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Uterine Transplants in Practice: Donor Selection, Procedure Technique & Immunosuppression

Author Taylor Spurgeon-Hess covers Uterine Transplants in Practice: Donor Selection, Procedure Technique & Immunosuppression on BackTable OBGYN

Taylor Spurgeon-Hess • May 24, 2023 • 57 hits

Uterine transplantation, a groundbreaking procedure offering hope to individuals facing uterine factor infertility, presents its own set of unique complexities. Essential to the process is the careful selection of donors, a task that requires balancing medical suitability with ethical and logistical considerations. The dynamic landscape of the procedure is underscored by evolving surgical techniques, particularly the importance of securing robust blood flow to the transplanted uterus. A notable feature of uterine transplantation is its "ephemeral" nature, requiring a shorter duration of immunosuppression therapy than other organ transplants. This introduces a different set of challenges and considerations, highlighting the crucial role of continued research and careful patient management in improving outcomes in this rapidly evolving field.

This article features excerpts from the BackTable OBGYN Podcast. We’ve provided the highlight reel in this article, and you can listen to the full podcast below.

The BackTable OBGYN Brief

• The choice of uterine donor, whether living or deceased, requires careful consideration of medical suitability, ethical parameters, and logistical issues. Diverse models exist, each with its unique advantages and drawbacks.

• The success of a uterine transplant largely depends on establishing adequate blood flow to the graft. Surgical techniques typically involve connecting uterine arteries and veins to the recipient's external iliac vessels. In the face of complications, innovative strategies such as using a Y graft may prove beneficial.

• Recognizing the anatomical and functional importance of utero-ovarian veins, now referred to as superior uterine veins, is crucial. These veins can offer alternative outflow routes during challenging procedures.

• Uterine transplants are unique as they are designed to be temporary, often removed after one or two successful pregnancies. This necessitates a different approach to immunosuppression therapy, which is typically only required for a limited period.

• Immunosuppression, while necessary, carries potential risks and costs. The typical induction therapy involves MMF, tacrolimus, and steroids, with potential later transition to azathioprine. Close monitoring and medication adjustments are essential.

• Selecting patients without significant comorbidities can help mitigate potential complications and improve the chances of successful pregnancies post-transplant.

A team preparing for a uterine transplant

Table of Contents

(1) The Complexities of Uterine Transplant Donor Selection

(2) Uterine Transplant Procedure Techniques: Securing Blood Flow

(3) Immunosuppression Considerations in Uterine Transplant: Graft Survival & Pregnancy Viability

The Complexities of Uterine Transplant Donor Selection

The selection of donors for uterine transplants carries its own set of complexities, striking a delicate balance between medical, ethical, and logistical considerations. Historically, European trials often relied on directed donors, typically a family member. This approach, however, introduces an emotional burden and potential guilt, particularly when complications occur. The use of non-directed donors, as practiced in Dallas, offers an alternative solution, with many multiparous women showing significant interest in becoming donors out of altruism. Meanwhile, the Cleveland Clinic exclusively employs a deceased donor model, mitigating the ethical concerns around subjecting living donors to the risk of complications. Yet, there are pros and cons to both approaches: deceased donors allow for wider tissue excision and less risk to living individuals, but the surgery is less predictable and lacks comprehensive donor medical history. As the field matures, there's an increasing push towards minimally invasive surgeries and faster operation times, opening up the possibilities for hybrid donor models in future trials.

[Dr. Mark Hoffman]
There was a massive interest in being a donor?

[Dr. Elliott Richards]
Being a donor. Correct.

[Dr. Mark Hoffman]
Wow.

[Dr. Amy Park]
Is it just because hysterectomy, they were going to get their uterus out anyway or they just--

[Dr. Mark Hoffman]
I would think you wouldn't want a uterus that somebody else wants out though, right? If someone's got big fibroids or heavy periods or adenomyosis, these have to be like great shape uteruses?

[Dr. Elliott Richards]
These are multiparous women who felt that their childbearing was done and they wanted to give that gift to another woman, and I think that was something that-- I mean, truly acting from--

[Dr. Amy Park]
Altruism?

[Dr. Elliott Richards]
Yes. Now, at the Cleveland Clinic, we use exclusively a deceased donor model. We decided the ethical complexity of subjecting a living donor to the risk of this procedure because procuring a uterus is not the same even as a radical hysterectomy. In every major series, there's been complications to living donors. We decided early on to pursue a exclusively deceased donor. I do think now that the science as well, that so much more is known, that there's a high likelihood that we will consider having a hybrid approach for our next trial. That was our rationale for being deceased donor only. There's certainly pros and cons of both, and I'm happy to talk about the relative merits because it's not as black-and-white issue there either.

[Dr. Mark Hoffman]
There's a great video, I think it's from your fertility sterility article on YouTube about your program and with the video of the organ procurement of the hysterectomy. It's a fascinating video. It really is an incredible video to show. It's not a simple hysterectomy what you guys are doing.

