How Surgical Research Gave Birth to a New Clinical Surgical Field: A Viewpoint from the Dallas Uterus Transplant Study

Abstract

Background: Uterus transplantation (UTx) has come of age in the 21st Century, building on the 20th Century developments in vascular anastomosis and effective immunosuppressive protocols enabling solid organ transplantation to become the life extending and life improving treatment option we know today. However, UTx has the goal of enabling reproduction, meaning that research focused on establishment of pregnancy and healthy live birth in addition to surgical technique and immunosuppression. Summary: The Dallas UtErus Transplant Study (DUETS), established at Baylor University Medical Center in 2015 is one of four UTx programs in the United States, and holds the distinction of being home not only to the first U.S. live birth, but also the highest volume UTx program worldwide, with 23 uterus transplants performed to date, resulting in 15 live births. Innovations pioneered at our center span all aspects of the Utx process, seeking to improve success in terms of achieving pregnancy and live birth, while also minimizing the burden on donors and recipients. The have included: 1) a deceased donor hysterectomy approach that allows the uterus to be procured prior to cross-clamp; 2) proof of concept with use of only superior uterine veins after procuring both the superior and inferior uterine veins during the donor surgery, enabling the choice of the best option in terms of size and location for outflow, while also preserving ovary viability in living donors; 3) contribution to robot assisted technique/minimal invasive technique with vaginal extraction of the uterus graft for living donor surgeries, shortening donor recovery times; 4) developing a robot-assisted technique for graft hysterectomies, improving recovery times for recipients at the end of their UTx journey; 5) refining immunosuppression protocols to enable embryo transfer 3 months after induction therapy, increasing recipients’ chances for achieving up to two live births during the 5 years post-transplant the UTx protocol specifies; and 6) building on our clinical trial experience to now offer UTx in the U.S. outside of a clinical study. Key Messages: Our center along with others throughout the world have demonstrated that UTx can be reproducible, result in live births from both living and deceased donors, and safely introduced as a clinical option. Due to the complexity of UTx as well as the need for long-term multidisciplinary care, centers implementing UTx should have an established abdominal transplant program, gynecologic surgery program, high-risk obstetric and neonatal care, and institutional support and oversight, and should partner with established UTx programs for protocol development and operative proctoring.

Living-Donor Uterus Transplantation: A Clinical Review

“…However, an open procedure has a higher incidence of postoperative surgical complications and graft failure [27]. A total of 59 living-donor hysterectomies have been reported in the literature (Table 1), including 35 performed with a laparotomic approach, 20 with a robotic approach and 4 with a laparoscopic approach [6,15,16,20,22,[44][45][46][47][48][49][50][51][52][53][54][55][56][57]. The mean donor age was 45.6 ± 9.1 years, and 22 were unrelated with the recipients, 34 were emotionally related (27 mothers, 5 sisters, 2 mother's sisters), while in three cases, the relationship was not reported.…”

“…The mean donor age was 45.6 ± 9.1 years, and 22 were unrelated with the recipients, 34 were emotionally related (27 mothers, 5 sisters, 2 mother's sisters), while in three cases, the relationship was not reported. The mean recipient age was 28.8 ± 4.5 years, and the MRKH syndrome was the most common indication for uterus transplant (52 patients), while 2 patients required UTx after hysterectomy for myomectomy and 1 patient following hysterectomy for cervical cancer [6,15,16,20,22,[44][45][46][47][48][49][50][51][52][53][54][55][56][57]. With the open technique, a subumbilical midline incision is used while five working ports are used in robotics.…”

Uterine Transplantation and Fertility Preservation: A Hopeful Horizon for Cancer Survivors

“…Advances in surgical techniques and technology have contributed to developing and improving UTx procedures. For example, robotic-assisted surgery has been introduced to reduce operative time for donors and recipients [ 21 , 32 ]. Additionally, studies in cynomolgus macaques have demonstrated that using ovarian veins reduced the operative time for living donors [ 33 ].…”

“…Furthermore, advances in immunosuppressive therapy have improved the success rates of UTx procedures, reducing the risk of transplant rejection. The use of IVF has also been introduced to achieve pregnancy after UTx [ 32 ]. Overall, advances in surgical techniques and technology have contributed to the development and improvement of UTx procedures, reducing the risks and complications associated with the surgery and improving the success rates of the procedure.…”

Awareness and Interest in Uterus Transplantation over Time: Analysis of Those Seeking Surgical Correction for Uterine-Factor Infertility in the US

“…As UTx transitions from experimental to clinical practice [ 9 ], it is important to assess how well the population ultimately interested in undergoing the procedure matches the population for which safety and effectiveness data have been established. Both technical and ethical considerations for UTx may differ by recipient characteristics, such as the cause of infertility and parity [ 6 ].…”