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PubMed2026

ENTPD3 as a novel regulator of endometrial receptivity: suppressing EMT via the ATP-P2Y2 axis in patients with recurrent implantation failure.

BACKGROUND: Recurrent implantation failure (RIF) remains a major challenge in assisted reproductive technology and is primarily attributed to impaired endometrial receptivity. Despite its clinical significance, the precise mechanisms underlying RIF remain inadequately understood. METHODS: Single-cell RNA sequencing (scRNA-seq) was performed on endometrial samples from patients with RIF and healthy controls during the secretory phase using the 10X Genomics Chromium platform. The expression and localization of ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3) in the window of implantation (WOI) in the endometrium were examined using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemistry (IHC). A mouse model with ENTPD3 overexpression was utilized to assess embryo implantation in vivo, and an in vitro blastocyst adhesion assay was performed to evaluate endometrial receptivity. Additionally, Ishikawa cells were transduced with an ENTPD3 recombinant adenovirus to explore the underlying molecular mechanisms. RESULTS: ENTPD3 expression was significantly upregulated in the endometria of patients with RIF during the WOI, and its apical surface localization in endometrial epithelial cells was confirmed by single-cell data and IHC. Functional studies demonstrated that ENTPD3 overexpression impaired endometrial receptivity by suppressing epithelial-mesenchymal transition (EMT). In vivo, ENTPD3 overexpression markedly reduced endometrial receptivity and inhibited embryo implantation in mice. Consistently, in vitro assays revealed that ENTPD3 overexpression diminished blastocyst adhesion to endometrial epithelial cells. Mechanistically, ENTPD3 hydrolyzes ATP, thereby suppressing EMT via the P2Y2 signaling pathway and ultimately disrupting endometrial receptivity. CONCLUSIONS: Dysregulated ENTPD3 expression contributes to RIF pathogenesis by impairing endometrial receptivity through ATP hydrolysis-mediated suppression of EMT via P2Y2 signaling. These findings highlight ENTPD3 as a potential therapeutic target for improving implantation success in affected patients.

Female↗

PubMed2024

Comprehensive analysis of circRNA-miRNA-mRNA network related to angiogenesis in recurrent implantation failure.

BACKGROUND: Abnormal endometrial blood flow causes a decrease in endometrial receptivity and is considered a relatively independent risk factor for recurrent implantation failure (RIF). This study aimed to explore the potentially functional circRNA-miRNA-mRNA network in RIF, and further explore its mechanism. METHODS: Datasets were downloaded from the GEO database to identify differentially expressed circRNAs, miRNAs and mRNAs. The circRNA-miRNA-mRNA and PPI networks were constructed using Cytoscape 3.6.0 and the STRING database, the hub genes were identified with the cytoHubba plug-in, and a circRNA-miRNA-hub mRNA regulatory sub-network was constructed. Then, GO and KEGG pathway enrichment analyses of the hub genes were performed to comprehensively analyze the mechanism of hub mRNAs in RIF. Due to the results of circRNAs-miRNAs-hub mRNAs regulatory network, we verified the expression of circRNA_0001721, circRNA_0000714, miR-17-5p, miR-29b-3p, HIF1A and VEGFA in the RIF mouse model by qRT‒PCR and western blotting. RESULTS: We initially identified 175 DEmRNAs, 48 DEmiRNAs and 56 DEcircRNAs in RIF associated with angiogenesis and constructed a circRNA-miRNA‒mRNA network and PPI network. We further identified six hub genes in the acquired network. Based on these genes, functional enrichment analysis revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. In addition, the interaction networks of circRNA_0001721/miR-17-5p/HIF1A and the circRNA_0000714/miR-29b-3p/VEGFA axis were predicted. In the RIF mouse model, circRNA_0001721, circRNA_0000714, HIF1A and VEGFA were down-regulated, whereas miR-17-5p and miR-29b-3p were up-regulated according to qRT‒PCR and western blotting. CONCLUSION: This study revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. The circRNA_0001721/miR-17-5p/HIF1A and circRNA_0000714/miR-29b-3p/VEGFA axes might play a role in the pathogenesis of endometrial angiogenesis in RIF.

MicroRNAs↗

PubMed2024

Transcriptome-wide N6-methyladenosine modification profiling of long non-coding RNAs in patients with recurrent implantation failure.

