Premature Cervical Ripening Research Articles

Cervical Collagen Network Porosity Assessed by SHG Endomicroscopy Distinguishes Preterm and Normal Pregnancy - a Pilot Study.

Preterm birth (PTB) remains a pressing global health concern associated with premature cervical ripening and weakened cervical mechanical strength. Second harmonic generation (SHG) microscopy has proved instrumental in tracking progressive changes in cervical collagen morphology during pregnancy. To translate this imaging modality into clinical practice, we have developed a flexible SHG endomicroscope for label-free visualization of cervical collagen architecture. This study aims to assess the feasibility of our SHG endomicroscope for non-invasive differentiation of normal and PTB mouse models, with the ultimate goal of enabling early diagnosis and risk assessment of PTB in vivo. in this pilot investigation, we conducted endomicroscopic SHG imaging on frozen cervical tissue sections and intact cervices resected from both normal pregnant mice and mifepristone-induced PTB mouse models, and then analyzed the acquired images to identify collagen morphology characteristics associated with abnormal cervical collagen remodeling. quantitative image analysis revealed significantly altered collage spatial distribution, larger collagen fiber diameter and pore size, along with reduced pore numbers in SHG endomicroscopy images from PTB mouse models compared to normal pregnant mice. Similar trends were consistent across SHG endomicroscopy images of subepithelial collagen fibers acquired directly from intact cervices. overall, the experiment results underscore the potential of SHG endomicroscopy, coupled with quantitative image analysis, for clinically evaluating cervical collagen remodeling and PTB risk.

Characteristic impairment of progesterone response in cultured cervical fibroblasts obtained from patients with refractory cervical insufficiency

Preterm birth (PTB) is the leading cause of neonatal mortality, and reducing the PTB rate is one of the most critical issues in perinatal medicine. Cervical insufficiency (CI), a major cause of PTB, is characterised by premature cervical ripening in the second trimester, followed by recurrent pregnancy loss. Although multiple clinical trials have suggested that progesterone inhibits cervical ripening, no studies have focused on progesterone-induced molecular signalling in CI. Here, we established a primary culture system for human uterine cervical fibroblasts using a sample of patients with refractory innate CI who underwent transabdominal cervical cerclage and patients with low Bishop scores who underwent elective caesarean section as controls. RNA sequencing showed that the progesterone response observed in the control group was impaired in the CI group. This was consistent with the finding that progesterone receptor expression was markedly downregulated in CI. Furthermore, the inhibitory effect of progesterone on lipopolysaccharide-induced inflammatory stimuli was also impaired in CI. These results suggest that abnormal cervical ripening in CI is caused by the downregulation of progesterone signalling at the receptor level, and provide a novel insight into the molecular mechanism of PTB.

Metabonomics profile analysis in inflammation-induced preterm birth and the potential role of metabolites in regulating premature cervical ripening

BackgroundPreterm birth (PTB) is the primary cause of infant morbidity and mortality. Moreover, previous studies have established that PTB is related to premature cervical ripening. However, the underlying mechanism remains to be elucidated. This study sought to identify differentially expressed metabolites and investigate their potential biological functions in PTB.MethodsPregnant C57BL/6 J mice were treated with either LPS or normal saline and cervical alterations before labor were detected by staining. Metabolic profiles in the plasma of PTB and control mice were examined through non-targeted metabonomics analyses, quantitative polymerase chain reaction and immunofluorescence staining were performed on human cervical smooth cells.ResultsThe study demonstrated that the mRNA and protein levels of α-SMA, SM-22, and calponin in cervical smooth muscle cells of PTB mice were lower while OR was higher at both mRNA and protein levels compared to the CTL group. A total of 181 differentially expressed metabolites were analyzed, among them, 96 were upregulated, while 85 were downregulated in the PTB group. Differentially expressed metabolites may play a role in STAT3, RhoA, mTOR, TGF-β, and NK-κB signaling pathways. Furthermore, when treated with taurine, the levels of α-SMA and SM-22 in human cervical smooth muscle cells were elevated, whereas that of connexin-43 was decreased.ConclusionOur study highlighted the changes of metabolites in the peripheral blood changed prior to PTB and revealed that these differentially expressed metabolites might participate in the development of premature cervical ripening. Taurine was identified as an important metabolite may modulate human cervical smooth muscle cells. Our study provided new insights into the mechanism underlying premature cervical ripening in PTB.

