Ethical Considerations in Pediatric Fertility Preservation: Pediatric...

So now we'll go on to ethical considerations and we're lucky to have Doctor McGowan here to present. Great, thank you so much. I'm happy to be here today and thank you to my colleagues who have, um, provided us a background on the clinical and technical considerations around pediatric fertility preservation. So when considering the field of bioethics, we, uh, gen generally differentiate between ethics of a phenomenon of fertility preservation and ethics in the practice of fertility preservation. So I'll start with the ethics of, uh, the phenomenon, um, which is more of a bird's eye view of, um, the phenomenon of fertility preservation, and then I'll move on to the specifics of ethics in the practice of fertility preservation in the clinical and research context. So when considering um ethics of fertility preservation, we ought to first consider the social context in which assisted reproduction has emerged. So as many of you may be familiar, the first uh live birth with in vitro fertilization was in 1978, so coming up on 40 years ago. Um, but the field of bioethics, um, was an outgrowth of, um, the post-Nuremberg era and really got its footing and in the 1960s and 1970s it was really founded by philosophers and theologians who were grappling with the emergence of new technologies in the clinical context ranging from transplantation to life support to assisted reproduction. In in trying to determine what ought the field of medicine be doing in terms of managing and prolonging and creating life, um, this has spurred vast, um, reams of intellectual content as well as public discourse around. The degree to which we should be intervening with uh the trajectory of an individual's life, um, so for clinicians who are interested in working in the field of fertility preservation, they ought to consider that individuals coming into the space probably have some familiarity with assisted reproduction, and they may their greatest familiarity with it is likely to have come from a media source, um, or from a religious or or cultural background. So I don't expect that any uh clinician would necessarily have all the answers around the ethical conundrums that have been raised by assisted reproduction. Um, but they ought to engage with the, um, patients and their families around what, if any, values they have around assisted reproduction. So, as Doctor Shrine mentioned, um, this, the question around masturbation, for instance, comes up in the context of fertility preservation because there are some religious doctrines that have restrictions on. On the practice of masturbation, some religious traditions, uh, are opposed to, uh, any form of assisted reproduction. Catholicism is the most prominent in its teachings around this, and there may be socio-cultural, um, taboos around talking about reproduction, around sexuality, um, and around future reproduction with. Individuals who are not at the point in their lives where they would be considering having a family of their own, so it's possible that patients and their families will have had, uh, a very robust understanding of, um, their feelings about assisted reproduction and, um, and as that as that may relate to fertility preservation as they're introduced to the topic, um, but it's, um, an opportunity. That clinicians and fertility navigators might take to have uh patients or prospective patients reflect upon the values that they have around what gametes mean, what embryos mean, what it means to remove gametes and create embryos and store them for for later use, and what, um, what it means to dispose of embryos on the national stage we have regulate. And regulations around the disposition of human embryos, their use in research purposes, and there's been much less discussion around, um, research and use of testicular and ovarian tissue. So we have to keep this in mind that there has been probably less information available to patients and families to consider, um, but they may have associations that they're making, uh. Between existing known established technologies and um more experimental techniques that may be offered in the in the fertility pres preservation context, we also ought to consider the gendered moral dimensions of fertility preservation as my colleagues presentations have shown there are vast differences in terms of the degrees of intervention, um, that are taken depending on the sex of the patient. So the most established technique that's available in assisted reproduction is of sperm retrieval and um and uh freezing for later use with uh artificial insemination um and uh and this is a much less invasive technique for um than any technique that would be used with a female population. So in the bioethics literature we've referred to this as the gendered moral burden of responsibility around fertility preservation, that it means something qualitatively different to suggest fertility preservation with a post puberile male than it would for a female of any age, for instance. Um, moving on, um, I think that it's also important for clinicians to be aware that, um, that there will be, uh, some discrepancy in terms of the degrees to which, uh, decisions about fertility preservation presume a particular type of life after treatment. What we've heard a lot about today is this