N6-methyladenosine (m6A) is involved in most biological processes and actively participates in the regulation of reproduction. According to recent research, long non-coding RNAs (lncRNAs) and their m6A modifications are involved in reproductive diseases. In the present study, using m6A-modified RNA immunoprecipitation sequencing (m6A-seq), we established the m6A methylation transcription profiles in patients with recurrent implantation failure (RIF) for the first time. There were 1443 significantly upregulated m6A peaks and 425 significantly downregulated m6A peaks in RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that genes associated with differentially methylated lncRNAs are involved in the p53 signalling pathway and amino acid metabolism. The competing endogenous RNA network revealed a regulatory relationship between lncRNAs, microRNAs and messenger RNAs. We verified the m6A methylation abundances of lncRNAs by using m6A-RNA immunoprecipitation (MeRIP)-real-time polymerase chain reaction. This study lays a foundation for further exploration of the potential role of m6A modification in the pathogenesis of RIF.

Humans↗

PubMed2026

IVF patient subgroups benefit from preimplantation genetic testing for aneuploidy: a prospective multicentre cohort study.

RESEARCH QUESTION: Can preimplantation genetic testing for aneuploidy (PGT-A) improve the ongoing pregnancy rate per transfer and reduce miscarriage rate in patients with advanced maternal age (AMA), recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or both, without affecting cumulative pregnancy rate? DESIGN: Prospective cohort study of 260 patients undergoing PGT-A aged 36 years or over (AMA group), with a history of three or more blastocyst transfers without birth (RIF group), two or more early pregnancy losses (RPL group), or all. Trophectoderm biopsy was conducted day 5 or 6, and comprehensive chromosome screening was used for PGT-A before single frozen embryo transfer (PGT-A-FET). A total of 3060 patients undergoing single conventional frozen embryo transfer (FET) served as a historical reference group. RESULTS: Patients had increased odds of positive serum beta-HCG after PGT-A-FET compared with FET in the AMA (OR 1.53, 95% CI 1.06 to 2.21) and RIF (OR 2.11, 95% CI 1.41 to 3.14) groups. The PGT-A-FET group significantly improved the odds of ongoing pregnancy in the AMA (OR 2.20, 95% CI 1.52 to 3.18), RIF (OR 3.96, 95% CI 2.60 to 6.04) and RPL (OR 2.81, 95% CI 1.52 to 5.21) groups. The odds of pregnancy loss were significantly reduced with PGT-A-FET in the AMA (OR 0.36, 95% CI 0.21 to 0.64), RIF (OR 0.10, 95% CI 0.04 to 0.26) and RPL (OR 0.14, 95% CI 0.04 to 0.53) groups. Cumulative pregnancy rate did not differ between PGT-A and conventional cycles (RR 0.94, 95% CI 0.80 to 1.10). CONCLUSIONS: PGT-A improved the odds of ongoing pregnancy and reduced the odds of pregnancy loss in all groups. The cumulative pregnancy rate did not differ between PGT-A and conventional cycles. Findings should be interpreted in the context of the observational design.

Adult↗

PubMed2025

Genotyping of natural killer cell immunoglobulin-like receptors in human early reproductive losses.

Genotyping of killer cell immunoglobulin-like receptors (KIR) of NK-cells was performed in 634 women with early pregnancy losses (EPL), including 158 women with recurrent implantation failure (RIF) after at least three IVF cycles, and 110 women with at least two intrauterine pregnancy losses characterized by clinically confirmed retention of a non-viable fetus in the uterus without spontaneous miscarriage, defined as recurrent pregnancy loss (RPL). The control group consisted of 431 women with at least two healthy children. In the RIF, a significant shift in the frequency of KIR-genotypes was observed compared with both the control and the RPL groups. A significantly higher frequency of the KIR-AA genotype was observed in the RIF group compared to the control group (χ² = 26.78; p < 0.0001; OR = 2.7) and the RPL group (χ² = 15.83; p < 0.0001; OR = 2.86). Analysis of the frequency of full-length/deletion alleles of KIR2DS4 among AA genotype carriers showed an increased frequency of the 2DS4-del in the RIF compared with the RPL and control groups. A significantly higher frequency of the cenAA was also observed in RIF compared with the control (χ² = 20.10; p < 0.0001) and the RPL(χ² = 12.05; p < 0.005). The significantly increased frequency of the KIR-AA genotype with predominance of deletion KIR2DS4 alleles, along with the elevated frequency of the cenAA in RIF, may indicate insufficient NK-cell activation at the stage of embryo implantation. These findings suggest different etiological mechanisms for RIF and RPL.

Humans↗

PubMed1977

Renal allograft artery stenosis.

