy.
Dara: So that’s good for people to realize.
Teresa: And you can’t tell that just by looking at the embryos so the PGT helps give us more information in that regard.
Dara: I didn't realize that you this was something new for me, that you just take a part of some cells surrounding it. My whole thought was like, Oh, you cut part of the embryo! I thought it was very invasive and it's actually quite gentle.
Teresa: Correct And this is why it's become, I think, a little bit more prevalent, PGT now I’d say in the last five years, because previously, back when you were a patient, we could not grow embryos to that day 5 to 7 stage, we could only grow them to day 3 and taking a biopsy on Day three, at that point, that embryo was only eight cells and size, or so taking a couple of cells that would actually be very harmful and invasive to the embryo. So back in the day, we used to only do PGT for very severe, specific circumstances. Now, by growing that embryo to day 5 to 7 at that phase, the embryo starts to actually split into two different areas of cells. So all of the cells that are eventually going to become the fetus if it's a healthy embryo, I tell patients to think about a tennis ball. If you were to cut a tennis ball in half and there's the foam part on the inside and the fuzzy part on the outside, the cells that are gonna become the fetus are the part on the inside. So they all pull to the center of the embryo, sort of in compact, tightly together, and we can't touch them or see them, actually, just by looking, unless we cut the embryo open. So those cells are sort of protecting themselves. It's the embryo saying, these are the cells that are really important. Don't touch these. And then the cells that all migrate to the outside of the embryo, which, using the same analogy, is sort of like the fuzzy part on the outside of a tennis ball, those are all of the cells that are going to become the placenta and the supporting structures of the pregnancy. And between days five and seven, some of them actually start to hatch out of the embryo so what we can do is we can capture a little biopsy of that part that's hatching out and send that off for genetic testing, and those cells are really regenerative. You know, taking that little biopsy is not an issue and they've done many, many studies that have shown up that there's no damage to the embryo at all. And that part that's going to come to the fetus, all those really important sells its remaining untouched.
Dara: It’s protected.
Teresa: Yeah, so that's why the now it's much more safe for us to do this sort of testing whereas and the main impetus in that was the development of that being able to culture embryos in the lab to day, 5 to 7, as opposed to previously, we really only had that, you know, day three option and that was a lot more dangerous. So now, you know, what we see, we see people do PGT for a couple of different reasons, and there's one reason that's pretty much universal to everyone. That's the one I guess I'll talk about first since what most of our patients or people listening probably will be recommended to do. Preimplantation genetic testing for aneuploidy. So PGT-A as in Apple. That is what we pretty much at least at RMA and a lot of clinics are getting to the face where they're doing this, we pretty much recommend that across the board for anyone who's doing IVF, because aneuploidy is the fancy word for chromosome abnormalities and chromosomal abnormalities can happen to anyone. It's not something that is inherited. It's not really based on family history, for the most part, so again, to take us back to high school bio, when our bodies are creating eggs and sperm, we go from having through a process called miosis, we go from having 46 chromosomes and that are split into 23 pairs. If you guys remember, are when we create eggs and sperm and go down to having only 23 chromosomes or one of each pair so those pairs basically get cut in half, and then we go back up to the not normal number 46 which humans need to be so, you know, healthy and functional. We go back up to the normal number 46 when the egg and the sperm come together. They each have 23 or 1/2 of each pair that comes together to make those 23 pairs. So when our bodies are cutting those pairs in half and creating our eggs and sperm as humans, we're actually awful at that, and we make errors all the time. So we make eggs and sperm that have the incorrect number of chromosomes. So extra or missing chromosomes, missing a chromosome one or having an extra chromosome 20 all the time, and so if that results in the creation of an embryo with extra missing chromosomes that usually is not compatible with a healthy pregnancy in the majority of cases,
Dara: I want to interrupt you quickly. It’s a random question, but can the environment affect the quality of those chromosomes?
Teresa:So no. So the chromosome issue is usually just random errors that occur you know, when our bodies are creating eggs and sperm. You're thinking about epigenetics which is turning genes on and off on chromosomes. So that would be, I think, a separate process after the embryo has already been created. This is really thinking more before any of that is possible, creating that initial egg and sperm that could come together to become an embryo.