Breaking Down the Barrier: The Role of Cervical Infection and Inflammation in Preterm Birth

Approximately 40% of cases of spontaneous preterm birth (sPTB) are associated with ascending intrauterine infections. The cervix serves as a physical and immunological gatekeeper, preventing the ascent of microorganisms from the vagina to the amniotic cavity. The cervix undergoes remodeling during pregnancy. It remains firm and closed from the start until the late third trimester of pregnancy and then dilates and effaces to accommodate the passage of the fetus during delivery. Remodeling proceeds appropriately and timely to maintain the pregnancy until term delivery. However, risk factors, such as acute and chronic infection and local inflammation in the cervix, may compromise cervical integrity and result in premature remodeling, predisposing to sPTB. Previous clinical studies have established bacterial (i.e., chlamydia, gonorrhea, mycoplasma, etc.) and viral infections (i.e., herpesviruses and human papillomaviruses) as risk factors of PTB. However, the exact mechanism leading to PTB is still unknown. This review focuses on: (1) the epidemiology of cervical infections in pregnant patients; (2) cellular mechanisms that may explain the association of cervical infections to premature cervical ripening and PTB; (3) endogenous defense mechanisms of the cervix that protect the uterine cavity from infection and inflammation; and (4) potential inflammatory biomarkers associated with cervical infection that can serve as prognostic markers for premature cervical ripening and PTB. This review will provide mechanistic insights on cervical functions to assist in managing cervical infections during pregnancy.

Oxidative stress promotes cellular damages in the cervix: implications for normal and pathologic cervical function in human pregnancy†.

A physiologic increase in reactive oxygen species throughout pregnancy is required to remodel the cervix. Oxidative stress can cause cellular damage that contributes to dysfunctional tissue. This study determined the oxidative stress-induced cell fate of human cervical epithelial and cervical stromal cells. We treated the ectocervical and endocervical epithelial cells and cervical stromal cells with cigarette smoke extract, an oxidative stress inducer, for 48 h. Cell viability (crystal violet assay); cell cycle, apoptosis, and necrosis (flow cytometry); senescence (senescence-associated β-galactosidase staining); autophagy (staining for autophagosome protein, microtubule-associated protein 1 light chain 3B); stress signaler p38 mitogen-activated protein kinases pathway activation (western blot analyses); and inflammation by measuring interleukin-6 (enzyme-linked immunosorbent assay) were conducted after 48 h of cigarette smoke extract treatment. Oxidative stress induced reactive oxygen species production in cervical cells, which was inhibited by N-acetylcysteine. Oxidative stress promoted cell cycle arrest and induced necrosis in cervical cells. High senescence and low autophagy were observed in cervical stromal cells under oxidative stress. Conversely, senescence was low and autophagy was high in endocervical epithelial cells. Oxidative stress induced p38 mitogen-activated protein kinases (p38MAPK) activation in all cervical cells but only increased interleukin-6 production by the ectocervical epithelial cells. Inhibition of interleukin-6 production by a p38 mitogen-activated protein kinases inhibitor confirmed the activation of an oxidative stress-induced pathway. In conclusion, oxidative stress can promote cell death and sterile inflammation that is mediated by p38 mitogen-activated protein kinases activation in the cellular components of the cervix. These cellular damages may contribute to the normal and premature cervical ripening, which can promote preterm birth.

