The Use of Evening Primrose Oil for Cervical Ripening in Low-Risk Women with Term Pregnancy: A Randomized Double-Blinded Controlled Trial.

BACKGROUND: Several methods have been developed for cervical ripening. The data regarding the efficiency of evening primrose oil (EPO) are inconsistent. The purpose of this study was to investigate the outcomes of EPO use on cervical ripening in low-risk women with term pregnancy. PATIENTS AND METHODS: Low-risk term pregnant women referred to the obstetrics clinic of Imam Hossein Hospital in Tehran who were eligible according to the inclusion were randomized either to the case or control group. The case group received 1,000 mg vaginal EPO capsule, and the other group received a vaginal placebo capsule daily, similar to the original drug. The primary outcome was Bishop score, while the duration of labor phases and the inducing procedures were the secondary outcomes. RESULTS: Forty-eight participants were randomized to each group and were considered for data analysis. Although Bishop score was not statistically different before the intervention, it was significantly higher in case group compared to the placebo group after the intervention (EPO = 5.83 ± 1.68, placebo = 5.19 ± 1.52, p value = 0.002). Four participants in the case group and two in the control group underwent cesarean section (p value = 0.677). The need for labor induction was significantly higher in the placebo group than EPO group (oxytocin injection: 10.4% vs. 31.3%, p value = 0.012, amniotomy: 75% vs. 41.7, p value = 0.001). CONCLUSION: The vaginal use of EPO could be considered as a safe and efficient approach for cervical ripening in low-risk term pregnant women.Es wurden verschiedene Methoden zur Zervixreifung entwickelt. Die Daten zur Wirksamkeit von Nachtkerzenöl (evening primrose oil, EPO) sind uneinheitlich. Mit dieser Studie sollen die Ergebnisse der Anwendung von EPO zur Zervixreifung bei Frauen mit niedrigem Risiko und termingerechter Schwangerschaft untersucht werden.Schwangere Frauen mit niedrigem Risiko und termingerechter Schwangerschaft, die in die Geburtsklinik des Imam-Hossein-Krankenhauses in Teheran eingewiesen wurden und gemäss den Einschlusskriterien für die Teilnahme infrage kamen, wurden randomisiert der Fall- oder der Kontrollgruppe zugewiesen. Die Fallgruppe erhielt 1.000 mg EPO als Vaginalkapseln, während die andere Gruppe täglich eine vaginale Placebokapsel erhielt, die dem Originalpräparat ähnelte. Primäres Zielkriterium war der Bishop-Score und sekundäre Zielkriterien waren die Dauer der Wehenphasen sowie die Verfahren zur Geburtseinleitung.Jeder Gruppe wurden randomisiert 48 Teilnehmerinnen zugewiesen und bei der Datenanalyse berücksichtigt. Während vor der Intervention kein statistisch signifikanter Unterschied im Bishop-Score bestand, fiel dieser nach der Intervention in der Fallgruppe signifikant höher aus als in der Placebogruppe (EPO = 5,83 ± 1,68, Placebo = 5,19 ± 1,52, p-Wert = 0,002). Bei vier Teilnehmerinnen in der Fallgruppe und zwei in der Kontrollgruppe wurde ein Kaiserschnitt durchgeführt (p-Wert = 0,677). Die Notwendigkeit einer Weheneinleitung war in der Placebogruppe signifikant höher als in der EPO-Gruppe (Oxytocin-Injektion: 10,4% vs. 31,3%, p-Wert = 0,012, Amniotomie: 75% vs. 41,7%, p-Wert = 0,001).Die vaginale Anwendung von EPO kann als sicherer und wirksamer Ansatz zur Zervixreifung bei Frauen mit niedrigem Risiko und termingerechter Schwangerschaft angesehen werden.

The intervention effect of nicotine on cervical fibroblast-myofibroblast differentiation in lipopolysaccharide-induced preterm birth model through activating the TGF-ß1/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-ß1/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-ß/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-ß1 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-ß1/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-ß/Smad3 pathway and promoting fibroblast to differentiate into myofibroblasts.

Effects of macrophage depletion on characteristics of cervix remodeling and pregnancy in CD11b-dtr mice.