Thirteen renal artery stenoses occurred in 127 renal allograft transplantations performed at the University of Cincinnati Medical Center over a four year period. The most common symptoms were hypertension and decreasing renal function occurring from three days to three years post transplantation. Eight lesions occurred in patients with a single artery and five when double arteries had been joined together prior to anastomosis rather than implanted separately. The most common causes of renal artery stenosis was intimal hyperplasia of the donor vessel distal to the anastomosis (8 patients), atheromatous plaques (2), technical failure (2), and external compression (1). Surgical correction was facilitated by a midline incision. Resection of the stenotic segment and reanastomosis was the preferred procedure. Surgical failure and recurrence of hypertension were associated with involvement of small arteries or distal arteriolar level. When kidneys with multiple arteries are available, Carrel patches should be used when possible; if not, they should be implanted separately rather than joined together prior to anastomosis, thus decreasing the possibility of creating turbulent blood flow.

Blood Vessel Prosthesis↗

PubMed1979

[Functional reinnervation of the larynx. Experimental study (author's transl)].

This study of reinnervation of the larynx results from the research for a functional method of treatment for laryngeal paralysis of peripheral origin. The physiological reality of reinnervation of a denervated muscle by a nerve other than that anatomically destined for it, or "neurotisation", is now an established fact. This experimental study in 12 dogs consisted of neurotisation of a posterior crico-thyroid muscle, denervated by section of the recurrent laryngeal nerve, by implantation of a graft of sub-hyoid muscle with a nerve pedicle. Only one positive result at six months was seen. 8 failures could be explained by the absence of ventilatory difficulty necessary for the sub-hyoid muscles to be brought into action, and the other 3 failures two months after the operation by muscular fibrosis of the graft before neurotisation could occur. Physiology and the experience of other teams justify the continuation of this study.

Animals↗

PubMed1978

[Recurrence of intramembraneous glomerulonephritis in 2 consecutive kidney transplantations].

A case of dense intramembranous deposit disease, partial lipodystrophy, hypocomplementemia, and nephritic factor-like activity in the serum is presented. Recurrence of underlying renal disease was noted in two consecutive renal allografts. The first transplant was lost 7 months after implantation, chronic renal rejection being an additional cause of graft failure. A favourable clinical course, however, was observed after the second renal transplantation. 22 months after surgery, the patient was fully rehabilitated and transplant function only slightly reduced despite electron microscopic evidence of typical dense intramembranous deposit lesions. Low C3-serum complement and normal C4-serum complement levels were constant findings throughout observation time. The case supports the assumption that patients with dense intramembranous deposit disease should not be excluded from renal transplantation As shown in the literature, maintenance of satisfactory graft function is usually obtained for a long period of time despite recurrence of original disease.

Adult↗

PubMed1977

Complete heart block following therapeutic irradiation of the left side of the chest.

Two female patients had received therapeutic irradiation of the left side of the chest for adenocarcinoma of the left breast and 18 and 23 years later, respectively, developed atrioventricular block. Both patients had early and late cutaneous reactions, as well as fibrosis of the left lung, lymphedema of the left arm, and pathologic rib fractures but had no signs of recurrence of the carcinoma. One patient developed signs of congestive heart failure while the electrocardiogram revealed second and third degree atrioventricular block; subsequent pacemaker implantation relieved the congestive heart failure. In the second patient, fatigue was the only symptom leading to the diagnosis of transient second and third degree atrioventricular block; this symptom subsided after pacemaker implantation. Based on reports of radiation-induced cardiac damage, it is assumed that the heart block in these two patients might have been due to postirradiation fibrosis of the atrioventricular node, either direct or mediated by fibro-occlusive changes in the coronary vessels.

Adenocarcinoma↗

PubMed1978

Long-term follow-up after cardiac pacing in bradyarrhythmias.

Fifty-nine patients aged 39-80 years underwent implantation of a cardiac pacemaker and were followed for up to 9 years (average duration of pacing 39 months). Atrioventricular conduction disturbances (complete atrioventricular block, 2 : 1 atrioventricular block, bifascicular block, and atrial fibrillation with slow ventricular rate) were present in 49 patients and sick sinus syndrome (sinus arrest or sino-atrial block, and bradycardia-tachycardia syndrome) in 10. Pacing was required because of Adams-Stokes attacks in 41 patients, 2 of whom also had congestive heart failure. It was required in 6 because of frequent dizziness, in 10 because of congestive heart failure, and in 2 because of low cardiac output. The symptomatic improvement after cardiac pacing was well recognized in most of our patients, and 32 (54 percent) of the 59 patients pursued normal physical and daily activity. Although the efficacy of pacemaker therapy was of limited value in some patients with congestive heart failure or underlying or coexisting diseases, the beneficial effects following pacemaker implantation were: (1) abolishment of transient neurologic symptoms such as Adams-Stokes attack, (2) relief from a constant fear of a recurrence of an Adams-Stokes attack or sudden cardiac death, and (3) improvement in restricted physical activity due to low cardiac output. Thus, we conclude that pacemaker implantation in most patients with bradyarrhythmias is beneficial not only for the treatment of the acute problem but also because it prolongs life and greatly enhances its quality. However, in spite of the beneficial effects after pacemaker implantation, we still observe a number of complications connected with the use of a permanent pacemaker. Therefore, our policy is to implant a permanent pacemaker following the execution of sufficient studies of the bradyarrhythmia and the etiology of symptoms, and then under taking long-term follow-up of the patients.

