Long-term health-related quality-of-life and psychosocial outcomes after uterus transplantation: a 5-year follow-up of donors and recipients.

STUDY QUESTION: What are the outcomes regarding health-related quality-of-life, mood, and marital relationship of recipients and donors 5 years after uterus transplantation (UTx) and uterus donation? SUMMARY ANSWER: Both recipients and donors generally demonstrated long-term stability regarding psychosocial outcomes but with negative deviations associated with unsuccessful outcomes. WHAT IS KNOWN ALREADY: UTx is the first infertility treatment for women with absolute uterine factor infertility. The procedure can be performed with either a uterus donation from a live donor (LD), typically a close relative, or from a deceased, multi-organ donor. There are many potential stressful events over several years after UTx both for recipients and for LDs and these events may have impacts on quality-of-life and mental well-being. STUDY DESIGN, SIZE, DURATION: This, prospective observational cohort study includes the nine recipients and LDs of the first human UTx trial. They were assessed in 2017-2018 by questionnaires 5 years after UTx. PARTICIPANTS/MATERIALS, SETTING, METHODS: The nine recipients (ages 32-43 years) and their respective LDs (ages 44-67 years) were either related (n = 8) or friends (n = 1). Eight recipients had congenital uterine absence and one was hysterectomized due to cervical cancer. For two recipients, UTx resulted in early graft failures, while six of the other seven recipients gave birth to a total of eight babies over the following 5 years. Physical and mental component summaries of health-related quality-of-life were measured with the SF-36 questionnaire. Mood was assessed by the Hospital Anxiety and Depression Scale. Relationship with partner was measured with the Dyadic Adjustment Scale. Comparisons were made between the values after 5 years and the values before uterus donation/transplantation. MAIN RESULTS AND THE ROLE OF CHANCE: Five years after primary UTx, the majority of recipients scored above the predicted value of the general population on quality-of-life, except for two women, one of whom had a viable graft but no live birth and one recipient who was strained by quality-of-life changes, possibly related to parenthood transitions. Regarding mood, only one value (anxiety) was above the threshold for further clinical assessment. Recipients showed declining satisfaction with their marital relationships, but all reported scores above the 'at risk for divorce' threshold at the time of the final assessment in our study. The LDs were all found to be stable and above the predicted value of the general population regarding mental components of quality-of-life. Three LDs showed declined physical components, possibly related to older age. Only one LD reported a value in mood (anxiety) that would need further assessment. The marital satisfaction of LDs remained stable and unchanged compared to baseline values. Notably, the two recipients with early graft failures, and their related LDs, regained their mental well-being during the first years after graft failure and remained stable after 5 years. LIMITATIONS, REASONS FOR CAUTION: The restricted sample size and the single-centre study-design are limitations of this study. Additionally the study was limited to LD UTx, as opposed to deceased donor UTx. WIDER IMPLICATIONS OF THE FINDINGS: Our study shows that both LDs and recipients had acceptable or favourable quality-of-life outcomes, including mood assessment, at the 5-year follow-up mark, and that failure to achieve a live birth negatively affected these modalities both for LDs and recipients. Moreover, an important finding was that LDs and recipients are not reacting with depression after hysterectomy, which is common after hysterectomy in the general population. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the Jane and Dan Olsson Foundation for Science, Knut and Alice Wallenberg Foundation, Handlanden Hjalmar Svensson Foundation, Swedish Governmental ALF Grant, and Swedish Research Council. There are no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: NCT01844362.

The first Australian uterus transplantation procedure: A result of a long-term Australian-Swedish research collaboration.

AIMS: The aim is to report the results of Australia's first uterus transplantation (UTx). METHODS: Following long-standing collaboration between the Swedish and Australian teams, Human Research Ethics approval was obtained to perform six UTx procedures in a collaborative multi-site research study (Western Sydney Local District Health 2019/ETH13038), including Royal Hospital for Women, Prince of Wales Hospital, and Westmead Hospital in New Souh Wales. Surgeries were approved in both the live donor (LD) and deceased donor models in collaboration with the inaugural Swedish UTx team. RESULTS: This is the first UTx procedure to occur in Australia, involving a mother donating her uterus to her daughter. The total operative time for the donor was 9 h 54 min. Concurrently, recipient surgery was synchronised to minimise graft ischaemic time, and the total operative time for the recipient was 6 h 12 min. Surgery was by laparotomy in the LD and recipient. The total warm ischaemic time of the graft was 1 h 53 min, and the cold ischaemic time was 2 h 17 min (total ischaemic time 4 h 10 min). The patient's first menstruation occurred 33 days after the UTx procedure. CONCLUSION: Twenty-five years of Swedish and Australian collaboration has led to Australia's first successfully performed UTx surgery at The Royal Hospital for Women, Sydney, Australia.

