26 results about "Implantation failure" patented technology

The invention discloses application of 2-aminoethoxy diphenyl borate (2-APB) in preparation of a medicine for improving endometrial receptivity and treating diseases related to the endometrial receptivity, and belongs to the technical field of biological medicine. A large number of experiments prove that 2-APB specifically activates a TRPM6 channel, enhances calcium ion influx and activates a calcium-dependent CaM-CaMKII-Ecadherin signal axis, so that expression of receptivity markers (such as E-cadherin and ICAM-1) is up-regulated, and endometrial receptivity is improved. The problems of poor targeting property and high toxicity of the traditional calcium ion carrier are solved, and a safe and effective treatment strategy is provided for a patient suffering from repeated implantation failure (RIF).

The application provides a candidate drug for promoting embryo implantation efficiency of patients with uterine redox imbalance type RIF, and belongs to the technical field of embryo implantation. In order to solve the problem of how to find potential intervention drugs for the pathological mechanism of uterine redox imbalance type RIF, a five-step high-efficiency drug screening strategy based on an in-vitro implantation model of uterine redox imbalance type repeated embryo implantation failure is adopted to ensure the reliability and functional correlation of the screening results. The candidate drug screened by the five-step high-efficiency drug screening strategy includes any one of the following drugs: avobenzone, vasopressin, ethylenediaminetetraacetic acid dipotassium, larotrectinib sulfate, citicoline, opicapone, iclapa, L-leucine, fulvestrant, malic acid and lucotinib. Among these candidate drugs, avobenzone, vasopressin and ethylenediaminetetraacetic acid dipotassium are the best three drugs for promoting the implantation efficiency of patients with uterine redox imbalance type RIF.

The present application belongs to the field of biological medicine and molecular biology technology, and particularly relates to a marker for predicting the occurrence of repeated implantation failure and application thereof. The present application finds that abnormal lipid peroxidation in uterine epithelium can cause implantation defects, and the lipid peroxidation level of the uterus in patients with repeated implantation failure or repeated spontaneous abortion is enhanced, wherein the content of active aldehyde substance MDA and non-heme iron in serum can be used as a new non-invasive clinical index for predicting RIF patients; further, eliminating uterine lipid ROS to improve endometrial receptivity can be used as a potential new treatment strategy to improve embryo implantation and clinical pregnancy rate, and therefore has good practical application value.

The invention discloses application of rutin hydrate in preventing and treating repeated embryo planting failure, and belongs to the technical field of assisted reproduction. It is found for the first time that CD36 is a key membrane protein for lipid transport and uptake of EECs, rutin hydrate competitively inhibits combination of CD36 and natural ligands of CD36, abnormal lipid excessive uptake is remarkably blocked, lipid accumulation and lipid toxicity damage in cells are effectively relieved, and the effect of inhibiting EECs lipid transport and uptake is achieved. And finally, the endometrial receptivity defect related to RIF is reversed, and the embryo adhesion and implantation capability is remarkably improved. Therefore, rutin hydrate provides a brand new strategy for developing targeted therapy drugs for RIF, especially for lipid metabolism disorder type endometrial receptivity badness, and has remarkable clinical application and transformation prospects.

The application provides a candidate drug for promoting embryo implantation efficiency of a patient with endometrial microcirculation disorder type RIF, and belongs to the technical field of embryo implantation. In order to solve the problem of how to find a potential intervention drug for the pathological mechanism of microcirculation disorder type RIF, a five-step high-efficiency drug screening strategy based on an in-vitro implantation model of endometrial microcirculation disorder type repeated embryo implantation failure is adopted to ensure the reliability and functional correlation of the screening result. The candidate drug screened by the five-step high-efficiency drug screening strategy includes any one of the following drugs: phenylbutazone, ferulic acid, L-proline, indinavir, solfazone, teneligliptin and gemcitabine. Among the candidate drugs, phenylbutazone, ferulic acid and L-proline are the best three drugs for promoting the implantation efficiency of the patient with endometrial microcirculation disorder type RIF.

The invention provides a candidate medicine for promoting the embryo implantation efficiency of a uterus redox imbalance type RIF patient, and belongs to the technical field of embryo implantation. In order to solve the problem of how to discover a potential intervention drug aiming at a uterine redox imbalance type RIF pathological mechanism, a five-step efficient drug screening strategy based on an in-vitro implantation model of uterine redox imbalance type repeated embryo implantation failure is adopted, so that the reliability and functional correlation of a screening result are ensured. A candidate drug screened by adopting a five-step method efficient drug screening strategy comprises any one of the following drugs: avobenzone, vasopressin, dipotassium ethylene diamine tetraacetate, lalotinib sulfate, citicoline, olprinone, eltrombopag, L-leucine, fulvestrant, malic acid and rucotinib. Among the candidate drugs, avobenzone, vasopressin and dipotassium ethylenediaminetetraacetate are three drugs with optimal implantation promotion efficiency for patients with uterine redox imbalance type RIF.

