Objectives: Absolute uterine factor infertility is a condition characterized by the absence of a functional uterus, resulting in the inability to achieve or maintain pregnancy. Uterus transplantation has emerged as an experimental therapeutic option aimed at restoring reproductive capacity in women with absolute uterine factor infertility. Here, we reviewed the current clinical experience with uterus transplantation, focusing on surgical approaches, donor sources, reproductive outcomes, and ethical considerations.
Materials and Methods: We conducted a narrative review of the literature using the PubMed, Scopus, and Google Scholar databases. We screened publications from 2000 through 2025 using the keywords “uterus transplantation,” “absolute uterine factor infertility,” and “MRKH syndrome.” We included 42 relevant publications that described clinical outcomes, surgical techniques, and ethical aspects of uterus transplantation. We focused on reports of successful pregnancies and births following uterus transplantation.
Results: Uterus transplantation has progressed from experimental animal models to clinical application. To date, more than 90 transplants have been performed worldwide, resulting in over 50 live births. The procedure involves complex microsurgical vascular anastomoses and requires long-term immunosup-pression until childbirth. All pregnancies are achieved through in vitro fertilization with cryopreserved embryos. Both living and deceased donors have been successfully used, each associated with specific ethical and surgical considerations.
Conclusions: Uterus transplantation represents a promising experimental therapy for women with absol-ute uterine factor infertility. Although encouraging reproductive outcomes have been reported, the proce-dure remains technically demanding and associated with substantial ethical, surgical, and immunological challenges. Further multicenter studies and long-term follow-up are required to establish standardized protocols and evaluate long-term maternal and neonatal outcomes.

Key words : Immunosuppression, In vitro fertilization, MRKH syndrome, Reconstructive surgery

Introduction

Absolute uterine factor infertility (AUFI) remains one of the most complex and ethically sensitive challenges in modern reproductive medicine. This condition is characterized by the complete inability to achieve pregnancy and successfully carry a fetus due to the absence of the uterus (congenital or acquired) or severe anatomical or functional abnormalities of the organ.^1-5 The most common cause of congenital AUFI is Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, which affects approximately 1 in 4500 women worldwide.^6-10 Traditionally, patients with AUFI had only 2 options for achieving parenthood: adoption or gestational surrogacy.^11,12 However, the emergence of uterus transplant as a reconstructive surgical approach has created the possibility of true gestational motherhood, that is, the ability of a woman to carry and deliver her own genetically related child.^1,2,9,13,14 Uterine transplant represents a unique form of “temporary” transplant: the organ is transplanted only for the period required to achieve childbirth and is subse-quently removed to allow discontinuation of immuno-suppressive therapy. Based on an analysis of global clinical experience, including successful clinical cases reported in the United Kingdom from 2023 through 2025,^15-21 we aimed to evaluate the effectiveness of uterus transplant as a treatment for AUFI and to analyze the surgical challenges and immunological risks associated with this procedure.^22-25

Materials and Methods

This study was conducted as a narrative literature review aimed at summarizing current knowledge on uterus transplant as a therapeutic option for AUFI. We performed a literature search using the electronic databases PubMed, Scopus, and Google Scholar.

We screened studies published from January
2000 through March 2025 and used the following key words (individually and in combination): “uterus transplantation,” “uterine transplantation,” “absolute uterine factor infertility,” and “MRKH syndrome.” We analyzed the collected data using descriptive and comparative approaches to summarize the current clinical experience with uterus transplant.

