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Akbari R, Ghaemi M, Panahi Z. Uterus transplantation: A bibliometric review of six-decade study from 1960 to 2024. Acta Obstet Gynecol Scand 2025; 104:437-451. [PMID: 39579060 PMCID: PMC11871124 DOI: 10.1111/aogs.14977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 08/11/2024] [Accepted: 08/29/2024] [Indexed: 11/25/2024]
Abstract
INTRODUCTION Some women are unable to become pregnant because they do not have a functional uterus. Over the last decade, it has become possible for these women to get pregnant through uterus transplantation, which has been the subject of numerous research studies. Therefore, the purpose of this study is to review published articles in the uterus transplantation area. MATERIAL AND METHODS We conducted a cross-sectional bibliometric review to study the 100 highly cited papers in the Web of Science and Scopus databases from 1960 to 2024. Our research applied bibliometric analysis to these top 100 highly cited papers. Document citation and co-occurrence analysis were used for the data study. VOSviewer along with Bibliometrix® software was used to design the maps. RESULTS The trend of uterus transplantation publications increased exponentially after 2010. Sweden is the leading country, followed by the USA and Spain. Fertility and Sterility, Lancet, American Journal of Transplantation, and Human Reproduction were the highly cited journals. Collaboration among countries showed that the most collaboration took place between Sweden and Spain (18), Sweden and the USA (14), the USA and Spain (8), Sweden and Australia (6), and the USA and the United Kingdom (6). Furthermore, the results found that more than one-third of the highly cited papers were review papers (39%) and 27% were clinical trial studies. CONCLUSIONS This bibliometric review provides a valuable contribution to the literature on uterine transplantation by synthesizing and analyzing existing research findings. It offers insights into current trends, key themes, geographic distribution, and potential areas for future research within this rapidly evolving field.
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Affiliation(s)
- Razieh Akbari
- Department of Gynecology and Obstetrics, School of MedicineTehran University of Medical SciencesTehranIran
| | - Marjan Ghaemi
- Department of Gynecology and Obstetrics, School of MedicineTehran University of Medical SciencesTehranIran
| | - Zahra Panahi
- Department of Gynecology and Obstetrics, School of MedicineTehran University of Medical SciencesTehranIran
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Brännström M, Adashi EY, Wu JH, Tsiartas P, Racowsky C. Uterus Transplantation: the Translational Evolution of a Clinical Breakthrough. Physiology (Bethesda) 2024; 39:0. [PMID: 38954427 DOI: 10.1152/physiol.00011.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 07/01/2024] [Accepted: 07/01/2024] [Indexed: 07/04/2024] Open
Abstract
Women suffering from absolute uterine factor infertility (AUFI), due to either lack of a uterus or one unable to sustain neonatal viability, presented as one of the last frontiers in conquering infertility. Following systematic animal research for over a decade, uterus transplantation was tested as a treatment for AUFI in 2012, which culminated in the first human live birth in 2014. The development of uterus transplantation from mouse to human has followed both the Moore criteria for introduction of a surgical innovation and the IDEAL concept for evaluation of a novel major surgical procedure. In this article we review the important preclinical animal and human studies that paved the way for the successful introduction of human uterus transplantation a decade ago. We discuss this in the context of the Moore criteria and describe the different procedures of preparation, surgeries, postoperative monitoring, and use of assisted reproduction in human uterus transplantation. We review the worldwide activities and associated results in the context of the IDEAL concept for evaluation of surgical innovation and appraise the ethical considerations relevant to uterus transplantation. We conclude that rigorous application of the Moore criteria and strict alignment with the IDEAL concept have resulted in the establishment of uterus transplantation as a novel, safe, and effective infertility therapy that is now being used worldwide for the treatment of women suffering from AUFI.
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Affiliation(s)
- Mats Brännström
- Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Stockholm IVF-EUGIN, Stockholm, Sweden
- Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Foch, Suresnes, France
| | - Eli Y Adashi
- Warren Alpert Medical School, Brown University, Providence, Rhode Island, United States
| | - Joseph H Wu
- Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
| | - Panagiotis Tsiartas
- Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Obstetrics and Gynecology, Karolinska Institute, Stockholm, Sweden
- Nordic IVF-EUGIN, Solna, Sweden
| | - Catherine Racowsky
- Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Foch, Suresnes, France
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
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Pecorino B, Scibilia G, Ferrara M, Veroux P, Chiofalo B, Scollo P. Deceased Donor Uterus Transplantation: A Narrative Review of the First 24 Published Cases. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1348. [PMID: 39202629 PMCID: PMC11356378 DOI: 10.3390/medicina60081348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 08/05/2024] [Accepted: 08/15/2024] [Indexed: 09/03/2024]
Abstract
Uterus transplantation is the surgical treatment for absolute uterine factor infertility (AUFI), a congenital or acquired condition characterized by the absence of a uterus. More than 80 transplants have been performed worldwide, resulting in more than 30 live births, originating both from living and deceased donors. The collection of published articles on deceased donor uterus transplantations was performed in PubMed and SCOPUS by searching for the terms "Uterus transplantation" AND "deceased donor"; from the 107 articles obtained, only case reports and systematic reviews of deceased donor uterus transplantations and the resulting live births were considered for the present manuscript. The extracted data included the date of surgery (year), country, recipient (age and cause of AUFI) and donor (age and parity) details, outcome of recipient surgery (hysterectomy), and live births (date and gestational age). The search of peer-reviewed publications showed 24 deceased donor uterus transplantations and 12 live births (a birth rate of 66%) with a 25% occurrence of graft loss during follow-up (6 of 24). Among this series, twelve transplants were performed in the USA (seven births), five in the Czech Republic (one birth), three in Italy (one birth), two in Turkey (two births), and two in Brazil (one birth). The median recipient age was 29.8 years (range 21-36), while the median donor age was 36.1 years (range 20-57). Of 24 recipients, 100% were affected by MRKH (Mayer-Rokitanski-Kuster-Hauser) syndrome. Two live births were reported from nulliparous donors. Deceased donor uterus transplantation birth rates are very similar to the living donor rates reported in the literature, but ethical implications could be less important in the first group. It is necessary to register every case in the International Registry for Uterus Transplantation in order to perform a systematic review and comparison with living donor rates.
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Affiliation(s)
- Basilio Pecorino
- Obstetrics and Gynecology Umberto I Hospital, Kore University of Enna, 94100 Enna, Italy;
| | - Giuseppe Scibilia
- Obstetrics and Gynecology Giovanni Paolo II Hospital, 97100 Ragusa, Italy;
| | - Martina Ferrara
- Obstetrics and Gynecology Cannizzaro Hospital, 95126 Catania, Italy;
| | - Pierfrancesco Veroux
- Vascular Surgery and Organ Transplant Unit, Department of General Surgery and Medical-Surgical Specialties, University Hospital of Catania, 95124 Catania, Italy;
| | - Benito Chiofalo
- Obstetrics and Gynecology Cannizzaro Hospital, Kore University of Enna, 95126 Catania, Italy;
| | - Paolo Scollo
- Obstetrics and Gynecology Cannizzaro Hospital, Kore University of Enna, 95126 Catania, Italy;
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Wu T, Wu Y, Nie K, Yan J, Chen Y, Wang S, Zhang J. Bibliometric analysis and global trends in uterus transplantation. Int J Surg 2024; 110:4932-4946. [PMID: 38626445 PMCID: PMC11326002 DOI: 10.1097/js9.0000000000001470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 03/31/2024] [Indexed: 04/18/2024]
Abstract
AIM The purpose of this study was to characterize publication patterns, academic influence, research trends, and the recent developments in uterus transplantation (UTx) across the globe. METHODS The Web of Science Core Collection database was searched for documents published from the time the database began to include relevant articles to 15 December 2023. With the use of VOSviewer, Citespace, BICOMB, and Incites, a cross-sectional bibliometric analysis was conducted to extract or calculate the evaluative indexes. Publications were categorized by country, institution, author, journal, highly cited papers, and keywords. The variables were compared in terms of publication and academic influence, which further included citation count, citation impact, Hirsh index, journal impact factor, total link strength, collaboration metrics, and impact relative to the world. RESULTS A total of 581 papers concerning UTx were initially identified after retrieval, and 425 documents were included. Of the 41 countries participating in relevant studies, the USA and Sweden were in leading positions in terms of publications, citations, and academic influence. The most versatile institution was the University of Gothenburg, followed by Baylor University. The most productive scholars and journals were Brännström M. and Fertility and Sterility , respectively. Five groups of cutting-edge keywords were identified: venous drainage, donors and donation, women, fertility preservation, and fertility. Topics about surgery, first live birth, risk, and in vitro fertilization remain hot in this field. CONCLUSIONS UTx is anticipated to enter a golden era in the coming years. This study provides some guidance concerning the authors involved in promoting UTx research, the current development of UTx, and journals to submit their innovative research. This also helps to reach a comprehensive insight and prospect in the near future. In order to establish recognized standards and benefit more patients who are disturbed by uterine infertility, large-scale and well-designed clinical trials are required.
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Affiliation(s)
- Tong Wu
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Yangyang Wu
- College of Animal Science and Technology, Sichuan Agricultural University, Sichuan, People's Republic of China
| | - Kebing Nie
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Jinfeng Yan
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
- School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan
| | - Ying Chen
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Shixuan Wang
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Jinjin Zhang
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
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Loverro M, Bizzarri N, Capomacchia FM, Watrowski R, Querleu D, Gioè A, Naldini A, Santullo F, Foschi N, Fagotti A, Scambia G, Fanfani F. Indocyanine green fluorescence applied to gynecologic oncology: beyond sentinel lymph node. Int J Surg 2024; 110:3641-3653. [PMID: 38489558 PMCID: PMC11175818 DOI: 10.1097/js9.0000000000001318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Accepted: 02/26/2024] [Indexed: 03/17/2024]
Abstract
Indocyanine green (ICG), a well-known molecule employed in medicine for over five decades, has emerged as a versatile dye widely embraced across various surgical disciplines. In gynecologic oncology, its prevalent use revolves around the detection of sentinel lymph nodes. However, the true potential of ICG extends beyond this singular application, owing to its pragmatic utility, cost-effectiveness, and safety profile. Furthermore, ICG has been introduced in the theranostic landscape, marking a significant juncture in the evolution of its clinical utility. This narrative review aims to describe the expanding horizons of ICG fluorescence in gynecologic oncology, beyond the sentinel lymph node biopsy. The manifold applications reported within this manuscript include: 1) lymphography; 2) angiography; 3) nerve visualization; 4) ICG-driven resections; and 5) theranostic. The extensive exploration across these numerous applications, some of which are still in the preclinical phase, serves as a hypothesis generator, aiming to stimulate the development of clinical studies capable of expanding the use of this drug in our field, enhancing the care of gynecological cancer patients.
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Affiliation(s)
- Matteo Loverro
- UOC Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS
| | - Nicolò Bizzarri
- UOC Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS
| | | | - Rafał Watrowski
- Department of Gynecology and Obsterics, Helios Hospital Müllheim, Teaching Hospital of the University of Freiburg, 79379 Müllheim
- Faculty of Medicine, Medical Center - University of Freiburg, 79106 Freiburg, Germany
| | - Denis Querleu
- UOC Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS
| | - Alessandro Gioè
- UOC Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS
| | - Angelica Naldini
- UOC Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS
| | - Francesco Santullo
- Operational Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli
| | - Nazario Foschi
- Urology Division, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy
| | - Anna Fagotti
- UOC Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS
- Università Cattolica del Sacro Cuore
| | - Giovanni Scambia
- UOC Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS
- Università Cattolica del Sacro Cuore
| | - Francesco Fanfani
- UOC Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS
- Università Cattolica del Sacro Cuore
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D'Amico G, Hashimoto K, Del Prete L, Richards E, Ricci S, Flyck R, Eghtesad B, Diago T, Falcone T, Miller C, Tzakis A, Quintini C. Uterus transplantation: a rescue technique to save the viability and functionality of the graft after intra-operative outflow thrombosis. F S Rep 2024; 5:223-227. [PMID: 38983730 PMCID: PMC11228784 DOI: 10.1016/j.xfre.2024.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 02/07/2024] [Accepted: 02/07/2024] [Indexed: 07/11/2024] Open
Abstract
Objective To study a surgical approach to venous vascular thrombosis after uterus transplantation (UTx). Uterus transplantation is the only treatment for uterine factor infertility when conventional therapies are not possible. One of the major limitations of UTx is the high incidence of vascular thrombosis, which in most series reaches approximately 20%. Design A case report. Setting Hospital. Patients We report here a technique used in a 30-year-old woman with congenital absence of the uterus who developed intraoperative thrombosis after a UTx from a brain-dead donor. Intervention The UTx was performed by revascularizing the graft through bilateral donor internal iliac vessels (artery and vein) anastomosed end-to-side to the external iliac vessels of the recipient. The superior uterine veins were not anastomosed and were left unreconstructed. An end-to-end graft to the recipient's vaginal anastomosis was performed. After uterus reperfusion, congestion of the organ was noted, and bilateral venous thrombosis of the internal iliac veins of the graft was found. A "Y-shaped" venous jump graft was used to restore venous outflow of the left superior uterine vein and the internal iliac vein of the graft after thrombectomy. Main Outcome Measures Viability and functionality of the uterus graft after intraoperative bilateral venous thrombosis. Results The postoperative course was uneventful, and this UTx resulted in the delivery of a healthy infant. Conclusion To our knowledge, this is the first successful rescue technique used to restore venous outflow and save the viability and functionality of a transplanted uterus. We demonstrated that a transplanted uterus from a deceased donor with a monolateral outflow could succeed in pregnancy and the delivery of a healthy infant.
