Combined vaginal progesterone and cervical cerclage in the prevention of preterm birth: a systematic review and meta-analysis.

OBJECTIVE: Vaginal progesterone and cervical cerclage are both effective interventions for reducing preterm birth. It is currently unclear whether combined therapy offers superior effectiveness than single therapy. This study aimed to determine the efficacy of combining cervical cerclage and vaginal progesterone in the prevention of preterm birth. DATA SOURCES: We searched Medline (Ovid), EMBASE (Ovid), PsycINFO (Ovid), CINAHL (EBSCOhost), Cochrane Library (Wiley), and Scopus (from their inception to 2020). STUDY ELIGIBILITY CRITERIA: The review accepted randomized and pseudorandomized control trials, nonrandomized experimental control trials, and cohort studies. High risk patients (shortened cervical length <25mm or previous preterm birth) who were assigned cervical cerclage, vaginal progesterone, or both for the prevention of preterm birth were included. Only singleton pregnancies were assessed. METHODS: The primary outcome was birth <37 weeks. Secondary outcomes included birth <28 weeks, <32 weeks and <34 weeks, gestational age at delivery, days between intervention and delivery, preterm premature rupture of membranes, cesarean delivery, neonatal mortality, neonatal intensive care unit admission, intubation, and birthweight. Following title and full-text screening, 11 studies were included in the final analysis. Risk of bias was assessed using the Cochrane Collaboration tool for assessing the risk of bias (ROBINS-I and RoB-2). Quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) tool. RESULTS: Combined therapy was associated with lower risk of preterm birth at <37 weeks than cerclage alone (risk ratio, 0.51; 95% confidence interval, 0.37-0.79) or progesterone alone (risk ratio, 0.75; 95% confidence interval, 0.58-0.96). Compared with cerclage only, combined therapy was associated with preterm birth at <34 weeks, <32 weeks, or <28 weeks, decreased neonatal mortality, increased birthweight, increased gestational age, and a longer interval between intervention and delivery. Compared with progesterone alone, combined therapy was associated with preterm birth at <32 weeks, <28 weeks, decreased neonatal mortality, increased birthweight, and increased gestational age. There were no differences in any other secondary outcomes. CONCLUSION: Combined treatment of cervical cerclage and vaginal progesterone could potentially result in a greater reduction in preterm birth than in single therapy. Further, well-conducted and adequately powered randomized controlled trials are needed to assess these promising findings.

McDonald versus Shirodkar cerclage technique in the prevention of preterm birth: A systematic review and meta-analysis.

BACKGROUND: Cervical cerclage has been used for decades to reduce preterm birth. The Shirodkar and McDonald cerclage are the most commonly used techniques with no current consensus on the preferred technique. OBJECTIVE: To compare the efficacy of the Shirodkar and McDonald cerclage techniques in preventing preterm birth. 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 analyses at 28, 32, 34 and 35 weeks. Secondary data were also collected on neonatal, maternal and obstetric outcomes. MAIN RESULTS: Seventeen papers were included: 16 were retrospective cohort studies and one was a randomised controlled trial. The Shirodkar technique was significantly less likely to result in preterm birth before 37 weeks than the McDonald technique (relative risk [RR] 0.91, 95% CI 0.85-0.98). This finding was supported by a statistically significant reduction in rates of preterm birth before 35, 34 and 32 weeks, PPROM, difference in cervical length, cerclage to delivery interval, and an increase in birthweight in the Shirodkar group. No difference was seen in preterm birth rates <28 weeks, neonatal mortality, chorioamnionitis, cervical laceration or caesarean section rates. The RR for preterm birth prior to 37 weeks was no longer significant when sensitivity analyses were performed removing studies with a serious risk of bias. However, similar analyses removing studies that utilised adjunctive progesterone strengthened the primary outcome (RR 0.83, 95% CI 0.74-0.93). CONCLUSION: Shirodkar cerclage reduces the rate of preterm birth prior to 35, 34 and 32 weeks' gestation when compared with McDonald cerclage; however, the overall quality of the studies in this review is low. Further, large, well-designed randomised controlled trials are required to address this important question to optimise care for women who may benefit from cervical cerclage.

