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Biomarkers and agents for recurrent implant failure

A technology of biomarkers and medicaments, applied in the fields of biochemical equipment and methods, microbial determination/inspection, drug combination, etc., can solve the problems of lack of curative effect and treatment methods, etc.

Pending Publication Date: 2022-03-01
中国人民解放军总医院第六医学中心
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these therapies to improve embryo quality and endometrial receptivity can only successfully treat some patients, but for those RIF patients whose etiology is unknown, RIF patients whose etiology cannot be clearly determined also account for a certain proportion. This is the first case of implantation disorder that failed to conceive after in vitro fertilization-based treatment. Due to the unknown etiology, there is still a lack of curative effect and treatment methods for RIF patients with unknown etiology.

Method used

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  • Biomarkers and agents for recurrent implant failure
  • Biomarkers and agents for recurrent implant failure
  • Biomarkers and agents for recurrent implant failure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] sample

[0062] The overall condition of the patient was good, with no immune and chromosomal abnormalities, and no history of recurrent miscarriage. We analyzed a total of 84 patients with low progesterone levels and RIF from the Sixth Medical Center of the Chinese People's Liberation Army General Hospital, and all patients signed the informed consent. The characteristics of the patients are as follows: (1) repeated implantation failure (RIF, no clinical pregnancy was observed in three consecutive high-quality embryo transfers); (2) aged between 35 and 45 years old. This study was approved by the ethics committee of the medical center.

[0063] According to progesterone support therapy, patients were divided into two groups: experimental group and control group. The experimental group received low-dose human chorionic gonadotropin (HCG) on the basis of traditional progesterone therapy, and the control group maintained traditional progesterone therapy.

[0064] All s...

Embodiment 2

[0076] For the samples in Example 1, different luteal phase support schemes were adopted, and the patients were divided into a control group and an experimental group.

[0077] Experimental group: On the day of endometrial transition, the patients began to take femotone (yellow tablet, containing 2 mg estradiol, 10 mg dydrogesterone), progesterone soft capsules and prednisone (adrenocortical hormone). The dosage is as follows: femotone 1 tablet / time, 3 times / day, progesterone soft capsule 0.2g / time, 2 times / day, aspirin 25mg / time, 3 times / day, prednisone 5mg / time / day; ovulation Three types of hormones (E 2 , LH, P) The dose was determined according to the estrogen and progesterone levels on D2. On the next day after transplantation, the patient received 500 IU intramuscular injection of HCG every day, and other drugs and doses remained the same as before. On the seventh day after implantation, evaluate HCG, E 2 , LH,, P level, when the HCG level is higher than 50mIU / mL, the...

Embodiment 3

[0094] For the samples in Example 1, all samples were sequenced while being treated with the luteal phase support regimen, and peripheral blood was extracted from the patient to obtain genomic DNA, and all blood samples for sequencing were collected before the patient became pregnant.

[0095] DNA extraction, sequencing library construction

[0096] DNeasy tissue and blood kit was used for peripheral blood DNA extraction. In order to confirm the DNA degradation and contamination status, we chose Qubit DNA detection kit and used Qubit 3.0 fluorescent agent for 1% agarose gel electrophoresis test. The DNA extracted from the sample The quality and quantity status are shown in Table A. Samples with DNA content greater than 0.6ug were selected for library construction. Afterwards, the Agilent Human All-Exon V6 Kit was used to enrich DNA in the human exon region and generate a sequencing library according to the instructions. After the library is built, use Qubit 2.0 for prelimin...

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Abstract

The invention provides a biomarker and a medicament for recurrent implantation failure. The biomarker comprises one or more of pathway related genes with the G0 annotation being GO: 0030286, GO: 0003777, GO: 0007018, GO: 0016887, GO: 0005874, GO: 0005858, GO: 0060285 and GO: 0005871, or / and the KEGG annotation being hsa05016, and one or more of pathway related genes with the G0 annotation being GO: 0030286, GO: 0003777, GO: 0007018, GO: 0016887, GO: 0005874, GO: 0005858, GO: 0060285 and GO: The biomarkers are used for characterizing, diagnosing or classifying'subclinical hypopituitary hypofunction 'patients with repeated implantation failure and predicting the therapeutic reactivity of the patients with repeated implantation failure to luteal support therapy; the invention also provides a medicament for repeated implantation failure, a lutein therapy medicament and a luteinizing activity related medicament, the lutein therapy medicament is a medicament for regulating estrogen and / or progestational hormone, and the luteinizing activity related medicament is a medicament for regulating the estrogen and / or progestational hormone after embryo implantation by applying human chorionic gonadotropin. The repeated implantation failure object has the characteristics that (1) clinical pregnancy is not observed in continuous three or more times of high-quality embryo transplantation, (2) the pathogenesis of RIF is indefinite, and (3) the blood luteinizing hormone level is less than or equal to 5IU / L on the second day (D2 day) after ovulation.

Description

technical field [0001] The present invention relates to the field of biotechnology, and more particularly, to biomarkers and agents for repeated implantation failures. Background technique [0002] Repeated implantation failure (RIF) is a special disease treated by assisted reproductive technology. Although there are many reports about RIF, there is still no unified diagnostic standard established in the academic circle. Orvieto et al., Zeyneloglu and Onalan gave the concept definition of RIF: three consecutive high-quality embryo implantation failed to obtain clinical pregnancy. The incidence of RIF in the IVF-embryo implantation process is 10-15%. The cause of RIF is 1 / 3 due to embryo quality and 2 / 3 due to genetic factors. Koot et al. considered that the gene expression profile contained 303 genes that could accurately predict and distinguish RIF patients. Haouzi D et al. found 5 genes that may evaluate endometrial receptivity. Wagnini LD et al found that the AA geno...

Claims

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Application Information

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IPC IPC(8): C12Q1/6883A61K45/06A61K31/565A61K31/57A61K31/616A61K31/573A61K38/24A61P15/08
CPCC12Q1/6883A61K45/06A61K31/565A61K31/57A61K31/616A61K31/573A61K38/24A61K9/0019A61P15/08C12Q2600/156C12Q2600/112C12Q2600/106A61K2300/00
Inventor 商微郭翊明陆思嘉邹央云孙悦
Owner 中国人民解放军总医院第六医学中心
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