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Affiliation(s)
- Giuseppe D'Amico
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Koji Hashimoto
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Luca Del Prete
- IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico di Milano, General Surgery and Liver Transplant Unit, Milan, Italy
| | - Elliott Richards
- Department of Obstetrics, Gynecology and Reproductive Biology, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio
| | - Stephanie Ricci
- Department of Obstetrics, Gynecology and Reproductive Biology, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio
| | - Rebecca Flyck
- Division of Reproductive Endocrinology and Infertility, University Hospitals, Beachwood, Ohio
| | - Bijan Eghtesad
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Teresa Diago
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Tommaso Falcone
- Department of Obstetrics, Gynecology and Reproductive Biology, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio
| | - Charles Miller
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Andreas Tzakis
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Cristiano Quintini
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
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Van Dieren L, Tawa P, Coppens M, Naenen L, Dogan O, Quisenaerts T, Lancia HH, Oubari H, Dabi Y, De Fré M, Thiessen Ef F, Cetrulo CL, Lellouch AG. Acute Rejection Rates in Vascularized Composite Allografts: A Systematic Review of Case Reports. J Surg Res 2024; 298:137-148. [PMID: 38603944 DOI: 10.1016/j.jss.2024.02.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 01/20/2024] [Accepted: 02/29/2024] [Indexed: 04/13/2024]
Abstract
INTRODUCTION Vascularized Composite Allografts (VCA) are usually performed in a full major histocompatibility complex mismatch setting, with a risk of acute rejection depending on factors such as the type of immunosuppression therapy and the quality of graft preservation. In this systematic review, we present the different immunosuppression protocols used in VCA and point out relationships between acute rejection rates and possible factors that might influence it. METHODS This systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We systematically searched Medline (PubMed), Embase, and The Cochrane Library between November 2022 and February 2023, using following Mesh Terms: Transplant, Transplantation, Hand, Face, Uterus, Penis, Abdominal Wall, Larynx, and Composite Tissue Allografts. All VCA case reports and reviews describing multiple case reports were included. RESULTS We discovered 211 VCA cases reported. The preferred treatment was a combination of antithymocyte globulins, mycophenolate mofetil (MMF), tacrolimus, and steroids; and a combination of MMF, tacrolimus, and steroids for induction and maintenance treatment, respectively. Burn patients showed a higher acute rejection rate (P = 0.073) and were administered higher MMF doses (P = 0.020). CONCLUSIONS In contrast to previous statements, the field of VCA is not rapidly evolving, as it has encountered challenges in addressing immune-related concerns. This is highlighted by the absence of a standardized immunosuppression regimen. Consequently, more substantial data are required to draw more conclusive results regarding the immunogenicity of VCAs and the potential superiority of one immunosuppressive treatment over another. Future efforts should be made to report the VCA surgeries comprehensively, and muti-institutional long-term prospective follow-up studies should be performed to compare the number of acute rejections with influencing factors.
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Affiliation(s)
- Loïc Van Dieren
- Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Faculty of Medicine and Health Sciences, Antwerp, Belgium; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Pierre Tawa
- Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, Massachusetts; Shriners Hospitals for Children-Boston, Boston, Massachusetts
| | - Marie Coppens
- Faculty of Medicine and Health Sciences, Antwerp, Belgium
| | - Laura Naenen
- Faculty of Medicine and Health Sciences, Antwerp, Belgium
| | - Omer Dogan
- Faculty of Medicine and Health Sciences, Antwerp, Belgium
| | | | - Hyshem H Lancia
- Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Haïzam Oubari
- Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Yohann Dabi
- Department of Obstetrics, Gynecology and Reproductive Medicine, Sorbonne University, Tenon Hospital (AP-HP), Paris, France
| | - Maxime De Fré
- Department of Plastic, Reconstructive and Aesthetic Surgery, Antwerp University Hospital, Antwerp, Belgium
| | - Filip Thiessen Ef
- Department of Plastic, Reconstructive and Aesthetic Surgery, Antwerp University Hospital, Antwerp, Belgium
| | - Curtis L Cetrulo
- Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, Massachusetts; Shriners Hospitals for Children-Boston, Boston, Massachusetts
| | - Alexandre G Lellouch
- Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, Massachusetts; Shriners Hospitals for Children-Boston, Boston, Massachusetts.
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8
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Veroux M, Scollo P, Giambra MM, Roscitano G, Giaquinta A, Setacci F, Veroux P. Living-Donor Uterus Transplantation: A Clinical Review. J Clin Med 2024; 13:775. [PMID: 38337468 PMCID: PMC10856556 DOI: 10.3390/jcm13030775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 01/22/2024] [Accepted: 01/27/2024] [Indexed: 02/12/2024] Open
Abstract
Uterus transplantation (UTx) is currently the only available treatment for absolute uterine factor infertility. More than 90 uterus transplantations have been performed worldwide, mostly from living donors. Living-donor (LD) UTx is a challenging surgical procedure since it poses ethical issues, and it is a high-risk and invasive surgery with higher hysterectomy-related risks compared to conventional hysterectomy. A total of 59 living-donor hysterectomies have been reported in the literature, including 35 performed with a laparotomic approach, 20 with a robotic approach and 4 with a laparoscopic approach. 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). The mean recipient age was 28.8 ± 4.5 years. Mayer-Rokitansky-Küster-Hauser syndrome was the most common indication for uterus transplant. Robotic living-donor hysterectomy had the longest operative time but resulted in a lower blood loss and postoperative stay compared to laparotomic and laparoscopic approaches. Twenty-nine births from LD-UTx have been reported, four after robotic living-donor hysterectomy and twenty-five after a laparotomic procedure. UTx is now an effective treatment for women with UFI. While living-donor UTx in some cases may be considered an experimental procedure, it offers the extraordinary possibility to give women the opportunity to have a pregnancy. Many efforts should be made to reduce the potential risks for donors, including the use of mini-invasive techniques, and the efficacy of UTx in the recipients, giving the potential harm of immunosuppression in a recipient of a non-life-saving organ.
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Affiliation(s)
- Massimiliano Veroux
- Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, 95123 Catania, Italy; (M.M.G.); (G.R.); (A.G.); (F.S.); (P.V.)
| | - Paolo Scollo
- Maternal and Child Department, Obstetrics and Gynecology, Cannizzaro Hospital, 95123 Catania, Italy;
| | - Martina Maria Giambra
- Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, 95123 Catania, Italy; (M.M.G.); (G.R.); (A.G.); (F.S.); (P.V.)
| | - Giuseppe Roscitano
- Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, 95123 Catania, Italy; (M.M.G.); (G.R.); (A.G.); (F.S.); (P.V.)
| | - Alessia Giaquinta
- Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, 95123 Catania, Italy; (M.M.G.); (G.R.); (A.G.); (F.S.); (P.V.)
| | - Francesco Setacci
- Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, 95123 Catania, Italy; (M.M.G.); (G.R.); (A.G.); (F.S.); (P.V.)
| | - Pierfrancesco Veroux
- Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, 95123 Catania, Italy; (M.M.G.); (G.R.); (A.G.); (F.S.); (P.V.)
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9
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Dion L, Sousa C, Boudjema K, Val-Laillet D, Jaillard S, Rioux-Leclercq N, Flecher E, Lavoue V. Hypothermic machine perfusion for uterus transplantation. Fertil Steril 2023; 120:1259-1261. [PMID: 37660880 DOI: 10.1016/j.fertnstert.2023.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 08/14/2023] [Accepted: 08/15/2023] [Indexed: 09/05/2023]
Abstract
OBJECTIVE To describe the feasibility of hypothermic machine perfusion (HMP) in uterus transplantation (UT) to potentially improve the preservation of the uterus and enhance graft preservation in the donation after brainstem death (DBD) context. Uterus transplantation is a new surgical approach to treating absolute uterine infertility; it can be performed after living donation or after DBD. In the DBD context, the uterus is typically the last organ removed after other vital organs, with the exception of the Baylor team, which removes the uterus first. This key aspect imposes an unavoidable mild temperature ischemia for >1 hour on the uterus during the removal of the vital abdominal and chest organs. In renal transplantation, the perfusion machine reduces the risk of delayed graft function; thus, we hypothesized that machine perfusion could result in a reduction of uterus graft dysfunction. The uterus graft dysfunction could be expressed by a low embryo implantation rate, pregnancy loss, or vascular pregnancy diseases such as preeclampsia or fetal growth restriction." To date, static cold storage of the uterus is the only standard method for preservation before transplantation. HMP is an emerging method that could potentially improve the preservation of the uterus to enhance graft preservation in the DBD context. DESIGN This video article shows all the technical details of using the HMP for uterine transplantation. SETTING University. ANIMALS Porcine model. INTERVENTION Porcine uterus was retrieved from a DBD domestic animal model and flushed with KPS MP (Bridge To Life Ltd in UK) at 4 °C. After vascular preparation on the back table, the uterus was perfused using KPS MP through a cannula in the aorta using the VitaSmart device (Bridge To Life Ltd in UK) for 18 hours. Then, the uterus was transplanted to the porcine recipient. MAIN OUTCOME MEASURES The macroscopic appearance of the uterus at the end of HMP and the assessment of the uterus vascularization after transplantation in the recipient compared with the native uterus. RESULTS This video shows the cannulation of the iliac vessels, cooling and removal of the uterus on a porcine model, uterus preservation using HMP during 18 hours, and then UT in a new recipient pig with the reperfusion of the transplanted uterus next to the native, intact uterus of the recipient. The macroscopic appearance of the uterus at the end of HMP appeared viable and was perfectly flushed. The assessment of the uterus vascularization after transplantation in the recipient was similar to that of the native uterus. To our knowledge, we describe here for the first time the UT procedure in DBD context on an animal model and the use of HMP for uterus preservation in UT programs; this could increase the number of uterine grafts available for a greater number of female recipients. CONCLUSION Hypothermic machine perfusion could allow the duration of cold ischemia to be prolonged without altering the uterine graft. Nevertheless, this assertion has to be validated in a human context.