The NOD Mouse Beyond Autoimmune Diabetes.

Autoimmune diabetes arises spontaneously in Non-Obese Diabetic (NOD) mice, and the pathophysiology of this disease shares many similarities with human type 1 diabetes. Since its generation in 1980, the NOD mouse, derived from the Cataract Shinogi strain, has represented the gold standard of spontaneous disease models, allowing to investigate autoimmune diabetes disease progression and susceptibility traits, as well as to test a wide array of potential treatments and therapies. Beyond autoimmune diabetes, NOD mice also exhibit polyautoimmunity, presenting with a low incidence of autoimmune thyroiditis and Sjögren's syndrome. Genetic manipulation of the NOD strain has led to the generation of new mouse models facilitating the study of these and other autoimmune pathologies. For instance, following deletion of specific genes or via insertion of resistance alleles at genetic loci, NOD mice can become fully resistant to autoimmune diabetes; yet the newly generated diabetes-resistant NOD strains often show a high incidence of other autoimmune diseases. This suggests that the NOD genetic background is highly autoimmune-prone and that genetic manipulations can shift the autoimmune response from the pancreas to other organs. Overall, multiple NOD variant strains have become invaluable tools for understanding the pathophysiology of and for dissecting the genetic susceptibility of organ-specific autoimmune diseases. An interesting commonality to all autoimmune diseases developing in variant strains of the NOD mice is the presence of autoantibodies. This review will present the NOD mouse as a model for studying autoimmune diseases beyond autoimmune diabetes.

Effectiveness of combined vaginal progesterone and cervical cerclage in preventing preterm birth: a systematic review and meta-analysis protocol.

INTRODUCTION: Preterm 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 ANALYSIS: Studies 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 DISSEMINATION: Not applicable due to nature of the study type. PROSPERO REGISTRATION NUMBER: CRD42020195975.

McDonald versus Shirodkar cerclage technique in women requiring a prophylactic cerclage: a systematic review and meta-analysis protocol.

BACKGROUND: Preterm birth (PTB) is the leading cause of death in children under five years. Spontaneous preterm birth (SPTB) is the major cause of preterm delivery. The key risk factors for SPTB are women who have a short cervix and women who have had previous preterm birth. Cervical cerclage has been used for several decades and has shown to decrease rates of preterm birth. The most commonly used cerclage techniques were described by Shirodkar and McDonald, with no current consensus on the preferred technique. The objective of this review is to determine and compare the effectiveness of both techniques. METHODS: Studies will be sourced from six electronic databases, as well as from experts in the field, reference lists, and grey literature. Eligible studies will include pregnant women, with a singleton or twin pregnancy, requiring a cervical cerclage, using either the Shirodkar or McDonald technique and run comparative analyses between the two techniques. Randomized control trials (RCT)s, non-randomized control trials, and cohort studies will be eligible. Two independent reviewers will conduct study screening at abstract and full-text level, data extraction and risk of bias assessment. Discrepancies will be resolved by a consensus third reviewer if required. Fixed-effects or random-effects models will be used where appropriate to synthesize results. Alternative synthesis methods will be investigated in instances where a meta-analysis is not appropriate, such as summarizing effect estimates, combining P values, vote counting based on direction of effect, or synthesis in narrative form. DISCUSSION: This review will synthesize the evidence on both the Shirodkar and McDonald cerclage method, and will help clinicians and health services to determine and deliver best practice antenatal care that has the potential to make an impact on preterm birth. SYSTEMATIC REVIEW REGISTRATION: PROSPERO on 25 of May, 2020 with registration number CRD42020177386.

Vaginal progesterone for prevention of preterm birth in asymptomatic high-risk women with a normal cervical length: a systematic review and meta-analysis protocol.

BACKGROUND: Preterm 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. METHODS: Studies 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. DISCUSSION: This 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 REGISTRATION: PROSPERO CRD42020152051.