Research Spotlight

Johnson, N., Wall, A. and Johannesson, L. (2021). “Implementing regulations and policies for uterus transplantation.” Curr Opin Organ Transplant 26(6): 660-663.

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PURPOSE OF REVIEW: Policy development for uterus transplantation (UTx) is in its infancy. Understanding current oversight of UTx programmes can inform further development. RECENT FINDINGS: Currently, the United States has the most comprehensive regulations for UTx. Much of the policy outside the USA is focused on candidate selection. In the USA, UTx is categorized as, and follows policies of, a vascular composite allograft. Some considerations for UTx have not yet been addressed in policy, including the need for candidates to have a viable embryo before listing and transplantation, additional factors that may be warranted in organ allocation and the need to report data on the infant as well as the recipient. SUMMARY: Oversight of UTx falls within the governance of solid organ transplantation with unique aspects to be considered. Guidelines for multidisciplinary care, transplant-focused infrastructure and defined outcome metrics found in other solid organ transplant programmes provide a useful framework for UTx programmes.

Johannesson, L. and Wall, A. (2021). “Uterus transplantation – donor and recipient work-up.” Curr Opin Organ Transplant 26(6): 634-639.

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PURPOSE OF REVIEW: Uterus transplantation (UTx) is transitioning from an experimental procedure to a clinical treatment for absolute uterine factor infertility (AUFI). Standardized protocols for the evaluation and selection of donors and recipients that maximize chances of success – a healthy live birth – are needed. RECENT FINDINGS: To date, recipient eligibility has been limited to otherwise healthy women with AUFI who are of childbearing age and are good candidates for in-vitro fertilization (IVF). For donors (living or deceased), selection criteria vary, apart from basic requirements of blood-type compatibility and freedom from critical infectious diseases, but generally require a term birth and a uterus free from uterine pathologies. The stepwise evaluation process for candidate recipients and living donors moves through health screening (medical and psychosocial); initial selection committee review; IVF (recipients only); and final selection committee review. This eliminates candidates with poor chances of success before exposure to unnecessary risks. SUMMARY: The currently stringent selection criteria for prospective recipients and donors will likely broaden, as UTx becomes more widely available. Continued research is needed to define the donor, recipient and uterine graft factors associated with successful outcomes, and to support the development of standardized selection criteria.

Dorafshar, A.H., Jahromi, A.H., Horen, S.R., Schechter, L.S., Johannesson, L., Testa, G., Hertl, M., Dewdney, S., Aschkenasy, J., Molo, M.W., Brincat, C., Cherullo, E., Behel, J.M., Hebert, C., Shulman, R., Bassi, S., Alecci, A.T. and Konety, B. (2021). “Strategic Planning and Essential Steps for Establishing a Uterine Transplant and Rehabilitation Program: From Idea to Reality.” Ann Surg Nov 18. [Epub ahead of print].

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Uterine transplant (UTx) is performed to address absolute uterine infertility in the presence of uterine agenesis, a non-functional uterus, or following a prior hysterectomy. Following the initial success of UTx resulting in a livebirth (2014) in Sweden, there are over 70 reported UTx surgeries resulting in more than 40 livebirths worldwide. Currently, UTx has been performed in over 10 countries. As UTx is transitioning from an “experimental procedure” to a clinical option, an increasing number of centers may contemplate a UTx program. This article discusses essential steps for establishment of a successful UTx program. These principles may be implemented in cis- and transgender UTx candidates.

Daly, S.R., Nguyen, A.V., Zhang, Y., Feng, D. and Huang, J.H. (2021). “The relationship between COVID-19 infection and intracranial hemorrhage: A systematic review.” Brain Hemorrhages 2(4): 141-150.

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INTRODUCTION: In addition to the deleterious effects Covid-19 has on the pulmonary and cardiovascular systems, COVID-19 can also result in damage to the nervous system. This review aims to explore current literature on the association between COVID-19 and intracranial hemorrhage (ICH). METHODS: We conducted a systematic review of PubMed for literature published on COVID-19 and ICH. Ninety-four of 295 screened papers met inclusion criteria. RESULTS: The literature addressed incidence and mortality of ICH associated with Covid-19. It also revealed cases of COVID-19 patients with subarachnoid hemorrhage, intraparenchymal hemorrhage, subdural hematomas, and hemorrhage secondary to cerebral venous thrombosis and ischemic stroke. ICH during COVID-19 infections was associated with increased morbidity and mortality. Risk factors for ICH appeared to be therapeutic anticoagulation, ECMO, and mechanical ventilation. Outcomes varied widely, depending on the severity of COVID-19 infection and neurologic injury. CONCLUSION: Although treatment for severe Covid-19 infections is often aimed at addressing acute respiratory distress syndrome, vasculopathy, and coagulopathy, neurologic injury can also occur. Evidence-based treatments that improve COVID-19 mortality may also increase risk for developing ICH. Providers should be aware of potential neurologic sequelae of COVID-19, diagnostic methods to rule out other causes of ICH, and treatment regimens.

Afzal, A., Alam, A., van Zyl, J.S., Zafar, H., Felius, J., Hall, S.A. and Carey, S.A. (2021). “Observed Elevated Donor-Derived Cell Free DNA in Orthotopic Heart Transplant Recipients Without Clinical Evidence of Rejection.” Clin Transplant Dec 4;e14549. [Epub ahead of print]. e14549.

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Donor-derived cell free DNA (dd-cfDNA) has rapidly become part of rejection surveillance following orthotopic heart transplantation. However, some patients show elevated dd-cfDNA without clinical evidence of rejection. With the aim to provide a clinical description of this subpopulation, we retrospectively analyzed 35 cardiac transplant recipients at our center who experienced elevated (≥0.20%) dd-cfDNA in the absence of clinical rejection, out of a total 106 recipients who had dd-cfDNA results available during the first year. The median time to first elevated dd-cfDNA level was 46 days, and the highest dd-cfDNA recorded within 1 year was 0.31% [inter-quartile range, 0.23 – 0.45]. Twenty-two (63%) patients experienced infections (cytomegalovirus (CMV) or other), and 16 (46%) presented with de novo donor-specific antibodies. Cluster analysis revealed 4 distinct groups characterized by (a) subclinical rejection with 50% CMV (n = 16), (b) non-CMV infections and the longest time to first elevated dd-cfDNA (187 days) (n = 8), (c) right ventricular dysfunction (n = 6), and (d) women who showed the youngest median age (45 years) and highest median dd-cfDNA (0.50%) (n = 5). Continued prospective analysis is needed to determine if these observations warrant changes in patient management to optimize the utilization of this vital non-invasive graft surveillance tool.