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Background: Cervical cerclage has been used for decades to decrease rates of preterm birth. The Shirodkar and McDonald cerclage are the two most commonly used cerclage techniques with no current consensus on the preferred technique. Objective: To compare the efficacy of the two techniques. Search strategy: Studies were sourced from six electronic databases and reference lists. Selection criteria: Studies including women with a singleton pregnancy, requiring a cervical cerclage, using either the Shirodkar or McDonald technique that ran comparative analyses between the two techniques. Data collection and analysis: The primary outcome was preterm birth before 37 weeks, with sub analyses at 28, 32, 34 and 35 weeks. Secondary data was also collected on neonatal, maternal and obstetric outcomes. Main results: Seventeen papers were included - analysis showed the Shirodkar group had significantly less chance of preterm birth before 37 weeks (RR 0.91, 95% CI 0.85-0.98). This finding is reinforced by statistically significant reduction in rates of preterm birth before 37, 35, 34 and 32 weeks, PPROM (RR 0.87 ,95% CI 0.77 – 0.99), difference in cervical length (mean difference 5.25, 95% CI 4.68–5.83), cerclage to delivery interval (mean difference 10.79, 95% CI 8.20-13.38), and an increase in birthweight (mean difference 348 grams, 95% CI 291–406) in the Shirodkar group. Conclusion: Shirodkar cerclage leads to a significant reduction in preterm birth and delivers better maternal and neonatal outcomes when compared to McDonald cerclage. Funding: No funding was required for this review. Keywords: Cervical, Stitch, Cerclage, McDonald, Shirodkar, Preterm birth

The mechanism by which human labor is initiated in the presence of elevated circulating progesterone levels remains unknown. Recent evidence indicates that the progesterone-metabolizing enzyme, 20α-hydroxysteroid dehydrogenase (20α-HSD), encoded by the gene AKR1C1, may contribute to functional progesterone withdrawal. We found that AKR1C1 expression significantly increased with labor onset in term myometrium, but not in preterm myometrium. Among preterm laboring deliveries, clinically diagnosed chorioamnionitis was associated with significantly elevated AKR1C1 expression. AKR1C1 expression positively correlated with BMI before labor and negatively correlated with BMI during labor. Analysis by fetal sex showed that AKR1C1 expression was significantly higher in women who delivered male babies compared to women who delivered female babies at term, but not preterm. Further, in pregnancies where the fetus was female, AKR1C1 expression positively correlated with the mother’s age and BMI at the time of delivery. In conclusion, the increase in myometrial AKR1C1 expression with term labor is consistent with 20α-HSD playing a role in local progesterone metabolism to promote birth. Interestingly, this role appears to be specific to term pregnancies where the fetus is male. Upregulated AKR1C1 expression in the myometrium at preterm in-labor with clinical chorioamnionitis suggests that increased 20α-HSD activity is a mechanism through which inflammation drives progesterone withdrawal in preterm labor. The link between AKR1C1 expression and maternal BMI may provide insight into why maternal obesity is often associated with dysfunctional labor. Higher myometrial AKR1C1 expression in male pregnancies may indicate fetal sex-related differences in the mechanisms that precipitate labor onset at term.

This study assesses outcomes of colposcopy referrals for post‐coital, intermenstrual, or other abnormal bleeding with negative oncogenic human papillomavirus and negative to low‐grade cytology. Of 112 cases with median age of 34.5 years, cervical biopsy occurred in 19%, treatment of ectropion in 19%, endometrial sampling in 8%, polypectomy in 4%, and contraceptive change in 2%. No cervical or endometrial neoplasia was detected. Patients with bleeding symptoms and reassuring co‐test may instead attend a general gynaecology clinic.

