Creating a Family: Talk about Adoption & Foster Care

Genetics, Genetic Testing, and Miscarriage

April 06, 2022 Creating a Family Season 16 Episode 14
Creating a Family: Talk about Adoption & Foster Care
Genetics, Genetic Testing, and Miscarriage
Show Notes Transcript

Have you experienced a miscarriage? What type of genetic tests should you consider to prevent another miscarriage? We will talk about Genetics, Genetic Testing, and Miscarriage with Kim Skellington, a laboratory genetic counselor with CooperGenomics providing pre-test and post-test counseling to patients regarding genetic testing, and Dr. Rachel Gerber, a board-certified Reproductive Endocrinologist and Infertility Specialist with RMA NY.

In this episode, we cover:

  • What causes a woman to miscarry a pregnancy? 
  • How common is miscarriage? 
  • What is considered Recurrent Pregnancy Loss (RPL)? 
  • How common is recurrent pregnancy loss? 
  • Basic introduction to DNA, genes, and chromosomes. 
  • Genetic Testing of Products of Conception
    • What can go wrong with the genes of a fetus that would likely result in a miscarriage? 
    • What genetic tests on the products of conception are available after a miscarriage to determine the cause? 
    • At what point does a doctor consider genetic testing of the products of conception to determine the cause of the miscarriage? After the first miscarriage? Second? Third? How does a woman’s age impact this decision? 
    • How are the products of conception tested? What are patients told to do? 
  • Genetic Testing of Embryo
    • What is preimplantation genetic testing? 
    • Distinction between PGT-A, PGT-M, PGT-SR?
    • Is PGT effective at preventing miscarriage? What does the research currently show? 
    • Are mosaic embryos more likely to miscarry?
  • Genetic Testing of Parents
    • What parental chromosomal abnormalities can cause a miscarriage? 
    • What is a chromosomal translocations and can that cause a miscarriage? 
    • Is there a gene or genes that has been found that makes it more likely that a woman will miscarry a pregnancy of a chromosomally normal fetus? 
    • If a woman’s mother had multiple miscarriages, is she likely to have miscarriages?
    • Can these genetic anomalies by found by Parental karyotyping?
  • What is the prognosis for women trying to get pregnant after having had recurrent miscarriages? 

This podcast is produced  by We are a national non-profit with the mission to strengthen and inspire adoptive, foster & kinship parents and the professionals who support them. Creating a Family brings you the following trauma-informed, expert-based content:

Please leave us a rating or review

Support the show

Please pardon the errors, this is an automatic transcription.
Welcome, everyone to creating a family talk about infertility. I'm Dawn Davenport. I'm the host as well as the director of the nonprofit creating a family dot for today we're going to be talking about genetics, genetic testing and miscarriages. We will be talking with Kim Skellington. She is a laboratory genetic counselor with Cooper Genomics providing pretest and post test counseling to patients regarding genetic testing. She previously work as a genetic counselor in a prenatal clinic, where she discussed genetic testing options available in pregnancy and for those planning for a pregnancy. We will also be talking with Dr. Rachel Gerber. She is a board certified reproductive endocrinologist and infertility specialist with our RMA of New York. Welcome Dr. Gerber and Kim Skellington. We are so glad to have you here.

Thank you so much for having me. I'm happy to be here.

Right we're gonna start with since we're talking about genetics and miscarriage, we're going to start with a deeper dive in to miscarriage to understand kind of the the what we're how we're genetics is going to fit in we first need to understand miscarriage. So, Dr. Gerber, what causes a woman to miscarry a pregnancy? And yes, I realized that is a very basic question, but But let's start with the basics of workup.

Okay, so I think we can really break it down into different categories, you can have embryo factors, which have to do with the viability of the embryo, the most common of which would be a chromosomal issue with the embryo where you have the wrong number of chromosomes. But there are also other genetic conditions as well as other kind of other things having to do with the embryo and its ability to differentiate and move from one stage of development to the next that we know goes into going from a fertilized egg to viable pregnancy. So I think one category, like I said, is really focusing on the embryo. And then the the other is more maternal babies. So having to do with the the mother, the uterus that it's trying to implant into, or the the health of the, of the carrying mother. So in that those categories, you know, we have hormonal issues, we have clotting issues, and structural issues having to do with the uterus. So that's some basic overview. And it definitely gets a little more detailed, but that's some basic overview about the reasons we know about.

Okay, and then we can also talk about miscarriage can happen at different stages of the pregnancy. And when would how do those factors, the embryonic factors and the well uterine? are I guess, it's actually not just uterine, it's, it's the woman factor her the factors that are related to her. For first trimester pregnancies, what is the greatest cause of miscarriage there?

