Search Results (44)

In recent years, advances in organ transplantation medicine have led to an increase in pregnancies and births following transplantation. Pregnancy after organ transplantation is considered high-risk, and its impact on both the recipient and the child must be carefully evaluated. In this review, we summarize the current landscape of pregnancy and childbirth after organ transplantation, with a particular focus on uterus transplantation (UTx). Traditionally, organ transplants have involved vital organs; however, UTx, developed for women with absolute uterine factor infertility, represents a novel approach. Although the number of births following UTx remains limited, it is expected to grow due to the international expansion of this procedure. Importantly, the concept of pregnancy and delivery following UTx is fundamentally different from that of other organ transplants. UTx is a life-enhancing, non-vital, and temporary transplant uniquely intended to enable the creation of new life. Pregnancy after UTx carries specific risks such as a higher incidence of miscarriage, preterm birth, hypertensive disorders of pregnancy, and gestational diabetes. All deliveries are performed via cesarean section, and conception is typically allowed after a relatively short period following transplantation, given the temporary nature of the graft and the goal to minimize recipient burden, with generally good neonatal outcomes. As pregnancies after both solid organ transplantation and UTx continue to rise worldwide, the development of standardized, organ-specific perinatal management strategies, particularly for UTx, is essential. Multidisciplinary collaboration will be critical to supporting these high-risk pregnancies and ensuring the best possible maternal and neonatal outcomes. Full article

Background/Objective: Thrombosis is the leading cause of graft failure and immediate hysterectomy following uterus transplantation (UTx). Currently, there is no standardized method for real-time assessment of UTx graft perfusion. This feasibility study aims to evaluate the utility of a near-infrared spectroscopy (NIRS) probe for non-invasive monitoring of local cervical tissue oxygenation (StO₂) during UTx. As proof-of-concept for the NIRS device, cervical StO₂ was also measured during non-donor hysterectomy and bilateral salpingo-oophorectomy to establish its capacity to reflect perfusion changes corresponding to vascular ligation. Methods: The ViOptix T. Ox Tissue Oximeter NIRS probe was attached to four uterine cervices during hysterectomy procedures and three separate donor cervices during UTx. Real-time StO₂ measurements were recorded at critical surgical steps: baseline, ovarian vessel ligation, contralateral ovarian vessel ligation, uterine vessel ligation, contralateral uterine vessel ligation, and colpotomy for hysterectomy; donor internal iliac vein anastomosis to recipient external iliac vein, donor internal iliac artery anastomosis to recipient external iliac artery, contralateral donor internal iliac vein anastomosis to recipient external iliac vein, contralateral donor internal iliac artery anastomosis to recipient external iliac artery, and donor and recipient vagina anastomosis for UTx. Results: During hysterectomy, average StO₂ levels sequentially decreased: 70.2% (baseline), 56.7% (ovarian vessel ligation), 62.1% (contralateral ovarian vessel ligation), 50.5% (uterine vessel ligation), 35.8% (contralateral uterine vessel ligation), and 8.5% (colpotomy). Conversely, during UTx, StO₂ progressive increased with each anastomosis: 8.9% (internal iliac vein- external iliac vein), 27.9% (internal iliac artery-external iliac artery), 56.9% (contralateral internal iliac vein-contralateral external iliac vein), 65.9% (contralateral internal iliac artery-contralateral external iliac artery), and 65.2% (vaginal anastomosis). Conclusions: The inverse correlation between StO₂ and vascular ligation during hysterectomy and the progressive rise in StO₂ during UTx suggests that cervical tissue oximetry may serve as a non-invasive modality for monitoring uterine graft perfusion. Further studies are warranted to determine whether these devices complement current assessments of uterine graft viability and salvage thrombosed grafts. Full article