[Dr. Amy Park]
What are the pros and cons since you alluded to it? I am assuming that tissue is better with a living donor versus the deceased. Deceased, you can get more radical, I guess to the parametrium.

[Dr. Elliott Richards]
First of all, with a deceased donor, you can take the internal iliacs with the uterine artery vein, and so you're just getting much more wide excision than you can with a living donor obviously. There is potentially longer cold ischemia time with the deceased donor, especially if you're procuring. We've altered our radius a couple times in terms of procurement radius, how far out from our institution that we'll go. A further-out procurement means that you have longer cold ischemia time for that organ.

Although our data, especially as we've shared and compared with the Baylor group, we don't see any difference in outcomes. These are still small sample size number. I'd say the biggest disadvantage of using a deceased donor-- Well, there's three actually. One is that we really don't get as much history. We're relying on secondhand information in the medical record. Whether it's a living donor, you can get just such extensive information from that individual. The second thing is that there's really something to be said about a planned surgery. You can put on a date. You can assemble all the teams. Doing a uterus transplantation is an incredibly complex endeavor. Really, you need to have coordination between transplant teams. You have a procurement team, of course, and then you have the transplant team itself. The vaginal anastomosis and the vessel anastomosis, these are done by different teams. If you can do with the living donor and you can set everything up ahead of time, that has great advantages over a deceased donor where the call is always in the middle of the night and it's suddenly, everyone's canceling all their clinic. Transplant surgeons are used to that. Gynecologists, that's not really how we roll. The challenge is there.

[Dr. Mark Hoffman]
Well, you had mentioned on the video, one of the benefits of the deceased donor was that you could take more vagina because you're trying to take a lot less tissue than the living donor, right?

[Dr. Elliott Richards]
Yes. Number one is that you're not putting a living donor at risk. It's not just vagina. Typically, I think it's an interesting question for transgender transplants because now, you're suddenly making a neo vagina and attaching this uterus. Having potentially a bigger donor vagina to add may be an advantage, but really, it's the increased vessels and also time of procurement.

Our first deceased donor procurement, our portion, obviously, it's combined with other transplant groups and they're harvesting lifesaving organs first, and we're doing our first dissection at the beginning and then they harvest and then we're right at the end because we're, of course, doing a vaginotomy and there's a concern for those lifesaving organs potentially seeding bacteria and whatnot.

The uterine veins is what's technically most challenging and why a uterus procurement is not the same as a radical hysterectomy because these uterine veins, they're anomalous, they're different. Oftentimes, they're wrapping around the ureter and it's critical for venous outflow. It's really those veins that are so challenging. When you have a deceased donor that you don't need to preserve the ureter, you can move a lot quicker and faster. The living donor groups have really brought the operative time down. There's been a big push and focus on robotic and minimally evasive surgery. That's why I think that the field is much more mature in terms of using living donors. In the beginning, they were doing 12 plus hours surgeries to procure this uterus, so by no means a radical hysterectomy, much more complex.

Listen to the Full Podcast

Uterine Transplant with Dr. Elliott Richards on the BackTable OBGYN Podcast)
Ep 20 Uterine Transplant with Dr. Elliott Richards
00:00 / 01:04

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Uterine Transplant Procedure Techniques: Securing Blood Flow

The provision of adequate blood supply is crucial for the success of uterine transplants. This typically involves connecting the uterine arteries to the external iliac arteries, though variations involving the internal iliacs are also possible. The primary challenge lies in ensuring appropriate venous outflow, typically achieved by connecting the uterine vein to the external iliac vein. In cases of complications such as intraoperative venous outflow clotting, innovative solutions like the use of a Y graft from the same deceased donor have proven beneficial. The collaborative efforts of the United States Uterus Transplant Consortium have led to a terminology shift, emphasizing the anatomical and functional significance of the utero-ovarian veins, now referred to as superior uterine veins. These veins could offer an alternative outflow route in challenging cases. However, it is imperative to avoid ethically unacceptable practices such as oophorectomy on living donors for this purpose.

[Dr. Mark Hoffman]
Once you've got a uterus out, I imagine putting it back in looks a little different. What's the major blood supply that you're using on the recipient to attach the uterus to? I guess you've got some collateral blood supply with the utero-ovarians as well. Are you using all four primary blood supplies for the uterus, and where are you attaching them?

[Dr. Elliott Richards]
Inflow is typically just hooking up the uterine arteries to the external iliacs.

[Dr. Mark Hoffman]
External. Okay.

[Dr. Elliott Richards]
There's some variations that have been shown and proposed and I've seen with the internal iliacs before. In terms of outflow, because that really is the biggest challenge, it's typically the uterine vein to the external iliac vein. As you say, the utero variant has been used as an alternate outflow. Our group has actually published a paper using a Y graft. We actually had a intraoperative, the venous outflow completely clotted off. We thought we were done.

