Anesthesia for uterine transplantation
Article information
Abstract
Uterine transplantation (UTx) represents a groundbreaking fertility-enabling procedure for women with absolute uterine factor infertility. Since the first successful live birth in 2014, the field has advanced rapidly, supported by accumulating clinical experience and evolving surgical techniques. As a complex and multidisciplinary operation, UTx requires meticulous coordination among specialties such as gynecology, transplant surgery, reproductive medicine, and anesthesiology. Anesthesiologists play a pivotal role in maintaining physiological stability throughout the surgical process, from donor organ retrieval to recipient graft implantation, reperfusion, and immediate postoperative recovery. This review examines the historical background, current status, and future directions of UTx, with a particular emphasis on anesthetic management. Key aspects include preoperative assessment and intraoperative management strategies. Additionally, the review discusses anesthetic considerations for pregnancy and cesarean delivery following successful transplantation. As clinical programs expand, anesthetic protocols must continue to adapt based on emerging evidence, collaborative research, and increasing procedural experience. Through comprehensive perioperative care, anesthesiologists contribute significantly to the success of UTx and the realization of childbirth in women previously considered infertile.
INTRODUCTION
Uterine transplantation (UTx) represents a major advancement in reproductive medicine and transplant surgery. It is the first and only therapeutic option that enables women with absolute uterine factor infertility—resulting from congenital absence of the uterus (e.g., Mayer–Rokitansky–Kuster–Hauser syndrome [MRKH]), acquired absence (e.g., hysterectomy), or severe uterine malformation—to achieve biological motherhood. Unlike other solid organ transplantations, UTx is distinctive in that it is a temporary and non–life-saving procedure, intended to enable fertility rather than sustain life. Consequently, it presents a range of ethical, surgical, and medical challenges.
UTx was first successfully performed in Saudi Arabia in 2000, marking a paradigm shift in reproductive medicine, although acute thrombosis necessitated graft removal on the 99th postoperative day [1]. The first successful live birth following living donor UTx was reported in Sweden in 2014 [2], followed by the first successful live birth after deceased donor UTx in 2017 by a Brazilian team [3]. Since then, the number of procedures has increased globally. As of 2024, more than 78 UTx procedures have been performed worldwide, resulting in over 40 live births [4]. UTx requires coordinated multidisciplinary care involving gynecologic surgery, transplant medicine, reproductive endocrinology, and anesthesiology. Among these disciplines, anesthesiologists play a vital role during the most dynamic stages of the transplant process—the surgical phases spanning donor organ retrieval, recipient implantation, and graft reperfusion. They are responsible for maintaining hemodynamic stability, ensuring adequate graft perfusion, implementing thromboprophylaxis, and collaborating closely with the surgical team to manage intraoperative changes. This review emphasizes anesthetic considerations essential for optimizing outcomes in UTx and discusses evolving practices informed by current literature and expanding clinical experience.
THE COURSE OF UTERINE TRANSPLANTATION
Success in UTx is evaluated through three sequential stages that extend well beyond the perioperative period. The initial indicator of success is a favorable surgical outcome, commonly assessed by graft viability within the first three months. The second stage involves confirmation of graft function, typically demonstrated by the establishment of regular menstruation over several months. The final marker of success is the achievement of pregnancy and the delivery of a healthy infant. Pregnancy attempts are generally deferred for at least 12 months after transplantation to allow sufficient recovery and to confirm sustained graft function. This stepwise assessment underscores the importance of long-term planning, multidisciplinary collaboration, and patient endurance throughout the process. Following successful live birth(s), the graft is removed to avoid the need for lifelong immunosuppressive therapy [5].