Background: Infertility is a multifactorial condition with medical, psychological, demographic, and economic impacts. Around 3–5% of cases are due to uterine dysfunction. Absolute uterine factor infertility (AUFI) refers to infertility caused entirely by the absence or abnormality of the uterus, which prevents embryo implantation or pregnancy viability. Uterus transplantation (UTx) has emerged as a promising treatment for AUFI and has been successfully performed in over 10 countries. Objectives: This study aims to conduct a systematic review of uterus transplantation, evaluating its efficacy and safety, as well as maternal, neonatal, and long-term outcomes. It also explores current challenges and future directions. Methods: The methodology was registered on the PROSPERO platform. A literature search was performed in January 2025 across PubMed, Web of Science, and Scopus for articles published from January 2002 to December 2024 in English or Portuguese. The query was: “uterus/transplantation AND (pregnancy OR complications OR newborn OR premature OR diseases)”. Study quality was assessed by journal impact factor (IF). Data were analyzed using Microsoft Excel. Results: A total of 10 studies were included: four from Sweden, three from the DUETS group, two from the Czech Republic, and one multi-institutional American study. The UTx success rate was 74.0%; clinical pregnancy rate (CPR) and live birth rates (LBR) per embryo transfer (ET) were 36.3% and 22.0%, respectively. No significant increase in congenital or neurological complications was observed. Adverse psychological outcomes were associated with transplant failure or pregnancy loss. Conclusions: UTx is a promising treatment for AUFI, showing favorable pregnancy and birth outcomes without major fetal or neonatal risks. Full article

Introduction: Uterine transplantation is currently the only treatment that allows women with absolute uterine factor infertility (AUFI) to gestate and give birth. Objective: This systematic review aims to analyze the available evidence on uterine transplantation, focusing on the medical process, associated complications, ethical dilemmas, and the psychological and social impact on recipients. Methods: A systematic review of PubMed, Medline, MedNar, and Cinahl databases was conducted. The inclusion criteria included articles related to uterine transplantation published in English or Spanish between 2019 and 2024, excluding animal studies or other uterine procedures. Results: A total of 46 articles were analyzed. The review describes ethical considerations and recipients’ perceptions, two variables that have received limited attention in recent studies. Additionally, the transplant and gestation processes, along with associated complications, were detailed. Discussion: The limited availability of studies on ethical aspects and recipient perceptions presented challenges in the research. Moreover, the role of nurses and midwives, despite their importance in the process, is scarcely discussed in the literature. Conclusions: Although uterine transplantation remains an emerging treatment, its development suggests that the benefits may outweigh the risks, offering new hope for women with AUFI. Full article

Transplantation of decellularized uterus tissue showed promise in supporting regeneration following uterine injury in animal models, suggesting an alternative to complete uterus transplantation for uterine factor infertility treatment. However, most animal studies utilized small grafts, limiting their clinical relevance. Hence, we used larger grafts (20 × 10 mm), equivalent to nearly one uterine horn in rats, to better evaluate the bioengineering challenges associated with structural support, revascularization, and tissue regeneration. We analyzed histopathology, employed immunohistochemistry, and investigated gene expression discrepancies in growth-related proteins over four months post-transplantation in acellular grafts and those recellularized (RC) with bone marrow-derived mesenchymal stem cells (bmMSCs). RC grafts exhibited less inflammation and faster epithelialization and migration of endogenous cells into the graft compared with acellular grafts. Despite the lack of a significant difference in the density of CD31 positive blood vessels between groups, the RC group demonstrated a better organized myometrial layer and an overall faster regenerative progress. Elevated gene expression for Vegf, Cd44, and Itgb1 correlated with the enhanced tissue regeneration in this group. Elevated Tgfb expression was noted in both groups, potentially contributing to the rapid revascularization. Our findings suggest that large uterine injuries can be regenerated using decellularized tissue, with bmMSCs enhancing the endogenous repair mechanisms. Full article

Background: Uterus transplantation (UTx) is currently the only available treatment for absolute uterine factor infertility. Deceased donors have recently emerged as a valid alternative to living donors for uterus transplantation, with similar results. Methods: We report the first experience in Italy of uterus transplantation from deceased donors. Three uterus transplantations from deceased donors were performed at the Organ Transplant Unit of the University Hospital of Catania, Italy, between August 2020 and January 2022. Results: Two patients underwent UTx due to Mayer–Rokitansky–Küster–Hauser syndrome, while one patient had a previous hysterectomy due to benign disease. The donors’ ages were between 25 and 43 years and the mean cold ischemia time was 18.3 h. The mean age of the recipients was 31.6 years, and the mean recipient surgery duration was 5.3 h, with a mean blood loss of 766.66 mL. Two recipients developed a post-transplant hematoma, which was treated conservatively. No uterus recipient needed a re-operation during the first 30 days after transplantation. No histological signs of acute rejection were detected at the cervical biopsies performed at 1, 3, and 6 months after transplantation. First menstruation occurred in all recipients after 39 ± 12 days after transplantation. One live birth was reported 15 months after UTx. One graft was lost three months after UTx due to graft thrombosis. Conclusions: Uterus transplantation from deceased donors is emerging as a valid alternative to living donors in order to increase the donor pool. Full article

