Living donor uterus transplant research project in Singapore: Progress of the first case.

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Author

Tan Hak Koon, Ho Tew Hong, Jeyaraj P, Brannstrom Mats: supervision and conceptualization. Tan Lay Kok and Terence Kee: writing original draft and subsequent revisions. Tan Yin Ru: data curation. Lim EC Leslie and Lim Crystal: psychiatric and psychological assessment and support. Wong Shih Lih: pathology. Law Yan Mee: radiology. Tan Ban Hock: infection management. Kee YS Terence and Thanaraju S: immunosuppression management. Brannstrom Mats, Dahm‐Kahler P, Kvarnstrom N, Ravinchandran N, Chew Khong Yik and Tan Bien Keem: performed the surgery. Wong Loong Tat, Lee SE John and Poopalingam R: anesthesiology.

Ethics

Approval of this approval project was obtained from SingHealth Centralised Institutional Review Board (CIRB) on July 10, 2018 (CIRB Ref: 2017/2742).

Results

The patient was assessed to be at low immunological risk for rejection. As a result, the antibody induction agent of choice was basiliximab 20 mg given on the day of the surgery and fourth postoperative day. Tacrolimus was started 3 days in advance prior to the admission for transplant surgery at an oral dose of 0.05 mg/kg twice a day to achieve adequate drug concentration levels prior to surgery. After surgery, the oral doses were converted to intravenous (IV) formulation until the patient was able to tolerate oral feeds and medications. The doses of tacrolimus were subsequently adjusted to posttransplant trough concentration levels of 10–12 ng/mL (0–1 month), 8–10 ng/mL (2nd–3rd month) and 6–8 ng/mL (thereafter). IV methylprednisolone 500 mg was given on Day 0 and postoperative Day 1 followed by IV hydrocortisone 50 mg 8‐hourly which was then converted to a starting dose of per oral (PO) prednisolone at 30 mg daily when the patient was able to take orally. The dose of PO prednisolone was subsequently reduced by 2 mg every week till a nadir dose of 5 mg daily was reached. PO Azathioprine was started postoperatively at 2 mg/kg daily and this dose was maintained unless there were adverse effects requiring dose reduction or discontinuation. For the recipient, perioperative prophylaxis included IV cefepime, IV metronidazole, IV anidulafungin, PO doxycycline and IV ganciclovir for 3 days before switching to PO nystatin and PO valganciclovir for 1 month. PO co‐trimoxazole was also commenced and to be continued till pregnancy. Following the discontinuation of valganciclovir, preemptive CMV prophylaxis was introduced with weekly monitoring of CMV PCR for 16 weeks, and commencement of antiviral therapy if the CMV viral load was 1000 copies/mL or more. CMV cell‐mediated immunity assay was also performed upon completion of the valganciclovir prophylaxis to determine the risks of post‐prophylaxis CMV infection. Acyclovir prophylaxis was given for 3 months following the discontinuation of valganciclovir for herpes simplex virus prevention. The donor received IV gentamicin and vlindamycin as perioperative prophylaxis because she was allergic to penicillin and erythromycin. The patient was also commenced on aspirin, folic acid and ferrous fumarate. Postoperative thromboprophylaxis included calf compression stockings and 3 days of subcutaneous enoxaparin for both donor and recipient. After general anesthesia was administered, a cystoscopy was first performed followed by bilateral ureteric stenting to facilitate intraoperative identification of the ureters. An infraumbilical midline laparotomy was performed followed by a radical total hysterectomy, bilateral salpingectomy and oophorectomy. The round ligaments were also included in the