-
American Journal of Reproductive... Feb 2018Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory... (Review)
Review
Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory biomarkers linked to labor, a comprehensive profile of them in each of the uterine compartments is not available to better understand their mechanistic contributions to labor. This systematic review investigated the pro- and anti-inflammatory biomarkers reported in intra-uterine tissues (amnion, chorion, decidua, placenta, and myometrium) at term labor. We conducted a systematic review of studies on pro- and anti-inflammatory biomarkers (mRNA and/or protein) reported in feto-maternal tissues during normal human term labor, published in English (1980-2016), in 3 electronic data bases. From a total of 3712 citations, 172 were included for final review. Each tissue expresses a unique set of biomarkers at the time of term labor, but there is significant overlap between tissues. All tissues had IL-6, IL-8, IL-1β, COX-2, PGE-2, TNF-α, and hCAP18 in common at term labor. Common and unique inflammatory biomarkers are expressed in various feto-maternal compartments at term labor. Increase in pro-inflammatory markers in all gestational tissue signifies their harmonious functional role in promoting labor. Anti-inflammatory markers at term labor are hardly reported.
Topics: Animals; Antimicrobial Cationic Peptides; Biomarkers; Cathelicidins; Cyclooxygenase 2; Female; Humans; Inflammation; Inflammation Mediators; Metalloporphyrins; Parturition; Pregnancy; Uterus
PubMed: 29076197
DOI: 10.1111/aji.12776 -
The Journal of Maternal-fetal &... Feb 2020The identification of women at risk for preterm birth should allow interventions which could improve neonatal outcome. Fetal fibronectin, a glycoprotein which acts... (Meta-Analysis)
Meta-Analysis
The identification of women at risk for preterm birth should allow interventions which could improve neonatal outcome. Fetal fibronectin, a glycoprotein which acts normally as glue between decidua and amniotic membranes could be a good marker of impending labour when its concentration in cervicovaginal secretions between 22 and 36 weeks of gestation is ≥50 ng/mL. Many authors worldwide have tested this marker with many different methodologies and clinical settings, but conclusions about its clinical use are mixed. It is time for a comprehensive update through a systematic review and meta-analysis. We searched PubMed, Cochrane Library, and Embase, supplemented by manual search of bibliographies of known primary and review articles, international conference papers, and contact with experts from 1-1990 to 2-2018. We have selected all type of studies involving fetal fibronectin test accuracy for preterm delivery. Two authors independently extracted data about study characteristics and quality from identified publications. Contingency tables were constructed. Reference standards were preterm delivery before 37, 36, 35, 34, and 32 weeks, within 28, 21, 14, or 7 d and within 48 h. Data were pooled to produce summary likelihood ratios for positive and negative tests results. One hundred and ninety-three primary studies were identified allowing analysis of 53 subgroups. In all settings, none of the summary likelihood ratios were >10 or <0.1, thus indicating moderate prediction, particularly in asymptomatic women and in multiple gestations. The fetal fibronectin test should not be used as a screening test for asymptomatic women. For high-risk asymptomatic women, and especially for women with multiple pregnancies, the performance of the fetal fibronectin test was also too low to be clinically relevant. Consensual use as a diagnostic tool for women with suspected preterm labor, the best use policy probably still depends on local contingencies, future cost-effectiveness analysis, and comparison with other more recent available biochemical markers.
Topics: Female; Fibronectins; Humans; Obstetric Labor, Premature; Pregnancy
PubMed: 29914277
DOI: 10.1080/14767058.2018.1491031 -
Frontiers in Physiology 2021Genome-wide transcriptomic studies on gestational tissues in labor provide molecular insights in mechanism of normal parturition. This systematic review aimed to...
Genome-wide transcriptomic studies on gestational tissues in labor provide molecular insights in mechanism of normal parturition. This systematic review aimed to summarize the important genes in various gestational tissues around labor onset, and to dissect the underlying molecular regulations and pathways that trigger the labor in term pregnancies. PubMed and Web of Science were searched from inception to January 2021. Untargeted genome-wide transcriptomic studies comparing the gene expression of various gestational tissues in normal term pregnant women with and without labor were included. Every differentially expressed gene was retrieved. Consistently expressed genes with same direction in different studies were identified, then gene ontology and KEGG analysis were conducted to understand molecular pathways and functions. Gene-gene association analysis was performed to determine the key regulatory gene(s) in labor onset. A total of 15 studies, including 266 subjects, were included. 136, 26, 15, 7, and 3 genes were significantly changed during labor in the myometrium (seven studies, = 108), uterine cervix (four studies, = 64), decidua (two studies, = 42), amnion (two studies, = 44) and placenta (two studies, = 41), respectively. These genes were overrepresented in annotation terms related to inflammatory and immune responses. TNF and NOD-like receptor signaling pathways were overrepresented in all mentioned tissues, except the placenta. was the only gene included in both pathways, the most common reported gene in all included studies, and also the gene in the central hub of molecular regulatory network. This systematic review identified that genes involved in immunological and inflammatory regulations are expressed in specific gestational tissues in labor. We put forward the hypothesis that IL6 might be the key gene triggering specific mechanism in different gestational tissues, eventually leading to labor onset through inducing uterine contraction, wakening fetal membranes and stimulating cervical ripening. Identifier [CRD42020187975].
