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.

Evolving clinical challenges in uterus transplantation.

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.

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.

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.

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.

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.

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.

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.

Preoperative psychological evaluation of uterus transplant recipients, partners, and living donors: Suggested framework.

Uterus transplant has become a real option for women with uterine-factor infertility to become pregnant and give birth. The screening before uterus transplant consists of a multidisciplinary evaluation and includes the potential recipient, living donor, and, to some extent, the recipient's partner and future co-parent. The psychological evaluation has evolved from broad-based screening in the first uterus transplant trial, where the aim was to find suitable candidates for a novel experimental procedure with an unknown outcome, to a more directed screening with specific psychological domains for a complex infertility treatment with promising results. This report outlines a consensus by investigators with pioneering experience in the field of the key factors and suggests a framework for psychological evaluation of recipients and their partners as well as for live uterus donors before uterus transplant. We identify the main areas of particular value to the recipient screening (general psychological health, factors associated with infertility, and medication adherence), the partner (general psychological health and factors associated with infertility), and the living donor (psychological health and motivation to donate, especially in the case of the nondirected donor).

Selecting living donors for uterus transplantation: lessons learned from two transplantations resulting in menstrual functionality and another attempt, aborted after organ retrieval.

PURPOSE: To contribute to establishing donor selection criteria based on our experience with two successful living-donor human uterus transplantations (UTx) and an aborted attempt. METHODS: This interventional study included three patients with uterine agenesis, aged 23, 34, and 23 years, scheduled for UTx, and their uterus-donating mothers, aged 46, 61, and 46 years, respectively. Interventions included preoperative investigations, donor surgery, back-table preparation, and recipient surgery. Preoperative imaging, surgical data, histopathology, menstrual pattern, and uterine blood flow were the main outcome measures. RESULTS: In the first case (46-year-old mother/23-year-old daughter), donor/recipient surgery took 12.12/5.95 h. Regular spontaneous menstruations started 6-week post-transplantation, continuing at 24-28-day intervals throughout the 6-month observation period. Repeated follow-up cervical biopsies showed no signs of rejection. In the second case (61-year-old donor), surgery lasted 13.10 h; attempts to flush the retrieved uterus failed due to extreme resistance of the left uterine artery (UA) and inability to perfuse the right UA. Transplantation was aborted to avoid graft vessel thrombosis or insufficient blood flow during potential pregnancy. Histopathology revealed intimal fibrosis and initial sclerosis (right UA), extensive intimal fibrosis (parametric arterial segments), and subtotal arterial stenosis (myometrial vascular network). In the third case (46-year-old mother/23-year-old daughter), donor/recipient surgery took 9.05/4.52 h. Menstruations started 6-week post-transplantation. Repeated cervical biopsies showed no signs of rejection during the initial 12-week follow-up period. CONCLUSIONS: Meticulous preoperative evaluation of potential living uterus donors is essential. This may include selective contrast-enhanced UA angiograms and limitation of donor age, at least in donors with risk factors for atherosclerosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03048396.

Livebirth after uterus transplantation.

BACKGROUND: Uterus transplantation is the first available treatment for absolute uterine infertility, which is caused by absence of the uterus or the presence of a non-functional uterus. Eleven human uterus transplantation attempts have been done worldwide but no livebirth has yet been reported. METHODS: In 2013, a 35-year-old woman with congenital absence of the uterus (Rokitansky syndrome) underwent transplantation of the uterus in Sahlgrenska University Hospital, Gothenburg, Sweden. The uterus was donated from a living, 61-year-old, two-parous woman. In-vitro fertilisation treatment of the recipient and her partner had been done before transplantation, from which 11 embryos were cryopreserved. FINDINGS: The recipient and the donor had essentially uneventful postoperative recoveries. The recipient's first menstruation occurred 43 days after transplantation and she continued to menstruate at regular intervals of between 26 and 36 days (median 32 days). 1 year after transplantation, the recipient underwent her first single embryo transfer, which resulted in pregnancy. She was then given triple immunosuppression (tacrolimus, azathioprine, and corticosteroids), which was continued throughout pregnancy. She had three episodes of mild rejection, one of which occurred during pregnancy. These episodes were all reversed by corticosteroid treatment. Fetal growth parameters and blood flows of the uterine arteries and umbilical cord were normal throughout pregnancy. The patient was admitted with pre-eclampsia at 31 full weeks and 5 days, and 16 h later a caesarean section was done because of abnormal cardiotocography. A male baby with a normal birthweight for gestational age (1775 g) and with APGAR scores 9, 9, 10 was born. INTERPRETATION: We describe the first livebirth after uterus transplantation. This report is a proof-of-concept for uterus transplantation as a treatment for uterine factor infertility. Furthermore, the results show the feasibility of live uterus donation, even from a postmenopausal donor. FUNDING: Jane and Dan Olsson Foundation for Science.

