“Preimplantation Genetic Testing: PG-Rated!” – with Dr. Rachel Gerber
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Dr. Fox: Welcome to today’s episode of “Healthful Woman.” A podcast designed to explore topics in women’s health at all stages of life. I’m your host, Dr. Nathan Fox. An OBGYN and maternal-fetal medicine specialist practicing in New York City. At “Healthful Woman,” I speak with leaders in the field to help you learn more about women’s health, pregnancy, and wellness.
All right. Rachel Schwartz Gerber, how are you doing from RMA of New York? Welcome back to “Healthful Woman” podcast.
Rachel: Thank you. I’m happy to be here.
Dr. Fox: This is great. Your podcast in November on egg freezing was a huge success. You said people are just flocking to you to get their eggs frozen?
Rachel: Well, yeah, I’ve had a couple patients come and say they heard it and that they connected to it. And that they really enjoyed listening and they wanted to come see me.
Dr. Fox: That’s amazing.
Rachel: So it’s excellent.
Dr. Fox: Yeah, that’s good. And in this weather with 26 inches of snow, I guess it’s very temporal to talk about freezing things.
Rachel: That’s true. And more to come with the snow.
Dr. Fox: There was some controversy over the podcast. So one might think that the controversy might be over reproductive ethics, and this and that, but no, it was totally over the title, further proof that men are useless. You got a lot of flak for that, yes?
Rachel: I did get some people telling me, I don’t know if this is going to be taken in the right way, especially for our male patients, since we do treat both men and women. I was like, it’s a joke. It’s light hearted. I am a fan of all sexes, of humans.
Dr. Fox: Yes. And also, it’s like the whole thing when someone writes an article, and then there’s like a crazy title. And the author is, “No, no, the author doesn’t write the title, the editor does it.” So you just blame Fox. He picked the title. I pick the title.
Rachel: Well, of course. I say I didn’t choose it, but I think that it’s giving it some clicks. So I think that ultimately…
Dr. Fox: Some buzz.
Rachel: Some buzz. So I think that’s good.
Dr. Fox: Excellent. All right. So we’re talking about Preimplantation Genetic Testing. So, what is that? Tell our listeners, what are we talking about here?
Rachel: So this is something that’s been developed over the last 10 years or so. So it’s a somewhat new technology, but has gone quickly. And the technologies have just gotten better and better with time. Essentially, what we do is we do IVF simulation, retrieve eggs, and then combine them with sperm and grow them out into embryos. So it used to be that we more focused on day three embryos, when our culture systems, our ability to grow them in our petri dishes, in our incubators, wasn’t as good. Originally, what they were doing is on day three, taking one cell out of about eight, and actually sending that cell for genetic analysis. And they were able to tell you…at first they were just looking for Down syndrome, and some of the other chromosomes that could produce viable children that are compatible with life, and to rule those out. But the technology advanced where they would get all 23 sets of chromosomes, and they were able to tell you this is likely to be a genetically normal 46 XX which is female, or 46 XY, which is male embryo. So that’s how it all started.
Dr. Fox: So the concept is, for people who are undergoing IVF, for either another reason, or if they choose to do IVF, for this reason, before you decide which embryo to put in, you can sort of select out which ones are genetically, I guess, better, in a sense, or don’t have a specific genetic disease that they’re looking for, or to screen for genetic diseases that they may be at risk for. Correct?
Rachel: Exactly. So one of the most common reasons why people miscarry or why IVF doesn’t work and the embryos don’t take, is because the genetics or the chromosome numbers of the embryos are not correct. So there’s the wrong number of chromosomes, which are your large pieces of DNA that code for everything that makes us human. Ultimately, what they thought…the original concept was, well, we know that this abnormal chromosome number is a major factor in infertility as women get older. And so, if we can actually find these genetically normal embryos from a chromosome standpoint, we can focus our energy on those and potentially have better outcomes than putting in embryos where we don’t have that information.
Dr. Fox: And prior to this or either in conjunction with it, you basically went with how the embryos looked, right, there’s certain criteria that this embryo looks healthy. You graded them, correct?
Dr. Fox: Like school, they got grades.
Rachel: They get grades and they still get grades.
Dr. Fox: They still get graded. So we’re not pass, fail yet.
Rachel: No. We’re not…
Dr. Fox: Everyone’s a winner. Yes.
Rachel: Medical school is pass, fail, but no, the embryos still get the grades.
Dr. Fox: Yeah. So at RMA, you do not hold that every embryo is a winner.