Dara: So there's no way to streamline it or make those chromosomes that much better? Or the...
Teresa: At this phase we have done so much research because this is the one thing that seems to be sort of one of those biological mechanisms of nature that we can't really influence at all. Yeah, and so those errors, you know, they, what we see is they occur in the creation of sperm cells at about the same rate, approximately across a man's lifetime as he's creating sperm, we see maybe like 10 to 20% of the sperm are abnormal. That is not as much the case when they're in much later age, sixties, seventies, eighties, but the majority of reproductive life it's about the same, whereas women we start off in our twenties and thirties with about 10 to 20 to 30% of our eggs abnormal. So even at that phase we still will have a fair amount of abnormal eggs.And then by the time we're in our mid early to mid forties, it's 90% abnormal, and that number starts to really accelerate after around age 37 or so.
Rena: That’s such a harsh reality too and it’s something I have to explain to patients. It’s just and I just for myself too at 34 You know, the biological clock is real. That’s a huge stat. Big number.
Teresa: I always feel like when I'm explaining this, I'm sort of playing into that, you know.
Rena: Same. I hate it, but you have to give people the information.
Teresa: You know our society has advanced in many wonderful ways in terms of you know, women have, you know, being able to think about having many, many aspects of their life outside of having Children, including myself included. But that piece that biological clock has not caught up. The biology has not changed.
Dara: I hope it does.
Teresa: Yeah, whoever unlocks the secret to stopping our eggs aging and and all that will be, you know, a gazillionaire, but it is not something that has been figured out yet. So we do you know, means that when we're doing IVF, or when we’re trying to conceive, you know, each, for example, someone who's in their mid to late thirties, each egg or embryo has about a 15% chance of being normal and a 50% chance of being abnormal and those abnormal ones if we were to put them back into the body and attempts pregnancy, they would either just not implant, so it would be a failed transfer cycle or in someone who's trying naturally, honestly, the months where everything's been timed correctly, but we don't get pregnant, that's the reason a lot of the time.
Rena: Or miscarriage, right?
Teresa: Exactly. That's the other possibility is that could implant and result in an early pregnancy loss having extra or missing chromosomes. So chromosomes are the structures that hold all of those genes that we were talking about, each chromosome has hundreds to thousands of genes on it. So if you're suddenly having extra or missing of hundreds to thousands of genes that your body needs, it’s, the body's really sensitive to that, you know it wants to have exactly two of each gene, and if so, having that many missing is usually incompatible with life and the body knows that so that's why we see pregnancy failing to occur or early losses. There are a couple of chromosome abnormalities that can make it further into pregnancy though. Down syndrome is the one that most people have heard of. We can also see two different conditions called trisomy 13 and 18 that could make it to live birth but those are usually very severe individuals. They pass away shortly after birth with those. So you know what we're what we can do now is if we have embryos in the lab. So let's say again, same patient I was talking about earlier. You know, mid to late thirties, we have six embryos from them sitting in the lab in front of us. We could say, Okay, these three are the ones that we should avoid for pregnancy. These are the 50% abnormal and these are the ones that are normal, they could become viable pregnancies. These are the ones to use for embryo transfers.
Dara: By saying the word normal, does that mean that they still may have some things, but overall, it's still, the percentage is higher?
Teresa: Thank you, yes. So when I'm talking about normal and saying chromosomally normal, that process PGT-A does not zoom in to look at the genes on the chromosomes. We’ll talk about that in a second. That's a different type of PGT. So it's overall just looking and chromosomes. Obviously, any pregnancy still has there's in any pregnancy regardless of how much screening we've got ahead of time there's always a risk of random birth defects: autism, intellectual disabilities. A lot of those things don't have specific genetic causes, and you can't screen for them ahead of time. But by doing the PGT-A we are significantly reducing the chance of failed implantation, pregnancy loss or the birth of a child with a chromosomal abnormality.
Rena: So it seems like, and I think it sounds like these days this is recommended to most people that walk through this door?
