Get close. Ready? Hi everyone, welcome. If you're wondering what this session is, you're in the right spot.
This is the Fertility and Sterility Journal Club Global Live from the ASRM. Please bring your lunch, bring a friend, have a seat, and for those who are already seated, thank you so much for joining us. My name is Pietro Bordaletto.
I am the Interactive Associate-in-Chief for Fertility and Sterility and Media Editor for FNS Reports, and I'm joined by my co-host, Dr. Eve Feinberg. Good afternoon, I'm Eve Feinberg. I'm the Editorial Editor, and I'm going to be introducing the topic and the panelists.
Today we're going to be talking about pre-implantation genetic testing for polygenic scoring. Should we continue this or should we cut it out? Our panelists are Dr. Nathan Treff, who's the Chief Scientific Officer at Genomic Prediction, which is a genetic testing company based out of New Jersey on the pro-side. Joining him is Dr. Marja Brodlinson, who's a Senior Fellow at the NIH.
On the con-side, we have Dr. Lee Schulman, who's a Professor of Obstetrics and Gynecology at Northwestern University, and Dr. Heather Huddleston, who's also a professor at UCSF. The two authors, there are four authors on the initial paper that was published in Fertility and Sterility, and I am thrilled and honored that two of the original authors, Dr. Treff and Dr. Schulman, are here live today. So welcome.
We want to just also point out that we sometimes ask people to take positions that they don't necessarily agree with for the interest of a healthy debate, so we thank the panelists both from the pro and con side for humoring us and being selected for the side that they are currently debating. I want to start by just introducing the rules of engagement. Like a healthy debate, we're going to start off with opening statements from both sides.
I've tasked them with 60 seconds or less to introduce their key thesis, what they want you to know about polygenic risk scoring. Should it be, is it cutting-edge or should it be left out? And then at the end, we're going to open this up for open debate. They're going to have the opportunity for rebuttals and to talk to each other, but at the end, we also want to hear from the audience.
So towards the end of the debate, please feel free to line up, and I'll just make a note for people when we're ready for Q&A. If you have a question for the audience, they're going to have to answer it in front of a live audience here, but also being broadcasted globally through Fertility and Sterility Journal Club. I'm going to start with the pro side.
Dr. Traff, do you mind telling us why you think PGTP is cutting-edge? Yeah, and just to point out, I do strongly believe that it is, just to clarify. You know, I think it's exciting that we're all up here to talk about it, and there are people in the audience here to listen to us talk about it, and it's important that we have these conversations. I do think that some people get a little too excited about it and scared by the idea of testing embryos for polygenic disease risk, and really, I'm not sure why that is.
I think we should probably all be a little bit more concerned about things like misdiagnosis of mosaicism and discarding healthy embryos, which is a big problem in our field. PGTP is really just a way to rank embryos instead of using morphology, so there's nothing crazy happening. We're looking at the genetics of the embryo and using that to make decisions about which embryos to transfer.
I think many of the arguments against it have ignored the fact that there are several papers validating this technology. In actual, 12,000 adult siblings choosing one with genetics significantly reduces the disease risks and the disease prevalence compared to randomly choosing one, and that's the situation we have in the clinic when we have two euploid embryos and we want to choose one. Exactly the same information can be used to decide which one to transfer.
Of course, it's not for everyone. I think patients do need to be adequately counseled and informed about the opportunity to test their embryos. It doesn't mean that everyone has to do it, and I think we'll hear a little bit more about ethics around this, but the important part is that it is, in fact, validated, and not just by my group, but three others who've published in New England Journal of Medicine, Nature Medicine, and eLife.
And then the final point is that, you know, most of the patients who've actually used PGTP have done so in a clinical trial, and what we found is that over half the patients offered the use of PGTP after being adequately counseled have decided to do so. So patients, this is something patients want and are capable of understanding. Thank you.
Dr. Shulman, your thoughts. Good afternoon. Thank you first for inviting me here today.
So the topic is, is PGTP cutting-edge, or should we cut it out? And I think my point of view is that PGTP is truly cutting-edge technology that needs to be cut out. It's genetic testing that, in my opinion, provides a result that truly is not actionable from a clinical point of view. And while it's important to develop new technologies to evaluate embryos, as well as people, in addition, the fact that we now have the ability to perform this technology does not mean that, at least at this point or, in my opinion, in the foreseeable future, that it should be a part of the process by which embryos are selected for transfer.