PubMed: 34566691
DOI: 10.3389/fphys.2021.730030 -
International Journal of Molecular... May 2023Recurrent miscarriage (RM) can be defined as two or more consecutive miscarriages before 20 weeks' gestation. Vascular endothelial growth factors (VEGFs) play an... (Review)
Review
Recurrent miscarriage (RM) can be defined as two or more consecutive miscarriages before 20 weeks' gestation. Vascular endothelial growth factors (VEGFs) play an important role in endometrial angiogenesis and decidualization, prerequisites for successful pregnancy outcomes. We conducted a systematic review of the published literature investigating the role of VEGFs in RM. In particular, we explored the methodological inconsistencies between the published reports on this topic. To our knowledge, this is the first systematic literature review to examine the role of VEGFs in RM. Our systematic search followed PRISMA guidelines. Three databases, Medline (Ovid), PubMed, and Embase, were searched. Assessment-bias analyses were conducted using the Joanna Bigger Institute critical appraisal method for case-control studies. Thirteen papers were included in the final analyses. These studies included 677 cases with RM and 724 controls. Endometrial levels of VEGFs were consistently lower in RM cases compared to controls. There were no consistent significant findings with respect to VEGFs levels in decidua, fetoplacental tissues, and serum when RM cases were compared to controls. The interpretation of studies that explored the relationship between VEGFs and RM is hampered by inconsistencies in defining clinical, sampling, and analytical variables. To clarify the association between VEGF and RM in future studies, researchers ideally should use similarly defined clinical groups, similar samples collected in the same way, and laboratory analyses undertaken using the same methods.
Topics: Pregnancy; Female; Humans; Vascular Endothelial Growth Factor A; Abortion, Habitual; Vascular Endothelial Growth Factors; Pregnancy Outcome; Endometrium
PubMed: 37298399
DOI: 10.3390/ijms24119449 -
Human Reproduction Update 2009Adaptation of the maternal immune response to accommodate the semi-allogeneic fetus is necessary for pregnancy success, and disturbances in maternal tolerance are... (Review)
Review
BACKGROUND
Adaptation of the maternal immune response to accommodate the semi-allogeneic fetus is necessary for pregnancy success, and disturbances in maternal tolerance are implicated in infertility and reproductive pathologies. T regulatory (Treg) cells are a recently discovered subset of T-lymphocytes with potent suppressive activity and pivotal roles in curtailing destructive immune responses and preventing autoimmune disease.
METHODS
A systematic review was undertaken of the published literature on Treg cells in the ovary, testes, uterus and gestational tissues in pregnancy, and their link with infertility, miscarriage and pathologies of pregnancy. An overview of current knowledge on the generation, activation and modes of action of Treg cells in controlling immune responses is provided, and strategies for manipulating regulatory T-cells for potential applications in reproductive medicine are discussed.
RESULTS
Studies in mouse models show that Treg cells are essential for maternal tolerance of the conceptus, and that expansion of the Treg cell pool through antigen-specific and antigen non-specific pathways allows their suppressive actions to be exerted in the critical peri-implantation phase of pregnancy. In women, Treg cells accumulate in the decidua and are elevated in maternal blood from early in the first trimester. Inadequate numbers of Treg cells or their functional deficiency are linked with infertility, miscarriage and pre-eclampsia.
CONCLUSIONS
The potency and wide-ranging involvement of Treg cells in immune homeostasis and disease pathology indicates the considerable potential of these cells as therapeutic agents, raising the prospect of their utility in novel treatments for reproductive pathologies.
Topics: Abortion, Spontaneous; Animals; Cytokines; Dendritic Cells; Female; Humans; Immune Tolerance; Indoleamine-Pyrrole 2,3,-Dioxygenase; Infertility; Male; Mice; Models, Immunological; Ovary; Pregnancy; Pregnancy Complications; Prostaglandins; Semen; Signal Transduction; T-Lymphocytes, Regulatory; Testis; Toll-Like Receptors
PubMed: 19279047
DOI: 10.1093/humupd/dmp004 -
Gynecologic and Obstetric Investigation 2023The uterine caesarean scar defect, also known as uterine niche or isthmocele, is an irregularity in the anterior uterine wall at the site of a previous cesarean section...
