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Bringing to Life New Options for Motherhood

kate o'neill paige porrett until trial
As they lead the first clinical trial for uterus transplantation in the Northeast, co-principal investigators Kate O’Neill, MD, MTR, (left) and Paige Porrett, MD, PhD, have combined their complementary expertise and their own “journey to motherhood” experiences.

In addition to offering an alternative to women who are unable to give birth due to an abnormal, damaged, or missing uterus, the UNTIL trial also aims to explore the biological and immunological mysteries of pregnancy. Learn more about the research potential in the new issue of Penn Medicine Magazine.

Morning sickness, all-over aches, constant bathroom breaks, “mom-nesia” caused by “pregnancy brain” — for many mothers-to-be, these and other pregnancy-related challenges become the bane of their existence for nine months. However, for approximately 6 million women in the United States struggling with infertility – including the nearly 50,000 women with irreversible uterine factor infertility (UFI) due to a missing or non-functioning uterus – these temporary annoyances would be more than welcome if they accompanied a chance at parenthood.

While fertility treatments like in vitro fertilization (IVF) provide hope for some women, the choices for those with UFI have long been limited to only adoption or gestational surrogacy. That’s where the experimental realm of uterus transplantation comes in. Since the first live birth of a child following a uterus transplant occurred in 2014 at Sahlgrenska University Hospital in Gothenburg, Sweden, more than a dozen children have been born to women with uterus transplants across the globe, including two in the United States. Penn Medicine hopes to continue propelling advancements in this groundbreaking field through the Uterus Transplantation for Uterine Factor Infertility (UNTIL) trial, one of the first of its kind in the nation.

Kate O’Neill, MD, MTR, an assistant professor of Obstetrics and Gynecology at the Hospital of the University of Pennsylvania (HUP), and co-principal investigator on the UNTIL trial, discusses the path that led her to develop the trial and the significance of expanding the options that allow women to take control of their reproductive choices and bring their dreams of parenthood into reality.

kate o'neill head shot
“I tell all my patients, ‘It might not be what you planned originally, but if the goal is to help you build a family, we can do that.’”

Q: Uterus transplantation seems to fall squarely where your personal and professional interests converge. What shaped your passion for this complex, challenging work?

A: I had always wanted to start a family, but I knew balancing a pregnancy with the demands of medical school and a residency would be complicated, so my husband and I decided to hold off until my fellowship in Reproductive Endocrinology and Infertility began. Six months passed, and we still hadn’t conceived, and I started to worry. I was acutely aware of the statistics related to infertility, so I decided to investigate. I was diagnosed with endometriosis [a disorder in which tissue that normally lines the inside of the uterus – the endometrium – is displaced and grows outside of the uterus], which meant I’d still be able to conceive, but we’d have to adjust our plans through IVF.

During my first year of fellowship, I was learning the ins and outs of IVF from the physician side while also going through IVF as a patient. My first cycle ended with a miscarriage, but after a second round, I became pregnant with my now four-year old son. When considering whether to go through the process again, I spontaneously became pregnant with my now two-year old son, which can happen in fertile patients post-IVF.

The whole experience was kind of surreal — I was getting monitored in the morning, then monitoring my patients in the afternoon. I felt like I’d always known how to reassure patients struggling with infertility, but now I was in the same boat, and it came with a shift in perspective. I experienced firsthand many of the difficulties I help my patients work through, including a miscarriage, and it was strange to be going through it while also counseling patients. I think in a lot of ways it helped me become a more empathetic doctor. It definitely gave me a unique insight into the patient experience. I understand the lengths patients are willing to go to, and I understand how having to change your expectations and plans feels.  I tell all my patients, “It might not be what you planned originally, but if the goal is to help you build a family, we can do that.”

Q: And through all of this, you were also trying to figure out where your research would go?

A: Right. I’m a physician-scientist, so in addition to my clinical work, I’m interested in furthering reproductive medicine research. There’s so much we still don’t know about early pregnancy and how an embryo implants into the uterus. I have long been particularly fascinated by the endometrium, the layer of the uterus in which an embryo attaches. When I was a second year fellow, I heard about the first successful birth following a uterus transplant in Sweden. It sounded like science fiction, and I could only imagine how it could completely change the lives of patients with UFI in the now near future. I thought it was incredible, and I was so invested in the potential.

From a research perspective, it was a game-changer that could help us understand the mysteries of pregnancy that haven’t been answered in animal models, and from a clinical perspective, it could change so many lives. My family and colleagues encouraged me to start investigating whether a similar trial could be formed at Penn.

Q: The UNTIL trial has been described as a multidisciplinary effort involving dozens of specialists. Can you talk more about the different clinicians and researchers who are involved in this work?