idea of, uh, preserving and promoting the idea of hope for life after treatment and a full and robust quality of life after treatment. Um, and, and yet we also ought to consider the, the degree to which, um, a future that involves having children has ever been considered by patients and their families. Um, this is particularly relevant when we're talking about a very young children who have probably never articulated, um, any sort of stance about whether they want to have a child in the future. Now this is a more of an esoteric problem than a practical one, but if you were to look at the bioethics literature, we will, you'll see quite a bit of discussion about whether clinicians should be engaging in discussions about presuming a particular kind of heteronormative or, uh, family centric future for, um, children who are undergoing treatments before they would be able to make decisions. On their own, um, but in the context of fertility preservation programs such as the one at Cincinnati Children's, I think that, um, it, we, it's very important to discuss the idea without foreclosing the possibility that this wouldn't be a practical or that this might not be what somebody would want, um, so leaving open all of the options is, um, the dire the direction that we have tended to go here. And lastly, um, there has also been some discussion in the, the literature about what it means to engage in fertility preservation when the, the, uh, in terms of future offspring we have heard a lot today about, um, success rates or the lack thereof, um, the lack of knowledge that we have about the, the potential implications, but. In general there's very little tracking of the offspring of fertility treatments. Um, increasingly we're starting to see, um, more data being collected at the national level around children who are the product of fertility treatments. Um, that's been largely limited in vitro fertilization. And so um what is going to be important to consider down the road is um whether and how it might be important to trace not just the satisfaction levels of patients and their families who are considering fertility preservation who have undergone it, um, but also to think about what it means to be. Child of fertility preservation. So this, um, is obviously very long off in the future in many ways since the birth rates are relatively, um, in small numbers at this point, but something to consider as a field as to whether and how we ought to be tracking, um, the lives of the children who are born of these techniques. OK, now, uh, transitioning more to the ethical issues in the context of the practice of fertility preservation, my colleagues have mentioned many of these issues already that when we are introducing fertility preservation, um, techniques in the context of, uh, um, the clinic, uh, it's important to. Engage with a variety of issues, um, and I have a link here embedded here in the in the middle of the slide that points you to one of the patient facing, um, uh, websites that we have here at Cincinnati Children's that articulates many of these particular issues that are raised above about efficacy around particular risks associated with various fertility preservation techniques around the costs and they're broken down by costs, um, they, and, um, and how we might consider, um. Who could, what kind of cost coverage is available, uh, Doctor Hefkin mentioned insurance coverage, which is a particularly hot issue in ethics and policy because there's highly variable insurance coverage for fertility treatments nationwide. It varies on a state by state basis. She mentioned Connecticut, which has recently changed its definition of, um, people who are experiencing, uh, infertility from 6 to 12 months of, um, not being able to get pregnant to anyone who has a medical necessity. Um, now there are some states that already have, um, that medical necessity language in place, but the legislators that produce this type of legislation around in for insurance mandates around fertility, um, don't necessarily know very much about medicine. And so we have to keep in mind that the way that these laws are written is not necessarily reflective of the realities of clinical practice, um, and so this is an opportunity for people who work in the field of fertility preservation to partner with, um, their legislative. Um, advocacy groups, uh, to try to ensure that there's more even insurance coverage and not just on a state by state basis but on a national basis, um, and so that we can maximize the amount of insurance coverage available for. Um, patients who are considering a variety of fertility preservation options, um, and I also mentioned on the slide here this idea of a use-by date. So Doctor, uh, Woodruff mentioned earlier that there are some patients that are undergoing fertility preservation techniques today who we anticipate will be keeping their tissues or cells in storage for 20 to 30 years. We do not have any data at this point in the assisted reproduction realm about people who have stored tissues. For that long in terms of the success rates of using tissues that have been stored for 20 to 30 years, we're starting to get more and more data now about, um, sperm that have been stored for a particularly long, um, lengths of time and embryos, but these are the most established techniques we have. So it's important