Historical Development of Uterus Transplantation

The first experimental studies on uterus transplant were conducted with animal models. Successful pregnancies following uterus transplant were initially achieved in rodents and later in nonhuman primates, providing important proof of concept for the feasibility of this procedure in reproductive medicine.^1,26,27 However, success in nonhuman primates or any large mammal remained debatable until the birth of the first human offspring from the transplanted uterus in Sweden.
The first documented attempt at human uterus transplant was performed in 1931 in Germany. The recipient was the Danish artist Lili Elbe, one of the earliest known transgender women to undergo gender-affirming surgery. The experimental procedure ultimately had a tragic outcome: the patient died 3 months later due to graft rejection and severe infectious complications.²⁸ In the 21st century, several important milestones significantly advanced the field. The first modern clinical attempt at uterus transplant was performed in 2000 in Saudi Arabia, when a 26-year-old woman received a uterus from a living donor. Although initial graft function was observed, the transplanted uterus had to be removed after 99 days because of vascular thrombosis and subsequent tissue necrosis.^28,29 The first technically successful uterus transplant was reported in 2011 in Turkey. The recipient, Derya Sert, received a uterus from a deceased donor. The graft remained viable, and after several years of treatment and assisted reproductive procedures, the patient successfully delivered a child in 2020.30 A major breakthrough in the field occurred in 2014, when the first live birth following uterus transplant was reported in Gothenburg, Sweden.^13,14 The procedure was perfor-med by a team led by Mats Brännström at the University of Gothenburg. This landmark case resulted in the birth of a healthy child and marked a turning point in the development of reproductive transplantation.

