 Welcome, everyone. I am waiting to see the participant numbers slow down in terms of their rise, because I know that everybody's being admitted to the room at the moment. So I'm gonna wait just a moment. Welcome, everyone, to the Lawrence later lecture for 2020. My name is Louise King, and I'm the chair of the later lecture committee here at Harvard Medical School. Thank you so much for joining us. This slide that's up in front of you gives you some details about this event. You should know that it's being recorded and live streamed via Facebook. The video will be posted on our Center for Bioethics Facebook and YouTube pages. Please submit questions at any time during the lecture using the Q&A feature found in the meeting controls at the bottom of your screen, and I'll be reviewing those questions. And at the end of the lecture, we will be able to submit them to Dean Dar for a response. Selective questions will be discussed after the presentation, as I mentioned. But also we can continue this conversation on Twitter. I'm an avid Twitterer, so I'll be out there answering your questions if you like. If you have any technical issues, use the chat feature to send a message to all panelists and we'll help you. And if you're interested in any upcoming events from our center, news, education programs, please subscribe to our email, which is listed right here. I'll start briefly with an introduction to the later lecture itself for those of you who might not know the history and Dean Dar has offered to speak a little bit about Lawrence Lader himself, who was quite an exceptional person. This lecture began in 1997 and is supported by a gift from Lawrence Lader. The lecture is managed by our center, the Center for Bioethics, and organized by committee members who represent Harvard's teaching hospitals. It's a public forum to spotlight a broad range of medical, ethical, social, and scientific issues all surrounding human reproduction. To give you some background on the center for bioethics, at our center, we bring together the rich intellectual resources of Harvard Medical School and our mission is to integrate ethics, scientific, discovery, and clinical care. Our center offers multiple programs, including a masters of bioethics degree program, a fellowship in bioethics, professional educational conferences, and lectures such as this one, all of which address healthcare and social justice issues. This year, as the chair of the Lader Lecture Committee, it is my honor to introduce Dean Judith Dar, who will be speaking with us tonight. Dean Dar is likely known to most of you or to at least many of you and her list of accomplishments and accolades is justifiably long. I'm only gonna highlight some of them and very quickly, because I wanna get right to the lecture. Dean Dar is the ambassador, Patricia L. Herbold, Dean and Professor of Law at the Chase College of Law and Northern Kentucky University. She joined the Chase Law community in July of 2019, having previously served as a clinical professor at the University of California Irvine School of Medicine and a visiting professor at the University of California Irvine School of Law. She's also the former interim dean and professor of law at Whittier Law School in Costa Mesa, California. Her academic career in health law focuses on emerging technologies and family formation. Since November of 2014, Dean Dar held the position of chair at the Ethics Committee of the American Society for Reproductive Medicine, also ASRM. She was elected president of the American Society of Law and Medicine and Ethics from 2009 to 11, where she also sat on the board of directors and she was recently elected in 2012 to the American Law Institute. And those are just a few of what I could have gone on quite some time about. I count myself lucky enough to have known and worked with Dean Dar for a number of years. She is a rare example of someone who's truly gifted and the expert in her field, yet she is also incredibly humble and always approachable and ready to help and answer any question you might have, which I've posed many to her. I'm so grateful for all that I've learned from you, Dean Dar, really sincerely over the years and I'm sure to learn much more in the future, including during this wonderful talk. So please, without further ado, I'd love to hear your talk. Thank you, Dr. King, so much. Oh, it's such a pleasure to be here and I know that we've talked about this now for quite some time, never expecting at the outset that it would be in this fashion, but I'm just delighted to be here and thanks everyone for joining. Pleased to hear there was a truly robust response to this topic and I'm so honored to be able to present it. As Louise said, I learned a little bit about the benefactor of this program, Lawrence, later, just in doing a bit of research and he's been described by Betty Friedan, for example, as the father of reproductive and abortion rights. He's an author and a journalist who wrote really prolifically on the topic, everything from abortion itself to other topics, including a number of biographies. He's been cited by the US Supreme Court and some of their jurisprudence. And so I'm really grateful to the family for continuing this lectureship. And also I checked out the predecessors in this role over the past near quarter century and it's a veritable who's who of reproductive medicine, reproductive rights, reproductive justice and I'm really honored and quite honestly a little intimidated to be in this cast and I thank those of you who have joined in previous years and perhaps those who even had the opportunity to deliver this lecture. Well, I'm gonna begin with just a photo if I can go ahead and advance my slide, all right. Let's see, I'm not able to do that with my computer. Let's see. Ashley, maybe go ahead and advance. I'm not able to do so from my end. You should be able to do it by clicking your screen, I think. All right, thank you for saying earlier. Yeah, thank you. All right, thank you so much. So this is a tribute to Lawrence later. I thought this photograph was quite lovely. He left us in 2006, but again, the legacy is really persistent. Well, this photograph of the puzzle pieces going to make up this baby really is a metaphor for the field that many of us dwell in, the field of assisted reproductive technologies. We know that reproduction can be a step-wise piece-by-piece endeavor that's aided by more than the two individuals who may plan to parent the resulting child. And it's this collaboration and the inputs from the community that I'm gonna speak about today and particularly some of the conflicts that can and do arise within this structure. The next photo comes from my iPhone. This is a picture, a couple of pictures that I took in November of 2018 when I was asked to represent ASRM at the Second International Summit on Human Genome Editing. And of course, when we all agreed to attend that meeting, nobody knew that it would be up the historic note that it has come to be regarded as. And there you see Heiji and Hui at the podium. I know it's a little distant. I didn't have an upfront seat at the time. But maybe you can also see the crush of media that appear kind of midway in the slide. And of course, this was the day that