Fertility and Sterility On Air - Roundtable: In Vitro Gametogenesis

Welcome to Fertility & Sterility Roundtable! Each week, we will host a discussion with the authors of "Views and Reviews" and "Fertile Battle" articles published in a recent issue of Fertility & Sterility. 

This week, we welcome Dr. Paula Amato and Professor Glenn Cohen to discuss the legal and ethical implications of in vitro gametogenesis (IVG) - the creation of human eggs and sperm in a laboratory setting using non-reproductive cells, such as skin or blood cells. Through our discussion, we will explore several issues raised by this nacent technology, including safety, Food and Drug Administration review, embryo destruction, eugenics, enhancement, unauthorized parenthood, inequitable access, and evolving conceptions of parenthood.

Dr. Paula Amato is Professor of Obstetrics & Gynecology and Director of the Division of Reproductive Endocrinology & Infertility at Oregon Health & Science University. She received her medical degree from the University of Toronto in Canada, where she also completed her Residency in Obstetrics & Gynecology, followed by a Fellowship in Reproductive Endocrinology & Infertility at the University of California, San Diego. Dr. Amato is past-president of the American Society for Reproductive Medicine. Her research focuses on innovative assisted reproductive technologies for the treatment of infertility and ovarian aging.

Professor Glenn Cohen is the James A. Attwood and Leslie Williams Professor of Law at Harvard Law School, where he directs the Center for Health Law Policy, Biotechnology, and Bioethics. A member of the National Academy of Medicine, his work focuses on the intersection of bioethics and the law. He has advised policymakers and global organizations on topics such as genetic privacy, medical AI, and reproductive rights, and his work has been featured by several prominent news outlets, including PBS, NPR, CNN, and The New York Times.

View Fertility and Sterility at https://www.fertstert.org/

Welcome to Fertility and Sterility Roundtable. This podcast will delve into sections of the journal previously unexplored in the Fertility and Sterility podcast family. Articles that we would consider some of the most timely, cutting edge, thought provoking, and dare I say controversial.

We will be joined by a couple of the authors each month to explore the themes, debate the pros and cons, and generally expand our knowledge in a conversational format. I'm your host and FNS Interactive Associate, Dr. Emily Barnard. And I'm your co-host and producer, Dr. Ben Peipert.

We will be covering articles in the fertile battle and views and reviews portions of Fertility and Sterility. This podcast is brought to you by the Fertility and Sterility family of journals in conjunction with the American Society for Reproductive Medicine. Welcome to Fertility and Sterility Roundtable.

I'm your host, Dr. Emily Barnard, and I am joined by my co-host and producer, Dr. Ben Peipert. We are excited to bring to you what we think is going to be a really fascinating discussion today on the views and reviews from the July 2025 issue of Fertility and Sterility entitled, Where Will Science Take Assisted Reproduction? We have two esteemed authors and discussants joining us here today. I would first like to introduce Professor Glenn Cohen.

Professor Cohen is the James A. Atwood and Leslie Williams Professor of Law at Harvard Law School, where he directs the Center for Health Law Policy, Biotechnology, and Bioethics. He's a member of the National Academy of Medicine, and his work focuses on the intersection of bioethics and the law. He has advised policymakers and global organizations on topics such as genetic privacy, medical AI, and reproductive rights, and his work has been featured by several prominent news outlets, including PBS, NPR, CNN, and the New York Times.

Thank you so much for joining us, Professor Cohen. Thank you for having me. It's a real pleasure.

We are also joined by Dr. Paula Amato. Dr. Amato is a professor of obstetrics and gynecology and the director of the Division of Reproductive Endocrinology and Infertility at Oregon Health and Science University. Dr. Amato received her medical degree from the University of Toronto in Canada.

She completed her residency in obstetrics and gynecology, and then followed that by fellowship in reproductive endocrinology and infertility at the University of California in San Diego. Dr. Amato is a past president of the American Society for Reproductive Medicine. Her research focuses on innovative assisted reproductive technologies for the treatment of infertility and ovarian aging.