So by far the most common cause is the is a chromosomal count issue with the embryo. So either the embryo has an extra chromosome, or it's missing a chromosome. And that is the most common reason for miscarriage. And it's something that, you know, a woman doesn't do or a person doesn't, doesn't do or they can't control. So it's not that you're doing something wrong, or, you know, you made this happen in some way. It's something that is a random events that we know increases as a woman gets older, the likelihood of it, but ultimately, it is not something that you know, we can prevent or predict

or control or predict in advance. Yeah, okay. Yes. In advance. Yeah. So how common Dr. Gerber is miscarriage.

So, you know, it's there's a lot of different numbers.

I was doing some research on this, and it's all over the board. Yeah.

Right. Because some people talk about clinically recognized pregnancies, which means, you know, you know, you're pregnant with either positive pregnancy tests or even an ultrasound that confirms a pregnancy. You know, in that case, probably when you're talking about clinically recognized pregnancy, it's very age dependent, but on average, about 25% of all pregnant 20 25% of all pregnancies. That being said, when you talk about all pregnancy loss, including those that are not recognized, because they happen usually too early for someone to know about, or you know, maybe you get a period, it's a little late, it's a little different, but you you just kind of assume oh, that's my period when really, you know, we know sometimes there is a very early pregnancy that failed. And in that case, it can be up to 50% or more. You know, there's some studies that really look at that. It's, it's hard to study, but it's in studies where we have looked at kind of drawing really early pregnancy hormones on patients who are trying that they wouldn't have otherwise had beta hCG or pregnancy hormone drawn, that we do see positives, before even the period or at the time of the period that are very low, much more frequently than we have clinically recognized miscarriages.

And so, so, so miscarriages are not uncommon. But at some point when a woman has so when a woman has one miscarriage, that's what she is told this is, this is common, this has nothing to worry about. Take some time off and try again. But if after you've had more than one, then things begin to shift, at least in the woman's mind. So what is considered recurrent pregnancy loss? How many pregnancies must you lose before the medical professions? It says, Okay, this is a problem. No, that's I'm saying that more callously because of course any miscarriage is a problem for that one who is experiencing it?

Absolutely. So the definition of recurrent pregnancy loss is three early pregnancy losses. However, we will do a workup even at to the arteries, the reproductive endocrinologist side of our society say it's reasonable to start a workup after two. But technically the definition of recurrent pregnancy loss or RPL, is the acronym is defined as three early pregnancy losses.

What about a late pregnancy loss? Is that does that change? You said that it was three early pregnancies, which I assume means first trimester? What about second trimester losses? Do things shift if you've had a second trimester loss? Yes,

second trimester losses or or even, you know, third trimester losses are very are very uncommon. And when they happen, you know, there is a whole workup that goes on related to that that is different from the first trimester. There's some overlap. But it's also somewhat different from the first trimester losses. And that is typically covered by more of the OB is in the maternal fetal medicine, doctors who cover pregnancy and pregnancy complications. While the RAs are our eyes, we we deal with recurrent pregnancy loss, but once it's over 20 weeks, it's really something that, you know, there's more to think about in terms of, could it be something with the fetal growth? Could it be an infection, you know, and that is something that has its own set of testing and workup? That is a little bit different from early pregnancy losses.

Okay, so how common is early recurrent pregnancy loss? In other words, what percentage of women who are trying to get pregnant will experience two or more miscarriages or maybe we should say three or more since the technical definition is, is three losses.

So it is it comes down, you know, from the 20 25%, that when you have one pregnancy loss, you have about 20 25% chance of a clinically recognized pregnancy loss, it comes down to less than 5%. Okay, is having but it's also age dependent. So if somebody is in their 40s, for example, and we know that the chance of producing a viable embryo that has the correct number of chromosomes is actually quite low, then recurrent miscarriage can be higher. But I mean, you're more, you know, young, healthy population, it would be more like, you know, less than 5%. Okay?

Do you appreciate the evidence base content that creating a brings to you each week, we would be so grateful, if you would say so in a comment or review. Wherever you're listening to today's podcast, Your feedback helps us get this kind of expert based resources out to even more listeners who will benefit. So we know that, as you said that the majority of early pregnancy loss first trimester losses are chromosomal so that leads us in to the overall arts of this discussion, which is genetics and genetic testing. But let's pause here and do Some basic intro to genetics or to DNA genes and chromosomes. Kim Skellington, can you tell us kind of give us a basic introduction to what we're talking about with genetics and how it relates to conception?