Teresa: Every person has a chance of creating chromosomally abnormal embryos. And if we could, you know, have you do fewer transfer cycles because we're only using chromosomally normal embryos. That's it. We'll do it. Like I said, even people in their twenties and thirties we will see in their embryos a handful of ones that are abnormal. We want to make sure we're avoiding those.
Rena: And I think also back when I did it, it was different. It was extremely expensive. It wasn't recommended to everyone, and now I think the costs for this is a lot more manageable.
Teresa: And that was also that next generation sequencing technology that I've talked about for carrier screening also impacted PGT very positively. So now the technology is much, much cheaper. It varies based on which lab that your particular fertility clinic is using. But I know that for us and for our patients it’s between 100 and 200 dollars an embryo I think.
Rena: So much better than it was. And that actually too. So a lot of times you know patients ask me or I see kind of in this space people always talk about, well, what lab do you use, what lab is the best, they use this lab it’s not as good. Can you speak to kind of the difference in the labs and sort of what that's about for people that don’t know?
Teresa: So the difference in the labs, I would say, You know, there are a lot of different reasons in New York state. New York state has very special credentialing. So we actually, if you were a clinic, look it in New York State, you are limited to only labs that are New York State licensed. So for us actually limits us to a particular pool. There also are not a lot of PGT labs in the country it’s a very specialized type testing. For PGT-A for the aneuploidy screening. They all use that and the next generation sequencing technology. There's some small differences lab to lab, but I personally would not have a lot of concerns using one lab or another. All of them at this stage have similar accuracies, and again, they're all using that same technology. So I have a very high degree of trust in all of them. I would say the lab to lab thing can sometimes more come into play when we're talking about the different type of PGT which is kind of a good segue. PGT-M, so preimplantation genetic testing for monogenic disease. So M as in Mary. That is the new terminology for PGD. Preimplantation genetic diagnosis. So it used to be called that.
Rena: Are we not calling it PGD anymore?
Teresa: Not anymore.
Dara: I haven’t heard that term in a long time.
Teresa: PGT-M. Yeah, so it is a mouthful, but one of the reasons they updated the terminology was the PGD the diagnosis, it’s not, when we test embryos were not really diagnosing them where, you know, it's not sort of actually to circle back to what you were saying earlier Dara, testing embryos is not we can’t do it with 100% accuracy. It's usually 97 to 99% accuracy. So diagnosis really wasn't an appropriate word. Diagnosis reflects sort of a 100% accuracy, so the it's preimplantation genetic testing. Like I said and these different types have different letters or subtypes so A was the chromosome screening.
Rena: And that’s kind of the basic?
Teresa: Exactly the basic and M, as in Mary, is testing for specific conditions.
Dara: So not done by all? Or not necessarily recommended for every patient that comes here?
Teresa: We can only do PGT-M if we know that there is a specific genetic condition that that family is at risk for.
Rena: And now if this is the new PGD now this would mean this is what you build a probe for?
Teresa: Exactly. So exactly. So when we test embryos not for aneuploidy not for chromosome stuff but for specific genetic conditions, so again zooming in to look at the individual genes on those chromosomes, we have to build specialized technology because testing embryos works a little bit differently than testing people so that embryo biopsy that we talked about earlier that we're taking from the outer part of the embryo that becomes the placenta that’s also called the trophectoderm that area of the embryo. That biopsy has about 5 to 8 cells worth of DNA in it. Where is when you take a blood or a saliva sample from someone you get millions and millions of cells. That's what most genetic technology that NGS the next generation sequencing technology we're talking about. It's used to having that much DNA. So when you suddenly go down to 5 to 8 cells, if you were to use the regular technology, there's a very high chance we would not get correct results. So what we have to do instead is we have to build customized technology, which we refer to as a probe that’s sort of an outdated term because it implies that there's a physical entity.
Dara: I think of a probe at the doctor’s office!
Rena: I think of this giant, alien thing which makes no sense. That’s totally my vision too. Spaceship for a teeny embryo.
Teresa: It’s really more of a compter entity at this point. But it's basically identifying unique genetic markers to that particular couple or pairing if it's a patient using donor sperm or something like that. That particular pairings combination of DNA marker so is unique to every egg and sperm pairing. So one couple, even if two different couples are testing for the same condition their probes will be different.
