The Ethical Evolution of Uterus Transplantation From Concept to Clinical Procedure

Graca, Briget da; Johannesson, Liza; Testa, Giuliano; Wall, Anji

doi:10.1097/grf.0000000000000687

Cited by 3 publications

(3 citation statements)

References 67 publications

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“…The potential for harm to living uterus donors-who stand to receive no physical benefit from the donation surgery-has raised substantial debate regarding the ethics of UTx. 3 Reports place the risk of complications for living donor hysterectomy between those of simple and radical hysterectomy, 21,22 with the development of minimally invasive and robotic-assisted approaches reducing some of this initial burden on donors. 23,24 Although it has been recognized that living donors may experience some psychological or emotional benefit through their altruism, 24 or incur psychological harm should the graft fail or the postdonation course deviate from expectations, 22 little is known about effects in the first year after donation.…”

Section: Discussionmentioning

confidence: 99%

“…1 The majority of uterus transplants performed have used living donors. 1,2 Although substantial data are available regarding short-term physical risks to donors, 3 much less is known about psychological risks/ benefits after donation. Some early clinical trials 4 relied exclusively on directed donations from relatives or friends, meaning evidence is particularly lacking for nondirected donors.…”

Section: Introductionmentioning

confidence: 99%

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Psychosocial Outcomes in Nondirected Uterus Donors 1 Y After Donation

Warren,

da Graca,

Wall

et al. 2023

Transplantation

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Background. As uterus transplantation transitions to a clinical procedure for women with absolute uterine-factor infertility, transplant centers performing uterus transplantation need information about the experience of living donors. This study examined the psychosocial impact on 17 nondirected uterus donors in the Dallas UtErus Transplant Study 1 y following donation. Methods. A prospective longitudinal study was conducted to measure psychosocial outcomes of depression, anxiety, posttraumatic stress, quality of life, and resilience [measured using the Hospital Anxiety and Depression Scale or Patient Health Questionnaire 9-Item, Generalized Anxiety Disorder 7-Item, Posttraumatic Stress Disorder Checklist for the DSM-5, health-related quality of life Short Form-36, and Connor-Davidson Resilience Scale 10-Item, respectively) assessed at baseline, at 6-mo and 1-y follow-up. Differences among baseline, 6-mo, and 1-y postdonation were analyzed. Results. The median age was 38.0 y, 16 were married, 15 were of non-Hispanic/Latino ethnicity. Most donors did not report psychosocial distress; however, 1 donor reported decline on the role limitations because of Emotional Problems Scale and also showed an increase in depression symptoms at the 6 mo, but at 1 y was below the clinical cutoff for depression. A second donor showed modest decline in emotional well-being. Improvements were seen in other donors on the Physical Functioning Scale and posttraumatic stress symptoms. Conclusions. Although most nondirected donors appeared to remain stable, both positive and negative changes were observed over the first year. Larger studies are needed to determine psychosocial risks and benefit and what additional resources might be needed to ensure optimal psychosocial outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Psychosocial Outcomes in Nondirected Uterus Donors 1 Y After Donation

Warren,

da Graca,

Wall

et al. 2023

Transplantation

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“…In the USA, four institutions have started UTx programs since 2015/2016, but only two programs have performed more than three cases each [46]. This reflects the challenges associated with establishing, financing, and maintaining a uterus transplant program.…”

Section: Establishing the First Successful Us Uterus Transplant Progr...mentioning

confidence: 99%

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

et al. 2023

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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.

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Unique Lessons From the Natural Progression of Rejection in Human Uterine Allografts

Johannesson,

Wood‐Trageser,

Lesniak

et al. 2024

Clinical Transplantation

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IntroductionUterus transplantation (UTx) is a novel treatment for absolute uterine infertility. Acute T cell–mediated rejection (TCMR) can be monitored only through serial cervical biopsies.MethodsThis study, the first of its kind in human transplantation, evaluated clinical, serological, and pathophysiological manifestations of allograft rejection from immunosuppression withdrawal (ISW) to graft hysterectomy (Hx).ResultsFollowing live birth, immunosuppression was abruptly withdrawn from six living‐donor UTx recipients. ISW occurred at a median of 7.4 weeks before graft Hx. Post‐ISW signs of rejection included: (1) discoloration of the cervix; (2) increased uterine size compared to day of ISW; (3) serological evidence of eosinophilia and progressive development of donor‐specific antibodies (DSA) or child‐specific antibodies (CSA); (4) histopathological evidence of TCMR in cervical biopsies preceding the development of antibodies in serum; and (5) C4d deposition in tissue before formation of DSA or CSA in all but two recipients. At graft Hx, endometrial glands were preferentially targeted for destruction over stroma while parametrial arteries displayed variable arteritis and fibrointimal hyperplasia.ConclusionRecognition of the progression of uterine allograft rejection may be important for other human organ recipients and drive research on modulation of immunosuppression and the paradoxical relationship between adaptive cellular and humoral immunity in natural pregnancies.Trial RegistrationClinicalTrials.gov identifier: NCT02656550

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The Ethical Evolution of Uterus Transplantation From Concept to Clinical Procedure

Cited by 3 publications

References 67 publications

Psychosocial Outcomes in Nondirected Uterus Donors 1 Y After Donation

Psychosocial Outcomes in Nondirected Uterus Donors 1 Y After Donation

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

Unique Lessons From the Natural Progression of Rejection in Human Uterine Allografts

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