Absolutely. So it's definitely helpful to take a step back and review what DNA and genes are. So as everyone may be familiar, our genes sometimes referred to as our DNA or genetic information. These are really are what are telling our bodies how to grow and develop. So our genes are the reason why we are the height that we are our hair color, eye color, you know how our hearts should form and develop. This is all because of those genes. And as humans, we roughly have about 20,000 genes that are telling our bodies to grow and develop, whereas for other animals, they have maybe more or less genes. And the way that these genes fit into the tiny cells of our bodies, or by packaging up into chromosomes that we keep mentioning. So the way I like to think about a chromosome is essentially like a string, and you have beads on that string, those beads are representing our genes. And then if you held one end of that string and twisted the other end, over and over and over again, that string kind of condenses, or coils up. That's essentially what a chromosome is, it's this package of genes. And so with the chromosomes where we get them, we get usually half of them from the egg cell, or for my mom and the other half from the stem cell or from our dad. And generally we should have a total of 46 chromosomes, that's what's considered the typical number, because that's totaling out the 20,000 genes that our bodies need to grow and develop.

Okay, so we we have 23 from our mom 23 from our data are 23 from the egg and 23 from the sperm for a total of 46 chromosomes. Alright, so now we're going to talk about genetic testing of embryos, or the products of conception, because when we're talking about miscarriage, that's often what we are working with. So and again, this is a fairly general question. And I apologize Kim up front for these these broad ones, but I do think it's helpful to to establish the foundation. So what can go wrong with the genes, or the genetics or the chromosomes, however you want to say it of a fetus that would allow an embryo that would likely result in miscarriage?

Right, so what can happen is that thinking back to that original egg cell or sperm cell, typically there should be 23 chromosomes, and each of those two then leads into an embryo with 46 chromosomes. But what can happen and happens relatively frequently in this stage is that there can be either the egg or sperm cell can have an extra missing chromosome, which then leads to that embryo with that chromosomal abnormality. And a chromosomal abnormality means that there's either an extra missing chromosome, which means there's either too many or too few genes. And so that's what's going to be impacting growth and development, sometimes so much so that a pregnancy results in a miscarriage.

And would the the egg or the sperm that had the extra or the missing chromosome. So with the parent, that is the the person that is carrying the egg or the sperm, they would not show any signs, even though their egg in their sperm has an added or missing chromosome. Am I correct there?

Exactly. So it's not anything again, like Dr. Gerber had mentioned, that really is caused or really can be prevented, in most cases that, you know, for whatever reason, it's really by chance that that initial egg or sperm just didn't have that chromosome or maybe had that extra chromosome.

Okay, so now, what is the step if a woman has had two to three, Miss gateless stock early first trimester miscarriages, that's what we'll be primarily talking about. So if a woman has had two to three, early trimester, first trimester miscarriages, what genetic tests are done or available after a miscarriage? To determine the cause? And I'm assuming at this point, well, I shouldn't assume so. Would the genetic testing be on the product of conception? Or would it be on the woman herself? So I've doubled up on you less than one.

Right, right. Excellent. So there's two pieces to that. So kind of could be both. So if a woman is having or a couple is having two or more miscarriages, genetic testing, or chromosome testing can be done on that couple. So that's kind of something I'll answer next, but firstly, they're investing. Yeah, definitely. We're kind of table that for just a second. But for the actual are products of conception, there's also jet testing that can be done, particularly even if a woman had one miscarriage or a couple excuse me, because, you know, it's helpful to actually confirm that there was that chromosomal abnormality. You know, that is the most common cause in the first trimester. But it is helpful to have that actually confirmed. And so there are two different tests that can be done on a product of conception. Historically, the test that was done was something called a karyotype. So if you Googled chromosomes, the picture that usually comes up is actually that karyotype. It's a snapshot of what the chromosomes actually look like in the individual cells. And this is really helpful because it allows a scientist and provider to interpret the results, and literally count the number of chromosomes that that were in that cell. Also, what's helpful about the karyotype is that it lets the provider and scientists know if that chromosomal abnormality was likely sporadic or by chance, or if it was possibly inherited, so that karyotype is able to provide a little bit of guidance about how that extra chromosomal material arose. But the con of this karyotype, though, is that it does require cells to be growing and dividing, which is not always the case after a miscarriage. And so there really is a good not a good chance, but a substantial chance that there could be test failure with that karyotype. So there's actually this other genetic test that is now what's recommended to be performed for products of conception, and this is called a microarray. There's still very similar to that query type, and that it's able to assess the number of chromosomes, it's also able to take it a step further and look at there's smaller pieces of the chromosome that might be missing or extra. These are called micro deletions, or micro duplication syndrome. But what it's not able to do is let us know how that extra material or missing material arose. If it was by chance, or possibly inherited, with the microarray test, sometimes it might be needed to be followed up with chromosome testing of the couple, to double check to see could this have been something that was inherited?

Interesting, okay. And I take it that the second test, the microanalysis test that you mentioned, does not require that there be tissue that can grow or cells that can grow?

