Although uterus transplantation is still in the experimental stage, it has promising potential as a treatment for women with absolute uterine factor infertility based on the childbirths from living donor trials conducted in Sweden and the United States. We report the main characteristics and perioperative and postoperative courses of both recipients and donors following 4 deceased donor and 5 living donor uterus transplantations. Three main priorities differentiate this study from the previously reported uterus transplantations. First, clinical experience with the largest worldwide group of deceased donor uterine transplants is described. Second, in the majority of living donor uterine recipients, only 2 ovarian veins were used for venous blood outflow. All of these recipient procedures were surgically successful, and follow-up posttransplant ultrasound examinations revealed normal uterine blood supply and outflow. Third, in only one living and one deceased donor recipient, the transplanted uterus relied on only 2 uterine veins for venous outflow with a 50% surgical success rate. In all other recipients, 2 uterine and 2 ovarian veins were utilized. Although a successful pregnancy has not yet been achieved, the presented surgical and functional results of our trial are promising.
The geometric shape of the distal anastomosis in an infrainguinal bypass has an influence on its durability. In this article, we compared three different angles of the anastomosis with regard to the hemodynamics. Three experimental models of the distal infrainguinal anastomosis with angles of 25°, 45°, and 60° respectively were constructed according to the similarity theory to assess flow in the anastomoses using particle image velocimetry and computational fluid dynamics. In the toe, heel, and floor of the anastomosis that correspond to the locations worst affected by intimal hyperplasia, adverse blood flow and wall shear stress were observed in the 45° and 60° models. In the 25° model, laminar blood flow was apparent more peripherally from the anastomosis. In conclusions, decreasing the distal anastomosis angle in a femoropopliteal bypass results in more favorable hemodynamics including the flow pattern and wall shear stress in locations susceptible to intimal hyperplasia.
Aim: To describe our first clinical pregnancy following a uterus transplant from a brain-dead donor and to discuss current issues with deceased donor uterus transplantation as they relate to obstetrical success. Methods: In August 2016, a 26-year-old woman with Mayer-Rokitansky-Küster-Hauser syndrome was the fourth person worldwide to receive a uterine transplant from a deceased donor and was the second in our trial. in vitro fertilization treatments using the long gonadotropin-releasing hormone agonist protocol preceded the transplantation procedure. Frozen embryo transfers were performed in months 12, 13, 16, 19 and 23 after transplant. Results: Recovery of the uterus of a 24-year-old brain-dead nulliparous donor and the transplant procedure itself was uncomplicated. No abnormalities were revealed on Pap smears, which were performed every 6 months during the post-transplant period, and cervical biopsies showed no epithelial dysplasia. The fifth frozen embryo transfer resulted in a clinical pregnancy. Three weeks after embryo transfer, an intrauterine gestational sac containing an embryo with a heartbeat was detected. One week later, signs of a missed abortion were revealed by ultrasound. Two weeks later, spontaneous bleeding occurred, and an ultrasound examination performed a week later confirmed an empty uterine cavity. Conclusion: In light of present research, both deceased donor uterine procurement and transplantation surgeries are technically feasible; however, more experience is needed to determine the pregnancy success rate associated with this method. Thus, additional trials of deceased donor uterine transplantation should be performed in the future to continue research related to this promising concept for the treatment of absolute uterine factor infertility.
Hemodynamics in the distal end-to-side anastomosis is related to early development of intimal hyperplasia and bypass failure. In this study we investigated the effect of diameter ratios between the target artery and the bypass at three different angles of the connection. The pulsatile flow field was visualized using particle image velocimetry in transparent models with three different angles of the connection (25°, 45°, 60°) and the diameter ratio between the bypass and the target artery was 4.6 mm : 6 mm, 6 mm : 6 mm, and 7.5 mm : 6 mm. Six parameters including location and oscillation of the stagnation point, local energy dissipation, wall shear stress (WSS), oscillatory shear index, spatial and temporal gradient of WSS and their distribution in the target artery were calculated from the flow field. In the wider bypass, the stagnation point oscillated in a greater range and was located more proximal to the anastomosis. Energy dissipation was minimal in a wider bypass with a more acute angle. The maximum WSS values were tree times greater in a narrow bypass and concentrated in a smaller circular region at the floor of the anastomosis. The oscillatory shear index increased with wider bypass and more acute angle. The maximum of spatial gradient of WSS concentrated around the floor and toe of the anastomosis and decreased with more acute angle and wider bypass, the temporal gradient of WSS was stretched more towards the side wall. Greater bypass to target vessel ratio and more acute anastomosis angle promote hemodynamics known to reduce formation of intimal hyperplasia.
Background and Aims. Uterine transplantation (UTx) is an experimental sterility treatment method in women with absolute uterine factor infertility. This article describes the current trends and risks in UTx and provides an overview of our experience with this method, to date. Methods. Based on our experience with the Czech UTx trial and the published results of other trials, we describe the possibilities and risks of this perspective method in the treatment of absolute uterine factor infertility (AUFI). Results. Twelve healthy babies were born in 2014-2018 after more than 40 uterine transplantations. There is no general consensus whether it is more suitable to transplant uteri from living or deceased donors, and nulliparous or parous women (with proven obstetrical functionality). Most centers prefer to collect at least ten frozen embryos from in vitro fertilization (IVF) cycles before transplantation. The serious complication of a surgically successful uterine transplantation is posttransplant partial stenosis of the uterine-vaginal anastomosis that may be a technical problem for embryo transfer, outflow of menstrual blood, and sexual satisfaction due to the narrowed and shortened vagina. This paper concludes that, currently, procurement of the uterus and the transplant procedure are surgically feasible and that none of the transplanted uteri have been lost due to rejection but only because of graft thrombosis or infection. Conclusion. Uterine transplantation, after optimization of surgical methods, selection of suitable donors, standardization of immunosuppressive therapy, adjustment of assisted reproductive technologies and obstetrical proceedings might be an effective therapeutic method for women with AUFI who wish to have their own biological child.
Human amniotic membrane (HAM) is used as an allograft in regenerative medicine or as a source of pluripotent cells for stem cell research. Various decontamination protocols and solutions are used to sterilize HAM before its application, but little is known about the toxicity of disinfectants on HAM cells. In this study, we tested two decontamination solutions, commercial (BASE·128) and laboratory decontamination solution (LDS), with an analogous content of antimycotic/antibiotics for their cytotoxic effect on HAM epithelial (EC) and mesenchymal stromal cells (MSC). HAM was processed in a standard way, placed on nitrocellulose scaffold, and decontaminated, following three protocols: (1) 6 h, 37 °C; (2) 24 h, room temperature; (3) 24 h, 4 °C. The viability of EC was assessed via trypan blue staining. The apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). The mean % (±SD) of dead EC (%DEC) from six fresh placentas was 12.9 ± 18.1. Decontamination increased %DEC compared to culture medium. Decontamination with BASE·128 for 6 h, 37 °C led to the highest EC viability (81.7%). Treatment with LDS at 24 h, 4 °C resulted in the lowest EC viability (55.9%) in the set. MSC were more affected by apoptosis than EC. Although the BASE·128 expresses lower toxicity compared to LDS, we present LDS as an alternative decontamination solution with a satisfactory preservation of cell viability. The basic formula of LDS will be optimised by enrichment with nutrient components, such as glucose or vitamins, to improve cell viability.
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