Thank you so much for being here, Dr. Amato. Thank you. Glad to be here.

So our conversation today is really going to focus on the ethical and legal implications of in vitro gametogenesis. And so I'd just like to start us off by getting some definitions. Dr. Amato, could you tell us a little bit about what in vitro gametogenesis is and some of the potential clinical applications? Sure.

For short, it's usually, we call it IVG, so you don't have to say the whole term. But basically, in simple terms, what it is, is trying to make gametes, so either sperm or egg cells, from somatic cells, for example, from a skin cell. And probably the more common, the most common indications would be advanced maternal age.

So women who are older, we know that their egg number and egg quality decreases. So they would be potentially candidates for IVG after they've gone through menopause, or someone with premature ovarian insufficiency who is prematurely postmenopausal due to either genetic reasons or potentially previous chemotherapy for cancer treatment, etc. And of course, men with azoospermia, men who lack sperm.

And the other sort of group of people that would benefit from this type of technology would be same-sex couples. So currently, female same-sex couples need to use a sperm donor to have a family. Male same-sex couples need to use an egg donor and a gestational carrier.

If IVG were to become a reality, then potentially same-sex couples could have a child that's genetically related to both partners. That's fascinating. And Professor Cohen, you mentioned a couple other potential clinical applications in your article I found very interesting.

Could you go into a couple of those as well? Sure. But what's interesting is the way Dr. Amato delivered this in such an even and cool tone. This stuff is really cool.

And of all the things I talk about, when people think I'm making things up in terms of medical science, this is the topic. When I cross-sex gametes from skin cells, people are like, their mind is blown and they don't believe me. They think I'm talking Star Trek and science fiction, not science facts.

I just wanted to acknowledge that at the front end. This is sort of amazing technology. And also just emphasize that we have not done a human birth with this yet.

We're talking about significant animal models. We're talking about some work in embryos, but we're deriving the gametes. But we haven't yet done a human birth with this sort of stuff.

But back to your question, doctor, which is to say some of the other use cases. So one, and this one I credit my friend, Hank Greely at Stanford. He has a great book called The End of Sex.

It's a fun title. But essentially, he's interested in what he calls EZPGT. And that is the combination of using in vitro gametogenesis, IVG, to produce large numbers of embryos, perhaps 100 or 1,000.

And then using cheap, fast, accurate genetic sequencing. And the idea is, especially as advances in sequencing, polygenic risk scores and the like, to pick out embryos that we have a reason to think are going to be the most likely to implant, but also perhaps some forms of trait selection. So one of his views is that it's not just for people who are suffering from infertility, but in the future, and he's talking about a 20 to 40 year time frame, there's a possibility this becomes the way reproduction happens for most of us.

So that's one of the use cases we haven't talked about. There are some other use cases that are sort of interesting that I'll just mention, even if we don't kind of spend too much time on them. One is what's called solo IVG, where an individual would derive both sperm and egg from themselves.

So it's not cloning, to be clear, but it achieves something very similar to cloning, but the idea of being both the sperm and egg provider for the same child. And then there's what's called multiplex parenting, a little hard to describe, but the idea would be that we'd have four or more individuals contributing genetic information, and there's a way in which we would collapse generations. We'd basically make people, take four people and produce a child that's the equivalent of being that child's grandparent, but skip the middle generation.

We'd say more of that if people are interested, but those are two uses that I think are a little further out. Yeah. I would like to add one more thing, actually.

If this technology became a reality, it might change the way we do IVF. So even for people who do have eggs and sperm, if you could make eggs and sperm from a skin cell biopsy, why do ovarian stimulation egg retrieval, which carries a fair amount of risk and discomfort, et cetera, so it might totally reduce the morbidity and mortality associated with IVF in general. Yeah, this is so fascinating.

