(Abstracted from JAMA 2024;332:817–824) Absolute uterine-factor infertility, caused by the absence or dysfunction of the uterus due to hereditary conditions or acquired factors such as hysterectomy, traditionally left women with only adoption or surrogacy as reproductive options. However, the first successful uterus transplant in 2011 introduced a novel alternative.
Donation after circulatory death (DCD) donors now represent over 30% of the deceased donor pool in the United States. Compared to donation after brain death, DCD is less likely to result in transplantation. For each potential donor whose organs cannot be utilized for transplantation (ie, dry run), fees are associated with the attempted donation, which add to the overall costs of organ acquisition. To better characterize the true costs of DCD liver acquisition, we performed a cost comparison of the fees associated with organ acquisition for DCD versus donation after brain death at a single transplant institute that comprises 2 liver transplant centers. Cost, recipient, and transportation data for all cases, including fees associated with liver acquisition from July 1, 2019, to October 31, 2021, were collected. We found that the total cost of DCD liver acquisition per liver transplant was $15,029 more than that for donation after brain death donation, with 18% of the costs of the DCD transplant attributed to dry runs. Overall, the costs associated with DCD transplantation accounted for 34.5% of the total organ acquisition costs; however, DCD transplantation accounted for 30.3% of the transplantation volume. Because the expansion of DCD is essential to increasing the availability of liver grafts for transplantation, strategies need to be implemented to decrease the costs associated with dry runs, including using local recovery, transferring donors to hospitals close to transplant centers, and performing more prerecovery organ analysis. Moreover, these strategies are needed to ensure that financial disincentives to DCD procurement and utilization do not reverse the gains made by expanding the organ donor pool using machine perfusion technologies.
Importance:Uterus transplant in women with absolute uterine-factor infertility offers the possibility of carrying their own pregnancy. Objective:To determine whether uterus transplant is feasible and safe and results in births of healthy infants. Design, Setting, and Participants:A case series including 20 participants with uterine-factor infertility and at least 1 functioning ovary who underwent uterus transplant in a large US tertiary care center between September 14, 2016, and August 23, 2019. Intervention:The uterus transplant (from 18 living donors and 2 deceased donors) was surgically placed in an orthotopic position with vascular anastomoses to the external iliac vessels. Participants received immunosuppression until the transplanted uterus was removed following 1 or 2 live births or after graft failure. Main Outcomes and Measures:Uterus graft survival and subsequent live births. Results:Of 20 participants (median age, 30 years [range, 20-36]; 2 Asian, 1 Black, and 16 White), 14 (70%) had a successful uterus allograft; all 14 recipients gave birth to at least 1 live-born infant. Eleven of 20 recipients had at least 1 complication. Maternal and/or obstetrical complications occurred in 50% of the successful pregnancies, with the most common being gestational hypertension (2 [14%]), cervical insufficiency (2 [14%]), and preterm labor (2 [14%]). Among the 16 live-born infants, there were no congenital malformations. Four of 18 living donors had grade 3 complications. Conclusions and Relevance:Uterus transplant was technically feasible and was associated with a high live birth rate following successful graft survival. Adverse events were common, with medical and surgical risks affecting recipients as well as donors. Congenital abnormalities and developmental delays have not occurred to date in the live-born children. Trial Registration:ClinicalTrials.gov Identifier: NCT02656550.
Despite a significant increase in utilization over the past decade, the number of donation after circulatory death (DCD) organs that are procured and transplanted in the United States (US) remains well below its potential. There is still room for expansion, as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in transplantation. We convened a multidisciplinary transplantation summit to examine various aspects of DCD, with faculty members from around the world with clinical and academic interest in DCD donation and transplantation, including abdominal and cardiothoracic surgeons, organ procurement organization directors, hepatologists, and gastroenterologists. The conference focused on identifying barriers to DCD organ utilization and strategies to overcome these barriers. We divide the barriers to DCD utilization into three mains categories: (I) policy and process variation; (II) logistical and transportation challenges; and (III) higher risk perceptions related to DCD outcomes. For each barrier, we proposed a variety of solutions, providing an overview of the status of DCD donation in the US and suggestions on how to increase the use of DCD. There is a specific focus on ex situ machine perfusion, normothermic regional perfusion, and other opportunities to expand DCD utilization without negatively impacting recipient outcomes.
INTRODUCTION:Normothermic regional perfusion (NRP) represents an innovative technology that improves the outcomes for liver and kidney recipients of donation after circulatory determination of death (DCD) organs but protocols for abdominal-only NRP (A-NRP) DCD are lacking in the US.METHODS:We describe the implementation and expansion strategies of a transplant-center-based A-NRP DCD program that has grown in volume, geographical reach, and donor acceptance parameters, presented as four eras.RESULTS:In the implementation era, two donors were attempted, and one liver graft was transplanted. In the local expansion era, 33% of attempted donors resulted in transplantation and 42% of liver grafts from donors who died within the functional warm ischemic time (fWIT) limit were transplanted. In the Regional Expansion era, 25% of attempted donors resulted in transplantation and 50% of liver grafts from donors who died within the fWIT limit were transplanted. In the Donor Acceptance Expansion era, 46% of attempted donors resulted in transplantation and 72% of liver grafts from donors who died within the fWIT limit were transplanted. Eight discarded grafts demonstrated a potential opportunity for utilization.CONCLUSION:The stepwise approach to building an A-NRP program described here can serve as a model for other transplant centers.