Case Report: Post-Partum SARS-CoV-2 Infection After the First French Uterus Transplantation.

Absolute uterus factor infertility, whether congenital or acquired, renders the woman unable to carry a child. Although uterus transplantation (UTx) is being increasingly performed as a non-vital procedure to address this unfortunate condition, the immunosuppression required presents risks that are further compounded by pregnancy and during the puerperium period. These vulnerabilities require avoidance of SARS-CoV-2 infection in pregnant UTx recipients especially during the third trimester, as accumulating evidence reveals increased risks of morbidity and mortality. Here we describe a successful UTx case with delivery of a healthy child, but in which both mother and neonate developed asymptomatic SARS-CoV-2 infection seven days after RNA vaccination, on day 35 post-partum. Although the patient was successfully treated with a combination therapy comprised of two monoclonal antibodies, this case highlights the challenges associated with performing UTx in the era of Covid-19. More broadly, the risks of performing non-vital organ transplantation during a pandemic should be discussed among team members and prospective patients, weighing the risks against the benefits in improving the quality of life, which were considerable for our patient who achieved motherhood with the birth of a healthy child.

Imaging evaluation of uterine arteries in potential living donors for uterus transplantation: a comparative study of MRA, CTA, and DSA.

OBJECTIVE: To evaluate uterine arteries (UA) of potential living donors for uterus transplantation (UTx) by comparison of CT angiography (CTA), digital subtraction angiography (DSA), and MR angiography (MRA) with care taken to minimize radiation doses. METHODS: Prospective donors for a clinical UTx trial were included. CTA, DSA, and MRA measurements in three predefined segments of the UAs were evaluated. Radiation doses were estimated and 1-year graft survival was recorded. RESULTS: Twelve potential donors (age 37-62 years) were investigated. There was no difference in visualized average UA lumen diameter when comparing CTA (mean 2.0 mm, SD 0.4), DSA (mean 2.1 mm, SD 0.6), and MRA (mean 2.0 mm, SD 0.3). MRA was not able to fully evaluate 10 (43%) out of 23 UA that proved to be patent on DSA. One UA was not identified by any of the modalities, and three MRA-absent UAs were identified by both CTA and DSA. The estimated mean effective dose was lower for DSA (5.1 mSv, SD 2.8) than CTA (7.1 mSv, SD 2.0), but not significantly (p value = 0.06). Three potential donors were excluded due to UA pathology and one due to adenomyosis. Eight donors underwent hysterectomy, with 1-year graft survival in six women. CONCLUSION: MRI including MRA should be the initial modality to examine potential UTx donors to acquire valuable details of uterine anatomy, and if UAs are fully visualized, there is no need for further angiographic methods with radiation. If UAs are not visualized by MRA, CTA may be performed and in selective cases with addition of the invasive modality DSA. KEY POINTS: • For uterine transplantation, pelvic MRI with MRA provides information of the uterine structure and of the diameters of uterine arteries in living donors. • Failure of MRA to demonstrate uterine arteries could be followed by CTA which will visualize the uterine arteries in a majority of cases. If MRA and additional CTA provide inconclusive results, the uterine arteries should be further evaluated by DSA. • Information of CTA can be used in the angio-system for DSA settings to minimize the radiation and contrast media doses.

Hysterectomy after uterus transplantation and detailed analyses of graft failures.