for patients considering fertility preservation to be aware of what's known, but also what's known, not known about success rates using any of the established techniques and the experimental techniques, um, that are available. Um, the last thing I'll mention here around ethical issues in the practice of fertility preservation that are universal, not unique to the pediatric population are, um, the very uncomfortable issues, um, around the disposition of cryopreserved gametes or embryos, uh, or in this case of, of testicular ovarian tissue as well, um, should the patient not survive. This is raised um in the context of the bio bioethics literature around posthumous reproduction. We largely only have experience with uh ethical and legal cases using posthumous reproduction um involving cryo-preserved sperm. And so it's important to consider what the legal ramifications are, um, in terms of who will have access to gametes, can they be used to create a human child, um, even if the patient doesn't survive, um, and there are no clear guidelines, um, at the national level around how to proceed with, um, disposition of gametes for reproductive. Purposes, um, and so we are seeing some of these issues, uh, resolve themselves in the courts, but for those of you who are familiar with, um, court proceedings around assisted reproduction, there can be intense variability in terms of how courts decide these issues on a state by state basis, um, so as, as we move forward with the further integration of fertility preservation into the clinical context. It's important that that patients and their families, particularly in the pediatric context, be aware of what the range of possibilities are and whenever possible to make dis disposition decisions prior to undergoing any sort of fertility preservation, um, process, um, so that the patient and their family's wishes are known and can hopefully be honored, uh, at a later date if necessary. Now when thinking about the unique issues of pediatric fertility preservation, the most important thing to keep in mind is that um we we have this gold standard in bioethics of informed consent, but with pediatric patients there is a gradation of consent. The degree to which uh pediatric patients are involved in their own medical decision making is uh dependent on age and maturity. So as you see here on the screen I have. Um, three particular domains, uh, uh, that we talk about in, in bioethics in terms of guidelines for, uh, determining the degree to which pediatric patients are involved in decision making. We have the gold standard of informed consent which, um, typically is, is seen as only at the age of, of maturation. So, uh, after age 18, um, we have pediatric assent which depending on the particular clinical domain can be anywhere between like age 11 to 13. Um, when we would have patients, um, assenting to have their parents give permission or give consent to, uh, have them undergo particular treatments and. For younger or less mature patients or who lack capacity despite regardless of age, we generally apply a best interest standard. A best interest standard means that we are trying to make a decision about in this case, pediatric fertility preservation based on balancing the prospective benefits against the prospective risks for a patient who can't, um, make decisions for themselves. So this is can be for some. Parents or other care givers who are responsible for making decisions, um, this can be a very burdensome responsibility. We expect parents to make a wide range of ethically and morally charged decisions for their children on a daily basis, ranging from what to feed them to where to send them to school. But when it comes to making decisions about deciding whether or not your child should have. Preserve the opportunity to potentially have a child one day. This can feel very, very morally burdensome to parents, particularly if they don't have a sense of what their child might want, either because that child's too young to be able to articulate that stance or, um, because they have given them in some ways, um, mixed or idealistic, um, representations of the future that may not may or may not be realistic, so. What we ought to consider is that um with pediatric patients in particular we have to uh be attentive to the degree to which patients themselves will be involved in decision making and who which other parties need to be involved in that decision and how do we ensure that they're adequately making um uh in a balanced assessment as a surrogate decision maker for um their pediatric patient um that they're making decisions for. Um, the second issue that's unique to pediatric fertility preservation, which my colleagues, I think, have addressed at great length, is this idea of the pubertal and gendered complexities of established treatments versus versus experimental procedures. So in the context of bioethics. It's very, very important for us to, uh, ensure that patients understand whether they are undergoing an established treatment that has known or relatively well known success rates, um, and established risk thresholds, uh, established benefit thresholds, um, so to use the example of embryo cryopreservation that. We were talking about earlier and we know that um there's a 33 to 52% um success rate with embryo cryopreservation but with uh oocyte cryopreservation we still don't have quite a good sense of the numbers since it has just transitioned in the last five years from um an experimental procedure to an established, um, standard of care treatment. Um, and so, uh, in terms of, uh, whether people are, uh, are pursuing an established treatment versus an experimental procedure, they need to know, um, that the know the benefits and risks are better known with established treatments, but there it's also a moving target. So what we know is the, the, uh, the risks and benefits associated with embryo cryopreservation today may change. 