REPORTED OUTCOMES AND COMPLICATIONS
Living donor morbidity
Living donor morbidity reflects the technical complexity of donor hysterectomy and varies depending on the surgical approach. Reported mean operative times are approximately 11 h and 45 min for robotic procedures, 8 h and 10 min for open procedures, and 3 h and 30 min for laparoscopic procedures, illustrating distinct differences in resource utilization and recovery profiles [6]. The mean estimated blood loss in donor procedures has been reported as 600 ± 581 ml (range, 100–2,400 ml) [7]. Although open donor hysterectomy has traditionally been considered the standard approach, minimally invasive techniques are increasingly being adopted to promote faster donor recovery. Robot-assisted procedures, in particular, remain in an early developmental phase and are often associated with longer operative times [5]. Consequently, the donor surgical approach can influence the total operative duration and, in turn, may affect the risk of graft thrombosis—an important factor to consider in perioperative planning. As operative duration increases, the potential for venous thromboembolism requires careful attention. Furthermore, dissection around the uterine venous plexus—where vascular density is high and the ureter lies in close proximity—poses a risk of ureteral injury and significant blood loss [5,8].
Operative metrics
Operative demands and variability have been consistently reported across published series. For recipient implantation, the mean operative duration has been reported as approximately 5 h and 5 min, with a range from about 3 h and 30 min to 11 h, depending on anatomical complexity, donor type, and history of prior surgery. The mean estimated blood loss has been reported as 632 ± 397 ml (range, approximately 200–2,000 ml). Ischemic parameters demonstrate similar variability, with mean cold ischemia times of approximately 2 h and 50 min ± 1 h and 47 min for living donors and 5 h and 42 min ± 2 h and 7 min for deceased donors. The average warm ischemia interval during implantation is approximately 1 h and 6 min ± 21 min [7]. These values should be interpreted with caution because of differences in case composition and institutional practices.
Graft survival and recipient complications
According to a report analyzing the first 45 cases of UTx, graft survival outcomes were as follows: 55.6% of grafts retained function, 28.9% required emergency hysterectomy, and 15.5% underwent planned hysterectomy, most often following successful delivery. Overall, 33.3% of recipients experienced complications classified as Clavien–Dindo grade IIIb or higher. Most emergency hysterectomies (76.9%) occurred within the first two postoperative weeks [7]. The primary precipitating factor was graft thrombosis, while other reported causes included infection, graft ischemia, necrosis, inadequate venous outflow, and hemorrhage originating from branches of the internal iliac artery [7,9].
Additional recipient complications have included graft hypoperfusion, intrauterine infection, post-transplant lymphoproliferative disorder, and recurrent miscarriage or implantation failure [8].
Updated registry data encompassing 78 UTx cases worldwide, reported in 2024, indicated a graft survival rate of approximately 74%, with major complications (Clavien–Dindo grade ≥ IIIb) observed in about 14% of recipients—representing a notable improvement compared with the earlier cohort of 45 cases [4]. This improvement likely reflects continued refinement in surgical techniques and perioperative management strategies.
Obstetric and neonatal outcomes
Across contemporary cohorts, UTx has resulted in live births in 36% to 58% of recipients overall, increasing to approximately 83% when the graft remains viable at one year. The median gestational age at delivery ranges from 35 to 36 + 6 weeks [10,11]. Cesarean delivery is universal, with emergency cesarean section reported in 47.5% of cases. The incidence of preterm birth following UTx is high—approximately 70% in early pooled analyses. Earlier cohorts commonly scheduled cesarean delivery before 37 weeks, whereas more recent programs increasingly plan delivery at ≥ 37 weeks to reduce prematurity-related morbidity [12,13]. Maternal morbidity is primarily characterized by hypertensive disorders (gestational hypertension or preeclampsia) in 12–26%, gestational diabetes in 5–12%, placenta previa in 5–13%, and preterm premature rupture of membranes in 10–47%; importantly, no maternal deaths have been reported in major series [13]. Neonatal outcomes closely reflect gestational age, with low birth weight (< 2,500 g) in 43% and neonatal intensive care unit admission in 47%, typically for brief durations (median 2.5–18 days). Congenital anomalies remain rare, with rates comparable to those in the general population [11,13]. Based on current evidence, neonatal outcomes appear more closely related to gestational age at delivery than to transplant-specific factors.