BackgroundPreterm birth (PTB) is estimated to affect 14.9 million babies globally every year. Global rates of PTB continue to increase from 9.8 to 10.6% over a 15-year period from 2000 to 2014. Vaginal progesterone is commonly used by clinicians as a prevention strategy, with recent evidence affirming the benefit of vaginal (micronised) progesterone to prevent PTB in women with a shortened cervix (< 25 mm). Given the low incidence of a short cervix at mid-gestation in high-risk populations further evidence is required. The objective of this review is to determine if vaginal progesterone reduces spontaneous preterm birth (sPTB) before 37 weeks in asymptomatic high-risk women with a singleton pregnancy with a normal mid-gestation cervical length.MethodsStudies will be sourced from MEDLINE, Embase and Cochrane Register of Trials (CENTRAL) from their inception onwards with the search terms ‘progesterone’ and ‘preterm birth’. Studies will be screened and included if they assess vaginal progesterone compared to placebo in women with a normal cervical length. The primary outcome will be sPTB < 37 weeks, with secondary outcomes of sPTB < 34 weeks.Two independent reviewers will conduct study screening at abstract and full text level, data extraction and risk of bias assessment with disagreements resolved by an experienced researcher. The Mantel-Haenszel statistical method and random effects analysis model will be used to produce treatment effect odds ratios and corresponding 95% confidence intervals.DiscussionThis review will assess the current body of evidence and provide clarity regarding the potential benefits and best practice of use of vaginal progesterone in asymptomatic women with high-risk singleton pregnancies and normal cervical length.Trial registrationPROSPEROCRD42020152051

Background: Aspirin has been shown to reduce prevalence of both early‐onset pre‐eclampsia (ePET) and fetal growth restriction (FGR). Aims: To determine whether aspirin prescribed for risk of ePET reduces the prevalence of small for gestational age (SGA) neonates. Material and Methods: Two prospective cohorts were consecutively recruited in a large university hospital in Sydney. The Observational cohort (April 2010 to March 2012) validated an algorithm for ePET screening, where risk for ePET was modelled on history, mean arterial pressure, uterine artery pulsatility index and pregnancy‐associated plasma protein A. The Interventional cohort (April 2012 to December 2017) were screened and allocated women at high risk of developing ePET to aspirin 150 mg. The prevalence of preterm and term SGA was compared using regression analysis. Result: There were 3013 and 8424 women screened in the Observational and Interventional cohorts respectively. Women who screened high risk for ePET were three to four times more likely to give birth to a neonate classified as SGA in the Observational (6.8% vs 1.9%) and Interventional cohorts (6.0% vs 1.8%). In women who screened high risk, there were no statistically significant differences in the prevalence of SGA neonates (6.6% vs 6.0%; adjusted odds ratio 0.84 (0.50–1.42)) in women who received aspirin compared to women who did not. Conclusions: Women who screen high risk for ePET have an increased chance of delivering an SGA infant. A reduction in the prevalence of SGA neonates when aspirin was prescribed to women who screened high risk for ePET did not reach clinical significance in our cohort.