Uterus transplantation is the surgical treatment for absolute uterine factor infertility (AUFI), a congenital or acquired condition characterized by the absence of a uterus. More than 80 transplants have been performed worldwide, resulting in more than 30 live births, originating both from living and deceased donors. The collection of published articles on deceased donor uterus transplantations was performed in PubMed and SCOPUS by searching for the terms “Uterus transplantation” AND “deceased donor”; from the 107 articles obtained, only case reports and systematic reviews of deceased donor uterus transplantations and the resulting live births were considered for the present manuscript. The extracted data included the date of surgery (year), country, recipient (age and cause of AUFI) and donor (age and parity) details, outcome of recipient surgery (hysterectomy), and live births (date and gestational age). The search of peer-reviewed publications showed 24 deceased donor uterus transplantations and 12 live births (a birth rate of 66%) with a 25% occurrence of graft loss during follow-up (6 of 24). Among this series, twelve transplants were performed in the USA (seven births), five in the Czech Republic (one birth), three in Italy (one birth), two in Turkey (two births), and two in Brazil (one birth). The median recipient age was 29.8 years (range 21–36), while the median donor age was 36.1 years (range 20–57). Of 24 recipients, 100% were affected by MRKH (Mayer-Rokitanski-Kuster-Hauser) syndrome. Two live births were reported from nulliparous donors. Deceased donor uterus transplantation birth rates are very similar to the living donor rates reported in the literature, but ethical implications could be less important in the first group. It is necessary to register every case in the International Registry for Uterus Transplantation in order to perform a systematic review and comparison with living donor rates. Full article

Background/Objectives: Uterus transplantation (UTx) has evolved into a clinical reality for women with absolute uterine infertility. The international experience with UTx has predominantly utilized living donor grafts—and strategies to minimize harm to donors remain paramount. Robotic living donor hysterectomy represents a minimally invasive approach to facilitate rapid donor recovery, improve pelvic visualization and operative access, and maintain UTx recipient outcomes. The aim of this study is to describe donor, recipient, graft, and pregnancy outcomes after adoption of a robotic living donor hysterectomy program. Methods: The Dallas UtErus Transplant Study (DUETS) incorporated a robotic living donor hysterectomy operative protocol, including transvaginal extraction, from April 2019. Prospectively collected data were analyzed, and a case series presented, to describe donor intra- and post-operative outcomes and recipient intra-operative outcomes, graft viability, established pregnancies, and live births. Early cases were compared to later cases to better describe the learning curve associated with the technique. Results: Sixteen robotic living donor hysterectomies were performed with 100% graft viability after implantation demonstrated by myometrial flow and onset of menses. Early experience (eight cases) demonstrated two cases of ureteric injury. Later experience (eight cases) demonstrated a reduction in operative time (11 h 10 min vs. 6 h 38 min), with no ureteric injuries and a reduction in major operative morbidity from 25% to 12.5% (Clavien–Dindo grade ≥3). At the time of reporting, nine successful live births have occurred, with six ongoing pregnancies. Conclusions: Robotic living donor hysterectomy represents a safe approach to minimize donor harm without compromising UTx recipient, graft, and pregnancy-related outcomes. A learning curve is demonstrated with the adoption of the novel technique—with particularly care required to prevent ureteric injuries, and ongoing vigilance and reporting necessary given the small case numbers of robotic living donor hysterectomy reported internationally. Full article

