| BackgroundAbsolute uterine infertility(AUFI)is a disease in which a patient fails to get pregnant normally due to lack of uterus(congenital / surgical)or uterine abnormality(structural /functional).The treatment of AUFI is based on improving the quality of life of patients.In the past,the offspring’s problems could only be solved by surrogacy and adoption but it’s not the point.At the beginning of this century,uterine transplantation technology(UTx)has been researched worldwide as the only medical method to treat AUFI.At present,both living donors(LD)and brain-dead donors(DBD)have been reported that the recipient was pregnant and delivered after the UTx.Although more than 60 clinical trials of UTx have been reported worldwide,there are only 19 cases of live birth.It can be seen that there are still many problems to be solved in this field and technology.At present,the research on the potential recipient of UTx in China is blank,and the preoperative screening strategy adopted may not be suitable for Chinese national conditions.Although we have completed the first domestic pregnancy and childbirth after UTx in 2019,there is no pathological evidence of the feasibility for immune anti-rejection protocol.Besides,whether the UTx is a high-risk factor for preeclampsia during pregnancy has not been studied.In addition,basic research on uterine ischemia-reperfusion injury(IRI)and exploration of potential treatment during warm ischemia time in UTx of menopausal donors is currently rarely reported.ObjectiveExploring effective methods for preoperative screening of potential recipients and donors of uterine transplantation,and summarize the clinical characteristics of the current Chinese population who is interested in UTx through the investigation and research in a single center.Observing the effect of ischemia-reperfusion injury in premenopausal and postmenopausal rats on uterine structure during the process.Exploring the potential treatment of human-derived umbilical cord mesenchymal stem cells(h UC-MSCs)in the damage.Providing theoretical support for the treatment of menopausal donors of UTx trial in the future.Using pathological staining and immunohistochemistry to analyze the placenta and myometrium obtained from the first uterine transplant recipient in China to explore possible pathological evidence related to immune anti-rejection in case.Comparing with the kidney transplant recipient,preeclampsia patients and normal pregnancy to analyze the histological differences.MethodThe target population is a follow-up survey of AUFI patients and their possible uterine donors.According to clinical needs and previous research experience,8 aspects of survey content were formulated.Registration forms will be issued to people who consulted clinical trials of UTx through an outpatient or telephone call between November2018 and October 2019.Collect the information which is accepted into the survey,and process the analytical data.Uterine ischemia-reperfusion injury models in premenopausal and postmenopausal rats are established to simulate the organ warm-ischemia state during transplantation.The treatment group included orthotopic transplantation and in vitro injection with human umbilical cord mesenchymal stem cells,and estrogen subcutaneous injection therapy.The potential effect of stem cell repair of menopausal ischemia-reperfusion injury was preliminarily explored by comparing the differences in macroscopic and section staining of samples between groups.Clinical data,transplantation procedures and immune anti-rejection program of the pregnant patient after Chinese first UTx trial were summarized.Samples of myometrium and placenta were collected after the termination of pregnancy.Collecting the data and samples of patients with normal pregnancy and pregnancy after kidney transplantation,which were used to be a comparative research.The levels of inflammatory cells and preeclampsia biomarkers in each group of samples by means of clinical outcome comparison,pathological and immunohistochemical staining to verify the feasibility of pregnancy and immune anti-rejection protocol in China.ResultA total of 102 potential recipients and their donors were enrolled in the consultation,but 18 of them were unable to provide complete survey data for subjective reasons.The valid number of potential recipients was 84,and the number of recipients that could provide donors was 37.The average age of potential recipients was 26.0(18-47)years.Among the potential recipients,76(90.5%)were diagnosed congenital AUFI and 8(9.5%)were diagnosed acquired AUFI.The average age of potential donors with available organ donation was 47.5(32-64)years,and the proportion of postmenopausal or peri-menopausal status was 56.7%.What’s more,the social burden of potential recipients mainly comes from economic factors,health factors and psychological factors.All of them are equally important.The postmenopausal rat model was established.Prepared and identified human umbilical cord mesenchymal stem cells,which showed its multi-source differential ability.The rat uterine ischemia-reperfusion injury model based on previous research experience are established,which includes menopausal animal models undergoing therapeutic studies.From the pathological results,the samples of the injured group showed obvious damage in endometrium and submatrix,which were manifested as the degeneration of epithelial cells,the edema of tissue,the reduction of glandular cells,and inflammatory cell aggregation.The degree of injury in the menopausal group was more obvious,with endometrial necrosis and submatrix gland atrophy.The tissue morphology of the stem cell treatment group was almost normal,with a small amount of inflammatory cell infiltration and no obvious intimal epithelial cell degeneration.There was no significant difference in pathological results between the stem cell treatment group and the combined treatment group.The differences of immune anti-rejection protocol between the transplantation groups were summarized.The patients in the group UTx increased the dose of methylprednisolone but decreased the dose of tamoxifen during the postoperative stable period compared with the kidney transplantation group.The pathological results showed that collagen fibers with lower expression were found in myometrium and placenta of the transplantation group compared with the control group.Immunohistochemical staining results showed that the uterine myometrium and placenta of the group UTx showed a lower degree of inflammatory cell infiltration than the kidney transplantation group except for monocytes/macrophages.Samples of the group UTx showed low levels of Flt-1,a credible biomarker of preeclampsia.ConclusionThe number of uterine transplant candidate recipients who meet the criteria and provide donor sources is not sufficient.Congenital AUFI is the main source of recipient for UTx.At present,the foremost problem facing pre-operative screening of UTx is that the recipient is not adequately prepared for the trial,and the potential donor is over-aged that the menopause ratio is too high.When consulting a hypothetical recipient,it is equally important to take into account the economic,health,and psychological factors of the patient.Therefore,uterine transplant clinical trials must increase the number of survey populations,while considering adequate and rigorous screening time and processes to improve the screening efficiency and trial rates.The degree of uterine ischemia-reperfusion injury in menopause rats seems to be more serious compared with the group control,which reflects that the uterus of a menopausal donor may have limited ability to tolerate warm ischemia during uterine transplant.Human umbilical cord mesenchymal stem cells has showed low immunogenicity and high differentiation potential could be used as a treatment or prevention for uterine ischemia-reperfusion injury.From the neonatal prognosis and pathological staining results,The UTx immune anti-rejection protocol has limited impact on the uterus and placenta of the recipient during pregnancy.In future clinical trials,minor adjustments referred to current protocol could be made based on the actual situation.The immunohistochemical staining results of pregnancy after UTx may not support evidence of high risk of preeclampsia.However,it needs more samples and longer follow-up research. |
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