The present invention also relates to methods for assessing the risk of pregnancy loss or embryo implantation failure, and to methods for monitoring or evaluating the effectiveness of treatments to reduce the risk of pregnancy loss or embryo implantation failure using specific biomarkers. The present invention also relates to the use of these biomarkers in methods for diagnosing reproductive disorders in individuals, as well as methods for treating reproductive disorders. Furthermore, the biomarkers can further be used in methods for selecting patients for treatment to reduce the risk of embryo implantation failure or miscarriage. The present invention also relates to kits for use in any of the methods described herein.

The invention discloses a preparation method for constructing a mouse embryo implantation failure model based on fusobacterium variabilis, and belongs to the technical field of animal models. The method comprises the following steps: carrying out anaerobic culture on fusobacterium varium, giving the fusobacterium varium to a female C57 mouse through an intragastric administration way, continuously treating for 28 days, and inducing the female C57 mouse to have a phenotype that the number of implanted embryos is reduced and the expression of a vascular endothelial growth factor (VEGF) in a uterine tissue is reduced. According to the method, embryo implantation failure caused by intestinal flora imbalance is simulated through the'intestine-uterus axis' for the first time, a reliable animal model is provided for studying the causal relationship between flora and pregnancy failure, and the method has important scientific research and clinical application value.

The invention discloses a repeated implantation failure analysis method based on a multi-modal data fusion model, and the method comprises the steps: collecting basic information of a patient, medical history, laboratory and iconography examination, embryo transplantation and other multi-modal data, integrating dispersed information, providing a comprehensive data basis for analysis, breaking an information island, and enabling the analysis to be based on a complete image; meanwhile, a neural network model is trained according to the preprocessed data to obtain a multi-modal data fusion model, potential correlation among factors can be mined, internal relations can be accurately reflected through fusion features, complex disease causes can be comprehensively revealed, and the limitation that only one aspect can be concerned in the prior art is overcome; besides, a prediction method based on the multi-modal data fusion model is more accurate and reliable than traditional experience judgment and single index analysis, targeted suggestions can be given according to prediction, personalized guidance is provided for clinicians, formulation of precise strategies is assisted, and the defects of precise prediction and personalized suggestions in the prior art are overcome.

The invention belongs to the technical field of assisted reproduction, and particularly relates to a biological response type memristor for in-vitro embryo monitoring and application of the biological response type memristor. The memristor comprises a substrate, a bottom electrode, a dielectric layer and a top electrode which are sequentially arranged from bottom to top, the dielectric layer is a double-layer functional layer composed of an Nb2O5 thin film and a barium titanate thin film, the barium titanate thin film is located on the upper layer of the bottom electrode, and the Nb2O5 thin film is located on the upper layer of the barium titanate thin film. The memristor realizes response to biological information by monitoring metabolic byproducts and oxidative stress markers in an embryo in-vitro culture solution in real time, realizes operation by inducing redistribution of surface charges of an interface through ion adsorption, and shows a resistance state transformation characteristic. Besides, the system breaks through the limitation of traditional microscope visual evaluation, realizes direct, sensitive and quantitative electric signal reading of the embryo metabolism state and the oxidative stress level, and solves the problem of embryo development potential evaluation caused by the increase of aneuploid rate in old lying-in women and recurrent implantation failure groups.

The present invention relates to determining the carrier status of Annexin A5 M2 haplotype of parents (both male and female) prior to and / or after pregnancy to minimize the risk of pregnancy complications, including, but not limited to, recurrent pregnancy loss (RPL), infertility, miscarriage, in vitro fertilization (IVF) failure, IUI failure, implantation failure, foetal growth restriction (FGR), small for gestational age (SGA) newborn, intra-uterine foetal death (IUFD), gestational hypertension (GH), pre-eclampsia (PE) and / or venous thromboembolism (VTE). Once M2 carrier status is determined, methods of intervention, including administration of low molecular weight heparin (LMWH) and / or other anti-coagulants can be administered either prior to and / or after pregnancy. Methods of detecting the carrier status as well as method of diagnosing and or predicting prognosis based on the M2 carrier status of a patient and / or couple is also contemplated.

The present invention relates to pharmaceutical, dietary and / or food compositions exerting the ability to activate the endogenous production of hydrogen sulfide (H2S) so to feed the redox buffer capacity and to boost the natural ability to compensate both oxidative and reductive stress.The invention further relates to the use of the aforementioned compositions to correct signs of metabolic derangements such as: oxy-redox imbalances including reductive stress, mitochondrial dysfunction and bioenergetics, insulin resistance, endothelial dysfunction and hyperhomocysteinemia. Accordingly, the composition of the present invention can be used as a medicament for the treatment of hypertension, atherosclerosis and cardiovascular disease, erectile dysfunction, viral infections and inflammatory lung injuries, diabetes and PCOS, autoimmune diseases, neurodegeneration, repeated implantation failure and repeated miscarriage and infertility in both men and women.