Exactly, exactly. That's what makes it helpful is that it usually is able to be successful as the test.

Dr. Gerber, I have a practical question. What is a patient told about and how how do you capture the product of conception? You're losing the pregnancy? At what point and and is, what is a woman told as far as what she needs to do? Or do you even worry about it with the first miscarriage,

I like to get the information regardless. But I'd say most obese that are out in the, you know, world, they don't necessarily, you know, our societies don't necessarily say you need to. And so I think after one, it frequently is not done. It's not necessarily something that is promoted by our societies to do to push for genetic testing after one. But I find the patients that I see frequently are now you know, have been going through infertility are very anxious, you know, have already reached a level of frustration and anxiety that they want answers and that it's mean, often very meaningful for them. So I give it to the option, I give that option for all my patients, regardless of if it's the first or not, the easiest way to get, you know, to obtain the product of conception would be to do a procedure like a DNC or MVA, which is a manual vacuum aspiration. So some sort of emptying manual emptying of the uterus, and then actually taking what you've gotten from the evacuation and sending that partially for pathology and partially for the karyotype and microarray. So, you know, it used to be when when you were just doing the karyotype, you really needed live cells to be able to perform the karyotype they need to actually grow them and culture. And so if you didn't do a DNC it was very unlikely to be able to obtain tissue that you could get a result on for a karyotype now that we do the microarray and you don't need live cells, you know, it's a woman or a person could actually collect the products of conception themselves. So you know, if they are motivated at And, you know, able to do essentially could find the tissue part of the bleed from when you have a miscarriage. And often, you know, sometimes you use medication to help it along. So you might know when it's gonna, you know, have an idea of when it's gonna come and actually put it in, you know, a Tupperware or sterile container and and bring it to the physician's office. And you can actually get results from that now that we use microarray which is better at obtaining DNA from cells that aren't necessarily in as good condition as when we get it from the, from the DNC.

Right, because oftentimes, you know, women are not going in for a DNC, they're right. They're being given either they're, they're losing the baby naturally, or they are being given medication to help speed the process up. So yeah, so I could see how that would make a huge difference as far as being able to bring it in and microarray making that a possibility. Before we move on to talking about genetic testing of parents, I wanted to shift to talk to the because many of the many of the people that are patients that are we were working with Dr. Gerber and actually you to Kim Skellington, would be people who are going through infertility and going through IVF. So they have they have embryos that can also be tested. So let's talk just some about Kim, I'm going to direct this to you what is pre Implantation Genetic testing. And so first of all, what type of pre Implantation Genetic testing exists? Let's start with that.

Right, so there are a couple of different types of pre Implantation Genetic testing, or rpgt. So there are three main types at this time, one type is able to test for those chromosomal conditions. So it's able to look at every single pair of those chromosomes for the embryo to identify is there, you know, the total 46 Could there be extra missing copies of those chromosomes, and so that's called PGT. A, A stands for aneuploidy. The second type is called PGT M and stands for monogenic conditions. So this is going to be single gene disorders such as cystic fibrosis, or sickle cell disease. So this embryo test is best suited for maybe a couple who have been identified as carriers of sickle cell or cystic fibrosis, or an individual who has a personal diagnosis of a genetic condition, such as BRCA one. So that is the embryo test where you're able to actually test for those single gene conditions. And then there's a third type that's called PGT S, R. S. R stands for structural rearrangements. And this test is again assessing the number of chromosomes. However, it's also incorporating possible unbalanced versions of chromosomes. So what I mean by that is this type of PGT test is really best suited when one member of a couple or an individual has been identified to have a chromosomal rearrangement themselves, meaning they have the correct number of chromosomes. But those chromosomes are rearranged in a way such that when they go to conceive a pregnancy, they may accidentally be giving too many or too few of the same chromosome, leading to chromosomal imbalances in those conceptions. And so this PGT s, our cast is able to evaluate for those possible imbalances that would result from that rearrangement of the individual.

So we can get really a great deal of information. And the but now that makes the $64 million question, Dr. Gerber is PGT any of the three that were mentioned, effective at preventing miscarriage? Is this information, which is a lot can we use this information? What is the research show? And if so, which of the tests are most effective there?

