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In View: People in Transplantation

Mats Brännström, MD, PhD: Pioneer in Uterus Transplantation

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doi: 10.1097/TP.0000000000003153
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Uterus transplantation has not been on the map until the first baby was born to a recipient of a live donor uterus transplant. You have been the pioneer of the field and driving force of the first series of uterus transplants in Gothenburg, Sweden. What motivated you to move forward with this unique and novel treatment for patients with absolute uterine infertility?

MB: The concept of uterus transplantation was presented to me by a young woman with cervical cancer who was about to undergo a radical hysterectomy with pelvic lymph node dissection. This was in 1998 in Adelaide, Australia, where I did a fellowship in Gyne-oncology surgery. I had been totally surprised when she suggested to be transplanted with her mother’s uterus after her own hysterectomy to restore her fertility. I believe that my background in reproductive medicine, ovarian physiology, and as a trained Gynecological surgeon was the basis in motivating me to move the project of clinical uterus transplantation forward. A fertility expert may have thought that the surgery would be impossible, whereas a cancer surgeon may have only focused on curing the patient and less concerned with fertility. Now, with >10 babies born in Sweden from uterus transplant recipients, my biggest motivation to continue our successful project comes to me when seeing the joy we have brought to the parents and their families.

What have been preparatory steps on the way to a successful clinical implementation? If you had to do it all over again, would you have done anything differently?

MB: After completing my MD, I did a PhD in physiology, working in several animal models (mostly rodents) for many years. Thus, it was natural for me to start mouse uterus transplants to see if this could be done surgically with the success of delivering healthy mouse pups. My first PhD student on this uterus transplantation project, Randa Akouri, was able to master the complex microsurgery in mouse, and we presented, for the first time ever, babies born from a syngeneic uterus transplantation model in 2002. During more than a decade of research, my research team systematically studied all relevant aspects for the success of uterus transplantation, including surgery, immunosuppression, the diagnosis of rejection, the course of pregnancy, and the birth of babies. This was done first in mice and rats, then in large domestic species (sheep, pig), and finally in baboons. A significant contribution of our success has been our structured and systematic animal-based research, which has been instrumental in the introduction of uterus transplantation as a relatively safe and effective infertility treatment.

Frankly, I would not have done the research and clinical implementation so much differently if I would have had the chance to do it again. I was naive in the beginning and thought that we would be ready to move forward with a clinical trial within 2–3 years after our initial experimental success. Today, I am glad that we took our time and that the surgical team was able to train together for many years in several animal models before moving into the clinic.

The success of deceased donor uterus transplants lagged initially behind. Do you see an advantage of one approach over the other?

MB: I think that there will be a place for both deceased donors and live donors in uterus transplantation in the future. In Sweden, like in Prague and in some other centers around the world, we are now performing both deceased and live donor procedures within our clinical trials. The advantage of the live donor concept is that we have a lot more knowledge of the quality of the uterus to be transplanted compared to restricted evaluation options in the deceased donor situation. The drawback is, of course, that we expose a live donor to great surgical and postsurgical risks.

More recently, you have also conceptualized robotic donor hysterectomies. Do you see this approach dominating in the future?

MB: We have just completed a series of 8 robotic hysterectomies for live donor uterus transplants. Although we have not been able to reduce the time for surgery, we can see the advantage in surgical access, perioperative imaging of vessels, and in postoperative donor recovery. My prediction is that robotic surgery will be the favored surgical approach in live uterine donor surgery within 5 years, and during that time, robotic surgery will also be introduced as a mode of surgery in the recipient. When doing the procedure entirely robotically for both, donor and recipient, we may be able to reduce the hospital stay in a way that we see it today in patients undergoing robotic surgery for gynecological malignancies who leave the hospital after postoperative day 1.

You have been the leader of a fantastic team that includes expert gynecologists, transplant surgeons, and psychologists and many other specialists. What is your secret in motivating and managing this group?

MB: I think that teambuilding has been as important for the success of our initial uterus transplantation trial from 2013 as the large amount of research and training in complex uterus transplantation surgery in animals that we have performed. The entire team started to work together around 2005 in large animal models while engaging in ethical discussions and preparations for the human trial. It has been of critical importance that our team is all-inclusive, including not only physicians but also supportive staff, including operating room and anesthesia nurses.

Uterus Transplant Centers have opened around the world. You and your team have supported many teams during their first steps. Which centers have you backed thus far, and what has been your motivation to do so?

MB: We have been collaborating with >10 centers worldwide to gradually transfer the technology. The support from our side usually involves collaborative surgical training in the sheep uterus transplantation model, theoretical discussions, and the opportunity to visit our center observing our own surgeries. Robotic surgeries provide a great opportunity for a larger audience to follow procedures in detail. We also offer the opportunity to participate in the surgery when other centers start their own program. With that approach, we have supported the introduction of human uterus transplantation trials in centers in Europe, Asia, North- and Latin America.

Uterus Transplants have thus far mostly been supported by institutional funds and philanthropic support. How can we convince insurance carriers to support the procedure?

MB: I think that uterus transplantation already at this early stage has proven to be a highly effective infertility treatment. The take-home-baby rate in our initial Swedish trial was 85%, comparing favorably to efficiency rates achieved through in vitro fertilization only. Thus, absolute uterine factor infertility, which is the indication for uterus transplantation, should be regarded as any other cause of infertility (ie, male infertility, tubal factor infertility) and thereby be supported by any federal health system/insurance system that covers infertility treatment. It is likely that uterus transplantation will be fully covered within the Swedish public health insurance system soon, just like in vitro fertilization is today.

Uterus transplantation offers a unique collaborative effort. What do you see as critical research and clinical questions to move the field forward?

MB: There are many exciting open clinical and experimental research questions. Research areas that we and other groups are working on focus on imaging of uterine vasculature before donation, rejection mechanisms, optimal immunosuppression, specific assisted reproduction after uterus transplantation, such as techniques for embryo transfer and assessment of endometrial receptivity, as well as long-term consequences (medical, psychological, quality-of-life) after uterus donation or transplantation.

You have been the founder and inaugural President of the International Society of Uterus Transplantation. What do see as specific objectives and challenges of this society?

MB: The society aims to be an international and transparent platform for exchange of research and clinical data on uterus transplantation to advance the field in a safe and structured way. We have also formed an international uterus transplantation registry, much like the hand transplantation registry. Annual reports on activities will be published, and the registry is expected to become a key research tool for our field. The International Society of Uterus Transplantation has annual international meetings, and participants from 25 countries attended our meeting in Cleveland at the end of 2019.

You certainly have a time-occupying job. What are interests outside of your professional life?

MB: I do quite a bit of sailing and skiing, but at the moment, most of my nonprofessional time goes to helping out with the activities around my 2 youngest (11, 12 y) children being active in ice hockey, handball, and sailing.

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