916 The association between preterm birth and ultrasound visualization of the cervical gland area

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality. Yet, transvaginal ultrasound (TVUS) cervical length (CL) screening suboptimally predicts spontaneous PTB (SPTB). Abnormal remodeling of glandular crypts along the cervical canal may contribute to increased PTB risk via premature cervical ripening, which may correspond to no visualizable cervical gland area (CGA) on TVUS (Figure 1). This study aims to determine if no visualizable (“absent”) CGA at CL screening is predictive of PTB. We performed a retrospective cohort study of pregnant women carrying a singleton gestation who had CL screening between 180/7 – 236/7 weeks gestation and delivered a live neonate at a single academic institution between 1/1/18 and 12/31/18. 1000 of the most recent deliveries in 2018 were screened for inclusion. Patients with uterine anomalies, cerclage, suboptimal imaging, or with indicated preterm delivery were excluded. TVUS images were assessed for CL, CGA visualization, and if present, quantitative CGA measurements were performed. The primary outcome was SPTB prior to 37 weeks. Absent and present CGA groups were compared using χ2, Fischer’s exact, T-test, and logistic regression with significance at p<0.05. 784 women were included. Demographic and medical characteristics of the sonographically absent and present CGA groups were similar. The absent CGA group was more likely parous and to receive progesterone supplementation (77 vs 40% and 17 vs 4% respectively, p=0.03). Overall PTB rate was 2.7% and rate of absent CGA was 2.3%. Absent CGA was significantly associated with delivery <37, <34, and <32 weeks (p<0.005) (Table 1). Quantitative CGA width, length, and area did not individually correlate with PTB. A multiple logistic regression model demonstrated 8% improvement for prediction of PTB <37 weeks with the addition of CGA evaluation compared to CL alone (p<0.001). Patients with no visualizable CGA were more likely to experience spontaneous preterm delivery. Assessment of CGA visualization may improve the performance of CL screening for predicting SPTB.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The intervention effect of nicotine on cervical fibroblast-myofibroblast differentiation in lipopolysaccharide-induced preterm birth model through activating the TGF-β1/Smad3 pathway

Currently, the clinical treatment of preterm birth, mainly using uterine contraction inhibitors, does not fundamentally reduce the incidence of premature birth (PTB). Premature cervical ripening is an important factor in PTB. We previously found that nicotine-treated pregnant murine had significant cervical resistance to stretch and higher collagen cross-links compared to the control animals, and nicotine prolonged gestation and inhibited cervical ripening. However, the regulatory effects of nicotine on premature cervical ripening and its role in PTB remain unclear. To investigate the effects of nicotine on cervical TGF-β1/Smad3 pathway and fibroblast-myofibroblast differentiation regulated by this pathway in PTB-like models. Intraperitoneal injection with 15 μg lipopolysaccharide (LPS) in 200 μl PBS into pregnant mice was used to induce the PTB-like model. Mice were randomly divided into four groups: control group, LPS-treated group, LPS + Nicotine co-treated group and LPS + Nicotine+α-BGT co-treated group. Pregnancy outcomes were monitored. The collagen content was assessed by Picrosirius red staining. Expressions of genes and proteins in the TGF-β/Smad3 pathway were detected by double immunofluorescence staining and quantitative Real-time PCR (qRT-PCR). myofibroblast differentiation were investigated by double immunofluorescence staining and qRT-PCR. Ultrastructures were analyzed by conventional transmission electron microscopy. The rate of PTB and neonatal mortality at birth was significantly higher in the LPS-treated group than in the control group; collagen content also decreased remarkably; the expression of TGF-β1 in macrophages and p-Smad3 in fibroblasts were reduced; the expression of α-smooth muscle actin (α-SMA, markers for activated fibroblasts) was down-regulated while the expression of calponin and smoothelin (markers for fibroblasts at rest) was up-regulated. Nicotine improved pregnancy outcomes and inhibited collagen degradation, activated the TGF-β1/Smad3 pathway and promoted cervical fibroblast-myofibroblast differentiation in PTB-like mice; such effects could be reversed by α-bungarotoxin (α-BGT). Nicotine inhibited premature cervical ripening in PTB-like models in relation with up-regulating the TGF-β/Smad3 pathway and promoting fibroblast to differentiate into myofibroblasts.