So it depends what the cause of miscarriages so if you have done tests on products of conception after a woman miscarries and confirm that there is a chromosome count, you know, issue with the embryo that led to the miscarriage, then identifying embryos that don't have a chromosome count, you know, problem and have the correct number of chromosomes and selectively implanting those embryos would definitely fix the problem. So if the problem is a chromosome count condition in the embryo, then selecting embryos that have correct number of chromosomes would definitely fix that. So, the other thing is, is that what the PG TSR the rearrangements, so people who have what we call balanced translocations, in their karyotype. So people can have the correct number amount of chromosomes have the correct amount of genes, it's just arranged differently than tick, then it's typically arranged in those cases that can lead to recurrent miscarriage. And so if we can identify embryos that have the correct number of total genes in the end, which are harder to come by in patients who have these rearrangements, then we know that that would definitely decrease the chance of miscarriage. So, you know, if the problem is genetic, then this is a great technology to use. The question is, is that we frequently don't know. So what I find is people often have miscarriages, and they're either really early before we can get tissue to test, or, you know, they they just never had the opportunity or weren't told about it. And they come with, you know, recurrent pregnancy loss of unknown etiology. Show with unknown cause. And the question is, does PGT a help those patients? And there is some, you know, back and forth in the literature about that, but overall, you know, people believe it, it definitely does in those cases, again, if chromosome count conditions are the number one cause of miscarriage, then identifying embryos that are unaffected by that, you know, it should and does help prevent miscarriage going forward.

So what do you recommend to patients who are going through IVF? So they have embryos. Obviously, this is not an option, pre Implantation Genetic testing is not an option unless you have embryos outside of the body. So but you have you work with patients and in are doing IVF, so that we do have embryos. So if a person has not had a miscarriage before, would it make sense for them to do either PGT a or PTTs? Are? Because if you're going to have a choice on which embryo to to transfer, then choose the best one. But are there are downsides to that other than the financial and that is a substantial one.

So it really depends what what we know is that there is an age related decline in the chromosomal competence of an embryo, that maternal age related decline so that as a woman gets older, they're more likely to produce embryos that have the wrong number of chromosomes and are ultimately not viable for the most part. So, you know, some people say when you're when you're young, so let's say you're in your 20s or early 30s, the majority of your embryos are chromosomally normal. And, you know, it's it's not necessarily, you know, important to identify which out of most are because most will, most will be normal, and it might not be worth putting the extra money into that, after 35, you know, in 35 is somewhat of an arbitrary cut off, but it's something that we use, you know, it seems like chromosome abnormalities increase, especially when you reach your late 30s 40s, that were the majority of the embryos you produce are chromosomally abnormal. And so in those cases, so with advancing age, it can be important to identify the embryos that are chromosomally normal before putting them back. So for the most part, I recommend it more strongly in women with advancing age so late 30s, early 40s Well, in younger patients, particularly in their 20s, you know, it may not be as critical. The the reason why it's not universally offered is definitely fight, there's a financial component to it. And the other thing is that you don't always get an answer. So you can biopsy these embryos and sometimes you get something called no results, or, you know, there's not enough DNA. And then you know, you're in the position where like, well, we could just transfer it without a result or we can biopsy it again and try and get a result. And we know that when you buy up see more More than once, you know, you may be harming the embryo by all the manipulation you're doing. So you know, it's not always straightforward that you get a yes or no. And the other thing is, is that there's something called a mosaic embryo. And this is getting a little bit more complicated or in depth. But there are some times you get embryos where you get some cells within the biopsy. So you take about five cells, out of 100, at the stage that you buy up, see your embryo to get a genetic analysis. And you can find that sometimes some of those cells are normal, and some of them are abnormal. And that's called a mosaic embryo. And we know that mosaic embryos do have a lower implantation potential. But, you know, we know that you can also get a healthy live birth from them. But it's a little complicated, because, you know, there's a worry, well, what if you now have a child affected by some mosaic condition, and, you know, so, it, it can create a situation where some clinics are actually uncomfortable transferring mosaics. And now you've kind of locked your embryos in purgatory a little bit. And this is not something that happens commonly, you know, it's it varies by lab, but maybe, you know, 10% of embryos at most will give you this result. And it can add a little bit of confusion

and concern just from a patient standpoint, exactly.

And anxiety, and then it requires extra counseling. And really, in the end, you know, we probably have been transferring embryos that are, quote, unquote, mosaic, since we started doing IVF. And even probably, embryos that implant spontaneously are mosaic. And, you know, in the end, you know, maybe not, sometimes you have too much knowledge, or you know, not there's, there's knowledge or information overload, where now you have anxiety about something that may not actually be worth having anxiety over. I would say that I don't personally believe that that necessarily is a reason in of itself to to not use the technology. But it's, it's certainly there's complications to it. It's not straightforward, like like everything else, where you always get a yes or no, on your first try with with these biopsies. And so, in addition to it being a financial burden, that may be in younger patients may not pay off financially, you know, you have to consider that you may not get straightforward results. And you have to be aware of that and enable to counsel and support your patients in that.

Kim, how often do and I would assume in your practice, you would see a fair number of Mosaic results. How often does that happen? Is there been research that shows how often PGT comes back with a mosaic result?