I agree that mosaicism poses a far greater challenge to us currently and in the foreseeable future. But for me, as a geneticist and not as an infertility specialist, providing information that, whether or not it's been validated on a technology point of view, it clearly has not been validated at a clinical point of view and cannot be possibly validated at a clinical point of view, because you use a diabetes type 2 as an example, to find out whether that individual that results from that embryo that has had a polygenic score that has either increased or decreased for diabetes, you're likely not going to be able to clinically validate that outcome for decades to come. So, for me, from a purely genetics point of view, this represents information that is not actionable and that provides a layer of anxiety, as well as discrimination, that the embryo selection process does not need at this time or in the foreseeable future.
I told you this was going to be a good debate. Dr. Brawlinton. Thank you so much for giving me the opportunity to debate today.
I'm speaking to the panelists and to the audience. As a parent, what would you do so that your child could have a better life? Would you read to them? Would you help them with their homework? Would you take them to foreign language classes or have them participate in sports? You hope that these actions you take will help to enhance their future life. There are some actions that we don't often think about.
What if you could reduce their chance for coronary artery disease and heart attack or hypertension or diabetes? Would you help them reduce their risk for cancer? Patients who are carriers of monogenic diseases, such as cystic fibrosis or Huntington's, can already come to us and choose to do just that so that their child never has to experience their genetic disease. What if we could extend this benefit to polygenic diseases? Preimplantation genetic testing for polygenic disease or PGTP offers a new tool to aid in embryo selection and help us achieve better health outcomes. It is natural to wish for your child to have a better life than you.
As a society, it is better to have a future with less disease than with more. As fertility physicians, isn't it our goal to not only help patients to achieve a pregnancy, but to help achieve and build a healthy family? Dr. Hendelson. Take us home.
Thank you very much. It's exciting to be here. I think this is a very important topic and I definitely want to take the side of thinking that we should probably cut this out.
So Dr. Shulman really expanded on why this technology is really too early, not ready for primetime, but I'm gonna take a little bit of a thought exercise and think about even if it were ready for primetime, even if this worked, would it be something that is going to enhance the health of our patients and our society? And I think for a number of reasons the answer to that question is no. So number one, I think if you have patients who are desperate for, you know, the desire to make their children healthier, there's no doubt that patients will feel compelled to do this testing. But what happens when the few embryos that they have that are euploid maybe don't have a good score? They're going to do IVF again.
There are risks to that. There's societal expense to that. But more concerningly, there are going to be patients who are not fertility patients who feel compelled to do this technology for a very, very small benefit.
And they are now putting themselves through a fertility treatment that may have long-term consequences. We do not really even know what the long-term consequences are for cardiovascular disease at midlife and beyond for children born from IVF, but there is some data out there suggesting that there's impaired glucose tolerance, slightly higher rates of hypertension for these cohorts. We need to follow these further on to know for sure, but I would be very concerned that any tiny benefit we would get from doing this type of score risk risk scoring would actually potentially be outweighed by the risk that's taken on by additional IVF for patients who don't need it.
Thank you. I'm going to start off by giving the pro side an opportunity to rebut any of those items that you heard. There are several points that were raised.
Does the test actually tell us what we think it tells us? Is this an ethical thing to be doing? Is this what we should be prioritizing as a field? And pro side, how do you respond? Yeah, I think there's a lot of misconceptions about whether it works, how it works from what we've just heard, suggesting that there's a small benefit. You know, for example, I'm diabetic and if I had an opportunity to reduce the risk in my children by 70%, for me that's important, and that's not small, particularly for a family that's already affected with diabetes. So this is true for other diseases as well, Crohn's, schizophrenia, and of course I think the amount of benefit, while that might seem small to some people, you know, families that are affected by these diseases may have different opinions and I think they should be able to make those decisions on their own and not have those decisions made by other people.
Just a quick question there. So you use the percentage 70%. Is that an absolute reduction in risk or is that a relative reduction in risk and how are these scores actually calculated? Yeah, so there's also this idea that, you know, relative risk reduction is less important than absolute risk reduction, and it's obviously difficult to apply general population risk levels to an individual couple.
