Waiting as a frontier: (Un)making patients for uterus transplantation in Denmark.

Progressive Success in Uterus Transplants—From Experimental to Clinical Reality

This study aimed to assess medical students' attitudes toward integrating socioscientific issues (SSI) into female reproductive anatomy teaching across multiple academic years, using the novel case of China's first uterus transplantation, and to apply artificial intelligence (AI)-based sentiment analysis to evaluate their emotional responses. A cross-sectional study was conducted among 163 medical students across three academic cohorts (2022, 2023, and 2024-2025) at a medical university in China. Over 95% of students rated the SSI-based teaching positively. AI-based sentiment analysis revealed that attitudes toward ethical questions varied: for embarrassment in close-relative transplantation, no significant differences were found across cohorts (χ² = 5.78, df = 4, p = 0.216); for adoption as an alternative to childbirth, attitudes also did not differ significantly (χ² = 6.62, df = 4, p = 0.157). Mean sentiment scores for ovarian transplantation were neutral to slightly negative across all cohorts (2022: -0.31; 2023: -0.08; 2024-2025: -0.12, weighted average of -0.17 for 2024 and - 0.02 for 2025). SSI integration using a culturally relevant case was well-received by medical students. AI-based sentiment analysis proved a valuable tool for quantifying emotional responses. Attitudes toward ethical issues did not differ significantly across the three cohorts, suggesting a rationale for the sustained integration of SSI in preclinical curricula to foster ethical reasoning.

Uterine transplantation (UTx) offers a novel option for women with absolute uterine factor infertility, yet its psychological impact remains understudied. We explored the experiences of two recipient-donor dyads involved in Spain’s first UTx procedures: two recipients with Mayer-Rokitansky-Küster-Hauser syndrome and their living donors (a sister and a mother). Semistructured interviews were analyzed using reflexive thematic analysis. Participants reported distress after infertility diagnosis, exacerbated by poor clinical communication, and anxiety regarding medical risks, sequelae, financial strain, and relocation-related isolation. Family cohesion, optimism, and spirituality were key coping resources. Findings support empathic communication and stronger socioeconomic and psychological support throughout UTx.

OPTN/SRTR 2024 Annual Data Report: Vascularized Composite Allograft.

Uterine transplantation (UTx) is an innovative and exciting development that is aimed at making available the experience of gestation to those for whom it may otherwise be out of reach. Given the personal and social importance of this experience to many people, this is a laudable goal. Outside of at least one historic outlier, this practice has primarily been discussed in the context of resolving uterine factor infertility (UFI) for cisgender women. The guidelines and protocols that have been established around UTx understand Uterine Factor Infertility (UFI) as the indication for UTx. This article critically evaluates the Montreal Criteria (2012, 2013) as the primary ethical guidelines regarding UTx. This evaluation focuses on and challenges the way the Criteria structure the discussion around UFI as indication for UTx and the requirement for female genetics. I argue that, outside of the initial experimental design of UTx, there are prima facie grounds for making UTx available outside of the indication of UFI, and that for reasons both internal and external to the Montreal Criteria's analysis of UTx, there are no overwriting ethical reasons to limit UTx to cis-gender women.

Uterus transplantation (UTx) is a treatment option for women with absolute uterine factor infertility who wish to become pregnant and have a healthy live birth. Tissue biopsy is the gold standard for diagnosing allograft rejection. Circulating donor-derived cell-free DNA (dd-cfDNA) has recently emerged as a non-invasive biomarker with strong predictive value for rejection in solid organ transplants. dd-cfDNA quantification by next-generation sequencing (NGS) was evaluated in two UTx patients from transplantation to childbirth. The results were compared with cervical biopsies. Additionally, capillary electrophoresis was used to characterize cfDNA fragmentation pattern. dd-cfDNA levels significantly increase during biopsy-proven rejection episodes (0.39% vs 0.17% in patient 1 and 0.34% vs 0.26% in patient 2). Additionally, cfDNA fragment analysis shows an elevation of high molecular weight cfDNA fragments during rejection. These findings support dd-cfDNA as a promising non-invasive tool for monitoring UTx rejection. Future studies should focus on characterizing dd-cfDNA kinetics and cfDNA fragmentomics in larger cohorts to optimize rejection detection and improve patient outcomes.