To test the hypothesis that macrophages are essential for remodeling the cervix in preparation for birth, pregnant homozygous CD11b-dtr mice were injected with diphtheria toxin (DT) on days 14 and 16 postbreeding. On day 15 postbreeding, macrophages (F4/80+) were depleted in cervix and kidney, but not in liver, ovary, or other non-reproductive tissues in DT-compared to saline-treated dtr mice or wild-type controls given DT or saline. Within 24 h of DT-treatment, the density of cell nuclei and macrophages declined in cervix stroma in dtr mice versus controls, but birefringence of collagen, as an indication of extracellular cross-linked structure, remained unchanged. Only in the cervix of DT-treated dtr mice was an apoptotic morphology evident in macrophages. DT-treatment did not alter the sparse presence or morphology of neutrophils. By day 18 postbreeding, macrophages repopulated the cervix in DT-treated dtr mice so that the numbers were comparable to that in controls. However, at term, evidence of fetal mortality without cervix ripening occurred in most dtr mice given DT-a possible consequence of treatment effects on placental function. These findings suggest that CD11b+ F4/80+ macrophages are important to sustain pregnancy and are required for processes that remodel the cervix in preparation for parturition.

[Clinical multicenter study of carboprost methylate suppository for cervical ripening prior to diagnostic hysteroscopy].

Objective: To evaluate the effectiveness of carboprost methylate suppository for cervical ripening before diagnostic hysteroscopy in premenopausal women. Methods: From July 2014 to July 2015, 1 614 women who were undergone diagnostic hysteroscopy in 12 hospitals were randomly assigned into study group (n=1 209) and control group (n=405) . The cases in study group were given 1 mg carboprost methylate suppository in vagina before hysteroscopy, the cases in control group were given 1 mg placebo. The extent of cervical ripening, the time of dilated cervix, pain scoring, incidence of drug side reactions after 24, 48, 72 hours, satisfaction degree of operators and patients, the time of hysteroscopy, incidence of complications between the two groups were observed and compared. Results: (1) Mean cervical widths in the study and control groups were 6.11±1.11 and 5.95±1.11, and showed a significant difference (P=0.034) ; the percentage of women requiring cervical dilatation in study group was lower than the percentage in control group significantly [28.3% (342/1 209) versus 34.6% (140/405) , P=0.020]. (2) The time of dilated cervix in study group was shorter than the time in control group significantly [ (34±25) versus (52±49) s, P=0.028] for the patients whose mean cervical widths≤4. (3) There was no significant difference in pain scores between the two groups (P>0.05) . (4) The incidence of side reactions 24, 48, 72 hours after operation were no significant difference between the two groups (P>0.05) . (5) The satisfaction degree of operators and patients, the time of hysteroscopy, incidence of complications between the two groups were no singnifcant difference between the two groups (all P>0.05) . Conclusion: Application of carboprost methylate suppository by vagina before hysteroscopy is an effective and safe method of cervical ripening.

Is nitric oxide an essential mediator in cervical inflammation and preterm birth?

OBJECTIVE: Cervical ripening is an obligatory step in the process of preterm birth. We hypothesize an inflammatory challenge to the cervix, which leads to an increase in nitric oxide production, disrupting the cervical epithelial barrier leading to preterm birth. STUDY DESIGN: For this study, three experiments were performed: (i) Using a mouse model, pregnant mice were treated with an intrauterine injection of saline or lipopolysaccharide (LPS). Mice were sacrificed and cervices were collected for molecular analysis. (ii) Immortalized ectocervical and endocervical cells were treated with either LPS or the nitric oxide donor sodium nitroprusside (SNP). Media and RNA was collected for analysis. (iii) The integrity of the epithelial cell barrier was evaluated using an in vitro permeability assay. RESULTS: The expression of inducible nitric oxide synthase (iNOS) was increased in our mouse model with LPS (p < .005). In vitro, LPS did not increase nitrate or nitrite concentrations or mRNA expression of iNOS. Permeability increased in the presence of LPS (p < .01), but was unchanged after treatment with SNP. CONCLUSIONS: These studies show that LPS increases the expression of the iNOS in an animal model of preterm birth, but the nitric oxide metabolites nitrate and nitrite do not initiate the pro-inflammatory LPS-induced breakdown of the cervical epithelial barrier.