INTRODUCTION: The first live birth after uterus transplantation occurred in Sweden in 2014. Uterus transplantation has repeatedly, and at many centers worldwide, proven to be a feasible treatment for absolute uterine factor infertility. Hysterectomy in live donors and transplantation are well described in numerous reports. However, there are no reports of hysterectomy in the recipient after uterus transplantation, which will occur at either graft failure, after childbirth, or after numerous failed pregnancy attempts. We present the first report of hysterectomy in recipients after uterus transplantation with detailed analyses of findings in conjunction with graft failures. MATERIAL AND METHODS: An analysis of recipient hysterectomies (n = 10), performed in 2012-2020, was conducted. Data from the international uterus transplantation registry (ISUTx registry) were extracted, and medical records were systematically reviewed, to collect and compile characteristics of recipients and donors, as well as pre-, per-, and postoperative data, including clinical course of graft failures. RESULTS: Hysterectomy in recipients was performed in conjunction with cesarean section (n = 3), 3-6 months after cesarean section (n = 3), or after failed pregnancy attempts (n = 1) or graft failure (n = 3). The durations of anesthesia (2 h 36 min to 7 h 35 min) and hysterectomy surgery (1 h 42 min to 5 h 52 min) ranged widely, with long perioperative interruptions for insertion of ureteral catheters in two cases. Adhesions to the uterus were abundant, the majority being mild. Three uteri that subsequently showed graft failure (hysterectomy at 1, 3, and 8 months post transplantation) showed histological signs of ischemia in biopsies taken 1-week post-transplant and early signs of central hypoperfusion by Doppler ultrasound. In these graft failure explants, there were no epithelial linings in the uterine cavity or in the cervix. The inner uterine wall was severely ischemic and/or necrotic, whereas outer parts were partly viable. There were signs of moderate atherosclerosis of uterine arteries but no rejection. Mild postoperative complications were frequent (6/10), with one supravaginal hematoma requiring surgical drainage. CONCLUSIONS: Hysterectomy after uterus transplantation is a complex and time-consuming procedure, and perioperative ureteral catheters may be helpful. Histopathology of early cervical biopsies showing ischemic signs may indicate subsequent irreversible damage, leading to graft failure.

Robotic live donor hysterectomy.

PURPOSE OF REVIEW: Donor hysterectomy for live donor uterus transplantation was from the start performed by laparotomy, but minimal invasive surgery has entered the scene. In particular robotic-assisted laparoscopy is used since robotics is advantageous in the complex donor hysterectomy surgery in narrow space. This review covers the development and benefits of robotics and the published robotic donor hysterectomy experiences. RECENT FINDINGS: Robotic donor hysterectomy publications are scarce with eight cases in Sweden, five in USA, and one each in China and Spain. Robotics have been performed for either the entire donor hysterectomy or with conversion to laparotomy for the last steps of the surgical procedure. The total operative times are in line with open surgery, although a decrease is expected in the future. The estimated blood loss and hospital stays are less than at open surgery. The complication panorama includes hydronephrosis, ureteric fistula and pressure alopecia. Live births with healthy babies have been reported. SUMMARY: In uterus transplantation, robotic live donor hysterectomy has proven to be feasible, safe and associated with successful live births. The robotic donor hysterectomy is a low-volume procedure and an international registry to gather collective information is crucial for further evaluation and development.

Radiopaque Fiducials Guiding Laparoscopic Resection of Liver Tumors.

BACKGROUND: Minimal invasive laparoscopic resection of liver tumors is less traumatic compared with open surgical resection and may be a better option for many patients. However, localization of intrahepatic tumors remains a challenge. Availability of hybrid operating rooms, equipped for high performance radiologic imaging, allows for new methods of surgical navigation. METHODS: Twelve patients planned for laparoscopic resection of liver tumors were included. Before resection started, tumors were marked with radiopaque fiducials. Four fiducials were positioned with ultrasound within 1 cm of the tumor. Tumor and fiducials were localized with contrast enhanced cone beam computed tomography. Fluoroscopy with an overlay of cone beam computed tomography markings was projected side-by-side on the same screen as the laparoscopic view to visualize tumor location. The fiducials were eventually removed. Laparoscopic ultrasound, the standard method of localizing a tumor, was also used. The benefits of the 2 visualization methods were estimated by the operator. Procedure times, radiation doses and resection margins were recorded. RESULTS: Fluoroscopy with radiopaque fiducials provided valuable information, complementing the laparoscopic ultrasound, particularly during the early phase of resection. In the later phase, mobilization of the tumor-containing liver segment caused significant displacement of the fluoroscopic overlay. The technique evolved during course of the study, with decreasing procedure times and radiation doses. Radical resection was achieved for all patients. CONCLUSIONS: Radiopaque fiducials and fluoroscopy can complement laparoscopic ultrasound for guiding resection of liver tumors. Combining radiologic and optical imaging in a hybrid operating suit may facilitate development of augmented reality techniques for surgical navigation.

