Aug 19, 2019, 16:28 PM by Jen Taylor

Andreas Tzakis, MD
Cleveland Clinic

ASTS, in collaboration with AST, the American Society for Reproductive Medicine (ASRM), and the American Society for Reconstructive Transplantation (ASRT), is organizing a workshop on face, hand, and uterus transplants to take place at the Uniformed Services University on November 8, 2019. Invited are leaders of private and public funding and regulatory organizations. Presentations will be made by the leading active programs in the United States.

This workshop is a continuum of a symposium convened in Baltimore in 2017. It aims to update our guests on the current state of VCA. Indeed, significant progress has been made since then toward:

• Establishing the indications
• Standardizing the procedures
• Quantifying and presenting the results using common functional dashboards
• Accumulating more data on cost benefit analysis
• Collaborating with third party payers to develop reimbursement plans

VCAs differ in regard to the clinical problems they address, the organs transplanted, and the qualifications and background of the caregivers. Face and hand transplants have a longer history and slow buildup of the experience. Possible candidates nationwide are numbered in the hundreds. Uterus is the most recent. Experience is building more rapidly, and possible candidates are numbered in the thousands.

Although spotty, coverage of the medical cost has been provided for exceptional cases. These include military service-related injuries as well as with Local Coverage Determinations (LCDs). In general, reimbursement has been an extremely difficult problem.

One serious obstacle has been the small number of clinical cases performed. Historically, data is sparse and not standardized. Collaboration among centers is highly desirable.

Abdominal wall transplants, although VCAs, will not be discussed in this workshop because they have been packaged with intestinal or multivisceral transplants.

The latest addition, uterus transplants, are also very different. They have been segregated from VCAs and are now included with the other solid organs.

Indeed, the uterus is a solid organ rather than a composite tissue graft. Whereas transplant surgeons play a consulting role in VCAs, in uterus transplants transplant surgeons and gynecologists play a vital role in the development and performance of these procedures.

The active clinical programs (Baylor Hospital, University of Pennsylvania, and Cleveland Clinic) already share clinical information through regular meetings and conference calls. They have agreed to form a consortium. Sharing will include a database and tissue repositories in order to expedite learning and research as well as training of new staff.

Pursuing Current Procedural Terminology (CPT) codes for VCAs to enable tracking has been a priority but is a very elaborate process. It has now been reinvigorated thanks to the personal interest of ASTS President Dr. Lloyd Ratner.

We hope that this workshop will bring face, hand, and uterus transplants closer to acceptance in clinical practice.

Uterus Transplant: A personal perspective on the occasion of the International State of the Art International meeting in Cleveland (September 6-7, 2019)

The 2^nd Congress of the International Society of Uterus Transplantation is planned to take place in Cleveland on September 6^th and 7^th, 2019. More than 100 participants are expected to attend. More than 50 uterus transplants and more than 15 babies born as a result worldwide. Lively and informative discussions are eagerly expected.

My introduction to uterus transplants started when I was a junior staff surgeon at the University of Pittsburgh. A novelist approached me at the direction of Dr T. E. Starzl; his heroine, a renowned transplant surgeon, had to perform a uterus transplant. He did not disclose the plot. The question was: how would she do it?

I went to my anatomy books and conceived the operation for him. The book was published successfully. I was included in the credits and did not give it a second thought for several years.

Then, a young woman in her 20’s presented to me at the University of Miami in need of a multivisceral transplant, a transplant which would include all abdominal organs. She had a prior hysterectomy and no children. Would it not be nice to restore everything back to normal?

A seminal event had just occurred in my own life and made me sensitive: my wife gave birth to our daughter… I will never forget the day our daughter was born. It was a pivotal event, the happiest day of my life, and had an everlasting effect!

Indeed, I don’t know anything more valuable to my wife and I than our daughter. The thought of adding a uterus to my patient’s multivisceral transplant was insistent. Prudence prevailed and I abandoned the thought for this particular patient. It would be too much risk for an unknown procedure. But what about doing a uterus transplant for patients who could not have children because of lack of a functioning uterus?

I had to study it.

Having resolved the anatomical considerations, at least in theory, I had to study the immunology of the uterus, particularly because of its role in the tolerance of the offspring by the mother.

There were 3 volunteers on the team, eager to participate in the studies: Werviston (Tom) DeFaria, Akin Tekin, and Takis Tryfonopoulos, all surgeons with passion for research. We obtained mini swines, which Dr. David Sachs was kind enough to provide. We designed a heterotopic variant of the operation in order to study the uterus, rejection, its treatment, and the longevity of the graft. The feasibility, at least in animals, was demonstrated.

By good fortune, while working on the mini swine model, I received an Honorary Degree from the University of Gothenburg in Sweden, home of my good friend Michael Olausson and also Mats Brannstrom, the Chairman of Gynecology who was working diligently with his team, including Michael, on uterus transplants. They were ahead of us!

It was the beginning of a collaboration that took us to Nairobi, Kenya, and Homestead, Florida, for experiments on primates and then to Gothenburg for the first clinical trial at the Sahlgrenska University Hospital.

This was a great inspiration, particularly because at that time I was relocating to the Cleveland Clinic, an institution with an excellent record in transplant research and an exceptionally good gynecological program led by Dr. Tommaso Falcone.

Dr. Falcone expressed some skepticism in the beginning. It took a visit to Gothenburg and meeting the recipients of the transplants to persuade him. It was clear that this was an operation that these women really wanted in their quest to have their own children. Once persuaded, Falcone and his team were perfect partners.

Contrary to most other programs, our preference for these transplants has been that they should be performed with uteri from deceased donors in order to avoid any risk to a living donor.

We performed our first uterus transplant on February 24, 2016. It was the first attempt in the U.S., which unfortunately failed due to a fungal infection which caused a rupture of one of the arterial anastomoses.

As a result, there was a very elaborate review of our trial.

In the meantime, the excellent team at Baylor Hospital in Dallas, Texas, led by Drs. Testa and Klintmalm, with the assistance of Drs. Michael Olausson and Liza Johannesson of the Gothenburg team, performed the first successful uterus transplants in the U.S., which resulted in the births of 2 healthy babies. These were the first babies in the U.S. born from transplanted uteruses.

We resumed our program as soon as all necessary precautions were taken to avoid another infection. We have now performed an additional 6 transplants, 5 of them successful. One of them resulted in the delivery of a beautiful, healthy baby this July.

That baby was the first born from a deceased donor in the U.S. and second in the world, confirming the efficacy of this approach.

Uterus transplantation is evolving rapidly, even in today’s heavily regulated environment. We hope it will be a valuable option to the many women who cannot have children simply because one non-vital part of their body is missing.