he announced how proud he was to have altered the genome of twin girls that were born to a Chinese couple, the father being HIV infected for the purpose of knocking out genes to make them resistant to contraction of HIV. And he spoke about his pride. He spoke about this advance in medicine and the future that he saw was one that was very rosy and exciting. Well, this is, we all know, launched years of hand-wringing in the bioethics field that of course continues today over this prospect of germline gene editing. Now, the physician scientists journey ended in prison sentence this past January. He was sentenced to three years in prison for the essentially illegal and improper practice of medicine. But nevertheless, this legacy is a very strong one and it motivates and directs and really gives us pause as we continue to advance in the field of assisted reproductive technologies. And I'll just say as an aside before I move on that this reaction which I call at the end of the talk moral panic and it's been described by others in that way is not new to us. If you trace the introduction of reproductive technologies and I'll only go back as far as the 1950s with the introduction of therapeutic donor insemination or assisted donor insemination. There was that same very concerned reaction about altering the way that we reproduce. Likewise, with the introduction of IDF in the 1970s you did hear the same type of reaction. So it doesn't surprise me to see it in action. And I try to study it a bit from a distance just to learn the lessons that it can impart to us. So moving ahead, I wanna remind us of some of the technologies that are in the works that are brewing if you will that are causing us to at least think about what role if any they can play in our human future. And so briefly we'll talk about advances in mitochondrial replacement therapy. And this is a therapy that's used to combat mitochondrial disease. And the idea of course is that a woman who has mitochondrial disease can use the nucleus from her egg cell that essentially transferred to a healthy donor egg in which the cytoplasm is not affected by the mitochondrial disease. And then the reproduction of fertilization can take place. And again, I know I'm describing it at a very non-sophisticated level, not the scientific explanation, but just to get to the point that the controversy over this is that ultimately the child would bear the DNA of three individuals, the egg donor, the intended mother that is her nuclear DNA, which is the vast majority of the DNA that the child would have and the male, the sperm provider. And of course importantly, this could persist for generations in a female pedigree. So we're concerned about making an alteration at one point that has a persistence opportunity really in perpetuity. And so MRT is discussed often without concern. In vitro gametogenesis or IBG is again more theoretical in the human clinical application than it is in its realization in the animal population. But the idea is that we would have the ability to create our own gametes using somatic cells, typically skin cells, or there are also other methodologies using embryonic stem cells. But again, we have enough technology to know that we can essentially reverse engineer our somatic cells back to a stem type state in which they could then be prompted to mature into gametes, eggs or sperm. That's allowing us to create our own gametes. And the idea behind IBG, at least as imagined, is that it could permit single individuals to parent their own children. If after all, they could create both eggs and sperm, they might be able to form embryos through that process. Same-sex couples likewise could create the appropriate gametes and reproduce. So this notion of multiplex parenting looms large should IBG eventually make its way into human clinical applications. And then finally, germline genome editing, which got a tremendous shout out this morning. We woke up this morning to the news that the developers of the CRISPR technology have won the Nobel Prize in chemistry, notably the first time that two women secured this prestigious award. And their award is for Nobel purposes, rather young, rather new, only a little under a decade in contemplation. But the germline genome editing is what Dr. Hei Jin Kuei talked about in Hong Kong. And the idea is that the technology permit scientists to cut, you see my image there, parts of the genome for purposes of replacing or deleting genes that are associated with disease. So even before the embryo is transferred and planted or it really even develops beyond a one or two-cell stage, the opportunity is to essentially repair or edit that embryo using this technology of replacement or editing. And again, just as with MRT, the concern is that it has a persistence in the pedigree, again, perhaps in perpetuity, but certainly for generations down the road. And we just have concerns about altering the genome in this way. And I'm not gonna really talk about the merits or the arguments associated with these, but just to raise them in the context of today's sort of main presentation topic. And let me move to that. I wanna introduce Louise Brown, who's probably well known to everyone, by saying that she represents to us in the field of reproductive technologies, a kind of norm, that is we are somewhat accustomed to IVF and its role in American society. But it's important for us to, I think, reflect and interrogate the way that we regard IVF in these more routine reproductive technologies so that we understand when the technologies that I mentioned previously, those that are in development, those that are in our mind's eye, when they do or may become part of the clinical scenario that we have a grounding and a framework for the distribution, for the usage, and the dilemmas that are going to surround those technologies. So I ground my talk today in the technologies that we have and have used now for over 40 years. But I do so with the purpose of trying to develop and anticipate usage of far more sophisticated technologies in the future. I had the privilege of meeting Louise Brown a number of years ago when she was doing a book tour actually for this book. And it was interesting in so many ways. But one of the comments I won't forget is she was saying that her biography, the biographer, the person that helped her with this book kept reminding her what a kind of below average person she really is and not to let her head be swelled with all of this talk about her being a first of a kind and monumental and historic. She said, he really grounds me by telling me that I'm actually not just average, she said, but below average. So there you go. I think the message there is don't hire a biographer. I just do the job yourself. Anyway, let's look at some of the epidemiology here. And again, I know for many of you on the call, this is extremely well known. So I'll just breeze through this, but the numbers indicate that the use of IVF yields about 74,000 babies every year. These are the most recent stats that we have. Therapeutic donor insemination, we don't keep numbers quite as carefully. We don't have a federal law that mandates reporting and the estimates are that about 60,000 babies are born every year. If you combine