We were closing up and just said, oh, let's do Doppler studies, and then it completely clotted off. Our team, brilliant, used a graft of vessel from that same deceased donor and patched in to the external iliac through this patch. The utero-ovarian effect, the United States Uterus Transplant Consortium, that's this group that I mentioned that's highly collaborative. We published a paper really arguing that we should change terminology somewhat. We've argued for the change in nomenclature for the inferior uterine veins and arteries and the superior uterine veins and arteries to really emphasize that this utero-ovarian calling it the superior uterine veins because they, of course, anastomose with that plexus along the lateral edge of the uterus. A lot of groups will certainly, if they have difficulty, they're not able to get a good outflow or good specimen, inferiorly, they'll use the superior veins for outflow.

There's some then ethically problematic cases in China and India where they did oophorectomy on a living donor to get access to that outflow through the ovaries. That's just simply not acceptable for a living donor. It's really just that short branch that can be used on the superior uterine veins.

Immunosuppression Considerations in Uterine Transplant: Graft Survival & Pregnancy Viability

The management of graft versus host response in uterine transplant patients is a multifaceted endeavor that requires the unique application of established knowledge from other transplantation fields, such as liver and kidney transplantation. This process becomes even more complex considering the distinct nature of the uterus as the first recognized "ephemeral transplant", that is, a transplant intended to be removed at a later stage. In this context, immunosuppression therapy is not lifelong but rather temporary, typically lasting for about one to two years. Initial induction therapy usually involves the use of mycophenolate mofetil (MMF), tacrolimus, and corticosteroids, with routine surveillance and medication adjustments, and potential later transition to azathioprine.

Despite the inherent risks and costs associated with immunosuppression, the temporary duration of uterine transplantation permits an encouraging prognosis. Even in cases where adverse effects, like renal impairment, are observed, post-transplant recovery is generally promising. The initial patient selection for uterine transplant trials is crucial and involves focusing on individuals without significant comorbidities, which helps to decrease possible complications and increase the chances of successful pregnancies post-transplant.

[Dr. Mark Hoffman]
Once it's in place, we've got two pretty big things to think about, one of which is this is a donor organ, a graft, so patient's immune system has to be managed in a way that will allow that graft not just surgically but also immunologically to be able to survive. You're putting little extra added challenge of having a pregnancy. Obstetricians deal with complicated pregnancies in regular uterus all day. How do you manage the graft versus host, and how do you do that in a way that is safe for pregnancy?

[Dr. Elliott Richards]
We had the advantage of liver-kidney transplantation has been around now for several decades, and those transplant recipients get pregnant. We had a lot of prior data to go on. The advantage that we have with uterus transplant, of course, is that most liver kidney recipients who are pregnant oftentimes have comorbidities that are, again, selected patient population that we're doing for these initial uterus transplant trials are selected because of their lack of comorbidities.

A couple things on that point, another thing that differentiates uterus transplant from other organs is that it's truly the first and only ephemeral transplant, a term coined by Dr. Tzakis at Cleveland Clinic, meaning that this is an organ that's put in with the expectation that it's removed later. This isn't lifelong immunosuppression, it's potentially just a year or two of immunosuppression. Then that immunosuppression is stopped. Patients who undergo uterus transplantation, first, there's an initial induction therapy. Oftentimes, that's done with MMF, tacrolimus, steroids, and then often switched to azathioprine. Typically, our patients are on just tacrolimus and a low dose of prednisone with levels checked essentially weekly for their tacrolimus levels. We've been monitoring kidney function, and in fact, there's a study hopefully coming out soon from the consortium where we've, again, pooled our data to look at any evidence of renal damage in these patients. Again, that advantage is is that once they've completed their childbearing, which is typically one or sometimes two live-born children, the graft is removed. Even in those patients where we see increase in their creatinine, we see a recovery.

[Dr. Mark Hoffman]
That's incredible.

[Dr. Elliott Richards]
Absolutely, immunosuppression is not something to be taken lightly. It definitely has its own risks and particularly costs. That's actually where a big portion of the cost of uterus transplant actually comes in because they're not cheap medications.

Podcast Contributors

Dr. Elliott Richards discusses Uterine Transplant on the BackTable 20 Podcast

Dr. Elliott Richards

Dr. Elliot Richards is the Director of Research in the Department of Reproductive Endocrinology and Infertility at the Cleveland Clinic.

Dr. Amy Park discusses Uterine Transplant on the BackTable 20 Podcast

Dr. Amy Park

Dr. Amy Park is the Section Head of Female Pelvic Medicine & Reconstructive Surgery at the Cleveland Clinic, and a co-host of the BackTable OBGYN Podcast.

Dr. Mark Hoffman discusses Uterine Transplant on the BackTable 20 Podcast

Dr. Mark Hoffman

Dr. Mark Hoffman is a minimally invasive gynecologic surgeon at the University of Kentucky.

Cite This Podcast

BackTable, LLC (Producer). (2023, April 6). Ep. 20 – Uterine Transplant [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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