Misoprostol With Foley Bulb Compared With Misoprostol Alone for Cervical Ripening: A Randomized Controlled Trial.

OBJECTIVE: To test the hypothesis that cervical ripening using a combination of misoprostol and a transcervical Foley bulb leads to delivery within a shorter time compared with misoprostol alone. METHODS: This randomized controlled trial was offered to women admitted for cervical ripening. Inclusion criteria were gestational age 37 weeks or greater with intact membranes, singleton fetus, cephalic presentation, and Bishop score 6 or less. Exclusion criteria included, among others, prior uterine surgery, ruptured membranes, and any contraindication to vaginal delivery. Patients were randomized to cervical ripening using misoprostol and a transcervical Foley bulb simultaneously or misoprostol alone. Primary outcome was time from placement of the misoprostol to delivery. Secondary outcomes included time to active phase, time from active phase to delivery, cesarean delivery rate, uterine tachysystole, estimated blood loss, chorioamnionitis, cord pH, 5-minute Apgar score, and neonatal intensive care unit admission. Sample size calculation revealed that 94 participants were required in each group to detect a 3-hour difference with 80% power and α error of 0.05. Intention-to-treat analysis was performed. RESULTS: From September 2015 to July 2016, a total of 200 patients were randomized, 100 to each group. There were no differences between groups with respect to parity, body mass index, gestational age, Bishop score, birth weight, or indication for induction. Time to delivery was significantly shorter in the combined misoprostol-transcervical Foley group: 15.0 (11.0-21.8) hours (median [interquartile range]) vs 19.0 (14.0-27.3) hours in the misoprostol-only group (P=.001). This time difference remained significant after subanalysis by parity or after excluding cesarean deliveries. There was no difference between groups with respect to the rate or indication for cesarean delivery, estimated blood loss, rate of tachysystole, chorioamnionitis, or neonatal outcomes. CONCLUSION: Cervical ripening using misoprostol in combination with a transcervical Foley bulb is an effective method to shorten the course of labor compared with misoprostol alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02566005.

Prostaglandin-Endoperoxide Synthase 1 Mediates the Timing of Parturition in Mice Despite Unhindered Uterine Contractility.

Cyclooxygenase (COX)-derived prostaglandins stimulate uterine contractions and prepare the cervix for parturition. Prior reports suggest Cox-1 knockout (KO) mice exhibit delayed parturition due to impaired luteolysis, yet the mechanism for late-onset delivery remains unclear. Here, we examined key factors for normal onset of parturition to determine whether any could account for the delayed parturition phenotype. Pregnant Cox-1KO mice did not display altered timing of embryo implantation or postimplantation growth. Although messenger RNAs of contraction-associated proteins (CAPs) were differentially expressed between Cox-1KO and wild-type (WT) myometrium, there were no differences in CAP agonist-induced intracellular calcium release, spontaneous or oxytocin (OT)-induced ex vivo uterine contractility, or in vivo uterine contractile pressure. Delayed parturition in Cox-1KO mice persisted despite exogenous OT treatment. Progesterone (P4) withdrawal, by ovariectomy or administration of the P4-antagonist RU486, diminished the delayed parturition phenotype of Cox-1KO mice. Because antepartum P4 levels do not decline in Cox-1KO females, P4-treated WT mice were examined for the effect of this hormone on in vivo uterine contractility and ex vivo cervical dilation. P4-treated WT mice had delayed parturition but normal uterine contractility. Cervical distensibility was decreased in Cox-1KO mice on the day of expected delivery and reduced in WT mice with long-term P4 treatment. Collectively, these findings show that delayed parturition in Cox-1KO mice is the result of impaired luteolysis and cervical dilation, despite the presence of strong uterine contractions.

Castor oil for induction of labour: a retrospective study.