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Affiliation(s)
- Ludivine Dion
- Department of Gynecology, Rennes University Hospital, Hôpital Sud, France; Irset - Inserm UMR_S 1085, Rennes, France.
| | - Carla Sousa
- Department of Gynecology, Rennes University Hospital, Hôpital Sud, France
| | - Karim Boudjema
- Department of Hepatobiliary Surgery and Liver Transplantation, Rennes University Hospital, Pontchaillou, France
| | - David Val-Laillet
- Nutrition Metabolisms and Cancer (NuMeCan), INRAE, INSERM, Univ Rennes, St Gilles, France
| | - Sylvie Jaillard
- Irset - Inserm UMR_S 1085, Rennes, France; Department of Cytogenetics and Cell Biology, Rennes University Hospital, Pontchaillou, France
| | - Nathalie Rioux-Leclercq
- Irset - Inserm UMR_S 1085, Rennes, France; Department of Pathology, Rennes University Hospital, Pontchaillou, France
| | - Erwan Flecher
- Department of Thoracic and Cardiovascular Surgery, Rennes University Hospital, Pontchaillou, France; Signal and Image Treatment Laboratory (LTSI), Inserm U1099, Rennes, France
| | - Vincent Lavoue
- Department of Gynecology, Rennes University Hospital, Hôpital Sud, France; Irset - Inserm UMR_S 1085, Rennes, France
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10
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Brännström M, Racowsky C, Carbonnel M, Wu J, Gargiulo A, Adashi EY, Ayoubi JM. Uterus transplantation: from research, through human trials and into the future. Hum Reprod Update 2023; 29:521-544. [PMID: 37328434 PMCID: PMC10477946 DOI: 10.1093/humupd/dmad012] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 03/29/2023] [Indexed: 06/18/2023] Open
Abstract
Women suffering from absolute uterine factor infertility (AUFI) had no hope of childbearing until clinical feasibility of uterus transplantation (UTx) was documented in 2014 with the birth of a healthy baby. This landmark accomplishment followed extensive foundational work with a wide range of animal species including higher primates. In the present review, we provide a summary of the animal research and describe the results of cases and clinical trials on UTx. Surgical advances for graft removal from live donors and transplantation to recipients are improving, with a recent trend away from laparotomy to robotic approaches, although challenges persist regarding optimum immunosuppressive therapies and tests for graft rejection. Because UTx does not involve transplantation of the Fallopian tubes, IVF is required as part of the UTx process. We provide a unique focus on the intersection between these two processes, with consideration of when oocyte retrieval should be performed, whether, and for whom, preimplantation genetic testing for aneuploidy should be used, whether oocytes or embryos should be frozen and when the first embryo transfer should be performed post-UTx. We also address the utility of an international society UTx (ISUTx) registry for assessing overall UTx success rates, complications, and live births. The long-term health outcomes of all parties involved-the uterus donor (if live donor), the recipient, her partner and any children born from the transplanted graft-are also reviewed. Unlike traditional solid organ transplantation procedures, UTx is not lifesaving, but is life-giving, although as with traditional types of transplantation, costs, and ethical considerations are inevitable. We discuss the likelihood that costs will decrease as efficiency and efficacy improve, and that ethical complexities for and against acceptability of the procedure sharpen the distinctions between genetic, gestational, and social parenthood. As more programs wish to offer the procedure, we suggest a scheme for setting up a UTx program as well as future directions of this rapidly evolving field. In our 2010 review, we described the future of clinical UTx based on development of the procedure in animal models. This Grand Theme Review offers a closing loop to this previous review of more than a decade ago. The clinical feasibility of UTx has now been proved. Advancements include widening the criteria for acceptance of donors and recipients, improving surgery, shortening time to pregnancy, and improving post-UTx management. Together, these improvements catalyze the transition of UTx from experimental into mainstream clinical practice. The procedure will then represent a realistic and accessible alternative to gestational surrogacy for the treatment of AUFI and should become part of the armamentarium of reproductive specialists worldwide.
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Affiliation(s)
- Mats Brännström
- Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Stockholm IVF-EUGIN, Stockholm, Sweden
- Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Foch, Suresnes, France
| | - Catherine Racowsky
- Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Foch, Suresnes, France
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Marie Carbonnel
- Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Foch, Suresnes, France
- University Versailles, Saint-Quentin en Yvelines, France
| | - Joseph Wu
- Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Antonio Gargiulo
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Eli Y Adashi
- Department of Medical Science, Brown University, Providence, RI, USA
| | - Jean Marc Ayoubi
- Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Foch, Suresnes, France
- University Versailles, Saint-Quentin en Yvelines, France
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11
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Hunter SA, Feldman MK. Imaging of Uterine Transplantation. Radiol Clin North Am 2023; 61:889-899. [PMID: 37495295 DOI: 10.1016/j.rcl.2023.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
Abstract
Uterus transplantation (UTx) is a novel procedure being studied as a treatment of absolute uterine factor infertility. Imaging plays an important role throughout the life cycle of a uterus transplant. In this review, we will first describe the surgical technique of UTx. The article will then focus on the importance of imaging in the evaluation of potential recipients and donors and during the immediate post-surgical time course as graft viability is established. Imaging as part of including in vitro fertilization, pregnancy, and complications will also be discussed.
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Affiliation(s)
- Sara A Hunter
- Section of Abdominal Imaging, Imaging Institute, Cleveland Clinic, 9500 Euclid Avenue, L-10, Cleveland, OH 44195, USA
| | - Myra K Feldman
- Section of Abdominal Imaging, Imaging Institute, Cleveland Clinic, 9500 Euclid Avenue, A-21, Cleveland, OH 44195, USA.
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12
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Mendilcioglu I, Dogan NU, Ozkan O, Bahceci M, Boynukalin K, Dogan S, Ozkan O. Pregnancy management and outcome after uterus transplantation. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2023; 62:328-335. [PMID: 36468688 DOI: 10.1002/uog.26134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 10/30/2022] [Accepted: 11/18/2022] [Indexed: 06/17/2023]
Abstract
Uterus transplantation is a novel approach in women whose uterus is absent or severely abnormal. However, it is still an experimental procedure that poses risks to both mother and baby. To date, 32 live births after uterus transplantation have been reported in peer-reviewed journals, with several maternal, fetal and neonatal complications. The most common complications were preterm delivery, hypertensive disorders and placenta previa. Four patients experienced episodes of transplant rejection during pregnancy. The appropriate management of complicated and non-complicated pregnancies following uterus transplantation is still unresolved. In this review, obstetric outcomes after uterus transplantation and optimal management during pregnancy are discussed in light of the available data. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
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Affiliation(s)
- I Mendilcioglu
- Department of Obstetrics and Gynecology, Akdeniz University, Antalya, Turkey
| | - N U Dogan
- Department of Obstetrics and Gynecology, Akdeniz University, Antalya, Turkey
| | - O Ozkan
- Department of Plastic and Reconstructive Surgery, Akdeniz University, Antalya, Turkey
| | - M Bahceci
- Bahçeci IVF Center, Istanbul, Turkey
| | | | - S Dogan
- Department of Obstetrics and Gynecology, Akdeniz University, Antalya, Turkey
| | - O Ozkan
- Department of Plastic and Reconstructive Surgery, Akdeniz University, Antalya, Turkey
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13
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Vali S, Jones BP, Sheikh S, Saso S, Quiroga I, Smith JR. Attitudes, knowledge, and perceptions among women toward uterus transplantation and donation in the United Kingdom. Front Med (Lausanne) 2023; 10:1223228. [PMID: 37654655 PMCID: PMC10467283 DOI: 10.3389/fmed.2023.1223228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 07/27/2023] [Indexed: 09/02/2023] Open
Abstract
Objective To assess the motivations and perceptions of the general public in the United Kingdom toward donating their uterus for Uterus Transplantation after death (UTx). Design A cross sectional study. Setting A 32-item electronic questionnaire. Population One hundred fifty nine females over the age of 16 living in the United Kingdom, consented and took part in the study. Main outcome measures The motivations and perceptions toward UTx among the general public including the willingness to donate and barriers preventing donation. Results One hundred fifty nine women completed the questionnaire. The majority had never heard of UTx (n = 107, 71%) and most were not aware the uterus could be donated after death (n = 130, 92%). 43% of the cohort were willing to donate their uterus after death (n = 57). 8% stated they wished to donate their organs but not their uterus (n = 10). 30% of women (n = 42) believed the child born following UTx would have genetic links to the donor. Over half of the respondents (n = 65, 51%) strongly agreed or agreed they would feel joy in the knowledge that donation would lead to bringing a new life into the world. A quarter of respondents strongly agreed or agreed (n = 45, 25%) that the use of their uterus by another woman would feel like an extension of life. Conclusion The findings indicate a favorable opinion toward UTx and a positive attitude toward donation of the uterus after death among the general public in the United Kingdom. The findings also highlight the need for education around UTx now this therapeutic option is available.
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Affiliation(s)
- Saaliha Vali
- West London Gynaecological Cancer Centre, Hammersmith Hospital, Imperial College NHS Trust, London, United Kingdom
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
- Cutrale Perioperative and Ageing Group, Sir Michael Uren Hub, Imperial College London, London, United Kingdom
| | - Benjamin P. Jones
- West London Gynaecological Cancer Centre, Hammersmith Hospital, Imperial College NHS Trust, London, United Kingdom
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
| | - Sairah Sheikh
- Queen Mary University of London, London, United Kingdom
| | - Srdjan Saso
- West London Gynaecological Cancer Centre, Hammersmith Hospital, Imperial College NHS Trust, London, United Kingdom
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
| | - Isabel Quiroga
- The Oxford Transplant Centre, The Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
| | - J. Richard Smith
- West London Gynaecological Cancer Centre, Hammersmith Hospital, Imperial College NHS Trust, London, United Kingdom
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
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14
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Ozkan O, Ozkan O, Dogan NU. The Ozkan Technique in Current Use in Uterus Transplantation: From the First Ever Successful Attempt to Clinical Reality. J Clin Med 2023; 12:jcm12082812. [PMID: 37109148 PMCID: PMC10144529 DOI: 10.3390/jcm12082812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 02/10/2023] [Accepted: 03/08/2023] [Indexed: 04/29/2023] Open
Abstract
Uterus-related infertility affects 3-5% of all young women, including Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, hysterectomy, or severe Asherman syndrome. For these women with uterus-related infertility, uterus transplantation is now a viable option. We performed the first surgically successful uterus transplant in September 2011. The Donor was a 22-year-old nulliparous woman. After five failed pregnancy attempts (pregnancy losses), ET attempts were discontinued in the first case, and a search for underlying etiology was performed, including static and dynamic imaging studies. Perfusion computed tomography revealed an obstructed blood outflow, particularly in the left anterolateral part of the uterus. In order to correct blood flow obstruction, a revision surgery was planned. By laparotomy, a saphenous vein graft was anastomosed between the left utero-ovarian and left ovarian vein. Perfusion computed tomography performed after the revision surgery confirmed the resolution of venous congestion and a decrease in uterine volume as well. Following surgical intervention, the patient was able to conceive after the first embryo transfer attempt. The baby was delivered with cesarean section at 28 weeks' gestation due to intrauterine growth restriction and abnormal Doppler ultrasonography findings. Following this case, our team performed the second uterus transplantation in July 2021. The recipient was a 32-year-old female with MRKH syndrome, and the donor was a 37-year-old multiparous braindead woman due to intracranial bleeding. After the transplant surgery, the second patient experienced menstrual bleeding six weeks after the operation. Seven months after the transplant, in the first ET attempt, pregnancy was achieved, and she delivered a healthy baby at 29 weeks of pregnancy. Uterus transplantation from a deceased donor is a feasible option for treating uterus-related infertility. When confronted with recurrent pregnancy losses, vascular revision surgery via arterial or venous supercharging could be an option in order to deal with focal underperfused areas defined by imaging studies.
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Affiliation(s)
- Omer Ozkan
- Department of Plastic Surgery, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey
| | - Ozlenen Ozkan
- Department of Plastic Surgery, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey
| | - Nasuh Utku Dogan
- Department of Gynecology, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey
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15
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Graft Failure after Uterus Transplantation in 16 Recipients: A Review. J Clin Med 2023; 12:jcm12052032. [PMID: 36902818 PMCID: PMC10003853 DOI: 10.3390/jcm12052032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 02/26/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
Uterus transplantation (UTx) is now an alternative to surrogacy and adoption for women with uterine factor infertility to have children; however, there are still unresolved clinical and technical issues. One of these is that the graft failure rate after transplantation is somewhat higher than that of other life-saving organ transplants, which is a critical concern. Herein, we summarize the details of 16 graft failures after UTx with living or deceased donors using the published literature in order to learn from these negative outcomes. To date, the main causes of graft failure are vascular factors (arterial and/or venous thrombosis, atherosclerosis, and poor perfusion). Many recipients with thrombosis develop graft failure within one month of surgery. Therefore, it is necessary to devise a safe and stable surgical technique with higher success rates for further development in the UTx field.