Contractile function of the cervix plays a role in normal and pathological pregnancy and parturition

The cervix plays an integral part in ensuring the proper timing of pregnancy and parturition. It maintains the fetus within the uterus and protects it from pathogens present in the vaginal canal. The cervix undergoes extensive remodeling during pregnancy and parturition. This process is associated with collagen degradation, an increase in immune cell response and inflammation in the cervix. However, our understanding of the role of cervical smooth muscles and their contribution to cervical remodeling is still lacking. In this paper, we propose that the active contractile function of the cervix influences cervical remodeling during pregnancy and parturition. Contraction of the cervical smooth muscles helps the cervix to remain firm and closed during early pregnancy, while relaxation of the cervical smooth muscles help facilitate cervical dilatation during labor. This contractile function of the cervix can be influenced by endocrine signals, such as estrogen, progesterone, and oxytocin; local paracrine signals, such as inflammatory chemokines and cytokines, as well as extracellular vesicles, such as exosomes and ectosomes; and by pharmacological agents used for cervical ripening and the induction of labor. A deeper understanding of the role of smooth muscles in cervical remodeling can help us elucidate the cellular processes in the cervix during pregnancy and parturition. This can also help in finding critical signaling pathways and therapeutic targets in the cervix that may decrease the rates of premature cervical ripening and preterm birth.

α7nAChR Prevents Premature Cervical Ripening by Inducing M2 Macrophage Polarization and Myofibroblast Differentiation

Clinical treatment of spontaneous preterm birth (sPTB) is usually dependent on drugs that inhibit uterine contractions. Such therapy is only effective in the short-term; inhibition of premature cervical maturation may represent a more effective approach to the prevention of sPTB. Cervical remodeling in sPTB is associated with invasion of macrophages, which produce proinflammatory cytokines. Activation of the alpha-7 nicotinic acetylcholine receptor (α7nAChR) alleviates the inflammatory response and prevents preterm labor, but the underlying mechanisms remain unclear. In our mouse model of lipopolysaccharide (LPS) induced preterm birth, α7nAChR expression on cervical macrophages was decreased, the number of M1 cervical macrophages was increased, and cervical collagen content was decreased compared to normal pregnant controls. Activation of α7nAchR by nicotine increased polarization of cervical macrophages toward the anti-inflammatory M2 phenotype, possibly by suppressing activation of the MAP kinases JNK and ERK1/2 and nuclear translocation of NF-κB and rescuing the inhibited JAK2/STAT3 and PI3K/AKT pathways. α7nAchR activation also maintained components of the cervical extracellular matrix, including collagen and α-smooth muscle actin; these actions were associated with upregulation of the TGF-β1/Smad3 pathway and myofibroblast differentiation. The effects of nicotine were reversed by the α7nAChR antagonist α-BGT. Findings from this study suggest that upregulating α7nAChR activity in macrophages strengthens crosstalk between macrophages and fibroblasts, and inhibits premature cervical ripening during preterm labor. Funding Statement: This study was supported by the National Natural Science Foundation of China (81971417, 81901568 and 81871181), the Guangdong Health and Family Planning Commission Project (A2017332), the Hospital fund project from Guangzhou Women and Children’s Medical Center (Pre-NSFC-2016-001), and the Guangzhou Science and Technology Project (2016A020218001). Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of the Guangzhou Women and Children Medical Center (No. 2018041701 and No. 201922200), and all included patients provided written informed consent. All animal protocols were approved by the Committee on the Ethics of Animal Experiments of Guangzhou Medical University (Permit Number: 2012–50).

Cervical cerclage for singleton pregnant patients on vaginal progesterone with progressive cervical shortening