those numbers and you look at the US census, these technologies account for well over 3% of the US birth rate. And again, just to give a little perspective, this is far in excess of the number of families that are formed through neonatal adoption. So it's a really significant part of our social schema. And to get to 3% is a very significant number in the life of our reproductive picture. Worldwide, we've had over 8 million children born through IVF, some of the success rates you see there. And then I'll just skip to the bottom bullet point. The use of pre-implantation genetic testing, every day we seem to add another opportunity for investigating the health of the embryo, well over 400 uses. And I'll speak about some of the dilemmas associated with PGT as we move on. I wanna say a word before I look at the dilemmas themselves. At the disparities and stratification that is just classically and very embedded in the use of reproductive technologies, particularly IVF. And there are numerous barriers to access that should not go unaddressed or unmentioned. So I think it's important early on in the presentation to talk about these. There are social, there are racial, there are ethnic, there are economic and distributive justice barriers that really do prevent the widespread use of these technologies. And again, I've listed some of them and there really are others. The cost of these technologies can be for many individuals absolutely prohibited. And that's coupled with reimbursement and insurance coverage scheme that is just in the main, not friendly to fertility care. About 85% of all patients who seek treatment do so with their own pocket books, sometimes crowdfunding, but it's because it's not covered generally through insurance. There's only about a quarter of states that mandate that insurance carriers provide coverage. It's been a lot of advocacy and I've been part of that through ASRM over the past number of years, but the progress is really quite slow. The average cycle these days is about 15 to $19,000 and that's just unaffordable for many. And that doesn't even include some add-ons that might be part of the treatment cycle. We know that race and ethnicity does play a tremendous role in creating barriers to access. And there's an inverse relationship between the incidents of infertility in women of color and their treatment seeking. They do experience infertility at higher numbers and higher rates and they seek treatment in lower numbers and lower rates. And again, I'd love to talk at length about this, but there's a number of factors, including a history of racism and a history of really suppressing and devaluing the reproductive rights and abilities of women of color, such that there is suspicion that's grounded in very public and well-known incidents of this kind of suppression and maltreatment. Marital status, sexual orientation, and gender identity, I don't mean to short-trip them by handling them together, but it's just by saying that even though we think in some ways we've made tremendous progress with the Obergefell decision from the Supreme Court in 2015, marital equality and so on across those categories, the fact is that there are still barriers to access, whether it's the provider's discretion because in the majority of states, more or less a fair majority, but nevertheless a majority, state laws that address civil rights claims do not prohibit discrimination on the basis of these features in the healthcare setting. Again, we're getting better, but there are still not a vast majority of states that prevent discrimination by providers based on these features. And so if a provider just simply does not want to provide treatment for these reasons, then he or she may be at least legal in doing so, and that is highly problematic. Even some of the statutes that provide for insurance coverage are marriage-based, or they're based on infertility defined by heterosexual intercourse, the kind of classic definition of infertility, 12 months and no conception and pregnancy. So we still have a lot of work to do in overcoming that barrier. Disability individuals with sensory or cognitive disabilities experience a difficult time accessing treatment, there's stigma surrounding that and suspicion on the part of providers. And so my final point about provider discretion really looms large in the access area. And it's something that I know at ASRM, we've spent a lot of time thinking about and trying to make some headway in that field. I'm gonna talk for the next part of my time here about what the topic is in the title at least, these disputes over embryo transfer. And so these are bedside disputes that do dominate the field. And I wanna say also as a lawyer, it's always important to say, I think that the legal problems and dilemmas that we often discuss tend to not be overwhelming in the field, that is the field progresses, problem free for the most part. And the lawyers are there when the problems do occur. And so I'm not suggesting that these are common or that they dominate the field, but I am saying that they're worthy of discussion and they're at least relevant and they persist enough to make it worth our while to look at these dilemmas. And I'm gonna really talk about three different dilemmas, kind of classified as dilemmas over quantity, over quality and over purpose. So we're gonna talk about this embryo number, how many embryos to transfer, the numbers game. We'll talk about which of the embryos to transfer, again, figuring in our ability to look at the genetic makeup of the embryos. And then finally, this phenomenon of what we call compassionate transfer, a request for transfer for non-reproductive purposes. So I'll speak briefly about that as we move along. All right, so patient requests to exceed embryo transfer best practices. Here you see, and I assume you're probably familiar with this photo of the octamon who gave birth to her eight children and there you see them at age 10. And she gave birth in 2009 and so they're now nearing their 11th birthday. And of course, at the time that she gave birth and we weren't sure about their health and well-being, there were a lot of movements to limit the number of transfers that could take place by law, by insurance policy and so on. I mean, interestingly, there was a biopic, if you will, done on her and a piece that appeared in the New York Times about a year or so ago that describes the octuplets as bookish, vegan, model, fourth graders. And the title of the article is, Octamom has proven us all wrong. And just curious to see when you see this healthy brood here and they are according to their mom, how vulnerable are we to predictions? Again, this is an outlier for so many reasons but we always have to question ourselves when we predict future health because we really do never know. I'm not advocating for octopolis, just saying it's one of those really rare examples where it gives us a chance to pause. But in the realm of numbers game, survey data reveals that about 20% of all fertility patients who undergo IVF are seeking actively to have twins. And so the phenomenon as transferred to the bedside is even if the guidelines would dictate a single embryo transfer, there are patients who persist in their request for