I think, can you talk a little bit, Dr. Amato, on how we go from a skin cell to an egg? Like what are kind of some of the steps there and maybe some of the challenges getting through those steps? Yes. Very good question. It's quite complex, actually, but there's different approaches, but probably the most common one is what we call IPS cell reprogramming.

So the idea is that you would take a differentiated somatic cell, like a skin cell, and then reprogram that cell into a stem cell. And of course, we know stem cells can then differentiate into any kind of cells, including egg cells and sperm, et cetera. So the idea would be to recapitulate that process from a somatic cell to a stem cell into a GAMI.

And this has been done so far successfully, as Dr. Cohen said, just in animal models, specifically in a mouse model. So a group in Japan led by Dr. Hayashi successfully did this in a mouse model where he was able to obtain live mice pipes, I guess you would call them, using reprogramming technology. And it's been tried with human skin cells, but so far they haven't, using the same technology, they haven't been quite as successful in getting to the mature OSI stage where you can actually fertilize and create an embryo.

In our recent paper, we used an approach that tries to leverage a technology called somatic cell nuclear transfer, and it's the same technology that we use for cloning. And it involves basically taking the nucleus from a skin cell, transferring it into a donor egg cell that's had its nucleus removed. And then instead of creating a clone, trying to induce that now SCNT oocyte that we call it, to extrude half of its chromosomes to allow for fertilization.

So a skin cell, of course, is what we call diploid. It has two sets of chromosomes. So when we do this nuclear transfer, we want to reduce those chromosomes to one set so that we can fertilize that egg with sperm with its own set of chromosomes, and then produce a unique embryo that could then hopefully develop into a baby.

This has been done successfully, again, in mice. It's very inefficient. It's a human eggs and sperm and human skin cells.

And we were successful in producing embryos, but all the embryos were antiploid or chromosomally abnormal. So obviously, that would not be viable in terms of producing a baby. I love that our conversation here really borders on science fiction.

What do we think is holding us back from implementing this clinically today? Of course, there seem to be technological challenges as well as legal and ethical ones. But how would you answer that question? Maybe I'll start with the legal and ethical, and then I'll turn it over to Dr. Amato for the more technical challenges. So one set of challenges has to do with whether it would be legal to actually produce a baby in this way in the United States.

And the difficulty is that we have what's sometimes called the Aderholt Amendment, which was an amendment initially put in an appropriations rider in 2016. It's a little bit funny about how this works, but I'll do the quick version because, again, we don't have to bore you with the legal details. It prevents FDA from basically accepting a submission.

And the term of art is in research in which a human embryo is intentionally created or modified to include a heritable genetic modification. And one of the questions is whether that language that Congress has passed every year, which really does seem to have been introduced and kind of with the focus on Dr. Ho's kind of experiments in China and gene editing, whether it's actually capacious enough that it also captures IVG applications. And if so, FDA could not consider such a submission, it could not approve such a submission, such that it might be a violation of Food, Drug, and Cosmetics Act to engage in offering that in a clinical way or marketing it here in the United States.

So that's like a very baseline legal question. When it comes to, I think, the more general ethical questions, there's a few of them, and we can talk about them as interests you. There's questions in general, as Dr. Amato suggested, especially in the early days, would probably be creating a lot of embryos that would not be viable and or would not be used in this process.

And so there are people for whom the creation of embryos that will likely be unviable and destroyed for this purpose is a problem in and of itself. There's also people who are concerned about predicting the safety of this technology going forward, and this question about whether the risks involved for offspring and for future generations is predictable, and if it's not predictable, how do we think about that? And that unlike other kinds of medical treatments, but like much of infertility treatments, you cannot pre-consent the entity that's going to come into existence, we're talking about consent from the parents. And so for some people, that is a big question.