explant. Both uterine arteries were procured up to the anterior division of the internal iliac arteries. The left uterine vein, and the left and right ovarian veins were also procured. In total of 5 blood vessels were conserved with the explant (Figure  1 ). IV heparin 4000 units was given prior to the ligation and division of the uterine vessels. The explant included a vaginal cuff of 15 mm. Immediately after removal, the uterus explant was placed in ice and flushed copiously with histidine‐tryptophan‐ketoglutarate (HTK) solution and prepared for transplant. The duration of the surgery was 10 h and 30 min with an estimated blood loss was 300 mL. Uterus explant with uterine vessels conserved. The surgery for the recipient started at the 8th hour into the donor's surgery. A midline infraumbilical laparotomy was performed. A rudimentary horn was identified atop the vagina. A cruciate incision was made in the horn and the underlying blind‐ending vagina was opened. The external iliac arteries and veins were skeletonized in readiness for anastomosis with the explant. The graft was then brought into pelvis in an orthotopic position, and vascular anastomoses were undertaken; Using 7/0 polypropylene, a continuous suture technique was employed to secure end‐to‐side arterial anastomoses with the recipient's external iliac arteries. Similarly, venous anastomoses were completed between the left uterine vein and left ovarian veins to the left external iliac vein, as well as the right ovarian vein to the right external iliac vein, making a total of five vascular anastomoses. The vaginal cuff of the explant was sutured to the opened vaginal end via continuous suture. The round ligaments were also anastomosed to the pelvic side wall. A noticeable return of color of the uterus after reperfusion was observed (Figure  2 ). Before closure of the abdominal incision, Doppler ultrasound confirmed perfusion via the uterine arteries bilaterally. Blood loss was estimated at 300 mL. The total implantation operative time for the recipient was 6 h 20 min. The total warm ischemic time of the graft was 45 min, and the cold ischemic time was 1 h 45 min (total ischemic time 2 h 30 min). Reperfusion of the transplanted uterus as evidenced by the return of color in the uterus. The donor was cared for in the intensive care unit (ICU) for 1 day before being transferred to the high dependency ward for 1 day and then general ward thereafter. During her inpatient stay, the donor had macroscopic hematuria attributed to the anticoagulation and indwelling urinary catheter which required discontinuation of anticoagulation. Despite being in a single room, she also developed an upper parainfluenza viral respiratory tract infection room which was treated symptomatically with spontaneous resolution. After a week stay in hospital, the donor was discharged and has recovered without further complications. The ureteric stents were removed 3 weeks after the surgery. After surgery, the recipient was cared for in the ICU for 3 days. She remained clinically stable in the ICU and was subsequently transferred to a transplant‐specific isolation bed for further care. During the first week, she experienced 3 days of significant postoperative nausea and vomiting which required multiple antiemetics for relief. Abdominal imaging did not reveal any ileus or intestinal obstruction. Postoperative daily ultrasound Doppler of the UTx showed normal perfusion (Figures  3 , 4 , 5 ) of the allograft and a cervical biopsy on the fifth postoperative day showed no signs of rejection. During her 1 week stay in hospital, she received postoperative physiotherapy and was counseled by the transplant