The invention relates to methods for assessing the risk of miscarriage or embryo implantation failure, and also for monitoring or evaluating the effect of a treatment to reduce the risk of miscarriage or embryo implantation failure using specific biomarkers. The invention also relates to the use of these biomarkers in methods of diagnosing a reproductive disorder in an individual, and also to methods of treating a reproductive disorder. In addition, the biomarkers can further be used in methods of selecting patients for treatment to reduce risk of embryo implantation failure or miscarriage. The invention also relates to kits for use in any of the methods described herein.

The invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition for treating repeated planting failure and a preparation method and application thereof. The traditional Chinese medicine composition disclosed by the invention has the effects of removing blood stasis, tonifying kidney and warming meridians by promoting blood circulation, removing blood stasis and tonifying kidney; furthermore, the uterus-warming and kidney-tonifying treatment traditional Chinese medicine composition is used for warming meridians and uterus, tonifying kidney and nourishing blood to improve the intimal receptivity; further, the post-transplantation implantation miscarriage prevention treatment traditional Chinese medicine composition is used for achieving the effects of strengthening heart, assisting embryo, nourishing blood, preventing miscarriage and supporting early pregnancy; the three groups of traditional Chinese medicine components are subjected to progressive three-stage treatment to realize systematic intervention from eliminating evil to strengthening the body resistance and then to miscarriage prevention, so that the embryo implantation rate and the clinical pregnancy rate of a patient with repeated implantation failure are improved.

This invention belongs to the field of biomedicine and discloses the application of triacetylglycerol (GTA) in the preparation of drugs for the prevention or treatment of infertility. This invention bypasses ACLY defects by supplementing with acetyl donor substances, restoring histone acetylation levels and thereby improving decidualization function. It can be effectively applied to the prevention and treatment of recurrent miscarriage (RSA) and repeated implantation failure, expanding the new applications of GTA in the pharmaceutical field.

The present disclosure relates to a prediction method, a prediction model based on transcriptome analysis for predicting the window of implantation (WOI) of the endometrium, and its use in patients with recurrent implantation failure (RIF), in particular in patients with endometrium-derived recurrent implantation failure. The present disclosure also relates to a device or system for said method and said use.

The present application relates to the technical field of medicine, in particular to the use of an Integrin alpha4 beta1 agonist in the preparation of a product for improving the success rate of hematopoietic stem cell implantation, wherein the Integrin alpha4 beta1 agonist is selected from a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a compound of formula (II) or a pharmaceutically acceptable salt thereof. The Integrin alpha4 beta1 agonist of the present application can improve the hematopoietic stem cell implantation capacity by agonizing the Integrin alpha4 beta1 on the surface of hematopoietic stem cells, promote the implantation of hematopoietic stem cells, thereby improve the success rate of implantation, and provide a new prevention and treatment scheme for patients with a large number of implantation failures.

The invention provides an application of an IGFBP5 (Insulin-like Growth Factor Binding Protein 5) gene in preparation of a medicine for improving endometrial receptivity impairment, and the IGFBP5 gene is used for preparing the medicine for improving the endometrial receptivity impairment. The number of embryo implantation sites can be effectively increased, abnormal proliferation of endometrial epithelial cells is reduced, and the relative expression level of estrogen response genes and progestational hormone response genes is improved. The IGFBP5 gene disclosed by the invention is a key downstream effector molecule of an IL-22-STAT3 signal channel, and the endometrial receptivity can be enhanced by supplementing IGFBP5 protein so as to save embryo implantation failure.

The application belongs to the technical field of genetic engineering, and discloses a uterus-specific Ctcf Construction method and application of an infertility animal model based on uterus-specific knockout. The research results show that CTCF deletion leads to complete loss of fertility in mice, which is manifested as implantation failure and blocked decidualization response. Unlike the embryonic lethality caused by systemic CTCF knockout, the uterus-specific knockout strategy mediated by Pgr-Cre successfully avoids the problem of early death, making it possible to study the function of CTCF in the adult uterus. The model provides an ideal tool for studying the physiological function of CTCF in the female reproductive process. In addition, the model shows a clear and stable infertility phenotype, and can be used as a platform for screening fertility drugs or studying decidualization mechanisms.

