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Uterus Transplantation at UAB

Paige Porrett MD provides an update on the UAB uterine transplant program, including indications, current state, and future challenges. Listen as the specialists from UAB Medicine share and advocate for this innovative therapy.
Uterus Transplantation at UAB
Featuring:
Paige Porrett, MD, PhD
Paige Porrett, MD, PhD Specialties include Transplant Surgery. 

Learn more about Paige Porrett, MD, PhD
Transcription:

Dr. Warner Huh: Hello. This is Dr. Warner Huh, the Chair of Obstetrics and Gynecology at the University of Alabama at Birmingham. And I'd like to welcome you to this monthly episode of Women's Health with Dr. Huh. Today, we're discussing a truly novel topic and there perhaps isn't anything more cutting edge in women's health than this. Today, we're going to talk about uterine transplantation today with Dr. Paige Porrett, who is the Associate Professor of Surgery, as well as the Director of VCA Transplantation at the UAB Comprehensive Transplant Institute. And she's also the Director of Clinical and Translational Research also at the UAB Comprehensive Transplant Institute.

Paige Porrett, MD, PhD: Thanks, Dr. Huh. Great to be here.

Dr. Warner Huh: I think some of the listeners may have already read about this in the press or online and I'm pretty sure that they're interested in learning more. And you are a true expert in this area and we're really lucky to recruit you from the University of Pennsylvania to build perhaps the only uterine transplantation program in the Southeast region. I think the next closest centers are actually in Texas and Ohio. So I thought maybe you could spend some time just talking about what is uterine transplantation and what medical purpose does it serve.

Paige Porrett, MD, PhD: Great. So uterus transplantation is a novel therapy to treat uterine factor infertility. And I'm going to take a moment, although your audience may be very versed with this topic, to explain a little bit about what uterine factor infertility is. So uterine factor infertility is a disease that results when a woman can not gestate a pregnancy or become pregnant or carry a baby, deliver a baby because of a problem with the uterus itself. So it's a subset of infertility as we know it.

There are different types of uterine factor infertility. We use uterus transplant to treat absolute uterine factor infertility. And what that means is that if a woman is either born without a uterus or has had her uterus surgically removed, which is often the case to treat a variety of diseases as you well know of the uterus, then absolute uterine factor infertility can result from that.

So we're using uterus transplantation to essentially restore fertility to women who do not presently have a uterus. Right now, uterus transplant is being used to treat this particular group of women. But we have hopes in the future that we can use uterus transplantation to treat women with other types of uterine factor infertility. So for example, if the uterus is in place, but it doesn't work because of fibroids or other types of conditions, that's the type of uterine factor infertility that we may treat in the future. But for now, this is primarily targeted for women who have an absent uterus.

Uterus transplant was first pioneered in Sweden. The first live birth in the world was as recent as 2014. So when we talk about this as a new therapy, that's the type of new that we're talking about. In the United States, uterus transplantation was first performed at the Cleveland Clinic. This was roughly in 2016. The Cleveland Clinic started the first uterus transplant trial in the United States and they were followed very quickly, a few months later by the Baylor University Medical Center in Dallas.

And I first became involved in uterus transplantation at the University of Pennsylvania in the early part of 2016, when we started to build our clinical trial of uterus transplantation at Penn. And I'll confess that as an abdominal organ transplant surgeon, I knew very little about the disease that is uterine factor infertility. And I had absolutely no understanding of the need for this treatment that was coming down the pipe that we were going to offer. to me, what was the novel patient population.

And I was initially frankly quite critical of uterus transplantation because, as an abdominal organ transplant surgeon, I use essentially life-saving intervention. It is quite risky, not just because of surgical risks, but also because of the risk that's attributed to the immunosuppression medications to essentially save lives. And I did not understand how this might impact the lives of patients who could be served by a transplant that improves quality of life, as opposed to enhancing the quantity of life.

And to make a very long story short, when I was initially introduced to uterus transplant, as I said, I was quite critical of it, but it was really through getting to know my colleagues and the Department of OB-GYN at University of Pennsylvania, who taught me about this disease as well as a better understanding of how amazing our science has become. So in 50 short years, we've really been able to propel the gift of transplant to patient populations that are no longer affected by just, I call it, end-stage organ disease.