ANATOMICAL AND SURGICAL ASPECTS
Pelvic anatomy relevant to UTx
The uterus receives its primary arterial supply from the uterine arteries, which arise from the anterior division of the internal iliac arteries, and is drained by a complex venous network that includes the deep uterine veins and the utero-ovarian or ovarian veins. The ureter passes in close proximity to the uterine artery at the level of the cervix (“water under the bridge”) and courses through the lateral parametria near the uterine venous plexus—an anatomical relationship that contributes to the difficulty of ureteral dissection in this region. The external iliac artery and vein are commonly utilized as recipient sites for end-to-side anastomoses; their exposure and control represent key steps from both anesthetic and surgical perspectives, as short periods of partial vascular clamping may be necessary [7,8].
Graft composition and variability
The transplanted graft generally includes the uterus with a vaginal cuff, parametrial tissue, and vascular pedicles. In deceased donor cases, longer segments of the internal iliac vessels are often available, whereas in living donor transplantation, the vascular pedicles are typically shorter and smaller in caliber. Vessel quality may vary depending on donor characteristics. Variations in venous outflow—whether through the deep uterine veins or the utero-ovarian pathways—have important implications for determining the number and configuration of venous anastomoses [5,14].
Recipient operation: key stages
• Exposure and vessel control: A midline vertical or transverse abdominal incision is chosen based on previous surgical history and the presence or likelihood of adhesions. The external iliac vessels are exposed and looped in preparation for end-to-side vascular anastomoses. Dense pelvic adhesions—particularly around the uterine venous plexus—are common and can increase the risk of intraoperative bleeding [4,15,16].
• Vaginal anastomosis: The graft’s vaginal cuff is anastomosed to the recipient’s vaginal vault to restore anatomical continuity and enable future obstetric management [17].
• Vascular anastomoses: Venous anastomoses are typically performed first—connecting the deep uterine and/or utero-ovarian or ovarian veins to the external iliac vein—followed by arterial inflow via anastomosis of the uterine artery to the external iliac artery. Some centers have reported the use of fluorescence imaging after clamp release to assess graft perfusion [8,18,19].
• Reperfusion and fixation: Following declamping, perfusion is evaluated clinically (based on color and turgor) and, when available, with adjunctive Doppler assessment. Hemostasis is achieved, and the graft is secured by suspending it with the round and uterosacral ligaments to maintain its anatomical position [20-22].
Anatomical and surgical features with anesthetic relevance
• Bleeding sources: The uterine venous plexus and branches of the internal iliac system are common sources of intraoperative hemorrhage; bleeding from the vaginal cuff may also occur. Cross-matched blood should be prepared in advance, and targeted transfusion strategies are emphasized to ensure hemodynamic stability [16,23,24].
• Temporary vascular clamping: Partial clamping of the external iliac vessels during end-to-side anastomosis necessitates maintaining stable systemic arterial pressure while avoiding excessive vasoconstriction that could impair graft inflow or outflow [25].
• Venous outflow configuration: Multiple small-caliber venous anastomoses may predispose to venous stasis and thrombosis, influencing anticoagulation timing and hemodynamic management around the reperfusion phase [8,9,16,26].
• Ureteral proximity: The ureter lies close to pelvic dissection planes. Although ureteral injury on the recipient side is rarely reported compared with living donors, early recipient series have documented urinary tract injuries—including intraoperative bladder injury and vesicovaginal fistula—indicating that high vigilance for urinary leakage or hematuria is warranted. During graft hysterectomy or technically challenging reoperations, some centers employ perioperative ureteral catheterization to help identify and protect the ureters [8,23,27].
ANESTHETIC CONSIDERATIONS
Perioperative goals
In 2021, the United Kingdom UTx team published perioperative anesthetic recommendations, advising that intraoperative and perioperative management adhere to the Enhanced Recovery After Surgery (ERAS) principles established for gynecologic oncology [28]. Among the different perioperative phases, intraoperative management is particularly critical. The primary objectives include maintaining normothermia, achieving optimal fluid balance, preventing postoperative nausea and vomiting (PONV), and minimizing opioid use. Detailed management strategies are described in the following sections.
