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Human Reproduction Update 2010Uterine contractile activity plays an important role in many and varied reproductive functions including sperm and embryo transport, implantation, menstruation,... (Review)
Review
BACKGROUND
Uterine contractile activity plays an important role in many and varied reproductive functions including sperm and embryo transport, implantation, menstruation, gestation and parturition. Abnormal contractility might underlie common and important disorders such as infertility, implantation failure, dysmenorrhea, endometriosis, spontaneous miscarriage or preterm birth.
METHODS
A systematic review of the US National Library of Medicine was performed linking 'uterus' or 'uterine myocyte' with 'calcium ion' (Ca(2+)), 'myosin light chain kinase' and 'myosin light chain phosphatase'. This led to many cross-references involving non-uterine myocytes and, where relevant, these data have been incorporated into the following synthesis.
RESULTS
We have grouped the data according to three main components that determine uterine contractility: the contractile apparatus; electrophysiology of the myocyte including excitation-contraction coupling; and regulation of the sensitivity of the contractile apparatus to Ca(2+). We also have included information regarding potential therapeutic methods for regulating uterine contractility.
CONCLUSIONS
More research is necessary to understand the mechanisms that generate the frequency, amplitude, duration and direction of propagation of uterine contractile activity. On the basis of current knowledge of the molecular control of uterine myocyte function, there are opportunities for systematic testing of the efficacy of a variety of available potential pharmacological agents and for the development of new agents. Taking advantage of these opportunities could result in an overall improvement in reproductive health.
Topics: Actin Cytoskeleton; Calcium Signaling; Electrophysiology; Female; Humans; Models, Biological; Myocytes, Smooth Muscle; Myometrium; Myosin-Light-Chain Kinase; Myosin-Light-Chain Phosphatase; Uterine Contraction; rho-Associated Kinases; rhoA GTP-Binding Protein
PubMed: 20551073
DOI: 10.1093/humupd/dmq016 -
Medicine Feb 2020The aim of this meta-analysis was to assess the clinicopathological features and to confirm prognostic value of POLE exonuclease domain mutations (EDM) in endometrial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this meta-analysis was to assess the clinicopathological features and to confirm prognostic value of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients.
METHODS
The PubMed, Web of Science, the data of China National Knowledge Infrastructure, and Wan fang Medical Network were systematically searched for relevant articles without a cut-off date. The keywords for the search were "endometrial cancer," "endometrial carcinoma," "EC," "POLE mutations," "POLE exonuclease domain mutations," "POLE-mutant," "clinical characteristics" "prognostic." Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using Review manager 5.3 and Stata 14.0 statistical software.
RESULTS
Six cohort studies assessing 179 EC patients with POLE EDMs were included. The results indicated a favorable progression-free survival in POLE-mutant patients (HR = 0.32; 95% CI: = [0.09-1.18]). Furthermore, the overall survival was great in patients with POLE-mutant (HR = 0.68; 95% CI = [0.41-1.13]). It was shown that a significantly higher incidence of POLE mutations with Federation of International of Gynecologists and Obstetricians (FIGO) I group compared to FIGO II-IV group (pooled ORs: 0.34, 95% CI: [0.12-0.94], P = .04), POLE-mutant EC was not significantly associated with histology (OR = 0.56,95% CI: 0.29-1.23), tumor grade (OR = 1.22,95% CI:0.85-1.74), lymph-vascular space invasion (OR = 0.40,95% 0.06-2.42), depth of myometrial invasion (OR = 0.70,95% CI: 0.41-1.18), lymph node status (OR = 0.41, 95% 0.04-4.50), and European Society for Medical Oncology risk groups (OR = 0.68,95% CI: 0.37-1.26).
CONCLUSION
This meta-analysis has confirmed POLE EDMs may serve as a predictive biomarker of favorable prognosis. Further studies are needed to explore the appropriate clinical utility of POLE EDMs in EC.
Topics: Biomarkers, Tumor; DNA Polymerase II; Endometrial Neoplasms; Female; Humans; Lymph Nodes; Mutation; Myometrium; Neoplasm Invasiveness; Poly-ADP-Ribose Binding Proteins; Prognosis; Progression-Free Survival
PubMed: 32080141
DOI: 10.1097/MD.0000000000019281 -
Toxins May 2021Contamination of the world's food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone...