Abstract Liver transplantation is now a widely accepted therapy for liver failure and complications from liver disease. The liver is complex with a multitude of synthetic, metabolic, excretory, and immunoregulatory functions. Understanding these and the pathophysiology of liver injury allows for better managing liver failure and recognizing the role for liver transplantation. When a patient with advanced liver disease is referred to a transplant centre, a multidisciplinary evaluation is undertaken which examines six things: indications, contraindications, cancer screening, anatomical evaluation, psychiatric assessment, and prioritization. Organ allocation systems such as the Model for End-Stage Liver Disease with sodium (MELD-Na) score are used to assess mortality risk and determine priority for transplant. After a liver transplant, there is a high potential for complications, and the key to improving outcomes and reducing mortality is to avoid these complications if possible, and effectively managing any that may occur. Additionally, it is imperative to manage immunosuppression to appropriately suppress the alloimmune response against donor alloantigen to prevent rejection, and also minimize side effects and avoid the drug toxicities that also impact survival. There has been great progress over the last five decades and both short- and long-term survival are excellent, with an approximately 92% survival at 1 year and 60% survival at 10 years.
There is a subset of patients with lower MELD scores who are at substantial risk of waitlist mortality. In order to transplant such patients, transplant centers must utilize "nonstandard" donors (eg, living donors, donation after circulatory death), which are traditionally offered to those patients who are not at the top of the waitlist. We used Organ Procurement and Transplantation data to evaluate center-level and region-level variability in the utilization of nonstandard donors and its impact on MELD at transplant among adult liver-alone non-status 1 patients transplanted from April 1, 2020, to September 30, 2022. The center-level variability in the utilization of nonstandard donors was 4-fold greater than the center-level variability in waitlisting practices (waitlistings with a MELD score of <20). While there was a moderate correlation between center-level waitlisting and transplantation of patients with a MELD score of <20 ( p = 0.58), there was a strong correlation between center-level utilization of nonstandard donors and center-level transplantation of patients with a MELD score of <20 ( p = 0.75). This strong correlation between center-level utilization of "nonstandard" donors and center-level transplantation of patients with a MELD score of <20 was limited to regions 2, 4, 5, 9, and 11. Transplant centers that utilize more nonstandard donors are more likely to successfully transplant patients at lower MELD scores. Public reporting of these data could benefit patients, caregivers, and referring providers, and be used to help maximize organ utilization.
Objective Limited data are available on the outcome of infants born after uterus transplantation. Our aim was to describe the hospital course and laboratory findings in the first 2 months of life of the 12 infants born in the Dallas UtErus Transplant Study (DUETS). Study Design Based on the trial protocol, information about infants was collected in a prospective fashion, including infant demographics, hospital course, and laboratory values. Results Twelve infants were delivered, all by cesarean section, from 11 mothers who had undergone uterus transplantation (one mother had two pregnancies and delivered two babies). All pregnancies were singleton. The mothers received immunosuppressive therapy, and one had a rejection episode that was detected during pregnancy. The rejection episode resolved after steroid treatment. The infants had a median gestational age of 366/7 weeks (range: 306/7–380/7 weeks) and median birth weight of 2,920 g (range: 1,770–3,470 g). The lowest Apgar's score at 5 minutes was 8. All infants were appropriate size for gestational age. Two infants presented with bandemia but negative blood cultures. At 2 months of age, all infants achieved the developmental and behavioral milestones outlined by the American Academy of Pediatrics. Conclusion The 12 infants born from mothers with uterus transplants had a neonatal course that reflected the gestational age at delivery. No baby was born with an identified malformation or organ dysfunction. Longer follow-up and a larger number of infants are needed to confirm these observations. Key Points
Standard US practice for donation after circulatory death (DCD) abdominal organ pro-curement is superrapid recovery (SRR). A newer approach using thoracoabdominal normothermic regional perfusion (TA-NRP) shows promise for better recipient outcomes for all organs, but there are few reports of abdominal recipient outcomes from TA-NRP donors. We used the United Network for Organ Sharing data to identify all cardiac DCD donors from October 1, 2020, to May 20, 2022, and categorized them by recovery procedure (SRR vs TA-NRP). We then identified all liver, kidney, and pancreas recipients of these donors for whom 6-month outcome data were available and compared patient and graft survival, kidney delayed graft function (DGF), and biliary complications between TA-NRP DCD and SRR DCD organ recipients. Patient and graft survival did not differ significantly between groups for either kidney or liver recipients. Significantly fewer TA-NRP kidney recipients developed DGF (12.7% [15/118] vs 42.0% [84/200], P <.001), and TA-NRP and pumped kidneys had lower odds for DGF on multivariate analysis. No liver recipients in either group had biliary complications or were relisted for transplantation for ischemic cholangiopathy. Although long-term outcomes need to be investigated, our early results show similar outcomes for recipients of TA-NRP DCD abdominal organs versus recipients of SRR DCD abdominal organs. We believe that TA-NRP is an effective approach to expand the use of DCD organs.