coordinator, dietician, pharmacist, medical social worker, and nurse clinician. The patient was discharged on the seventh postoperative day. Doppler waveform of the left uterine artery of the uterus allograft posttransplant. Doppler waveform of the left uterine vein of the uterus allograft posttransplant. Myometrial perfusion demonstrated on Doppler scan in the uterus allograft. On outpatient follow‐up, the patient was reviewed by the Principal Investigator and Transplant Physician at the SGH Gynecology and Obstetrics center weekly for the first 4 weeks following discharge. During these visits, a clinical examination, speculum vaginal inspection and protocol cervical biopsy was performed. Transabdominal pelvic ultrasonography of the uterus was performed at each visit to assess the uterus size, echogenicity and evolving endometrial thickness. Uterine vessels as well as intramyometrial (marginal, arcuate, radial, and spiral arteries) Doppler waveforms were also assessed. During the second and third months postoperatively, the patient was reviewed every 2 and then 3 weekly, respectively, with protocol‐based cervical biopsies being performed at each visit. 8 The patient experienced her first menstrual period 38 days after the surgery. The menstrual flow was normal, and no pain was reported. She subsequently menstruated regularly at 27–29 day intervals. Between her first postoperative cervical biopsy to her first admission for CMV infection, she underwent 5 cervical biopsies, all showing no rejection except one borderline change which was left untreated. Following the discontinuation of valganciclovir prophylaxis, the patient was monitored for CMV reactivation and developed significant asymptomatic viremia of 8270 copies/mL on the 67th postoperative day. This led to the admission of the patient for IV ganciclovir and IV artesunate. A scheduled protocol cervical biopsy was also performed and showed CMV viral inclusions in the uterus transplant, confirming primary allograft infection by CMV. The dose of azathioprine was reduced, and the target trough concentration level of tacrolimus was readjusted to a lower range of 6 to 8 ng/mL. During this first admission for CMV, she developed significant neutropenia to IV ganciclovir which required repeated doses of granulocyte colony stimulating factor and an eventual switch to IV foscarnet. However, the patient could not tolerate foscarnet due to significant nausea. Fortunately, the CMV viral load continued to fall and on the 80th postoperative day, the patient was switched to PO valganciclovir for an additional 3 weeks. Subsequent protocol cervical biopsies also did not show any further CMV viral inclusions. A repeat CMV IgG was now tested positive, but a CMV T‐cell immunity test following discontinuation of valganciclovir did not show any significant immune response. As a result, weekly monitoring of CMV viral load continued and the target trough concentration level of tacrolimus readjusted again to an even lower range of 4 to 6 ng/mL. The patient was subsequently discharged. To date, the patient remains well and has had 4 menstrual cycles. A total of 10 cervical biopsies were performed and did not show any rejection except for borderline changes on the 5th and 8th biopsies. The borderline changes were left untreated without any adverse consequences. Apart from the CMV infections, the patient has been otherwise tolerating immunosuppression with normal renal and liver function. The current plan is to watch the patient for another 2 months to ensure no further episodes of CMV infection and to retest the patient for CMV T‐cell immunity. Prior to planned pregnancy, the team will review her immunosuppressant therapy.