double embryo transfer or even more. In the case of Octamon, Nadia Suleiman, she had 12 embryos transferred, which was not recommended under any guidelines at any time. But the doctor testifying at his hearing before the medical board, which he did not prevail in, but he testified repeatedly that she had begged him, that she prevailed upon him, that she wouldn't take no for an answer. And so it was the patient persistence that resulted in the scenario that you see here. In a happy note, there's been an effort on the part of ASRM and other professional groups to reduce multiple pregnancy, which is the number one morbidity associated with IVF. And there has been success. The most recent data has a multiple pregnancy rates dropped to under 20%. And that was very good considering it was really persisting at about 35% for many, many years. So we have made progress. And again, the idea being that the best practices are guiding this. Nevertheless, we know from providers that it's difficult to address patients who really are willing to accept whatever risks there are associated with twins or even higher order multiples, given that perhaps for them, they don't have the finances for another cycle. They've had a long journey. They want a family with more than one child and so on. And also we know that the health status of twins is fairly similar to Singleton. Again, I know that there are nuances there, but enough similarity that the patient could make a reasonable argument about accepting that particular risk. Let's move on and talk about this quality issue. So the advent of pre-implantation genetic testing introduced to us in the late 1980s and really increasingly sophisticated today does give prospective parents an opportunity to really learn a lot about the health status of their future children. And again, you're probably very familiar with this and what we can look at is a couple of ways to investigate and interrogate the blastocysts around five day embryo. We can detect single gene disorders. I mean, just some common examples, cystic fibrosis, Tasex, sickle cell, and of course there are many, many others. We can also look for aneuploidy or too few or too many chromosomes in any particular pair and some of the more well-known aneuploidy diseases down Edwards, Patel's, Turner's and so on. Attended to the aneuploidy more recently or the search for the numbers often referred PGTA or pre-implantation genetic testing aneuploidy is this phenomenon of mosaicism or the presence of more than one cell line in the embryo upon investigation. And this phenomenon has really challenged us scientifically and legally and ethically to think about informed consent for transferring embryos that are mosaic and also to really plumb with our patients. Their notions of disability and the way that they perceive themselves as parents of a potentially disabled child moving forward. The counseling patients about these discoveries is difficult because we're only really, I think in the midst of learning more about this topic scientifically. There are of course studies underway there are number of studies underway and many of them have been and you'll see the next light kind of reassuring in that the second bullet point is what we're seeing that aneuploidic embryos that are mosaic have yielded genetically normal offspring. And so again, it's even more confounding to try to counsel the patient about what she can expect from a mosaic embryo. We just don't have enough information to know. And again, the data is no more sophisticated and interrogating different parts of the mosaicism in terms of percentages and so on. But still there are no certainties in this area. There can be self-correction, migration to the trifectoderm and these are some of the theories being explored as to why an embryo would appear mosaic would appear abnormal and ultimately yield a normal offspring. The answer in practice committee has looked at this very recently as you can see this past year. And basically what they say is there's very little data the data is reassuring. But nevertheless it doesn't confirm that transferring a mosaic embryo will result in a phenotypically and genetically normal child. So what we recommended ASRM or policies in place, the policies you see should be shared with staff. And in fact, we would recommend staff be involved in formulating those policies. And that patients should consult with genetic specialists. Again, just one more slide about this. I don't think it really adds anything more to what we've said other than these are some of the features that a practice could consider in developing a policy. Some practices will not transfer mosaics if there are normals in the batch even if the patient wants, say for example, a double embryo transfer. Some practices won't transfer the mosaics if there are fresh embryos that were non mosaic. Some practices will look at poor prognosis patients that have at least an advanced maternal age or repeated pregnancy loss. And will make decisions about transfer based on those features and so on. So these are just some of the factors that clinics consider in making decisions about transfer. This is just language from one of the clinics that I pulled out because they have published what their position is. And they say that centers should offer poor prognosis patients without normal embryo. So you can see already we're kind of limiting the individuals who can access these embryos from poor prognosis patients who have no normal embryos, the option of transferring. But then again, it gets narrowed even more because this clinic says that they should only utilize embryos with so-called presumed lethal chromosomal abnormalities. And so those that could transfer an implant and survive to birth like Turner, Downs and so on, this clinic said should not be transferred. So there's a lot of judgments and conclusions to unpack with that particular policy, but I wanted to give you a sense of that. So on the ethics committee, we discussed this issue for several years. I say that that was one of our longer ingestation policies. And we heard from a number of different experts and practitioners in the field about their patients making demands or requests for the transfer of these mosaic embryos and just their struggle to figure out what the right thing is to do. And I'll talk to you a little bit about the provider perspective on that as we move along. Again, just to finish up this topic, in addition to the PGTA, there is PGTM in which we look for monogenic disorders. And again, there are requests to transfer those embryos even though the prediction is that the child will express that genetic disorder. And there's a host of reasons why patient would make that request. Again, sometimes there are so-called normal embryos and the patients express a willingness to raise the child. The impairments can range from very severe at birth to deferred until adulthood. And from a parent's perspective, they may feel that medical science is forging ahead and that there will be treatments and therapeutics for the child when they reach that third decade or fourth decade. And that they feel that it's in the child's best interest to be born, that having a child over a no child is a better result for everyone. And