Uterus transplantation for fertility preservation in patients with gynecologic cancer.

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.

Evaluation of a novel navigation platform for laparoscopic liver surgery with organ deformation compensation using injected fiducials.

In laparoscopic liver resection, surgeons conventionally rely on anatomical landmarks detected through a laparoscope, preoperative volumetric images and laparoscopic ultrasound to compensate for the challenges of minimally invasive access. Image guidance using optical tracking and registration procedures is a promising tool, although often undermined by its inaccuracy. This study evaluates a novel surgical navigation solution that can compensate for liver deformations using an accurate and effective registration method. The proposed solution relies on a robotic C-arm to perform registration to preoperative CT/MRI image data and allows for intraoperative updates during resection using fluoroscopic images. Navigation is offered both as a 3D liver model with real-time instrument visualization, as well as an augmented reality overlay on the laparoscope camera view. Testing was conducted through a pre-clinical trial which included four porcine models. Accuracy of the navigation system was measured through two evaluation methods: liver surface fiducials reprojection and a comparison between planned and navigated resection margins. Target Registration Error with the fiducials evaluation shows that the accuracy in the vicinity of the lesion was 3.78±1.89 mm. Resection margin evaluations resulted in an overall median accuracy of 4.44 mm with a maximum error of 9.75 mm over the four subjects. The presented solution is accurate enough to be potentially clinically beneficial for surgical guidance in laparoscopic liver surgery.

Psychosocial risk factors for impaired health-related quality of life in living kidney donors: results from the ELIPSY prospective study.

Living kidney donors' follow-up is usually focused on the assessment of the surgical and medical outcomes. Whilst the psychosocial follow-up is advocated in literature. It is still not entirely clear which exact psychosocial factors are related to a poor psychosocial outcome of donors. The aim of our study is to prospectively assess the donors' psychosocial risks factors to impaired health-related quality of life at 1-year post-donation and link their psychosocial profile before donation with their respective outcomes. The influence of the recipient's medical outcomes on their donor's psychosocial outcome was also examined. Sixty donors completed a battery of standardized psychometric instruments (quality of life, mental health, coping strategies, personality, socio-economic status), and ad hoc items regarding the donation process (e.g., motivations for donation, decision-making, risk assessment, and donor-recipient relationship). Donors' 1-year psychosocial follow-up was favorable and comparable with the general population. So far, cluster-analysis identified a subgroup of donors (28%) with a post-donation reduction of their health-related quality of life. This subgroup expressed comparatively to the rest, the need for more pre-donation information regarding surgery risks, and elevated fear of losing the recipient and commitment to stop their suffering.

Novel approaches in uterus transplantation.

PURPOSE OF REVIEW: Uterus transplantation (UTx) is the first existing infertility treatment for women with no uterus and for women with a present nonfunctional uterus, which is unable to carry a pregnancy. This type of transplantation is a novel addition within the field of vascularized composite allografts and is the first ephemeral kind of transplantation, with the graft intended for only a restricted number of years, until the desired numbers of children have been born and with subsequent graft removal. The proof-of-concept of UTx, as an infertility treatment for women with uterine factor infertility, came with the report of the first live birth after UTx, occurring in Sweden in 2014. This UTx live birth has been followed by around 30 births, taking place in four continents. Despite the initial clinical success, UTx should still be regarded as an experimental procedure, at a developmental phase. The clinical UTx activities at several centers around the globe take place within scientific clinical trials and aim to advance UTx further. This review describes certain developmental areas around UTx. These relate to surgery, donor selection, assisted reproduction, and inclusion of new recipient groups. RECENT FINDINGS: Successful UTx procedures, with live births, have been reported both after live and deceased donor transplantation. There exist developments in the areas of robotic surgery for live donor hysterectomy, of alternate vascular connections to the graft, modifications of inclusion criteria/investigations of donors, assisted reproduction in conjunction with UTx, as well as discussions concerning expanding the pool of eligible recipients. SUMMARY: Uterus transplantation has repeatedly proven to be a feasible infertility treatment for women with absolute uterine factor infertility. Ongoing studies aim to increase safety and efficiency of the procedure as well as to better define suitable donors and recipients.