INTRODUCTION
The uterine caesarean scar defect, also known as uterine niche or isthmocele, is an irregularity in the anterior uterine wall at the site of a previous cesarean section scar. It is associated with obstetrical complications such as caesarean scar, ectopic pregnancy, uterine rupture, and the placenta accreta spectrum. Women with cesarean scar defects are frequently asymptomatic but may also experience abnormal vaginal bleeding, chronic pelvic pain, and infertility.
METHODS
This systematic review aims to determine the best hysterotomy closure technique to prevent subsequent development of uterine scar defects. An electronic search in Medline, Embase, Cochrane Database of Systematic Reviews, ClinicalTrials.gov was performed from January 2001 until December 2020 for studies evaluating hysterotomy closure techniques.
RESULTS
Our systematic search strategy identified 1,781 titles. Six studies fulfilled inclusion criteria and were included in the final analysis. The results supported the superiority of the double-layer closure over the single-layer closure.
CONCLUSIONS
Hysterotomy closure with continuous running sutures in two layers represents a suitable option to prevent cesarean scar defect formation. Particularly, the first layer should include the decidua and the second layer should overlap the first.
Topics: Female; Humans; Pregnancy; Cesarean Section; Cicatrix; Hysterotomy; Uterus
PubMed: 36724750
DOI: 10.1159/000528144 -
BJOG : An International Journal of... Aug 2018Caesarean section (CS) rates are rising globally. Long-term adverse outcomes after CS might be reduced when the optimal uterine closure technique becomes evident. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Caesarean section (CS) rates are rising globally. Long-term adverse outcomes after CS might be reduced when the optimal uterine closure technique becomes evident.
OBJECTIVE
To determine the effect of uterine closure techniques after CS on maternal and ultrasound outcomes.
SEARCH STRATEGY
Literature search in electronic databases.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or prospective cohort studies that evaluated uterine closure techniques and reported on ultrasound findings, perioperative or long-term outcomes.
DATA COLLECTION AND ANALYSIS
Twenty studies (15 053 women) were included in our meta-analyses for various outcomes. We calculated pooled risk ratios (RR) and weighted mean differences (WMD) with 95% CI through random-effect analysis.
MAIN RESULTS
Residual myometrium thickness (RMT), reported in eight studies (508 women), decreased by 1.26 mm after single- compared with double-layer closure (95% CI -1.93 to -0.58), particularly when locked sutures were used. Healing ratio [RMT/adjacent myometrium thickness (AMT)] decreased after single-layer closure (WMD -7.74%, 95% CI -13.31 to -2.17), particularly in the case of locked sutures. Niche prevalence increased (RR 1.71, 95% CI 1.11-2.62) when the decidua was excluded. Dysmenorrhea occurred more often in the single-layer group (RR 1.23, 95% CI 1.01-1.48), whereas incidence of uterine rupture was similar (RR 1.91, 95% CI 0.63-5.74).
CONCLUSION
Double-layer unlocked sutures are preferable to single-layer locked sutures regarding RMT, healing ratio and dysmenorrhoea. Excluding the decidua seems to result in higher niche prevalence. As thin residual myometrium or niches may serve as intermediates for gynaecological and reproductive outcomes, future studies should focus on these outcomes. TWEETABLE ABSTRACT: #Uterineclosuretechniques after #caesarean affect #longtermoutcomes.
Topics: Abdominal Wound Closure Techniques; Cesarean Section; Dysmenorrhea; Female; Humans; Myometrium; Postoperative Complications; Pregnancy; Prospective Studies; Randomized Controlled Trials as Topic; Suture Techniques; Treatment Outcome; Ultrasonography; Uterine Rupture; Uterus; Wound Healing
PubMed: 29215795
DOI: 10.1111/1471-0528.15048 -
Fertility and Sterility Jun 2022Implantation is a critical step in the establishment of a successful pregnancy, depending on a complex immune-endocrine dialogue between the developing embryo and... (Meta-Analysis)
Meta-Analysis Review
Implantation is a critical step in the establishment of a successful pregnancy, depending on a complex immune-endocrine dialogue between the developing embryo and maternal endometrium. Research suggests that altered immunity in the maternal decidua results in implantation impairment and failure. Immunomodulatory drugs have, thus, been widely used in assisted conception to aid embryo implantation, despite an absence of consensus on their effectiveness and safety. We conducted a systematic review and meta-analysis of interventional studies investigating the use of immunomodulators in women undergoing assisted reproduction. Evidence was uncertain of an effect for most of the included interventions, owing to heterogeneous findings and a paucity of high-quality studies. For certain patient subgroups, however, the use of specific immunomodulatory therapies may offer some benefit. There is a need for further large randomized controlled trials to corroborate these findings.