10 years from now, what we know about the risks and benefits of experimental procedures such as testicular, um, tissue cryopreservation, which currently has no live birth rates with humans, it will change dramatically in the next 10 years, but patients and their families need to be making decisions based on what's currently known about the state of the science, and the uncertainty of this field of science is and how quickly it has moved in the. Since I've first become familiar with it, you know, is something that we have to try to impress upon our patients and families as, as much as possible. We want them to know what risks they are taking on, but they, we want them to also know that this is a field that's moving very quickly and so the ways in which they assess risks and benefits will be dependent on their individual values and their thresholds for risk rather than our own. So thinking in a broader sense about um the implications of the the increasingly widespread practice of pediatric and adult fertility preservation um I'll I'll close with some justice implications. These are bigger picture structural issues which um individual institutions ought to consider but are really, uh, bigger questions for the field of fertility fertility preservation as a whole. So in particular we raise questions and ethics around the fair distribution of scarce medical resources and the fair distribution of benefits and burdens associated with fertility preservation. Are the ways in which the benefits and burdens of fertility preservation adequately distributed across pubertal and gendered lines, for instance? And do we see fertility preservation as, uh, and the and distribution of particular types of techniques within the fertility preservation, um. Practices to be uh a useful and just and fair distribution of of scarce medical resources. This raises questions about fair equality of opportunity which justice scholars are particularly concerned with because they they raise questions like, um, is fertility preservation equally available to all those who could benefit from it. Fair equality of opportunity theory would argue that it ought to be made equally available to all those who could benefit, and that would mean we have to change some of our institutional and larger societal practices around who has access to health care and at what types so we know that we're very privileged to be in the context of an academic medical center that has a robust. Pediatric fertility preservation program, but even the example that was given earlier about um your own institution that um would doesn't have a pediatric gynecologist, you know, we know that there isn't fair equality of opportunity to have access to the expertise of something such as, uh, pediatric gynecology across institutions and across contexts and so. This raises the potential for exclusionary access along lines of both insurance coverage, um, and socioeconomic status of individual patients, but where they actually go to receive care, you know, where patients go to receive care may be geographically limited, um, they. They just go to the first clinic that they see down the road, right, instead of seeking out care from specialists and so how can we ensure the broadest distribution of fertility preservation across sites across insurance statuses, and across socioeconomic statuses of, of patients? Beef here for a second for fun? No, no, no, no, no, just ruffle feathers and no, no, no, no, I think it's, I think so, uh, just in general, I don't wanna derail the whole thing, but. Um, since when do we ever have uniform care in anything in this country? We don't, OK, I mean, that should be quite obvious, you know, so we do not, however. Ethicists are concerned with ideal theory, so we are aware of the limitations of the pra the practical realities of distribution of care though justice theorists would argue that in order for us to have a just society we ought to have just distribution of health resources. Now does that trickle down to individual fields like fertility preservation? I would. Argue that yes we have to be considering how to best distribute the resources that are available. Certainly that brings up the uncomfortable questions around rationing of care um and it also um takes head on the question around competition between institutions. So institutions want to be known for their particular areas of of specialty, but does that in any way. Um, challenge or exacerbate, um, the potential for what, uh, reproductive justice scholars have called stratified reproduction, which is in very, very simple terms a distribution between the haves and the have-nots in reproductive terms and we already see. Stratified reproduction in lots of ways assisted reproduction is already stratified. The