Living-Donor Uterus Transplantation: Pre-, Intra-, and Postoperative Parameters Relevant to Surgical Success, Pregnancy, and Obstetrics with Live Births.

Uterus transplantation (UTx) can provide a route to motherhood for women with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), a congenital disorder characterized by uterovaginal aplasia, but with functional ovaries. Based on our four successful living-donor transplantations and two resulting births, this analysis presents parameters relevant to standardizing recipient/donor selection, UTx surgery, and postoperative treatment, and their implementation in routine settings. We descriptively analyzed prospectively collected observational data from our four uterus recipients, all with MRKHS, their living donors, and the two newborns born to two recipients, including 1-year postnatal follow-ups. Analysis included only living-donor/recipient pairs with completed donor/recipient surgery. Two recipients, both requiring ovarian restimulation under immunosuppression after missed pregnancy loss in one case and no pregnancy in the other, each delivered a healthy boy by cesarean section. We conclude that parameters crucial to successful transplantation, pregnancy, and childbirth include careful selection of donor/recipient pairs, donor organ quality, meticulous surgical technique, a multidisciplinary team approach, and comprehensive follow-up. Surgery duration and blood vessel selection await further optimization, as do the choice and duration of immunosuppression, which are crucial to timing the first embryo transfer. Data need to be collected in an international registry due to the low prevalence of MRKHS.

Evolution of surgical steps in robotics-assisted donor surgery for uterus transplantation: results of the eight cases in the Swedish trial.

OBJECTIVE: To perform a stepwise development of the surgical method for robotics-assisted laparoscopy in donor hysterectomy for uterus transplantation (UTx), a unique treatment for absolute uterine-factor infertility. DESIGN: Prospective observational study. SETTING: University hospital. PATIENT(S): Eight donors, aged 38-62 years, underwent surgery for retrieval of the uterus and vasculature. INTERVENTION(S): Robotics-assisted laparoscopy was performed in donors for 6-7 h with video recording. Conversion to laparotomy was performed for last parts of retrieval surgery. MAIN OUTCOME MEASURE(S): Description, evaluation, and timing of 12 specific surgical steps, as well as surgical outcomes and complications. RESULT(S): There was a progression during the course of eight surgeries. In the initial two cases, seven and six items were completed with robotics compared with all 12 items in the last three procedures. The passive surgical time decreased from ∼20% in the first four cases to ∼8% in the last three procedures. The estimated median (range) blood loss, total surgical time, and length of hospital stay were, respectively, 125 mL (100-600), 11.25 h (10-13), and 5.5 days (5-6). Two reversible complications occurred: One patient acquired pressure alopecia, and one developed pyelonephritis. CONCLUSION(S): The study demonstrates a clear evolution of a strategy toward fully robotic donor surgery in UTx. This is likely to become the main approach in donor surgery of live UTx donors. CLINICAL TRIAL REGISTRATION NUMBER: NCT02987023.

Outcome of Recipient Surgery and 6-Month Follow-Up of the Swedish Live Donor Robotic Uterus Transplantation Trial.

Uterus transplantation has proved to be a feasible treatment for uterine factor infertility. Herein, we report on recipient outcome in the robotic uterus transplantation trial of 2017-2019. The eight recipients had congenital uterine aplasia. The donors were six mothers, one sister, and one family friend. Donor surgery was by robotic-assisted laparoscopy. Recipient surgery was by laparotomy and vascular anastomoses to the external iliacs. The duration (median (ranges)) of recipient surgery, blood loss, measured (left/right) uterine artery blood flow after reperfusion, and length of hospital stay were 5.15 h (4.5-6.6), 300 mL (150-600), 43.5 mL/min (20-125)/37.5 mL/min (10-98), and 6 days (5-9), respectively. Postoperative uterine perfusion evaluated by color Doppler showed open anastomoses but restricted blood distribution in two cases. Repeated cervical biopsies in these two cases initially showed ischemia and, later, necrosis. Endometrial growth was not seen, and hysterectomy was later performed, with pathology showing partly viable myometrium and fibrosis but necrosis towards the cavity. The other six patients acquired regular menstrual cyclicity. Surgery was performed in two patients to correct vaginal stenosis. Reversible rejection episodes were seen in two patients. In conclusion, the rate of viable uterine grafts during the initial 6-months of the present study (75%) leaves room for improvement in the inclusion/exclusion criteria of donors and in surgical techniques. Initial low blood flow may indicate subsequent graft failure.