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16
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Investigation of the relationship between reproductive disorders and chromosomal abnormalities in a large-scale, single-center 10-year retrospective study. J Gynecol Obstet Hum Reprod 2022; 51:102467. [DOI: 10.1016/j.jogoh.2022.102467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 06/29/2022] [Accepted: 08/27/2022] [Indexed: 11/24/2022]
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17
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Ozkan O, Dogan NU, Ozkan O. Response to "The History of Uterus Transplantation, Rewritten.". ANNALS OF SURGERY OPEN 2022; 3:e189. [PMID: 37601157 PMCID: PMC10431429 DOI: 10.1097/as9.0000000000000189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 06/24/2022] [Indexed: 11/27/2022] Open
Affiliation(s)
- Omer Ozkan
- From the Department of Plastic Surgery, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Nasuh Utku Dogan
- Department of Gynecology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Ozlenen Ozkan
- From the Department of Plastic Surgery, Akdeniz University Faculty of Medicine, Antalya, Turkey
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18
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Uterus Transplantation: From a Deceased Donor or Living Donor? J Clin Med 2022; 11:jcm11164840. [PMID: 36013080 PMCID: PMC9409724 DOI: 10.3390/jcm11164840] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 08/16/2022] [Indexed: 01/07/2023] Open
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19
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Dorafshar AH, Hamidian Jahromi A, Horen SR, Schechter LS, Johannesson L, Testa G, Hertl M, Dewdney S, Aschkenasy J, Wood-Molo M, Brincat C, Cherullo E, Behel JM, Hebert C, Shulman R, Bassi S, Alecci AT, Konety B. Strategic Planning and Essential Steps for Establishing a Uterine Transplant and Rehabilitation Program: From Idea to Reality. Ann Surg 2022; 276:74-80. [PMID: 34793341 DOI: 10.1097/sla.0000000000005301] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
UTx is performed to address absolute uterine infertility in the presence of uterine agenesis, a nonfunctional uterus, or after a prior hysterectomy. After the initial success of UTx resulting in a livebirth (2014) in Sweden, there are over 70 reported UTx surgeries resulting in more than 40 livebirths worldwide. Currently, UTx has been performed in over 10 countries. As UTx is transitioning from an "experimental procedure" to a clinical option, an increasing number of centers may contemplate a UTx program. This article discusses essential steps for establishment of a successful UTx program. These principles may be implemented in cis- and transgender UTx candidates.
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Affiliation(s)
- Amir H Dorafshar
- Division of Plastic & Reconstructive Surgery, Rush University Medical Center, Chicago, IL
| | | | - Sydney R Horen
- Division of Plastic & Reconstructive Surgery, Rush University Medical Center, Chicago, IL
| | - Loren S Schechter
- Division of Plastic & Reconstructive Surgery, Rush University Medical Center, Chicago, IL
- The Center for Gender Confirmation Surgery, Weiss Memorial Hospital, Chicago, IL
| | - Liza Johannesson
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
- Department of Obstetrics and Gynecology, Baylor University Medical Center, Dallas, TX
| | - Giuliano Testa
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | - Martin Hertl
- Division of Transplant Surgery, Rush University Medical Center, Chicago, IL
| | - Summer Dewdney
- Division of Gynecologic Oncology, Rush University Medical Center, Chicago, IL
| | | | - Mary Wood-Molo
- Division of Reproductive Endocrinology and Infertility, Rush University Medical Center, Chicago, IL
| | - Cynthia Brincat
- Department of Obstetrics and Gynecology, Rush University Medical Center, Chicago, IL
| | - Edward Cherullo
- Department of Urology, Rush University Medical Center, Chicago, IL
| | - Jay M Behel
- Department of Psychiatry, Rush University Medical Center, Chicago, IL
- Rush Center for Gender, Sexuality & Reproductive Health, Chicago, IL
| | - Charles Hebert
- Department of Psychiatry, Rush University Medical Center, Chicago, IL
- Department of Internal Medicine, Rush University Medical Center, Chicago, IL
| | - Robert Shulman
- Department of Psychiatry, Rush University Medical Center, Chicago, IL
| | - Shruti Bassi
- Department of Anesthesiology, Rush University Medical Center, Chicago, IL
| | | | - Badrinath Konety
- Department of Surgery, Rush University Medical Center, Chicago, IL
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20
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Kisu I, Banno K. Comment on "Birth of a Healthy Baby 9 years after a Surgically Successful Deceased Donor Uterus Transplant". ANNALS OF SURGERY OPEN 2022; 3:e172. [PMID: 37601602 PMCID: PMC10431319 DOI: 10.1097/as9.0000000000000172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 01/29/2022] [Indexed: 11/26/2022] Open
Affiliation(s)
- Iori Kisu
- From the Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
| | - Kouji Banno
- From the Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
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21
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da Graca B, Johannesson L, Testa G, Wall AE. The Ethical Evolution of Uterus Transplantation From Concept to Clinical Procedure. Clin Obstet Gynecol 2022; 65:24-36. [PMID: 35045022 DOI: 10.1097/grf.0000000000000687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Uterus transplantation (UTx) offers women with absolute uterine factor infertility a path to motherhood that enables them to carry their own pregnancy. Debates about the ethics of UTx have evolved in tandem with its clinical evolution: clinical trials have provided evidence regarding risks and benefits to donors and recipients that were initially uncertain; technical advances have altered the balance between risks and benefits; and the experiences of donors and recipients has revealed questions that were not anticipated. As UTx transitions to a clinical procedure, questions remain about long-term risks and benefits, applications beyond carrying a pregnancy, and cost and access.
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Affiliation(s)
| | - Liza Johannesson
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center
- Department of Obstetrics and Gynecology, Baylor University Medical Center, Dallas, Texas
| | - Giuliano Testa
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center
| | - Anji E Wall
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center
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22
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Dion L, Santin G, Nyangoh Timoh K, Boudjema K, Jacquot Thierry L, Gauthier T, Carbonnel M, Ayoubi JM, Kerbaul F, Lavoue V. Procurement of Uterus in a Deceased Donor Multi-Organ Donation National Program in France: A Scarce Resource for Uterus Transplantation? J Clin Med 2022; 11:jcm11030730. [PMID: 35160178 PMCID: PMC8836780 DOI: 10.3390/jcm11030730] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 01/26/2022] [Accepted: 01/27/2022] [Indexed: 02/01/2023] Open
Abstract
Uterus transplantation is a new possibility for women suffering from absolute uterine infertility to become pregnant and have children. In the case of a deceased donor, a list of exclusion criteria is defined to ensure the high quality of the uterus graft. This study evaluates the number of potentially available uterus grafts based on the pre-defined exclusion criteria in a national deceased donor multi-organ donation program in France. We analyzed the data reported in the CRISTAL database regarding all women aged 18 to 60 on whom organ procurement was performed between 2014 and 2019. Potential deceased women donors were classified into three categories: very ideal donor, ideal donor, and expanded criteria donor. Between 2014 and 2019, 4544 women underwent organ procurement. Using the very ideal donor, ideal donor, and expanded criteria donor classification, we found that, respectively, only 124, 264, and 936 donors were potentially eligible for UTx. This represents 2.8 per million people (PMP) very ideal donors, 3.8 PMP ideal donors, 8.6 PMP expanded criteria donors (ECDs). The restricted number of grafts requires a complementary strategy of living and deceased donors to meet the demand of all women with AUI.
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Affiliation(s)
- Ludivine Dion
- Department of Gynecology, Hôpital Sud, Rennes University Hospital, CEDEX 9, 35200 Rennes, France; (K.N.T.); (L.J.T.); (V.L.)
- UMR_S 1085, IRSET-INSERM, 35000 Rennes, France
- Correspondence:
| | - Gaëlle Santin
- Organ and Tissue Transplant Management, Biomedicine Agency, CEDEX, 93212 La Plaine-Saint-Denis, France; (G.S.); (F.K.)
| | - Krystel Nyangoh Timoh
- Department of Gynecology, Hôpital Sud, Rennes University Hospital, CEDEX 9, 35200 Rennes, France; (K.N.T.); (L.J.T.); (V.L.)
| | - Karim Boudjema
- Department of Hepatobiliary Surgery and Liver Transplantation, Pontchaillou, Rennes University Hospital, CEDEX 9, 35000 Rennes, France;
| | - Louise Jacquot Thierry
- Department of Gynecology, Hôpital Sud, Rennes University Hospital, CEDEX 9, 35200 Rennes, France; (K.N.T.); (L.J.T.); (V.L.)
| | - Tristan Gauthier
- Department of Gynecology, Limoges University Hospital, 87042 Limoges, France;
| | - Marie Carbonnel
- Department of Obstetrics Gynecology and Reproductive Medicine, Foch Hospital, 92150 Suresnes, France; (M.C.); (J.M.A.)
| | - Jean Marc Ayoubi
- Department of Obstetrics Gynecology and Reproductive Medicine, Foch Hospital, 92150 Suresnes, France; (M.C.); (J.M.A.)
| | - François Kerbaul
- Organ and Tissue Transplant Management, Biomedicine Agency, CEDEX, 93212 La Plaine-Saint-Denis, France; (G.S.); (F.K.)
| | - Vincent Lavoue
- Department of Gynecology, Hôpital Sud, Rennes University Hospital, CEDEX 9, 35200 Rennes, France; (K.N.T.); (L.J.T.); (V.L.)
- UMR_S 1085, IRSET-INSERM, 35000 Rennes, France
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24
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25
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Birth of a Healthy Baby 9 years after a Surgically Successful Deceased Donor Uterus Transplant. Ann Surg 2021; 275:825-832. [DOI: 10.1097/sla.0000000000005346] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Abstract
PURPOSE OF REVIEW Uterus transplantation (UTx) is transitioning from an experimental procedure to a clinical treatment for absolute uterine factor infertility (AUFI). Standardized protocols for the evaluation and selection of donors and recipients that maximize chances of success - a healthy live birth - are needed. RECENT FINDINGS To date, recipient eligibility has been limited to otherwise healthy women with AUFI who are of childbearing age and are good candidates for in-vitro fertilization (IVF). For donors (living or deceased), selection criteria vary, apart from basic requirements of blood-type compatibility and freedom from critical infectious diseases, but generally require a term birth and a uterus free from uterine pathologies. The stepwise evaluation process for candidate recipients and living donors moves through health screening (medical and psychosocial); initial selection committee review; IVF (recipients only); and final selection committee review. This eliminates candidates with poor chances of success before exposure to unnecessary risks. SUMMARY The currently stringent selection criteria for prospective recipients and donors will likely broaden, as UTx becomes more widely available. Continued research is needed to define the donor, recipient and uterine graft factors associated with successful outcomes, and to support the development of standardized selection criteria.
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27
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Martin F, Tullius SG. Immunosuppression after uterus transplantation. Curr Opin Organ Transplant 2021; 26:627-633. [PMID: 34581290 DOI: 10.1097/mot.0000000000000925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Clinical uterus transplantation (UTx) is growing rapidly. The procedure represents the only therapy for women with absolute uterine factor infertility to give birth to a biological baby. Immunosuppression after UTx needs to carefully balance effects with the healthy mother and baby. Unique for UTx is the 'temporary' character of the procedure with a transplant hysterectomy being performed after delivery. Most of the practice on immunosuppression in UTx is currently based on the experience in solid organ transplantation (SOT). RECENT FINDINGS Clinical UTx-trials have been performed in centers worldwide during the recent years and experience on immunosuppression has accumulated. SUMMARY Immunosuppression in UTx has been successfully applied as maintenance treatment in addition to effectively treating acute T- and B-cell mediated rejections. Understanding the biology of UTx in more detail is expected to refine future approaches.