The onset of preterm labor is associated with inflammation. Previous studies suggested that this is distinct from the inflammation observed during term labor. Our previous work on 44 genes differentially expressed in myometria in term labor demonstrated a different pattern of gene expression from that observed in preterm laboring and nonlaboring myometria. We found increased expression of inflammatory genes in preterm labor associated with chorioamnionitis, but in the absence of chorioamnionitis observed no difference in gene expression in preterm myometria regardless of laboring status, suggesting that preterm labor is associated with different myometrial genes or signals originating from outside the myometrium. Given that a small subset of genes were assessed, this study aimed to use RNA sequencing and bioinformatics to assess the myometrial transcriptome during preterm labor in the presence and absence of chorioamnionitis.This study aimed to comprehensively determine protein-coding transcriptomic differences between preterm nonlaboring and preterm laboring myometria with and without chorioamnionitis.Myometria were collected at cesarean delivery from preterm patients not in labor (n=16) and preterm patients in labor with chorioamnionitis (n=8) or without chorioamnionitis (n=6). Extracted RNA from myometrial tissue was prepared and sequenced using Illumina NovaSeq. Gene expression was quantified by mapping the sequence reads to the human reference genome (hg38). Differential gene expression analysis, gene set enrichment analysis, and weighted gene coexpression network analysis were used to comprehensively interrogate transcriptomic differences and their associated biology.Differential gene expression analysis comparing preterm patients in labor with chorioamnionitis with preterm patients not in labor identified 931 differentially expressed genes, whereas comparing preterm patients in labor without chorioamnionitis with preterm patients not in labor identified no statistically significant gene expression changes. In contrast, gene set enrichment analysis and weighted gene coexpression network analysis demonstrated that preterm labor with and without chorioamnionitis was associated with enrichment of pathways involved in activation of the innate immune system and inflammation, and activation of G protein-coupled receptors. Key genes identified included chemotactic CYP4F3, CXCL8, DOCK2, and IRF1 in preterm labor with chorioamnionitis and CYP4F3, FCAR, CHUK, and IL13RA2 in preterm labor without chorioamnionitis. There was marked overlap in the pathways enriched in both preterm labor subtypes.Differential gene expression analysis demonstrated that myometria from preterm patients in labor without chorioamnionitis and preterm patients not in labor were transcriptionally similar, whereas the presence of chorioamnionitis was associated with marked gene changes. In contrast, comprehensive bioinformatic analysis indicated that preterm labor with or without chorioamnionitis was associated with innate immune activation. All causes of preterm labor were associated with activation of the innate immune system, but this was more marked in the presence of chorioamnionitis. These data suggest that anti-inflammatory therapy may be relevant in managing preterm labor of all etiologies.

Objective: To determine whether vaginal progesterone reduces spontaneous preterm birth (sPTB) before 37 weeks in asymptomatic high-risk women with a singleton pregnancy and normal mid-gestation cer...

IntroductionPreterm birth (PTB) is the leading cause of death in children under 5 years. Preventive therapies targeted towards women with risk factors such as a prior PTB or a short cervix reduce the rate of PTB. Cervical cerclage, vaginal progesterone and a combination of the two have been used with no consensus as to whether combined treatment is more effective than any single treatment alone. The objective of this review is to determine the efficacy of combined treatment compared with cerclage alone and combined treatment compared with progesterone alone.Methods and analysisStudies will be sourced from the electronic databases Medline (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Scopus, CINAHL (EBSCOhost) and Cochrane Library (Wiley) and reference lists. We will not exclude any papers due to publication date. Randomised control trials (RCTs), non-RCTs and cohort studies assessing single therapy (either progesterone or cerclage) versus combined therapy in women with a singleton pregnancy will be included. Two independent reviewers will conduct study screening (at abstract and full-text level), data extraction and risk of bias assessment with disagreements resolved by an experienced researcher. Random or fixed effects models will be used depending on data heterogeneity and data will be presented as risk ratio for dichotomous data or mean difference for continuous data with a CI of 95% used for all outcomes.Ethics and disseminationNot applicable due to nature of the study type.PROSPERO registration numberCRD42020195975.

The onset of the term human parturition involves myometrial gene expression changes to transform the uterus from a quiescent to a contractile phenotype. It is uncertain whether the same changes occur in the uterus during preterm labor.This study aimed to compare the myometrial gene expression between term and preterm labor and to determine whether the presence of acute clinical chorioamnionitis or twin gestation affects these signatures.Myometrial specimens were collected during cesarean delivery from the following 7 different groups of patients: term not in labor (n=31), term labor (n=13), preterm not in labor (n=21), preterm labor with acute clinical chorioamnionitis (n=6), preterm labor with no acute clinical chorioamnionitis (n=9), twin preterm not in labor (n=8), and twin preterm labor with no acute clinical chorioamnionitis (n=5). RNA was extracted, reverse transcribed and quantitative polymerase chain reactions were performed on 44 candidate genes (with evidence for differential expression in human term labor) using the Fluidigm platform. Computational analysis was performed using 2-class unpaired Wilcoxon tests and principal component analysis.Computational analysis revealed that gene expression in the preterm myometrium, irrespective of whether in labor or not in labor, clustered tightly and is clearly different from the term labor and term not-in-labor groups. This was true for both singleton and twin pregnancies. Principal component analysis showed that 57% of the variation was explained by 3 principal components. These 44 genes interact in themes of prostaglandin activity and inflammatory signaling known to be important during term labor, but are not a full representation of the myometrium transcriptional activity.The myometrial contractions associated with preterm labor are associated with a pattern of gene expression that is distinct from term labor. Therefore, preterm labor may be initiated by a different myometrial process or processes outside the myometrium.