Rena: And so this process takes quite awhile, right?
Teresa: It takes some time, exactly.Because it's so individualized and because they're only like I said, a handful of labs in the country that do this sort of testing it usually takes about two months or so to build a probe
Rena: I know that’s very frustrating for people.
Teresa: I would be frustrated myself. I always feel awful telling someone they have to hold off for two months to build the probe, but in many cases it's important. You know that for if it was a situation where that two months is really going to change prognosis, we obviously would have that discussion.
Rena: Well, it’s two months versus a lifetime
Teresa: So two months of delaying versus a lifetime of potentially at having a child with a severe genetic disorder. While those two months are excruciating and there's no sort of getting around that, and I admit that that is tough. In the end, it's usually worth it. And building a prove is a onetime thing.
Rena: Ok. I was gonna say if you have more than one children can you reuse the probe?
Teresa: So you build it once at the very beginning, before, so you need to build it before you start your IVF cycle, because you want to make sure that it's done before we have any embryos in the lab to test, and once it's built, it's there forever. And see if you need to do future IVF cycles, you know more than one you don't have to take time to build the probe again and once it's done, it's done. The only time that we've ever had to redo all this, if someone switched partners is.
Rena: And then for this I hate to ask, but is this one much more expensive then?
Teresa: It does tend to be much more expensive. The test usually runs a couple $1000 I would say, but I have seen lately and particularly the major insurance companies be actually there. If there is a genetic indication so if that family is at risk to have a child with a genetic disorder and it's a definable risk we know it's there. I am seeing a lot of insurance companies start to cover it.
Rena: Well, it just makes sense because for them, a couple of $1000 versus then the care for a person with…
Teresa: It makes huge sense. So, we’re starting to see that happen a lot. And now that, for me at least, is often dictating what lab I’m using. Because different insurance companies have different PGT labs that their in network with and for the majority of you know, genetic conditions, I have to be honest, it doesn't make a huge difference. There are a handful of conditions where I might recommend one lab over another, building the probe, you can use different, there are different approaches to that different technologies for most conditions one technology is as good as the other it’s just that lab’s particular specialty. But there are certain conditions that I might recommend one lab over another.
Dara: And in terms of the major people that you typically suggest this for…
Dara: Are there any common threads that you see?
Teresa: Yep. So going back to what we were talking about earlier, those recessive conditions. If a couple does come back, where both the egg and the sperm source, both members of that pairing are carriers for the same disease, that's when we can create a probe. So we know that couple has a risk of having a child with a specific condition. We could build a pro for that condition.
Rena: So what are some examples?
Teresa: Sure. So I would say some of the common ones, cystic fibrosis that’s a common one for two members of a couple to be carriers for. Sickle cell anemia. Tay Sachs. There's a couple of other ones that we're seeing more frequently. We’re seeing a very high carrier frequency in the general population for something called non syndromic hearing loss?
Dara: I have not heard of that.
Teresa: It’s now included on the carrier screening. So we're seeing it. You know, people be screened for it a lot more often. It's basically hearing loss in the absence of other you know, sort of any other bodily or issues. So we don't see typically an effect on lifespan or intelligence. But it does obviously it is a disability. It can be quite impactful. So we're seeing that pop up. A lot of people do PGT for that.
Dara: What about BRCA? The BRCA gene.
Teresa: So BRCA is not something that's typically screened on the carrier screenings. This is sort of a great question that ties in multiple things. So when we do that carrier screening that we were talking about, we're only testing for recessive conditions, or things that you might be at reproductive risk for that you don't know about that aren’t impacting your own health. BRCA and other conditions and its same category or what we call dominant conditions. So they’re conditions where a patient or partner could actually have that condition themselves. For BRCA, that condition is hereditary breast and ovarian cancer. But there are other dominant conditions that we might see a couple walk in, and one member of the couple has a dominant genetic condition. They can also use PGT to avoid passing that to the next generation. So I do see people use that for a number of different dominant conditions. Usually ones that are either associated with cancer syndromes or are later adult onset. So they may be in their reproductive years and not yet be having an impact on their life. But wanting to make sure it doesn't get passed on to the next generation.