And I'll just mention two more, and again, there's plenty more, but just two more that I'll throw out here. There's an interesting question, this relates, I think, especially to the same-sex uses, in that much of the progress of same-sex rights and same-sex parenthood rights, certain sectors of it, is to kind of get rid of the notion that genetic parenthood is the key to being a real parent, and to legitimize the idea that even if you are a parent that does not have a genetic tie to your offspring, you are still very much a parent. And there's a question about all the use cases, or most of the use cases for IVG could be satisfied through donor gamete.

So they really are about forming a genetic connection with your offspring, and how we view that goal in light of these other kinds of considerations is something that is sometimes brought up. And the last thing I'll say, and again, this is kind of the opposite direction, that all of these are concerns about this technology being introduced. On the flip side, there's a concern that if the technology is widely successful and actually works, who will have access to it, how much will it cost, what is the effect on equity, and in the same-sex context, also its relationship to the need to use surrogacy, especially for male-male parents who use this technology to produce a new site.

Yeah, I would agree with Dr. Cohen. I think, you know, first and foremost, safety is the primary concern. If the technology is not safe, then obviously it shouldn't be used.

So there's a number of technical challenges to address that. The embryos have to be chromosomally normal. We still have to investigate issues such as recombination, imprinting, all those things would need to be satisfied before we would ever use this in humans.

I would like to point out, though, it's kind of interesting, Glenn, that a lot of the issues you mentioned are very similar to the issues people brought up when IVF first came online like 50 years ago. They're almost identical, actually. If I could pick up on that, I completely agree with you, Dr. Amato.

And so I find this parallel very interesting, and I think one way to think about this problem is a litmus test about how you felt about the early days of IVF, right? So we have a little bit of hindsight bias in that IVF has produced amazing results to enable so many people. So right now we're like, this is a great technology. When you look at the first moment, the first human moment, right, you ask yourself, what was the data looking like then? What was our confidence? What did we think about future generations? What was that based on? And then, actually, an interesting question about what regulatory review was necessarily a part of this.

And there's a way in which actually our current regulatory regime was not nearly as mature as it is now. And if you try to imagine what today's FDA would require if today was the first day that IVF came online, I think the process would look very different. And whether that makes you happy or sad about this, I think it's an interesting litmus test about your feelings about this technology.

Agree, agree. And one more issue, especially when it comes to women of advanced maternal age, and this applies even to egg donations. So just because women in their, let's say, 60s and 70s can now produce eggs, it isn't necessarily ethical or medically recommended that someone of that age would actually carry a pregnancy, right? All the sort of risks of pregnancy would be extremely elevated in someone who's a lot older.

Now, yes, of course, some of those can be circumvented with use of a gestational carrier, but that's not available everywhere. And even where it is available, it's quite, can be prohibitively expensive. So that's another thing to keep in mind.

One of the issues that you brought up, Professor Cohen, was the issue of safety with respect to IVG being implemented in clinical practice. What sort of safety endpoints would we need to be seeing in order for this to enter widespread clinical practice? So here, I think there's really a very difficult design problem in thinking about what you want, because ideally, what you would want would actually be, I think, what I would call multi-generational data. You'd want to look at basically the health of offspring and maybe the offspring of offspring from this process.

But of course, that data is not available in large numbers until you've actually allowed the process to go forward. A good analogy here, I think, is to actually mitochondrial replacement techniques, MRT for short. And in the US, by the way, this is not a technology that is available.

In the UK, they have a licensing process through the HFPA, and there is Newcastle Group that has been carrying this out. And essentially, there was many, many years of reports, consideration. There was actually debates in the parliament about it.

I think actually the Archbishop of Canterbury, of all things, wrote like a op-ed on this. So this is actually a great example to me of both scientific engagement, public engagement, and regulatory engagement for a technology. And a technology, in many ways, that's actually, I think, less disruptive than what we're imagining IVG would, because the number of people who would use it are small by comparison.