For example, if one of the members of the couple has diabetes, their risk of having a child with diabetes is significantly higher than the general population. So a 70% risk reduction there might take you from 5% to 2%, whereas if it were someone not affected with diabetes, then the absolute risk reduction is smaller. Again, it's just difficult, I think, to apply these general population risks to individual couples, and it is dependent on family history, and of course patients who have a strong family history are going to be more interested in using this kind of testing.
Dr. Shulman and Dr. Huddleston. Let me remind the audience about a very distinct, important genetic concept. So we're talking about polygenic multifactorial conditions, inheritance.
Not single gene. I agree with Dr. Brolanson. We want to reduce cancer.
We want to reduce cystic fibrosis. These are, for the most part, cystic fibrosis is a single gene disorder. We understand the pathogenic variants that lead to its development, and we appropriately can prevent it in at-risk embryos.
But a lot of the discussions of this, I just hear sort of a mixing of single gene issues and polygenic issues. This may get the pro side very angry, but in a lot of situations type 2 diabetes is not a single gene disorder. Hypertension is not a single gene disorder.
If there are single genes that are associated with the development of disease, I am strongly in favor and enthusiastic about adding that to a particular offering of a laboratory to do single gene testing. That being said, if one wants to reduce a variety of cardiovascular and metabolic issues, just don't take your children to McDonald's when they're growing up, because you also have to consider the environmental factors for which this testing does not address. Now, are we going to find more robust genetic risk factors for these diseases in the future? I sure hope so.
But for now, for these conditions where we just have clearly a genetic predisposition to an increased risk, I just do not see that these results provide truly actionable information for us. And to what Heather said, I think it complicates the process for those couples that are going through the embryo selection process, reducing an already small number of embryos and potentially bringing people to the IVF practice that we don't have the capacity to take care of at this point. I want to run with that issue for a moment.
We may soon start to see patients who access infertility care without a true diagnosis of infertility, but for the purposes primarily of risk reduction. Is that something that the pro side thinks is something that's sustainable in the current way that we provide infertility care, something that we should strive for, or is that potentially something that worries the pro side? So, at this, I agree with your points. I would like to argue, bring up two points here.
The first, I'm an answer to Dr. Schulman. These polygenic risk scores are already in use in the medical world. For example, they're utilized currently to identify patients at an elevated risk for breast cancer, helping to revolutionize early detection and prevention through individual risk management strategies.
Studies have shown that patients with infertility do have a higher risk or maybe at an increased risk of cancer, heart disease, and diabetes, and that is precisely why patients who are undergoing IVF should be informed of the option to help reduce their risk to their offspring through PGTP. Now, to address the question of could this potentially bring patients without infertility to our clinics, given that PGTP is something that's already in existence, the ASRM Ethics Committee opinion defines reproduction as a basic human right, and the Inter-American Court of Human Rights recognizes reproductive autonomy and privacy. So, out of respect for procreative autonomy, patients should be informed of all of their options and allowed to make their own decisions regarding PGTP.
Reproductive liberty is not possible when patients are not informed of all the options they have during treatment. If this is truly something that can help revolutionize care on a societal level, this could become part of the argument as to why infertility care should be accessible for all individuals. Dr. Huddleston, do you mind commenting on reproductive autonomy? Do you think this this fits into your definition of reproductive autonomy in the classic sense? Well, I think, no, I mean, I don't really.
I mean, I think that I would have grave concerns about patients being essentially marketed a technology that we really don't know if it works or what the long-term ramifications are. As Dr. Shulman said, it's going to take 40 years to know if these risk scores really actually translate into risk reduction in the way we think they might. This has not been used for embryos before.
So, to market that to patients, because it's a vulnerable time as a parent. Anyone who's a parent wants anything they can do for their child. I mean, there is no doubt that you would do anything, but it's a very vulnerable position to be in.
If someone says, like, this might, you know, this might slightly improve your child's life, I think patients are going to feel very compelled to do it in ways that, you know, may ultimately be putting themselves at risk. And then I also think, beyond that, we also have to think of the societal implications. And I think we haven't really touched on that.