Rachel: If it produces a baby, it’s a winner. We ultimately don’t care what the…once you have a baby in your arms, we don’t really care, and it doesn’t mean that the baby is going to be any… There’s no association between the grade and any development or features of the baby. It does help kind of triage which ones are the most likely to implant. So yeah, they still get grades, and people often have more than one genetically normal embryo in a very good situation. And so, at that point, they might say, just put in the one that looks the best.
Dr. Fox: Amongst your genetically normal embryos.
Rachel: And so, amongst your genetically chromosomally normal embryos.
Dr. Fox: Obviously, the people who determine what the grades are, these are what, like the embryologists who work in the lab?
Rachel: The embryologists.
Dr. Fox: They look under a microscope and it’s based on how healthy the cells are dividing or whatever, do some criteria.
Rachel: Exactly. So the embryologists are like the unsung heroes, right?
Dr. Fox: No one knows who they are.
Rachel: No one knows who they are. The doctors get to be the faces, but the embryologists are so important. I mean, a huge part of what makes a successful IVF program are the embryologists. So that’s something that…patients definitely focus more potentially on choosing their doctor, but they really also need to think about choosing a lab, and look at the outcomes of that lab, because the doctor can be the best doctor in the world. If you don’t have the embryology lab behind you, it’s going to affect the pregnancy rates. So we also joke that they’re like the first babysitters.
Dr. Fox: And it’s true because in the lab it’s… I guess that makes the lab as the first daycare.
Rachel: Exactly, something like that.
Dr. Fox: It’s full board, though. They’re there the whole time, and potentially for years and years and years when they’re frozen. But the embryology lab is using its embryologists, so there’s professionals who are trained to look at them and handle them, but also, like you’re saying, there’s just, what is the fluid that’s in the petri dish that can make or break how the embryo goes? What is the air quality in the room? What is the backup generator like in the room in case the power goes? I mean, there’s so many things that go into a successful lab that people do not think about obviously.
Rachel: Yes, all that stuff has been well studied. And it’s a big part of our field. And you can imagine, New York, it’s expensive to put in place all those systems, but we have it all. And it’s where you spend the money, is to make sure you have the right filtration systems, and all your generators. That’s where you focus your finances.
Dr. Fox: So now you have these embryos. And you were saying that when they first started this technology, they would take out one cell on day three, because at that point it’s only like 8 or 10 or 12 cells.
Rachel: Yeah, 8 to 10. Yeah.
Dr. Fox: So you take out one, and you test it. And nowadays, it’s done later, correct?
Rachel: Exactly. So we now have the technology, and again, the media, the fluid, the embryo is growing, everything has advanced so much. Also, our incubators, the air quality, that we are now really able to grow embryos efficiently to day five. And by day five, I actually mean five to six. We say day five, but really, it encompasses both day five and six. What that means is the embryo has a form that we call a blastocyst. And that means that the inner cells which are going to become the baby ultimately, have kind of separated from the outer cells, we call the trophectoderm, that’s going to become the placenta. So there’s already started to be some identification of which cells are going to be what? So as opposed on day three, the cells can still all become anything, so they have what we call differentiated into different destinies.
On day five, you now have cells that have been identified as this is going to be the placenta, this is going to be the baby. And then there’s fluid in between. So at that point, we now know we can actually choose to take cells specifically from the area that will become the placenta versus the area that will become the baby.
Dr. Fox: And what’s the advantage that has, because it lowers the chance of sort of harming the embryo in the process, or because you could take more cells, or what is it?
Rachel: So at that point, there’s about 100 cells. So you now take about 5 from 100 versus 1 from 8. So you’re taking fewer. If you were to actually biopsy the inner cell mass, you would ultimately destroy the embryo, because ultimately, you can’t replace that. And that’s kind of a big question. Does the outer cells actually always match with the inner cells? Except in research studies, which are research done on embryos to figure out some of this science, we assume that the outer cells represent the inner cells. And I think most of the time they do.
Dr. Fox: Yeah, we have conceptually the same thing when we do a CVS, and we do CVS, we’re doing a biopsy at 10, 11, 12, 13 weeks of the placenta. And it’s the same thing that 99% of the time, the DNA in the placenta matches the DNA in the baby. And by 12 weeks, it’s only 1% of the time that it’s not a match. I imagine it’s probably higher earlier in gestation, yeah.
Rachel: It’s more even. Exactly. So you can almost think of PGT-A, or Preimplantation Genetic Testing as like an early form of a test like a CVS or an amnio. It does not replace that, but it kind of gives you similar information, that those tests do in terms of getting a chromosome count and understanding, is this a chromosomally normal male or female?