Adult↗

PubMedDate not supplied

Pain suppression by peripheral nerve stimulation. Chronic effects of implanted devices.

This is a study of the long range effects of pain suppression obtained by electrical stimulation of peripheral nerves. These cases were followed during 12--46 months and evaluated personally and by questionnaires. Selection for surgery was done exclusively on the basis of the results of a preoperative peripheral nerve stimulation test. Of 37 cases observations, 18 were considered significantly relieved; that is, more than 50% of the intensity and/or duration of pain was consistently admitted. The results obtained in the acute preoperative trial could be reproduced indefinitely in some cases for as long as 46 months. Correlation of the results with the disease producing the pain revealed as benefitting for painful syndromes associated with peripheral nerve disorders, amputation, soft tissue injuries (nerves?), and some recurrent lumbar disc surgeries. Sciatic, ulnar and occipital nerve implantations were particularly rewarding. The best and worse results were analyzed. The complications appear to be largely preventable and of no serious consequences. Our analysis suggests that most failures take place within 2 years from implantation. Experience seems to be accumulating showing that a number of patients may receive sustained relief beyond this period.

Adult↗

PubMed1977

The fishmouth phenomenon. II. Wedge scleral buckling.

Radial retinal folding, associated with equatorial scleral buckling, contributes to the difficulty in repairing a retinal detachment due to a fishmouth break. To minimize this effect, a wedge-shaped implant was designed to approximate more closely the same relative reduction in the circumference of the circles of the globe along the meridian of the break. The surgical details of use of the implant are described. In a consecutive series of 56 eyes in which the fishmouth phenomenon was expected, 49 (88%) were successfully managed at first encounter using a wedge buckling device. Revised scleral bucklings and open-sky vitrectomies, in early failures and delayed recurrences, salvaged additional eyes for final success in 52 (93%) of the eyes.

Adolescent↗

PubMed1978

[Complete bundle-branch block and myocardial infarct. Natural history. Comparative study].

Myocardial infarction (MI), (and especially anteriorly situated necrosis) was complicated by complete branch block (CBB) in 9.7% of cases (45 patients out of 462). A comparison of the short- and long-term outcome in two groups of patients (group A: 45 cases of MI complicated by CBB; group B: 45 cases of MI with no atrio-ventricular or intra-ventricular conduction defects) showed that there was a much bigger immediate mortality in group A, which was not changed by temporary cardiac pacemaking, and depended on the extent of myocardial destruction. A study of the long-term outcome showed that there were more deaths in group A (recurrence of MI, intractable cardiac failure). However, the incidence of sudden death was equal in the two groups (group A 15%, group B 13%), and there was no obvious explanation in the absence of electrocardiographic tracings. Therefore this study lends no support to the argument which favours prophylactic implantation of a cardiac pacemaker during the course of MI complicated by CBB.

Adult↗

PubMed1978

[Multiple recurrence of Cushing's syndrome after bilateral adrenalectomy and pituitary gland surgery. Cure with o,p'-DDD].

A pituitary-dependent Cushing's syndrome in a young woman had an unusually protracted course and was extremely resistant to therapy. After unsuccessful pituitary irradiation, bilateral total adrenalectomy was performed. A piece of an excised adrenal gland was reimplanted into a buttock. Nevertheless, the patient went into adrenocortical failure and had to be given replacement therapy. After three years the Cushing's syndrome reappeared, this time combined with general hyperpigmentation. The implanted adrenal tissue was no longer to be found. Neither stereotactic pituitary coagulation nor implantation of 90-Yttrium into the pituitary resulted in remission of Cushing's syndrome. All attempts to localize the--very probably ectopic--cortisol-producing adrenocortical tissue failed. However, complete remission was finally achieved by treatment with o,p'-DDD.

Adolescent↗

PubMedDate not supplied

The lumbar shield: a preliminary report.