Contamination of the world's food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone (ZEN), an estrogenic mycotoxin produced by fungi, is a common contaminant of cereal grains and has also been detected at lower levels in meat, milk, and spices. ZEN's synthetic derivative, zeranol, is used as a growth promoter in United States (US) and Canadian beef production. Experimental research suggests that ZEN and zeranol disrupt the endocrine and reproductive systems, leading to infertility, polycystic ovarian syndrome-like phenotypes, pregnancy loss, and low birth weight. With widespread human dietary exposure and growing experimental evidence of endocrine-disrupting properties, a comprehensive review of the impact of ZEN, zeranol, and their metabolites on the female reproductive system is warranted. The objective of this systematic review was to summarize the in vitro, in vivo, and epidemiological literature and evaluate the potential impact of ZEN, zeranol, and their metabolites (commonly referred to as mycoestrogens) on female reproductive outcomes. We conducted a systematic review (PROSPERO registration CRD42020166469) of the literature (2000-2020) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The data sources were primary literature published in English obtained from searching PubMed, Web of Science, and Scopus. The ToxR tool was applied to assess risk of bias. In vitro and in vivo studies ( = 104) were identified and, overall, evidence consistently supported adverse effects of mycoestrogens on physiological processes, organs, and tissues associated with female reproduction. In non-pregnant animals, mycoestrogens alter follicular profiles in the ovary, disrupt estrus cycling, and increase myometrium thickness. Furthermore, during pregnancy, mycoestrogen exposure contributes to placental hemorrhage, stillbirth, and impaired fetal growth. No epidemiological studies fitting the inclusion criteria were identified.
Topics: Animals; Estrogens, Non-Steroidal; Female; Fetal Development; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Placenta; Pregnancy; Reproduction; Uterus; Zearalenone; Zeranol
PubMed: 34073731
DOI: 10.3390/toxins13060373 -
Pathobiology : Journal of... 2022A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been hypothesized based on a different prevalence of favorable EC histological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been hypothesized based on a different prevalence of favorable EC histological prognostic factors. However, pooled risk of EC unfavorable histological prognostic factors in patients with adenomyosis has never been calculated.
OBJECTIVES
We aimed to assess the risk of EC unfavorable histological prognostic factors in patients with adenomyosis.
METHODS
All studies with data about histological prognostic factors of EC in patients with and without adenomyosis were included. Relative risk for each unfavorable histological prognostic factor of EC, such as nonendometrioid histotype, FIGO grade 3, FIGO stage II-IV, lymphovascular space invasion (LVSI), and deep myometrial invasion, was calculated in patients with adenomyosis compared to patients without adenomyosis.
RESULTS
Seven studies with 4,439 patients were included in the quantitative analysis. EC patients with adenomyosis showed a pooled RR of 0.77 (p = 0.05) for nonendometrioid histotype, 0.55 (p < 0.00001) for FIGO grade 3, 0.60 (p = 0.005) for FIGO stage II-IV, 0.75 (p = 0.004) for LVSI, and 0.65 (p = 0.001) for deep myometrial invasion.
CONCLUSION
EC patients with adenomyosis have a significantly decreased risk for unfavorable histological prognostic factors of EC compared to EC patients without adenomyosis. Such findings might explain the supposed better EC prognosis in patients with adenomyosis.
Topics: Adenomyosis; Endometrial Neoplasms; Female; Humans; Lymphoma, Follicular; Prevalence; Prognosis; Retrospective Studies
PubMed: 35051948
DOI: 10.1159/000521105 -
Acta Obstetricia Et Gynecologica... Aug 2021Magnetic resonance imaging (MRI) diagnosis of adenomyosis is considered the most accurate non-invasive technique, but remains subjective, with no consensus on which... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Magnetic resonance imaging (MRI) diagnosis of adenomyosis is considered the most accurate non-invasive technique, but remains subjective, with no consensus on which diagnostic parameters are most accurate. We aimed to systematically review the literature on how adenomyosis can be objectively quantified on MRI in a scoping manner, to review the diagnostic performance of these characteristics compared with histopathological diagnosis, and to summarize correlations between measures of adenomyosis on MRI and clinical outcomes.
MATERIAL AND METHODS
We searched databases Pubmed, Embase, and Cochrane for relevant literature up to April 2020 according to PRISMA guidelines. We included studies that objectively assessed adenomyosis on MRI, and separately assessed studies investigating the diagnostic performance of MRI vs histopathology for inclusion in a meta-analysis. The QUADAS-2 tool was used for risk of bias, with many studies showing an unclear or high risk of bias.