so in some ways, those are some of the arguments, especially when you have these adult onset diseases. And they do create these clashes, as I say, between patient reproductive autonomy and professional conscience of the provider. And again, in the ASRM's position, which I'll show you at the end, we do say that patients really ideally should hear voices from the disease community and the patient community in order to help them with their decision-making. All right, I'm gonna shift over just really briefly what are the arguments that are advanced when there are these disputes between patients and physicians as to embryo transfer, whether it's as to the number of embryos to transfer or which embryos to transfer, knowing that there might be health issues that impact the child, either severely or even mildly, but still of concern to the provider. So I have this sort of shortcut and I have some slides on each of these, but just to summarize, the patients usually make assertions or could about their reproductive liberty. There's a derivative equal protection argument, which I'll advance that essentially attempts to position individuals who reproduce naturally with those who reproduce with a medical assistance. There's some arguments about patients' dispositional authority over embryos. Then the next two bullets about indeterminate results and false positives are well known to the scientific community and do create risk profiles that the patients have to really navigate through that are sometimes very impenetrable. And then also the arguments about the variability and phenotype of some of these presentations. On the provider side, I'll talk about provider autonomy and what that means. Providers have child welfare concerns. I'm not saying that patients don't. I'm just placing it for purposes of allocating these arguments in the provider column. I'll talk about these theoretical really advances of reproductive non-malphesans and procreative beneficence. And then finally the legal one, liability avoidance. And so let's just quickly march through these. I hope that for the audience, I don't know how many of you are lawyers or law types. So I hope you don't mind, I'm gonna take a minute to just really talk about this reproductive liberty argument because it gets advanced fairly often in the sort of realm of patient provider disputes. And it seems almost like a brass ring that patients or advocates will hang onto to sort of give comprehensive authority to a patient to make decisions about her reproductive life. And in theory, and as I say it in that way, I mean, I think that sounds completely reasonable. But let's explore a little bit what the actual legal basis for that argument is. And I just picked this one time point to start the argument, although there are other places you could begin. But I'm gonna begin with the 1992 Supreme Court decision in Casey versus Planned Parenthood. And Justice O'Connor in authoring the plurality decision in that case, which struck down some provisions of a Pennsylvania abortion statute set out what we today call the undue burden test that we use to measure the legality of abortion restrictions that are enacted by the government, either the state or the federal government. And simply put, the test is that a state cannot place a substantial obstacle in the path of a woman seeking an abortion before the fetus attains viability. Some people call it the viability argument, the undue burden test, the substantial obstacle test. But there you have it. And it has survived, it has persisted, even a concern over its viability this past summer when the court took on yet another abortion case with restrictions on physician practice. And Casey survived and lives to die another day, perhaps, I don't mean it that way, but just to say that it is a proposition that many disagree with and the litigation continues. So moving on, and by the way, I know that my picture of the court is not recent and I have to express a moment of sadness. I just could not take Ruth out of this picture myself. And so I prepared this slide before I would have had notice to take her out. And I think it's important for me to keep her in this picture. So thank you for that. And so the question is, does this thin read that language from Casey about substantial obstacles regarding abortion? You know, what the heck does that have to do with IVF? I mean, after all, abortion is about not being pregnant and IVF, of course, is about welcoming and wanting a pregnancy. So how is it that the Supreme Court's dialogue on pregnancy termination can have anything to do with pregnancy in inception and the manner in which it comes about? So let's talk for a moment about that. Well, the argument would be that the basic underlying support for melding both affirmative and negative aspects of reproduction really stem from an earlier Supreme Court decision, actually from the 1940s, in which Justice Douglas in a case called Skinner versus Oklahoma, which was about striking down a eugenics era law, said that procreation is a basic civil right, that the ability to reproduce is a basic right of man. And it's really the only time that the Supreme Court has ever talked about the affirmative right to reproduce rather than the negative right, the right to avoid through contraception or abortion. But Casey really finds its home in that language. So even though I showed you the viability test, the undue burden test, the fact is that it rests in a much broader concept of what it means to be a free person in American society. And that is to navigate your own reproductive course. So we could make the argument that the undue burden test as applied in Casey was addressing the law at stake in that case, but that the broader context of our reproductive freedom acknowledges the right to proceed with reproduction in the way that we find meaningful for our lives. So that's the kind of link and that's how the argument is made. And if I have you so far moving along with me, and some of you might have dropped off already, which I understand, but for those of you who are still with me, well, then how does Casey really support procreative autonomy for asking, even demanding, even forcing physicians to make embryo transfers that they think is not in their medical judgment the way to proceed? Or how do we make that transfer? Well, it's a very tough argument to make for a number of reasons. First of all, as you might know, the Constitution is a document written to navigate the relationship between the government and its citizens. And so it's mostly directed at what the government can and cannot do. It's not really designed to tell you and me how we act with respect to each other. It's not a private action document in the main. And so when a physician says, I won't transfer this embryo because it's aneuploidic and I don't wanna facilitate the birth of an unhealthy child, typically there's no state action involved. So you can't really make a reproductive liberty argument because no state is making a decision to interact with the patient's reproductive liberty. So that's problem number one. Problem number two is just this sort of match between avoiding procreation and engaging in procreation. I've made the argument because I think it's