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Affiliation(s)
- Friederike Martin
- Department of General, Visceral and Transplant Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Stefan G Tullius
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
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28
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Brännström M, Belfort MA, Ayoubi JM. Uterus transplantation worldwide: clinical activities and outcomes. Curr Opin Organ Transplant 2021; 26:616-626. [PMID: 34636769 DOI: 10.1097/mot.0000000000000936] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Women with absolute uterine factor infertility, because of uterine absence, or the presence of a nonfunctional uterus, were regarded as being untreatable until 2014 when the first birth following uterus transplantation (UTx) took place in Sweden. This proof-of-concept occurred in a woman with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHs) with congenital uterine absence, who received a uterus from a 61-year-old live donor (LD). Since then, several births after UTx have occurred in Sweden and subsequently in other countries, including both LD and deceased donor (DD) transplants. A great majority of the recipients were women with MRKHs. The efficiency and safety of UTx can be determined only when a complete study cohort of transplanted women have reached the definitive endpoint of graft hysterectomy. The different outcomes of transplanted women include graft failure, as well as graft survival with failure to achieve livebirth, or livebirth(s). Published data from a completed trial are not yet available. The results that we have to rely on are reports of completed surgeries and interim outcomes that may be as early as a few months after surgery and up to several years after UTx. The purpose of this review is to give an update on all published clinical UTx data and major results, including live births up to mid 2021. RECENT FINDINGS The interim results of a number of UTx studies have been published. LD UTx procedures have been reported from four European countries (Sweden, the Czech Republic, Germany, Spain), four Asian nations (Saudi Arabia, India, China, Lebanon), as well as some from the USA. DD UTx procedures have been reported from Turkey, the Czech Republic, the USA and Brazil. To our knowledge, there also exist unpublished UTx cases from some of the countries mentioned above and from at least four other countries (Serbia, France, Mexico, Italy). We estimate that at least 80 UTx procedures have been performed, resulting in more than 40 births. The present study includes only data from published, peer-reviewed, research papers. The results of 62 UTx cases show an overall surgical success rate, as defined by a technically successful transplantation with a subsequent regular menstrual pattern, of 76%. The success rates for LD and DD UTx procedures were 78% and 64%, respectively. The rate of serious postsurgical complications requiring invasive or radiological intervention was 18% for LDs and 19% for recipients. The cumulative live birth rate in successful UTx procedures is estimated to be above 80%. Twenty-four births after UTx have been reported and the results show a high rate of preterm birth, with an associated high proportion of respiratory distress syndrome. SUMMARY UTx has proven to be a successful treatment for uterine factor infertility at several centers around the world. The modest success rate and the fairly high complication rate among LDs, indicate that further research and development under strict governance are needed before this option should be widely offered.
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Affiliation(s)
- Mats Brännström
- Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg
- Stockholm IVF-EUGIN, Stockholm, Sweden
- Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA
- Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Foch - Faculté de Medicine Paris Ouest (UVSQ), Suresnes, France
| | - Michael A Belfort
- Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA
| | - Jean Marc Ayoubi
- Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Foch - Faculté de Medicine Paris Ouest (UVSQ), Suresnes, France
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29
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Escandón JM, Bustos VP, Santamaría E, Langstein HN, Ciudad P, Hernandez-Alejandro R, Moore RG, Leckenby JI, Manrique OJ. Evolution and Transformation of Uterine Transplantation: A Systematic Review of Surgical Techniques and Outcomes. J Reconstr Microsurg 2021; 38:429-440. [PMID: 34535036 DOI: 10.1055/s-0041-1735261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND Uterine transplantation (UTx) is acknowledged to be on the second (2A) of five steps of development in accordance with the staging system for the evaluation of surgical innovations. Accordingly, we aimed to systematically review the available evidence of the surgical techniques and outcomes of UTx in terms of graft survival. METHODS A comprehensive search was conducted across PubMed Medline, Cochrane-EBMR, Scopus, Web of Science, and CENTRAL through November 2020. RESULTS Forty studies, reporting 64 recipients and 64 donors, satisfied inclusion criteria. The surgical time and the estimated blood loss were 515 minutes and 679 mL for graft procurement via laparotomy, 210 minutes and 100 mL for laparoscopic-assisted graft harvest, and 660 minutes and 173 mL for robotic-assisted procedures, respectively. Urinary tract infections (n = 8) and injury to the urinary system (n = 6) were the most common donor complications. Using the donor's internal iliac system, two arterial anastomoses were performed in all cases. Venous outflow was accomplished through the uterine veins (UVs) in 13 cases, a combination of the UVs and the ovarian/uteroovarian veins (OVs/UOVs) in 36 cases, and solely through the OVs/UOVs in 13 cases. Ischemia time was 161 and 258 minutes when using living donors (LD) and deceased donors (DD), respectively. Forty-eight uteri were successfully transplanted or fulfilled the purpose of transplantation, 41 from LDs and 7 from DDs. Twenty-five and four live childbirths from LDs and DDs have been reported, respectively. CONCLUSION UTx is still experimental. Further series are required to recommend specific surgical techniques that best yield a successful transplant and reduce complications for donors and recipients.
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Affiliation(s)
- Joseph M Escandón
- Division of Plastic and Reconstructive Surgery, Strong Memorial Hospital, University of Rochester Medical Center, New York
| | - Valeria P Bustos
- Division of Plastic and Reconstructive Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Eric Santamaría
- Department of Plastic and Reconstructive Surgery, Hospital General Dr. Manuel Gea Gonzalez, National Cancer Institute, Mexico City, Mexico
| | - Howard N Langstein
- Division of Plastic and Reconstructive Surgery, Strong Memorial Hospital, University of Rochester Medical Center, New York
| | - Pedro Ciudad
- Department of Plastic, Reconstructive and Burn Surgery, Arzobispo Loayza National Hospital, Lima, Peru
| | - Roberto Hernandez-Alejandro
- Department of Surgery and Division of Abdominal Transplantation and Hepatobiliary Surgery, Strong Memorial Hospital, University of Rochester Medical Center, New York
| | - Richard G Moore
- Department of Obstetrics and Gynecology, Strong Memorial Hospital, University of Rochester Medical Center, New York
| | - Jonathan I Leckenby
- Division of Plastic and Reconstructive Surgery, Strong Memorial Hospital, University of Rochester Medical Center, New York
| | - Oscar J Manrique
- Division of Plastic and Reconstructive Surgery, Strong Memorial Hospital, University of Rochester Medical Center, New York
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30
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Almeida GHDR, Iglesia RP, Araújo MS, Carreira ACO, Dos Santos EX, Calomeno CVAQ, Miglino MA. Uterine Tissue Engineering: Where We Stand and the Challenges Ahead. TISSUE ENGINEERING PART B-REVIEWS 2021; 28:861-890. [PMID: 34476997 DOI: 10.1089/ten.teb.2021.0062] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Tissue engineering is an innovative approach to develop allogeneic tissues and organs. The uterus is a very sensitive and complex organ, which requires refined techniques to properly regenerate and even, to rebuild itself. Many therapies were developed in 20th century to solve reproductive issues related to uterus failure and, more recently, tissue engineering techniques provided a significant evolution in this issue. Herein we aim to provide a broad overview and highlights of the general concepts involved in bioengineering to reconstruct the uterus and its tissues, focusing on strategies for tissue repair, production of uterine scaffolds, biomaterials and reproductive animal models, highlighting the most recent and effective tissue engineering protocols in literature and their application in regenerative medicine. In addition, we provide a discussion about what was achieved in uterine tissue engineering, the main limitations, the challenges to overcome and future perspectives in this research field.
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Affiliation(s)
- Gustavo Henrique Doná Rodrigues Almeida
- University of São Paulo, Faculty of Veterinary and Animal Science, Professor Orlando Marques de Paiva Avenue, 87, Butantã, SP, Sao Paulo, São Paulo, Brazil, 05508-900.,University of São Paulo Institute of Biomedical Sciences, 54544, Cell and Developmental Biology, Professor Lineu Prestes Avenue, 1374, Butantã, SP, Sao Paulo, São Paulo, Brazil, 05508-900;
| | - Rebeca Piatniczka Iglesia
- University of São Paulo Institute of Biomedical Sciences, 54544, Cell and Developmental Biology, Sao Paulo, São Paulo, Brazil;
| | - Michelle Silva Araújo
- University of São Paulo, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil., São Paulo, São Paulo, Brazil;
| | - Ana Claudia Oliveira Carreira
- University of São Paulo, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, SP, Brazil, São Paulo, São Paulo, Brazil;
| | - Erika Xavier Dos Santos
- State University of Maringá, 42487, Department of Morphological Sciences, State University of Maringá, Maringá, PR, Brazil, Maringa, PR, Brazil;
| | - Celso Vitor Alves Queiroz Calomeno
- State University of Maringá, 42487, Department of Morphological Sciences, State University of Maringá, Maringá, PR, Brazil, Maringa, PR, Brazil;
| | - Maria Angélica Miglino
- University of São Paulo, Faculty of Veterinary and Animal Science Professor Orlando Marques de Paiva Avenue, 87 Butantã SP Sao Paulo, São Paulo, BR 05508-900, São Paulo, São Paulo, Brazil;
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31
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Fronek J, Janousek L, Kristek J, Chlupac J, Pluta M, Novotny R, Maluskova J, Olausson M. Live Birth Following Uterine Transplantation From a Nulliparous Deceased Donor. Transplantation 2021; 105:1077-1081. [PMID: 32541565 DOI: 10.1097/tp.0000000000003346] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Nulliparous uterine grafts have never been used in uterus transplantation (UTx), possibly due to presumed infertility. Our objective was to verify the feasibility of nulliparous uterine graft transplantation. METHODS The Czech Uterus Transplant Trial (registered under ClinicalTrials.gov, identifier NCT03277430) is a 2-arm trial comparing the efficacy of deceased donor (DD) versus live-donor uterus transplant (10 patients in both arms). A 25-year-old patient suffering from inborn absolute uterine factor infertility underwent a DD uterus transplant. The donor was a 20-year-old nulliparous brain-dead donor. RESULTS The transplant procedure was uneventful. The posttransplant period was complicated by (1) recurrent episodes of acute cellular rejection, (2) neutropenia necessitating the administration of granulocyte colony-stimulating factor, (3) vaginal anastomotic stenosis treated with the insertion of a self-expanding stent, (4) the concurrence of Clostridium difficile colitis and acute appendicitis, and (5) temporary renal function impairment of a combined cause. Two years after the UTx, after the fourth embryo transfer, the patient became pregnant. Apart from gestational diabetes mellitus, the pregnancy was uneventful. Due to preterm contractions, delivery was achieved via caesarean section at gestational age 34 + 6 years. The postoperative course was uneventful for both the mother and the newborn. CONCLUSIONS Herein, we report the first live birth after a DD UTx in Europe. This report provides a proof of concept that nulliparous uteri may present a suitable source of uterine grafts for UTx. Stenting may serve as a feasible treatment method for vaginal anastomotic stenosis.
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Affiliation(s)
- Jiri Fronek
- Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.,Second Faculty of Medicine, Charles University, Prague, Czech Republic.,First Faculty of Medicine, Charles University, Prague, Czech Republic.,Department of Anatomy, Second Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Libor Janousek
- Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.,First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jakub Kristek
- Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.,Department of Anatomy, Second Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jaroslav Chlupac
- Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.,Second Faculty of Medicine, Charles University, Prague, Czech Republic.,Department of Anatomy, Second Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Marek Pluta
- Department of Obstetrics and Gynaecology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
| | - Robert Novotny
- Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Jana Maluskova
- Department of Clinical and Transplant Pathology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic
| | - Michael Olausson
- Department of Transplantation Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
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32
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Hosseinirad H, Yadegari P, Mohanazadeh Falahieh F, Nouraei S, Paktinat S, Afsharzadeh N, Sadeghi Y. Disorders of sex development and female reproductive capacity: A literature review. Syst Biol Reprod Med 2021; 67:323-336. [PMID: 34196232 DOI: 10.1080/19396368.2021.1937376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Disorders of sex development (DSD) are a wide-ranging group of complex conditions that influence chromosomal, gonadal, and phenotypic sex. The prevalence of DSD is very low, but affected patients deserve individualized management to improve psychological, sexual, and reproductive outcomes. This review aims to clarify the fertility potential of DSD patients who can be reared as females and their chance of becoming pregnant, especially using assisted reproductive techniques (ART). Due to the effects of DSD on internal and external genital organs, these conditions result in varying degrees of fertility potential. Fertility rate depends on the phenotype and is inversely related to the severity of the disorder. Reproductive endocrinologists and infertility specialists must be considered active partners of the interdisciplinary treatment team. With current advances in ART, pregnancy is more achievable in patients who were considered infertile at first glance. Due to the complexity of the medical management in DSD patients, more studies should be conducted to conclusively suggest the best choice for improving their fertility potential.Abbreviations: AIS: Androgen Insensitivity Syndrome; AMH: Anti-Müllerian Hormone; ART: Assisted Reproductive Technology; ASRM: American Society for Reproductive Medicine; CAH: Congenital Adrenal Hyperplasia; CAIS: Complete Androgen Insensitivity Syndrome; DHT: Dihydrotestosterone; DSD: Disorders of Sexual Development; FSH: Follicle Stimulating Hormone; GD: Gonadal Dysgenesis; ICSI: Intracytoplasmic Sperm Injection; IUGR: Intrauterine Growth Restriction; IVF: In Vitro Fertilization; IVF-ET: IVF and Embryo Transfer; LH: Luteinizing Hormone; MGD: Mixed Gonadal Dysgenesis; MRI: Magnetic Resonance Imaging; MRKH: Mayer-Rokitansky-Kuster-Hauser; US: Ultrasonography; HSG: Hysterosalpingography; PAIS: Partial Androgen Insensitivity Syndrome; PGD: Preimplantation Genetic Diagnosis; POR: P450 Oxidoreductase; PROM: Premature Rupture of Membranes; TS: Turner Syndrome; 17β-HSD III: 17β-Hydroxysteroid Dehydrogenase III; 21-OHD: 21-hydroxylase deficiency; 5α-RD-2: 5α-reductase-2.
