Uterus transplantation: animal research and human possibilities

background: Techniques for uterus transplantation (UTx) have been developed in rodent/domestic animals towards future clinical introduction of UTx to treat uterine factor infertility. The aim of this study was to extend the UTx research into a non-human primate species by developing surgical techniques for uterus retrieval and transplantation in the baboon. methods: Female baboons (n ¼ 15) underwent surgery, with the initial five animals used for studies of pelvic vascular anatomy. Retrieval surgery included isolation of the ovarian veins and the uterine arteries together with the anterior branches of the internal iliacs. The utero- tubal-ovarian specimen was removed, flushed and kept ex vivo for 2 h when the two arterial ends and two venous ends were anastomosed side-to-side to construct one arterial and one venous end. These were, at auto-transplantation, anastomosed end-to-side to the external iliacs and the animals (n ¼ 10) were evaluated concerning cyclicity and later by laparoscopy/laparotomy. results: The total duration of organ retrieval, backtable preparation and transplantation was around 6 h with an overall ischaemic time of the specimen of about 3 h. One animal died due to cardiomyopathy. Five out of the nine surviving animals resumed cyclicity, as a sign of re- established ovarian function. Only two out of these five animals exhibited resumed menstruation, indicating re-established ovarian and uterine function. Laparoscopy confirmed normal-sized uteri in these two animals. conclusions: This study demonstrates the feasibility of UTx by vascular anastomosis in a non-human primate species. The low success rate demonstrates the complexity involved in UTx surgery and the need for further methodological developments.

Uterus transplantation in the baboon: methodology and long-term function after auto-transplantation

Pregnancy and outcome of uterine allotransplantation and assisted reproduction in sheep.

BACKGROUND Uterus transplantation (UTx) is developed in animal models as a future method to treat uterine factor infertility. METHODS All published studies in the area of UTx research were identified. Aspects relating to surgery, cold-ischemia/reperfusion, rejection, immunosuppression, pregnancy, ethics and institutional requirements were examined. RESULTS Uterus retrieval surgery has been solved in animals, including primates. Studies on cold-ischemia/reperfusion indicate an ischemic tolerance of >24 h. The transplantation procedure, with vascular anastomosis, has not been fully developed in animal models, indicated by frequent thrombosis formation. Pregnancies have only been reported in syngenic/auto-UTx animal models. Several ethical issues in relation to UTx, and requirements for a team that would be suitable to undertake human UTx, exist. CONCLUSION Much research on UTx has been performed in appropriate animal models. Several aspects of the procedure have been optimized but some remain to be solved. It is predicted that the research will soon reach a stage that could merit introduction of human UTx as an experimental procedure.

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Experimental uterus transplantation

BACKGROUND Transplantation of the uterus has been suggested as a treatment of uterine factor infertility. This study investigates whether the sheep uterus can resume its capacity to harbour normal pregnancies after autotransplantation by vascular anastomosis. METHODS From 14 ewes, the uterus, excluding one uterine horn, was isolated along with its oviduct and ovary and preserved ex vivo and then transplanted back with end-to-side anastomosis of the vessels of the graft to the external iliac vessels. After recovery, the ewes underwent surgical examination and serum progesterone measurements to ascertain healing and ovarian activity. Afterwards, five autotransplanted and five control ewes were placed with a ram for mating. Caesarean sections were performed before the estimated term of pregnancy and data on fetal measures were compared. RESULTS Of the 14 ewes, seven survived surgery with ovarian activity intact and grafts showing normal appearance. Mating occurred in four of five transplanted ewes and in five out of five controls, and three transplanted animals and five control animals conceived. In one transplanted ewe, torsion of the uterus was observed after spontaneous initiation of labour. Foeti from transplanted mothers were comparable in size to those of controls. CONCLUSIONS Despite the encountered complications, this is the first report to demonstrate fertility and pregnancies going to term after autotransplantation of the uterus in an animal of a comparable size to the human.

V.T. Pillari

Papers

Modified uterine transplant procedure in the sheep model.

An animal model of uterine auto- and allo-transplantation with a successful pregnancy

An animal model of uterine auto and allo-transplantation with the achievement of pregnancy