a solid one, but as I said, many of you may not buy that or believe that and find it's just too broad of a leap. And so I might lose you if you will on that point. And further, even if we agreed that Casey and the whole prodigy of reproductive liberty cases applies to this affirmative right to navigate our own reproductive course, does it really apply to these ancillary choices about what type of child to birth? I mean, maybe we can make decisions that we want to use IVF, we need to use IVF, but does it really allow us to decide we want a child affirmatively with particular traits and someday we may have an ability to choose more traits than we currently do. Can we really add these ancillary choices about reproduction within that right? And then finally, I think the most important thing to say about this is that constitutional rights are not absolute. They are by nature subject to balancing. And what we always balance an individual right against is the state's interest that might be compelling in protecting the welfare of society. And in this particular case, the state's interest in child welfare is strong and that I think really probably would amount to a compelling state interest. So the reproductive liberty argument is nice and it's elegant and it's familiar, but in the end it might be failing just if we really pick apart its constitutional roots and meaning. Just to move along here, I want to save time for questions. I said I was going to make an equal protection argument and really the argument that a patient might make is that a patient who is pregnant and even in the earliest stages can make decisions about her body and her pregnancy without interference from a physician, but physician cannot tell a patient, you must have an abortion, you must gestate this child to birth. That's absurd in our culture and our legal structure would never imagine that. So this is my, you can be a little bit pregnant argument. This is the, if we back up the pregnancy to pre-transfer, then we could apply an equal protection veil and say that likewise, physicians shouldn't be able to tell patients which embryos they should or should not transfer just as a physician would not tell a patient who learned that their early fetus had genetic anomalies that were even lethal or very health affecting. So again, it's more theory than practice. Again, just moving along. There are many state cases about dispositional authority over embryos. There you see Sophia Burbier with her ex. These disputes arise mostly in the context of divorce, but the bottom line is that patients do have authority over their embryos. So if they can direct them to go to one spouse to not to go to one spouse and so on, why can't they direct them to be placed in their body? The fact that the physician has the technical expertise and the licensure to do that, some argue should not be a barrier to their exercising their dispositional authority. This slide is probably well known, the variability and phenotype. And again, we know that particularly some of these aneuploidic diseases down in CF can have extreme variability in their symptomology or affecting lifespan in a very unpredictable way. And so just to shut down the opportunities there seems unwise. Okay, just moving along to the physician perspective, let's talk about this. So we've sort of gone over the patient's arguments for transfer. What about physicians? Well, physicians, I argue, and I've done it in a number of places that I've written about this, are entitled to what I call equal dignity and equal humanity and the actions that they take in the clinical setting. Physician autonomy is much less discussed than patient autonomy. But I think it's real and I think it needs to be acknowledged. The AMA supports the physician refusal to care for patients for reasons of either medical non-benefit or personal conscience. And there's no reason why this wouldn't extend to the ART setting. Certainly physicians might make the argument that there's medical non-benefit to transferring 12 embryos or even in some cases three because the harms vastly outweigh the benefits and again, these are arguments that are viable arguments. There's some more varied arguments that providers who offer PGT do so to promote the birth of a healthy child that is defined as genetically normal. And so it would be a mismatch with their goal to require a transfer when in fact their reason for providing this clinical test is for a genetically normal transfer. And then I think it's fair to say, again, I've had the pleasure of working with so many wonderful caring, hardworking REIs over the years and I know that they feel this really deeply and the moral distress that they experience at these disputes is quite life-affecting for them. And I wanna acknowledge that. At ASRM, we've written about this and we've taken the position at least on child rearing abilities which is different than the welfare of the child. But we have said that there are lines and that there are certain lines that really shouldn't be crossed. And a provider has what do we call a substantial non-arbitrary basis for thinking that the parents won't provide adequate or unsafe child rearing that the providers should be free to refuse to provide treatment. These are just some of the more theoretical, ethical pronouncements at play. Australian board British bioethicists has a paper that's pretty well known in the field published in 2001 in which he advances this theory of procreative beneficence. And it's written in the context of PGT and he just says that couples should select the child that's expected to have the best life based on relevant available information. And this is a duty-based admonition and it's grounded in health features. I have of course laid out the whole theory but the idea being that if a patient has two embryos and one of them is aneuploidic and one of them is normal then the duty under procreative beneficence on the part of the parents would be to only transfer the normal embryo. And this theory has gotten a lot of discussion. There's a very vehement community that has spoken out against this for a number of reasons but just to give you a full play of it. And then finally the legal landscape. I mean, it's we can't not acknowledge that we all act in ways that want to manage our risks and doctors are no different. And from a liability perspective a patient for example might say to a doctor I won't sue you. Well, you know, that's not worth very much. And even if a patient has a paper that appears to waive liability if a child is born with health outcomes the truth is that parents cannot waive the legal claims for their future children. So that has no force and effect and a physician should not be welled into thinking that they can't be the subject of a very viable and successful lawsuit. And just doing a calculus, the truth is that in some cases where there has been liability the damages are tremendous because they can be for the lifelong medical expenses associated with this health impairment. On the other hand, there have not been and I haven't checked the literature recently but I'm not aware of any case in which the physician has had a large damage award for refusing to make the transfer. So, you know, if you do this