Surgical and Immunological Aspects of Uterus Transplantation

The procedure represents a complex surgical inter-vention that includes donor organ retrieval, preser-vation of the graft, subsequent implantation into the recipient, and restoration of vascular perfusion of the transplanted organ. The procedure requires the involvement of a multidisciplinary team of specialists, including transplant surgeons, obstetrician-gynecologists, vascular surgeons, anesthesiologists, microsurgery specialists, embryologists, and transplant immunologists.
Uterus transplantation is a complex medical procedure that includes several surgical and clinical stages aimed at ensuring successful graft implan-tation and function. The main stages of the transplant process and their key characteristics are presented in Table 1. Preoperative preparation involves a com-prehensive set of diagnostic and laboratory procedures aimed at assessing anatomical, functional, and immunological compatibility between the donor and the recipient. Imaging techniques such as magnetic resonance imaging of the pelvis and pelvic vascular angiography are used to evaluate vascular anatomy and identify possible anatomical variations. In addition, Doppler ultrasonography examinations are performed to assess blood flow characteristics. Immunological reactions play a critical role in the outcome of organ transplant.
Different mechanisms of immune response may lead to graft rejection if not properly controlled by immunosuppressive therapy. The main types of immunological reactions involved in transplant are summarized in Table 2. Immunological assessment includes HLA typing and the determination of panel reactive antibodies, which helps to minimize the risk of immunological incompatibility and subsequent graft rejection. At the preparatory stage, in vitro fertilization with embryo cryopreservation is always performed, since pregnancy after uterus transplant is always achieved using assisted reproductive technologies.
The surgical procedure of uterus transplant consists of 2 main stages: donor organ retrieval and implantation into the recipient. Retrieval of the uterus from the donor is considered a technically demanding operation that requires precise dissection of the pelvic tissues. Surgical access is most commonly achieved through laparotomy.^13,23,25 After the abdominal cavity is opened, sequential mobilization of the uterus is performed, including the uterine body and cervix, as well as the isolation of the vascular structures that provide blood supply to the organ.
A critical step is the dissection of the uterine arteries and veins with maximal preservation of their length to allow for subsequent vascular anastomoses. During this stage, identification and protection of the ureters is essential, as they pass in close proximity to the uterine vessels and may be damaged during dissection. The vascular structures are mobilized up to the level of the internal iliac vessels, allowing sufficient vessel length for subsequent connection to the recipient’s vasculature. Typically, 2 uterine arteries and several venous vessels are preserved to ensure adequate venous drainage. In addition, a small segment of the upper vagina, known as the vaginal cuff, is preserved, as it is required for later reconstruction of the vaginal connection in the recipient. After completion of the mobilization process, the vessels are divided and the uterus is removed.
Immediately after retrieval, the graft is placed in a sterile container containing a cold preservation solution. Maintaining a temperature of approximately 4 °C greatly slows metabolic processes within the tissues and reduces ischemic injury before reperfusion.
The second stage of the procedure involves implantation of the donor uterus into the recipient. After laparotomy is performed, an anatomical space is created within the pelvic cavity to accommodate the graft. Subsequently, large pelvic vessels, most commonly the external iliac artery and the external iliac vein, are exposed and prepared for vascular anastomoses. The donor uterus is then positioned within the pelvic cavity in an orientation that closely resembles its natural anatomical placement. The restoration of blood supply to the transplanted organ represents the most critical stage of the procedure. Under an operating microscope, arterial and venous anastomoses are performed between the uterine vessels of the donor and the pelvic vessels of the recipient. These vascular connections are created using fine nonabsorbable microsurgical sutures, typically polypropylene sutures sized 8-0 or 9-0. Once the anastomoses are completed, vascular clamps are removed, allowing blood flow to be restored and reperfusion of the transplanted organ to occur. Adequate perfusion is assessed visually by observing changes in the color of the graft tissue and the appearance of vascular pulsation, as well as by Doppler ultrasonography evaluation of blood flow. After restoration of perfusion, the transplanted uterus is fixed within the pelvic cavity. Fixation is achieved by suturing the organ to the supporting ligamentous structures of the pelvis, including the uterosacral and round ligaments. This ensures stable positioning of the graft and prevents displacement of the organ. Reconstruction of the vaginal connection is then performed, during which the vaginal cuff of the donor uterus is surgically connected to the recipient’s vagina. This reconstruction enables physiological menstrual drainage, facilitates gynecological monitoring, and establishes the anatomical conditions necessary for a future pregnancy. After completion of the recons-tructive stages, careful hemostatic control and evaluation of graft positioning are performed. An important aspect is ensuring the absence of torsion of the vascular pedicles, which could compromise blood supply to the organ.^1-3 After placement of surgical drains, the abdominal incision is closed in layers.
Immunosuppressive therapy constitutes an es-sential component of uterus transplant, as it prevents immunological rejection of the transplanted organ. The recipient’s immune system is capable of recog-nizing donor antigens as foreign, which may trigger activation of both cellular and humoral immune responses. To suppress these reactions, combination immunosuppressive therapy is administered. The most commonly used agents include calcineurin inhibitors such as tacrolimus, antimetabolites such as mycophenolate mofetil, and glucocorticoids. However, mycophenolate is replaced with azathioprine because of possible teratogenic effects on the embryo either from the outset or at least before embryo implantation. These medications suppress the activation and proliferation of T lymphocytes and significantly reduce the risk of both acute and chronic graft rejection.^10,33-35
Postoperative follow-up is aimed at early detection of potential complications and monitoring the functional status of the transplanted uterus. Monitoring protocols include regular pelvic ultra-sonography examinations, Doppler assessment of graft blood flow, and periodic cervical biopsies to detect early signs of immunological rejection. One of the clinical indicators of successful graft function is the restoration of the menstrual cycle, which suggests adequate vascular perfusion of the organ and normal hormonal responsiveness of the endometrium.^23,31,36
After stabilization of the graft, typically within 6 to 12 months, embryo transfer may be performed. Pregnancy following uterus transplant is considered high risk and is associated with an increased incidence of complications such as preeclampsia, fetal growth restriction, and preterm birth. These risks are related both to the effects of immuno-suppressive therapy and to the vascular charac-teristics of the transplanted uterus.^4,37 Delivery is usually performed by planned cesarean section because the anatomical features of the transplanted uterus and the presence of vascular anastomoses make vaginal delivery unsafe.^25,37 Most pregnancies are delivered between 32 and 36 weeks of gestation. Neonates are usually born preterm and are usually small for age, and no malformations have been seen. However, long-term follow-up data remain limited.
Potential complications of uterus transplant include surgical complications such as bleeding, thrombosis, and infection; immunological complica-tions including acute rejection (reported in approxi-mately 10% to 20% of cases); and psychological challenges related to the high emotional burden and fear of graft loss. Donor-related aspects also require careful consideration. Uterus transplant can be per-formed with organs from either living or deceased donors. Living donor transplant, often involving relatives, requires complex hysterectomy procedures with potential risks, including ureteral injury and significant blood loss. This approach also raises ethical concerns regarding the risks imposed on a healthy donor. Conversely, transplant from deceased donors avoids these risks but introduces additional logistical challenges and longer ischemia times.^35,38-40

Illustrative Clinical Case From the United Kingdom

The following case is presented as an illustrative example based on previously published reports describing the first uterus transplant performed in the United Kingdom.^15-19 In 2023, the first uterus transplant in the history of the United Kingdom was performed at the Oxford Transplant Centre at Churchill Hospital. This milestone was the result of more than 25 years of research conducted by the Womb Transplant UK program under the leadership of Richard Smith and transplant surgeon Isabel Quiroga. The procedure demonstrated the successful adaptation of the Swedish uterus transplant protocol developed by Mats Brännström and colleagues to the British health care system.