people who have access to all forms of assisted reproduction have more privileges than those who do not. However, I just leave it on the table as something for people to keep in mind, um. As we go forward, uh, I don't expect practitioners of fertility preservation to solve these problems, but I want them to consider the ways in which their own practices, um, exacerbate or may minimize some of these justice implications. Actually there's some other opportunities here, right, because collaboration and networking. I know Doctor Hefkin has. Been working on a regional network that it allows us to work within the resources and confines and limitations that we might have in an institution to use things like telehealth to provide consultation right to make sort of a hub maybe you wanna comment about that opportunity. Yeah, I mean, I think the idea is right it's difficult for all institutions. To be able to offer all the resources that we're talking about, right? I mean there's just, there's not enough pediatric gynecologists to think that every institution could have that or that every institution could hold the IRB protocols to have all of these resources available, right? but you want to make something like fertility preservation available to all patients, so. Um, the thought is kind of a wheel and spoke sort of an idea, right? Could you take an institution that's large enough like Cincinnati Children's and has a built up fertility preservation program. And you know like we'll talk about in our next section, a lot of patient education standardization type of resources and be able to use that as a central location to then branch out to provide those resources to the other smaller centers so you know could those centers use your resources and your expertise to then provide the consultations at your centers um those standard. Standard of care options are available at most of those places where you have adult REIs in in most any academic center, um, but then bring patients to that central hub to be able to do these more experimental procedures where there are pediatric urologists and pediatric gynecologists or at least where the, the, um, the IRB protocols can be housed, um, because you need to do a fair. Amount of these procedures on an annual basis um to uh to be sufficient in them and to be able to do them safely and and uh and efficiently. Do you consider that a lot of hospitals where I was before, um, in Cleveland we were not a free standing children's hospital. We were combined with adult hospital and we had way more resources because we had tons of gynecologists attached to us and they said that they were at pediatric. Gynecologists, but I don't know how much they did. So the question is, is there a difference, but, you know, I don't, I guess I, the lines get blurred, um, when you get to free standing children's hospitals and what they should and shouldn't have, and I, I think that's just a, I've talked about this a lot before, this is an area that I think if any hospital administrators are listening to. Uh, this is something that I think is important, I guess the difference would be with their particular comfort and and where they would be comfortable doing their surgeries, right? Most gynecologists I know feel very comfortable. Adult gynecologists was doing adolescent gynecology, right, where usually the discomfort comes is with how young of a patient you are comfortable doing surgery on, right? the. The difference with doing ovarian tissue cryopreservation is you may be then doing an oophrectomy on a 1 month old or a 2 month old. That's usually where most of my adult colleagues will say it's not really where I am trained and that's not really where my comfort level is. And that's where I would rather have someone specialized in that doing that procedure, right. Um, whereas that may be where pediatric surgery in those institutions may, may be more comfortable because you, you, you're comfortable doing laparoscopies on a one month old, right? Um, and so maybe in those institutions, those, those entities work together because that's the resources that you have at that institution, right? So that's kind of where we talk about you work with the resources that you have who are interested in the program that you're doing. Because I think it's more important about who's interested in what you're doing, who wants to invest in the program. Um, and make it something that that is important to them. It's probably similar for pediatric urology at some level, right? I think that there are some of those resources and where do you draw the line between pediatric urology, adult urologists, and pediatric surgeons, right? I think it's a phenomenon where it depends on the age of the patient. If you have someone that's nearing an adult age, then they may be comfortable doing it, but in some of the younger age groups and certainly with some of these experimental technologies, they would probably defer someone else who has more experience. There you go. OK, sorry. All right. Oh, we got, we got a little dicey right there at the end, but that was the real end, right? That was really the end. Awesome, great, great, perfect, yeah, you caused us to think about many things that was a little uncomfortable to us, but I think it was good for us to think about. We had a number of questions, right? So we had planned