Rena: And for BRCA II, refer back to our episodes with Dr Matthew Lederman and Amy Switzer because in those episodes we really dug pretty deep and specifically about how to go get tested for BRCA and who should get tested.
Teresa: Yeah Dr. Lederman is the expert on that.
Dara: He’s great. And then, in terms of so people, sometimes you recommend generally carrier screening number one. For patients that do IVF it is mentioned to do PGT-A.
Dara: And then, for specifics...
Teresa: Yep, so for joint carrier couples on the carrier screen
Dara: Do all three?
Teresa: Exactly. Or people who have specific genetic conditions that they are either themselves affected with. There's also a category of conditions called X-linked conditions, which are conditions that only women carry. Some of those are on that carrier screening panel. So we would do embryo testing in those scenarios as well.
Rena: And then Okay, so we talked about you could test embryos for these now what if you're a patient that comes in and is freezing eggs? Then you test, eggs?
Teresa: No, you do not wanna test eggs. So there is a technology called polar body biopsy which is a method of testing eggs for genetic conditions. But it is pretty invasive. You think about that egg is one cell in size. Remember I said even back in the day when we were doing an eight cell trying to biopsy an eight-celled embryo that was somewhat invasive. In addition, eggs have not fully completed their maturation process, so the exact DNA compliment is not always such. So it’s usually a better, you know, bet to test at the embryo stage.
Rena: So now there's really no way to test egg quality?
Teresa: So individual, exactly. Individual eggs or sperm, usually testing them is invasive enough that then that egg or sperm is not really usable. So you really have to wait until there's an embryo that's formed with multiple cells. Because remember, when the egg and the sperm come together, it goes from being one cell to over the course of the following days, two cells, four cells, eight cells, sixteen cells it gets bigger and bigger and bigger, and not until it's reached that you know, 100 to 150 cell stage between days five and seven is it really safe for us to be taking away material to test
Rena: OK so all of this is really just for embryos?
Dara: I also want to ask. I know you're quite involved here at RMA with the research aspect. Is there any new research that you kind of want to discuss or anything or another question would be, any research that you would like to do in the future?
Teresa: Yeah. So I think one area that a lot of research is gonna be going into soon is the idea of mosaicism, so that's sort of a big a big topic that could honestly be a whole podcast in itself.
Rena: Very controversial.
Dara: Part 2.
Teresa: Yeah, exactly. To sort of summarize on PGT-A So on the chromosomes screening it is possible to get embryos where their results show some normal cells. So some cells with the right number of chromosomes and some abnormal cells, some with the wrong number of chromosomes, so a mixture instead of just one or the other. We see that in approximately 7% of embryos. So it sort of is this gray area not normal, but not abnormal. And not until that we had that new technology change the next generation sequencing a couple of years ago could we detect that. So there isn't a lot of data on the safety or reproductive viability of those embryos. You know, we don't really recommend attempting pregnancy with them unless you have no other option or no other choice. So you know, if it is possible to do another IVF cycle and create more embryos to try to get fully normal embryos we say do that first. But, you know, we are in some situations, maybe going forward, going to be considering transferring some of those for patients who have no other option. There are some clinics in the city that that started doing that. You know as well this is gonna be interesting to see in the next couple of years.
Dara: The research is…
Teresa: Exactly so far, it seems like those embryos have a much lower reproductive potential, much lower chance of implanting much higher chance of resulting in a pregnancy loss. Then using a fully euploid or fully normal embryo. But there are a handful of live births that have been reported, so it'll be interesting. Now, those babies, are still very young, I believe under two years old. This is a fairly new finding. So it's, you know, we really don't have much information until we see long term development and see a lot higher numbers. But it's gonna be interesting to see where that goes. It’s something we're feeling very cautious about right now, but we want to see where it goes in the future.
Rena: And that could make a big difference too to people maybe they have diminished ovarian reserve...