Premature cervical ripening plays a significant role in spontaneous preterm birth. Vaginal progesterone is the recommended treatment in singleton pregnancy with incidental short cervix. There is lack of evidence on whether it is beneficial to reinforce the cervix with cerclage when the cervical length becomes progressively shortened <10 mm while on vaginal progesterone. Our aims are to determine whether cerclage with vaginal progesterone will: (1) reduce the overall spontaneous preterm birth rate, (2) prolong pregnancy latency, and (3) improve neonatal outcomes compared to vaginal progesterone alone. This was a retrospective cohort study at the University of Illinois at Chicago of all women with singleton pregnancy on vaginal progesterone for incidental short cervix, cervical length <20 mm. Only those with progressive cervical length shortening <10 mm who delivered at the University of Illinois at Chicago from January 2013 through December 2016 were included. The decision to perform cerclage was based on individual physician preference. Demographic data; information on serial cervical length status; medical, obstetric, and social history; cerclage vs no cerclage; and neonatal outcomes were compared. A total of 310 women with incidental short cervix on vaginal progesterone were identified, and of these, 75 had progressive shortening cervical length <10 mm and met inclusion criteria. Among the women with extremely shortened cervical length <10 mm, 36 women (48%) had cervical cerclage plus vaginal progesterone, and 39 women (52%) continued on vaginal progesterone alone. The baseline characteristics, mean cervical length (5.06 vs 5.52 mm), and mean gestational age at diagnosis of extreme short cervix (21.5 vs 21.3 weeks) were similar between women who received cerclage vs those who did not, respectively. The mean gestational age at delivery was significantly greater for those with cerclage (34 weeks and 3 days vs 27 weeks and 2 days; P < .001). The rate of spontaneous preterm birth at <37, 35, 32, 28, and 24 weeks were significantly lower in the cerclage group: 44.1% vs 84.2%, 38.2% vs 81.6%, 23.5% vs 78.9%, 14.7% vs 63.2%, and 11.8% vs 39.5%, respectively. The rate of spontaneous preterm birth <37 weeks remained significant after controlling for confounders (relative risk, 0.11; 95% confidence interval, 0.03-0.41; P < .001). The average pregnancy latency was 14 weeks in the cerclage combined with vaginal progesterone group compared to vaginal progesterone alone group. Neonatal intensive care unit admission and development of respiratory distress syndrome were significantly lower in the cerclage group compared to vaginal progesterone alone group: 13 (36.1%) vs 23 (65.7%) (relative risk, 0.55; 95% confidence interval, 0.34-0.90; P= .018) and 8 (22.2%) vs 17 (43.6%) (relative risk, 0.59; 95% confidence interval, 0.29-0.90; P= .027), respectively. Neonates of women with cerclage were also significantly less likely to develop necrotizing enterocolitis or experience neonatal death. Our study showed that cerclage plus vaginal progesterone in women with extremely shortened cervix significantly decreased overall spontaneous preterm birth rates, prolonged pregnancy latency by 2-fold, and decreased the overall neonatal morbidity and mortality.

Correction: Cervical HSV-2 infection causes cervical remodeling and increases risk for ascending infection and preterm birth.

[This corrects the article DOI: 10.1371/journal.pone.0188645.].

Cervical HSV-2 infection causes cervical remodeling and increases risk for ascending infection and preterm birth.

Preterm birth (PTB), or birth before 37 weeks gestation, is the leading cause of neonatal mortality worldwide. Cervical viral infections have been established as risk factors for PTB in women, although the mechanism leading to increased risk is unknown. Using a mouse model of pregnancy, we determined that intra-vaginal HSV2 infection caused increased rates of preterm birth following an intra-vaginal bacterial infection. HSV2 infection resulted in histological changes in the cervix mimicking cervical ripening, including significant collagen remodeling and increased hyaluronic acid synthesis. Viral infection also caused aberrant expression of estrogen and progesterone receptor in the cervical epithelium. Further analysis using human ectocervical cells demonstrated a role for Src kinase in virus-mediated changes in estrogen receptor and hyaluronic acid expression. In conclusion, HSV2 affects proteins involved in tissue hormone responsiveness, causes significant changes reminiscent of premature cervical ripening, and increases risk of preterm birth. Studies such as this improve our chances of identifying clinical interventions in the future.

Distinct reorganization of collagen architecture in lipopolysaccharide-mediated premature cervical remodeling.

Previous work has identified divergent mechanisms by which cervical remodeling is achieved in preterm birth (PTB) induced by hormone withdrawal (mifepristone) or lipopolysaccharide (LPS). Our current study aims to document how collagen architecture is modified to achieve premature cervical remodeling in mice treated with LPS as a model of infection-induced inflammation. Cervices were collected on gestation day (d) 15 from mice with premature cervical ripening induced by LPS and compared to d15 and d18 controls as well as a hormone withdrawal PTB model. Second harmonic generation (SHG) and electron microscopy were utilized for visualization of collagen morphology and ultrastructure. LPS-mediated premature cervical ripening is characterized by unique structural changes in collagen fiber morphology. LPS treatment increased the interfibrillar spacing of collagen fibrils. A preferential disruption of collagen fiber architecture in the subepithelial region compared to midstroma region was evidenced by increased pores lacking collagen signal in SHG images in the LPS-treated mice. Coinciding with this alteration, the infiltration of neutrophils was concentrated in the subepithelial stromal region as compared to midstromal region implicating the potential role of immune cells to extracellular matrix reorganization in inflammation-induced preterm cervical ripening. The current study demonstrates a preferential disorganization of collagen interfibrillar spacing and collagen fiber structure in LPS-mediated ripening.