for a panel at the end so that we can address some of those questions. I don't know if Todd, you wanted to throw them at us or how would you like that to me roll first go through some of these poll results. Oh great, and, uh, see if you guys wanna comment them or just move on. So, um. We already did that one. So this is about male after your talk, uh, does your institution currently provide service to male patients who are at risk for loss of fertility due to treatment for cancer? So let's play, play a game. What percentage do you think said yes, that they, um, they provide a service for male patients? Now this is a biased audience, but still for male male patients what percentage of the, what's that? 20, 80%. Whoa, I'm on 20 or 80. I'm on 20, so it's 67%. That shocks me, but again, this is a biased audience. If you poll the rest of the country, it'd be 20% or or less. But males, we gotta find that out because of Cincinnati Children's people. These are services for males after treatment. Just a service for males that are at risk of loss of fertility. The ability to sperm bank, sperm banks. That's what I'm saying. So that's what I'm saying so they can write them a prescription, but just sperm banking. If it's just sperm banking. I'll go up with my. OK, fine. This is a better one then. OK, this will be great. Does your institution currently provide testicular tissue cryopreservation as an option for fertility preservation in prepubertal children? 10%, 5%, except a lot of people are 40%. 40%. Yes, I think a lot of our nurses are. All right, next question. Do you, um, do you offer Oocyte cryopreservation in children? Oh, this is the question we put together. Do you offer OScyte cryopreservation in children under 16? And if so, do you get IRB approval? This is because of having to do the transvaginal. And so 75% said we, we don't do it under 16. Um, now that also might include they just don't do it at all, but they don't do under 16, um, and then of those who do it in children under 16, um, so we have total numbers 15.4% said yes we do it but we get IRB approval and, um, 7.7% said they don't get IRB. So I just to comment on what we do, so we work with the University of Cincinnati, uh, REI group. Uh, we have sent them a number of our patients. Most of them are in the post-treatment, um, time frame, but we've sent 2 or 3 patients pre-treatment, 32 or 3 patients pre-treatment. Um, a number of those patients are under 16 years old, but we are not doing that under an IRB protocol. I wanted to add something on this too that um today was the first time that I heard this recommendation from the Onco fertility Consortium around an age um you know an age limit for oocyte cryopreservation and I think that it's important for us to consider that the standard of care of embryo cryopreservation is really impractical for most pediatric patients and even for a lot of young adults because the average age of first birth in the US is increasingly getting higher. And so we and part of the reason for that is that people are partnering later so it's not necessarily practical, you know, for even young adults in the 18 to 25 year old range to be enthusiastic about, um, or practically oriented towards embryo cryopreservation which would need a partner's sperm or, um, sperm from a sperm bank. And so this is why in the field of uh fertility preservation we see so much more enthusiasm for oocyte cryopreservation and this was, you know, such a landmark shift in 2012. So the idea that now there's some hesitation around which patients would benefit from it, um, it seems, I'm sure I, I think that there are definitely. Um, you know, scientific questions that need to be answered around this aneuploidy issue, but I also think we ought to consider, are there ethical reasons for limiting it to experimental procedurals for children under the age of 16 when the American Society for Reproductive Medicine has argued that it's no longer an experimental procedure, you know, so I think that we just ought to grapple with this particular question a bit further, um, you know, as, as a community. So experimentation versus innovation, it's a new procedure and not necessarily experimental. I mean, if they're not doing research, do you need to get IRB approval on something that's an innovative technique? Well, innovative techniques can be considered research. I mean, it, it really depends on the field. If you were to go into a field of surgeons, they would say like we innovate all the time in, in surgery, and, and, you know, it might just mean like, you know, using a different stitch or something like that, and we don't necessarily consider that research. Um, whereas when you're talking about things that are happening in more of the basic science context, there's a much more robust understanding of when we're shifting, you know, from the experimental to the, the care model, um, I think in fields like surgery there's a lot, lot more slipperiness in terms of what we consider to be under the purview of the IRB. Um. Do you, do we have time now to go through questions, or do you wanna do them later? Uh, with the, with the agenda. OK, let's keep going then. OK, um, the boss down there tells him we're gonna keep moving, although I think that those, uh, topics are really great and we wanna hit those later, so you're gonna hold them, yep, got it.