Preoperative evaluation
The preoperative assessment largely parallels that of solid organ transplantation, with emphasis on uterine arterial and venous patency as well as comprehensive infection screening. Donors tend to be older—mean ages of approximately 45 years for living donors and 38 years for deceased donors—whereas recipients are generally younger (mean 28 years) and typically have fewer comorbidities than other solid organ transplantation candidates, preserving sufficient physiological reserve to tolerate perioperative stress [28]. Because MRKH syndrome represents the most common indication, associated congenital anomalies are not rare, most often involving renal and skeletal malformations and, less commonly, congenital cardiac defects. These findings warrant targeted preoperative evaluation. Reported prevalences include single kidney in approximately 25% and spinal anomalies in 30–40%, although actual rates among UTx candidates vary across centers depending on recipient selection criteria [29]. While most programs currently maintain strict recipient selection protocols, increasing program maturity and wider access are expected to raise the frequency of candidates presenting with such anomalies.
The preoperative workup typically includes computed tomography angiography or magnetic resonance angiography for vascular mapping; human leukocyte antigen typing, panel reactive antibody testing, and crossmatching; vaccination updates; and embryo cryopreservation before transplantation. Individualized assessments should also address thromboembolic risk, anesthetic fitness, and oncologic screening to ensure procedural safety and optimize both graft function and reproductive outcomes. Institutional preparedness may additionally involve establishing standardized protocols for anticoagulation, antibiotic prophylaxis, and immunosuppression before surgery [14].
Intraoperative management
1. General concept
UTx remains an emerging surgical procedure, and definitive, universally accepted anesthetic guidelines have not yet been established. The following considerations summarize expert consensus and institutional practices derived from reported successful cases [28,30]. UTx is most commonly conducted under balanced general anesthesia using either a volatile anesthetic agent or total intravenous anesthesia, in combination with a non-depolarizing neuromuscular blocker and multimodal, opioid-sparing analgesia. Whenever feasible, tracheal extubation is performed in the operating room. Elements of the ERAS protocol for gynecologic oncology may be incorporated to minimize PONV, reduce perioperative opioid exposure, and facilitate early mobilization.
2. Monitoring, vascular access, positioning, and temperature
• Monitoring and vascular access: Standard American Society of Anesthesiologists monitors should be supplemented with an invasive arterial line, typically in the radial artery, to enable beat-to-beat blood pressure monitoring and arterial blood gas analysis. Two large-bore peripheral intravenous lines or a central venous catheter (internal jugular or subclavian vein) should be secured to allow vasoactive drug infusions and ensure reliable vascular access. Femoral cannulation should be avoided because it may interfere with exposure of the operative field. Depth of anesthesia monitoring, using either age-adjusted minimum alveolar concentration or an electroencephalography (EEG)-based index, is advisable during these prolonged operations. Advanced hemodynamic monitoring systems (e.g., FloTrac for cardiac output, cardiac index, stroke volume variation, and systemic vascular resistance) may aid goal-directed fluid therapy in selected cases.
• Positioning and temperature: Recipients are placed in the lithotomy position to facilitate pelvic exposure. To accommodate self-retaining retractors, one arm is typically tucked at the patient’s side while the other is abducted to less than 90°. All pressure points must be carefully padded. Active warming measures include an underbody warming blanket or upper body forced-air warming device along with warmed intravenous fluids to maintain normothermia.
3. Fluid strategy and preparation of blood products
Balanced crystalloids are preferred for maintenance fluid therapy. Fluids should be titrated according to dynamic hemodynamic parameters, urine output, and acid–base status rather than administered at fixed rates. Colloid solutions (e.g., 5% albumin or 6% hydroxyethyl starch [HES 130/0.4]) may be considered in selected cases. Cross-matched blood products should be prepared in advance—typically two to four units of leukoreduced, irradiated packed red blood cells. Preoperative blood preparation should take into account each patient’s surgical and medical history. Factors such as prior hysterectomy, previous abdominal surgery, or a history of pelvic radiotherapy may increase the risk of intraoperative bleeding; therefore, securing large-bore venous access and arranging adequate blood product availability are recommended. Autologous cell salvage is employed in selected centers.