Discussion

We describe the first Living Donor Uterus Transplant Research Project surgery in Singapore on a 30‐year‐old woman with MRKH, transplanting the uterus donated from her mother‐in‐law, with good postoperative outcomes for both recipient and donor, and with the transplanted uterus successfully menstruating in the recipient. This marks a significant milestone for the research project which has spanned over a decade, including the COVID‐19 pandemic which necessitated a temporary suspension of the project. At the time of reporting, the recipient has yet to undergo embryo transfer to achieve a pregnancy. UTx remains under research study regulations in Singapore and is not an approved clinical service. Our donor–recipient pair met most of the inclusion criteria detailed in Table  1 , other than the donor having a single 3 cm subserosal fibroid (exceeding the 1 cm stipulated limit) and the recipient having only six blastocysts produced from the IVF cycle, four short of the requisite 10. The fibroid was not submucosal and the solitary 3 cm dimension was considered not to be detrimental to any subsequent intrauterine pregnancy. Indeed the first successful Australian UTx had a larger 4 cm fibroid, which was also subserosal. 9 , 10 While patients with MRKH syndrome have been reported to have diminished ovarian reserve leading to challenges in assisted reproduction, this was fortunately not the case for our recipient. 11 With regard to the number of blastocysts produced, the recipient was unwilling to undergo a second IVF cycle. In the Swedish series of nine women who underwent UTx, six women needed two pre‐UTx IVF cycles and one woman had three pre‐UTX IVF cycles to attain the goal of 10 or more embryos. 12 The UK UTx case had also only six euploid blastocysts produced. 13 The team convened and after discussion, and taking the above into consideration and further discussion with the patients, decided to allow the procedure to proceed. Like all other successful UTx programs, a multidisciplinary team was extremely important. The spectrum of clinical specialties was very wide, including transplantation medicine, surgery, gynecological surgeons experienced in extraperitoneal pelvic surgery, fertility specialists experienced in management of women with unique physical and psychological aspects of MRKH, radiologists, maternal fetal medicine specialists, anesthetists, pathologists, pharmacists, and psychologists. Collaboration with the pioneering Swedish team was critical in having the necessary experience and expertise performing the surgery. The operative metrics of our case compared favorably with results from other centers. The surgical time for both donor and recipient in the UTx surgery in our research project is well within the range reported internationally. 14 More importantly, the blood loss for both donor and recipient were only 300 mL and neither required blood transfusion. This is very different from the experience reported by the UK team describing their first UTx where there was significant blood loss requiring blood transfusion and red cell salvage, granted that they encountered abnormal vasculature in their case. 13 Our surgical results compare very favorably with the initial series performed and reported some 10 years ago by the pioneering Swedish team, 1 with similar operating times and no blood transfusions required. Neither of our patients developed any serious postoperative complications such as sepsis requiring readmission or surgery to remove the graft. It must be emphasized that the Singapore team benefited from the surgical expertise rendered by the surgeons of the same Swedish team. The immunosuppression protocol employed for the research project followed similar regimens used in kidney transplantation. Notably, we decided to use corticosteroids for immunosuppression given the observation that rejection of UTx was more frequent in corticosteroid‐free immunosuppression protocols. CMV infection is the most common viral infection to affect posttransplant patients, and the risk is higher in our case where the donor is seropositive and the recipient seronegative. 15 The adverse antenatal and perinatal effects of CMV on pregnancy are well known, including fetal structural abnormalities, fetal growth restriction, intrauterine death, sensorineural deafness and long‐term neurodevelopmental disability such as cerebral palsy. 16 Moreover, treatment of CMV during pregnancy is also potentially teratogenic. 17 Despite her high risk for CMV infection, we decided to give her only 1 month of antiviral prophylaxis when immunosuppression doses were high. This was subsequently followed by preemptive prophylaxis with a view to allow her to develop early primary CMV infection which could then lead to establishment of CMV immunity that would be important for protection of the fetus and mother during pregnancy. At the time of reporting, she remains free of CMV and is being closely monitored with CMV PCR to ensure she stays infection free prior to embryo transfer. Globally, UTx as a fertility option is viewed favorably by women with AUFI. 18 The attitudes of the medical community 19 and the public 20 towards UTx for women with AUFI are generally positive. Importantly, similar surveys carried out in Asian societies 10 with a predominance of Oriental ethnicity showed a similarly favorable attitude to UTx. Interestingly in the Japanese survey, UTx was viewed as a preferred option to gestational surrogacy and adoption for women with AUFI. Indeed a third of women responders would offer to donate their own uteri if their daughters had AUFI, and 37% of the men responders in this situation would ask their wives to be donors. Cultural differences from western societies are unlikely to be a societal hindrance to the eventual adoption of UTx as a viable fertility option. The strength of this study is that, to our knowledge, this is the first UTx performed in Singapore and South‐East Asia, and is the culmination of a long‐term research project requiring considerable investment and collaboration, drawing on collective experience and expertise, on a multidisciplinary and international scale. The weakness of this study is that no pregnancy has occurred yet in the recipient, but this is a preliminary progress report of a long‐term study, and the occurrence of normal regular menstruation is promising. This is similar to the Australian 9 and British 13 case reports of their respective first UTx, neither of which have thus far reported any pregnancies.