PURPOSE: The aim of this study is to investigate the safety and efficacy of castor oil to induce labour. MATERIALS AND METHODS: A retrospective observational case control study was conducted over five years. Castor oil was proposed to women referred to the Birth Centre (Castor Oil group (COG)). They were compared to women who chose to be followed by the traditional doctor-led unit (control group (CG)). Castor oil was administered in a 60 ml single dose in 200 ml of warm water. Inclusion criteria were gestational age between 40 and 41 weeks plus premature rupture of membranes between 12 and 18 hours or amniotic fluid index ≤4 or Bishop Score of ≤4 or absence of spontaneous labour over 41 + 4 weeks. RESULTS: Pharmacological induction of labour was required for 18 women in the COG (45%) and 36 in the CG (90%) (p < .001). The mode of delivery differed significantly between groups: women assuming castor oil showed a higher incidence of vaginal delivery, whereas the incidence of caesarean section was lower in the COG, but no statistical significance was reached. CONCLUSIONS: The use of castor oil is related to a higher probability of labour initiation within 24 hours. Castor oil can be considered a safe non-pharmacological method for labour induction.

Progesterone Receptor-Mediated Actions Regulate Remodeling of the Cervix in Preparation for Preterm Parturition.

This study determined whether a progesterone (P) receptor (PR)-mediated mechanism regulates morphological characteristics associated with prepartum cervix remodeling at term and with preterm birth. With focus on the transition from a soft to ripe cervix, the cervix stroma of untreated controls had reduced cell nuclei density/area and less organized extracellular collagen, while the density of macrophages/area, but not neutrophils, increased just 2 days before birth (day 17 vs day 15 or 16.5 postbreeding). Preterm birth was induced within 24 hours of treatment on day 16 postbreeding with PR antagonist or ovariectomy (Ovx). Pure or mixed PR antagonists increased the density of macrophages in the cervix within 8 hours (day 16.5 postbreeding), in advance of preterm birth. However, neither PR antagonists nor P withdrawal after Ovx affected the densities of cell nuclei and neutrophils or extracellular collagen compared to the same day controls-an indication that the cervix was sufficiently remodeled for birth to occur. To block the effect of systemic P withdrawal, Ovx pregnant mice were given a PR agonist, either pure or mixed. These treatments forestalled preterm birth and prevented further morphological remodeling of the cervix. The resulting increase in macrophage density in cervix stroma following Ovx was only blocked by a pure PR agonist. These findings support the hypothesis that inflammatory processes in the prepartum cervix that include residency of macrophages, cellular hypertrophy, and extracellular collagen structure are regulated by genomic actions of PR in a final common mechanism both at term and with induced preterm birth.

Mifepristone and misoprostol for cervical ripening in surgical abortion between 12 and 14 weeks of gestation: a randomized controlled trial.

OBJECTIVE: Misoprostol and mifepristone are the two substances recommended for cervical preparation during first-trimester surgical abortions to decrease intraoperative bleeding and complications. The objective of the study was to evaluate whether the combination of mifepristone and misoprostol for cervical preparation in an elective surgical abortion between 12 and 14 weeks of gestation can reduce blood loss in comparison to misoprostol or mifepristone alone. STUDY DESIGN: A randomized controlled trial was performed in Marseille, France between May 2013 and May 2014. Women requesting a surgical abortion under general anesthesia between 12 and 14 weeks of gestation were 198, randomized into three groups: one received 400µg oral misoprostol 3h before surgery, one 200mg oral mifepristone 36h before surgery, and the other, both treatments. The main outcome was the quantity of intraoperative bleeding. The secondary outcomes were duration of intervention, ease of dilatation, and complications. RESULTS: The quantity of intraoperative bleeding differed significantly between the groups (p=0.001): 222±64mL in the combination group, 329±129mL in the misoprostol group, and 276±119mL in the mifepristone group. The combination was associated with a shorter operative duration (p=0.001): 5±2min in the combination group, 7±5min in the misoprostol group, and 7±3min in the mifepristone group. A hemorrhage was observed for 5 of 55 women (9%) in the combination group, 13 of 51 (25%) in the misoprostol group, and 9 of 56 (16%) in the mifepristone group (p=0.08). No cervical laceration or uterine perforation was reported. CONCLUSIONS: The combination of mifepristone and misoprostol in cervical preparation for elective surgical abortions between 12 and 14 weeks of gestation significantly reduced blood loss in comparison to misoprostol or mifepristone alone.