Background: Uterus transplantation (UTx) provides women with absolute uterine-factor infertility (AUFI) the opportunity to carry their own pregnancy and deliver a child. There are multiple ethical and medical concerns associated with UTx. Since the last survey of US provider perceptions of UTx in 2018, there have been additional reports of successful transplantations and pregnancies. This study aimed to identify the perception of UTx among providers involved in the diagnosis of AUFI and on the transplant team to help us understand knowledge gaps and determine what barriers must be overcome for UTx to be used in general clinical practice. Methods: We administered REDCap surveys to conference attendees at the 2023 American College of Obstetricians and Gynecologists (ACOG) conference and 2023 American Transplant Congress (ATC). Participants were recruited by medical student volunteers. Results: Two hundred ACOG and ATC attendees completed the survey. Medical concerns related to UTx were reported by 42% of providers from ACOG compared to 22% of providers from ATC. Overall, 76% of participants agreed that UTx should be an option for patients with congenital AUFI. Lastly, 68% of participants agreed that the procedure should be presented as an option for transgender women. Conclusions: This study further elucidates the perception of UTx among obstetricians/gynecologists and transplant physicians. We found greater support for the procedure than in previous studies. This study also demonstrates provider support for presenting this procedure as an option for transgender women. Full article

Background: The aim of this systematic review is to summarize the evidence regarding the acceptance of uterine transplantation as infertility treatment among gynecological cancer survivors, surgical and pregnancy outcomes post-transplantation for gynecological cancer survivors, as well as relevant adverse events. Methods: PubMed and Embase were searched for records published since 2000, and extensive reference screening was performed. Results: Out of 1901 unique records identified, 7 are included in this review; 4 examined the proportion of gynecological cancer survivors among applicants for uterine transplantation, 2 examined rejection rates, pregnancy rates, and outcomes after uterine transplantation among gynecological cancer survivors, and 2 reported the frequency of relevant adverse events. Among the applicants, 60/701 (8.6%) were gynecological cancer survivors, only 1 transplanted patient was a cervical cancer survivor and achieved two live births after eight embryo transfers, and 2/27 (7.4%) of uterus transplantation recipients were diagnosed with CIN post-transplantation. Conclusions: Uterus transplantation can be regarded as an infertility treatment for absolute uterine factor infertility (AUFI), although only one gynecological cancer survivor has received a uterus transplantation. The efficacy, safety, and ethical considerations for gynecological cancer survivors need to be addressed for uterine transplantation to become an infertility treatment option for AUFI among gynecological cancer survivors. Full article

Uterus transplantation (UTx) is a rapidly evolving treatment for uterine factor infertility. New centers offering this treatment must decide whether to utilize living donors, deceased donors, or both. Although limiting UTx to deceased donors eliminates the surgical risks for living donors, an adequate supply of suitable deceased uterus donors in the United States is an emerging concern. Previous studies describing the paucity of deceased uterus donors failed to consider key donor characteristics, potentially overestimating the available organ pool. To estimate the United States’ supply of deceased donor uteri; we extrapolated detailed clinical and demographic information from the regional donor datasets available from three organ procurement organizations to the national Organ Procurement and Transplantation Network donor pool. We estimate there are approximately 3700 possible and 400 optimal uterus donors annually in the United States. Given these projections and the number of women with uterine factor infertility in the U.S. who pursue parenthood through alternative strategies, we conclude that, as uterus transplant transitions from research to established clinical care, demand could quickly exceed the deceased donor supply. The liberalization of deceased donor selection criteria may be insufficient to address this imbalance; therefore, fulfilling the anticipated increased demand for uterus transplantation may require and justify greater use of living donors. Full article

