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American Journal of Reproductive... Dec 2018Oxidative stress (OS) plays a role in uterine tissue remodeling during pregnancy and parturition. While p38 MAPK is an OS-response kinase, a precise functional role is...
Oxidative stress (OS) plays a role in uterine tissue remodeling during pregnancy and parturition. While p38 MAPK is an OS-response kinase, a precise functional role is unknown. Therefore, we conducted a systematic review of literature on p38 MAPK expression, activation, and function in reproductive tissues throughout pregnancy and parturition, published between January 1980 and August 2017, using four electronic databases (Web of Science, PubMed, Medline, and CoCHRANE). We identified 418 reports; 108 were selected for full-text evaluation and 74 were included in final review. p38 MAPK was investigated using feto-maternal primary or immortalized cells, tissue explants, and animal models. Western blot was most commonly used to report phosphorylated (active) p38 MAPK. Human placenta (27), chorioamniotic membranes (14), myometrium (13), decidua (8), and cervix (1) were the studied tissues. p38 MAPK's functions were tissue and gestational age dependent. Isoform specificity was hardly reported. p38 MAPK activity was induced by ROS or proinflammatory cytokines to promote cell signaling linked to cell fate, primed uterus, ripened cervix, and proinflammatory cytokine/chemokine production. In 35 years, reports on p38 MAPK's role during pregnancy and parturition are scarce and current literature is insufficient to provide a comprehensive description of p38 MAPK's mechanistic role during pregnancy and parturition.
Topics: Animals; Disease Models, Animal; Female; Gene Expression Regulation; Genitalia, Female; Humans; Inflammation; Oxidative Stress; Parturition; Pregnancy; Reproduction; Signal Transduction; p38 Mitogen-Activated Protein Kinases
PubMed: 30178469
DOI: 10.1111/aji.13047 -
American Journal of Obstetrics and... Nov 2014A systematic review and metaanalysis were performed through electronic database searches to estimate the effect of uterine closure at cesarean on the risk of adverse... (Comparative Study)
Comparative Study Meta-Analysis Review
A systematic review and metaanalysis were performed through electronic database searches to estimate the effect of uterine closure at cesarean on the risk of adverse maternal outcome and on uterine scar evaluated by ultrasound. Randomized controlled trials, which compared single vs double layers and locking vs unlocking sutures for uterine closure of low transverse cesarean, were included. Outcomes were short-term complications (endometritis, wound infection, maternal infectious morbidity, blood transfusion, duration of surgical procedure, length of hospital stay, mean blood loss), uterine rupture or dehiscence at next pregnancy, and uterine scar evaluation by ultrasound. Twenty of 1278 citations were included in the analysis. We found that all types of closure were comparable for short-term maternal outcomes, except for single-layer closure, which had shorter operative time (-6.1 minutes; 95% confidence interval [CI], -8.7 to -3.4; P < .001) than double-layer closure. Single layer (-2.6 mm; 95% CI, -3.1 to -2.1; P < .001) and locked first layer (mean difference, -2.5 mm; 95% CI, -3.2 to -1.8; P < .001) were associated with lower residual myometrial thickness. Two studies reported no significant difference between single- vs double-layer closure for uterine dehiscence (relative risk, 1.86; 95% CI, 0.44-7.90; P = .40) or uterine rupture (no case). In conclusion, current evidence based on randomized trials does not support a specific type of uterine closure for optimal maternal outcomes and is insufficient to conclude about the risk of uterine rupture. Single-layer closure and locked first layer are possibly coupled with thinner residual myometrium thickness.
Topics: Cesarean Section; Cicatrix; Endometritis; Female; Humans; Length of Stay; Operative Time; Postoperative Complications; Pregnancy; Surgical Wound Dehiscence; Surgical Wound Infection; Suture Techniques; Treatment Outcome; Ultrasonography; Uterine Rupture; Uterus; Wound Closure Techniques
PubMed: 24912096
DOI: 10.1016/j.ajog.2014.06.014 -
European Journal of Obstetrics,... Aug 2023Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The... (Review)
Review
BACKGROUND
Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The current management of uterine leiomyomas mainly includes surgical interventions such as hysterectomy and myomectomy, either by laparoscopy or laparotomy, which have several complications and are not ideal for preserving fertility. Therefore, there is a need to develop or repurpose medical treatments that do not require surgical intervention.
OBJECTIVE
Many drugs are used to treat the symptoms associated with uterine fibroids. The main objective of this systematic review is to give an up-to-date account of potential pharmacological agents (non-surgical methods) for the management of uterine leiomyomas.
