| Background : Absolute uterine factor infertility (AUFI) is the only major type of female infertility that still viewed as untreatable. The major causes are congenital absence of the uterus (Mayer-Rokitansky-Kuster-Hauser syndrome), after hysterectomyat an early age,which is often a life-saving procedure following early stage cervical cancer or intractableperipartum hemorrhageand a non-functional uterus for severe intrauterine adhesions. The purpose of uterus transplantation (UTx) is to enable provide a uterus and live birth from a woman that lacksthe uterus or in a woman that has a defective uterus.To develop UTx into human clinically safe procedure with pregnancy and live birth outcome many aspects of the procedures involved need to be thoroughly addressed in animal models,it is therefore to use defferent species animal models is appropriate contexts, at domestic, large animal experimental studyof UTx has being exploration stage, in addition,attitude of patients with reproductive age uterine factors infertility towards UTx is unknown.Objective: 1. The aim of this study is to examine the allowable feasibility and safety of technology of allogeneic UTx from a living donor and to oberserved the long-term graft survival and reproductive function recovery in the miniature swine. 2. establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a living donor in cynomolgus macaque, and to evaluation tolerating time and histopathological changes in cold ischemia injury of the uterus in cynomolgus macaque as amodel for uterus transplantation. 3. We were surveys attitude and willingness of patients with the MRKH syndrome for UTx, and to providing clinic data and volunteers for the next step human UTx.Methods : 1. Ten female miniature swines with regular menstrual cycles were used, the animals were either donors or recipients (n=5) depending on their sibling born and body weight, the uterus with vaginal canal and main blood vessels were resected from living donors in the after general anesthesia, isolated organ was performed with cold storage and continuous flushing at 4℃ organ preservation solution in the bake-table preparation,internal iliac arteryof grafte were end-side anastomosed with external iliac arteries. 2.Transplanted uterus of five cases were offered immunosuppress maintenance treatment and transplanted uterine that were evaluated arteryblood flow signals by transabdominal ultrasonography and observed by secondary laparotomy in the postoperative, heating recovery was monitored and performed artificial embryo transfer after UTx. 3. Two female cynomolgus macaque with regular menstrual cycles were used, the animals were either donor or recipient (n=1) depending on their blood type and body weight, uterus and major vessles were transplanted, transplanted uterine were evaluated artery blood flow signals and pelvic by ultrasonography inpostoperative. Myometrium tissue of uterine were resected before cold storage as the control group and uterus tissue to be cold storaged 4h and 8h by 4℃UW (University of Wisconsin) liquid as the study group, the histological changes of the uterine tissues were observed by electron and light microscope at different cold preservation times from recipient’s uterus. 5. To collected hospitalization patients that MRKH (mayer-rokitansky-kuster-hauser) syndrome with congenital absence of the uterus and vaginal were performed vaginoplasty a total of 31 cases in the PLA general hospital and CAPF general hospital on the December 2005 - December 2015, The patient will be asked about the UTx attitudeand implement of raising a child by telephone follow-up .Results :1.All five cases showed that the iliac vascular were anastomosed successfully, all recipient survived for more than 3 months after the surgery without any surgical complications except UTx5 case, transabdominal ultrasonography showed that pulsatile arterial blood flow in the transplanted uterine artery within 1 week and 1 month after surgery in all cases, The UTx5 case was died after surgery3 days from acute rejection or infection caused necrosis of the uterus, the uterus transplant success rate 100%, receptor long-term survival rate of 80%, UTx2 case was recovery heating and peformed artificial embryo transplant in the after UTx 3 months, no found apparent pregnancy by Doppler ultrasonography. 2. The iliac vascular were anastomosed successfully in the cynomolgus macaque, receptor animal was deid from chronic failure after surgery 28 days. Uterus tissue were no changed for cold ischemia 4hunder the electron microscope, but, plasma membrane swelling, nuclear fragmentation along with mitochondrial swelling were found in cold ischemia 8h. There were no particular findings in light microscopy. 3. 31 cases MRKH syndrome patients of reproductive age, intention for UTx: 6 cases, 19.3%, need to consider or discuss: 18 cases, 58%, did not intention for UTx: 4 cases, 12.9%, did not express opinions: 3 cases, 9.6%, 18 cases discuss for UTx major concerns: economic problems 6 cases, 33.3%, operation risk 5 cases, 27.7%, postoperative immunosuppressant effects 3, 16.6%, support of family4 cases, 22.2%, Of the respondents, 25.8%,19.3%,38.7%,16.1%, favored UTxand gestational surrogacy, adoptionand others.Conclusion: 1. Uterus allotransplantation is feasible in large animal model from living donor,laboratory animal can be a long time survival and resumed heating after UTx,doppler ultrasonography can be monitoring grafted artery blood flow. 2. Cynomolgus macaque is the appropriated for UTx animal models, uterus myometrium tissue can be tolerate cold storage 4h by 4℃UW organ preservation solution at least. 3. Patients withe MRKH syndrome of reproductive age were more tendency for UTx thangestational surrogacy. |