Postoperative perineural adhesions between the lumbar nerve root and the partially removed intervertebral disc are thought to be a cause of failure of the standard operative procedure for the removal of a ruptured lumbar intervertebral disc. Attempts have been made to reduce postoperative perineural adhesions by the use of epidural muscle, fat, gelatin sponge, silicone, and steroids. The present communication introduces a new implantable silicone device, a lumbar shield, designed to: (a) provide a radiopaque marker on the dorsal perimeter of the excavated lumbar disc so that the presence or absence of a recurrent disc herniation can easily be determined on plain postoperative x-ray films, (b) provide ready access to the operative site in the event of a recurrent disc herniation, (c) prevent postoperative perineural adhesions between the lumbar dura and the nerve root and the partially removed intervertebral disc, and (d) prevent postoperative adhesions between the lumbar dura and the nerve root and the paraspinal muscles. Satisfactory results of lumbar disc surgery over the past 44 years have occurred in about 90% of routine patients. The value of the lumbar shield in 82 patients (59 routine and 23 workmen's compensation/medicolegal patients) followed for 6 months is described. A satisfactory result, i.e., relief of pain or the presence of occasional postoperative pain, occurred in 85% of routine patients at 1 month, 97% at 3 months, and 95% at 6 months.

Animals↗

PubMed1978

Surgical treatment of urinary fistulae.

A survey is presented, based upon a personal material of 225 cases of urinary fistulae. 173 of them were postoperative or obstetric fistulae, whereas 52 had appeared after a radiological or combined radiological and surgical treatment for cancer of the uterus. --The author's method for preparing the fistula region from a transverse incision under the external urethral orifice is described as well as his grafting techniques. Vessels are brought to the fistula region by using flaps from one or both pubococcygeus muscles, the rectus abdominis muscle or the gracilis muscle. --For vesico-vaginal fistulae situated high up in the fundus a graft from the omentum majus or an appendix epiploica is sometimes used. They can usually be grasped from below after the peritoneum has been opened. --In cases where the ureters were also damaged by irradiation a special technique was used. After the damaged part of the ureter had been resected the ureters were implanted into an ileum segment which was anastomosed to the bladder fistula. --In one of the 173 non-irradiated cases, a Bricker-bladder had finally to be made because of the failure to achieve a functioning urethra. The others were all cured after one or in a few cases two operations. --Among the 52 cases, which had been irradiated, 46 coud to be made, one got a fast growing local recurrence of the carcinoma and one had too bad general condition to allow a diversion operation. Two patients have rest fistulae but may be possible to cure conservatively.

Diagnosis, Differential↗

PubMed1978

Experience with 220 cases of mandibular reconstruction.

Extensive resections of the mandible are usually carried out for malignat tumours or non-malignant tumours with a tendency to reccur, such as ameloblastomas. These hemi-resections include the ascending and horizontal ramus of the mandible. Such mutilations have serious functional and aesthetic consequences. In order to avoid these drawbacks we use two sorts of implants. The first are made from metallic and plastic materials. They are used when patients are too weak to support a bone graft, when there is insufficient soft tissue coverage, or when a recurrence of the tumour is feared. In order to be well tolerated they must be made of materials which are fully accepted by the tissues. For the plastic part we use methyl-methacrylate and, for the metal part, "durallium". The second type is used to maintain a bone graft in good position. It is completely metallic. The pattern is made in wax and reproduced in durallium. They are made and adjusted in the same way as plastic implants. The results are analysed separately covering two periods. In the first (1955-1967), the failures have been relatively large (25%). During the second period (1967-1974), a better choice of operative indications and a more precise technique gave better results (failure: 13%).

Ameloblastoma↗

PubMed1975

Results of treatment of incisional hernias with extractable prostheses.

A series of 80 patients with an incisional ventral hernia were treated with an extractable prosthesis in the period 1 January 1965--1 January 1974. The results are discussed. After a description of the advantages of an extractable prosthesis, attention is given to a number of factors which are possibly of importance in the development of such a hernia. This is most probably a multifactorial process, in which suturing technique, wound infection, obesity and postoperative rise of intra-abdominal pressure may play a part. The technique of inserting the extractable prosthesis is accurately described and illustrated with drawings and photographs. Success was ultimately obtained in 86.25% of the cases. The failure rate was 13.75%. In comparison with the data from the literature, this is a low percentage, the more so because the author's series consisted mainly of large incisional hernias. Recurrences can be treated successfully several times with an extractable prosthesis. This is, in general, easy in view of the smaller dimensions of the hernial orifices. The extractable prosthesis is recommended both for the treatment and prevention of incisional ventral hernia.

Abdominal Muscles↗