4. Hemodynamic goals and vasoactive support
Common intraoperative hemodynamic targets include maintaining systolic blood pressure above 100 mmHg and mean arterial pressure above 65 mmHg or within 20% of baseline values, with heightened vigilance during vascular anastomosis and reperfusion. Vasoactive drugs may be administered to preserve graft perfusion and hemodynamic stability. Excessive vasoconstriction that could impair graft perfusion should be avoided whenever possible.
5. Anticoagulation and coagulation management
Graft thrombosis has been reported in approximately 20–25% of recipients and represents the leading cause of graft loss [4,11]. Identifying risk factors in advance may be beneficial; the likelihood of thrombosis appears higher when organ retrieval is prolonged or when vascular reconstruction is required. Given this high risk, a structured, protocol-based approach to anticoagulation is essential. For intraoperative thromboprophylaxis, systemic heparinization is frequently used in both donors and recipients [31]. In donors, administration of 5,000 IU of heparin before clamping the uterine vessels has been described [32]. In recipients, intravenous unfractionated heparin is typically administered before vascular anastomosis. Reported regimens include fixed-dose boluses (e.g., 5,000 IU [26]), weight-based dosing (e.g., 0.5 mg/kg [33]), and, in non-human primate studies, 3,000 IU [34-36]; dosing should be individualized based on bleeding risk and the operating surgeon’s plan. The United Kingdom UTx team recommends administering 5,000 IU of subcutaneous heparin [16,28]. The same guidance also advocates performing thromboelastography at induction, during vascular anastomosis, and postoperatively to assess thrombotic risk and guide targeted component therapy. Activated clotting time (ACT) monitoring may also be performed throughout the procedure.
6. Immunosuppression and adjunct medications
Intraoperative immunosuppressive induction follows institutional transplant protocols. Induction agents commonly used in solid organ transplantation have been applied in UTx. Among these, the polyclonal antibody anti-thymocyte globulin (Atgam) is most frequently utilized [37,38], and the use of monoclonal antibody basiliximab (Simulect) has also been reported [38,39]. Additionally, at least two centers have described the use of alemtuzumab as induction immunosuppressive therapy for UTx [16,40]. High-dose corticosteroids (e.g., methylprednisolone 500 mg) and osmotic diuretics (e.g., mannitol 20%, 62.5 ml or 15%, 83 ml) are commonly administered before reperfusion. Given the risk of early post-transplant infections associated with immunosuppression and potential exposure to commensal organisms of the lower genital tract, antimicrobial prophylaxis—often including antifungal coverage targeting Candida species—is commonly employed in UTx protocols [28,41].
7. Reperfusion management and laboratory surveillance
The reperfusion phase may be associated with transient acidemia and hyperkalemia due to washout of preservation solutions and ischemic metabolites. A baseline arterial blood gas analysis is obtained early in the procedure, with repeat measurements taken 20–30 min before reperfusion (e.g., at the initiation of iliac vessel anastomosis), after reperfusion, and before surgical closure. Metabolic acidosis and potassium abnormalities should be corrected proactively to minimize the risk of arrhythmias. Published experience to date has not demonstrated major hemodynamic instability or clinically significant acid–base disturbances specifically attributable to the reperfusion phase in UTx. Nonetheless, therapies for potential hyperkalemia—such as intravenous calcium, insulin with dextrose, beta-adrenergic agonists, and sodium bicarbonate—should be prepared in advance.
8. Analgesia, antiemesis, and ERAS elements
A multimodal, opioid-sparing analgesic regimen is preferred, incorporating agents such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and surgeon-directed local anesthetic infiltration [42-44]. NSAIDs may be used selectively, balancing potential bleeding and renal risks in transplant candidates [45]. PONV prophylaxis is recommended based on patient risk, often using dual or triple antiemetic therapy [46,47]. Early removal of invasive lines, prompt mobilization, and standardized venous thromboembolism prophylaxis should be coordinated closely with the postoperative care team [42,43,48].
