ASRM Today: Genetics - Episode Eight

In recent years, advances in genetic technologies have revolutionized reproductive medicine, offering unprecedented possibilities for screening, diagnosis and treatment. However, with these innovations come complex ethical dilemmas. To explore these issues in depth we interviewed Dr. Sigal Klipstein, MD, chair of the ASRM Ethics Committee.

Welcome to ASRM Today, a podcast that takes a deeper dive into the current topics in reproductive medicine. I'm Jeffrey Hayes and today on the show we're continuing our season-long discussion of genetics, specifically today some ethical considerations. Joining me in this discussion is Dr. Sigal Klipstein, who is chair of the ASRM Ethics Committee.

Dr. Klipstein, thank you for being on the show today. Thank you so much, appreciate being here. So, we now live in a world of almost limitless genetic possibilities.

Today we should talk a little bit about sort of what limits should we place on that and I wanted to start with, there recently was an opinion put out on the transfer of anomalous embryos. My question then is, since we can test for many things and given that not all patients will have unaffected embryos, how are decisions regarding which embryos to transfer should be made or would be made? Yeah, it's an interesting question because we have this ability to test for almost anything that we know the genetic sequence of and many patients are finding out that either their carrier is most often of an autosomal recessive disorder, sometimes of an autosomal dominant or an X-linked and so we're testing many more people for these disorders and the question then becomes what happens if you have a situation in which someone comes to you to test for a specific disorder in order to exclude it because they're concerned about having a child who's affected but yet then they end up with only affected embryos and so how do we manage that? And so we put out an opinion because we realized that this happens not infrequently either because the only available embryos are affected because people aren't able to do another IVF cycle or maybe they've done multiple cycles and have only had affected embryos, maybe they can't afford to do additional cycles and so despite their efforts, this is what they're ending up with and so this is kind of interesting, right, because they come to you to avoid the birth of a child that's affected but now they're in the situation where they know the child will be affected, right, so let's say it's an autosomal recessive condition, they come to you with a one in four chance of having a baby with the disorder but now you know that all the embryos are affected so it's a one in one chance, it's a 100% chance that they'll have this disorder and so we said well we need to think about kind of how to help physicians make these decisions when a patient asks you specifically to transfer an embryo that you know will be affected and so we said that there's a lot of autonomy here on the part of physicians to make these decisions in a shared decision-making model with their patients and that the most important thing of course is counseling. Patients should of course be counseled by a genetic counselor who has expertise in the specific disease and inheritance pattern and then should also seek out an expert that understands the potential manifestations of the hereditary condition.