The invention belongs to the technical field of assisted reproduction, and particularly relates to a biomarker combination and a method for evaluating the failure risk of embryo implantation and early pregnancy of in-vitro assisted pregnancy patients. According to the method, the risk of embryo implantation failure is evaluated by detecting the oxidative stress marker concentration of an in-vitro pregnancy assisting patient at a specific time point. The multivariate logistic regression analysis proves that the increase of MDA, non-heme, 12-HETE and 15-HETE in serum is an independent risk factor of embryo implantation failure in the period; wherein the elevation of MDA and non-iron heme is a risk factor of occurrence of repeated implantation failure (RIF); the increase of MDA in uterine cavity fluid is an independent risk factor for early pregnancy failure. The invention provides a risk assessment method, which is characterized in that the concentration of the corresponding marker in the specific sample is detected, and the risk of the patient is assessed according to logistic regression analysis. The method has the advantages that high-risk patients can be recognized before transplantation, individualized diagnosis and treatment are achieved, and the accumulative pregnancy rate is increased.

The traditional Chinese medicine composition of charred astragalus root, herba lycopi, fried atractylodes, poria, radix cyathulae, radix cyathulae, semen cuscutae, radix puerariae, fried white peony root, albizia flower, and charred licorice can be used for treating gynecological diseases or symptoms such as intrauterine adhesion, thin endometrium, oligomenorrhea, postmenstrual error, dysmenorrhea, endometritis, pelvic inflammatory disease, decreased ovarian reserve, repeated implantation failure, and infertility, or preparing drugs for treating gynecological diseases or symptoms.

The invention relates to methods for assessing the risk of pregnancy loss or embryo implantation failure, and also for monitoring or evaluating the effect of a treatment to reduce the risk of pregnancy loss or embryo implantation failure using specific biomarkers. The invention also relates to the use of these biomarkers in methods of diagnosing a reproductive disorder in an individual, and also to methods of treating a reproductive disorder. In addition, the biomarkers can further be used in methods of selecting patients for treatment to reduce risk of embryo implantation failure or miscarriage. The invention also relates to kits for use in any of the methods described herein.

The invention discloses an AI auxiliary diagnosis and intervention system for a patient with repeated implantation failure, and relates to the technical field of reproductive medicine auxiliary diagnosis and treatment. After the data is processed by the data standardization processing module, the AI multi-dimensional analysis module carries out multi-dimensional analysis such as implantation window prediction and the like; the etiological diagnosis analysis module generates a report and evaluates and analyzes defects; finally, the personalized scheme generation module determines transplantation time, selects embryos and formulates a uterine cavity pretreatment scheme; according to the method, a multi-source data acquisition and standardization system is constructed, data barriers are eliminated, dynamic changes of endometrial receptivity are accurately captured by means of an AI algorithm, multi-index association strength and implantation probability are quantified, and a system quantification basis is provided; through the etiological diagnosis analysis and personalized scheme generation module, an intervention target is defined, a transplantation scheme conforming to the state of a patient is formulated, individual requirements are met, and the implantation success rate is increased.

The invention provides a candidate medicine for promoting the embryo implantation efficiency of an endometrial microcirculation disturbance type RIF patient, and belongs to the technical field of embryo implantation. In order to solve the problem of how to find a potential intervention drug aiming at a microcirculation disturbance RIF pathological mechanism, a five-step efficient drug screening strategy based on an in-vitro implantation model of an endometrial microcirculation disturbance type repeated embryo implantation failure is adopted, so that the reliability and functional correlation of a screening result are ensured. The candidate drug screened by adopting a five-step method efficient drug screening strategy comprises any one of the following drugs: phenylbutazone, ferulic acid, L-proline, indinavir, sofalone, trelagliptin and gemcitabine. In the candidate medicines, the phenylbutazone, the ferulic acid and the L-proline are three medicines with the best implantation promoting efficiency for patients with the endometrial microcirculation disturbance type RIF.

The invention discloses a method for constructing a rat embryo implantation failure model based on staphylococcus aureus, and belongs to the technical field of animal models. According to the method, ATCC23235 (purchased from ATCC with the strain number of ATCC 23235) staphylococcus aureus bacterial liquid (1 * 10 < 8 > CFU / mL, 200 [mu] L / mouse, and continuous 28 days) is perfused in vagina to induce SD rat embryo implantation number reduction and endometrial receptivity related factor expression reduction, and the pathological state of embryo implantation failure is successfully simulated. The model disclosed by the invention avoids limitation of hormone or gene intervention, is closer to a clinical infection mechanism, and is suitable for etiological research and therapeutic drug screening of embryo implantation failure.

The invention relates to methods for assessing the risk of pregnancy loss or embryo implantation failure, and also for monitoring or evaluating the effect of a treatment to reduce the risk of pregnancy loss or embryo implantation failure using specific biomarkers. The invention also relates to the use of these biomarkers in methods of diagnosing a reproductive disorder in an individual, and also to methods of treating a reproductive disorder. In addition, the biomarkers can further be used in methods of selecting patients for treatment to reduce risk of embryo implantation failure or miscarriage. The invention also relates to kits for use in any of the methods described herein.