Topics: Embryo Implantation; Endometrium; Female; Fertilization in Vitro; Humans; Immunotherapy; Infertility; Pregnancy
PubMed: 35618357
DOI: 10.1016/j.fertnstert.2022.04.015 -
The Cochrane Database of Systematic... Oct 2008Fetal fibronectin (FFN) is an extracellular matrix glycoprotein localized at the maternal-fetal interface of the amniotic membranes, between chorion and decidua, where... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fetal fibronectin (FFN) is an extracellular matrix glycoprotein localized at the maternal-fetal interface of the amniotic membranes, between chorion and decidua, where it is concentrated in this area between decidua and trophoblast. In normal conditions, FFN is found at very low levels in cervico-vaginal secretions. Levels greater than or equal to 50 ng/mL at or after 22 weeks have been associated with an increased risk of spontaneous preterm birth. In fact, FFN is one of the best predictors of preterm birth in all populations studied so far, and can help selecting which women are at significant risk for preterm birth.
OBJECTIVES
To assess the effectiveness of management based on knowledge of FFN testing results for preventing preterm birth.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2008), MEDLINE (1966 to December 2007) and all references in identified articles.
SELECTION CRITERIA
Randomized controlled trials of pregnant women between the gestational ages of 22 and 34 weeks screened with FFN for risk of preterm birth. Studies included are based exclusively on knowledge of FFN results versus no such knowledge, and we have excluded studies including women with only positive or only negative FFN results.
DATA COLLECTION AND ANALYSIS
All four authors assessed studies for inclusion and quality and extracted data.
MAIN RESULTS
We identified 13 trials, of which five were eligible for inclusion. The five included studies randomized 474 women, of which 235 were randomized to knowledge and 249 to no knowledge of FFN.Preterm birth less than 37 weeks was significantly decreased with management based on knowledge of FFN results (15.6%) versus controls without such knowledge (28.6%; risk ratio 0.54; 95% confidence interval 0.34 to 0.87). All other outcomes for which there were available data (preterm birth at less than 34, 32, or 28 weeks; gestational age at delivery; birthweight less than 2500 grams; perinatal death; maternal hospitalization; tocolysis; steroids for fetal lung maturity; and time to evaluate) were similar in the two groups. No other maternal or neonatal outcome was available for meaningful analysis.
AUTHORS' CONCLUSIONS
Although FFN is commonly used in labor and delivery units to help in the management of women with symptoms of preterm labor, currently there is not sufficient evidence to recommend its use. Since this review found an association between knowledge of FFN results and a lower incidence of preterm birth before 37 weeks, further research should be encouraged.
Topics: Biomarkers; Female; Fetus; Fibronectins; Humans; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic
PubMed: 18843732
DOI: 10.1002/14651858.CD006843.pub2 -
Obstetrics and Gynecology Sep 2009To appraise critically the diagnostic accuracy of cervicovaginal fetal fibronectin as a short-term predictor of preterm birth in patients with signs and symptoms of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To appraise critically the diagnostic accuracy of cervicovaginal fetal fibronectin as a short-term predictor of preterm birth in patients with signs and symptoms of preterm labor.
DATA SOURCES
We searched MEDLINE, Current Contents, Index Medicus, EMBASE, the Cochrane Library, and syllabi from scientific meetings, and we performed manual searches of references from textbooks and of known primary and systematic review articles. We also contacted authors, experts on this subject, and the manufacturer.
METHODS OF STUDY SELECTION
We targeted cohort studies reporting data on the diagnostic accuracy of fetal fibronectin for the prediction of preterm birth within 7 days in symptomatic patients before 37 weeks of gestation. Case-control studies were excluded. The total analysis included 32 trials with 5,355 overall participants.
TABULATION, INTEGRATION, AND RESULTS
Two authors independently assessed methodological quality and constructed 2x2 tables for assessment of diagnostic measures. Pooled estimates of sensitivity, specificity, and likelihood ratios were obtained using a bivariate random effects model. Tests for publication bias and meta-regression were performed. Sensitivity analyses were performed for studies using different fetal fibronectin assays. The overall pooled estimates for sensitivity and specificity were 76.1% (95% confidence interval [CI] 69.1-81.9) and 81.9% (95% CI 78.9-84.5), respectively. Likelihood ratios for a positive and negative fetal fibronectin test were 4.20 (95% CI 3.53-4.99) and 0.29 (95% CI 0.22-0.38), respectively. Meta-regression analyses found that test accuracy was affected by prevalence, publication year, and blinding of studies. When subgroup analyses were performed for studies using the same assay, the results were similar.
CONCLUSION
The cervicovaginal fetal fibronectin assay has limited accuracy in predicting preterm birth within 7 days of sampling in symptomatic pregnant women.
Topics: Biomarkers; Chorion; Decidua; Female; Fibronectins; Humans; Predictive Value of Tests; Pregnancy; Premature Birth; Reproducibility of Results; Vaginal Smears
PubMed: 19701045
DOI: 10.1097/AOG.0b013e3181b47217