We've been really focusing on the individual couple, but there are really huge societal ramifications, I think, of going down the road of thinking that certain people can have access to a technology that is somehow giving them a healthier child when we know that there's no way that everyone in this country, and certainly not everyone in this world, will ever have that kind of choice. Do we want to live in a world where we're now stratifying patients and people based on their ability to sort of make these types of choices? So that is profoundly scary to me as well. And what about the potential for this being a slippery slope in terms of other traits? I think for right here, right now, the discussion has been focused on heart disease and diabetes, but certainly, and I'm gonna ask Dr. Schulman this question, does the technology have the potential to look at other traits? Things like height, things like intelligence, and in the wrong hands, the development of this technology.
Might that be more scary? You know, I think that question would be appropriate even if we were not discussing PGTP. I think all embryonic testing, starting with basic aneuploidy and going to single gene, I think that slippery slope has been there throughout, and I think it's something that we as geneticists and infertility specialists need to be cognizant of. I think when you get to, let me at least say, a less robust testing assay, clearly it gets a more slippery and the incline gets greater.
We don't have, and it's good that we don't have, we don't have governmental oversight outside of insurance companies or what they're going to pay or not, but we don't have governmental oversight as to what laboratories can test for, and we have all been exposed to labs and to, you know, to businesses that have arisen to provide better assessment and more accurate assessment. I'm concerned about this not so much as that slippery slope because that sort of is ingrained in my concern for genetic testing, whether for embryo, fetus, or adult. My concern is that at least at this point, outside of a, and it was mentioned about study, about research, which I am fine with, this getting out in a sense prematurely and becoming a part of a diagnostic algorithm that, again for me, not only gets us down a slippery slope but provides the patients without a real valuable bit of information to make decisions on.
Sorry, I just need to jump in. You know, I don't know how many times we've heard that it's of small value and limited benefit and it hasn't been validated and we don't know if it works. This is an example of laziness.
You know, you need to read peer-reviewed research before you can make that conclusion, and it's clear that you haven't. I think over half of what you learn in medical school will be proven wrong during the time that you practice medicine, and this is a perfect example of people just not keeping up with what's been published. We don't need to wait for years for embryos to turn into adults.
We have large cohorts of adults who've lived through whatever environment they have, and we have sibling pairs to look at. In some cases, those pairs, one sibling is affected with a disease and the other sibling is not, and if you use that information on actual people who have lived their lives, using genetic selection significantly reduces diseases and the prevalence of those diseases than random selection. What we're doing now is going to be seen as archaic.
We're selecting embryos by morphology. It's craziness. Well, what's crazy is you attributing the genetic component to adults with diseases purely on the basis of the genetic component and not taking into account the environmental.
So I'll go back and I'll say that no, I have definitely kept up with the literature as opposed to others, where I do agree that many have, but to ignore the environmental factor with adults that actually have the disease and to say that their genome is in fact the sole reason why they developed type 2 diabetes or hypertension ignores the disease concept and is therefore, to me, further affirming that this is something that is not only not ready for primetime, but is providing an unactionable set of information for that couple. No one is ignoring the environment. In all of the literature, everyone acknowledges that the environment can contribute to disease and that genetics can contribute to disease.
And in most cases, the best predictors can predict up to 70% of the variation observed. Not a hundred percent. No one's ever said it's a hundred percent, but there is significant predictive value based on the genome as to whether or not you will develop a disease.
It's clear. So I want to jump in with the idea of trade-offs because in order to access this technology, we have to remove the egg from the body, fertilize it in vitro, and go forward with a frozen embryo transfer. And while we know that ART is acceptable risk for those couples that cannot have children, we do question whether or not the risks of ART, namely preeclampsia, premature delivery, abnormal placentation, are we trading off one set of problems for another? Dr. Huddleston, can you comment a little bit on that? Yes.
I mean, I think that is one of my larger concerns about this is that we're sort of ignoring the sort of inherent risks that we think may exist for children born from in vitro fertilization, which, again, the risks are relatively small, and I think we all accept that they're something that we would put up with because there's patients that are not otherwise going to be able to have children. And this is an incredible technology to allow them to have children, and so we accept those small risks. But those risks are definitely there.
We have not cracked that code, and quite honestly, we haven't even really studied it enough, which is, I think, another little bit of a theme running through this is, like, the introduction of technologies that, you know, we don't really, we haven't really assessed what the sort of long-term implications are. And that's somewhat true of IVF. I mean, we are still really at the point where we're studying the midlife health of the first children born from IVF, and there are data out there that, as I said, that there may be some differences in metabolic health.