A Decade of Progress in Uterus Transplantation in the United States: Results From the World Transplant Congress 2025.

To study the existing knowledge, interests, and attitudes of medical students regarding fertility preservation measures. A multi-center nationwide survey was conducted among medical students across Germany. The survey consisted of 15 multiple-choice questions and six questions asking participants their level of agreement of a statement. 346 medical students in Germany. A multiple-choice questionnaire was used to evaluate the existing knowledge, interest and attitudes of medical students regarding fertility preservation measures. Regarding the assessment of ovarian reserve, Anti-Müllerian hormone testing was known by 38.8% of students, while only 15.9% were familiar with the antral follicle count method. The most widely recognized fertility preservation (FP) method was oocyte cryopreservation (91.0%), followed by ovarian tissue cryopreservation (45.1%), ovarian transposition surgery prior to pelvic radiation (38.2%), and the use of gonadotropin-releasing hormone analogs for ovarian protection during chemotherapy (28.6%). Regarding reproductive technologies, such as IVF, ICSI, or hormonal stimulation, 87.5% of students expressed a positive opinion. Oocyte donation was perceived positively by 77.6%. The acceptance for uterus transplantation was high among participants with 61.4%. The acceptance for surrogacy was lower with 53.2% of respondents. Social freezing was positively received by most respondents (72.7%). 80.0% of respondents expressed interest in expanding their knowledge of fertility and cancer, and 65.9% desired additional training. To ensure high-quality fertility preservation counseling and the implementation of necessary FP measures for all cancer patients of childbearing age, it is crucial that future physicians are familiar with methods for assessing ovarian reserve and fertility preservation techniques. Strengthening oncofertility training in medical education will enhance future physicians' ability to provide informed counseling and timely referrals, ultimately improving patient care and quality of life. This study highlights the urgent need to systematically integrate fertility preservation and oncofertility into the curriculum of medical schools in Germany.

Background: Uterus transplantation (UTx) is an emerging treatment for absolute uterine factor infertility. However, the use of deceased donors is limited, and donation after circulatory death (DCD) has not yet been utilized. Ischemic injury remains a major barrier, particularly compared with living donor procedures. Hypothermic oxygenated perfusion (HOPE), which has shown protective effects in heart, liver, and kidney transplantation, may offer similar benefits for uterine grafts. Methods: We report the first series applying HOPE to human uteri to improve preservation and enable metabolic injury assessment during perfusion. Six uteri (3 DBD, 3 DCD; median donor age 53 years) underwent 8 h of HOPE following procurement, while paired tissue controls were preserved using static cold storage (SCS). Perfusion was delivered using a pressure-controlled system (15 mmHg, 10 ± 1 °C, VitaSmart®). Perfusate and tissue samples were analyzed for mitochondrial injury, inflammation, and transcriptional responses. Results: HOPE maintained stable flows (70-150 mL/min), delivered high oxygen levels (pO2 ≈ 1000 hPa), and increased tissue ATP levels. Stratification based on perfusate flavin mononucleotide (FMN) release identified grafts with greater Complex I/II injury. HOPE was associated with lower levels of mitochondrial injury markers and inflammatory signals, preserved tissue architecture, and promoted gene expression patterns consistent with metabolic recovery compared with paired SCS tissue controls. Conclusions: These findings suggest that HOPE may serve as a preservation approach that enables metabolic and ischemic injury assessment and may facilitate broader use of deceased donor uteri for transplantation.

Effects of letrozole alone or combined with a gonadotropin-releasing hormone agonist on inflammation, folliculogenesis, and estrogen levels in a rat model of peritoneal endometriosis.