RESULTS
Eighty studies were included, of which 14 assessed the diagnostic performance of individual MRI parameters, with four included in the meta-analysis of diagnostic accuracy. Common MRI parameters were: junctional zone (JZ) characteristics, such as maximum JZ thickness-pooled sensitivity 71.6% (95% CI 46.0%-88.2%), specificity 85.5% (52.3%-97.0%); JZ differential-pooled sensitivity 58.9% (95% CI 44.3%-72.1%), specificity 83.2% (95% CI 71.3%-90.8%); and JZ to myometrial ratio-pooled sensitivity 63.3% (95% CI 51.9%-73.4%), specificity 79.4% (95% CI 42.0%-95.4%); adenomyosis lesion size, uterine morphology (pooled sensitivity 42.9% (95% CI 15.9%-74.9%), specificity 87.7%, (95% CI 37.9-98.8) and changes in signal intensity-eg, presence of myometrium cysts; pooled 59.6% (95% CI 41.6%-75.4%) and specificity of 96.1% (95% CI 80.7%-99.3%). Other MRI parameters have been used for adenomyosis diagnosis, but their diagnostic performance is unknown. Few studies attempted to correlate adenomyosis MRI phenotype to clinical outcomes.
CONCLUSIONS
A wide range of objective parameters for adenomyosis exist on MRI; however, in many cases their individual diagnostic performance remains uncertain. JZ characteristics remain the most widely used and investigated with acceptable diagnostic accuracy. Specific research is needed into how these objective measures of adenomyosis can be correlated to clinical outcomes.
Topics: Adenomyosis; Female; Humans; Magnetic Resonance Imaging; Predictive Value of Tests
PubMed: 33682087
DOI: 10.1111/aogs.14139 -
Reproductive Biology and Endocrinology... Nov 2020Previous caesarean scar pregnancy is one type of ectopic pregnancy in myometrium and fibrous tissue of previous caesarean scar. One of the therapeutic methods of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous caesarean scar pregnancy is one type of ectopic pregnancy in myometrium and fibrous tissue of previous caesarean scar. One of the therapeutic methods of this type of ectopic pregnancy is treatment with methotrexate. Given various findings on the treatment of caesarean scar pregnancy with methotrexate and lack of global report in this regard, we aimed to achieve a global report on the treatment of CSP with methotrexate through related literature review and analysis of the results of the studies, to enable more precise planning to reduce complications of CSP.
METHOD
This review study extracted information through searching national and international databases of SID،, Embase, ScienceDirect, ، Scopus, ، PubMed, Web of Science (ISI) between 2003 and January 2020. To perform the meta-analysis, random-effects model and heterogeneity of the studies with I index were investigated. Data were sanalysed using Comprehensive Meta-Analysis version 2.
RESULTS
In total, 26 articles with a sample size of 600 individuals were enrolled in the meta-analysis. According to the results of the study, the mean level of β-hCG was 28,744.98 ± 4425.1 mIU/ml before the intervention and was 23,836.78 ± 4533.1 mIU/ml after the intervention. The mean intraoperative blood loss (ml) was 4.8 ± 3.76 ml, mean hospital stay (days) was 11.7 ± 1.2 days, mean time for serum-hCG normalization (days) was 41.6 ± 3.2 days, success was 90.7% (95% CI: 86.7-93.5%), and complication was 9% (95% CI: 6.3-12.8%).
CONCLUSION
The results of the current study show methotrexate significantly reduces β-hCG levels and can be effective in treating caesarean scar pregnancy and its complications.
Topics: Adult; Cesarean Section; Cicatrix; Female; Humans; Methotrexate; Pregnancy; Pregnancy, Ectopic; Treatment Outcome; Uterine Artery Embolization
PubMed: 33168010
DOI: 10.1186/s12958-020-00666-0 -
Human Reproduction Update Jan 2021Adenomyosis is a benign gynecological disorder associated with subfertility, pelvic pain and abnormal uterine bleeding that have significant consequences for the health...
BACKGROUND
Adenomyosis is a benign gynecological disorder associated with subfertility, pelvic pain and abnormal uterine bleeding that have significant consequences for the health and quality of life of women. Histologically, it is defined as the presence of ectopic endometrial islets within the myometrium. Its pathogenesis has not yet been elucidated and several pieces of the puzzle are still missing. One process involved in the development of adenomyosis is the increased capacity of some endometrial cells to infiltrate the myometrium. Moreover, the local and systemic immune systems are associated with the onset of the disease and with maintaining it. Numerous observations have highlighted the activation of immune cells and the release of immune soluble factors in adenomyosis. The contribution of immunity occurs in conjunction with hormonal aberrations and activation of the epithelial to mesenchymal transition (EMT) pathway, which promotes migration of endometrial cells. Here, we review current knowledge on the immunological changes in adenomyosis, with the aim of further elucidation of the pathogenesis of this disease.