Conclusions

The UTx research project in Singapore of over 10 years' duration has to date undertaken one UTx surgery and a favorable postoperative outcome for both donor and recipient. The success of this complex procedure required a well‐coordinated multidisciplinary team, a strong international collaborative effort, a supportive leadership team, excellent tertiary infrastructure and careful patient selection. To date the transplanted uterus is functional, with four regular menstrual periods, supported by ultrasonographic evidence of cyclical endometrial proliferation, and has no evidence of rejection so far. Beyond this early favorable surgical outcome, the research project will evaluate outcomes from assisted reproductive procedures and any ensuing pregnancy, as this would be inform the safety and efficacy of UTx in the Singapore context.

Introduction

Until the advent of uterus transplantation (UTx), patients with absolute uterine factor infertility (AUFI) had no prospect of reproduction and childbearing other than surrogacy and adoption. Once thought to be a fantasist impossibility, UTx is now established as a clinical service in several countries around the world. It is the only medical intervention that restores reproductive anatomy and functionality for AUFI while circumventing the challenges of adoption and surrogacy, UTx is a success story of a proof of concept intervention which has translated from animal and laboratory studies to human patient trials and now accepted in clinical practice. 1 , 2 , 3 To date there are over 90 UTx procedures performed and 49 livebirths from IVF. More recent reassuring data have reported no increased risk of intrauterine growth restriction in the antepartum period, while neonatal and developmental outcomes up to 2 years were age appropriate with no delay. 4 Singapore began exploring the possibility of UTx research in 2012, and the preliminary steps and measures as well as the challenges faced by this Singaporean endeavor have been described. 5 Singapore has several established solid organ, cell and tissue transplant programs which include an ovarian tissue transplant program. Initial interest in exploring the feasibility of establishing UTx research in Singapore led to informal discussions in 2012 between the Department of Obstetrics and Gynecology and Department of Plastic and Reconstructive Surgery at the Singapore General Hospital (SGH), Singapore's largest tertiary teaching hospital. In 2013, a UTx Team was formed, comprising gynecologists, vascular surgeons, plastic surgeons, transplant physicians, infectious disease physicians, high‐risk obstetricians, psychiatrists, histopathologists, pharmacists, medical social workers, and nurses. A study Team was subsequently sent to engage the Turkish and Japanese UTx Teams, followed by preclinical preparations in 2014–2015. 6 Starting with two animal studies and dissections on macaque monkeys (one auto‐transplantation followed by one allotransplantation) under the supervision of the Japanese team, successful uterine procurement and re‐implantation were achieved. Encouragingly, the allotransplant did not show any evidence of hyper‐acute rejection for up to 6 h postoperatively with the immunosuppression regime used. In 2015, the team met Professor Mats Brännström and his team in Sweden to discuss issues of training, faculty development, and funding. A joint human cadaveric uterine dissection workshop was conducted at end of 2015, resulting in the successful complete dissection of two uterus specimens. A further sheep uterine transplant workshop for the Singapore team was conducted in Gothenburg, Sweden, in August 2016, resulting in two successful sheep uterine harvests and transplantations. The Singapore team subsequently performed dissections on a total of three macaques, three sheep and five human cadavers in Singapore. The study obtained approval from the hospital's biomedical ethics committee, and UTx was officially accepted as a new research project. Further approval was next sought from the SingHealth Centralised Institutional Review Board (CIRB) and Ministry of Health Singapore to perform uterus transplant research, with the provision to perform UTx in up to five women. The protocol included inclusion and exclusion criteria for both donor and recipient (Table  1 ). This research was not registered under a public clinical trials registry. Inclusion and exclusion criteria for both donor and recipient. Female AUFI Normal ovarian reserve and function Aged 24–38 years (40 if embryos frozen <38 years) Normal length vagina No skin/intestinal neovagina Body mass index 21 years) Biological and/ or non‐biologically related Multiparous (1 Appropriate matching ABO/Rh compatibility (requisite) Cross‐matched (requisite) HLA tissue matching—A, B and DR >4/6 matched (preferable) Normal pelvic ultrasound Myoma <1 cm acceptable but not submucosal Macroscopically normal cervix Benign appearing polyp acceptable but send for urgent histology Negative smear + human papillomavirus Negative genitourinary medicine screen (Chlamydia, Gonorrhea, Trichomonas vaginalis) Negative infection screen (HIV, Hepatitis B, Hepatitis C, Syphilis) Previous children including adopted or born by surrogacy Previous multiple major abdominal/pelvic surgery Premature ovarian failure with no frozen mature eggs/embryos Severe endometriosis Significant medical problems including: renal pathology, thrombophilia Previous cancer <5 years in remission History of significant psychiatric illness History of cancer Previous multiple/significant uterine surgery ABO/Rh incompatibility One cesarean section acceptable No previous myomectomies Abnormal pelvic ultrasound Submucous fibroid(s) Moderate to severe adenomyosis Congenital uterine anomalies (other than mild arcuate uterus) Previous significant cervical surgery (Cone biopsy or LLETZ) Significant systemic disease (diabetes, systemic lupus erythematosus, etc.) Previous obstetric problems including delivery <37/40 Previous recurrent miscarriages (three or more) Current intravenous drug abuse Active bacteremia/fungemia Abbreviations: AUFI, absolute uterine factor infertility; LLETZ, large loop excision of the transformation zone. The objective of the Living Donor Uterus Transplant Research Project in Singapore is to safely introduce human donor UTx in Singapore and study the outcomes in the donors and recipients. In the present paper, we report the perioperative and postoperative outcomes for the first donor–recipient pair.