Clinical profile of the patients
The recipient was a 34-year-old woman diagnosed with congenital uterine aplasia associated with MRKH syndrome type I. Although the patient had preserved ovarian function, the anatomical absence of the uterus made independent gestation impossible. The donor was the recipient’s 40-year-old sister, who had previously delivered 2 children and voluntarily consented to donate her uterus to enable her sister to achieve biological motherhood. Before surgery, both the donor and recipient underwent extensive medical and psychological evaluation according to established transplant protocols.

Surgical procedure (donor retrieval and implantation)
The procedure was conducted by 2 surgical teams working simultaneously and lasted more than 17 hours in total. Donor organ retrieval required 8 hours and 12 minutes. The main surgical challenge involved meticulous dissection of the uterine arteries and veins together with segments of the internal iliac vessels to ensure adequate vascular pedicle length for subsequent anastomosis. Implantation lasted 9 hours and 20 minutes. Microsurgical vascular anastomoses were performed between the donor uterine vessels and the recipient’s external iliac vessels. After restoration of blood circulation, the uterus rapidly acquired a healthy pink coloration, indicating satisfactory perfusion. The transplanted uterus was then fixed to the pelvic ligamentous structures of the recipient to stabilize its anatomical position. To prevent acute rejection, a standard protocol for vascularized composite allografts was used. Immunosuppressive induction therapy inclu-ded antithymocyte globulin, and maintenance therapy consisted of tacrolimus and mycophenolate mofetil. During pregnancy planning, the dosage of immunosuppressive agents was carefully minimized to reduce potential teratogenic effects while main-taining graft tolerance.

Reproductive and functional outcomes
Two weeks after surgery, the patient experienced her first menstruation in her lifetime, representing a key indicator of successful graft function and endo-metrial activity. Before transplant, the patient underwent ovarian stimulation, which resulted in the retrieval and preservation of 5 embryos. Embryo transfer was planned for late 2023 after stabilization of immunological status.^15-17 The procedure confirmed that living related uterus transplant can represent a safe and effective alternative to gestational surrogacy.
The project was fully funded by the charitable organization Womb Transplant UK. The program aims to perform 30 uterus transplantations in total (15 from living donors and 15 from deceased donors), positioning the United Kingdom among the leading countries in reproductive transplant research. The clinical success of the transplant was confirmed 2 years later. On February 27, 2025, the first child in the United Kingdom carried in a transplanted uterus was born at Queen Charlotte’s and Chelsea Hospital. After stabilization of the recipient’s immunological condition, the patient underwent in vitro fertilization at Lister Fertility Clinic. Pregnancy was achieved after transfer of 1 of the embryos cryopreserved before transplant.^18,19,21
Throughout the pregnancy, the patient was closely monitored by a multidisciplinary team consisting of transplant surgeons, obstetricians, and reproductive medicine specialists. The patient continued immuno-suppressive therapy with tacrolimus, with dosage adjustments to maintain graft tolerance while ensuring fetal safety. Delivery was performed by planned cesarean section at 34 weeks of gestation. The newborn girl weighed 2.04 kg and showed no significant developmental abnormalities.^18,21

Ethical Considerations

The ethical aspects of uterus transplantation remain a topic of ongoing debate. The primary concerns involve the acceptability of potential risks for living donors and the justification of a major surgical procedure aimed at improving quality of life rather than preserving it.^11,12,41,42 Nevertheless, psychological studies indicate that, for women with absolute uterine infertility, the ability to experience pregnancy and childbirth has a profound positive effect on mental health and social well-being. For this reason, several transplant centers in countries such as the United States and Brazil are increasingly exploring the use of organs from deceased donors as a potentially more ethically acceptable alternative.^5,10,22 Another important issue is the accessibility of uterus transplantation given the high financial cost of the procedure. Legal regulations differ significantly between countries, contributing to inequalities in access to this innovative reproductive technology.⁴²