Dr. Fox: Conceptually, people, I think, get this. It’s really cool, obviously, that you can do this. And people who are doing IVF already make decisions about whether they want to test the embryos or don’t want to test the embryos. And there are people who sometimes choose to do IVF, because they want to test the embryos in advance. But I think some of the confusion is because the type of genetic testing done differs. There’s different types, and they now have different names. We used to call this PGD, Preimplantation Genetic Diagnosis, then we came up with the term PGS, Preimplantation Genetic Screening, I believe is the S. And now it’s PGT, Preimplantation Genetic Testing. But of course, since we’re doctors, we have to have subtypes to confuse people. So there’s PGT-M, PGT-SR, and PGT-A, so really just to make people confused. But those essentially, are differentiating the three reasons someone would have genetic testing.
Dr. Fox: So let’s go into those three reasons. So the PGT-A, aneuploidy, which is what you were discussing before. Is it Down syndrome? Is there an extra chromosome, a missing chromosome? Something like that. And is that something that’s always done, or something that people have a choice to do?
Rachel: It’s something that people have a choice to do. And there are certain situations where it may be advantageous. Some of those situations, commonly what you might hear is if you have a history of recurrent miscarriage, and particularly if you’ve had miscarriages where you’ve tested the pregnancy that passed, and you know that that pregnancy had a chromosome abnormality, right? That’s one scenario where it really clearly would have benefit, that hopefully, if you find a genetically normal embryo, you can overcome that problem. Another thing is just people with advancing reproductive age where we know after 35, and then as you move through your late 30s, early 40s, just a high percentage of the embryos women make are genetically abnormal. So you could end up kind of wasting time putting those embryos back that are abnormal or even them implanting and ending in a miscarriage because some of these abnormal embryos will implant, but then ultimately, cannot end up in a baby. So you can potentially lose time. So the best…
Dr. Fox: And also, it’s a lot of heartache, and sadness, and everything.
Rachel: Exactly. And it’s very difficult for patients. And the patients that had a history of miscarriages are often the ones that feels the most strongly, because they’re scarred.
Dr. Fox: They’re scarred.
Rachel: And they’re like, if I could do anything that may prevent me from having to go through that again, that’s what I want to do. Ultimately, it’s really best when you have an option. So an older woman with good egg counts, where you will have a choice, like you’ll get 4 embryos in a 39 year old, and you know 1 to 2 are going to be normal. Like let’s say one is going to be normal, three are going to be abnormal…
Dr. Fox: You could find that normal one.
Rachel: …you find that normal one and not just kind of put in embryos, until you get there.
Dr. Fox: And also, in the past, instead of testing, they just would put in all four.
Rachel: So that’s a huge advantage of testing. So it used to be exactly that to make up for the fact that so many embryos are genetically abnormal as you get older in a higher percentage, well, if you put back more, then you make up for that. So if you are at 35, let’s say, this is what it used to be, you’re at about a 50-50 for…well, if you put in 2, now you are kind of making up for that 50-50 chance.
Dr. Fox: For 25% time you get twins.
Rachel: Exactly. And ultimately, we were creating a lot of health issues for mothers and babies. The field had to kind of look itself in the mirror and say, are we actually doing something positive for society by, I mean, not only twins, I mean, triplets, quads?
Dr. Fox: Triplets. That was the heyday, between, let’s say, 10 and 20 years ago, it was…I mean, routinely, people would show up, “I’m pregnant with quintuplets. I’m pregnant with quadruplets. I’m pregnant with triplets.” And then that’s when all of the pregnancy reduction start getting very busy, because someone’s like, “I can’t carry six babies.” It was a whole situation. And now with the testing, it’s much, much lower. I mean, you guys are probably putting in one embryo almost all the time now, I would imagine.
Rachel: Yes. We are one of the, I’d say, most compliant IVF programs I know. And that’s one of the reasons why I joined because I was so proud of that. Ultimately, once the field started realizing we’re creating all of these health issues with these multiple pregnancy, we started putting strict guidelines on how many embryos should be transferred by age. But ultimately, and it’s very clear from the guideline, if you have a genetically normal embryo, the age goes out the window, you are putting in one. And so one thing, and there’s certainly controversy around PGT testing, some clinics are more in favor, some clinics are less in favor. Some clinics are more like, “No, let’s just put in more.” And are more in favor of not testing and just putting in more. But no one can argue that it helps increase the rate of one healthy baby at a time.
Dr. Fox: Okay. So one reason you might test is to check the total number of chromosomes, like you said, sort of make sure it’s genetically normal, so to speak. The other kind is this PGT-M, which is monogenic, which means like a very specific mutation in one gene and one chromosome, like a disease, like Tay-Sachs, for example.