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Affiliation(s)
- Hossein Hosseinirad
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pouya Yadegari
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Soheila Nouraei
- Department of Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahrokh Paktinat
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Yousef Sadeghi
- Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Victoria, Australia
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Bergmann S, Schindler M, Munger C, Penfold CA, Boroviak TE. Building a stem cell-based primate uterus. Commun Biol 2021; 4:749. [PMID: 34140619 PMCID: PMC8211708 DOI: 10.1038/s42003-021-02233-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 05/06/2021] [Indexed: 12/17/2022] Open
Abstract
The uterus is the organ for embryo implantation and fetal development. Most current models of the uterus are centred around capturing its function during later stages of pregnancy to increase the survival in pre-term births. However, in vitro models focusing on the uterine tissue itself would allow modelling of pathologies including endometriosis and uterine cancers, and open new avenues to investigate embryo implantation and human development. Motivated by these key questions, we discuss how stem cell-based uteri may be engineered from constituent cell parts, either as advanced self-organising cultures, or by controlled assembly through microfluidic and print-based technologies.
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Affiliation(s)
- Sophie Bergmann
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
- Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
- Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Cambridge, UK
| | - Magdalena Schindler
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
- Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
- Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Cambridge, UK
| | - Clara Munger
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
- Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
- Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Cambridge, UK
| | - Christopher A Penfold
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
- Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
- Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Cambridge, UK.
- Wellcome Trust - Cancer Research UK Gurdon Institute, Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Cambridge, UK.
| | - Thorsten E Boroviak
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
- Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
- Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Cambridge, UK.
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34
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Carbonnel M, Cornet N, Revaux A, Favre-Inhofer A, Galio L, Raliou M, Couturier-Tarrade A, Giraud-Delville C, Charpigny G, Gelin V, Dubois O, Hersant B, Bosc R, Coscas R, Vialard F, Chavatte-Palmer P, Richard C, Sandra O, Ayoubi JM. Analysis of blood parameters and molecular endometrial markers during early reperfusion in two ovine models of uterus transplantation. PLoS One 2021; 16:e0251474. [PMID: 34003831 PMCID: PMC8130915 DOI: 10.1371/journal.pone.0251474] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 04/27/2021] [Indexed: 11/30/2022] Open
Abstract
The dissection of the veins is the trickiest step of Uterine transplantation (UTx). Performing the anastomosis of a single uterine vein could bring a therapeutic benefit and simplification of surgery and serve for managing unilateral venous thromboses. The objectives of this project were to evaluate the expression of early markers of ischemia-reperfusion and to compare findings following one or two vein anastomoses. Orthotopic uterine auto-transplantations were performed on an ovine model with anastomosis of either two (group 1) or one utero-ovarian veins (group 2). Blood gases, histology and ischemia- reperfusion markers transcripts (PTGS2, IL6, IL8, SOD2, C3, BAX/BCL2 and TLR4) were analyzed as well as PTGS2 protein expression using Western Blot and fluorescence immunolocalization on endometrial biopsies after 3h of reperfusion. Ten ewes were included in the experimentation, 4 were in group1, 3 in group 2, the others being sham operated controls. No significant differences were observed between the two phenotypes. Based on these results, the anastomosis of one single uterine vein appears to be an approach consistent with short-term graft survival. Further experiments will be needed to confirm the reliability of this approach, especially the long-term follow-up of the uterine graft including its ability to support gestation to term.
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Affiliation(s)
- Marie Carbonnel
- Department of Gynaecology and Obstetrics, Foch Hospital, Suresnes, France
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
- * E-mail:
| | - Nathalie Cornet
- Department of Gynaecology and Obstetrics, Foch Hospital, Suresnes, France
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Aurélie Revaux
- Department of Gynaecology and Obstetrics, Foch Hospital, Suresnes, France
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
| | - Angéline Favre-Inhofer
- Department of Gynaecology and Obstetrics, Foch Hospital, Suresnes, France
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Laurent Galio
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Mariam Raliou
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Anne Couturier-Tarrade
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Corinne Giraud-Delville
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Gilles Charpigny
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Valérie Gelin
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Olivier Dubois
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Barbara Hersant
- Department of Plastic, Reconstructive, Aesthetic and Maxillofacial Surgery, Henri Mondor Hospital, Créteil, France
| | - Romain Bosc
- Department of Plastic, Reconstructive, Aesthetic and Maxillofacial Surgery, Henri Mondor Hospital, Créteil, France
| | - Raphael Coscas
- Department of Vascular Surgery, Ambroise Paré University Hospital, Boulogne-Billancourt, France
- UMR 1018, Inserm-Paris11 - CESP, Versailles Saint-Quentin-en-Yvelines University, Paris-Saclay University, Boulogne-Billancourt, France
| | - François Vialard
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Pascale Chavatte-Palmer
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Christophe Richard
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Olivier Sandra
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
- Ecole Nationale Vétérinaire d’Alfort, BREED, Maisons-Alfort, France
| | - Jean-Marc Ayoubi
- Department of Gynaecology and Obstetrics, Foch Hospital, Suresnes, France
- Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France
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Jones BP, Saso S, Yazbek J, Thum MY, Quiroga I, Ghaem-Maghami S, Smith JR. Uterine Transplantation: Scientific Impact Paper No. 65 April 2021. BJOG 2021; 128:e51-e66. [PMID: 33913235 DOI: 10.1111/1471-0528.16697] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
A uterine transplant, or womb transplant, provides a potential treatment for women who cannot become pregnant or carry a pregnancy because they do not have a womb, or have a womb that is unable to maintain a pregnancy. This is estimated to affect one in 500 women. Options for those who wish to start a family include adoption and surrogacy, but these are associated with legal, cultural, ethical and religious implications that may not be appropriate for some women and their families. A womb transplant is undertaken when the woman is ready to start a family, and is removed following the completion of their family. Womb transplants have been performed all over the world, with more than 70 procedures carried out so far. At least 23 babies have been born as a result, demonstrating that womb transplants can work. While the procedure offers a different option to adoption and surrogacy, it is associated with significant risks, including multiple major surgeries and the need to take medications that help to dampen the immune system to prevent rejection of the womb. To date there has been a 30% risk of a transplant being unsuccessful. Although the number of transplants to date is still relatively small, the number being performed globally is growing, providing an opportunity to learn from the experience gained so far. This paper looks at the issues that have been encountered, which may arise at each step of the process, and proposes a framework for the future. However, long term follow-up of cases will be essential to draw reliable conclusions about any overall benefits of this procedure.
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Affiliation(s)
- B P Jones
- Royal College of Obstetricians and Gynaecologists, 10-18 Union Street, London, SE1 1SZ, UK
| | - S Saso
- Royal College of Obstetricians and Gynaecologists, 10-18 Union Street, London, SE1 1SZ, UK
| | - J Yazbek
- Royal College of Obstetricians and Gynaecologists, 10-18 Union Street, London, SE1 1SZ, UK
| | - M-Y Thum
- Royal College of Obstetricians and Gynaecologists, 10-18 Union Street, London, SE1 1SZ, UK
| | - I Quiroga
- Royal College of Obstetricians and Gynaecologists, 10-18 Union Street, London, SE1 1SZ, UK
| | - S Ghaem-Maghami
- Royal College of Obstetricians and Gynaecologists, 10-18 Union Street, London, SE1 1SZ, UK
| | - J R Smith
- Royal College of Obstetricians and Gynaecologists, 10-18 Union Street, London, SE1 1SZ, UK
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Dahm-Kähler P, Kvarnström N, Alfonzo Rodriguez E, Skogsberg Dahlgren U, Brännström M. Uterus transplantation for fertility preservation in patients with gynecologic cancer. Int J Gynecol Cancer 2021; 31:371-378. [PMID: 33649004 DOI: 10.1136/ijgc-2020-001804] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/02/2020] [Accepted: 10/05/2020] [Indexed: 11/04/2022] Open
Abstract
Cervical and endometrial cancer may impact women interested in future fertility in approximately 5-25% of cases. The recommended treatment for patients with early stage disease is hysterectomy and/or radiation leading to infertility. This is referred to as absolute uterine factor infertility. Such infertility was considered untreatable until 2014, when the first child was born after uterus transplantation. Thereafter, multiple births have been reported, mainly from women with Mayer-Rokitansky-Küster-Hauser syndrome, with congenital uterine absence, although also from a patient with iatrogenic uterine factor infertility caused by radical hysterectomy secondary to an early stage cervical cancer 7 years before uterus transplantation. A live birth after uterus transplantation may be considered promising for many who may not otherwise have this option.Uterus transplantation is a complex process including careful patient selection in both recipients and donors, in vitro fertilization, and complex surgery in the organ procurement procedure including harvesting the vessel pedicles with the thin-walled veins. Thereafter, the transplantation surgery with anastomosis to ensure optimal blood inflow and outflow of the transplanted organ. Knowledge regarding immunosuppression and pregnancy is essential. Lastly there is the hysterectomy component as the uterus must be removed. Multidisciplinary teams working closely are essential to achieve successful uterus transplantation and, ultimately, delivery of a healthy child. Both the living and deceased donor concept may be considered and we address both the advantages and disadvantages. This review summarizes the animal research thus far published on uterus transplantation, the suggested recipient selections including former gynecologic cancer patients, the living and deceased donor uterus transplantation concepts with reported results, and updated fertility outcomes.
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Affiliation(s)
- Pernilla Dahm-Kähler
- Department of Obstetrics and Gynecology, Sahlgrenska Academy, Gothenburg, Sweden
| | - Niclas Kvarnström
- Department of Transplantation, Sahlgrenska Academy, Goteborg, Sweden
| | | | | | - Mats Brännström
- Department of Obstetrics and Gynecology, Sahlgrenska Academy, Gothenburg, Sweden
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The Evolution of Transplantation From Saving Lives to Fertility Treatment: DUETS (Dallas UtErus Transplant Study). Ann Surg 2021; 272:411-417. [PMID: 32657928 DOI: 10.1097/sla.0000000000004199] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE We report the results of the first 20 uterus transplants performed in our institution. SUMMARY BACKGROUND DATA Uterus transplantation (UTx) aims at giving women affected by absolute uterine-factor infertility the possibility of carrying their own pregnancy. UTx has evolved from experimental to an established surgical procedure. METHODS The Dallas Uterus Transplant Study (DUETS) program started in 2016. The uterus was transplanted in orthotopic position with vascular anastomoses to the external iliac vessels and removed when 1 or 2 live births were achieved. Immunosuppression lasted only for the duration of the uterus graft. RESULTS Twenty women, median age 29.7 years, enrolled in the study, with 10 in phase 1 and 10 in phase 2. All but 2 recipients had a congenital absence of the uterus. Eighteen recipients received uteri from living donors and 2 from deceased donors. In phase 1, 50% of recipients had a technically successful uterus transplant, compared to 90% in phase 2. Four recipients with a technical success in phase 1 have delivered 1 or 2 babies, and the fifth recipient with a technical success is >30 weeks pregnant. In phase 2, 2 recipients have delivered healthy babies and 5 are pregnant. CONCLUSIONS UTx is a unique type of transplant; whose only true success is a healthy child birth. Based on results presented here, involving refinement of the surgical technique and donor selection process, UTx is now an established solution for absolute uterine-factor infertility.