So I want to be clear and I don't mean to suggest that uterus transplantation is not without risk. I'm sure we'll talk about that in a few minutes, but I think that, in short, the risks associated with transplantation in general have become mitigated sufficiently that we can actually offer transplant to patients who have not previously been offered this to treat their problem.

Dr. Warner Huh: No, that's great. And so, I guess, what I'm hearing from you is that there is a subset of women who have uterine factor infertility and that, in many ways, uterine transplantation maybe their really only option for these patients in terms of conceiving. But what I'm also hearing from you is that you were a true skeptic of this whole process, and it sounds like at some point you had a transformational experience that convinced you otherwise in terms of the value of uterine transplantation. And it's remarkable to me because I remember going to a lecture with one of the Swedish investigators that you talked about many years ago. And I thought that this was all science fiction and there was no way that we would ever get to this point. And it's just remarkable to me that several years later, we're talking about potentially making this a real option for women who were trying to conceive and have children. It's really, truly remarkable.

Could you just comment? I think the listeners would love to know have there actually been some libraries associated with this approach and can you comment on how many and where?

Paige Porrett, MD, PhD: Absolutely. So, as I mentioned, the first live birth in the world happened in Sweden in 2014, and this field has really exploded and there's a lot to unpack there to discuss about why we've seen the type of growth that we've had and also what some of the limits on that growth are. But to answer your question more directly, there have been to date in the United States 32 uterus transplants. And from those 32 uterus transplants that have been performed primarily within the last three years, there's been a total of 14 live births to date.

We have a few ongoing pregnancies right now, but as you might imagine, the coronavirus has impacted the pace of transplantation in this field, certainly in the US as well as elsewhere in the world. It's hard to pinpoint exactly the total number of uterus transplants, as well as live bursts in the entire world. But thanks to the privilege I have of participating in the International Society for Uterus Transplantation, which is, as you mentioned led by the Swedish investigators, specifically Dr. Mats Brännström.

We do have, I call it, a gathering each year or every couple of months to discuss the growth in this field. And so from that particular engagement, I can tell you, we estimate right now there has been approximately a hundred uterus transplants performed. We are trying to build a registry right now that could house all of the patients transplanted in the world, so we can continue to monitor the progress that's being made in different countries.

Outside of the United States, the experience is really limited primarily to Europe. Although there have been live births from both living as well as deceased donor recipients, not just in Europe and the US but also in Asia as well as in South America, specifically in Brazil.

Dr. Warner Huh: So, I mean, it's truly remarkable to me because I think it's one thing to say that you can actually achieve pregnancy with this technique, but then to actually say that we can actually have a healthy live birth is truly remarkable. And so I would just expect that likely in the future, that number will continue to climb as we gain more and more experience. So you commented on this earlier, and I think it's important for us to provide a balanced perspective for the listeners and the audiences. But could you comment on what are the known risks associated with this approach? And also where does the uterus come from? I think the listeners would be interested to know where the donors come from.

Paige Porrett, MD, PhD: So in terms of risks, there are many, and as I alluded to before, this is not a procedure that is without risk. I'm going to kind of bucket the risks, if you will, for the audience. I think it'll be easier to follow. So I think of risk in uterus transplantation really falling in two primary categories. There's risks that we attribute to the surgery itself. And then there are risks that we attribute to the immunosuppression.

I should first mention that the goal of uterus transplantation is obviously a healthy mom, as well as a healthy baby. And so not all of the risks that I'm going to talk about affect either mom or baby equally. With respect to surgical risks, the primary risks that we worry about is something called graft thrombosis. And what this means is that there's a loss of blood flow in through the vessels that go from the recipient into the donor uterus. And this is, I call it, the Achilles' heel of uterus transplantation right now, because we know that approximately one in three or 30% of the grafts in the world that have been transplanted have been lost to graft thrombosis.

In the big picture, potential mom does well. Often this graft thrombosis happens relatively early within a few weeks of transplant and we have to go in and surgically remove the graft when that happens, because without blood flow, the uterus will die. So it's a very unfortunate and serious complication, but women can and have recovered from this in the global experience.