Rachel: Exactly. So this is where the technology I think, becomes really exciting, and kind of something we are able to do to really help our patients immensely. There’s two different kinds of diseases that we focus on, one would be an autosomal dominant disease, so where the patient or the husband actually come affected with that disease.
Dr. Fox: They have a condition.
Rachel: And in that case, 50% of the embryos…if we go back to high school biology and like the Punnett squares, so in that case, 50% of the embryos that are even chromosomally normal are going to carry that disease. And an example of this might be some of the hereditary cancer genes like BRCA.
Dr. Fox: BRCA, exactly.
Rachel: It’s a very personal decision at that point. A lot of people say, “Well, I have this and I’m happy, and I’m living a fulfilled life.” They don’t want to go through the testing. Others say, “My husband has this, and I really want to prevent my children from having to go through whatever medical interventions and risk that comes with it.” And then we basically have these patients meet with a genetic counselor, and really go through not just again, the medical side of it, but a lot of the psychological kind of emotional side of what this means, and…
Dr. Fox: Self-worth, and all of these. It’s complicated.
Rachel: Exactly. So we have social workers and a whole team that works with people around some of these conditions. And again, some are much more clear than others, especially when you have like adult onset diseases versus something that is going to be horrific for a child that is clearly not something that you would consider meaningful life.
Dr. Fox: The reason it’s tough with the autosomal dominant ones is the diseases that are really, really bad, they don’t tend to…they wouldn’t live to be having children.
Rachel: That’s true.
Dr. Fox: So if they walk in as adults undergoing IVF, usually the condition is such that clearly you can live with it. And that’s why those people are like, well, is it something I want to sort of take out of my family line, or not take out?
Rachel: Gene pool. Right.
Dr. Fox: So for example, like dwarfism, like little people. And it’s complicated, because on the one hand, they can do genetic testing to make sure their children don’t have it, but they may not feel that way, because they may feel that they have an identity this way, and they’re very fulfilled and happy. Again, and they may feel that it’s almost the opposite, that they don’t want to do that. And that’s why it gets very complicated for these types of conditions, because these are conditions where you live to adulthood. I found in my own practice, that people typically if they know they have a cancer gene, they’re more than happy to sort of get it out in that sense, because they’re like, this is annoying. At worst case, it’s dangerous, and at best case it’s annoying because you’re screened forever, you know it. But if they have an actual condition, it is complicated.
Rachel: Yes. So again, there’s a lot of like personal choice that goes into that. And it’s something that we have a team to help work through those decisions. So that’s one set of conditions. The other set is what we call recessive disorders, where you need two copies of the gene, typically one from each parent, and that they both have to pass on that gene. And then you have a one in four chance that your children will be affected with that condition.
Dr. Fox: So this is like…Tay-Sachs is a classic one. Cystic fibrosis is another one.
Rachel: Exactly. Cystic fibrosis. Yeah.
Dr. Fox: And these tend to be… Cystic fibrosis is an exception, because now the therapies are better, but something like Tay-Sachs is uniformly devastating, and neither of the parents has the condition, they just carry it. So they’re perfectly fine. This is one of the reasons we do those massive carrier screens either before or at the front end of pregnancy to find out which couples are at risk for this, because you wouldn’t know because it’s not a condition that runs in your family, because no one’s had the disease, they just carry it. And so you just find out like, “Whoa, I didn’t know that.” That must be a common reason you’re doing this kind of genetic testing.
Rachel: Yes. So every patient that walks through our door and walks through, I think, any New York City fertility practice, is going to be offered or I actually recommend what we call expanded carrier screen where you get screened to see if you carry one of two to 300 conditions that are the most common conditions we see in humanity. So ultimately, if you end up coming back as a carrier, and your partner comes back as a carrier as well, of the same thing, we then give you the option to actually screen embryos to find the ones that didn’t inherit both copies.
Dr. Fox: And it’s cool, because this isn’t something normally a geneticist is testing. If you’re looking at an embryo, the kind we’re counting the chromosomes is a certain technology we like look under the microscope and count the chromosomes, but this you have to specifically know the condition and send a probe in. You can’t like say, “Oh, just test me for everything,” because there’s too many conditions, you have to know which condition you’re looking for.
