At present, the evaluation indicators of the immune status of patients with recurrent abortion (RM) and repeated implantation failure (RIF) are very limited at home and abroad(it’s only limited to the detection of peripheral blood lymphocytes) or are blank. However, traditional evaluation indicators do not fully reflect the local immune status of patients' blood and endometrium. Therefore, in view of the current low cure rate of RM / RIF, clarifyingthe immunological mechanism of RM / RIF and establising a comprehensive system for assessing the immune status of RM / RIF patients are expected to provide an effective treatment strategy for uRM.

In recent years, the evaluation of endometrial immune status in patients with RM / RIF has focused on the study of one or two immune cells in the endometrium. The lack of a comprehensive analysis of all immune cells in the endometrium makes it impossible to comprehensively assess the overall immune status of uRM patients. At the same time, the traditional method of manual counting to analyze each immune cell by using immune tissues select fewer visual fields and the results are less credible. In order to overcome the instability caused by the subjective recognition of immunohistochemically positive cells, our reproductive immune center took the lead in introducing an automated immunohistochemical staining instrument and a multispectral digital pathological analysis system into the endometrial immune cell immunohistochemistry experiment in the field of reproduction. the experiment is fully automatic. At the same time, more fields of view are selected for analysis. Automatical analysis reduce human errors and provide accurate and stable endometrial immune cell results for clinical diagnosis and treatment. The results can accurately and quantitatively analyze the number of each endometrial immune cell, accurately determine the percentage of immune cells in the total endometrial cells, and simultaneously assess whether the changes in each endometrial immune cell affect each other. The application provides accurate diagnosis results for the personalized diagnosis and treatment system, and lays down the discipline influence and professionalism of our center in the field of reproduction. Based on this innovative technology, we have obtained a utility model patent and an invention patent, respectively, and won the first prize of Shenzhen Science and Technology Progress Award and the second prize of National Maternal and Child Health Science and Technology Award.

Since its establishment, the Reproductive Immunology Center has been adhering to the concept of “scientific research comes from the clinic and serves the clinic”, and has carried out scientific research around clinical problems and laid out the construction of reproductive immunology. In 2011, they were jointly approved by the Shenzhen Municipal Commission of Human Rights as "Shenzhen Key Medicine Key Discipline (Group)-Urology Andrology Group (Urology, Reproductive Laboratory)"; in 2012, they were approved by Shenzhen Science and Technology Commission "Shenzhen "Implantation Key Laboratory of Reproductive Immunity" and passed the acceptance test in early 2015; in 2013, with the understanding of reproductive immunity around the implantation stage, the center took the lead in establishing the endometrial immune cell profile in China to assess RM and Endometrial receptivity in patients with RIF; In 2014, in order to overcome the instability caused by the subjectivity of immunohistochemically positive cell recognition, the center took the lead in introducing a digital pathology analysis platform in the field of reproduction, which was provided through scanning equipment and signal recognition software Accurate and stable results of the number of endometrial immune cells; In 2015, based on the endometrial immune cell evaluation platform, patients were further classified based on immune indicators, and then targeted treatment plans such as intrauterine perfusion were developed. Improved the clinical pregnancy rate of patients on the basis of reducing drug abuse; in order to further improve the patient's hypercoagulability detection system in 2016, The center purchased a platelet aggregation rate detector to monitor the coagulation status of patients with multiple indicators. In addition, in order to further improve the accuracy of the endometrial immune cell evaluation system and reduce labor costs, the center purchased a fully automated immunohistochemical staining instrument; 2017 In order to strengthen the stability of the peripheral blood detection system and provide patients with more accurate results, it is planned to purchase automatic biochemical analyzers and flow cytometers. As of August 2017, the center's reproductive and immunological discipline construction has completed the layout of two major research directions: peripheral blood and endometrium.

As of August 2017, the center has invested about 50 million yuan. The center has about 400 square meters of sterile culture room and central laboratory, equipped with BD FACSCanto II flow cytometer, Beckman 13-color flow cytometer, BioTek micro Large-scale imported experiments such as workstations, full-function microplate readers, Luminex 200 liquid-phase chips, Lycra cryostats, fully automatic dehydrators, embedding and microtome, fully automatic immunohistochemical staining instruments, and digital multipath imaging imaging pathology analysis systems instrument. It provides a scientific research platform for discipline construction and development,such as flow cytometry, liquid microarray, immunohistochemistry, immunofluorescence, detection of hypercoagulability, ELISA, ELISPOT, and sequencing.

From the perspective of reproductive immunology, pregnancy is a phenomenon of semi-allograft, and the embryo is equivalent to an allograft. Normal pregnancy depends on the precise dynamic balance between the mother and fetal immune system. However, if the immune balance between the mother and the fetus is broken, it will cause the mother to reject the fetus and cause an abortion. Evidence shows that the onset of uRM, which is closely related to immune abnormalities, is caused by abnormal numbers and functions of local immune cells and abnormal secretion of cytokines in the implantation site of maternal blood and the maternal-fetal interface. Therefore, the evaluation of the immune status of uRM patients is conducive to reproductive doctors to do comprehensive diagnosis of uRM etiology and to apply accurate and timely treatment. It has important practical and social significance to improve the fertility rate of uRM patients. However, At present, the evaluation indicators of the immune status of patients with recurrent abortion (RM) and repeated implantation failure (RIF) are very limited at home and abroad(it’s only limited to the detection of peripheral blood lymphocytes) or are blank. However, traditional evaluation indicators do not fully reflect the local immune status of patients' blood and endometrium. Therefore, in view of the current low cure rate of RM / RIF, clarifyingthe immunological mechanism of RM / RIF and establising a comprehensive system for assessing the immune status of RM / RIF patients are expected to provide an effective treatment strategy for uRM.

In view of this situation, according to the results of previous retrospective case studies combined with the latest developments in international research, our center from the surrounding blood includes NK cell (killer cell) toxicity, Th cytokines, etc. and five types of immune cells (NK cells, Macrophages, T cells, dendritic cells-DCs, and B cells) evaluated the immune status of uRM patients during the implantation window period and at the implantation site. At the same time, combining large-scale clinical data to scientifically classify patients, the centre design individualized treatment plans for each patient, provide more accurate diagnosis and treatment, comply with the current concept of precision medicine, and prevent overdiagnosis and inspection, and cherish patients’precious fertility time,which optimize the diagnosis and treatment of uRM.

The establishment of a unique immune assessment system escorted for precise treatment and accurately identified the etiology of uRM patients, thereby significantly improving the fertility rate of uRM patients up to 86%, greatly reducing the pain and burden of patients, and also for the construction a warm family and a harmonious society have contributed, making our center a domestic reproductive immune diagnosis and treatment center for a comprehensive assessment of the immune status of uRM patients. At the same time, our center's research on the immune mechanism and treatment of uRM patients has also made pioneering progress, published a number of SCI papers, and spoke at conferences at home and abroad on reproductive immunity, and has been recognized by international peers. At present, it has cooperated with Yale University, Fudan University and other top domestic and foreign reproductive medical research institutions, and will continue to explore the immunological mechanism of uRM and new methods of immunotherapy.