But they face the same question as we did with IVF, which is you have a moment where you have to decide, when would we allow first in humans? What would our regime of testing look like? How would we gatekeep how many people had access? And then there are some subsidiary, interesting bioethical questions like, could you force the children born from IVG to contribute data going forward, given that they never consented? We do have examples of donor registries for recipients of organs and the like. So there are some kind of analogies roughly here. But it's an unusual configuration, is to say, to be born, to be a data subject for the rest of your life, is a complicated thing to wrap one's head about.

Yeah, I agree with that. The typical path from a scientific point of view would look something like, we do these experiments in vitro using human embryos, but eventually we would want to do the same experiments in a non-human primate model, probably, like monkey model or marmoset. And then ideally, as Glenn said, multiple generations of that, or at least two or three, which in a non-human primate is shorter than a human.

And then only then would we consider transferring an embryo into a human. But I came across this term recently called the translational dilemma, where it has to be safe enough to use in humans. But ultimately, you don't really know if it's safe to use in humans till you use it in humans.

So at some point, just like IVF in the early days, I imagine, you just have to take a vote of confidence, whatever it's called, and just kind of do it and hope for the best. So I think that's sort of what it's going to look like if it comes to that point. Also, kind of interesting to think, how do we weigh the potential harm or risks to offspring with kind of the autonomy of an intended parent if the technology exists? Do you have any thoughts or comments on that? Yeah, one thing I might say is that I don't know that all of the use cases are equal in thinking about this balancing.

Now, again, I'm treating these as tentative thoughts or ways of thinking about it rather than me trying to be definitive, right? You might think the more the use case matches your kind of typical view of disease or infertility as a disease, and we can debate what is disease versus a health state, but the idea of species-typical functioning, the more it's meeting a medical dysfunction, the stronger the argument for making it available to a population is. And the more it is not curing a disease or meeting a disease state, the less strong the argument is. So I think of, for example, instances of people who are not able to produce eggs because of infertility and stuff like that as the easiest case to justify, and I think of solo IVG as the hardest one.

Now, in between, though, we have some interesting and difficult questions, which is to say, if you're a same-sex person, right, we are now, I think, I'm happy to say, in this country, at a place where, and there are many countries for many years that wouldn't make IVF available to same-sex individuals and would just say, you are not infertile, you don't have a medical diagnosis of infertility. We're at a place now to realize that these are people who have needs and desires to have children that resemble those of people who suffer from infertility and are heterosexual and married, right? So I think we've come to a place to acknowledge these are weighty interests, but they don't fit so neatly into our model of disease and health, right? When we describe the interest, it's hard to think about this as satisfying a disease problem as opposed to thinking about it as doing something that's very important to someone that doesn't quite fit in the bucket of infertility as traditionally thought. So I think that's an interesting case where you might say, now, all that said, that was very true of IVF as well, right? There were periods of time where we had many more restrictions on IVF, including advanced paternal age.

There are countries that, for a long time, did not make that available, same-sex couples, single individuals, and we've come to a place with IVF where we're there. And so it might be just a process also of acculturation that IVG starts in the most compelling cases, and as we have more and more safety data and more and more confidence that this is helping, we start fanning out to cases that are a little bit less clearly defined by the medical model. And I would just add there's also a component of professional autonomy there as well, which is easier if you're dealing with prevention of a medical disease, but we start to see questions when we're dealing with doing assisted reproductive technology for non-medical traits.

So for example, sex selection would be a common kind of scenario where it's not a medical disease, but the patient, do they have autonomy to choose the sex of the embryo? And does the physician or the provider have the autonomy to offer that or not offer that or refuse to offer that? So that's debatable, and ASRM has a position statement on this. And one of the nice things about ASRM is that they have very well-reasoned and fairly comprehensive position statements on many of these issues. They change over time.

That's itself interesting to see how they reflect different attitudes over time, but they're a great repository. One wants to think through the ethics of something to see what ASRM has said on it. Read the rest of the literature, of course, but I think it's actually a very helpful thing that ASRM does.

Yeah. And I think you alluded to it earlier, Glenn. It's very important that we engage all the stakeholders in these conversations.