A systematic review and meta-analysis of randomized controlled trials on the effectiveness of cervical ripening with misoprostol administration before hysteroscopy.

BACKGROUND: Misoprostol is an effective cervical ripening agent. OBJECTIVES: To determine the effect of misoprostol on cervical ripening before hysteroscopy. SEARCH STRATEGY: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for pertinent studies published before November 2014, using the search terms "hysteroscopy," "ripening," and "misoprostol." SELECTION CRITERIA: Randomized controlled trials published in English were included that compared the effects of misoprostol versus placebo on cervical dilatation before diagnostic or operative hysteroscopy. DATA COLLECTION AND ANALYSIS: Random-effects models were used to calculate odds ratios or mean differences (MDs) with 95% confidence intervals (CIs). MAIN RESULTS: The analysis included 32 trials. Misoprostol had significant effects on the need for further cervical dilatation (odds ratio 0.29, 95% CI 0.17-0.50), the cervical width (MD 1.53, 95% CI 0.92-2.13), and the time taken for cervical dilatation (MD -0.35, 95% CI -0.50 to -0.20). Corresponding observations were made in the subgroup of premenopausal women, but not in the subgroup of postmenopausal women. Adverse effects were significantly more common with misoprostol than with placebo (risk difference 0.07, 95% CI 0.01-0.12). CONCLUSIONS: Misoprostol had a significant effect on cervical ripening before hysteroscopy, except in the postmenopausal population. However, it also resulted in more adverse effects.

Vaginal progesterone combined with cervical pessary: A chance for pregnancies at risk for preterm birth?

BACKGROUND: Precocious cervical ripening, as defined by cervical shortening on transvaginal sonography, has prompted a broad evaluation of secondary strategies (such as cerclage, vaginal progesterone, or a cervical pessary) to prevent preterm delivery. However, there is still a lack of direct comparisons between individual treatments or their combinations. OBJECTIVE: We sought to compare at-risk patients and screening patients who had been treated with cervical pessary alone with patients who had been treated with pessary plus vaginal progesterone. STUDY DESIGN: This is a pre- and postintervention cohort study from a preterm labor clinic where placement of a cervical pessary has been the standard treatment since 2008 for at-risk women defined by (1) a history of spontaneous preterm birth at <37 weeks of gestation, (2) conization, or (3) a cerclage because of a previous short cervical length of <3rd percentile and, additionally, with a cervical length of <10th percentile in the ongoing pregnancy. Patients who did not meet the criteria for the "at risk" group, but who had a cervical length of <3rd percentile comprised the screening group. From July 2011 onward, vaginal progesterone (200 mg, suppositories) was prescribed in addition to the pessary. Both at-risk patients (n = 55) and screening patients (n = 51) were treated at the time of diagnosis. The primary outcome was the rate of preterm deliveries at <34 weeks of gestation. Secondary outcomes included deliveries at <28, <32, and <37 weeks of gestation, the days from start of therapy until delivery, a composite index of neonatal outcome, and the number of days in the neonatal intensive care unit. Primary and secondary outcomes were compared between groups with the use of multivariable models to adjust for possible confounders. RESULTS: Delivery at <34 weeks of gestation occurred in 17 of 53 patients (32.1%) who were treated with pessary plus progesterone, compared with 13 of 53 patients (24.5%) who were treated with pessary alone (P = .57). Similarly, there was no difference in the rate of preterm delivery at <28, <32, or <37 weeks of gestation. The composite poor neonatal outcome was 15.1% in the pessary group vs 18.9% in the combined group (P = .96). The mean duration of stay in the neonatal intensive care unit was 46.5 days (range, 9-130 days) in the combined vs 52.0 days (range, 3-151 days) in the pessary group (P < .001). CONCLUSION: In this cohort study, treatment of precocious cervical ripening with cervical pessary plus vaginal progesterone did not reduce the rates of preterm delivery at <28, <32, <34, or <37 weeks of gestation compared with pessary alone. The neonatal intensive care use was shorter in patients who received additional vaginal progesterone, although there was no difference in composite poor neonatal outcome. These preliminary results may serve as a pilot for future trials and provide a basis for treatment until larger trials are completed.