Materials And Methods

The research program suffered a setback during the COVID‐19 pandemic between 2020 and 2022, during which it was not possible to start recruitment of suitable candidates. A suitable recipient–donor pair was subsequently identified and recruited. The recipient is a 30‐year‐old female who was diagnosed with Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome at 18 years of age when she was investigated for primary amenorrhoea. She was found to have complete absence of the uterus and cervix but had two ovaries, two kidneys and a blind‐ending vagina. Her past medical history was unremarkable apart from eczema and a history of having had COVID‐19 and dengue infection on separate occasions. There was no history of previous surgeries and no significant family history. She was not on any long‐term medications. She was a non‐smoker and only consumed alcohol occasionally. The recipient was married and practiced self‐dilatation of the vagina which on physical examination measured 8 cm long. Her body mass index was 20 kg/m 2 and the oral glucose tolerance test was normal. She underwent multidisciplinary medical and psychosocial evaluation that was based on the protocol from the SGH kidney transplant program (Table  2 ) as well as UTx specific evaluation by the gynecologist and high‐risk obstetrician. The evaluation also included the thiopurine methyltransferase test which showed normal metabolism status for azathioprine, while genotyping for CY3PA5 polymorphism revealed that she was a slow metabolizer for tacrolimus. There were no significant findings on evaluation except that she was seronegative for cytomegalovirus (CMV) immunoglobulin. Evaluation protocol for uterus transplant recipient (adapted from the SGH Kidney transplant protocol). Abbreviations: CMV, cytomegalovirus; CS, culture and sensitivity; CT, computed tomography; CXR, chest EX‐ray; EBV, epstein–barr virus; ECG, electrocardiogram; GFR, glomerular filtration rate; HAV, hepatitis A virus; HbA1c, glycated hemoglobin; HBV, hepatitis B virus; HCV, hepatitis C virus; HEV, hepatitis E virus; HIV, human immunodeficiency virus; HLA, human leukocyte antigen; MRI, magnetic resonance imaging; PRA, panel reactive antibody; TB‐SPOT, tuberculosis ELISpot assay; TPPA, treponema pallidum particle agglutination; VZV, varicella zoster virus. MRI of the pelvis revealed a cavitatory rudimentary right uterine horn, and a non‐cavitatory rudimentary left uterine horn. Both ovaries were normal. The scan also reported that the upper vagina vault was found to be atretic and lower non atretic vagina was 2.9 cm long. However, physical examination found that the vagina length measured 8 cm with no obvious obliteration of the vaginal walls. Her ovarian reserve was also evaluated and found to be satisfactory (luteinizing hormone 0.8 iU/L, estradiol 6136 pmol/L, follicular stimulating hormone 2.3 iU/L, anti‐Mullerian hormone 3.2 ng/mL, reference rage 0.89–9.85). Histocompatibility assessment identified her as ABO blood Team A Rhesus positive and crossmatching (complement‐dependent cytotoxicity and flow cytometric) was negative. High resolution donor and recipient HLA typing by next generation sequencing revealed no donor‐specific antibodies. The recipient's mother was originally considered to be the potential uterus donor but was subsequently excluded as her blood Team was AB Rhesus positive. As