Yeah, so that estimate would be about 12% of the embryo population. So it again, like Dr. Gerber mentioned, it's not the most common result to be received, you know, you're either getting that normal result or typical results, we're having the total 46 chromosomes, or that abnormal results. So there's going to be a chromosomal abnormality and then mosaic. So that's not thought to be as likely as the other two, but it definitely does come up. For my practice, because I'm offering the post test counseling after the results of the PGT a test. I see it much, much more frequently, I would say almost every patient I counsel, it's in regards to that mosaic results. So certainly, it's something I talk about quite often with patients, and it absolutely is something that can be really difficult to navigate and figure out what is the best next step for that patient and family. So it really is it's I always describe it as kind of this gray zone. So it is something that you know, some clinics and patients may be willing to transfer because there is that chance that you know the baby's chromosomes, because technically, with PGT, those cells that are biopsied are at from the outside layer of the embryo. Those cells are what are predicted to become the future placenta and supporting structures of that pregnancy. Whereas the cells that are going to become the future baby, they're called the inner cell mass, they're kind of the inner layer of that embryo. Those aren't actually technically being assessed. And so with the mosaic results, what makes it so challenging is that those cells, the chromosomes could be typical, but it could be that they're not or that they're also mosaic and where we're at in science right now, we can't tell which of those three things are occurring. to some patients and providers, that level of uncertainty going into a transfer you're not comfortable with, whereas other patients and providers feel like well, if there's any chance that those cells could be typical, let's go ahead and take that chance. So it's so it definitely is difficult to navigate.

And it usually comes up from a practical standpoint, when the patient doesn't have any chromosomally normal embryos to transfer. Because obviously, if you have a mosaic and you have a chromosome a normal, most people would choose the chromosomally normal to transfer but that the rubber meets the road, so to speak, when that's not an option, because there aren't any chromosomally normal. You know, and I, I have wondered this, as we're talking about miscarriage and genetic testing. Dr. Gerber, have you seen research on this now that we are able to because it used to be, and I don't remember which of you said it, but I appreciate the fact that for all we know, in fact, in most likelihood, many pregnancies that have been natural conception and carried on to for a healthy delivery, would have had mosaic chromosomes in them, and we just didn't know about it, but now we do know about them. So it's a research that indicates whether a when you get a mosaic embryo and you do transfer, are those resulting pregnancies more likely to miscarry? And and part of that question is tied into what Kim just said about the cells coming from the supporting structure, the placenta and other supporting structures for the pregnancy. And if those aren't strong than the pregnancy, even if the chrome chromosomes of the fetus are, are perfectly normal pregnancy, you need a healthy placenta in order to to support the pregnancy. So Dr. Gerber, what does the research show on this?

So we know that I think most people in our field believe that mosaicism it occurs and can even maybe be a normal part of embryo development, and does not necessarily mean that it's not a viable embryo. So, you know, I think people have come to the conclusion and understanding that this has probably been there all along is going on in natural conceptions as well. And we are only now identifying it, but this is not, this is not new. So what we also know is that when we do CVS or chorionic villus sampling at 12 to 14 weeks that they do you know, that you can see something called placental mosaicism. So, you know, or they call confined placental mosaicism. So they have identified even later on when the pregnancy is established that you can do a CVS which samples the placenta to try and get a genetic analysis of the fetus. At that point, you take blood from the placenta to try and, you know, out of the assumption that the placenta and the fetus should match, and that they can find mosaicism in placental cells, but that is much less common than what we're even seeing in, in our trophectoderm biopsies are in the biopsies of the outer cells of the embryos. So we think that probably there when a pregnancy establishes and is able to make it to 12 to 14 weeks, there's a most often a self correction mechanism whereby most of the cells, or the cells that are healthy, have kind of taken over and established themselves. Because when we do CVS is on patients who had mosaic results, we really are not seeing mosaic placental samplings. By and large, even though we know there is something called confined placental mosaicism that you can get as a result of a CVS. That is a much less common thing than a mosaic embryo and that we recommend everyone who transfers the mosaic embryo, get prenatal testing. So CVS, amnio, and that we really don't see the mosaicism continue on to the CVS in general.