SEARCH STRATEGY
PubMed was searched for scientific and clinical literature using the keyword 'uterine fibroids' along with the drug names described in each section. For example, 'uterine fibroids' and 'ulipristal acetate' were the keywords used to search for literature on ulipristal acetate (UPA).
RESULTS
Various preclinical and clinical studies have shown that some drugs and herbal formulations exhibit activity in the management of uterine leiomyomas. Recent studies found that drugs such as UPA, elagolix, EC313, asoprisnol, nutritional supplements and herbal preparations were helpful in treating the symptoms associated with uterine leiomyomas.
CONCLUSION
Many drugs show efficacy in patients with symptomatic uterine fibroids. UPA is one of the most studied and prescribed medicines for uterine fibroids; however, its usage has been restricted due to a few recent incidences of hepatic toxicity. Herbal drugs and natural supplements have also shown promising effects on uterine fibroids. The synergistic effects of nutritional and herbal supplements have been reported in certain cases, and should be studied in detail. Further research is warranted to identify the mode of action of the drugs, and to determine the precise conditions that would explain the causes of toxicity in some patients.
Topics: Female; Humans; Uterine Neoplasms; Quality of Life; Leiomyoma; Uterine Myomectomy; Acetates
PubMed: 37385088
DOI: 10.1016/j.ejogrb.2023.06.021 -
Frontiers in Pharmacology 2023Dysmenorrhea affects women throughout their reproductive years but there has been a lack of effective and well-tolerated treatment options. Pain symptoms mainly result...
Dysmenorrhea affects women throughout their reproductive years but there has been a lack of effective and well-tolerated treatment options. Pain symptoms mainly result from inflammatory processes and increased contractile activity in the myometrium. The reported use of preparations against inflammation and pain in ethnomedicine as well as current pharmacological data on their inhibition of myometrial contractility led us to hypothesize that this medicinal plant might be a new treatment option for dysmenorrhea. In the first part of the present work, clinical, and studies on the anti-nociceptive and anti-inflammatory, as well as on myometrium relaxing properties of are reviewed. In the second part, cases of five women with dysmenorrhea who were tentatively treated with a product are described. The review revealed thirty-three experimental and studies, but no clinical study, reporting anti-nociceptive and anti-inflammatory effects of extracts and compounds in a wide range of conditions. Moreover, sixteen publications on smooth muscle contractility revealed relaxing effects. The latter consisted of clinical evidence, as well as of and data. The evidence reviewed therefore provided a rational basis for the use of in the treatment of dysmenorrhea. We subsequently set out to tentatively treat patients with a well-tolerated product that is registered (without indication) and commonly used in obstetrics and gynecology in Switzerland. All five treated patients reported a reduction in pain symptoms and 4 out of 5 indicated a reduced intake of painkillers during menstruation. Taken together, the reviewed information on the pharmacological properties and clinical evidence of extracts and compounds as well as the outcomes of all five patients in the case series support our hypothesis in favor of as a new, well-tolerated therapeutic approach for dysmenorrhea. Prospective clinical studies are urgently needed.
PubMed: 38130407
DOI: 10.3389/fphar.2023.1292919 -
Journal of Minimally Invasive Gynecology Feb 2018Adenomyosis is characterized by the presence of ectopic foci of endometrial glandular tissue and/or stroma within the myometrium. The diagnosis of adenomyosis is... (Meta-Analysis)
Meta-Analysis
Adenomyosis is characterized by the presence of ectopic foci of endometrial glandular tissue and/or stroma within the myometrium. The diagnosis of adenomyosis is traditionally made through histologic evaluation of the postsurgical specimen. More recently, imaging with transvaginal ultrasound (TVUS) has been used for the preoperative diagnosis of adenomyosis. As yet, there is no consensus regarding the best imaging feature or combination thereof for the nonsurgical diagnosis of adenomyosis. This study systematically evaluated the literature in the last 10 years to determine the accuracy of 2-dimensional (2D) TVUS, different imaging features, enhancing methods such as 3-dimensional (3D) TVUS, elastography and color Doppler in the nonsurgical diagnosis of adenomyosis. A total of 8 studies were included. Pooled sensitivity and specificity for 2D TVUS for the diagnosis of adenomyosis for all combined imaging characteristics was 83.8% and 63.9%, respectively. Pooled sensitivity for 355 total patients with use of imaging feature of heterogeneous myometrium with 2D TVUS was highest (86.0%), and pooled specificity for 283 total patients with use of globular uterus was highest (78.1%). After including the "question mark" sign with other TVUS features, higher sensitivity and specificity, of 92% and 88%, respectively, were noted. For 3D TVUS, pooled sensitivity and specificity for all combined imaging characteristics was 88.9% and 56.0%, respectively. Poor definition of junctional zone showed the highest pooled sensitivity (86%) and the highest pooled specificity (56.0%) for the diagnosis of adenomyosis with 3D TVUS. There was no improvement in overall accuracy in 3D TVUS compared with 2D TVUS. Preliminary results of TVUS with color Doppler showed a high sensitivity and specificity for the differentiation between adenomyosis and myomas (95.6% and 93.4%, respectively). Also, TVUS elastography in 1 study showed an improvement in specificity (82.9%) compared with 2D TVUS (63.9%), albeit with comparable sensitivity. Larger studies are needed to advance our understanding of the different types of adenomyosis and their clinical impact.