A: The trial is a joint effort between Penn Medicine’s department of Obstetrics & Gynecology and the Penn Transplant Institute. My co-principal investigators are Paige Porrett, MD, PhD, [an assistant professor of Transplant Surgery], Eileen Wang, MD, [an associate professor of Obstetrics and Gynecology and Maternal Fetal Medicine], and Nawar Latif, MD, MPH, [an instructor of Obstetrics and Gynecology], but the team is comprised of over 50 doctors, surgeons, nurses, psychologists, social workers, bioethicists, and ancillary staff. We’re also sharing knowledge with other institutions across the country and the world, and especially with the team at Baylor University Medical Center.

In medicine, it’s easy for us to operate in our own silos without knowing what’s happening elsewhere, so this has been a hugely valuable learning experience. There are so many components involved in a complex trial like this. We need to follow the same patients for years and guide them through screenings, biopsies, surgeries, and hopefully births, and it’s only possible because of the determination and passion of everyone involved and their recognition of how important this is for women and families. We’re not going to be first in this space, but we can strive to be the best and do the best we can for our patients.

Q: Since the UNTIL trial was announced in November 2017, you’ve received over 100 applications. What will the process be like for those who are chosen as candidates?

A: After candidates have been screened, they’ll undergo IVF and have their eggs harvested and fertilized to create embryos. Then they’ll be evaluated as transplant recipients and will wait for an available uterus. We’re currently using uteruses from both living and deceased donors [who have successfully delivered children]. This is an amazing opportunity for women who have completed their childbearing to help another woman reach her goals, and we have been incredibly moved by the number of individuals who have reached out to be living donors already.

After the transplant surgery, we’ll monitor the patients for six months or so as they heal, and once they’ve started menstruating, we’ll implant one embryo at a time – and then we hope and wait! If they become pregnant, their pregnancies will be considered “high risk,” so they’ll be monitored closely throughout the process. The babies will be delivered via cesarean section, and the uterus will be removed after they’ve had one or two children so they don’t have to continue taking immunosuppresssants.

The sheer volume of interest has been really challenging because infertility has been a lifelong struggle for so many of these women. You want to pick them all, but we’re hoping that by starting with women who meet the stringent criteria we’ve set, we can maximize our success and then widen the pool in the future. Once we can show that uterus transplantation is a viable option for women with UFI, it’s a whole new ballgame for women’s health.

Q: Some have called uterus transplantation unnecessarily risky or costly when compared to options like adoption or gestational surrogacy. How do you respond to these concerns?

A: Adoption and surrogacy are great options for growing a family, and it’s important that they’re accessible, but saying to someone, “Oh, you can just do this instead,” isn’t actually helpful. It doesn’t take into consideration the complex range of emotions involved. Aside from the fact that for many patients, adoption and surrogacy aren’t options – neither process is easy or available to everyone – many of my patients want to experience their own pregnancy. So, is coming up with new ways to fulfill that desire a “waste of resources,” or is it an opportunity to knock down barriers and provide women new hope to conceive, carry, and deliver their own children?

I think the polarizing reactions uterus transplantation can receive often come because people don’t know how they’d feel in the same situation. But my goal is to offer these transplants as another fertility and family-building option. Adoption is great for some families. Surrogacy might be best for others. But no option is perfect for every single woman, and we need to trust that they can make the best decisions for their own lives and not judge them based on which option they choose.

Q: And what about the price tag? There has been speculation that insurers would not be willing to cover the costs associated with a uterus transplant since it’s not a “medically necessary” procedure.

A: That’s definitely fair, but IVF, surrogacy, and adoption can also cost tens or even hundreds of thousands of dollars. Importantly, at this point we cannot estimate what a uterus transplant will cost once the procedure has been perfected; that is why these trials are so important. Regardless, this is all about adding another option. Uterus transplantation may be controversial now, but there are so many research questions that it can answer, and as it becomes a more standardized procedure, we hope that we’ll be able to make it more widely available to the women who want to pursue it.

Q: A multidisciplinary team working to advance women’s health care and family planning options, three female co-principal investigators leading the charge, and female donors providing a chance at pregnancy for other women… This trial definitely gives me “women empowering women” vibes.

A: Yes! Reproductive medicine historically hasn’t received the level of attention it deserves. In medicine, we sometimes have a difficult time figuring out how to prioritize research and how much support should be given to certain topics, and it doesn’t help when there are still debates over the merits of birth control being covered by insurance and why men should still pay for maternity care even if they “don’t use it.”

We’re only at the beginning of this trial, but I’ve already come to realize that women are going to push this conversation forward, no matter how controversial it may initially seem. We generally don’t think of medicine as “uncomfortable” in any of realm, so why dismiss women’s voices when it comes to this? Especially when it comes to UFI — that patient population has been almost completely neglected by our repertoire of fertility treatments. In many ways, this trial is built on the idea that women can decide what to do with their bodies themselves. If we can expand their menu of options, that’s what we’re going to do.

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