Rachel: Exactly. With these, you actually have to what we call build probes that are specific to your DNA. So DNA has these small variations from person to person, and most of them are normal variation. And then you have some that are mutations that cause diseases. So they actually need to build a probe specific to your variations. So the probe knows exactly where to attach to when they put it together with the DNA. So that process takes time. And sometimes it’s even beneficial to have your parents involved, to further map exactly where it is, and get that kind of genetic fingerprint that is specific to you. They sometimes want your parent, which I find some patients get really freaked out about. Some are like, “No, no, no, parents are not involved.”
Dr. Fox: Not unless they’re paying for this.
Rachel: Others are more than happy. So that’s another thing. Everything comes with these like layers, in our field, of anxiety for people. And another very interesting thing is I always have couples, one could be from India and the other one is from South America, and they will carry the same thing way, where you’re just like, “What?”
Dr. Fox: How did that happen?
Rachel: Or like one is from Japan and one is from Europe, and they carry that, and you’re just like, “Wow.” You really never know.
Dr. Fox: Yeah. We used to test people for a specific genetic…to carry genetic diseases based on their ethnicity, their ancestry, all of your…from the Mediterranean, we’ll check you for thalassemia. And if you’re Ashkenazi Jews, do this. And we did that, because sort of the likelihood was higher, but what we’ve learned in these expanded screens is A, we’re all mutated, and B, it’s just an issue where…and so much of it is random, [inaudible 00:23:58].
Rachel: You’re just like, “What? That’s a disease from Northern Ireland. You’re from Japan.” I don’t know how to explain that.
Dr. Fox: These things can be passed down for literally hundreds and hundreds of years before it shows up in a family, because unless you coincidentally procreate with someone with the same mutation, and then still, it’s one out of four, even on top of that. So, that happens. That’s another reason. That’s a pretty cool reason because some of these diseases are really, really devastating. And it’s something that parents generally don’t wish to do that when they’re having IVF. And this is also one of the reasons some people specifically do IVF.
Rachel: Oh, yes.
Dr. Fox: Like they don’t need IVF otherwise, they’re like, “I don’t want to take the one in four chance,” because you could test in pregnancy and have an abortion, but they don’t want to do that. Or, either because they don’t want to have an abortion. They’re like, “Why would I do that when I can sort of fix this on the front end.” Or, abortion is off the table for them and like I don’t want to deliver a baby with this condition, and so they come to you for IVF, like IVF in order to do the testing.
Rachel: Yeah. So we get this in two different ways. We get a lot of patients that come having already gotten this, the expanded carrier genetic screen from like your office. I’ve gotten a lot of patients from your practice that come with the genetic screen, or are really…this is pretty standard now, at least in New York, because we’re kind of ahead of the curve, you might say, that people have caught on, that this is something…
Dr. Fox: And spending patterns. We’re ahead of the curve. Yeah.
Rachel: This is something it’s better to do before you get pregnant. So if you happen to catch someone, when they come to you and say, “Oh, I’m planning on becoming pregnant.” That’s actually the time to do it. I got it done when I was pregnant. And thank God, I carried something my husband didn’t that was that. And the funny thing is, between my two children, which are three years apart, I did it again.
Dr. Fox: Right, to update it.
Rachel: And a new thing I carried came up.
Dr. Fox: Not because you tested there, because the test was invented, developed.
Rachel: Yes, they added on not just new diseases, but new mutations within the disease. So I find, I have patients will come they carry two things like four years ago, and now they carry five things. I’m like, what’s going on?
Dr. Fox: Yeah. I’m told they’re about to expand from like 300 to about 500-plus. It’s coming. What ends up happening, though, is…and you can look at this in obviously, glass half full, glass half empty, even though there’s hundreds and hundreds and hundreds of mutations, what ends up happening on a couple level is the likelihood that any given couple is going to carry the same condition. It’s on the range of 1% to 2%. So on the one hand, that’s pretty low, meaning anyone’s doing this testing the likelihood it’s going to be fine, they’ll carry something else, and they’re good. But 1% to 2% is real. I mean, we deliver 1000 people a year. So 1% to 2% is 10 to 20 of them. And so it’s something, that’s why you have to screen because you’d otherwise never find out and it really does work. I mean, you can avoid a lot of really bad diseases by doing this.
Rachel: Yeah. And we actually run into the same issue, what I was saying with the autosomal dominant, where some things are like maybe they don’t want to do it, it’s not something that’s life threatening. Some of the disease, even the recessive diseases, are just some minor maybe likelihood to have high cholesterol, or where it’s going to be an adult onset issue, or it’s not something that’s very life altering, and you run into the same issue of, do they actually want to go through IVF for this? So it’s starting to trickle into the recessive diseases as well, that as they expand it…also, I’ll find there’s a lot of companies where one will carry one mutation, but it’s like not a very bad one, it’s only if the other person carries a very bad one. But if they both carry the mutation that’s not so disease causing, so you end up, like, it’s getting more and more complicated, and more and more hard to interpret sometimes. So that’s where our genetic counselors really come in. And they’re geniuses. For every genetic counselor, and they’re like…I mean, their memory is out of this world.