Discussion

Uterus transplantation has emerged as a novel therapeutic option for women with AUFI. Since the first successful live birth after uterus transplant reported in Sweden in 2014,^13,14 the field has prog-ressed rapidly, with several centers worldwide establishing experimental or clinical programs. The British case represents an important milestone in the global development of uterus transplant, demonstrating that surgical and clinical protocols originally developed by the Swedish research group can be successfully adapted to other health care systems.^15-19 The positive outcome of this procedure highlights the feasibility of living donor uterus transplant within a highly regulated medical framework.
From a surgical perspective, uterus transplant remains one of the most technically demanding procedures in modern transplant surgery. The long operative time, the need for microsurgical vascular anastomoses, and the risk of thrombosis or graft ischemia represent substantial challenges. However, improvements in microsurgical techniques and perioperative management have led to progressively better outcomes in recent years. The immunological management of uterus transplant also presents unique challenges. Unlike life-saving organ transplants such as kidney or liver transplant, uterus transplant is a temporary procedure intended to enable pregnancy. Consequently, immunosuppressive therapy must be carefully balanced to minimize both graft rejection and potential risks to the fetus.
The successful birth in the United Kingdom confirms that pregnancy after uterus transplant is achievable and can result in healthy neonatal outcomes. Nevertheless, such pregnancies are consi-dered high risk and require continuous monitoring by multidisciplinary medical teams. Preterm delivery and hypertensive disorders of pregnancy remain among the most frequently reported complications.
Ethical considerations continue to play a central role in the development of uterus transplant programs. Although living donor transplant provides higher organ quality and shorter ischemia times, living donor transplant raises ethical concerns regarding the risks imposed on healthy donors. Conversely, deceased donor transplant eliminates donor risk but introduces additional logistical and surgical challenges. In addition to ethical concerns, issues related to the cost and accessibility of the procedure must be addressed. At present, uterus transplant remains available only in specialized research centers, and the high financial cost limits widespread implementation. Despite these challenges, uterus transplant represents a significant advancement in reproductive medicine. Ongoing clinical research, technological innovations, and long-term follow-up studies will be essential to determine the safety, effectiveness, and ethical acceptability of this pro-cedure in the future.

Limitations

This review had several limitations. First, the number of published clinical cases were limited. Second, heterogeneity in surgical techniques and immuno-suppressive protocols made direct comparison between studies difficult. Finally, most available data originated from a small number of specialized transplant centers.

Conclusions

Uterus transplant represents a significant break-through in the treatment of AUFI. The procedure offers women who were previously unable to carry a pregnancy the possibility of achieving biological and gestational motherhood. The first successful uterus transplant performed in the United Kingdom in 2023, followed by the birth of a healthy child in 2025, demonstrates the feasibility and effectiveness of this innovative approach. The case confirms that living donor uterus transplant can be successfully implemented within a multidisciplinary clinical framework involving transplant surgeons, repro-ductive specialists, obstetricians, and immunologists.
Despite these promising outcomes, uterus transplant remains a highly complex procedure asso-ciated with substantial surgical, immunological, and ethical challenges. Long operative times, the risk of graft rejection, the need for immunosuppressive therapy, and potential pregnancy-related complica-tions require careful patient selection and rigorous clinical monitoring. Ethical considerations, particularly those related to risks for living donors and the accessibility of the procedure, remain central to ongoing discussions in the field. Future research should focus on improving surgical techniques, opti-mizing immuno-suppressive protocols, expanding the use of deceased donors, and evaluating long-term outco-mes for both mothers and children.
In conclusion, uterus transplant represents a promising and rapidly evolving field within repro-ductive and transplant medicine. Continued inter-national collaboration and clinical research will be essential for establishing standardized protocols and ensuring the safety and accessibility of this procedure.

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