Some of that may relate to differences in the intrauterine environment related to fertility care. So there's a lot for us to learn, but there is no doubt that there is a trade-off, and I'm not hearing the other side really acknowledge that or even tell me that they've considered that and they still feel like their test outweighs that. Certainly, I agree that we know that there are risks to patients who are undergoing IVF, in particular risks regarding premature delivery with abnormal placentation.
Dr. Feinberg discussed the risk of undergoing a frozen embryo transfer, and we're fortunate now to be living in an era where we are having the opportunity to study this further, potentially natural, or modify natural cycle may be an answer to that. So I think we, as fertility physicians, practice in a field where the technology advances rather quickly, and patients come to us asking about what are the risks of this, what could the benefits be, this is something I heard about. So I think it's really important when patients discuss this to be informed of what this additional screening may or may not indicate for their family.
I think we need to ensure that the patients can understand that this is a way to offer risk reduction. We're not specifically telling patients that this is an absolute fact that this embryo will not have this risk. We've now progressed to a point in IVF where we are often choosing to prioritize embryos for transfer.
We've come a long way from trying to just get one single embryo to make it to be able to transfer the embryo. Therefore, through the use of PGTP with a cohort of embryos that has already been created with the genetics of the intended parents, this offers an additional tool to help prioritize embryo transfer. Since we happen to have a geneticist on the panel, Dr. Shulman, do you mind talking to us a little bit about pleiotropy? We've talked a little bit about selecting against certain deleterious conditions, but in the process of selecting against something deleterious, might we also be selecting other conditions? Well, you know, that gets to where pre-implantation genetic testing has continued to go to.
We started out with somewhat rudimentary analysis of certain chromosomes. Interesting that those original fish studies really didn't show great improvement in live-born or et cetera or clinical outcomes. We eventually went to a raise and got a somewhat more expansive assessment of fetal chromosome abnormality, whole chromosome assays, and we did get better outcomes in that regard.
But as we dive deeper into the genome, all of us in this audience, wherever, in the hall or outside the hall, we all deal with genomic abnormalities. And there are many labs, academic, industry-related, that are moving forward with determining genomic issues that may be, in fact, associated with embryonic failure. It's the age-old question.
You have an aneuploid embryo, an ostensibly healthy mother, that embryo gets transplanted back and is lost at five to six weeks. Chromosomes are normal, even the POCs or analysis is normal. What happened? And again, there are studies that show that 25 to 30 percent of failed pregnancies are associated with whole genome or genomic abnormalities that are not inherited from the parents.
This is an important issue to consider. This is an important technology to develop and is being developed as we speak. But the reality is that looking at the genome and looking for certain points in the genome, whether they're single gene or sequences, etc., is invariably going to find certain things that are right or wrong and miss other things that are either right or wrong.
And so in any technology, this or any other technology, you're likely not going to have a highly accurate, completely comprehensive assessment of the genetic component that's going to lead to the development of that embryo, fetus, and individual. Dr. Treff, I'll give you an opportunity to respond. Well, I mean, even the summary of the history of PGTA is inaccurate, so I don't know where to start, and I'll just leave it there.
Well, I do have a question for you as well, then. So kind of getting back to the point about, are we selecting—okay, so natural selection has allowed us to have the genome we have, that we have now, because of millions of years, right, of the sort of intelligence of natural selection. And I worry a little bit that we start toying with that.
We think that we're selecting for genes that are somehow helpful to us, but somehow are we also now getting rid of genes or combinations of genes that maybe are really critical to other parts of what makes us human. And I don't know that we are as smart as we think we are, that we can sort of start taking these combinations of genes and thinking that that's, you know, a better life or a better, you know, population for this planet. I just, I would like to challenge you that, you know, to tell me that by selecting for certain traits, there is no way that we're selecting now against other traits that could be important in other ways.
Yeah, this is a question that has been asked and answered. What we've seen, and there are papers, peer-reviewed published papers, on looking at flyotropy. And it's not a situation where, when you select against one disease, you increase the risk of another.
And we're talking about common diseases. What actually happens is, when you say, when you select against one disease, you reduce other diseases in parallel. So again, this is published research that anyone can download and read.
So when we're talking about flyotropy, again, I think it's important to actually have looked at what we know. And it is, it does kind of make sense, you know, for example, people with diabetes have a higher risk of heart disease. And so that's actual peer-reviewed published science.