What about some cases? Because what that CVS tests the it's done earlier and it test, it only captures placental tissue. Okay, but then do it what is the amnio testing MDS an amnio

is considered fetal tissue

so and you're so when you do an amniocentesis of a mosaic embryo that had tested mosaic and then it was transferred and and and a viable pregnancy was attached, what does amniocentesis show so because at that point, you're looking at fetal tissue, right? So

right, so what we've really seen is that the amniotes are coming back normal. And this is something that's unfolding, because we just started really identifying mosaicism. And then transferring mosaic embryos, really in the last few years is when we just start doing so the date the data is like unfolding in front of us right now. Yeah, and some of the largest series that we have coming out are of 1000 patients. And, you know, they keep kind of as time goes on being able to add more and more. And really, what we're seeing is that they, if they implants and make it to viability and kind of out get out of that early first trimester, that they are really normal fetuses that create healthy live births. Now, you know, we can't i can't be overconfident and say that there is not potentially an issue that can come from this. And that's why we work with genetic counselors to counsel our patients. But so far, it has been very, very reassuring that if it implants, which we know it has a lower likelihood of implanting, but if it does, and you know, you end up with a heartbeat that is a growing fetus, that really what we're getting is chromosomally normal


It is it is truly we are living the Science right now, aren't we? It's interesting, it's it's exciting times from that standpoint. But Kim, I imagine from it's exciting from somebody outside or looking in, I imagine, as a person who is counseling patients that exciting would not be the word that you would use, because it's nerve racking, I could just, I can't even imagine,

it really is kind of can be a frustrating result to not have that clear kind of knowledge that absolutely if transferred, this would happen, or, you know, XYZ would happen. So there are a lot of potentials and that that uncertainty that goes into it. But it certainly is really interesting to see the study unfold in front of us, as Dr. Gerber mentioned. And it has been, you know, much more encouraging than kind of what was previously thought about these mosaic embryos. So we definitely are seeing, you know, pregnancies that are ongoing, and apparently healthy life born babies, and that's wonderful. And, you know, with these embryos, you know, again, it really could be with this mosaicism initially at, you know, day five or six of the embryos development, you know, once that embryo is transferred, and if it does implant and continue on in the pregnancy, that's kind of a natural selection process that's going on. And that embryo is going through that the pressures of the coming into a pregnancy. And so that's why a lot of times if there is that pregnancy, you know, that's encouraging to say that likely, those cells that are going to become the future baby, you know, likely are typical, we of course, can't say that with 100% certainty that that's the case. But it's a really good indication that likely is the situation. But there is testing on pregnancy to verify as well as testing the baby after birth as well.

I was just thinking that the I would hope that the research would continue to continue to watch these babies and then children develop to see now that we have this information that would be interesting. I don't know if that's down the road. But I would hope that that research would carry on so that we'd have even more information. Just in general. This show could not happen unless we had organizations and companies who believed in our mission of providing unbiased medically accurate information to the infertility patients. One such partner is cryos international sperm and egg. They are dedicated to providing a wide selection of high quality extensively screened frozen donor sperm and eggs from all races, ethnicities and phenotypes. And they do this for both home insemination and fertility treatment. cryo International is the world's largest sperm bank and first freestanding independent egg bank in the United States, helping to provide the gift to family. Thanks, cryos. Alright, now I want to move to talking about the we've talked about, we're talking about miscarriage and genetics. And we've talked about genetic testing of the products of conception, we've talked about genetic testing of the embryo. Now it's time to talk about genetic testing of the parents. And so let me turn to you Kim and say, Can the genes of the genes in the sperm or the egg can they contribute to the parents the genetics of the parents, can they contribute or the the donor the egg or sperm donor? Can they contribute to the likelihood of a of a miscarriage?

Right? So we've been definitely focused on chromosomal conditions or in chromosomes. So those are just kind of one way to look at Our genetic information. And with, you know, the chromosomes, we did discuss kind of all the different can pieces in terms of testing the embryos and the products of conception. You know, we can also test the the members of the couple as well to see if they have those rearrangements. But then, you know, if those things have been rolled out as possible causes, there's still evidence to suggest that there are other genetic factors that are at play. And so with these genetic factors, for example, how this is still evidence to believe that there are other genetic factors. You know, when someone has first degree relatives who have had a history of recurrent pregnancy loss, they themselves are at an increased chance to have a history of recurrent pregnancy loss.

pause for just a moment and ask how close the connection must be to the genetic relative, your mother, your aunt, your grandmother? How close does it need to be?

So first degree, so it'd be mom and sister? That sort of relation?

Okay, got your first degree? Got it.

Okay. As well, as there's been evidence of going back to thinking of those embryos, and the testing of embryos, what has been seen is that for women with that history of recurrent pregnancy laws, that they do have a higher incidence or can have a higher incidence of chromosomal abnormalities in their embryos compared to women who haven't had that history. So because of those two lines of evidence in this thought is that well, there must be some other genetic factors, obviously, once other reasons for pregnancy loss have been rolled out that there should be or can be these other genetic factors that are at play, kind of two ways to view these genetic factors, the first ways to view them as well, how are some of these genes involved in pregnancy laws and to group these genes based on their function and relationship to pregnancy. So there are genes that are being investigated that are ones that are known to be related to the immune system and implantation, genes involved in clotting processes, as well as genes that are involved in the process of meiosis, which is how chromosomes actually segregate in the first place. So there's definitely a lot of attempt to find some gene factors that are in play, when it comes to actually retaining a pregnancy. We were still in the early stages with this discovery, however. So it certainly is another area of research that needs to be continued on. Because at this time, there isn't this, you know, large gene panel available to have testing for to to see if someone has those genetic factors. There are some single genetic factors that can be tested for such as factor five Leiden, but that's still another area that's certainly being looked into.

