The PlA2 variant of the platelet glycoprotein IIIa as a genetic risk factor for IVF implantation failure: accumulating evidence.
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ABSTRACT:
SUBMITTER: Vlachadis N
PROVIDER: S-EPMC4930784 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Publications
The PlA2 variant of the platelet glycoprotein IIIa as a genetic risk factor for IVF implantation failure: accumulating evidence.
Vlachadis Nikolaos N Vrachnis Nikolaos N Economou Emmanuel E
Journal of assisted reproduction and genetics 20160430 7
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2015-12-31 | E-MTAB-2591 | biostudies-arrayexpress
Project description:Transcriptomic studies have identified gene expression profiles characteristic of the window of implantation and preliminary studies have indicated that these may be disrupted in some women with recurrent implantation failure (RIF). The aims of this study were to elucidate how the endometrial gene expression profile differs between women with RIF and controls, and to investigate whether a predictor set of genes could be identified able to distinguish between these women.
2015-06-01 | GSE58144 | GEO
Project description:The primary limiting factor for effective IVF treatment is successful embryo implantation. Recurrent implantation failure (RIF) is a condition whereby couples fail to achieve pregnancy despite consecutive embryo transfers. Here we describe the collection of gene expression profiles from mid-luteal phase endometrial biopsies (n = 115) from women experiencing RIF and healthy controls. Using a signature discovery set (n = 81) we identify a signature containing 303 genes predictive of RIF. Independent validation in 34 samples shows that the gene signature predicts RIF with 100% positive predictive value (PPV). The strength of the RIF associated expression signature also stratifies RIF patients into distinct groups with different subsequent implantation success rates. Exploration of the expression changes suggests that RIF is primarily associated with reduced cellular proliferation. The gene signature will be of value in counselling and guiding further treatment of women who fail to conceive upon IVF and suggests new avenues for developing intervention.
| S-EPMC4726345 | biostudies-literature
Project description:The present study was designed to examine the interaction of the purified platelet glycoprotein IIb-IIIa complex (GP IIb-IIIa or integrin alpha IIb beta 3) and the individual subunits of the complex with immobilized fibrinogen. Although 125I-GP IIb-IIIa binding to fibrinogen immobilized on Sepharose was specific, this interaction exhibited properties distinct from those of reversible fibrinogen binding to platelets: 125I-GP IIb-IIIa binding appeared irreversible, but non-covalent, Ca(2+)-independent, and was inhibited only weakly, or not at all, by the anti-(GP IIb-IIIa) monoclonal antibodies 10E5 and 7E3 and synthetic peptides from known platelet-binding domains of fibrinogen. Reversibly dissociated GP IIb or GP IIIa subunits inhibited 125I-GP IIb-IIIa binding to immobilized fibrinogen and bound directly to the fibrinogen. However, these subunits did not bind to peptides derived from known platelet-binding domains within the fibrinogen alpha- and gamma-chains, although the GP IIb-IIIa complex did. These results show that the complexed form of full-length GP IIb and GP IIIa is required for binding to these synthetic peptides, but not necessarily for binding to immobilized fibrinogen. Thus GP IIb-IIIa can bind to immobilized fibrinogen by a distinct mechanism that appears to involve novel binding sites on each subunit of the GP IIb-IIIa complex and on fibrinogen.
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Project description:BackgroundWe previously described a mouse model in which platelet immunization between selected strains leads to production of alloantibodies and severe autoimmune thrombocytopenia and mimics the human condition posttransfusion purpura (PTP). This report describes studies defining epitopes recognized by these alloantibodies.Study designHybridomas were produced from spleen cells of immunized mice. Glycoprotein (GP) targets of resulting monoclonal antibodies were characterized by immunoprecipitation using platelets from the immunizing strains. Antigens defined by single amino acid (AA) polymorphisms recognized by monoclonal antibodies were identified by mutagenizing target glycoproteins expressed in Chinese hamster ovary cells and observing the effects on antibody binding.ResultsThree monoclonal antibodies (417.1, 417.3, 425.1) were produced that recognized GPIIb on immunizing platelets. Monoclonal antibodies 417.1 and 417.3 both required G111 and 425.1 required V37, located on the beta propeller domain of GPIIb, for binding to platelets from the immunizing strains C57 and PWK, respectively. Injection of 417.3 and 425.1 into mice caused platelet destruction only in mice with GPIIb containing the targeted AAs.ConclusionsFindings made provide evidence that alloantibodies produced by mice experiencing thrombocytopenia in a mouse model of PTP are specific for single AA polymorphisms that differ in GPIIb/IIIa integrin of the immunizing and immunized strains and therefore closely resemble the potent alloantibodies found in patients with PTP. The observations show that naturally occurring single AA differences in GPIIb/IIIa integrin of various mouse strains are highly immunogenic in the mouse strains studied and readily induce antibodies comparable to human platelet antigen-specific antibodies found in transfused and pregnant humans.