Evolution of Gene Expression in the Uterine Cervix related to Steroid Signaling: Conserved features in the regulation of cervical ripening

The uterine cervix is the boundary structure between the uterus and the vagina and is key for the maintenance of pregnancy and timing of parturition. Here we report on a comparative transcriptomic study of the cervix of four placental mammals, mouse, guinea pig, rabbit and armadillo, and one marsupial, opossum. Our aim is to investigate the evolution of cervical gene expression as related to putative mechanisms for functional progesterone withdrawal. Our findings are: 1) The patterns of gene expression in eutherian (placental) mammals are consistent with the notion that an increase in the E/P4 signaling ratio is critical for cervical ripening. How the increased E/P4 ratio is achieved, however, is variable between species. 2) None of the genes related to steroid signaling, that are modulated in eutherian species, change expression during opossum gestation. 3) A tendency for decreased expression of progesterone receptor co-activators (NCOA1, -2 and -3, and CREBBP) towards term is a shared derived feature of eutherians. This suggests that parturition is associated with broad scale histone de-acetylation. Western-blotting on mouse cervix confirmed large scale histone de-acetylation in labor. This finding may have important implications for the control of premature cervical ripening and prevention of preterm birth in humans.

IGFBP-1 marker of cervical ripening and predictor of preterm birth

Aim To establish a correlation between positive values of IGFBP-1(>10 mg/L, Actim Partus Test, APT) and premature cervical ripening in imminent preterm labor. Methods A prospective study was conducted in primary health care centers in Tuzla, Gynecology and Obstetrics Clinic of the University Clinical Centre in Tuzla and General Hospital Tešanj. The study included 50 women (singleton pregnancy, 28-37 week) with imminent preterm labor diagnosed by cervical biometry and modified Bishop score) (examinees) and 30 healthy pregnant women (control group). The presence of IGFBP-1 was tested in cervical secretion several times in weeks 28-37 until a positive test was shown. Results IGFBP-1 was positive in 43 (86%) examinees and in six (20%) patients from the control group (p=0.001). In 31 (62%) examinees APT was positive in weeks 28-30, and in nine (18%) in weeks 31- 33, while three (6%) examinees had positive test in 34-37 week; in the control group, three (10%) were tested positive in weeks 31-33 and three (10%) in weeks 34-37. At first testing (28-30 weeks) APT was statistically significantly more frequently positive in the examined group (p<0.05). Later, tests did not find statistically significant difference in the frequency of positivity between the control and examined group (p=0.08). Conclusion Elevated values of IGFBP -1 in cervical secretion were highly correlated with preterm labor. Screening for IGFBP could help in preventing preterm labor and its complications.

Fish Oils as a Population Based Strategy to Reduce Early Preterm Birth

Preterm birth remains the leading challenge in perinatal mortality and morbidity in the developing world. Existing strategies to reduce preterm birth target at risk women and are not suitable as a population strategy because of their expense. However, more than 50% of preterm births are to women with no pre-existing risk factors. Therefore, population based strategies are desirable. We present the evidence for fish oil supplements as a population based strategy to reduce early preterm birth. Fish oils act as competitive antagonists of series two prostaglandins and can target premature cervical ripening as a cause of early preterm birth. These oils are safe and well tolerated by pregnant women. Analyses from randomised trials show that fish oils may be promising as a population based strategy for the prevention of early preterm birth.