The establishment and maintenance of pregnancy rely on a number of hormones, including progesterone and human chorionic gonadotrophin. Throughout gestation, pregnancy is under a progesterone block, which maintains uterine quiescence to permit fetal growth and maturation. As a woman approaches term, there is a functional progesterone withdrawal and functional estrogen activation that upregulate contraction-associated proteins. These hormonal changes appear to coincide with inflammatory changes that further encourage the transformation of the uterus from a resting to a contractile phenotype. During parturition, the release of oxytocin and prostaglandins enhances contractions, and increasing gap junctions allows the synchronization of myocyte activity and rhythmic contractions of the whole uterus. A number of factors can initiate preterm labor, including infection, sterile inflammation, and blood and cellular senescence.

Lithium-sulfur batteries (LSBs) have been of paramount interest due to their high specific energy, environmental benignity, and low-cost production as a promising candidate among the next generation of rechargeable batteries. Even they represent one of the most mature battery systems, the high discharging capacity and stable long cycling performance cannot be fully realized, especially under practical conditions, which hamper their entrance to the energy storage market in the near future. Solutions to unsolved issues that arise during the complex and multiphase conversion-type chemistry involved in LSBs are still being researched, including irreversible relocation of polysulfides, slow reaction kinetics, and low reliability of lithium anode. Achieving a scientific understanding of the current challenges toward the individual components in cells and the existing status of research strategies is vitally important to the development of LSBs. In this critical review, we attempt to summarize our current comprehension in this field, analyze and classify possible strategies to address the main concerns in the research on LSBs, and introduce design pathways for the further improvement of LSBs toward practical applications. Advanced methodology toward the synthesis of desirable host materials of the electrode with encapsulation effect via nanostructured design; the tailorable adsorption and catalysis property; chemical confinements function by covalent linking; modification of electronic structure, heteroatom doping, and defects are overviewed and highlighted. Methods for regulating salt anions, solvents, auxiliary additives in electrolytes, and the constructions of interlayers toward deployable separator and anode enabling interfacial protection; the establishment of novel electrode fabrication and functional batteries assembly systems technologies are discussed for the further development of viable LSBs. The strategies and perspectives outlined in this review will provide further research directions and help to achieve the aim of exploring high-performance LSBs technology with high energy density and long cycling stability.

This paper examines the interaction between short-run return reversals, momentum and idiosyncratic volatility in the Australian market. We confirm that stocks with high idiosyncratic volatility earn low average returns over the next month. Unlike US studies which attribute this negative relation to short-run return reversals, we find that it is partly caused by a group of loser stocks (formed over one month) which continue to exhibit negative return drift (over the next month). We also investigate whether these stocks continue to display negative returns over longer horizons. In turn, we broaden our study to examine whether the momentum effect is persistent in stocks with high idiosyncratic volatility. We find that stocks with high idiosyncratic volatility realize significant abnormal momentum returns over a six-month holding period relative to stocks with low idiosyncratic volatility. As we document the persistence of momentum profits amongst stocks with high idiosyncratic volatility, our work contributes to the existing literature which suggests that idiosyncratic volatility is an important limit to the arbitrage of the momentum effect.