Topics: Adenomyosis; Elasticity Imaging Techniques; Female; Humans; Imaging, Three-Dimensional; Myometrium; Sensitivity and Specificity; Ultrasonography
PubMed: 28864044
DOI: 10.1016/j.jmig.2017.08.653 -
International Journal of Gynaecology... May 2022Despite the high prevalence of adenomyosis in hysterectomy specimens of endometrial carcinoma (EC) patients, the relationship between adenomyosis and EC prognosis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite the high prevalence of adenomyosis in hysterectomy specimens of endometrial carcinoma (EC) patients, the relationship between adenomyosis and EC prognosis appears unclear.
OBJECTIVE
To assess the prognostic value of coexistent adenomyosis in patients with EC.
METHODS
A systematic review and meta-analysis was performed by searching six electronic databases for studies reporting data on prognosis of EC patients with and without coexistent adenomyosis. Studies with patient selection based on prognostic factors were excluded. Pooled univariate hazard ratio (HR) analyses for overall survival (OS) and disease-free survival (DRF) were performed, using EC patients without adenomyosis as a control group. For DFS, pooled multivariate HR analysis was also evaluable.
RESULTS
Three studies of 2505 EC patients (553 with and 1952 without adenomyosis) were included. Compared with EC patients without adenomyosis, EC patients with coexistent adenomyosis showed a pooled HR of 0.533 (CI 95%, 0.329-0.864) for OS at univariate analysis; 0.536 (CI 95%, 0.334-0.859) for DFS at univariate analysis; and 0.875 (CI 95%, 0.331-2.315) for DFS at multivariate analysis.
CONCLUSION
In EC patients with coexistent adenomyosis, the risk of death is halved compared with EC patients without adenomyosis. However, the independence of this association needs to be verified in future studies.
Topics: Adenomyosis; Disease-Free Survival; Endometrial Neoplasms; Female; Humans; Prognosis; Progression-Free Survival
PubMed: 34228822
DOI: 10.1002/ijgo.13818 -
The Cochrane Database of Systematic... Dec 2021Dysmenorrhoea (period pain) is a common condition with a substantial impact on the well-being and productivity of women. Primary dysmenorrhoea is defined as recurrent,... (Review)
Review
BACKGROUND
Dysmenorrhoea (period pain) is a common condition with a substantial impact on the well-being and productivity of women. Primary dysmenorrhoea is defined as recurrent, cramping pelvic pain that occurs with periods, in the presence of a normal uterus, ovaries and fallopian tubes. It is thought to be caused by uterine contractions (cramps) associated with a high level of production of local chemicals such as prostaglandins. The muscle of the uterus (the myometrium) responds to these high levels of prostaglandins by contracting forcefully, causing low oxygen levels and consequently pain. Nifedipine is a calcium channel blocker in widespread clinical use for preterm labour due to its ability to inhibit uterine contractions in that setting. This review addresses whether this effect of nifedipine also helps with relief of the uterine contractions during menstruation OBJECTIVES: To assess the effectiveness and safety of nifedipine for primary dysmenorrhoea.
SEARCH METHODS
We searched for all published and unpublished randomised controlled trials (RCTs) of nifedipine for dysmenorrhoea, without language restriction and in consultation with the Cochrane Gynaecology and Fertility Group (CGF) Information Specialist. The following databases were searched to 25 November 2021: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL. Also searched were the international trial registers: ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal, the Web of Science, OpenGrey, LILACS database, PubMed and Google Scholar. We checked the reference lists of relevant articles.
SELECTION CRITERIA
We included RCTs comparing nifedipine with placebo for the treatment of primary dysmenorrhoea.
DATA COLLECTION AND ANALYSIS
The primary outcomes to be assessed were pain, and health-related quality of life. Secondary outcomes were adverse effects, satisfaction, and need for additional medication. The two review authors independently assessed the included trials. There were insufficient data to allow meaningful meta-analysis.