Cervical remodeling in term and preterm birth: insights from an animal model

Proper cervical function is essential for a normal pregnancy and birth to occur. Understanding the mechanisms that take place in normal pregnancy will allow a better comprehension of the complications involved in premature cervical remodeling and lead to better methods of diagnostics and prevention for preterm birth. Unfortunately, human samples are not easily available, and samples that are collected are often confounded by variations in timing and region of cervix from which sample is collected. Animal models, specifically the mouse, have facilitated a great deal of exploration into the mechanisms of cervical function and pathways of preterm birth. This review highlights some of the groundbreaking discoveries that have arisen from murine research including 1) the identification of early pregnancy changes in collagen fibril processing and assembly that result in progressive modifications to collagen architecture with subsequent loss of tissue stiffness during pregnancy, 2) the determination that immune cells are not key to cervical ripening at term but have diverse phenotypes and functions in postpartum repair, and 3) the finding that the process of preterm cervical ripening can differ from term ripening and is dependent on the etiology of prematurity. These findings, which are relevant to human cervical biology, provide new insights that will allow targeted studies on the human cervix as well as identify potential biomarkers for early detection of premature cervical ripening and development of improved therapies to prevent premature ripening of the cervix and subsequent preterm birth.

Digital examination and transvaginal scan – competing or complementary for predicting preterm birth?

The transvaginal ultrasonographic cervix scan has partly replaced digital examination for diagnosing preterm birth; conflicting results are reported about their respective contribution to birth prediction. To review the predictive value of digital examination and transvaginal scan in low-risk asymptomatic and symptomatic women before treatment. A literature search of PubMed, Web of Science and Cochrane Databases from 1994 to 2010 and selected reference lists was carried out. Randomized controlled trials, retrospective and prospective cohort studies, outcome research and studies of clinical decision rules were included. The studies showed that methods for the estimation of cervical ripening are not unequivocal nor is the nomenclature for digital examination. Evidence for routine screening for premature cervical ripening in asymptomatic low-risk women is insufficient. Knowledge of ultrasonographic cervical length in symptomatic women was not associated with a significantly improved outcome in symptomatic women, but may help to reduce length of hospitalization. In women selected by the Bishop Score, a transvaginal scan may reduce the number of false-positive results. Clarification on the methods for performing cervical assessment is needed. The evidence that transvaginal scanning of the cervix improves outcome in symptomatic women is insufficient. The methods for assessing cervical change should be regarded as complementary.

Controlled Fine Needle Biopsy of the Uterine Cervix During Pregnancy

Cervical sampling could furnish tissue-based information regarding premature cervical ripening and effacement. This report assesses the effect of cervical fine needle biopsy (FNB) in the evaluation of cervical shortening. Retrospective cohort study evaluating adverse events during the first week following FNB in women with short cervix. Patients with a cervical length(CL) ≤25 mm had a cervical FNB between 16 and 24 weeks. The risk of FNB was compared to a control group that was similarly evaluated but did not undergo FNB. One hundred and thirty-two FNBs were performed in 94 participants. The mean gestational age and CL at enrollment were 20.4 ± 2.3 weeks and 15.7 ± 0.6 mm. Within 7 days of FNB, there were 3 adverse events (2.3%) in the study group compared to 5 in the control group (2.1%). FNB of the cervix in high risk gravidae is feasible in clinical situations. It did not increase the risk of adverse events compared to women studied under a similar protocol without FNB.

The Molecular Mechanisms of Cervical Ripening Differ between Term and Preterm Birth

In the current study, the mechanisms of premature cervical ripening in murine models of preterm birth resulting from infection or early progesterone withdrawal were compared with the process of term cervical ripening. Tissue morphology, weight, gene expression, and collagen content along with immune cell populations were evaluated. Premature ripening induced by the progesterone receptor antagonist mifepristone results from an acceleration of processes in place during term ripening as well as partial activation of proinflammatory and immunosuppressive processes observed during postpartum repair. In contrast to term or mifepristone-induced preterm ripening, premature ripening induced in an infection model occurs by a distinct mechanism which is dominated by an influx of neutrophils into the cervix, a robust proinflammatory response and increased expression of prostaglandin-cyclooxygenase-endoperoxide synthase 2, important in prostaglandin biosynthesis. Key findings from this study confirm that cervical ripening can be initiated by more than one mechanism and is not necessarily an acceleration of the physiologic process at term. These results will influence current strategies for identifying specific etiologies of preterm birth and developing subsequent therapies.