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Project description:BackgroundThe success rate of IVF treatment is low. A recent systematic review and meta-analysis found that the outcome of IVF treatment could be improved in patients who have experienced recurrent implantation failure if an outpatient hysteroscopy (OH) is performed before starting the new treatment cycle. However, the trials were of variable quality, leading to a call for a large and high-quality randomised trial. This protocol describes a multi-centre randomised controlled trial to test the hypothesis that performing an OH prior to starting an IVF cycle improves the live birth rate of the subsequent IVF cycle in women who have experienced two to four failed IVF cycles.Methods and designEligible and consenting women will be randomised to either OH or no OH using an internet based trial management programme that ensures allocation concealment and employs minimisation for important stratification variables including age, body mass index, basal follicle stimulating hormone level and number of previous failed IVF cycles. The primary outcome is live birth rate per IVF cycle started. Other outcomes include implantation, clinical pregnancy and miscarriage rates.The sample size for this study has been estimated as 758 participants with 379 participants in each arm. Interim analysis will be conducted by an independent Data Monitoring Committee (DMC), and final analysis will be by intention to treat. A favourable ethical opinion has been obtained (REC reference: 09/H0804/32).Trial registration[corrected] The trial has been assigned the following ISRCTN number: ISRCTN35859078.
| S-EPMC2795733 | biostudies-literature
Project description:The possible association of common polymorphic variants related to thrombophilia (the rs6025(A) allele encoding the Leiden mutation, rs1799963(A), i.e., the G20210A mutation of the prothrombin F2 gene, the rs1801133(T) variant of the methylenetetrahydrofolate reductase (MTHFR) gene that encodes an enzyme involved in folate metabolism, and rs5918(C), i.e., the 'A2' allele of the platelet-specific alloantigen system that increases platelet aggregation induced by agonists), with the risk of Legg-Calvé-Perthes disease (LCPD) and the degree of hip involvement (Catterall stages I to IV) was analyzed in a cohort study, including 41 children of ages 2 to 10.9 (mean 5.4, SD 2.2), on the basis of clinical and radiological criteria of LCPD. In 10 of the cases, hip involvement was bilateral; thus, a total of 51 hips were followed-up for a mean of 75.5 months. The distribution of genotypes among patients and 118 controls showed no significant differences, with a slightly increased risk for LCPD in rs6025(A) carriers (OR: 2.9, CI: 0.2-47.8). Regarding the severity of LCPD based on Catterall classification, the rs1801133(T) variant of the MTHFR gene and the rs5918(C) variant of the platelet glycoprotein IIb/IIIa were associated with more severe forms of Perthes disease (Catterall III-IV) (p < 0.05). The four children homozygous for mutated MTHFR had a severe form of the disease (Stage IV of Catterall) and a higher risk of non-favorable outcome (Stulberg IV-V).
| S-EPMC8307051 | biostudies-literature
Project description:BackgroundPatients with recurrent implantation failure (RIF) may have more uterine contractions. Several observational studies suggested that atosiban administration around embryo transfer resulted in higher pregnancy rates in RIF patients. This study aimed to evaluate the effect of atosiban given before fresh embryo transfer on pregnancy outcomes of women with RIF.MethodsA prospective, randomized, double-blind controlled clinical trial was performed in IVF center of Shanghai First Maternity and Infant Hospital. According to a computer-generated randomization list, 194 infertile women with RIF received fresh embryo transfer between July 2017 and December 2019 were randomly allocated into the atosiban (n = 97) and the placebo (n = 97) groups. Women in the treatment group received atosiban intravenously about 30 min before embryo transfer with a bolus dose of 6.75 mg over one minute. Those in the placebo group received only normal saline infusion for the same duration.ResultsThere was no significant difference in the live birth rate between the atosiban and placebo groups (42.3% vs 35.1%, P = 0.302, RR = 1.206 (0.844-1.723)). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and implantation rates. Similar results were found when stratified by the number of embryos previously transferred, number of previous failed embryo transfers, frequency of endometrial peristalsis on embryo transfer day (≥ 3 waves/min) or serum estradiol (E2) on the day of hCG above the median level. And, there was no correlation between the serum E2 level on the day of hCG and the frequency of endometrial peristalsis on embryo transfer day. The frequency of endometrial peristalsis on embryo transfer day, total FSH/HMG dosage and duration were the significant factors which independently predicted the likelihood of a live birth.ConclusionsThese results suggested that atosiban treatment before fresh embryo transfer might not improve the live birth rate in RIF patients.Trial registrationThe study had been approved by the Institutional Review Board of the hospital (2017 ethics No.43) and was registered under Clinicaltrials.gov with an identifier NCT02893722.
| S-EPMC9389813 | biostudies-literature
Project description:Endometrial receptivity on genomic level is one of the major cause of implantation failure in IVF patients with unexlained infertility and is a main obstacle in success of IVF. Gene expression profiles of implantation failure cases of unexplained infertility were compared with proven healthy oocyte donors as controls, both undergoing ovarian stimulation. The results provide additional information about gene expression profile related to endometrial receptivity in implantation failure cases especially under the influence of ovarian stimulation during IVF cycle.
2018-08-07 | GSE71835 | GEO
Project description:With the rapid development of assisted reproductive techniques (ART), the number and quality of embryos have been optimized, but the embryo implantation rate has not been significantly improved yet. Recurrent implantation failure (RIF), a condition that is typically diagnosed in patients who fail to achieve clinical pregnancy after having undergone at least 3 times of embryo transfers (including a total of ≥4 good-quality embryos), is a challenging problem in ART treatment. Previous studies about RIF are limited to clinical trials and the detection of limited biomarkers within peripheral blood, but few about gene expression within local endometrial tissue and RIF, the key factors involved in RIF remain unclear. Our study was designed with an aim to compare the gene expression profile of RIF women with that of healthy proven fertile controls to explore the influence factors of endometrial receptivity and the mechanisms of RIF.
2018-09-01 | GSE103465 | GEO