Maintenance of tissue-specific immunity is important for immunological fitness, but its establishment has been difficult to assess in humans. Here, we investigated reconstitution of the human uterine immune system by studying women who underwent uterus solid organ transplantation or hematopoietic stem cell transplantation (HSCT). Through single-cell identification based on single-nucleotide polymorphisms and disparate human leukocyte antigen expression using single-cell RNA sequencing or high-parameter flow cytometry, donor versus recipient cell origin was determined, and we examined the gene expression states, surface marker profiles, and spatial organization of these cells in the endometrium. Endometrial immune cell reconstitution occurred after both uterus transplant and HSCT at the transcriptomic, phenotypic, and spatial levels. Reconstitution involved restoration of all major immune lineages with frequencies comparable to those of healthy controls, with preservation of canonical endometrial immune architecture. Recipient-derived immune cells replaced donor immune cells after uterus transplant, whereas HSCT resulted in near-complete donor-derived immune reconstitution, including formation of tissue-resident lymphocytes. This occurred despite tacrolimus-induced, calcineurin-mediated inhibition of the nuclear factor of activated T cells (NFAT) pathway, which affected de novo induction of tissue-residency features in vitro. In one patient, immune cells of male origin reconstituted the endometrium after HSCT. Collectively, these data provide insights into tissue immune system persistence and reconstitution capabilities in the uterus, an organ that undergoes continuous regeneration.

To explore the experiences of women and clinicians during the introduction of uterine transplantation (UTx) to the UK. A qualitative study utilising prospective case study methodology (interviews and observations) over 6 years. In the UK, five uterine transplants have been completed to date-two using living donors and three using deceased donors. In addition, three deceased donor retrievals were undertaken but did not proceed to implantation. Data included 18 audio-recorded consultations with potential recipients and clinicians, 22 interviews with seven clinicians and eight follow-up interviews with women. Data were synthesised using thematic analytical methods. The first theme, 'Emotional and ethical dimensions of UTx decision-making', explores how women and clinicians navigated uncertainty, risk and hope, including dilemmas around living versus deceased donation. The second, 'Building and refining a UK UTx programme', reflects on bridging disciplines, managing initial cases and iteratively improving protocols through teamwork and reflection. The third, 'Living through the unknowns after transplantation', captures recipients' post-operative experiences, their collaboration with clinicians, and uncertainties surrounding recovery, embryo transfer and pregnancy. Prospective qualitative research enabled surgeons to reflect on their practice while generating insights to optimise uterine transplant delivery in the UK and internationally. Findings offer practical guidance for navigating uncertainty and risk when introducing new procedures and highlight ways to strengthen support for women throughout the process. Overall, this study demonstrates how prospective qualitative methods can provide crucial insights into the technical, ethical and emotional dimensions of innovative procedures like UTx.

After human uterus transplant, all uterine immune cell lineages were reconstituted but with alterations in tissue-resident NK cells, potentially due to tacrolimus (Asiimwe etal. and Strunz etal., this issue).

Uterine natural killer cells (uNKs) are a tissue resident lymphocyte population critical for pregnancy success. Although mouse models have demonstrated that uNK cell deficiency results in abnormal placentation and poor pregnancy outcomes, the generalizability of this knowledge to humans remains unclear. Here, we compared tissue samples collected from a cohort of human uterus transplant (UTx) recipients at high risk for pregnancy complications with healthy controls using flow cytometry, immunofluorescence microscopy, and single-cell RNA sequencing (scRNA-seq). Subsets of tissue-resident uNK cells were reduced in UTx endometrial and decidual samples compared to healthy control samples. Loss of tissue-resident uNK cells associated with histopathologic evidence of maternal vascular malperfusion in UTx placentas and related pregnancy complications including pre-eclampsia. scRNA-seq of UTx endometrial biopsies and deciduas further revealed that the NK cell reduction in UTx correlated with impaired transcriptional programming of NK tissue residency arising from the inhibition of signaling by nuclear factor of activated T cells (NFAT). In vitro culture of uNKs from healthy controls with the NFAT inhibitor tacrolimus resulted in downregulation of adhesion molecules. Altogether, these experiments suggested that NFAT-dependent genes modulate multiple molecular tissue residency programs in uNKs, including early residency programs involving activator protein-1 (AP-1) family transcription factors and later residency programs characterized by upregulation of surface integrins by transforming growth factor beta (TGF-β). Collectively, these data identify a previously undescribed role for NFAT in uNK tissue residency and provide mechanistic insights into the biologic basis of pregnancy complications due to alteration of tissue resident NK subsets in humans.