9. Communication, documentation, and checklists
Continuous, structured communication among the anesthesia, transplant surgery, and gynecology teams is essential during key intraoperative milestones, including vessel clamping, initiation of anastomosis, timing of heparin and immunosuppressive administration, readiness for reperfusion, and confirmation of hemostasis. Implementation of a standardized intraoperative checklist—covering monitoring, blood product preparation, anticoagulation timing, laboratory testing schedule, and warming measures—may enhance procedural reliability and team situational awareness.
10. Anticipated intraoperative challenges and donor factors
Several intraoperative challenges may arise during UTx procedures, influenced by both donor characteristics and surgical factors.
• Advanced donor age: Advanced donor age is associated with increased vascular calcification and arterial stiffness, which can complicate vascular dissection and anastomotic creation [5,14].
• Donor type: Donor type significantly affects the operative course. In living donors, the advantage lies in the ability to perform comprehensive preoperative evaluation; however, living donors tend to be older on average. Efforts to minimize donor morbidity may prolong operative and warm ischemia times, and the extent of vascular resection is often restricted. Conversely, deceased donors generally undergo less detailed preoperative assessment but are typically younger and allow more extensive vascular resection. This facilitates the use of larger-caliber vessels, potentially reducing the risk of graft thrombosis [4].
Postoperative management
Postoperative care typically begins in an intensive care unit or high-dependency unit for the first 24–48 h, with primary emphasis on hemodynamic stability, urine output, and early detection of vascular complications [8,21]. Graft surveillance is usually protocolized: bedside clinical assessments are combined with Doppler ultrasonography of the uterine and iliac vessels, along with scheduled cervical biopsies, as early rejection often presents without clinical symptoms [15,21,49]. Despite these monitoring measures, early graft failure necessitating emergency hysterectomy within the first two postoperative weeks may still occur—most commonly due to arterial or venous thrombosis. Therefore, clinical teams maintain a low threshold for urgent imaging and reoperation when graft compromise is suspected [8,18,50].
Table 1 summarizes the major anesthetic management principles for UTx across perioperative phases.
Summary of Anesthetic Management Strategies for Uterine Transplantation
ANESTHESIA FOR CESAREAN DELIVERY AFTER UTERINE TRANSPLANTATION
Overview and preoperative planning
Published experience regarding cesarean delivery following UTx remains limited; current clinical practice is largely derived from small case series and institutional reports. Owing to the marked paucity of clinical data, every aspect of anesthetic and obstetric management should be undertaken with caution, prioritizing both maternal and fetal safety. Preoperative evaluation should include careful review of the original transplant operative record, current immunosuppressive regimen, and recent laboratory investigations—including hemoglobin, platelet count, and coagulation profile—as well as screening for obstetric comorbidities such as preeclampsia [51].
Anticipated pregnancy and peridelivery issues
• Obstetric complications: Reported obstetric complications during pregnancy after UTx include preeclampsia, preterm delivery, and gestational hypertension or diabetes [52].
• Physiology of the transplanted uterus: The transplanted uterus is denervated; therefore, patients may not perceive uterine contractions during pregnancy or labor. No consistent alteration in uterine responsiveness to uterotonic agents has been documented.
• Concurrent procedures: A planned removal of the transplanted uterus (graft hysterectomy) is performed when no additional pregnancies are desired.
• Bleeding risk and adhesions: Previous pelvic operations and the transplantation procedure itself can result in dense adhesions, which may prolong surgical exposure and increase intraoperative bleeding risk. Additionally, vasoplegia of the uterine vasculature has been described, potentially predisposing patients to hemorrhage.
• Hematologic effects of immunosuppression: Anemia and thrombocytopenia are relatively common; therefore, platelet count should be verified before performing any neuraxial anesthetic technique, particularly in patients receiving immunosuppressive agents associated with thrombocytopenia. These hematologic considerations should inform perioperative blood product preparation and neuraxial safety assessment.
