| 1. |
- Brännström, Mats, 1958, et al.
(författare)
-
Uterus transplantation: from research, through human trials and into the future
- 2023
-
Ingår i: Human Reproduction Update. - 1355-4786. ; 29:5, s. 521-544
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Ayoubi, J. M., et al.
(författare)
-
Evolving clinical challenges in uterus transplantation
- 2022
-
Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483. ; 45:5, s. 947-960
-
Forskningsöversikt (refereegranskat)abstract
- Before the first live birth following uterus transplantation (UTx) in 2014, the 1–2% of women with an absent or non-functional uterus had no hope of childbearing. With 64 cases of UTx and 34 births reported in the scientific literature, this emerging technology has the potential for translation into mainstream clinical practice. However, limitations currently include donor availability, recipient suitability, surgical challenges regarding success and complications, and recipient management after UTx and during pregnancy. This review considers these challenges and ways to overcome them so that UTx could become part of the reproductive specialist's armamentarium when counselling patients with uterine factor infertility.
|
|
| 3. |
- Ayoubi, J. M., et al.
(författare)
-
Laparotomy or minimal invasive surgery in uterus transplantation: a comparison
- 2019
-
Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282. ; 112:1, s. 11-18
-
Tidskriftsartikel (refereegranskat)abstract
- Uterus transplantation (UTx) is the first available treatment for absolute uterine factor infertility, a condition due to absence of the uterus or presence of a non-functional uterus. The proof-of-concept of UTx as an infertility treatment for this group of patients occurred in 2014 in Sweden by the first birth after human UTx. That and subsequent cases of the Swedish trial were live-donor UTx procedures with laparotomy of both donor and recipient. Although results of the initial Swedish clinical UTx trial were very favorable in terms of take-home-baby rate, the drawback was the long duration (>10 h) of donor surgeries and associated long recovery periods. There exist three later publications, with uterus procurements from live donors by laparotomy with a range of surgical durations of 5.3 hours to 13 hours. Our collaborative Swedish-French team has initiated efforts to introduce minimal invasive surgery in one trial in Sweden and one in France. The principle of these UTx trials is to use modern concepts of robotic-assisted laparoscopy primarily in the live donor. There also exists a small number of published UTx procedures with donor surgery by partial conventional laparoscopy and one published case with total robotic-assisted laparoscopy procedure. This review discusses open versus minimal invasive surgery in relation to the accumulated knowledge in the field. Moreover, we propose some future directions for the development of this surgery in UTx. © 2019
|
|
| 4. |
- Brännström, Mats, 1958, et al.
(författare)
-
Registry of the International Society of Uterus Transplantation: First Report
- 2023
-
Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 107:1, s. 10-17
-
Tidskriftsartikel (refereegranskat)abstract
- Background.Uterus transplantation (UTx) is a novel type of transplantation to treat infertility in women with an absent or nonfunctioning uterus. The International Society of Uterus Transplantation (ISUTx) has developed a registry to monitor worldwide UTx activities while serving as a repository for specific research questions. Methods.The web-based registry has separate data fields for donor, recipient, surgeries, immunosuppression, rejections, pregnancies with live birth(s), and transplant hysterectomies. Data are prospectively registered. Results.A total of 45 UTx procedures have been registered; the majority (78%) of those procedures were live donor (LD) transplants. Median age of the LDs, deceased donors, and recipients were 50 y (range 32-62), 38.5 y (19-57), and 29 y (22-38), respectively. The duration of LD surgery was approximately twice as long as the recipient surgery. Postoperative complications of any Clavien-Dindo grade were registered in 20% of LDs and 24% of recipients. Rejection episodes were more frequent (33%) early after transplantation (months 1-5) compared with later time points (months 6-10; 21%). Healthy neonates were delivered by 16 recipients, with 3 women giving birth twice. The total live birth rate per embryo transfer was 35.8%. Median length of pregnancy was 35 gestational weeks. Twelve uteri were removed without childbirth, with 9 transplant hysterectomies occurring during the initial 7 mo post-UTx. Conclusions.A mandatory registry is critical to determine quality and process improvement for any novel transplantation. This registry provides a detailed analysis of 45 UTx procedures performed worldwide with a thorough analysis of outcomes and complications.
|
|
| 5. |
- Brännström, Mats, 1958, et al.