Uterus transplantation (UTx) is currently the only available treatment for absolute uterine factor infertility. More than 90 uterus transplantations have been performed worldwide, mostly from living donors. Living-donor (LD) UTx is a challenging surgical procedure since it poses ethical issues, and it is a high-risk and invasive surgery with higher hysterectomy-related risks compared to conventional hysterectomy. A total of 59 living-donor hysterectomies have been reported in the literature, including 35 performed with a laparotomic approach, 20 with a robotic approach and 4 with a laparoscopic approach. The mean donor age was 45.6 ± 9.1 years, and 22 were unrelated with the recipients, 34 were emotionally related (27 mothers, 5 sisters, 2 mother’s sisters). The mean recipient age was 28.8 ± 4.5 years. Mayer–Rokitansky–Küster–Hauser syndrome was the most common indication for uterus transplant. Robotic living-donor hysterectomy had the longest operative time but resulted in a lower blood loss and postoperative stay compared to laparotomic and laparoscopic approaches. Twenty-nine births from LD-UTx have been reported, four after robotic living-donor hysterectomy and twenty-five after a laparotomic procedure. UTx is now an effective treatment for women with UFI. While living-donor UTx in some cases may be considered an experimental procedure, it offers the extraordinary possibility to give women the opportunity to have a pregnancy. Many efforts should be made to reduce the potential risks for donors, including the use of mini-invasive techniques, and the efficacy of UTx in the recipients, giving the potential harm of immunosuppression in a recipient of a non-life-saving organ. Full article

Endometriosis (EM) is a prevalent gynecological disease characterized by the abnormal growth of tissue similar to the endometrium outside of the uterus. This condition is accompanied by the development of new blood vessels in endometriotic lesions. While surgical intervention is effective in removing endometriotic lesions, some patients require multiple surgeries. Therefore, finding non-surgical treatments for EM is of great interest. One of the promising approaches is anti-angiogenic therapy using siRNA-therapeutics to target the expression of the VEGFA gene. Peptide-based polymers have shown promise as siRNA delivery systems due to their biocompatibility and ease of modification. We conducted a study to evaluate the effectiveness of the R6p-cRGD peptide carrier as a non-viral vehicle for delivering siRNA to endothelial cells in vitro and endometrial implants in vivo. We investigated the physicochemical properties of the siRNA-complexes, assessed cellular toxicity, and examined the efficiency of GFP and VEGFA genes silencing. Furthermore, we tested the anti-angiogenic effects of these complexes in cellular and animal models. The transfection with siRNA complexes led to a significant increase in VEGFA gene knockdown efficiency and a decrease in the migration of endothelial cells. For the animal model, we induced endometriosis in rats by transplanting endometrial tissue subcutaneously. We evaluated the efficiency of anti-angiogenic therapy for EM in vivo using anti-VEGF siRNA/R6p-RGD complexes. During this assessment, we measured the volume of the implants, analyzed VEGFA gene expression, and conducted CD34 immunohistochemical staining. The results showed a significant decrease in the growth of endometriotic implants and in VEGFA gene expression. Overall, our findings demonstrate the potential of the R6p-cRGD peptide carrier as a delivery system for anti-angiogenic therapy of EM. Full article

Recipients of uterus transplantation have unique factors that may increase their risk of cervical insufficiency. This report describes a uterus transplant recipient with cervical insufficiency resulting in two second-trimester miscarriages. After McDonald cerclages (one that failed), she underwent an interval transabdominal cerclage and delivered a healthy term child in her third pregnancy. The longitudinal information of this case provides observations from which we can propose testable hypotheses that address venous outflow and inflammation. This case also suggests that there could be a role for prophylactic cerclage placement at the time of transplantation. Full article

This study describes the characteristics of women who contacted an active program performing uterus transplantation (UTx) in the US, expressing interest in becoming a uterus transplant recipient or a living donor. Basic demographic and self-reported clinical information was collected from women who contacted any of the three US UTx programs from 2015 to July 2022. The three centers received 5194 inquiries about becoming a UTx recipient during the study timeframe. Among those reporting a cause of infertility, almost all of the reports (4066/4331, 94%) were absence of a uterus, either congenitally (794/4066, 20%) or secondary to hysterectomy (3272/4066, 80%). The mean age was 34 years, and 49% (2545/5194) had at least one child at the time of application. The two centers using living donors received 2217 inquiries about becoming living donors. The mean age was 34 years, and 60% (1330/2217) had given birth to ≥1 child. While most of the UTx clinical trial evidence has focused on young women with congenital absence of the uterus, these results show interest from a much broader patient population in terms of age, cause of infertility, and parity. These results raise questions about whether and to what extent the indications and eligibility criteria for UTx should be expanded as the procedure transitions from the experimental phase to being offered as a clinical treatment. Full article