Dr. Fox: And on the lab level they… I mean, there are discussions in the genetic lab community, there is a community of genetic labs, believe it or not, I’m not in that community, but they exist, where they discuss and debate what conditions should and should not be on these panels. Because for exactly that reason, there is a lot of thought, like don’t put on conditions that are not significant illnesses, because people are not going to get the best counseling, potentially, and they may end up undergoing IVF. And they really don’t need to, or having an abortion where they don’t really need to, or just being super worried. And so there is an effort to try to choose which ones go on. But you can imagine, different people will look at it differently. So there is debate about it. But that is something they’re aware of. Meaning there are more things they could put on the panel that they choose not to, for good reason.
And then there is a third one I assume is less common, this PGT-SR for structural rearrangements and translocations.
Rachel: That one is less common but something we see. That is actually more for when pieces of chromosomes have rearranged, so you still have the correct number of chromosomes overall in the parent, but let’s say a piece of chromosome 1 swapped with a piece of chromosome 20.
Dr. Fox: They traded.
Rachel: They traded, and so when you try and reproduce, and you try and sort the chromosomes appropriately to get the right number in your offspring, you run into issues because the chromosomes of one parent don’t actually line up with the chromosomes of the other. That is a really specific case that is not…it’s more of something you hear about in the IVF community, but to the layperson is probably not as important to…or a common thing that you’ll hear about. It’s very specific.
Dr. Fox: It’s almost like the PGT-M, but instead of a small mutation, it’s like a big chunk type of thing, but the same concept.
Dr. Fox: Okay. So, question number one, when you’re doing these things, how accurate are they? You’re testing the embryo, and you’re saying this baby has the condition or this embryo has the condition, this embryo doesn’t have the condition. So what is the accuracy? And I assume it differs based on whether you’re doing the M for a specific mutation versus the aneuploidy one for the number of chromosomes.
Rachel: So, nothing is ever 100%, but the PGT-M gets very close, it could be greater than 99% accuracy.
Dr. Fox: It’s pretty impressive.
Rachel: But there are situations, like I mentioned, where maybe they say if your parent’s involved, we can get a couple more percentage points accuracy, but maybe a parent is deceased, or the parent is not involved. They’re in…
Dr. Fox: But it’s very high, either way.
Rachel: It’s very, very high. Like that’s one thing I know can make it a little higher, but ultimately, it’s considered a really excellent test.
Dr. Fox: But the one for aneuploidy, the number of chromosomes, there’s a lot of controversy over the accuracy. And why is that? Like, why isn’t that like, 100% of the time, when you test, you’ll know, this is abnormal, this is normal for the number of chromosomes?
Rachel: So, we’re ultimately only as good as our technologies and the ability to…when they do these tests, they amplify the DNA, which means they replicate it many, many times, and then they use machines to kind of take out…there’s often like noise they call it, so parts that don’t replicate. Ultimately, you have to rely on the technology, which is not perfect. I know, traditionally, we were much…the focus was really to make sure that we don’t call abnormals, normal. That was the main priority, that we don’t say, “Oh, this embryo is not affected with Down syndrome, not affected with trisomy 18,” like another one that could produce a baby that has a lot of severe health issues. That was more of what was considered to be the worst case scenario, is giving someone a reassurance that this is a normal embryo, and then it comes out. So I think we call that the positive predictive value. We were much more concerned at maximizing that to get in the high 90s.
The thing is, is that, we still recommend the same screening that every other patient goes through who did not have this technology. So we do not say that this replaces first trimester screening for Down syndrome, however that’s done with bloodwork and ultrasound. These patients should still be offered CVS and amnio, the same as every pregnant patient should be offered CVS and amnio. Our societies have been very clear that we need to make sure the OBs know that this is not a replacement for genetic screening. It’s a good test with very high rates of it being correct, but we still are humble enough to say still go through all the normal testing.
Dr. Fox: I think also when you have the DNA of the embryo is originally…it’s based on the egg and the sperm, so that’s from the parents. But then the cells start dividing. And when the cells start dividing, you’re not going to find like a new mutation that shows up in Tay-Sachs, but sometimes some of the cells will divide, and then two of them will be a little screwy. Like one got an extra one got a missing. So what happens is like, if you’re looking for extra and missing chromosomes, and like let’s say you take out one cell, and it’s normal, the assumption is the other 99 cells are also normal. But that might not be true. Or, on the flip side, you get one cell that’s abnormal, the other 99 aren’t necessarily abnormal, because it’s not that they’re always 100% the same at that point in gestation, or whatever, in embryology.