Intraoperative considerations
1. Anesthetic technique
For cesarean delivery following UTx, regional anesthesia—either epidural or combined spinal–epidural—is generally preferred. This approach avoids airway manipulation and fetal exposure to general anesthetic agents while permitting maternal consciousness and immediate bonding with the newborn, which represents an important emotional milestone for UTx recipients. When cesarean hysterectomy is planned immediately after delivery, both regional and general techniques have distinct advantages, and the anesthetic plan should remain adaptable. Regional anesthesia can often be maintained throughout the operation; however, conversion to general anesthesia may be required in prolonged or technically challenging cases, particularly when increased blood loss occurs due to postoperative adhesions or hematologic effects of immunosuppressive therapy. Epidural techniques also provide the additional benefit of postoperative pain control via patient-controlled epidural analgesia. Therefore, initiating anesthesia with a regional technique while maintaining readiness for conversion to general anesthesia constitutes a practical and flexible approach [51].
2. Adverse effects of immunosuppressants
Hematologic complications associated with immunosuppressive therapy may include pancytopenia. Among commonly used agents, azathioprine and mycophenolate mofetil have been particularly linked to anemia and thrombocytopenia [53]. In patients presenting with abnormal hematologic parameters, appropriate perioperative preparation—including the availability of leukoreduced, irradiated blood products—should be incorporated into anesthetic planning. Before initiating neuraxial anesthesia, coagulation status and platelet count must be reassessed to ensure procedural safety.
3. Drug interactions and anesthetic agent selection
Evidence concerning interactions between immunosuppressive and anesthetic agents remains limited, with most insights derived from clinical experience and small observational studies rather than controlled trials. Nevertheless, awareness of potential pharmacologic interactions is essential in perioperative management. Cyclosporine and tacrolimus, both calcineurin inhibitors widely used as maintenance immunosuppressive agents in solid organ transplantation [54], may modify patient responses to sedatives, opioids, and neuromuscular blocking agents, occasionally resulting in enhanced effects or delayed recovery. Most nondepolarizing neuromuscular blockers can be used safely; however, dose reduction and neuromuscular monitoring are advised, as cyclosporine may potentiate neuromuscular blockade. Prolonged effects have been reported with vecuronium and pancuronium, whereas atracurium and cisatracurium are often preferred because of their organ-independent metabolism [55]. Cyclosporine and tacrolimus may elevate plasma concentrations of benzodiazepines [56,57], and cyclosporine has been reported to enhance the analgesic effects of fentanyl [58]. Volatile anesthetics are commonly used and generally well tolerated in transplant recipients. Likewise, intravenous agents such as propofol, thiopental, and etomidate have not demonstrated clinically significant interactions with immunosuppressive therapy. Common neuraxial local anesthetics—including bupivacaine and ropivacaine—have also not been associated with adverse interactions in transplant recipients [59,60].
4. Infection control
During neuraxial anesthesia, meticulous aseptic technique is imperative because immunosuppressive therapy substantially increases the risk of infection [51]. Postoperative monitoring should be especially vigilant, as an attenuated inflammatory response may mask early clinical signs of infection. Similarly, vascular cannulation for invasive monitoring must be performed under strict aseptic conditions to minimize the risk of catheter-related infections [55].
UTERINE TRANSPLANTATION EXPERIENCE IN THE REPUBLIC OF KOREA
In the Republic of Korea, at least three UTx procedures have been reported by Samsung Medical Center. The first recipient was a 35-year-old woman with MRKH syndrome who initially received a graft from her 59-year-old mother, a living donor, in July 2022. Although early graft perfusion was confirmed, postoperative uterine artery and vein thrombosis developed, necessitating graft removal two weeks after transplantation [61].
Six months later, the same recipient underwent a second UTx using a graft from a 44-year-old deceased donor. The graft functioned well, with initiation of menstruation and no documented rejection episodes. Fourteen months after transplantation, the recipient achieved pregnancy following embryo transfer but unfortunately experienced a miscarriage during the early gestational period.