OBJECTIVE AND RATIONALE
The objective was to systematically review the literature regarding the role of the immune system in development of adenomyosis in the inner and the outer myometrium, in humans.
SEARCH METHODS
A systematic review of published human studies was performed in MEDLINE, EMBASE and Cochrane Library databases from 1970 to February 2019 using the combination of Medical Subject Headings (MeSH): Adenomyosis AND ('Immune System' OR 'Gonadal Steroid Hormones'), and free-text terms for the following search terms (and their variants): Adenomyosis AND (immunity OR immune OR macrophage OR 'natural killer cell' OR lymphocyte* OR leucocyte* OR HLA OR inflammation OR 'sex steroid' OR 'epithelial to mesenchymal transition' OR 'EMT'). Studies in which no comparison was made with control patients, without adenomyosis (systemic sample and/or eutopic endometrium), were excluded.
OUTCOMES
A total of 42 articles were included in our systematic review. Changes in innate and adaptive immune cell numbers were described in the eutopic and/or ectopic endometrium of women with adenomyosis compared to disease-free counterparts. They mostly described an increase in lymphocyte and macrophage cell populations in adenomyosis eutopic endometrium compared to controls. These observations underscore the immune contributions to the disease pathogenesis. Thirty-one cytokines and other markers involved in immune pathways were studied in the included articles. Pro-inflammatory cytokines (interleukin (IL) 6, IL1β, interferon (IFN) α, tumor necrosis factor α, IFNγ) as well as anti-inflammatory or regulatory mediators (IL10, transforming growth factor β…) were found to be elevated in the eutopic endometrium and/or in the ectopic endometrium of the myometrium in women with adenomyosis compared to controls. Moreover, in women affected by adenomyosis, immunity was reported to be directly or indirectly linked to sex steroid hormone aberrations (notably changes in progesterone receptor in eutopic and ectopic endometrium) in three studies and to EMT in four studies.
WIDER IMPLICATIONS
The available literature clearly depicts immunological changes that are associated with adenomyosis. Both systemic and local immune changes have been described in women affected by adenomyosis, with the coexistence of changes in inflammatory as well as anti-inflammatory signals. It is likely that these immune changes, through an EMT mechanism, stimulate the migration of endometrial cells into the myometrium that, together with an endocrine imbalance, promote this inflammatory process. In light of the considerable impact of adenomyosis on women's health, a better understanding of the role played by the immune system in adenomyosis is likely to yield new research opportunities to better understand its pathogenesis.
Topics: Adenomyosis; Endometriosis; Endometrium; Epithelial-Mesenchymal Transition; Female; Humans; Myometrium; Quality of Life
PubMed: 33099635
DOI: 10.1093/humupd/dmaa038 -
The Cochrane Database of Systematic... Jan 2005The frameless intrauterine device (IUD) dispenses with the frame in the classical IUD and holds the device in the uterus by anchoring one end of a nylon thread in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The frameless intrauterine device (IUD) dispenses with the frame in the classical IUD and holds the device in the uterus by anchoring one end of a nylon thread in the fundal myometrium, to which copper sleeves are attached.
OBJECTIVES
This review examines the hypothesis that the frameless IUD Gynefix reduces risk of expulsion and pregnancy, and the problems of bleeding and pain necessitating early removal.
SEARCH STRATEGY
We searched the Cochrane Controlled Trial Register (Cochrane Library Issue 2, 2004), MEDLINE, and Popline from 1980 to March 2004, and reference list of articles.
SELECTION CRITERIA
We selected for the review randomised trials that compared the frameless device to a classical framed device for contraception.
DATA COLLECTION AND ANALYSIS
Both authors extracted data independently. We contacted study author for additional data. We calculated rate ratios and rate differences for cumulative rates for each outcome at yearly intervals. We used the inverse variance-based method to combine trials, and tested the results for heterogeneity.
MAIN RESULTS
Four trials were included in the review involving 5,939 women randomised to either a frameless device or TCu380, with data up to eight years for the largest, and with a total experience of 23,180 years. Apart from one small trial, nulliparous women were excluded from the trials. The two earlier trials used a prototype introducer and there was a higher expulsion rate at one year (relative risk 2.48, 95% confidence intervals 1.89 to 3.26). However, between two and six years in the large WHO trial the risk of pregnancy was lower with the frameless device (relative risk 0.53, 95% confidence intervals 0.32 to 0.91). In a recent trial using GyneFix with a new introducer early expulsions and pregnancies were not statistically different from the control device. Removals rates for excessive bleeding and/or pain were no different between the devices (relative risks 0.92, 95% confidence intervals 0.74 to 1.14, at one year and 1.13, 0.93 to 1.37, at six years). There was a tendency towards fewer removals for pain in early years but no difference at six years (relative risk 1.13, 95% confidence intervals 0.93 to 1.37).