I mean, my impression is the science kind of moves forward and doesn't wait for the ethics or the legal aspects to kind of catch up. And it's really important to be talking about these issues as the science is happening. I don't expect that we will resolve them all, but we at least need to acknowledge them.

And we can't be in our little silos and just doing the science or the medicine. We really need to talk to the public, talk to legal scholars, ethical scholars, and really all the stakeholders involved. I completely agree.

I'll just add one more thing. And Dr. Mott and I have both been at meetings where we've met Silicon Valley entrepreneurs who are interested in the space and developing companies in the space. So it's sort of interesting to see that although we've discussed where the clinical medicine is and how far away we still are, there is actually a significant amount of investment and interest in this space and kind of keeping those in check and thinking about how they relate to law and ethics is no easy feat.

Yeah, there's this inherent tension between the pace of progress and doing things responsibly. Do you both think that it's likely we see IBG utilized outside of a condoned medical indication kind of similar to how we saw CRISPR used in human embryos in 2018? I said maybe I'll show my optimism side of me. I'm a lawyer, but occasionally I have bursts of optimism in that I think within the United States, I would be surprised if I heard that somebody had tried to create a live birth in the United States at the moment through IBG.

It really would surprise me. Yeah, there are other parts of the world where there may be less monitoring. Also, the legal regime might be a little bit different.

While the legal regime across the world is largely consonant right now on the topic of germline gene editing or human germline gene editing modifications, I'm less aware actually about whether all countries that I could imagine where people could work on this have legal prohibitions the way we could read perhaps the current Aderholtz Amendment to the Rider to prohibit in the United States. So that's a question to me is that I'm not sure I could map the legal status of IBG across the world and if there are more permissive jurisdictions, it's entirely possible we might see this in one of those jurisdictions where people try to do this quicker than in the United States. That's, you know, again, a guess and an optimistic guess perhaps.

Yeah, I think that that's, you know, illustrates one of the problems with these types of restrictions and calls for moratoriums, etc. is that it drives the science underground and it seems more likely to me that some rogue actor in a country that has maybe less robust human subjects protection would attempt to do this. Whereas I think, you know, United States has very well developed IRB system and human subjects protections.

This is exactly where this type of clinical trial should be happening. And that's the same frustration that I have with MRT. I mean, obviously, UK and Australia are very similar, but you also see MRT now happening in some other countries where I'm less sure about what sort of, you know, regulations they have there.

Maybe I'll just say one more thing on this. I'm tempted. So you can tell me this is too much is to say we also have a question about whether US-based individuals would be interested in going abroad for some of these treatments.

We saw some of this in a book years ago on medical travel, medical tourism. We saw some of this in the MRT circumstance where patients might have worked with a US physician, but had many of the steps take place in another country, and they came from a third country. And now when we're talking about people, samples, sperm, oocyte moving in international world, there's actually some very complicated questions about who has regulatory authority under what circumstances.

So that's like an additional problem when we have more permissive regimes and less permissive regimes. And we already see a lot of that in the, you know, fertility world, people going to different countries to kind of circumvent the laws in their own particular country, whether it's like same-sex couples or people using gamete donation, that type of thing. Even with IVF today, you see people circumventing access restrictions, right? We have plenty of patients who are in the United States who have to go abroad just because they don't have the financial means to afford the technology.

And so I could see something similar happening if this technology were to be implemented abroad. Yeah. The access issues, you know, are not unique to IVG, of course, right? All of IVF, probably all of medicine, but it does raise the issue of like, who will have access to this? And, you know, gene editing is a related technology.

And when you look at the comparison, editing an embryo is likely to be far less costly than somatic gene editing, for example. And we're seeing now somatic gene therapies come online and they're, you know, the cost is one to $3 million per patient. Like who can afford that? Hardly anybody.