calculus you might get sued for refusing to make the transfer. There's not many cases that are really in the appellate level on that claim. And even if you're not, if you're liable the damages, the calculus is going to be much less. I would advise then if you were held liable for the birth of a very unhealthy child. Again, at ASRM we've talked about this. We have a paper on this which I invite you if you're interested at some point to take a look at just to wrap up, because I do want to hear from you. I'll talk finally about compassionate transfer request for embryo transfer for non reproductive purposes. And we started to hear about this on the ethics committee I can say about four or five years ago. And again, in our speedy way we've talked about it for years and we did just publish a document on it. And these are situations and again they're rare but they're extent in which patients have completed their families or are not going to pursue treatment further. And they want to discard the embryos but not through thought or discard but in what they consider to be somewhat more natural scenario. So they asked their physician to do an embryo transfer typically not in uterus often in the vagina or at a time when pregnancy is not likely to occur. And it's been styled compassionate transfer and I confess that that language evokes some consternation and objection. It doesn't mean that other transfers are not compassionate for sure. But the idea being that the physician assists the patient in that way. There's some nice literature recent studies done on compassionate transfer. Some physicians are willing to make the transfer others are not. They feel that it's a misuse of medical resources. There are risks associated. Pregnancy is a risk and has been described. There's miscarriage infection whenever you do a transfer there's the risk of infection. And so again, it's one of those scenarios a bedside scenario where there can be a clash between what the patient wants and may demand in what the physician feels is in her best interest both the physician and the patient in that case. An issue that was recently resolved however was whether this counted as a transfer that was reportable under SART and the answer is no, it's in their FAQ. So at least we have that information. Okay, so finally, I said at the beginning that I'm hoping that investigating how we look at and deal with IVF our sort of basic baseline technology in the realm of patient choice and physician conscience can give us guidance on these down the pike technologies and just a few points. First of all, quite obviously the distributive justice stratification remains a significant barrier. If IVF, which has now come down the pike 42 years ago can still create inaccessibility clearly IVG and mitochondrial replacement therapy and germline genome editing, they are not going to be around the corner for us or at every clinic that is now established. And there are going to be significant distributive justice problems with these technologies. And I'll just add they're compounded today by the federal government's block of funding and of coverage for infertility. The funding piece of this is tremendous. The federal law since 1996 has essentially prohibited NIH from funding research in which embryos are destroyed. There are other blocks that are even greater. So we're not helping ourselves by not advancing my advocacy, I admit by not advancing these technologies with our biggest resource. A third point is to keep in mind, and this is a thread that really was implicit throughout what I said earlier but I'll just make it here more expressly. Patient demand for these technologies may be mismatched with what the technologies capabilities actually are. I mean, people tend to, we all do maybe overestimate the benefits of certain technologies, especially if we're looking for a certain outcome. And these are of such an other worldliness right now to us that the capabilities are maybe overestimated. They also play into the acceptance of these because there are thoughts about the kind of human future that we'll experience that really may not be the case. Also, and this is really also an access point, providers learning curves are gonna be huge and will limit broad access to these right now because of the federal government's activities. There's very few people in the US that are working on this. They are working on it abroad, but I would argue that some of the best scientists are not able to move forward because of political concerns. And then finally, ending with this concept of moral panic and we are experiencing moral panic. I mean, just the reaction in Hong Kong two years ago was so tremendous and it continues to really be quite top of mind in the reproductive medicine field. And I'll add just my own observation that dialoguing about this in the US is quite difficult, even elusive. We tend to dig in, we have our positions, we have our views about what these technologies actually need to us and to the world. And I found that it is rather difficult to have these discussions. Other countries admittedly more homogeneous than the US have had more success in gaining kind of a picture of public attitudes, but we have some work to do in that area. Maybe tonight at the vice presidential debate, Mr. Pence and Ms. Harris, maybe they'll resolve it for us tonight to have high hopes. And with that, I'll just say nobody's perfect, we're working on it. And I would love to hear from you and I thank you so much for this opportunity. Thank you, I'm still giggling a little bit about the debate. That was a wonderful talk, thank you so much. We have a number of questions and I think I know well enough that your answer to my request could we go a little bit long will be yes. So the first question I'd like to direct to you is have there been any court cases directly addressing genetic diminishment or intentional selection? For example, in the deaf community or in couples with genetic short stature, parents seek to have a child with similar abilities or for seek and therefore decide to terminate a normal pregnancy or seek to transfer and affected. And a lot of these terms I really need air quotes the lower four, but the person asking this question says this would seem to parallel selection of embryos bearing genetic abnormalities. And so are there any cases or jurisprudence that would guide? That's such a great question. And so just to frame it, the cases would be the status of the case would be either the child through a guardian ad litem suing the provider for making the transfer and again, the context of the question is that the parents requested the transfer of an embryo that was known to have this anomaly. I'm not aware of any cases at the appellate level in which the plaintiff was either the child or the parents in a scenario in which the embryo transfer had been requested. There are a handful probably growing up of cases in which the transfer was not wanted per se. That is that the transfer happened because the patient was not informed or there was a misdiagnosis that the embryo was affected. And so that's the more typical scenario in which the damage that the parent perceives is the health status of the child. But in terms of the kind of inverse and