MAIN RESULTS
The evidence assessed was of very low quality overall. We examined three small RCTs, with a total of 106 participants. Data for analysis could be extracted from only two of these trials (with a total of 66 participants); two trials were published in the 1980s, and the third in 1993. Nifedipine may be effective for "any pain relief" compared to placebo in women with primary dysmenorrhoea (odds ratio (OR) 9.04, 95% confidence interval (CI) 2.61 to 31.31; 2 studies, 66 participants; very low-quality evidence). The evidence suggests that if the rate of pain relief using placebo is 40%, the rate using nifedipine would be between 64% and 95%. For the outcome of "good" or "excellent" pain relief, nifedipine may be more effective than placebo; the confidence interval was very wide (OR 43.78, 95% CI 5.34 to 259.01; 2 studies, 66 participants; very low-quality evidence). We are uncertain if the use of nifedipine was associated with less requirement for additional analgesia use than placebo (OR 0.54, 95% CI 0.07 to 4.20, 1 study, 42 participants; very low-quality evidence). Participants indicated that they would choose to use nifedipine over their previous analgesic if the option was available. There were similar levels of adverse effects and menstruation-related symptoms in the placebo and intervention groups (OR 0.94, 95% CI 0.08 to 10.90; 1 study, 24 participants; very low-quality evidence); if the chance of adverse effects with placebo is 80%, the rate using nifedipine would be between 24% and 98%. There were no results regarding formal assessment of health-related quality of life.
AUTHORS' CONCLUSIONS
The evidence is insufficient to confirm whether nifedipine is a possible medical treatment for primary dysmenorrhoea. The trials included in this review had very low numbers and were of low quality. Notably, there was a large imbalance in numbers randomised between placebo and treatment groups in one of the two trials with data available for analysis. While there was no evidence of a difference noted in adverse effects between groups, more data from larger participant numbers are needed for this outcome. Larger, more well-conducted trials are required to elucidate the potential role of nifedipine in the treatment of this common condition, as it could be a useful addition to the therapeutic options available if shown to be well tolerated and effective. The safety of nifedipine in women of reproductive age is well established from trials of its use in preterm labour, and clinicians are accustomed to off-label use for this indication. The drug is inexpensive and readily available. Other options for relief of primary dysmenorrhoea are not suitable for all women; NSAIDs and the oral contraceptive pill (OCP) are contraindicated for some women, and the OCP is not suitable for women who are trying to conceive. In addition, the trials examined suggest there may be a participant preference for nifedipine.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dysmenorrhea; Female; Humans; Infant, Newborn; Menstruation; Nifedipine; Pelvic Pain; Pregnancy
PubMed: 34921554
DOI: 10.1002/14651858.CD012912.pub2 -
International Journal of Gynecological... Feb 2016The aim of this study was to perform a meta-analysis comparing diagnostic performance of intraoperative gross evaluation (IGE) and intraoperative frozen section (IFS)... (Meta-Analysis)
Meta-Analysis Review
Intraoperative Gross Examination and Intraoperative Frozen Section in Patients With Endometrial Cancer for Detecting Deep Myometrial Invasion: A Systematic Review and Meta-analysis.
OBJECTIVE
The aim of this study was to perform a meta-analysis comparing diagnostic performance of intraoperative gross evaluation (IGE) and intraoperative frozen section (IFS) for the assessment of myometrial invasion in patients with endometrial cancer.
METHODS
An extensive search was performed in several databases from January 1989 to May 2015. Eligibility criteria were studies using intraoperative gross evaluation or intraoperative frozen section to determine deep myometrial invasion in patients with endometrial cancer using the final histopathology report with reference standard. Quality was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Quality Assessment of Diagnostic Accuracy Studies 2 tool.
RESULTS
Forty-seven articles were identified. Of these, 35 studies were selected and included in the meta-analysis. A total of 6387 women were evaluated intraoperatively with any of the 2 methods mentioned. Pooled sensitivity and specificity for IGE were 71% (95% confidence interval [CI], 63%-77%) and 91% (95% CI, 89%-93%), respectively. Heterogeneity was found high for sensitivity (I2: 83.6%; Cochran Q: 79.4; P < 0.001) and moderate for specificity (I, 51.4%; Cochran Q, 29.8; P =0.01). Pooled sensitivity and specificity for IFS were 85% (95% CI, 81%-88%) and 97% (95% CI, 96%-98%), respectively. Heterogeneity was found moderate for sensitivity (I, 56.4%; Cochran Q, 45.9; P < 0.001) and high for specificity (I, 83.2%; Cochran Q, 118.9; P < 0.001). Both sensitivity (P = 0.0008) and specificity (P = 0.0021) were significantly higher for IFS compared to IGE.