And that's what we should be basing our opinion on. I also, I wanted to come back to the point of whether or not patients without infertility, you know, whether they should have access to this, or whether they should consider the fact that there are risks of IVF when going through PGT for polygenic risk scores. I mean, obviously, I think everybody should have access to the technology.
But of course, right now, most of the patients who are evaluating this, first of all, they have to be informed of it. But typically, they're already going through IVF. And typically, they're already doing PGT.
So you're not adding any additional risks by evaluating additional genetic information in those patients. And yes, it's significantly better than random. I think all of us should strive towards reducing disease in the population.
And that's what this does. Now, you might be a patient that doesn't want to do that, and that's your decision. But it's not for us to decide whether a patient should be informed and be able to make that decision.
I think they are capable of understanding the information and deciding whether or not they want to utilize it. I also want to point out that patients with infertility already have a higher risk of heart disease, cancer, and diabetes. So it's actually a, you know, a good population for this to be applied to in that sense.
As we wind down our time, I want to just open this part up now for questions from the audience. If you have a question, please feel free to line up. And once we have someone at the microphone, we'll stop what we're doing and turn our attention.
But I wanted to go back to you, Dr. Treff. Do you make a distinction between selection against deleterious traits and selection for non-deleterious traits? You're arguing that patients are already doing IVF, already doing PGT. This is something that they can add on.
Yeah, we generally, you know, we're not referring to these as traits. These are diseases. And actually, again, to go to the question of the slippery slope, people have actually asked whether or not this could work to improve intelligence or height, for example, and it doesn't work.
So that's been shown. It does work. And again, four different groups have demonstrated it does work to reduce a disease risk.
All right. So we have some questions. Just introduce your name and where you're from and your question, please.
So Michael DeHaan from McGill University of Montreal. You know, I think this is something that's going to come into play for our patients, but the reality is, as we deal with polygenic diseases and we know more and more about genetics over time, there are going to be many diseases that will test either negative or risk will be high or low in the embryo. And how would we deal with somebody who, where the embryo says there'll be a high risk of cancer but a low risk of heart disease, higher risk of heart disease, a lower risk of cancer.
We're going to get things that are positive in probably every embryo. The same way that when we screen our donors now, they're all carriers of some recessive disease. We're screening them for so many things.
And I wanted to open that up to the panel. Proside. Agreed that the question comes up about choice overload.
Maybe this is too much as a population. Every single one of us in this room, just as Dr. Shulman said, does have certain conditions. Knowing that this technology is coming and is here, I think that this opens up a kind of shared decision-making discussion with the patient regarding what they prioritize.
Building a family is a very personal decision. Different patients are going to take the information that's provided to them into account and make different decisions. So when the opportunity is there, certain patients may prioritize diabetes or cardiovascular disease or certain cancers over one or the other in terms of which embryo that they select.
Additionally, kind of in general looking at what can we offer, this information is partially derived from biobanks that are out there. And currently, kind of a majority, a large number of the patients that make up those biobanks are European. However, a study in JAMA in 2021 demonstrated that evaluating polygenic risk scores for breast cancer that was from these models that were derived from Northern European women could be widely applied to other ethnicities, specifically including Hispanic and Latin American and African American.
And as these biobanks continue to expand, this would then further allow us to improve our current technology. So just to be clear, I guess one quick question, and maybe this is for the pro side, is right here, right now, with the technology that's already been broken out, how generalizable is it to a population outside of a Northern European Caucasian couple? Yeah, I think as it was discussed that these predictors have been successfully developed and validated for more than just European Caucasian, but also Asian, African, and Hispanic populations. So they are available for more than just that particular population.
Just in the interest of getting to some more questions, you had one comment, go ahead. Yeah, it goes, it's nice to say that people will be able to choose what's more important to them, but I don't think it's realistic. Because if you say to a patient, this embryo is going to have a higher risk of breast cancer, and that embryo is going to have a higher risk of a heart attack, and that embryo is going to have a higher risk of stroke, and choose one, I don't think you could choose one.