We don't really understand a lot about why this happens. So it's hard to project a future where we're going to be able to diminish this risk. But to the point that you already made, I think that as we continue to build experience in the world with this, that we're going to understand the factors that contribute to that graft loss a lot better. I'm privileged to say that of the three uterus transplants that I performed at Penn. I have not yet lost any grafts, but I don't think that it's necessarily a surgeon-specific because virtually every center in the world that's done this has had a graft loss.

I want to move over to the other bucket of risk, which is really due to the immunosuppression. And while I mentioned earlier that we've gotten in the field of transplant much better with our immunosuppression practices over years, there are still quite a lot of risks associated with immunosuppression. These are necessary drugs because like any other transplant recipient, whether you've received a heart or a long or a kidney, the recipients of a uterus need to be on immunosuppression or they will reject and there have absolutely been cases of rejection reported around the world. Luckily to date, very few grafts have been lost to rejection because we can treat it effectively and we monitor for it. But that doesn't mean to say that it's not fairly significant risk.

The other facet of immunosuppression that's really important to talk about here and it influences how we select our candidates and also how we counsel our candidates and provide informed consent about uterus transplantation is the fact that we think the immunosuppression really increases the risk of pregnancy complications.

So no one, I think, on the planet would disagree with the fact that a uterus transplant pregnancy is quite high risk. This obviously has been and can be managed very well by expertise in high-risk obstetrics, such as occurs here at UAB with Dr. Casey and others around the world who are maternal-fetal medicine specialists. But the risk of preeclampsia and preterm birth, intrauterine growth restriction, et cetera, just as a subset of potential complications, we think is much higher in uterus transplant recipients, upwards of anywhere from three to five-fold compared to the general population. We're still determining the incidence or the prevalence of those particular complications, but there's no doubt in our minds right now that this is a high-risk pregnancy that needs to be very carefully supervised and managed.

So the average gestational age that a baby is born from a uterus transplant recipient in the world is about 35 weeks. So the reason that age is as young as it is, is because oftentimes mom is delivered because of one of the pregnancy complications that I discussed before.

So as you previously mentioned, it's really important to think about benefit as well as risk with uterus transplant. And because there are other options for many women to build their families when they're affected by uterine factor infertility, we have to counsel very carefully in this domain because we do not want to exaggerate the benefit and minimize the risks, especially when this is not a life-saving transplant and certainly uterus transplant, despite the benefits I talked about, is not for everyone. And not everyone who wants a uterus transplant or thinks they need a uterus transplant is going to be a candidate for one.

So the other options that we've mentioned here for family building may be obvious to this group, but I'll name them specifically just in the sake of completeness, and that's going to be adoption or using a gestational carrier. I would say the decision to either offer a uterus transplant or obtain a uterus transplant for a patient is a really complex and nuanced one. And I think that as, you know, we spend a tremendous amount of time counseling potential candidates about this, because it's not the world's easiest or fastest decision.

Dr. Warner Huh: Now, your response is actually the perfect segue for my next question. But you know, to expand on that, having been a part of the selection process for the early phases of this program. This is tough. I mean, it's really challenging because I don't want the listeners to believe that everyone is a candidate for this and that there's certain boxes that need to be checked off. And, you know, we're doing this in the best interest of obviously the patient and safety, but it's an incredibly complex process, which goes to my next question to you, Dr. Porrett, which is why do you think UAB is an ideal institution to host this kind of program?

Paige Porrett, MD, PhD: That's a really important question. I think the answer is couched in the complexity of this procedure. So, certainly, offering uterus transplant successfully is really a massive undertaking and a joint operation in a center between Departments of OB-GYN, as well as the transplant group. And that is amazing given the length of this experience with the transplant, the variety of procedures, the immunosuppression. It really takes, I call it, an all-hands-on-deck approach, where individuals from a variety of specialties, and I will not be exhaustive with my list here, but this requires expertise and reproductive endocrinology and infertility, for example, to generate and transfer the embryos; and GYN-oncologic surgery, so individuals who are very skilled with major pelvic operations; with transplantation and transplantation surgery experts such as myself who can actually perform the blood vessel connections that are required as part of the operation. And then certainly, last but not least is, as I mentioned, the expertise in maternal-fetal medicine, given the complexity of these high-risk pregnancies.