CONCLUSION
Intraoperative frozen section has better diagnostic performance than intraoperative gross evaluation for the intraoperative diagnosis of deep myometrial invasion in patients with endometrial cancer.
Topics: Endometrial Neoplasms; Female; Frozen Sections; Humans; Intraoperative Care; Myometrium
PubMed: 26807569
DOI: 10.1097/IGC.0000000000000618 -
Cureus Sep 2021Cesarean section (CS) delivery is a common procedure, and its incidence is increasing globally. To compare single-layer (SL) with double-layer (DL) uterine closure... (Review)
Review
Cesarean section (CS) delivery is a common procedure, and its incidence is increasing globally. To compare single-layer (SL) with double-layer (DL) uterine closure techniques after cesarean section in terms of ultrasonographic findings and rate of CS complications. PubMed, Scopus, Web of Science, and Cochrane Library were searched for relevant randomized clinical trials (RCTs). Retrieved articles were screened, and relevant studies were included in a meta-analysis. Continuous data were pooled as mean difference (MD) with 95% confidence interval (CI), and dichotomous data were pooled as relative risk (RR) and 95% CI. Analysis was conducted using RevMan software (Version 5.4). Eighteen RCTs were included in our study. Pooled results favored DL uterine closure in terms of residual myometrial thickness (MD = -1.15; 95% CI -1.69, -0.60; P < 0.0001) and dysmenorrhea (RR = 1.36; 95% CI 1.02, 1.81; P = 0.04), while SL closure had shorter operation time than DL closure (MD = -2.25; 95% CI -3.29, -1.21; P < 0.00001). Both techniques had similar results in terms of uterine dehiscence or rupture (RR = 1.88; 95% CI 0.63, 5.62; P = 0.26), healing ratio (MD = -5.00; 95% CI -12.40, 2.39; P = 0.18), maternal infectious morbidity (RR = 0.94; 95% CI 0.66, 1.34; P = 0.72), hospital stay (MD = -0.12; 95% CI -0.30, 0.06; P = 0.18), and readmission rate (RR = 0.95; 95% CI 0.64, 1.40; P = 0.78). Double-layer uterine closure shows more residual myometrial thickness and lower incidence of dysmenorrhea than single-layer uterine closure of cesarean section scar. But single-layer closure has the advantage of the shorter operation time. Both methods have comparable blood loss amount, healing ratio, hospital stay duration, maternal infection risk, readmission rate, and uterine dehiscence or rupture risk.
PubMed: 34729282
DOI: 10.7759/cureus.18405 -
Acta Obstetricia Et Gynecologica... Jan 2018Our objective was to elucidate the overall diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation (AIP). (Review)
Review
INTRODUCTION
Our objective was to elucidate the overall diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation (AIP).
MATERIAL AND METHODS
Medline, Embase, CINAHL and The Cochrane databases were searched. The ultrasound signs explored were: loss of hypoechoic (clear) zone in the placental-uterine interface, placental lacunae, bladder wall interruption, myometrial thinning, focal exophitic mass, placental lacunar flow, subplacental vascularity, and uterovesical hypervascularity.
RESULTS
Twenty studies (3209 pregnancies) were included. Ultrasound had an overall good diagnostic accuracy in identifying the depth of placental invasion with sensitivities of 90.6%, 93.0%, 89.5%, and 81.2% for placenta accreta, increta, accreta/increta, and percreta, respectively; the corresponding specificities were 97.1%, 98.4%, 94.7%, and 98.9%. Placental lacunae had sensitivities of 74.8%, 88.6%, and 76.3% for the detection of placenta accreta, increta, and percreta, respectively. Sensitivity and specificity of loss of the clear zone in identifying placenta accreta were 74.9% and 92.0%, whereas the corresponding figures for placenta increta and percreta were 91.6% and 76.9%, and 88.1% and 71.1%. Lacunar flow had sensitivities of 81.2%, 84.3%, and 45.2% for the detection of placenta accreta, increta, and percreta respectively; the corresponding figures for specificity were 84.0%, 79.7%, and 75.3%. Sensitivity of uterovesical hypervascularity was low for the detection of placenta accreta (12.3%) but high for placenta increta (94.4%) and percreta (86.2%); the corresponding figures for specificity were 90.8%, 88.0% and 88.2%, respectively.
CONCLUSIONS
Ultrasound has an overall good diagnostic accuracy in recognizing the depth and the topography of placental invasion.
Topics: Female; Humans; Myometrium; Placenta; Placenta Accreta; Pregnancy; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 28963728
DOI: 10.1111/aogs.13238