Fertility preservation (FP) has become an essential dimension of modern medicine, reflecting the paradigm shift from survival alone to survivorship. Once confined to oncology, FP now spans a broad spectrum of medical, social, and technological contexts. Surgical innovations, including fertility-sparing surgery and ovarian transposition, allow reproductive potential to be safeguarded without compromising oncological safety. Cryobiology has been transformed by the transition from slow-freezing to vitrification, establishing oocyte and embryo cryopreservation as gold-standard approaches with outcomes comparable to fresh cycles. Alongside onco-fertility, "social freezing" has emerged as a tool of reproductive autonomy, though it raises counselling and ethical challenges related to age, expectations, and equity of access. Resilience in FP also requires psychosocial support: while emotional distress is common, evidence shows that interventions such as mindfulness and structured counselling improve mental health even if conception outcomes remain unchanged. In parallel, ovarian tissue cryopreservation for patients unable to undergo stimulation and immature testicular tissue banking extend possibilities, with early clinical successes highlighting future translational pathways. Uterus transplantation has emerged as the first-line treatment of congenital absence of a uterus and can restore fertility after a hysterectomy performed for cervical cancer. Looking ahead, regenerative approaches, including stem-cell-based strategies, 3D bio-printing of genital tissues, tissue engineering, and artificial uterus systems, signal the next frontier, while underscoring the need for further research as well as robust ethical, legal, and safety frameworks. FP thus represents a multidisciplinary and rapidly evolving field that integrates oncology, reproductive medicine, gynaecology, transplantation surgery, psychology, and laboratory disciplines. Its trajectory is defined by both technological innovation and the imperative to align medical progress with patient autonomy, equity, and long-term quality of life.

What have been the activities, characteristics, and outcomes of uterus transplantation (UTx) performed worldwide from 2000 through 2024? In 91 UTx cases, 67 involved live donors and 80 of the recipients had Mayer-Rokitansky-Küster-Hauser syndrome, with 12-month graft survival of 74%, enabling pregnancy attempts that yielded 44 healthy singleton deliveries with a live birth rate per embryo transfer of 30.3%. UTx is the only treatment for women with absolute uterine factor infertility who wish to carry a pregnancy. According to a comprehensive report including data up to 2020 on 45 UTx cases, 19 live births occurred (35.8% per embryo transfer) at a mean of 35.3 weeks gestation. Data were extracted from the web-based registry of the International Society of Uterus Transplantation (ISUTx). This registry captures information on donor and recipient characteristics, transplantation procedures, postoperative complications, immunosuppression, complications including rejections, and reproductive outcome. Analyses were undertaken of the 91 transplants performed between 6 April 2000 and 31 December 2024, that were recorded in the registry. Twenty-four medical centers in five continents registered their uterus transplants by entering data from the day of transplantation until 3 months after graft removal. The following variables were assessed: the demographic and laboratory characteristics of donors and recipients, the source of graft (live versus deceased donor), surgical specifics including technique, duration, ischemic times, and post-op complications, immunosuppression, rejection data, pregnancy with live birth(s), and hysterectomy. In 91 uterus transplantations (67 from live donors, 24 from deceased donors), the overall surgical success rate, defined as graft viability by 12 months, was 75%. Most recipients (88%) had Mayer-Rokitansky-Küster-Hauser syndrome, with mothers being the most frequent (64%) live donors. Live donor hysterectomies were performed by laparotomy (54%), robotics (28%), or laparoscopy (18%). Total ischemic time was shorter in live- versus deceased-donor UTx procedures. Rejection episodes that were treated with escalations of immunosuppression were more frequent during months 1-5 (44%) than during months 6-10 (28%) post-UTx. Graft survival during the first 12 months was superior when grafts from premenopausal donors were used as compared to from postmenopausal donors. Forty-four singleton live births (mean gestational length of 34.5 weeks), including eight second births, were reported, with a live birth rate per embryo transfer of 30%. Preeclampsia was the most common pregnancy complication, occurring in 23% of live-birth pregnancies. Major postnatal complications occurred in 11 infants, 9 with respiratory distress syndrome; no major malformations were observed. Data in the registry are self-reported and not subjected to validation. Although the ISUTx registry represents the most comprehensive quality registry of UTx activity in the world, cases from at least four centers are excluded as they were not entered into the registry. Birth outcomes from some registry cases are as yet unknown as these ongoing cases have not yet reached the endpoint of hysterectomy. This study presents the most comprehensive analysis to date of UTx, the only fertility treatment for absolute uterine factor infertility. The registry serves as the prime source for quality assessment and process improvement in UTx. The establishment and operation of the registry were funded by the Swedish Research Council (2024-03487 to M.B.) and Jane and Dan Olsson Foundation (2024-11 to M.B.). There was no competing interest. Not applicable.