And even if you do, what are the implications now for that child and that family now with, you know, thinking about that sort of loaded information throughout that child's life? I, you know, I don't know that that's... And get back to the actionable situation, is that child who has a lower risk for heart disease and a higher risk for cancer going into a different cancer screening process as they go through teenage and all that? Do we have any interventions that are going to potentially detect the condition that she, the individuals at increased risk for, and perhaps not screen them for things they're not at increased risk for? Yeah, don't do the test. If you're going to be worried about all of those things, it's not for you. And if you have to have your expectations set that, yeah, you might have a situation where one embryo has a higher risk of breast cancer, and one embryo has a higher risk of heart disease.
And if you're not prepared to make a decision, then, you know, don't use the test. It's pretty simple. Another question from the audience.
Yeah, good. Just, I think two main objections come from the con side. One is about navigating risk or probability, both from the standpoint of science and the doctor, and from the standpoint of the patient.
Could produce anxiety, as you suggested. Uncertainty, you have to weigh all these trade-offs. Life's getting complicated.
Of course, it's getting complicated in many different domains. So one is about navigating probabilities. The other, I take it, is this natural selection argument and some of the other things have to do with, well, natural selection maybe is on the probabilities and uncertainties, but also inequality of access.
That was another point you brought up. Now, this is a really big general meta point. And by the way, yeah, I do bioethics, but I'll just put my cards on the table.
I'm in favor of using PGTP. So access to by patients. But would you just stigmatize this as immoral and express anxiety publicly, or would you make it illegal or heavily regulate it? And if you would make it illegal or heavily regulate it, would you worry about it exacerbating the inequalities of access and making worse the kinds of publicly available information that exists? And you can think of analogies with abortion, illegal drugs, kidney sales.
In all of these cases, people have a diversity of moral views, but there's inelastic demand, as we say, right? When price goes up, demand is still high, and what you get is actually the rich and famous getting access and everyone else getting both lower access and worse information. So the big question is, from ethics to policy, and would the policy actually exacerbate the very problems that you're raising? And I think they're interesting problems. Thanks.
You know, it's obvious that I'm not in favor of this at this point or in the near future, but making this illegal or making it is absolutely off the table. Anytime we put government or societies to start regulating this, we're heading into a far greater morass, and I think probably everybody on the panel would agree with that. Is this not covered by insurance? Yes.
Are there other ways to potentially dissuade this? Yes, but to make it illegal or to stop the development of it, I think ultimately harms everybody. So we disagree on this panel, clearly. Further research into this technology needs to continue, and, you know, hopefully at some point in the future, I'm not sitting on the right side of this table.
Another question from our audience over here. Hi, my name is Dr. Ghosh Dastidar. I'm from India.
I'm primarily a clinician, and I'm more or less inclined to agree more with the con side of the debate, that, you know, we can't really predict it all, and there are so many environmental factors, growing up, especially in the case of polygenic diseases, but my question is to Dr. Shulman and Dr. Huddleston. Do you see any possibility in the foreseeable future where PGTP may be applicable to certain selective, selected subsets of patients in terms of family tree or family history or geographical, demographic subsets, where you feel, despite your presentation today, that PGTP might have a role to play? I mean, I think if the tech, I think it's an interesting question. I think that, you know, certainly, I think everyone up here is, you know, fairly comfortable with doing PGT for, or PGT for single gene disorders that we think could cause morbidity or, you know, health problems for the child, and so I think we've accepted that.
That's something that we feel is overall societal good, so, you know, I suppose taken to, you know, its logical extreme, what you're suggesting is are there going to be certain families or certain conditions that would sort of rise to that level, and I think if we did feel that this technology could really differentiate high and low risk within a batch of embryos from the same two parents, which I'm not actually convinced you would see that much of a difference, but if you could and if this technology was thought to be successful in that way, then, you know, I suppose it would be something I could be behind. I would agree with that. I think there are likely, where I see this at least emerging for myself, not necessarily in general, but for myself, is a condition or a series of conditions for which this is no longer, I view this as harm.
So from me being Khan, I believe that this provides more harm than benefit. I think we will, as we delineate the genetic and genomic cause or the etiology of disease, I think that is likely for me where this will start, that there will be a series of conditions for which there is a far more profound determination of genomic genetic risk, and at that point, the harm actually is then less than the benefit. But again, I just don't see that in the immediate foreseeable future.
Thank you. We have time for two more questions, here in the middle. Hello, I'm from UCSF.