AUTHORS' CONCLUSIONS
There is insufficient data to show that problems of early expulsions have been overcome with the modified introducer used in GyneFix. Apart from that, the frameless device performs similarly to TCu380, and appears to have a lower pregnancy rate in later years, although the absolute difference is small.
Topics: Contraception; Equipment Design; Female; Humans; Intrauterine Devices; Randomized Controlled Trials as Topic
PubMed: 15674904
DOI: 10.1002/14651858.CD003282.pub2 -
Archives of Gynecology and Obstetrics Jan 2020To investigate the effectiveness and risks of different surgical therapies for isthmocele in symptomatic women with abnormal uterine bleeding, infertility, or for the... (Meta-Analysis)
Meta-Analysis
PURPOSE
To investigate the effectiveness and risks of different surgical therapies for isthmocele in symptomatic women with abnormal uterine bleeding, infertility, or for the prevention of obstetric complications, considering safety and surgical complications.
METHODS
PubMed/MEDLINE, Scopus, Embase, Science Direct, and Cochrane Library were systematically searched (n° CRD4201912035) for original articles on the surgical treatment of isthmocele published between 1950 and 2018. Data synthesis was completed using MedCalc 16.4.3. The body of evidence was assessed using the GRADE methodology.
RESULTS
We retrieved 33 publications: 28 focused on a single surgical technique, and five comparing different techniques. Meta-analysis showed an improvement of symptoms in 85.00% (75.05-92.76%) of women after hysteroscopic correction, 92.77% (85.53-97.64%) after laparoscopic/robotic correction, and 82.52% (67.53-93.57%) after vaginal correction. Hysteroscopic surgery was associated with the lowest risk of complications (0.76%, 0.20-1.66%).
CONCLUSIONS
We found adequate evidence supporting the use of surgery for the treatment of symptomatic isthmocele, as it was found to improve the bleeding symptoms in more than 80% of patients. Differently, we found a lack of evidence regarding the role of surgery with the purpose of improving fertility or reducing the risk of obstetric complications in women with asymptomatic isthmocele. The hysteroscopic correction of isthmocele may be the safest and most effective strategy in those patients with adequate residual myometrial thickness overlying the isthmocele. Laparoscopic and vaginal surgeries may be the preferred options for patients with a thinner residual myometrium over the defect (< 2.5 mm) and when hysteroscopic treatment is inconclusive.
Topics: Cicatrix; Female; Humans; Hysteroscopy; Laparoscopy; Uterine Diseases
PubMed: 31989288
DOI: 10.1007/s00404-020-05438-0 -
Reproductive Sciences (Thousand Oaks,... Feb 2024Adenomyosis is associated with pelvic pain, abnormal uterine bleeding, and infertility. Several ultrasound-based classifications have been reported, but it is not clear... (Review)
Review
Adenomyosis is associated with pelvic pain, abnormal uterine bleeding, and infertility. Several ultrasound-based classifications have been reported, but it is not clear which criteria reflect the severity of symptoms. The aim of this review is to summarize the ultrasound features that correlate with clinical manifestations of adenomyosis and to discuss diagnostic methods for predicting disease severity. A literature search of PubMed and Google Scholar published up to March 2022 was performed. A consensus-based classification was determined primarily by defining the mapping or topography of the lesion. Ultrasound features can be classified into direct (i.e., the presence of ectopic endometrial tissue within the myometrium) and indirect findings (i.e., changes in the myometrial structure and translesional vascularity secondary to myometrial invasion). There are some reports that symptoms are positively correlated with the location and spread of the disease. Indeed, the lesion thickness, diffuse or internal adenomyosis, and focal adenomyosis may be associated with increased risks of dysmenorrhea, abnormal uterine bleeding, and infertility, respectively. Two ultrasound markers (i.e., the presence of heterogeneous myometrium and myometrial cysts) appear to be the criteria most clinicians focus on. However, decision-making on treatment necessity is determined by symptom severity rather than the topography of the lesions. There is currently no consensus that symptom severity can be predicted based on ultrasound features, but the ultrasound-based criteria may be helpful in diagnosing adenomyosis.
Topics: Female; Humans; Adenomyosis; Uterine Diseases; Ultrasonography; Myometrium; Infertility; Uterine Hemorrhage
PubMed: 37584856
DOI: 10.1007/s43032-023-01318-5