So I just named a few of the many members of our multidisciplinary team that are required to navigate a patient safely through this complex procedure. And so to answer your question again more directly, only an institution that can offer, I call it, strength at every one of these key positions is going to be successful. And that's one of the, I think, major barriers that has really prevented expansion of uterus transplantation to even more individuals, because I think there's clear need for This treatment, but one of the limitations in terms of how much we can provide access to patients is the fact that this is a very big lift for an individual academic medical center.

And so I would certainly remind the audience that, right now, it will be a while before you can go down the street to your local hospital and have this treatment. But it's really a privilege to be able to expand this type of care to the Southeast. And that's primarily the reason why I made the move from Philly to Birmingham, so that we can offer uterus transplant to patients who wouldn't have otherwise been able to travel as far as Dallas or Cleveland or Philadelphia.

Dr. Warner Huh: Well, you know, I think solid organ transplantation just in general is a fascinating field and is sort of the epitome of multidisciplinary care. But uterine transplantation is like taking it to the next level. And now, I think that's what's really great about this is that we have so many levels of expertise that are trying to take care of one individual patient, really two patients eventually. But it's just remarkable to me. One additional question, how does one learn more about this or inquire about whether, you know, an individual might be a candidate? I was wondering if you could comment on that.

Paige Porrett, MD, PhD: Yeah, that's a great question. So we have a website that's accessible. And so if our audience here would like to just simply Google uterus transplant and UAB, you'll find the website that will showcase how to get more information. We have a variety of individuals on our team who are essentially standing by on their email as well as by on the phone to answer any questions that anyone has, whether that's a potential patient or even a provider who would be interested in pursuing more information about this.

As you might imagine, there's a lot of information about uterus transplantation on the web, but as with all things with the internet, I caution against everything that you read there. And so, by all means seek us out and we're happy to talk more directly with you about this.

Dr. Warner Huh: And you expanded even further, I mean, the staff that you have in your program are just truly fantastic and top-notch. And I know that they go out of their way to communicate with candidates and, you know, obviously be very fair and transparent about whether they think that they're candidates or not. So, you know, kudos to you and your team for really bringing some great people to lead this.

Dr. Porrett, I don't know if you have any other closing comments or thoughts for us today.

Paige Porrett, MD, PhD: I have plenty to say beyond this brief conversation today, but it's been really a privilege to join you and talk about this exciting topic. As you know, it's a real passion of mine. And I think the only other message or ask I would make of the community listening to this is to help us on our journey. We have a lot of work to do, and it's not just to provide access to a new treatment and really to optimize and improve outcomes of this treatment, but really to make it accessible in the sense that UAB is being extremely generous to support financially uterus transplants and offering this to our community. But this is a finite commitment because uterus transplantation as yet has not been embraced by third-party payers. And so as I look to the future and the variety of challenges and work that we have to do in front of us, to me, that's my primary mission here is to make this as accessible as possible, but there are some significant financial hurdles we'll have to overcome.

So I appreciate the time today and your listeners, and really ask anybody to engage me if they have contributions to make in this field. We need all the help we can get.

Dr. Warner Huh: No, that's great. And I don't see this as being the only podcast that you and I are going to do. I'm hoping that there's a part two to this, where we can talk about the experience and outcomes, lessons learned and how do we take this to the next level.

So, again, I like to thank Dr Porrett for really a fascinating discussion and sharing her vision and commitment to building a top-notch uterine transplantation program at UAB.

As always, please rate this podcast. And we welcome any comments, particularly on topics that you all are interested in. For more information on uterine transplantation, again, as Dr. Porrett said, you can Google uterine transplantation and UAB and the site will pop right up, or you can go to UABMedicine.org to learn more about the other clinical services that we provide at the University of Alabama at Birmingham. So until next time, thank you. And I hope you all have a great day.