a result, her mother‐in‐law, aged 51 years old, with ABO blood Team A Rhesus positive volunteered and consented to be the donor. The donor had no significant comorbidities but had an initial BMI of 28 kg/m 2 which she reduced to 26 kg/m 2 through diet and physical activity. Medical and psychosocial evaluation was also based on the kidney donor protocol from the SGH kidney transplant program (Table  3 ) which found her fit to be a uterus donor. Notably, she was seropositive for CMV immunoglobulin. The donor was a mother of two and had delivered her first child vaginally and the second via a cesarean section for a placenta praevia. Both pregnancies reached term and were uncomplicated. She was still having regular menstruation. Her uterus was bulky on ultrasonography, with a 3 cm subserosal fibroid and some features of adenomyosis. The fibroid was not encroaching nor disrupting the uterine cavity, and agreement was made by the team to grant an exception to the exclusion criteria as the solitary subserosal fibroid was considered to have minimal impact on subsequent pregnancy potential. The challenge of finding another suitable matched donor was also considered. A CT angiography of the pelvis was carried out to map the pelvic vasculature. The uterine arteries were identified, and the caliber was measured at 3 mm. The ovarian veins measured 5 mm. The tributaries of uterine venous plexus were visualized to drain into bilateral internal iliac veins. Evaluation protocol for uterus transplant living donor. Abbreviations: CMV, cytomegalovirus; CS, culture and sensitivity; CT, computed tomography; CXR, chest EX‐ray; EBV, epstein–barr virus; ECG, electrocardiogram; GFR, glomerular filtration rate; HAV, hepatitis A virus; HbA1c, glycated hemoglobin; HBV, hepatitis B virus; HCV, hepatitis C virus; HEV, hepatitis E virus; HIV, human immunodeficiency virus; HLA, human leukocyte antigen; MRI, magnetic resonance imaging; PRA, panel reactive antibody; TB‐SPOT, tuberculosis ELISpot assay; TPPA, treponema pallidum particle agglutination; VZV, varicella zoster virus. The pair underwent the requisite matching process as well as medical, psychiatric and psychosocial assessments. Pyschological evaluation followed closely the framework developed and used by the Swedish UTx team, focusing on the domains of psychopathology, substance abuse, quality of life, marital relations, adaptations to stressors and coping skills, childlessness and treatment with UTx. 7 Ethics approval was obtained from SingHealth Transplant, SGH Biomedical Ethic Committee and the National Transplant Ethics Committee to conduct the transplant procedure as an experimental procedure with a predefined research protocol. The recipient also underwent in vitro fertilization treatment resulting in six frozen blastocysts (three at Day 5 and three at Day 6). She did not wish to repeat another cycle of IVF to obtain more embryos in view of the entry criteria of 10 embryos, and agreement was reached to proceed with the UTx with six blastocysts. Preparations have also been made for the transplant surgery to be carried out on November 25, 2023 in SGH, aided by the three UTx experts from the Swedish Team (Prof Brännström, Prof Pernilla Kahler and Dr. Niclas Kvarnström), for whom temporary registration had been granted by the Singapore Medical Council.

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