if there's others in the family who know more about this, I'm not aware of any cases. So my talking with you about legal liability is really more theoretical and anticipating what the claims might be. Thank you. I'm not aware of any cases either and I think that there aren't any. Another question submitted was given what we know about the ability for PGTA identified and euclidic embryos to result in healthy births. So false positives. How do you think clinics should be allowed to advertise a charge for this test? So essentially it's a questionable test at least in terms of its diagnostic accuracy. So what representations and profits are appropriate and do you think you need a greater regulatory presence in this space? That's a great question in light of the fact that so many patients pay for these out of pocket because you can navigate the answer to that question through the norms and standards that are established by insurance companies when they do or do not reimburse for tests that are performed. And so I guess the analog for the patients who have to pay on their own would be to look at those norms and standards. When is it that, to the extent that you think those are valid? When is it that we do have to pay on their own when is it that we do provide coverage? When is it that things that are deemed experimental or that are ineffectual are not worthy of being covered? And so that's on the reimbursement side. And I think the question also is on the offering side. Is it appropriate to offer these technologies knowing that they are frail in their ability to truly and effectively predict the health of the child? And I think those of us in the field know that they are moving forward. If you look at the SAR database every year, the number of PGT cycles is going up every year. Don't quote me exactly, but I know that the number does continue to rise. So whatever the sensibility is about the ethical dimensions of offering tests with this profile of sort of insecurity, the practice is to the contrary. So that's worthy of consideration. Louise, what do you think? Sorry, I'm a law professor and just turning it over to somebody else. I love it. I'm a big proponent of heavier regulation. Although it is paradoxical that in truth assisted reproduction in the United States actually is fairly heavily regulated, but I would still like to see a stronger presence of regulatory bodies in this field. In part because of some of the things you alluded to in your talk where you mentioned inequity of access, you mentioned discriminatory practices that still occur, not simply based on the types of interventions that certain providers will offer, but also in terms of the certain, the persons that they are willing to treat. And the fact that none of that is uniform is incredibly bothersome to me, much more so than the add-ons issue. I know there's gonna be a big talk about add-ons in the next few months and then the issue of what is offered and what is not offered. It's still a field that's in development, so as long as there's a discussion about what the utility of the actual technology is that is adequate enough for informed consent, I'm actually okay with that. But I would prefer regulation in place to address those inequities that you alluded to in your talk, which I think are so... Absolutely, very reasonable. This is a comment more than a question, but I see room to respond. It seems to me a concern about the intentional selection of traits in an embryo in an engineered sense doesn't strike a significant distinction relative to the intentional selection of certain traits by choosing a partner, i.e. the old-fashioned way. I'm gonna select a partner that has certain features that I find desirable and lacks others that I find undesirable. True, there is a distribution of probabilities that a child would end up with given features derivative of its parents. In other words, we're playing the probabilities when we use assisted reproductions to a great extent. But the same is true, although played to a greater extent with an engineered IVF embryo. I'm adding a little bit to this. No, it's true. This makes a trait selection argument against embryo engineering weak, potentially, in the thinking of this commentator. I agree. It's just a 21st century and 22nd century version of anthropology that has been well known to us for as long as it has been known. I don't wanna place a time, but absolutely that's right. And that argument is made and advanced. And there's just, again, it's this notion there's kind of a hard stop when we start to intervene in ways that appear to be unnatural for some. But I agree 100%. It's just an elevated, more technically sophisticated way of doing what we've been doing in the wild forever. And I worry too, though, with the added technology and this expectations that might get set in using that technology. We all have expectations of our children. I know I drive my 14-year-old crazy for her, but if we start setting too many expectations, I do fear when parents get so granular about what they want out of a child that's not yet even an embryo. It worries me for the future in terms of how they're going to adjust. It's true, I mean, it's described as, it's whether you see it as a race to the top or a race to the bottom, but the race is underway. And you describe some of the features of it. We'll take a couple more questions. By the way, there are a number of excellent questions here. I can't quite keep up with them. And I think we can also potentially try to answer some of them on Twitter if possible. I think we'll end with this question as we're going a little bit over time, but how does the fact that most US physicians cannot complete their training without public funding at a minimum achieving clinical competencies by working on the bodies of Medicaid and Medicare-insured patients, impact their obligation to equally serve disabled and non-disabled community members as taxpayers, voters, and neighbors do disabled individuals have an equal claim to services as non-disabled individuals. For example, if they want to transfer an embryo with a disability and the commentator clarified to be clear, I mean, this is an ethical question. I'm aware this is not protected by law. It's true. The licensure comes with a lot of public support, confidence, and privilege. And I think that whoever submitted that wrote very eloquently about that and the duty that physicians have based on that licensure and the support that went into it to consider this much more broad distribution of their wealth in the form of their knowledge and practice abilities. Absolutely. Couldn't agree more. That's a great question. So that's why I wanted to end on it. I love it, absolutely. Thanks to everybody who has participated, all the questions, I'm gonna try to save them and see if there's a way that I can get to them through Twitter or some other modality. Dean Dara, thank you so much for all of your mentorship over the years and for participating tonight and give us such a wonderful, and I was gonna say overview, but really a very in-depth dive into a very thorny question. So thank you so much. Thank you. And I look forward to being together with you very soon with everybody. Thank you. Lovely. Thanks, everyone.