And so, I think what ends up happening is people sometimes get confused with these things. They’re like, “Well, they put back an abnormal embryo and had a normal baby.” Or, “I put in a normal embryo and I miscarried.” And that part, there’s something called mosaicism, which is when not every cell is the same. And so when we’re human adults, that happens, but it’s very rare. But when you’re an embryo, it’s much more common.
Rachel: Yes. So this is something that as the technologies for reading the DNA have gotten better…every advancement comes with its own set of challenges. It’s gotten better, but now it’s gotten so good that we can sometimes even identify different genetics, cell lines, within one embryo. And there’s still actually an argument how much of it is really, again, just the technology, an issue with the technology versus real mosaicism. But no one argues that there is definitely something called mosaicism, where you actually have cells with different genetic makeups within the same embryo, but people argue of how much mosaicism actually exists. So people argue that but everyone agrees that there’s some amount of mosaicism.
And this is where the counseling can become very complicated. And for patients who are not…again, they get like a real crash course in embryology and in genetics, and you get to really like, sometimes we just have so much information that you’re like, how much is too much? So essentially, when we have mosaic embryos we used to…and some still do say, these are abnormal, we will not transfer them. Slowly, some clinics and some kind of pioneers have said, you know what, some of these cells are normal, who’s to say the normal ones won’t end up dividing at a more rapid pace and kind of dictate the future of this embryo? And they went forward and started transferring these embryos. So there’s now hundreds to thousands of mosaics embryos that have been transferred, and really, what we know is that they have a lower live birth rate. So they’re less likely to implant, but when they do end up in a live birth, they are really finding that they end up in genetically normal babies.
Dr. Fox: Yeah, we just delivered a baby that was from a mosaic embryo, fine. Everything’s good. My understanding is when they take out, let’s say, 5 cells, or they take out a bunch of cells, as long as 80% of them are normal, they call the embryo normal, meaning that it’s assumed that up to 19% of the cells will be abnormal, so technically, they’re all mosaic. They just say, well, it’s low enough that it’s fine.
Rachel: Right. Well, that they actually consider noise from the technology. They said past 80%, we can’t use…past that, we’re not going to call it abnormal.
Dr. Fox: And the other end, if 80% are abnormal, they just say it’s abnormal, but 20% to 80%, that’s a wide range in the mosaics, so you can imagine that there are definitely people who are 60%, 70%, 75% normal, they call mosaic that probably will be fine. And you have to just look at those and decide.
Rachel: So this is where, again, our genetic counselors come in. So if you’re mosaic trisomy 21, that’s Down syndrome, or mosaic trisomy 18 or 13, which are other genetic conditions that could end up in a live birth. Those are not embryos that we would implant, because…
Dr. Fox: They’re not going to miscarry necessarily. Like a trisomy 2, you wouldn’t have a baby, you would just miscarry.
Rachel: Exactly. So we implant ones that it’s an all or nothing, we call it. That it’s either going to miscarry or be a genetically normal baby.
Dr. Fox: That makes a lot of sense.
Rachel: And so, we have already guidelines that our society put out that really already tell us these are the ones that are safer for transfer, and these are the ones to avoid.
Dr. Fox: With this, the one thing we didn’t mention, which is doing this, parents can select whether they’re going to have a boy or girl, XY or XX.
Dr. Fox: Two questions for you. Number one, how many people ask you to do IVF specifically for that reason? Like, “I have two girls, I want to have a boy, let’s do IVF,” and do it. And the second question is for everybody else who’s just having IVF, how much does that come into play?
Rachel: Doing IVF specifically for sex selection is something that is not that common, but we do see. And I have some patients who have come to me for that. The other question people are doing IVF anyways, it’s a part of almost every consultation that it’s brought up and spoken about, and there’s some at least conversation or interest, or opinion that the patient has about it. And I would say a large majority of our patients end up doing some form of sex selection in their reproductive process. So the most common thing we hear is for the first child, put the best morphologically normal embryo in. Typically, though, for the second child, I’d say more often than not, they have a preference.
Dr. Fox: Put the best boy in. The best…yeah, whatever.