The second recipient was a 32-year-old woman with MRKH syndrome who received a graft from a 38-year-old deceased donor and demonstrated stable graft function postoperatively.
Intraoperative anesthetic management for these recipients employed balanced general anesthesia using sevoflurane and remifentanil, with neuromuscular blockade and invasive hemodynamic monitoring that included arterial blood pressure measurement via the radial artery, with or without central venous pressure monitoring through the internal jugular vein. Advanced hemodynamic monitoring (FloTrac, Edwards Lifesciences Corp.) was used in most cases to monitor cardiac output, cardiac index, stroke volume variation, and systemic vascular resistance. Both balanced crystalloids (Plasma Solution A) and colloids (5% albumin or 6% HES 130/0.4 [Volulyte®]) were administered. No recipient required blood transfusion. Methylprednisolone 500 mg and 15% mannitol 83 ml were given before reperfusion, and 3,000 U of heparin was administered for intraoperative thromboprophylaxis, except in the first case. Serial arterial blood gas analyses and ACT monitoring were performed. All recipients remained hemodynamically stable during reperfusion, without significant metabolic disturbances. In the first three cases, the duration of surgery ranged from 5 h 57 min to 10 h 35 min, while anesthesia duration ranged from 6 h 56 min to 11 h 23 min. Total fluid input ranged from 3,300 to 4,750 ml, and estimated blood loss ranged from 800 to 1,300 ml. No continuous vasoactive drug infusions were used except in the last case, during which dopamine and norepinephrine were administered to treat hypotension secondary to surgical bleeding.
These early Korean experiences highlight both the feasibility and the challenges of performing UTx using living and deceased donors. They underscore the critical importance of meticulous anesthetic management, vigilant thromboprophylaxis, and close multidisciplinary coordination to achieve graft survival and support future fertility.
CHALLENGES AND FUTURE DIRECTIONS
Key ongoing challenges include establishing acceptable thresholds for warm and cold ischemia times, elucidating the clinical consequences of ischemia–reperfusion injury, optimizing both induction and maintenance immunosuppressive regimens, minimizing morbidity among living donors, and ensuring durable long-term follow-up—ideally coordinated through national or international registries such as the International Uterus Transplant Registry (ISUTx Registry) and the United States Uterus Transplant Consortium. Future priorities encompass the development of standardized anticoagulation protocols that align intraoperative heparin administration (dose and ACT targets) with postoperative management strategies; refinement of graft perfusion–preservation and monitoring methods; establishment of evidence-based vasopressor selection and titration algorithms to prevent excessive vasoconstriction of uterine vessels; and broader clinical adoption of robot-assisted donor hysterectomy to reduce donor morbidity and enhance recovery.
CONCLUSION
Anesthesia is integral to UTx, with anesthesiologists serving a central role in ensuring perioperative safety, maintaining optimal graft perfusion, and supporting maternal well-being. Comprehensive anesthetic planning, vigilant intraoperative monitoring, and sustained multidisciplinary collaboration are essential to optimize graft viability and reproductive outcomes, ultimately enabling successful pregnancy and live birth. As the field of UTx continues to develop, future research should prioritize long-term assessment of maternal and graft outcomes, optimization of anesthetic and hemodynamic strategies during reperfusion, and refinement of anesthetic management for subsequent pregnancies and deliveries. Continued, coordinated collaboration among anesthesiologists, transplant surgeons, obstetricians, and other specialists will be pivotal in advancing clinical practice, while perioperative protocols should be continuously refined in response to evolving evidence and technological innovation.
Notes
FUNDING
None.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
AUTHOR CONTRIBUTIONS
Conceptualization: Ja Eun Lee. Data curation: Ja Eun Lee. Methodology: Ja Eun Lee. Project administration: Gaab Soo Kim. Writing - original draft: Ja Eun Lee, Gaab Soo Kim. Writing - review & editing: Gaab Soo Kim. Investigation: Ja Eun Lee. Resources: Gaab Soo Kim. Supervision: Gaab Soo Kim. Validation: Gaab Soo Kim.