Cervical ripening before first trimester surgical evacuation for non-viable pregnancy.

BACKGROUND: Medications or mechanical dilators are often used to soften and dilate the cervix prior to surgical evacuation of the uterus for non-viable pregnancy, or miscarriage. The majority of miscarriages occur in the first trimester. The aim of cervical ripening is to reduce the possibility of injury to the uterus and cervix and improve the surgical ease of the procedure. Cervical ripening agents can have adverse effects and it is uncertain as to whether these risks outweigh the benefits of their use. OBJECTIVES: To systematically review the benefits and harms of using cervical ripening agents prior to surgical evacuation of non-viable pregnancy prior to 14 weeks' gestation. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2015) and reference lists of retrieved papers. SELECTION CRITERIA: Randomised controlled trials (published in full-text form, or as abstracts only), which assessed the use of pharmacological or mechanical agents to ripen the cervix in women undergoing dilation and curettage or vacuum aspiration for non-viable pregnancy at less than 14 weeks' gestation were eligible for inclusion. Cluster-randomised controlled trials and trials using a cross-over design were not eligible for inclusion.Unpublished randomised controlled trials and quasi-randomised trials would have been eligible for inclusion but none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data were checked for accuracy. MAIN RESULTS: We included nine trials with 469 women. A diverse set of medications and regimens were studied in these trials, making the comparisons available for meta-analysis limited. The comparisons draw data from six trials with 383 participants. All trials were relatively small and had several aspects of unclear risk of bias with few of this review's outcomes reported. Due to this, no data from three trials were able to be used despite them meeting inclusion criteria.We carried out four comparisons: isosorbide mononitrate or dinitrate compared with misoprostol; misoprostol compared with placebo; chemical dilation (use of medications) compared with mechanical dilation; and any cervical preparation compared with placebo.None of the included studies reported data on the review's primary outcome: cervical or uterine injury (perforation, laceration, creation of a false passage).No clear difference was shown between isosorbide compounds and misoprostol for the outcome need for manual cervical dilation (average risk ratio (RR) 0.76, 95% confidence interval (CI) 0.10 to 5.64; three trials, 150 women; Tau² = 2.11; I² = 69%), however the data were heterogenous. In terms of adverse effects, misoprostol was associated with more vomiting (RR 0.11, 95% CI 0.01 to 0.85; two trials, 120 women), however there were no clear differences between isosorbide compounds and misoprostol in relation to other reported adverse effects (headache, nausea or hypotension). The dosing regimens differed in terms of dose, number of administrations and route of administration in the different trials. Mechanical (Dilapan-S hygroscopic) dilators performed similarly to chemical dilators in a single trial (65 women) that measured difficulty in cervical dilation, excessive bleeding and adverse effects.Misoprostol was shown to be more effective than placebo for cervical ripening (reduced need for manual cervical dilation) (RR 0.14, 95% CI 0.08 to 0.26; one trial, 120 women), and surgical time was reduced when misoprostol was used (mean difference (MD) -3.15, 95% CI -3.59 to -2.70; one trial, 120 women). However, compared to placebo, misoprostol, was associated with more abdominal pain (RR 29.00, 95% CI 1.77 to 475.35; one trial, 120 women), although no clear differences in the risk of other adverse effects (nausea, vomiting, headache or fever) were observed between groups.There was no clear differences between chemical dilation and mechanical dilators for the outcomes: difficulty in cervical dilation, excessive bleeding or adverse effects.Compared with placebo, any cervical preparation reduced the need for manual cervical dilatation (average RR 0.25, 95% CI 0.07 to 0.89; two trials, 168 women; Tau² = 0.67; I² = 81%), and reduced surgical time (MD -2.55, 95% CI -3.67 to -1.43, two trials, 168 women; Tau² = 0.63; I² = 96%).None of the included trials reported on the review's other secondary outcomes, including: injury to bladder or bowel, miscarriage/preterm birth in a subsequent pregnancy, analgesia use after administration of ripening agent but before surgery, or analgesia use after surgery. AUTHORS' CONCLUSIONS: This review found no evidence to evaluate cervical ripening prior to first trimester surgical evacuation for miscarriage for reducing the rate of cervical or uterine injury, however, this may be because these outcomes are very rare. Cervical preparation was shown to reduce the need for manual cervical dilatation compared with placebo.Misoprostol and isosorbide mononitrate and dinitrate were similarly effective in ripening the cervix, however there was more vomiting with misoprostol. Mechanical (Dilapan-S hygroscopic) dilators performed similarly to chemical dilators.The nine studies included in this review were small and the methodological quality of the trials was mixed, and for the most part, not well-described; thus any conclusions drawn from the data included in this review must be treated with caution. Consequently, large, high-quality trials are required to determine whether the benefits of this treatment outweigh the risks. Further research should be powered to assess the rate of cervical and uterine injury between interventions. Future research should also guide clinicians in deciding whether the benefits of reduced manual cervical dilatation outweigh the risks of adverse effects associated with these agents (nausea, vomiting, headache, fever, diarrhoea and pain). Women's satisfaction and outcomes of future pregnancies should also be assessed.