Advances in oncologic therapies have markedly improved survival among reproductive-age female patients, making fertility preservation an essential component of comprehensive cancer care. Gonadotoxic treatments, including chemotherapy, radiotherapy, and surgery, can disrupt ovarian and uterine endocrine function, resulting in premature ovarian insufficiency and infertility. This narrative review summarizes current and emerging surgical approaches to fertility preservation, organized by anatomic focus on the ovary, uterus, and cervix. Ovarian transposition preserves ovarian endocrine function by relocating the ovaries outside the pelvic radiation field, while ovarian tissue cryopreservation preserves primordial follicles through surgical harvesting, cryostorage, and reimplantation to restore ovarian function and fertility. Emerging uterine-preserving strategies, such as uterine transposition and uterine transplantation, demonstrate growing feasibility for restoring reproductive and endocrine uterine function. Fertility-sparing cervical procedures, including radical and simple trachelectomy, maintain favorable oncologic outcomes while preserving reproductive potential in appropriately selected patients. Across all modalities, multidisciplinary collaboration and individualized counseling are critical to optimize both oncologic and reproductive outcomes. Continued research aimed at refining surgical techniques, improve graft viability, and expanding equitable access will be key to advancing fertility preservation as a standard component of comprehensive cancer care.

Uterine transplantation represents a groundbreaking fertility treatment for individuals with uterine factor infertility. Since the first successful live birth from uterine transplantation in 2014, surgical technique and outcomes have been widely reported yet published anaesthetic guidance remains limited. Australia's first uterine transplantation was performed in early 2023 at the Royal Hospital for Women, Sydney, Australia. Anaesthesia for uterine transplantation is complex, requiring multidisciplinary planning. Donor hysterectomy is an extended procedure (8 to 12 h) involving radical dissection, anticoagulation, thromboembolic prophylaxis, and postoperative pain control, with epidural analgesia. Recipient surgery, while shorter (4 to 7h), demands coordination between surgical teams to minimise graft ischaemia time and optimise immunosuppressant administration. Aseptic technique and haemodynamic monitoring are critical components of perioperative care. Following uterine transplantation, recipients may require anaesthesia for cervical biopsies for rejection surveillance or for embryo transfer. These procedures may be prior to, or during pregnancy. Obstetric anaesthetic considerations include the impact of immunosuppression, heightened risks of preeclampsia and acute kidney injury and preterm delivery, and requirements for perioperative planning of caesarean section. Elective and emergency caesarean deliveries can be successfully managed with combined spinal-epidural anaesthesia, with special attention to haemorrhage risk and postoperative analgesia. The final stage of the uterine transplantation pathway is graft hysterectomy, performed electively following completed fertility treatment or for medical indications. This review outlines the anaesthetic considerations for uterine transplantation and all related surgeries, providing insights into perioperative planning, multidisciplinary collaboration, and evolving protocols drawing on the experience at the Royal Hospital for Women. The uterine transplants referred to in this paper were part of a clinical trial, registration number ACTRN12622000917730, Ethics approval 2019/ETH13038.

Fertility preservation in transgender individuals: medical innovation in the service of inclusivity