Rachel: Right. It’s not always the opposite. I have many patients that have a girl and are like either, “Oh, I have this sister I’m really close with. I always wanted that for my kid.” Or, “I have all these girl stuff, I don’t want to buy a bunch of boy stuff,” or whatever it is. “I just want another girl.” Or the flip side. Or they say I have a boy, I want a girl. I’d say the majority of our patients for the second… When you have one sex and you want another, you call that family balancing. This concept of family balancing is something that the majority of our patients end up doing. The family balancing is choosing either sex but we got a lot that are happening with what they have and just want to go with that.
Dr. Fox: Do you ever have any situations where you start feeling troubled like ethically over the sex selection and maybe their…again, everyone’s got their own reasons, but where sometimes someone would say something, you’re like, “Uh,” like that seems like a very strange reason or something like that.
Rachel: Right. The whole concept of sex selection has ethically gone through stages in the U.S. It used to be ethically frowned upon in our field, and it’s come to the point where…it used to then move to, well, if you’re doing IVF anyways then it’s reasonable versus…but to do IVF for that, people found ethically troubling. Now we’ve come to the point where we believe in patient autonomy, and ultimately, we don’t have a problem with that except maybe a specific doctor does. As a society we’ve said, you can ethically participate in that.
The real issue becomes, and what you have to think about is that in countries where one sex tends to be preferred, you can actually cause some societal problems, which some countries are actually going through right now. Some countries that had limitations on the number of kids, actually have gender imbalance in play currently, which makes the dating scene very good for the women because men typically were preferred in certain societies and so people were having abortions or probably not using gender selection, but they were doing other things that were horrific to tip the scales to having a boy. The societies all universally say, if…in a country where you are changing the normal ratio of male and female, if that is going to happen, then it’s not considered ethical. Studies in the U.S. have shown it does not do that.
Dr. Fox: Right. Meaning it’s the same. Yeah, 50% preferred boy… Yeah. Okay.
Rachel: Boy. Right. Most people use it for family balancing is the most common thing. It’s more about wanting the variety. In the U.S., I don’t love hearing people say things that might be taken as demeaning towards one sex. Occasionally you might hear something where you’re like, “Okay, this does sound…”
Dr. Fox: Right. Maybe we should address your view on women before we deal with the IVF, or something like that.
Rachel: Exactly. That’s rear.
Dr. Fox: Yeah. I would imagine that’s rear around here.
Rachel: I’d say the majority like I said, is a second child situation, where they have a preference for the second child is by far the most common thing. I personally in my practice have not seen any sort of weight towards one gender, which is nice to see.
Dr. Fox: Any shenanigans. Yeah. Are there a lot of cases or any cases of people who do PGT to select an embryo who will eventually be a baby who’ll be an organ match, for a sibling or for a parent?
Rachel: Yes. You can do that. That is something that is in the literature, like leukemia, yes.
Dr. Fox: Right. If you have a child who has leukemia and you have another baby, let’s select a match to do a donor.
Rachel: You can. That’s something that’s been done.
Dr. Fox: That’s been done. Wow. That’s pretty crazy. Wow, Rachel.
Rachel: I know. Science fiction is here.
Dr. Fox: Yeah. Thank you so much for coming. It’s so nice to see you. I love seeing you. It’s a wonderful thing.
Rachel: I agree. Thank you for having me.
Dr. Fox: That’s awesome.
Rachel: It’s fun to be here. I’m so lucky to have met you again in medical school, years ago, in a chance happening on labor and delivery.
Dr. Fox: Yeah. More than I’d like to think. A chance happening. It’s because you met Rebarber. He recruited you. He found you, brought you in. Brought you in to the fold. Good stuff. I’m sure we’ll see you again. Thanks for coming. How about that? We’re doing PGT. That’s a new one.
Dr. Fox: It’s how you change a terminology on us again.
Rachel: Well, we might go back to S.
Dr. Fox: Oh, Jesus.
Rachel: I heard there’s now like a… We’re thinking of going backwards. Yes. To me it’s like just pick something and go with it, but doctors like to do this.
Dr. Fox: How about just PG, Preimplantation Genetics?
Rachel: I like that. I’m going to write to the…
Dr. Fox: Or rated PG. That’s it.
Rachel: Oh yes.
Dr. Fox: These embryos are rated PG. That’s amazing. Oh dude. All right. I’m going to have to copyright that.
Dr. Fox: All right Rachel, thanks a lot.
Rachel: Thank you.
Dr. Fox: Thank you for listening to the “Healthful Woman” podcast. To learn more about our podcast, please visit our website at www.healthfulwoman.com. If you have any questions about this podcast, or any other topic you would like us to address, please feel free to email us at firstname.lastname@example.org. Have a great day.
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