Have we discovered the genes I feel naive here? Have we discovered the genes that are connected to meiosis are connected to implantation? And they're there when Abby thinks something like immunity would be lots of genes? So have we Are we far enough in our genetic understanding to know what genes are connected to all this?

So it's, it's certainly in the early stages, so there are some candidate genes to some genes that are kind of predicted to potentially be involved in these processes. But it's still an area that we need to continue to to prove that those genes are in fact involved, as well as you know, how they are involved. So it again, is a hard early area of study.

Yeah, that makes sense. So and you may have answered this, and I didn't understand it, but what is a chromosomal translocation? And can that cause a miscarriage? In this part, we're talking about a chromosomal translocation and the one of the genetic parents.

Yeah, so the translocation, so I guess, to take one step back, we had been mentioning that with the members of the couple of those involved with creating those conceptions, you know, if there's this history of recurrent pregnancy loss, it's unexplained after two or more, that's when chromosome analysis can be done on on individuals. And what this is doing is looking to see if those chromosomes are rearranged in some way. And there are a couple of different rearrangements that can exist, one of which is called a translocation. And there's two subcategories of translocations. There are reciprocal translocations and robertsonian translocations. All of these are just to say how the chromosomes are rearranged. And again, for those individuals with a rearrangement, they have the typical number. They're just not in the typical arrangement. So one example I've heard of how reciprocal translocation can be kind of visualized is if you think about okay, you have four pens in your hand, two pens are black, and two pens are red. And so these pens are supposed to represent your chromosomes. We all have two copies of each chromosome pairs are set up So what can happen is that, for example, one of the black pens, the cap of it can actually be on top of one of the red pens. And vice versa, that cap of the red pen can be on the black pen. So you still have two black pens, two red pens, two red caps, two black cap, however, those two caps are kind of translocated on to the other chromosome or other pen. So that's what this reciprocal translocation is. And so when that person goes on to conceive a pregnancy, they may be giving that chromosome that has a little bit of, you know, one chromosome material and another chromosomal material, or that black pen with that red chap. That's what ends up being passed on to a conception, which may then result in an imbalance of either too much or too few of genetic material or chromosomal material,

and thus, a pregnancy that is more likely to miscarry. Exactly, exactly. Can these genetic anomalies be found by parental Kidwell parental genetic testing? And what type? Is it a carrier typing? What type of testing Do you normally do? And we're not looking for like a specific disease at this point, we're now looking for why this couple is having recurrent pregnancy loss.

Right. And so the the karyotype is really still the best test for the individual. So this is done through blood work. And so they're able to create that picture of the chromosomes or, or that snapshot, in order to literally visualizes chromosomes to see is there any of that rearrangement present? If so, then that establishes, potentially that underlying cause for that history of recurrent pregnancy loss.

Gotcha. Okay. So, I think that we want to end by just saying, for patients that have had recurrent pregnancy loss, Dr. Gerber, what is the prognosis for them being able to get pregnant and carry a baby to term

prognosis remains good, you know? And, of course, you know, it's important to do a workup, figure out if there's any reversible causes, like if it's a thyroid issue, or uncontrolled diabetes or a blood clotting issue, you know, and we can fix that, then, you know, really, the prognosis remains excellent. But even in cases where we don't find an answer, which, unfortunately, is a lot of the time that we do work up. And we we look into all the causes that we know about, and we still don't find the cause, which is incredibly frustrating. That still there's about a 50% chance, at least that you will go on to have a future pregnancy that that ends in a healthy baby, you know, that it's a 50% chance per pregnancy still, that that will go on to to end in a live birth. So, you know, it definitely remains positive. And we try and help keep patients in that mindset when we work with them.

And I wanted to end on that note, and it is frustrating for patients sometimes because we say that in their life. And they don't feel it because each loss is a loss. It's a it's a grief, but it is helpful to know that they the odds are still in your favor. Of course, depending on age, obviously that matters as well. Thank you so much, Kim Skellington and Dr. Rachel Gerber, for being with us today to talk about genetics, genetic testing, and miscarriage. And for our audience. Thanks for joining us and I will see you again next week.

Transcribed by