Reproductive, obstetric, and long-term health outcome after uterus transplantation: results of the first clinical trial.

OBJECTIVE: To evaluate reproductive, obstetric, and long-term health of the first completed study of uterus transplantation (UTx). DESIGN: Prospective. SETTING: University hospital. PATIENT(S): Nine live donor UTx procedures were conducted and seven were successful. Donors, recipients, and children born were observed. INTERVENTION(S): In vitro fertilization was performed with embryo transfer (ET) of day 2 or day 5 embryos in natural cycles. Pregnancies and growth trajectory of the children born were observed. Health-related quality of life, psychosocial outcome, and medical health of donors and recipients were evaluated by questionnaires. MAIN OUTCOME MEASURE(S): The results of in vitro fertilization, pregnancies, growth of children, and long-term health of patients were reported. RESULT(S): Six women delivered nine infants, with three women giving birth twice (cumulative birth rates of 86% and 67% in surgically successful and performed transplants, respectively). The overall clinical pregnancy rate (CPR) and live birth rate (LBR) per ET were 32.6% and 19.6%, respectively. For day 2 embryos, the CPR and LBR per ET were 12.5% and 8.6%, respectively. For day 5 embryos, the CPR and LBR per ET were 81.8% and 45.4%, respectively. Fetal growth and blood flow were normal in all pregnancies. Time of delivery (median in full pregnancy weeks + days [ranges]) by cesarean section and weight deviations was 35 + 3 (31 + 6 to 38 + 0) and -1% (-13% to 23%), respectively. Three women developed preeclampsia and four neonates acquired respiratory distress syndrome. All children were healthy and followed a normal growth trajectory. Measures of long-term health in both donors and recipients were noted to be favorable. When UTx resulted in a birth, scores for anxiety, depression, and relationship satisfaction were reassuring for both the donors and recipients. CONCLUSION(S): The results of this first complete UTx trial show that this is an effective infertility treatment, resulting in births of healthy children and associated with only minor psychological and medical long-term effects for donors and recipients. CLINICAL TRIAL REGISTRATION NUMBER: NCT02987023.

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.

Post-nephrectomy development of renal function in living kidney donors: a cross-sectional retrospective study.

BACKGROUND: Increasing numbers of living donor kidney transplantations calls for better knowledge about long-term donor outcomes and risks. METHODS: To explore long-term kidney donor outcomes and risks, we conducted a cross sectional retrospective study. To this end, we analysed renal function using measured glomerular filtration rate (mGFR) and estimated glomerular filtration rate (eGFR) as well as microalbuminuria, blood pressure (BP), body mass index, haemoglobin, albumin and parathyroid hormone in kidney donors nephrectomized between 1965 and 2005. RESULTS: A total number of 573 kidney donors agreed to undergo medical follow-up examinations. The mean age (standard deviation) at donation was 47 (11) years and the mean time since donation was 14 (9) years. Both mean mGFR [68 (15) mL/min/1.73 m(2) body surface; P = 0.028] and mean eGFR [71 (16) mL/min/1.73 m(2) body surface; P < 0.001], based on modified diet renal dysfunction and iohexol or Cr-EDTA clearance, respectively, were found to decrease with age and to increase with time since donation. Special multivariable regression analyses reveal that for 30-year old donors, the median eGFR typically increases during the first 17 years, then remains constant for ~8 years and slowly declines thereafter. For 50-year-old donors, the median eGFR is expected to increase during the first 15 years or so and then to enter a phase of slight progressive decline. In total, 23% (126/546) of the donors were on antihypertensive medication. An additional 22% (117/543) of the donors were found to suffer from hitherto undiagnosed hypertension (BP >140/90 mm Hg). CONCLUSION: Renal function of the remaining kidney in living donors is expected to improve for many years but will show signs of slight deterioration in the longer run.

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.

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 outcomes of uterine transplant recipients and partners up to 3 years after transplantation: results from the Swedish trial.

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.

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.