First clinical uterus transplantation trial: a six-month report.

OBJECTIVE: To report the 6-month results of the first clinical uterus transplantation (UTx) trial. This type of transplantation may become a treatment of absolute uterine-factor infertility (AUFI). DESIGN: Prospective observational study. SETTING: University hospital. PATIENT(S): Nine AUFI women and their live uterine donors, the majority being mothers. INTERVENTION(S): Live-donor UTx and low-dose induction immunosuppression. MAIN OUTCOME MEASURE(S): Data from preoperative investigations, surgery and follow-up for 6 months. RESULT(S): Durations of donor and recipient surgery ranged from 10 to 13 hours and from 4 to 6 hours, respectively. No immediate perioperative complications occurred in any of the recipients. After 6 months, seven uteri remained viable with regular menses. Mild rejection episodes occurred in four of these patients. These rejection episodes were effectively reversed by corticosteroid boluses. The two graft losses were because of acute bilateral thrombotic uterine artery occlusions and persistent intrauterine infection. CONCLUSION(S): The results demonstrate the feasibility of live-donor UTx with a low-dose immunosuppressive protocol. CLINICAL TRIAL REGISTRATION NUMBER: NCT01844362.

Transplantation of the uterus in sheep: methodology and early reperfusion events.

AIM: Uterine transplantation is developing into a clinical treatment for uterine factor infertility. An animal model with a similar uterus size and vessels to humans and with pregnancy extending over several months would be beneficial for research on uterine transplantation. The aim of this study was to develop and evaluate autotransplantation of the sheep uterus to an orthotopic position in the pelvis. METHODS: Female sheep (n=7) were subjected to laparotomy with the uterus and its vascular supply and drainage being surgically isolated. The excised uterus was kept ex vivo at +4 degrees C for 60 min and then autotransplanted with vascular end-to-side anastomoses to the external iliac vessels. The effects of uterine blood-reperfusion were assessed by measurements of pCO(2), pO(2), lactate and pH in uterine venous blood. Uterine contractility and histology was assessed after 3 h of reperfusion. RESULTS: Reperfusion of blood was observed in five out of seven transplanted uteri. The pCO(2)/pO(2)-ratio and the lactate level were initially elevated but decreased and became normal after 60 min. After 3 h of reperfusion there was a visible tissue blood flow and spontaneous uterine contractions were seen. Histological analysis revealed a mild inflammation, but no edema or stasis. CONCLUSIONS: This study demonstrates that the sheep uterus can successfully be autotransplanted to an orthotopic position with novel vascular connections. This model is suitable for future experiments studying long-term results concerning uterine viability and pregnancy using a transplanted uterus of similar size to the human uterus.

Auto-transplantation of the uterus in the domestic pig (Sus scrofa): Surgical technique and early reperfusion events.

AIM: To develop a method for auto-transplantation of the uterus in the pig and to evaluate the early reperfusion events after short-term cold ischemia. METHODS: The bicornate uterus, with the cervix but without ovaries, was dissected and isolated with its bilateral feeding and draining vessels. The uterine arteries were cannulated in situ and the uterus was flushed with heparinized Ringer Acetate. It was stored at 4 degrees C for 1-2 h during continuous flushing. The uterus was then placed in its original pelvic position and the uterine arteries and veins were anastomosed end-to-end to their origin. During approximately 100 min of reperfusion, blood samples and tissue biopsies were taken for monitoring of reperfusion events and detection of ischemia-reperfusion injuries. RESULTS: Out of 19 auto-transplanted pigs, seven were considered well flushed and were kept for cold ischemia. Of these seven, four showed satisfactory reperfusion judged by change in gross appearance and presence of appropriate venous blood flow. Analysis of blood-gas and metabolite parameters and histology indicated that at least two of these transplants were well reperfused, with no severe ischemia-reperfusion injuries. CONCLUSION: In this first report ever on auto-transplantation of the pig uterus it is demonstrated that an acceptable reperfusion can be achieved. Furthermore, it is suggested that because of the large total size of the pig uterus with long uterine horns and the small size of the vessels available for re-anastomosis, the pig is a fairly difficult model for further studies on transplantation of the uterus.