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Human Uterus Transplantation from Living and Deceased Donors: The Interim Results of the First 10 Cases of the Czech Trial. J Clin Med 2021; 10:jcm10040586. [PMID: 33557282 PMCID: PMC7916074 DOI: 10.3390/jcm10040586] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/26/2021] [Accepted: 02/01/2021] [Indexed: 01/16/2023] Open
Abstract
Introduction: Uterus transplantation (UTx) is a rapidly evolving treatment of uterine-factor infertility. We report the results of the first 10 UTx procedures performed at our institution. Methods: The program started in April 2016 as a two-arm study comparing the efficacy of UTx from live donors (LD) and deceased donors (DD). Results: Between April 2016 and April 2018, we performed five DD UTx and five LD UTx. Two grafts had to be removed early due to thrombosis. One graft was removed due to chronic rejection and previous herpes simplex infection at month 7. Graft survival is 70% at one year. Recipient survival is 100% at two years. Live donor survival is 100% at three years. Three live-births have been achieved, two from a LD and one from a graft from a nulliparous DD. Vaginal anastomotic stenosis occurred in 63% (5/8) of grafts. Self-expanding stents have shown preliminary suitability for the treatment of vaginal stenosis. Three recipients developed severe acute rejection. Conclusion: The interim results of our study demonstrate mid-term viability in 70% of grafts. The LD UTx produced two live births and the DD UTx produced one live birth. Nulliparous donors should be considered for donation.
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Tombak K, Özkan Ö, Uysal H, Özkan Ö. An Individualized Physiotherapy and Rehabilitation Program for Bilateral Hand Transplantations. Ann Plast Surg 2021; 86:217-222. [PMID: 33449466 DOI: 10.1097/sap.0000000000002668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
METHODS This article describes a rehabilitation program and the long-term results after its application in 2 double-hand transplantation patients after 9- and 4-year follow-up periods. A personal rehabilitation program was planned to commence as early as possible after postoperative patient stabilization. Splinting, edema, positioning, passive and active joint movements, daily life activity modification and education, and occupational therapy were also emphasized. RESULTS Positioning, edema, and passive joint movements were started in the acute phase. Strengthening and exercises were continued for 8 weeks and later for functional gains and adaptation to daily living activities. Subjective and overall results were quite satisfactory. The Hand Transplantation Score System, Disabilities of the Arm Shoulder and Hand, Semmes Weinstein Monofilaments, sensory tests, and modified Kapandji index improvements were all within good acceptable ranges. Although rapid recovery and functional development were observed in the first 4 years, these are still continuing at the time of writing. DISCUSSION The most important determining factors in the success of rehabilitation are to return to daily life and the ability to acquire functional skills. Long-term follow-up of the patients in this study showed that they were able to return to their independent daily lives and that external assistance decreased to a minimum.
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Affiliation(s)
- Kadriye Tombak
- From the Faculty of Medicine, Department of Physical Medicine and Rehabilitation
| | - Özlenen Özkan
- Faculty of Medicine, Department of Plastic, Reconstructive and Aesthetic Surgery
| | - Hilmi Uysal
- Faculty of Medicine, Department of Neurology, Akdeniz University, Antalya, Turkey
| | - Ömer Özkan
- Faculty of Medicine, Department of Plastic, Reconstructive and Aesthetic Surgery
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Clinicopathologic Analysis of Uterine Allografts Including Proposed Scoring of Ischemia-reperfusion Injury and T Cell-mediated Rejection-Dallas UtErus Transplant Study: A Pilot Study. Transplantation 2021; 106:167-177. [PMID: 33481553 DOI: 10.1097/tp.0000000000003633] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Uterus transplantation (UTx) enables pregnancy in infertile women. This study describes the histopathological changes of ischemia reperfusion injury and mostly acute T cell-mediated rejection (TCMR) in UTx and proposes modification toward a working formulation grading system with associated treatments. METHODS Protocol and indication biopsies from 11 living and 2 deceased donor UTx recipients were analyzed. Serving as a control were 49 age-matched nontransplanted uteri. All posttransplant histopathological specimens were evaluated in a blinded fashion by 3 pathologists. Response to treatment was assessed by follow-up biopsies. Serial serum donor-specific antibody (DSA) responses were also recorded. RESULTS Changes attributed to ischemia reperfusion resolved within 2 weeks of UTx in most of the patients. For TCMR grading, perivascular inflammation, focal capillary disruption, and interstitial hemorrhage were added to interface inflammation, intercellular edema, stromal inflammation, and epithelial apoptotic bodies. Of the 173 protocol biopsies, 98 were classified as negative for TCMR; 34, indeterminate-borderline; 35, mild; 3, moderate; and 3, severe, 1 of which occurred in a DSA-positive recipient and also showed microvascular injury. Corticosteroids successfully treated all moderate to severe TCMR episodes. Mild TCMR was treated by increasing existing baseline immunosuppression. Indeterminate-borderline episodes were not treated. Neither ischemia reperfusion injury nor TCMR with DSA adversely affected embryo transfer. CONCLUSION Relying on a modified histopathological grading system, we developed a treatment strategy resulting in resolution of TCMR and successful pregnancies.
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Carmona F, Rius M, Díaz-Feijoo B, Musquera M, Tort J, Alcaraz A. Uterine transplantation. First viable case in Southern Europe. Med Clin (Barc) 2020; 156:297-300. [PMID: 33380366 DOI: 10.1016/j.medcli.2020.12.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 12/10/2020] [Accepted: 12/10/2020] [Indexed: 12/13/2022]
Abstract
INTRODUCTION AND OBJECTIVES To describe the development and characteristics living donor uterine transplantation program of the Hospital Clínic (Barcelona, Spain) and to report the first successful procedure in Southern Europe. PATIENTS AND METHODS A 31-year-old female suffering of Rokitansky Syndrome underwent uterus transplant from her living sister, as a part of our research protocol. Before the transplant, the patient underwent an in vitro fertilization procedure and twelve embryos were obtained and cryopreserved. The uterus obtention procedure was performed entirely by robotic surgery and lasted 10h, being the main objective to obtain arterial and venous pedicles of good quality in order to ensure the vitality of the graft. The surgical procedure in the recipient was performed by laparotomy and the vascular anastomoses were performed in a terminolateral fashion, with polypropylene 8-0, the vaginal cuff of the graft was sutured to the recipient vaginal vault and the round and utero-sacral ligaments were fixed to the remaining recipient ligaments. Immunosuppressive treatment was prescribed following the protocols from other groups modified according to the solid organ transplantation protocols from our center. RESULTS The donor and recipient were discharged without any major complications. The recipient ultrasound scan showed a normal flow in both uterine arteries and veins. A grade II rejection was treated with high dose corticoids with subsequent normal biopsies and a vaginal stricture was treated with the placement of an esophageal stent for 4 weeks. The patient had her first menstrual period 47 days after the surgery. CONCLUSIONS The case reported here open new options in Spain for a wide group of patients that had no medical solution for a disease that deeply impairs their quality of life.
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Affiliation(s)
- Francisco Carmona
- Service of Gynecology, Institut Clínic de Ginecologia, Obstetrícia, i Neonatologia, Hospital Clinic of Barcelona, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain; Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Spain.
| | - Mariona Rius
- Service of Gynecology, Institut Clínic de Ginecologia, Obstetrícia, i Neonatologia, Hospital Clinic of Barcelona, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain
| | - Berta Díaz-Feijoo
- Service of Gynecology, Institut Clínic de Ginecologia, Obstetrícia, i Neonatologia, Hospital Clinic of Barcelona, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain; Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Spain
| | - Mireia Musquera
- Service of Urology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain
| | - Jaume Tort
- Organització Catalana de Trasplantaments (OCATT), Passeig del Taulat, 106-116, 08005 Barcelona, Spain
| | - Antonio Alcaraz
- Service of Urology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain
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Uterine Transplantation: Evolving Data, Success, and Clinical Importance. J Minim Invasive Gynecol 2020; 28:502-512. [PMID: 33348011 DOI: 10.1016/j.jmig.2020.12.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 12/09/2020] [Accepted: 12/15/2020] [Indexed: 11/22/2022]
Abstract
Uterine transplantation is an evolving procedure to allow for childbearing in paitents with absolute uterine factor infertility. The objective of this study was to review the existing literature using a comprehensive PubMed literature search. A systematic medical subheadings search strategy was used with the terms "uterus transplant" and "uterine transplantation". Of the 75 full-text articles assessed for eligibility, 68 were included in the qualitative synthesis. Of these, 9 were included in the meta-analysis on living donor uterine transplant, 5 on deceased donor uterine transplant, and 6 case reports of single uterine transplants. In conclusion, uterus transplant is a nascent field undergoing a rapid rate of evolution as programs mature their data and increase the number of procedures performed. The most recent publications and advances are thus summarized in this article to capture the most up-to-date information.
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Targeting connexins with Gap27 during cold storage of the human donor uterus protects against cell death. PLoS One 2020; 15:e0243663. [PMID: 33301511 PMCID: PMC7728185 DOI: 10.1371/journal.pone.0243663] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 11/25/2020] [Indexed: 11/30/2022] Open
Abstract
Uterus transplantation is an experimental infertility treatment for women with uterine factor infertility. During donor uterus retrieval and subsequent storage, ischemia and other stressors are likely to occur, resulting in the delayed restoration of organ function and increased graft rejection. The uterus expresses connexin-based hemichannels, the opening of which can promote ischemic cell death, as well as gap junctions that may expand cell death by bystander signaling. We investigated if connexin channel inhibition with connexin channel inhibitor Gap27 could protect the uterus against cell death during the storage period. The study involved 9 female patients undergoing gender-change surgery. Before uterus removal, it was exposed to in situ warm ischemia with or without reperfusion. Uterus biopsies were taken before, during, and after ischemia, with or without reperfusion, and were subsequently stored under cold (4ᵒC) or warm (37ᵒC) conditions. TUNEL cell death assay was done at various time points along the combined in vivo/ex vivo experimental timeline. We found that Gap27 protected against storage-related cell death under cold but not warm conditions when the uterus had experienced in situ ischemia/reperfusion. For in situ brief ischemia without reperfusion, Gap27 reduction of cell death was delayed and significantly less, suggesting that protection critically depends on processes initiated when the organ was still in the donor. Thus, the inclusion of the connexin channel inhibitor Gap27 during cold storage protects the uterus against cell death, and the degree of protection depends on the history of exposure to warm ischemia. Gap27 protection may be indicated for uteri from deceased donors, in which ischemia is likely because life-saving organs have retrieval priority.
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D'Amico G, Quintini C, Eghtesad B, Hashimoto K, Ricci S, Flyckt R, Del Prete L, Miller C, Falcone T, Tzakis A. Uterus Recovery from Deceased Donor: Simple Technique Securing Safety of Vital Organs and Uterus Graft. J Am Coll Surg 2020; 232:e1-e6. [PMID: 33217551 DOI: 10.1016/j.jamcollsurg.2020.11.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 11/09/2020] [Accepted: 11/10/2020] [Indexed: 01/16/2023]
Affiliation(s)
- Giuseppe D'Amico
- Departments of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH.
| | - Cristiano Quintini
- Departments of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Bijan Eghtesad
- Departments of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Koji Hashimoto
- Departments of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Stephanie Ricci
- Obstetrics and Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH
| | - Rebecca Flyckt
- Obstetrics and Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH
| | - Luca Del Prete
- Departments of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Charles Miller
- Departments of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Tommaso Falcone
- Obstetrics and Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH
| | - Andreas Tzakis
- Departments of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
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Aydogan Kirmizi D, Baser E, Doganyigit Z. The Activation of Cannabinoid Type-2 Receptor with JWH-133 Protects Uterine Ischemia/Reperfusion-Induced Damage. Pharmacology 2020; 106:106-113. [PMID: 33105141 DOI: 10.1159/000511457] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 09/04/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Uterus transplantation is a complex surgical procedure. Uterine ischemia/reperfusion (IR) damage occurring in this process may cause loss of function in the uterus. Cell damage must be prevented for a healthy uterine function and successful transplantation. Cannabinoids, with their increasing clinical use, are substances with strong anti-inflammatory and antioxidative effects and have a role in immune system regulation. However, their efficacy in uterine IR damage is still unknown. This study provides information on the potential applications cannabinoids agonist JWH-133 in uterine IR damage and, hence, in the transplant process. METHODS Rats were divided into 4 groups (n = 8), performed uterine IR, and treated 2 groups with JWH-133. After anesthesia, ischemia was applied for 1 h to the uterus while reperfusion was applied for 3 h. After the experiment, malondialdehyde (MDA) levels and phosphorylated nuclear factor-kappa B (p-NF-κB) expression were examined in the tissue samples. Also, cell damage was evaluated by histopathological imaging and TUNEL staining. RESULTS In the uterine IR group, NF-κB expression and MDA levels were detected at high levels. Histopathological examinations and TUNEL staining revealed extensive cell damage. On the other hand, in groups treated with JWH-133, dose-dependent NF-κB expression and MDA levels decreased (p < 0.05). Depending on the dose, the rate of surviving cells increased in TUNEL staining results. CONCLUSION The results showed that JWH-133 was effective in reducing uterine IR damage. Cannabinoids may be a new alternative that may be used in the transplantation process in the future.