Comparison of vaginal misoprostol and dinoprostone for cervical ripening before diagnostic hysteroscopy in nulliparous women.

OBJECTIVE: To compare the effectiveness of vaginal misoprostol and dinoprostone for cervical ripening before diagnostic hysteroscopy in nulliparous women. DESIGN: Placebo-controlled, double blind, randomized trial. SETTING: Teaching and research hospital. PATIENT(S): Ninety women of reproductive age eligible for diagnostic hysteroscopy. INTERVENTION(S): Randomly assignment to receive 400 µg of misoprostol (n = 30) or 10 mg of dinoprostone (n = 30) vaginally before diagnostic hysteroscopy, with a control group (n = 30) not receiving any cervical priming agent. PRIMARY OUTCOME: the number of women requiring cervical dilatation; secondary outcomes: cervical width before surgery, duration of dilatation time, ease of dilatation, complications during surgical procedure, and side effects of the drugs. RESULT(S): In the placebo group, 23 patients required cervical dilatation compared with 17 in the misoprostol group and 9 in the dinoprostone group. The mean (± standard deviation) cervical widths for the placebo, misoprostol, and dinoprostone groups were 4.23 ± 0.43 mm, 5.43 ± 0.5 mm, and 5.83 ± 0.64 mm, respectively. These widths were statistically significantly different. The duration of dilatation was also statistically significantly longer in the control group. CONCLUSION(S): Vaginally administered dinoprostone before diagnostic hysteroscopy is more effective than misoprostol for inducing cervical priming. Further studies are required to elucidate the most efficient option with the least side effects for cervical ripening. CLINICAL TRIAL REGISTRATION NUMBER: NCT01620814.

Sublingual misoprostol is better for cervical ripening prior to hysteroscopy in post-menopausal women.

BACKGROUND: The aim of the present study was to evaluate the efficacy of misoprostol administered sublingually, vaginally or rectally on cervical ripening before hysterescopic surgery in post-menopausal women. MATERIALS AND METHODS: Post-menopausal women were randomised to receive either 400 ug of misoprostol, administered sublingually, vaginally or rectally six hours and 12 hours prior to operative hysterescopy. RESULTS: Patients were randomized to receive receive sublingual (n = 30), rectal (n = 30) or vaginal (n = 30) misoprostol. The control group did not receive misoprostol (n = 30). The four groups were comparable in terms of preoperative cervical width after misoprostol administration. The mean cervical widths for control group was 9.0 +/- 1.1 mm and the mean post-treatment cervical widths for the sublingual, vaginal, and rectal groups were 7.1 +/- 1.1 mm, 8.9 +/- 1.3 mm, and 8.6 +/- 1.5 mm, respectively. The cervical widths of sublingual group were significantly different from control, vaginal; and rectal groups (p < 0.001). CONCLUSION: Four hundred micrograms of sublingual misoprostol, 12 and six hours prior to operative hysteroscopy has a significant cervical ripening effect compared with vaginal, rectal, and control groups in post-menopausal women.