So it's interesting access cuts both ways. And in some ways, allowing embryo editing would be a way to actually improve access by preventing disease. And I'll just add that even in universal healthcare systems with some fertility coverage or significant fertility coverage, the introduction of IVG would also raise the question about how much of the currently earmarked budget for infertility care ought to go to people seeking IVF versus people seeking IVG and how to do trade-offs like this.

And is it based on the indication you're using, or is it the fact that one technology might, especially upon the point of first introduction, be much more expensive? But for no fault of some of particular diagnoses, there's no way to have a genetically related child through IVF. IVG is their only alternative, but it's an alternative that might be chancier in terms of the likelihood of success and more expensive for each attempt, right? So I had to think about that dilemma as a financer of a healthcare system about how to spend your money. Speaking of money, I think I found it interesting in Professor Cohen's article talking about the Dickey-Wicker Amendment and limitations on using federal funding, but it sounds like maybe there could be some loopholes, like could this be something that could be covered? Perhaps not, but I'm just curious your thoughts on how that amendment is read and how could there ever be funding for this, or is this something we will be working with industry to get funded? Very good questions.

I'm sorry to say that as a lawyer, this is a place where it's a question of I'm not sure and it depends, and I'm just going to flag two of these. One you brought up, but first let me say something about the question of if FDA does have the authority to review this, which of the FDA pathways is this? It would be weird to describe it as a drug or a biological product because the human embryo would be very strange to describe it that way, but there's a way in which it's actually the most natural framework when you go through the FDA. Indeed, at an event that we hosted that we referred to in the paper, I should also acknowledge my co-author Dr. Dashi on this, Peter Marks, who was then the director of CBER, the Center for Biological Evaluation and Research at FDA, said they thought the ideal way to categorize in vitro-derived gametes in their embryos would be as human cell tissue or cellular and tissue-based products, and that's the right way to think of IVG, but he was worried about whether they were more than minimally manipulated during production, such that that category could not fit.

It made other people thinking that the best actual analogies is the regulation of chimeric antigen receptor T-cells, CAR-T therapies, and it's about the chain of custody of the cells and stuff like that. So, one issue is just to say this doesn't fit so naturally into existing verticals that we have in FDA, but the other, again, is the question you raised about the way to think about the Dickey-Windbaker Amendment, and it prohibits the use of federal funds for the creation of a human embryo or embryos for research purposes, or research in which a human embryo or embryos are destroyed, discarded, or normally subjected to the risks of injury or death greater than that allowed for research on fetuses. But then you say, what does the word embryo mean in that amendment? And it says it's something derived by fertilization, parthenogenesis, cloning, or any other means from one or more human gametes or human diploid cells.

And so, the question is whether that definition actually covers an embryo derived from IVG. And again, at this event that we both attended, we had some spirited discussion amongst people there, including the great bioethicist Alticiaro about exactly how to fit IVG into this language and how to think about it. Now, I will say that although this is a great debate, there is this question about if you try to say, well, it doesn't apply whether Congress would then just amend the Dickey-Wicker Amendment, the next appropriations rider, to make it clear.

It seems strange to me that the Congress that's interested in preventing the destruction of embryos in general would be very happy with the use of federal funds for IVG, which the research they're in might involve the destruction of a lot of human embryos. But maybe people think about them differently because of the way they're created. So, whether an embryo is about what you see and in terms of the final product, or whether the way in which it's created is relevant in thinking about the ethics of destruction is, I think, an interesting question.

Now, I'll just add that there is an argument to be made that we're not necessarily genetically modifying an embryo. The end product is actually the gamete. So, you could argue that the FDA rider does not apply.

So, that might be a loophole. The second thing is we have a new administration and I personally have no idea how the current administration thinks about some of these things. So, I don't know if you do, Dr. Stone, but it'd be interesting.

Yeah, it would be super interesting in that I think that we have an interesting mix of very, quite different attitudes on this. And I think we saw this a little bit in the dance around the executive order relating to infertility, that we have a constituency that I think supports the current president for whom embryo destruction and actually, you know, a lot of reproductive technologies. They're very kind of, they're kind of like the old Leon Kast line about turning reproduction into manufacture and the like and this sort of thing.