Live birth after robotic-assisted live donor uterus transplantation.

INTRODUCTION: The proof-of-concept of uterus transplantation, as a treatment for absolute uterine factor infertility, came with the first live birth after uterus transplantation, which took place in Sweden in 2014. This was after a live donor procedure, with laparotomy in both donor and recipient. In our second, ongoing trial we introduced a robotic-assisted laparoscopic surgery of the donor to develop minimal invasive surgery for this procedure. Here, we report the surgery and pregnancy behind the first live birth from that trial. MATERIAL AND METHODS: In the present study, within a prospective observational study, a 62-year-old mother was the uterus donor and her 33-year-old daughter with uterine absence as part of the Mayer-Rokitansky-Küster-Hauser syndrome, was the recipient. Donor surgery was mainly done by robotic-assisted laparoscopy, involving dissections of the utero-vaginal fossa, arteries and ureters. The last part of surgery was by laparotomy. Recipient laparotomy included vascular anastomoses to the external iliac vessels. Data relating to in vitro fertilization, surgery, follow up, obstetrics and postnatal growth are presented. RESULTS: Three in vitro fertilization cycles prior to transplantation gave 12 cryopreserved embryos. The surgical time of the donor in the robot was 360 minutes, according to protocol. The durations for robotic surgery for dissections of the utero-vaginal fossa, arteries and ureters were 30, 160 and 84 minutes, respectively. The remainder of donor surgery was by laparotomy. Recipient surgery included preparations of the vaginal vault, three end-to-side anastomoses (one arterial, two venous) on each side to the external iliacs and fixation of the uterus. Ten months after transplantation, one blastocyst was transferred and resulted in pregnancy, which proceeded uneventfully until elective cesarean section in week 36+1 . A healthy boy (Apgar 9-10-10) was delivered. Follow up of child has been uneventful for 12 months. CONCLUSIONS: This is the first report of a live birth after use of robotic-assisted laparoscopy in uterus transplantation and is thereby a proof-of-concept of use of minimal invasive surgery in this new type of transplantation.

Trasplante uterino: resultados actuales. Preparación de un equipo multidisciplinario en Argentina / Uterine transplant: current results. Preparation of a multidisciplinary team in argentina

El factor uterino absoluto como causa de infertilidad, ya sea la ausencia de útero o la presencia de útero no funcional, es actualmente una patología con posibilidad de tratamiento. El primer intento de trasplante uterino en humanos fue en el año 2000, este falló y el útero necrótico tuvo que ser removido luego de 99 días. Este caso pionero inspiró a varios grupos de investigación alrededor del mundo para comenzar estudios en animales para investigar el trasplante uterino en relación a cirugía, inmunosupresión, rechazo y resultados obstétricos. El primer estudio clínico de trasplante uterino comenzó en Suecia en el año 2013 donde se realizaron nueve procedimientos a partir de donantes vivas. El primer nacido vivo en el mundo a partir de un trasplante uterino se reportó en septiembre del año 2014, luego se comunicaron dos nacimientos más en noviembre de ese mismo año. Desde ese momento se han reportado nacimientos de trasplantes uterinos en Suecia, Estados Unidos y Brasil. El caso de nacido vivo en Brasil es el primer y único nacimiento en el mundo cuya donante fue cadavérica. Todos los casos publicados de trasplante uterino y nacidos vivos serán revisados en detalle en este artículo. En el año 2016 se realizó el primer simposio de trasplante uterino en América Latina bajo el auspicio de la Asociación Latinoamericana de Medicina Reproductiva (ALMER). En ese encuentro, el equipo de la Universidad de Gotemburgo, Suecia, compartió su experiencia en trasplante uterino en humanos. Este fue nuestro puntapié para comenzar un trabajo colaborativo entre nuestro equipo en Rosario y el equipo de Suecia, con la intención de preparar un estudio científico de trasplante uterino en Argentina. Los pasos importantes para este procedimiento serán revisados en este artículo (AU)