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Affiliation(s)
- Demet Aydogan Kirmizi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey,
| | - Emre Baser
- Department of Obstetrics and Gynecology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey
| | - Zuleyha Doganyigit
- Department of Histology and Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey
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Akouri R, Maalouf G, Abboud J, Nakad T, Bedran F, Hajj P, Beaini C, Cricu LM, Aftimos G, El Hajj C, Eid G, Waked A, Hallit R, Gerges C, Rached EA, Matta M, El Khoury M, Barakat A, Kvarnström N, Dahm-Kähler P, Brännström M. First live birth after uterus transplantation in the Middle East. MIDDLE EAST FERTILITY SOCIETY JOURNAL 2020. [DOI: 10.1186/s43043-020-00041-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Abstract
Background
The first live birth after uterus transplantation took place in Sweden in 2014. It was the first ever cure for absolute uterine factor infertility. We report the surgery, assisted reproduction, and pregnancy behind the first live birth after uterus transplantation in the Middle East, North Africa, and Turkey (MENAT) region.
A 24-year old woman with congenital absence of the uterus underwent transplantation of the uterus donated by her 50-year-old multiparous mother. In vitro fertilization was performed to cryopreserve embryos. Both graft retrieval and transplantation were performed by laparotomy. Donor surgery included isolation of the uterus, together with major uterine arteries and veins on segments of the internal iliac vessels bilaterally, the round ligaments, and the sacrouterine ligaments, as well as with bladder peritoneum. Recipient surgery included preparation of the vaginal vault, end-to-side anastomosis to the external iliac arteries and veins on each side, and then fixation of the uterus.
Results
One in vitro fertilization cycle prior to transplantation resulted in 11 cryopreserved embryos. Surgical time of the donor was 608 min, and blood loss was 900 mL. Cold ischemia time was 85 min. Recipient surgical time was 363 min, and blood loss was 700 mL. Anastomosis time was 105 min. Hospital stay was 7 days for both patients. Ten months after the transplantation, one previously cryopreserved blastocyst was transferred which resulted in viable pregnancy, which proceeded normally (except for one episode of minor vaginal bleeding in the 1st trimester) until cesarean section at 35 + 1 weeks due to premature contractions and shortened cervix. A healthy girl (Apgar 9-10-10) weighing 2620 g was born in January 2020, and her development has been normal during the first 6 months.
Conclusions
This is the first report of a healthy live birth after uterus transplantation in the MENAT region. We hope that this will motivate further progress and additional clinical trials in this area in the Middle East Region, where the first uterus transplantation attempt ever, however unsuccessful, was performed already three decades ago.
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Zhang R, Deng SL, Lian ZX, Yu K. Immunosuppression in uterine transplantation. Transpl Immunol 2020; 63:101335. [PMID: 32927095 DOI: 10.1016/j.trim.2020.101335] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 09/09/2020] [Indexed: 11/25/2022]
Abstract
Uterine transplantation (UTx) is the only effective treatment for uterine infertility patients to become genetic mothers. After decades of research, the surgical methods of UTx are very developed. There are numerous factors that affect the results of UTx, such as selection of the donor uterus before transplantation, immunosuppressive therapy post-transplantation, rejection monitoring, and immune tolerance. Studies have shown that immune rejection is a crucial factor affecting the survival rate after organ transplantation. Unlike liver or kidney transplantation, the aim of UTx is to obtain a functional uterus that is able to support successful pregnancy and birth of a healthy fetus. Because of the unique purpose of UTx, its immunosuppressive program is relatively specialized. Some immunosuppressive agents can cause perinatal complications, and inducing immune tolerance is necessary to resolve these side effects. Further understanding of the immune mechanism of UTx and the continuous development of new immunosuppressive agents, combined with the application of assisted reproductive technology, will be more conducive to the realization of UTx to breed offspring.
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Affiliation(s)
- Rui Zhang
- College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
| | - Shou-Long Deng
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101 Beijing, China.
| | - Zheng-Xing Lian
- College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Kun Yu
- College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
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Dion L, Jacquot Thierry L, Tardieu A, Carbonnel M, Ayoubi JM, Gauthier T, Lavoué V. [Uterus transplantation, current prospect and future indications. State of art with review of literature]. ACTA ACUST UNITED AC 2020; 49:193-203. [PMID: 32916317 DOI: 10.1016/j.gofs.2020.09.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Indexed: 11/27/2022]
Abstract
OBJECTIVES The aim of this review is to summarize the development of UT on worldwide and to develop the new questions posed by this technique in 2020. METHODS According to the PRISMA model, via Pubmed, we searched for publications containing the keywords: uterus transplantation; UT and cryopreservation from 2000 to 2020. RESULTS At least 76 UTx have been carried out around the world and 19 healthy babies were born. The main indication remains the uterine agenesis (MRKH Syndrome>85% cases) then the history of hysterectomy (hemorrhage of the delivery or cervical cancer) and the non-functional uterus (Asherman's syndrome, diffuse adenomyosis). The 2 types of donors (living and deceased) are developed representing respectively 75% and 25% of the TU; the success rate in terms of return of rules is better in the living donor group and is 79% vs 68% in the deceased donor group. The choice of donor type must take into account the constraints of both procedures. Surgical complications (grade III) for the donor are estimated to be 14% mainly represented by ureter wounds. Technical simplifications concerning the venous return of the graft but also the carrying out of robot-assisted surgery would reduce the operating time for the donor and facilitate the collection process. CONCLUSION TU is a complementary alternative to GPA and adoption allowing patients to be surrogates, legal and biological of the baby. An extension of the indications to patients with non absolute uterine infertility is in the process of democratization.
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Affiliation(s)
- L Dion
- Service de gynécologie, CHU de Rennes, hôpital Sud, 16, boulevard de Bulgarie, 35000 Rennes, France.
| | - L Jacquot Thierry
- Service de gynécologie, CHU de Rennes, hôpital Sud, 16, boulevard de Bulgarie, 35000 Rennes, France
| | - A Tardieu
- Département de gynécologie obstétrique, CHU Limoges, avenue Dominique Larrey, 87000 Limoges, France; Inserm, UMR-1248, CHU Limoges, 87000 Limoges, France
| | - M Carbonnel
- Service de gynécologie obstétrique et médecine de la reproduction, hôpital Foch, université de Versailles Saint-Quentin en Yvelines, 92150 Suresnes, France
| | - J-M Ayoubi
- Service de gynécologie obstétrique et médecine de la reproduction, hôpital Foch, université de Versailles Saint-Quentin en Yvelines, 92150 Suresnes, France
| | - T Gauthier
- Département de gynécologie obstétrique, CHU Limoges, avenue Dominique Larrey, 87000 Limoges, France; Inserm, UMR-1248, CHU Limoges, 87000 Limoges, France
| | - V Lavoué
- Service de gynécologie, CHU de Rennes, hôpital Sud, 16, boulevard de Bulgarie, 35000 Rennes, France
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Kristek J, Johannesson L, Novotny R, Kachlik D, Fronek J. Human uterine vasculature with respect to uterus transplantation: A comprehensive review. J Obstet Gynaecol Res 2020; 46:2199-2220. [PMID: 32840043 DOI: 10.1111/jog.14428] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 05/28/2020] [Accepted: 07/25/2020] [Indexed: 01/18/2023]
Abstract
Due to the novelty of uterus transplantation, data on preferable inflow and outflow of the graft are limited. This paper reviews the technique, type of vessels and the outcome. A systematic search of the PubMed database was conducted. We extracted and analyzed data on the arteries and veins utilized, types of anastomosis, types of donors, complications and the outcome. Thirty eight sources reported 51 human uterine transplantations, 10 graft thromboses and 25 live births. Inflow was established with two uterine arteries (UA) with/without the anterior division of the internal iliac artery in 62% (n = 31) of cases, two UA arteries with a segment/patch of the internal iliac artery in 34% (n = 17) of cases or two UA with a conduit in 4% of cases (n = 2). Both cases with a conduit developed thrombosis (n = 2). Arterial thrombosis/ischemia developed in 8 of the 51 cases. In 50% of cases with arterial thrombosis, atherosclerosis was identified as a possible cause. Outflow was established by two internal iliac veins with patches/segments in 27.5% of cases (n = 14) followed by two utero-ovarian veins in 25.5% (n = 13). Venous thrombosis occurred in 3 of the 51 cases. Uterine arteries with/without anterior division of the internal iliac artery were the most frequent arteries used for inflow and produced the highest patency rate. The presence of atherosclerosis and complex arterial reconstruction was associated with a high rate of arterial thrombosis. None of the veins utilized in the procedures appeared to be superior. There are insufficient data to draw a definite conclusion.
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Affiliation(s)
- Jakub Kristek
- Department of Transplantation Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.,Department of Anatomy, Second Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Liza Johannesson
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA
| | - Robert Novotny
- Department of Transplantation Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - David Kachlik
- Department of Anatomy, Second Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jiri Fronek
- Department of Transplantation Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.,Department of Anatomy, Second Faculty of Medicine, Charles University, Prague, Czech Republic.,First Faculty of Medicine, Charles University, Prague, Czech Republic
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50
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Järvholm S, Dahm-Kähler P, Kvarnström N, Brännström M. Psychosocial outcomes of uterine transplant recipients and partners up to 3 years after transplantation: results from the Swedish trial. Fertil Steril 2020; 114:407-415. [PMID: 32709381 DOI: 10.1016/j.fertnstert.2020.03.043] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 03/16/2020] [Accepted: 03/30/2020] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To assess the psychosocial outcomes of recipients and their partners 2 and 3 years after entering this first clinical uterus transplantation study. DESIGN Prospective observational study. SETTING University hospital. PATIENT(S) Nine women with absolute uterine factor infertility and their male partners participated. INTERVENTION(S) Psychosocial evaluations using questionnaires focusing on health-related quality-of-life, mood, relationship, and fertility-related quality-of-life were conducted at 2- and 3-year follow-up after transplantation. MAIN OUTCOME MEASURE(S) Scores were obtained on the validated questionnaires 36-Item Short Form Survey (SF-36), Hospital Anxiety and Depression Scale, Dyadic Adjustment Scale, and Fertility Quality of life measuring health-related quality-of-life, mood, relationship, and infertility-associated life quality, respectively. RESULT(S) There was a reversible decrease (at year 2) in the physical component of SF-36 concerning recipients, but not in partners. Negative deviations in the mental component of SF-36 were seen in four recipients, and in two of their partners at year 3, possibly related to the fact that live birth had not been achieved yet among three of these women. Childlessness also seemed to be related to reporting elevated anxiety scores. Most recipients and partners stated high satisfaction with marital relationship both at inclusion and at follow-up. CONCLUSION(S) The results of the present study show that even if the baseline psychosocial characteristics of the women to undergo transplantation and their partners were stable and equal or better compared with norm populations, graft failure and failure to achieve parenthood will pose psychological strains on couples in the period up to 3 years after transplantation. Psychological counseling should be offered past 3 years for recipients and their partners. CLINICAL TRIAL REGISTRATION NUMBER NCT01844362.
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Affiliation(s)
- Stina Järvholm
- Department of Obstetrics and Gynecology, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
| | - Pernilla Dahm-Kähler
- Department of Obstetrics and Gynecology, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden
| | - Niclas Kvarnström
- Department Transplantation, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden
| | - Mats Brännström
- Department of Obstetrics and Gynecology, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden; Stockholm IVF-EUGIN, Stockholm, Sweden
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