So, there's that group. Then we have another group that's incredibly worried about infertility and incredibly worried about birth rates and is actually very interested in facilitating a lot of reproductive medicine, including high-tech reproductive medicine. And both of these people are kind of influential, I think, and within the administration.

And so, that's quite an interesting and unusual configuration. I think probably one that historically, I don't think we've quite seen that configuration. And again, a lot of the people at FDA who had traditionally been the key regulators, been there for many years, have also left FDA.

So, I don't know, many of these people, we have no idea from their past records or speaking, they have any attitudes or ideas at all about this area of technology. So, that's also an open question. This is me as like a cultural critic or someone who's interested in culture.

And to say that we have a lot of folk ideas of parenthood that are connected in many ways to non-assisted reproduction. And we have thus far been able, and you see courts struggling with this with analogies about who is the parent and the like. We have this kind of procrustean tendency to fit in assisted reproduction, legally, culturally, our attitudes towards it, into the index case being non-assisted reproduction.

I do think what's interesting about vitrogamy to genesis is it makes that very hard to do. It is such an unusual and such a break from traditional ways of producing gametes that I think that for me, it really opens up the box to say, what is it about parenthood that we value? What is it about genetic connection that we value? And to me, these are exciting and worthwhile questions to ask, but I find this technology not only disruptive and perhaps as to techniques and as to technologies, but also even a little conceptually disruptive in a way that I think is actually healthy sometimes to be a bit disrupted. When historians look back 50 years from now, what do you both hope they will say about how our society and our scientists handled the emergence of in vitro gamete genesis? I can go first.

I'll say that I hope they think we were thoughtful. That's the word I would use and thoughtful and engaged and that the engagement was really among many very different kinds of stakeholders, right? So I do think that this is a technology that not only has lots of scientific questions, where of course we have to have deference to the scientific community, but lots of societal and ethical questions for which I think the greater polity has things to say and should be engaged. And I view a little bit, the gold standard that I would love to us to come close to is some of the engagement we saw with mitochondrial replacement techniques in the UK.

There's many people who think that was not good enough and other people who think that that might have been, had they gone the other way at the end of the day after that engagement, that would have been a problematic incursion on reproductive autonomy. But if you asked me the kind of process that I would love historians to be able to talk about, it would be that we had a similar process of engagement when we're ready for it on a technology like this. Yeah, I would agree with that.

I too think the MRT example is relevant and it's sort of an example of how this technology should move forward. Science will move forward as it always does, but we need to be having these conversations. I am always struck by the parallels with IVF, like I'm trying to imagine myself back then, 50 years ago.

I just think there's so many parallels. And my gut feeling is that 50 years is going to be sort of very similar when this technology, if and when it proves safe and effective, that people are going to say, oh yeah, of course. But I think it's going to be a struggle to get there.

And I don't think it's going to be easy. When it comes to some of these ethical issues, I think people are always looking for kind of a resolution, which I'm not really optimistic about. When it comes to even an issue like abortion or the moral status of the human embryo, I just don't find it realistic that everybody is going to agree on this question ever.

So that's not sort of what I'm looking for, but to Gillian's point, just people talking about it, debating it, but thoughtfully listening to other points of view, I think that's important. But this notion that there's going to be some sort of global or international consensus about whether this technology should move forward or I'm not optimistic that that will ever happen. We hope this podcast inspires both those experienced with advocacy efforts and newcomers alike, as this is a critical time in our field, both with potential opportunities and new challenges.

Thank you so much for listening. Until next time. Fertility and Sterility Roundtable was developed by Fertility and Sterility and ASRM as an educational resource and service to its members, other practicing clinicians, and members of the public.

The opinions expressed are those of the discussants and do not reflect the views of Fertility and Sterility or ASRM.