Absolute uterine factor infertility, due to absence or non-function of the uterus, is now treatable. The first attempt of human uterus transplantation was in year 2000, but it failed and a necrotic uterus had to be removed after 99 days. This pioneering case 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 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 the trial in November 2014. Births after uterus transplantation has since then been reported from Sweden, USA and Brazil. The live birth in Brazil is the first and only birth from a deceased donor so far. All published cases of uterus transplantation and the live births will be review in detail.In 2016 there was the first symposium on uterus transplantation in Latin-America under the auspice of ALMER. At the meeting, the Swedish team shared their experiences of human uterus transplantation. This was the starting point for a collaboration work between our team in Rosario and the Swedish team, with the aim to prepare for a scientific trial of uterus transplantation in Argentina. The important steps in this procedure will be reviewed (AU)

Laparotomy or minimal invasive surgery in uterus transplantation: a comparison.

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.

Global results of human uterus transplantation and strategies for pre-transplantation screening of donors.

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.

Donors' health-related quality-of-life and psychosocial outcomes 3 years after uterus donation for transplantation.

STUDY QUESTION: What are the effects on donors' health-related quality-of-life, mood and marital relationship 2 and 3 years after uterus donation for transplantation? SUMMARY ANSWER: Overall, uterus donors were relatively stable regarding health-related quality-of-life, mood and marital relationship after donation, although slight negative deviations existed in a few participants, presumably associated with older age or with continued non-pregnancy outcomes from the donation. WHAT IS KNOWN ALREADY: Uterus transplantation has recently proved to be a successful treatment for absolute uterine factor infertility. However, there is no previous research on health-related quality-of-life and long-term psychosocial outcomes of donors. The present cohort of nine donors represents the cases of the first clinical uterus transplantation study, which took place in Sweden. Long-term follow-up studies of health-related quality-of-life in other living donors, such as of kidneys and livers, suggest that donors have above average quality-of-life prior to donation and that this typically continues during the years after donation. In our previous 1-year report on psychosocial and quality-of-life outcomes, we found that two out of nine donors showed decreased health-related quality-of-life at 6 and 12 months post donation. STUDY DESIGN, SIZE, DURATION: This complete, prospective cohort study included the nine donors of the first uterus transplantation trial, which took place in Sweden in 2013. Donors were assessed by questionnaires 2 and 3 years after surgery for uterus donation. PARTICIPANTS/MATERIALS, SETTING, METHODS: The nine donors (aged 39 to 62 years) were all a close relative or friend of their recipient. Physical and mental component summaries of health-related quality-of-life were measured with the SF-36 questionnaire. Mood was assessed by the Hospital Anxiety Depression Scale. Relationship with partner was measured with the Dyadic Adjustment Scale. MAIN RESULTS AND THE ROLE OF CHANCE: The physical and mental components of the SF-36 were generally above the mean scores for a normative population. At Year 3, the two oldest donors (above 60 years of age at surgery) showed clear negative deviations in the physical component. The mental component summary of SF-36 was essentially unaltered overall at Year 2, but slight negative deviations were seen in three donors at Year 3. These three donors were among the four with unsuccessful pregnancy outcomes for the recipients following donation. Scores of anxiety and depression (mood) were within normative values for all donors at Year 2, but one donor presented with increased (worse) values for both variables at Year 3. Two donors showed signs of relationship distress during the follow-up period and another had divorced during this period. LIMITATIONS, REASONS FOR CAUTION: The small sample size is a limitation. WIDER IMPLICATIONS OF THE FINDINGS: The present study suggests that live uterus donation does not in general negatively influence health-related quality-of-life, mood and relationship in a 2 to 3-year perspective follow-up. Longer follow-up studies, including larger number of donors and in different cultural settings, are needed. STUDY FUNDING/COMPETING INTEREST(S): The Jane and Dan Olsson Foundation for Science; the Wallenberg Foundation; an ALF grant from the Swedish state under an agreement between the government and the county councils; the Swedish Research Council; a Ferring Pharmaceuticals scholarship in memory of Robert Edwards; and the Iris Jonzén-Sandbloms and Greta Jonzéns Foundation. The authors have no competing interests. TRIAL REGISTRATION NUMBER: NCT01844362.