Teresa: And those are the cases that we want to get the answers for. For those people where their only option is mosaic embryos. For people who have euploid embryos, you know, we're gonna use those obviously. But for those patients that were, that's their only you know, the only way that they could possibly go. We want to get more answers. So that's where the research I think it's gonna be going.
Rena: That’s fascinating. I know this is a little existential, but something I think about a lot kind of Just being in this space is and sort of seeing the shift and advent of new technology is, is all of this going to dramatically impact our population? You know, we're doing testing and screening, and we're now kind of shifting so that we're able to, you know, have healthy pregnancies and children born without defects that may have been born with, and so is all of the science and technology, you know, are we really sort of changing our population? I think it's fascinating to think about.
Teresa: It is and I think about that a lot myself. I think right now, no, because it is on when you think about it a very small percentage of the population does IVF still.
Rena: What percentage is doing IVF?
Teresa: I don't think they have…
Rena: It feels like 100 in New York City.
Teresa: To us it feels like everyone is doing IVF! But when you think about the numbers I think, was it last year? I think it is somewhere between one and 4% of babies in New York City were IVF so it's actually a very small number. And in New York City it’s higher than the rest of the country. ? So the number of babies being born through IVF is actually is an aggregate. It's a large number, but in comparison to the whole population is actually still a fairly small amount. And I think that, you know, when I see understandably how much difficulty a lot of our patients have with the idea of having to do IVF, and the only way we're ever gonna really be changing our evolutionary track as humans is if everyone is doing IVF and I find at least right now, based on my what I've seen our patients experience so far and maybe especially given right now. How time and emotionally intensive IVF is. I find it hard to believe that everyone would it would ever be doing IVF.
Rena: I agree.
Dara: Not in our lifetime at least.
Teresa: If the technology changes or becomes so much simpler and easier. And right now I don't think it's in enough, there’s not enough people to be significantly impacting. But I think in the people who are doing it, you know, we're really, you know, increasing their chance of success by a lot. Having a healthy pregnancy by a lot.
Dara: Look at what we’ve accomplished in 10 years time. I can’t wait to see what's ahead. So how you usually end our podcast is we talk about gratitude, and we ask everyone what we're grateful for today. So, Teresa, what at this moment, what are you grateful for?
Teresa: I am grateful for I think especially, you know, in the middle of the winter I feel like it's always a little bit of a bleak time, and I'm grateful to be working at RMA. To have such great coworkers surrounding me like you guys. I truly think it's a place that I'm happy to come to every day that I've been happy to come to for almost a decade so that today I'm grateful for that.
Dara: That’s so nice. Rena?
Rena: I guess same vein. You know, I felt like I was here pretty late last night came back very early this morning. But I’m so grateful for that because I almost prefer when you're living breathing work, because it means you love it. You know, and it's like I was here because I wanted to be. I came early because I wanted to and I had too much to do. And I love that feeling of feeling so inspired and wanting to be here, you know, and truly loving what I do. So I almost last night I was thinking when I left, I feel like I live in my office but I love it. And so I really love that feeling. And I think I feel you agree so grateful to have that and have such amazing people here and such strong, smart women. You know, I love that.
Teresa: So true it’s one of the great things about RMA.
Dara: Lots to be grateful for, but at this moment I was thinking I was when we were talking about genetics talking about high school. I want to give a shout out to my biology teacher. Mr. Dawson really was one of the hardest courses ever. But he really challenged me and made me excited. I really do think that was probably the first time I was like, Wow, I want to do something in the science realm. And then also just I'm so excited for what the research can do and where we can take all of this information and what new information we can get. So just the idea of learning continuously doing research. I didn't know much about this whole process. And so for me, it just opened my eyes to another area that I kind of wanna be involved in and just more educated on. So thank you so much, Teresa.
Teresa: You're welcome.
Dara: Such a pleasure
Teresa: Thank you for having me.
Rena: Thank you.
Dara: Thank you so much for listening today. And always remember, practice gratitude. Give a little love to someone else and yourself. And remember, you are not alone. Find us on Instagram @fertility_forward. And if you're looking for more support, visit us at www.rmany.com and tune in next week for more Fertility Forward.