Sometimes that involves talking to parents who have had an affected child, sometimes that involves going to seek an expert who manages patients, children or adults with this particular condition, so those are all things that are possibilities and then you know if the patient still wants to move ahead and do the transfer then the decision is really of course the patient's but we do leave kind of room for the physician to say look we don't feel comfortable transferring a baby or an embryo that might become a baby that will for sure be affected by this genetic disorder and so in many cases we say physicians can say yes you know we'll do this we feel comfortable, physicians say no we won't do this, we don't feel comfortable but there are a certain sort of subset of conditions in which we really feel like it's inappropriate for physicians to transfer and there's a very like we only left a very small window to say where we said like we really should say no and the way that we describe this is if the child is highly likely to be born and I'm quoting from the opinion now with a life-threatening condition that causes severe and early debility with no possibility of reasonable function it is ethically acceptable for provider to decline a patient's request to transfer such embryos. Physician assistance in the transfer of embryos in this category is ethically problematic and therefore highly discouraged so that's kind of how we navigated that kind of ethical quagmire. Yeah I want to turn while I have you I want to turn my attention towards PGT specifically PGTM for adult onset conditions you were talking in your answer about anomalous embryos about diseases that are appropriate for testing you know what diseases rise to the level of being appropriate for testing when we're talking about PGTM? Right so that's a question because as we're doing genetic testing or rather genetic carrier screening for many diseases some of them are very mild and some of them are adult onset so I think there are a couple the low-hanging fruit that we started with were like you know x-linked disorders that were severely affecting in children then we looked at disorders that caused death or disability in childhood things like Tay-Sachs and then we started looking at things like early onset Alzheimer's disease or you know other disorders that don't manifest until later in life and the question then becomes at what point does it make sense one to do IVF and take those potential risks and two to exclude you know the birth of children that might have these diseases that are adult onset so I think there are there are two categories right one is patients who need IVF anyways for other causes for infertility and they're doing genetic testing and they want to add on probably genetic testing for monogenic adult onset disorders and then there are people who are not infertile and would be coming to this technology without any infertility background so I think that's one distinction you have to make and then the other thing that one has to think about is that a lot of these diseases that are adult onset won't affect these you know children that might be born for decades and medicine marches on and many of these diseases may either have cures or really effective treatments and then the other thing I think that really is important to think about when we look at excluding people with disease is the effect on disability rights you can imagine it has a major impact on one people already living with the disease to say that oh you know we're kind of devaluing your life because we would not want children to be born with this disease that on the one hand and on the other hand the less people you have born with diseases the less there's an inclination to spend money and resources and researching these diseases and cures for these diseases so I think we have to think about all of the implications not that we should you know have more people with diseases so we can study them that's not the what I'm saying at all but I think we do have to think about these subtle nuances that affect society based on our decisions with embryos but what happens when no embryos remain that will only affected embryos remain you mean yeah I think that that becomes the the big question so maybe in the future this won't be such an issue because maybe we'll be able to do in vitro gametogenesis and have unlimited embryos and maybe we'll be able to do gene editing at the level of the embryo and that might affect the embryos and so but but right now we're dealing with a limited number members I think that in the general population there might be this sort of misconception that if you just test the embryos you're going to find unaffected embryos and that is really not the case because most people don't have very many embryos and those embryos they may end up with nothing unaffected and of course I think that sometimes we minimize how difficult emotionally and physically and financially it is to go through IVF it's not a minor thing to go through so even acquiring these embryos is quite the process yes you were beginning to talk a little bit about disability rights and research into diseases can you expand on that a little bit I mean I think for example if you look at trisomy 21 there's been an effort over many decades to do genetic screening in pregnancy and of course now pre-pregnancy pre-implantation for these embryos and then the question becomes if less babies with trisomy 21 are born are there going to be less resources spent on all the needs that they have and then I think the other thing is that how does this play into people already are born for example with down syndrome that you know there's this testing available to exclude them from ever coming to fruition from ever being born and so I think we have to we have to think about what this means for people living with diseases and differences yeah yeah your chair of the AASRM ethics committee uh is there anything coming up that that listeners should be looking forward to yeah I mean I think that there's a lot of conversation now about what we should be testing for one of the big questions is should we be testing for polygenic disorders we can now test for disease predispositions certainly things like BRCA or Lynch syndrome and these are you know kind of interesting cases because you don't know that you're going to ever develop the disease and yet we're testing for for this risk right but there are other risks and that sort of has been uh played out for the number for a number of years already when 25 30 years ago when you're looking at IVF people said oh no no why would you kind of use this resource for adult onset conditions I remember there was um early onset Alzheimer's I was able to be screened for and there's a huge outcry and I feel like like against it right and and now I feel like that's kind of become more standard of care in terms of societal acceptance at least but now we're looking at disease predispositions and again I think that that's becoming more and more acceptable as you know people are realizing the the impact of disease burden on families with these disease syndromes disease predispositions cancer syndromes I think then we also are now thinking of multifactorial diseases that the question becomes if you look at something like heart disease hypertension diabetes some of these disorders are most of these disorders are at least manageable and may be curable or even better managed in the future and the technology is such that the diagnostic capabilities of the technologies are not quite there yet so you can look at a little bit of a reduced risk but the question is does that slight reduced risk if if it is indeed there and it can be proven does that justify going through the technology especially for people who do not have baseline infertility and so the worry I have with the genetic testing for polygenic conditions is that we're kind of over overselling and and perhaps selling false promises of healthy babies I think in the end what we know is that perfection is elusive and there is no such really thing as as as perfection I guess to get a little philosophical here for a second and so to sort of market technologies not just PGTP but in general technologies to improve outcomes and health and so on I think that you have to be careful that people aren't hearing that you're going to be producing right you're going to be what you're promising is a is a healthy baby and what is a healthy baby and what is health anyways right but but there's no perfection and so people have to understand this I think as a field we have to understand the way that our technologies are being perceived and it's important that yes perhaps you can screen for predisposition for breast cancer but that doesn't mean that the baby couldn't one day have something else and you can't possibly screen for everything because in the end we all have you know diseases and lethal mutations and you know we saw this that when we were started looking for carrier status of two or three diseases a small percentage of people were positive and now when we're looking in screening for carried you know expanded carrier screening for 500 diseases it's hard to find a person who doesn't carry at least one of these diseases so what does that mean does that mean we're all flawed I think it's just reproduction and human nature is you know and diversity is such that you know this is part of what we have to accept in order to have a viable population of you know reproductive individuals and so so there is no perfection and then the question is what are the limits of what we should be testing for and how much are we willing to sacrifice for our health in the sense of of going through in vitro fertilization cycles and so at what point you say it's worth it or it's not worth it and much of that is of course an individual decision I don't think it's the same for for any two people and that's where the counseling becomes important and that's where important to make sure that people have a very good understanding of what exactly the disease burden might be for these diseases that they may or may not choose to test for similarly to transferring affected embryos you know we know that the phenotypes vary so the fact that you have a disease doesn't tell you anything about how severe that disease will be expressed in you it doesn't tell you anything about the sort of society in which you have that disease the family in which you grow up the ability you have that as an individual the capacity to deal with that disease and in some cases I think a lot of people feel that certain diseases or differences make them make their lives richer and so I don't think we need we can discount that completely and so when you take away one thing um perhaps you're taking away good with bad and and so we have to consider that as well a little bit counterintuitive maybe but I do think that that's important as a consideration well we're definitely going to have to bring you back when we talk about reproductive rights uh for for certain thank you so much for taking time out I know you're extremely busy person we really appreciate you coming on to talk about this today my guest has been Dr. Sigal Klipstein again thank you so much for being here my pleasure always a pleasure Jeffrey thank you so much and uh if you would please like subscribe rate the show on google apple wherever you smash that button as it were we would appreciate it as any feedback is always good and until next time I'm Jeffrey Hayes and this is ASRM Today.

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