Just curious, let's say we do the same testing for living human beings like us, and what is the really the percentage that you will get a genomically perfect desirable person? I'm just curious, I don't know the answer. God help us if that happens. I was going to say, none of us are genomically perfect.
God help us if that happens. Zero. Zero? Okay, yeah.
Thanks. We have another question here in the audience. Megan Ocean, U.S. Air Force.
So as a profession, we have tried to move towards more diversity and inclusion, and as you touched on, this is technology that's based on Northern Europeans. And yes, it has been tested in some other smaller subgroups, but how do we hope to improve that for our wider population, and should it be offered across the board until it's truly been been proven to address all of those members of society? Well, you know, I think that's a problem with all of medicine. It's not something that PGTP created, but I don't think that patients should not have access to it because it's not available for every single person in in the entire world.
Obviously, there are a lot of projects. I think we should be optimistic that those gaps will get closed, and these predictors will only improve and be more widely available than they are today. Thank you.
Final question from the audience here. Hi, thank you. Laurie Black.
I'm a genetic counselor with Inception, and I just wanted to go a little bit deeper into more of the human aspect of this and recognize and acknowledge that patients do testing because they're hoping to get good news, right? That's the hope. So thinking of that context for doing testing, and let's just say we're talking about a couple who needed to do IVF anyway. We're doing PGTA anyway, so we're not really adding any laboratory or clinical risk for them in offering PGTP.
There's a very real situation that could arise in which the only suitable embryo for transfer made it to the blastocyst stage is euploid, has high risk for something that's being screened on PGTP, mental health issues, cancer, whatnot. Can the panel speak to the more psycho-emotional impact of that kind of decision-making for the parents, for the future children and family? You were starting to speak to it, but I feel like it was kind of at a superficial level, and I just wanted to delve into that a little more. Yeah, I mean, I will say as a practicing clinician, I'll let Heather comment on this too, I worry a lot about true informed consent.
Like how much do our patients really understand? I often will talk about PGTA, and they will turn around and they will say, yes, but I want a healthy, I want the healthiest embryo. And so Heather, can you comment a little bit more upon that? Yeah, I mean, I think I think that's definitely one point, is that yes, you know, we want to, the point has been made by the other side, you know, that people can choose whether to do this, they can decline to do this testing, but I do think that really assumes a high level of literacy with genetics that I think is unrealistic to think that the broad population is going to have. And so, you know, I do think it will be easy for people to kind of get sucked into feeling like this somehow could be beneficial.
And then more to your point, yes, I do worry about that because we are sort of loading our patients with information that, as a species, we weren't really designed to have to make decisions about, you know, having that sort of knowledge and foresight about a child. And what does that mean for the sort of, I think, psychological load for that couple and for the child? I do think ultimately, though, what may happen in the scenario you bring up is that that person will end up potentially just doing more cycles and more cycles and getting, you know, then having more embryos to make decisions about. And, you know, I think we're asking a lot of our patients and, as was sort of mentioned by Dr. Shulman, like we really, I think we need to know that there is significant benefit that we're offering before we potentially introduce some real clear harms, I think, in terms of the psychological ramifications of going through this treatment.
And I'm just going to add one thing. I have been a clinical geneticist for 36 years, mostly prenatal, some cancer genetics, and the vast majority of the patients and couples that I see are dealing with binary questions. Does my fetus have this or that? I'm a carrier for this or that.
And to watch anxiety and angst and heartache going through a diagnostic and a counseling process, to now add a far less than binary assessment of risk, I'll actually add to what Eve said. The vast majority of our patients, no matter how well counseled and no matter how well educated, cannot adjudicate the concept of risk when it comes to clinical outcomes. Unfortunately, I wish we had another hour, but we've come up to the end of our hour and there are events after this.
I want to give Dr. Treff the final opportunity to close out, since we've just heard from the pro side or from the con side, with your final remarks from the pro side before we conclude. Well, I mean, a patient can't decline if they never know about it. That's one point.
And I think it's crazy to think that patients are too stupid to get it. So that's where I'll leave it. Thank you.
All right. Well, thank you, Eve. Thank you, panel.
Round of applause. And thank you all for the excellent questions. If you want to learn more about this topic, go back to the Fertile Battle from earlier this year, where we explored PGTP in depth, and stay tuned for our next Journal Club.
Thank you so much for joining.