(författare)
-
Uterus transplantation worldwide: clinical activities and outcomes
- 2021
-
Ingår i: Current Opinion in Organ Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1087-2418 .- 1531-7013. ; 26:6, s. 616-626
-
Tidskriftsartikel (refereegranskat)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-Kuster-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. 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.
|
|
| 6. |
- Carbonnel, M., et al.
(författare)
-
Adapting surgical skills from robotic-assisted radical hysterectomy in cervical cancer to uterine transplantation: a look to an optimistic future!
- 2020
-
Ingår i: Journal of Robotic Surgery. - : Springer Science and Business Media LLC. - 1863-2483 .- 1863-2491. ; 14, s. 841-847
-
Tidskriftsartikel (refereegranskat)abstract
- Uterus transplantation (UTx) is the first treatment for absolute uterine factor infertility. The first birth after human UTx in Sweden occurred in 2014 and very favourable results of the Swedish trial performed with laparotomy raised great hope. Several teams are leading their own trial among the world, but UTx is still in its experimental phase. Surgical intervention needs to be optimized. The long surgical duration (> 10 h), vascular dissection and risks of ureteral damages for live donors are major drawbacks. Minimal invasive surgery by means of robotic-assisted laparoscopy for live donors could become an improved option. Our collaborative Swedish-French team has initiated efforts to introduce minimal invasive surgery in one trial in Sweden and one in France. UTx is somewhat similar to a radical colpohysterectomy for arterial dissection. We describe a robotic-assisted radical colpohysterectomy and its transposition to uterus retrieval in a living donor. We report our experience on nine cases that were completed prior to our French UTx robot-assisted trial.
|
|
| 7. |
- Brännström, Mats, 1958, et al.
(författare)
-
Global results of human uterus transplantation and strategies for pre-transplantation screening of donors
- 2019
-
Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282. ; 112:1, s. 3-10
-
Tidskriftsartikel (refereegranskat)abstract
- Absolute uterine factor infertility, due to absence or non-function of the uterus, is one of the few major subgroups of infertility that has remained without any treatment. Uterus transplantation has now been proposed as treatment for this type of infertility. The first attempt of human uterus transplantation was in 2000. This was a live donor case, but due to suboptimal surgical solutions it resulted in a necrotic uterus being removed after 99 days. This first human case, although a failure, inspired several research groups around the globe to initiate animal-based studies to investigate uterus transplantation in relation to surgery, immunosuppression, rejection and pregnancy outcome. The research was carried out in several animal species and advanced the field substantially. In 2011, the second uterus transplantation attempt was performed, and this involved a deceased donor procedure. Although the case was surgically successful, with resumed menstruations, clinical pregnancy with live birth could not be achieved. The first clinical trial of uterus transplantation was initiated in Sweden in 2013 and involved nine live donor procedures. The world's first live birth was reported from that trial in September 2014 and this was followed by two more births within that trial in November 2014. Births after uterus transplantation has since been reported from Sweden and other centers in Europe, North America, Latin America, and Asia. Thirty human uterus transplantation procedures have been reported in the scientific literature so far but by our personal knowledge the double number of procedures have been performed. The published cases will be reviewed in detail, and we will also describe the pregnancies of the live births that have been published. A small number of graft failures have occurred. These may in part be linked to suboptimal selection of donors, specifically concerning the quality of the uterine arteries. Consequently, we will also address the issue of strategies for pre-surgical screening of donors. © 2019
|
|