Nicotine treatment prolongs gestation and inhibits cervical ripening in pregnant rats.

OBJECTIVE: The aims of this study were to examine the effects of nicotine treatment on the length of gestation, on fetal outcome, on cervical ripening, and on uterine contractility during pregnancy in rats. STUDY DESIGN: Pregnant rats were treated with various concentrations of nicotine (0.25, 0.5, 1, 2 mg/kg/d, subcutaneously). Delivery times and fetal weights were obtained. Cervical collagen cross-links were assessed in vivo by collagen light-induced fluorescence (LIF), and cervical resistance to stretch was measured by in vitro extensibility tests. RESULTS: Delivery time is significantly (P = .002) prolonged after high-dose nicotine treatments. There are no significant changes in pup weights and placenta weights after nicotine treatments. Cervical collagen LIF and extensibility progressively decrease throughout pregnancy in control rats. Nicotine-treated rats showed significant (P < .001) cervical resistance to stretch and higher LIF compared with the control rats. Nicotine treatment in vitro had little effect on uterine contractility. CONCLUSION: Nicotine exposure during pregnancy prolongs gestation and inhibits cervical ripening, possibly by suppression of a cholinergic antiinflammatory response.

[Elastography assessment of the cervix during cervical maturation]. / Elastographie du col utérin au cours de la maturation cervicale.

BACKGROUND: The issue of cervical tissue imaging is to enable the provision of Obstetricians an objective tool for measuring cervical changes more accurate than the vaginal touch. Hitachi software "Real-time Tissue Elastography" allows an analysis of tissue elasticity, evaluated on a Young's modulus theory. This imagery evaluated for mammary tumors and liver changes elasticity, would objectively show changes in cervical consistency. AIMS: The authors of the following work have attempted to: - Assess the usefulness of elastography in the uterine cervix examination. - Compare the modifications of the cervical module of elasticity before and during the maturation by prostaglandins indicated for medical reason with those raised in the clinical examination (score of Bishop). METHODS: It is about a non-interventional feasibility study with regulation of the machine, realized in forward-looking. We included 30 patients scheduled for a cervical maturation by prostaglandins for medical indication. We realized a measure of the cervical module of elasticity during an endo-vaginal ultrasound for measure of the cervix before the pose of prostaglandins, 6 hours then 12 hours after the stake in contact and we compared the measure every time with the score of bishop. RESULTS: All the patients who presented an index of high softening entered labor within the 3 hours following the examination. Furthermore, the modifications observed on the index of softening were correlated to those of the score of Bishop. CONCLUSION: The performance of the images of elastography with these regulations allowed a good confrontation of the results during the evaluation of the feasibility of the technique with the score of Bishop during cervical maturation. This promising technique remains a technique of research. Forward-looking studies on wide series of patients are going to be able to estimate the elastography as an additional and objective informer of the cervical maturation.

Combination of Foley bulb and vaginal misoprostol compared with vaginal misoprostol alone for cervical ripening and labor induction: a randomized controlled trial.

OBJECTIVE: To test the hypothesis that use of the Foley bulb plus vaginal misoprostol will result in shorter induction-to-delivery time compared with vaginal misoprostol alone. METHODS: We randomized 123 women undergoing induction of labor with singleton pregnancies at 24 weeks of gestation or greater with an unfavorable cervix (Bishop score 6 or lower) to Foley bulb plus vaginal misoprostol (n=56) or vaginal misoprostol alone (n=61). Women with fetal malpresentation, multifetal gestation, spontaneous labor, contraindication to prostaglandins, nonreassuring fetal heart rate tracing, intrauterine growth restriction, anomalous fetus, fetal demise, or previous cesarean delivery or other significant uterine surgery were excluded. The primary outcome measure was induction-to-delivery time. Secondary outcomes were mode of delivery, tachysystole with fetal decelerations, terbutaline use, postpartum hemorrhage, chorioamnionitis, neonatal Apgar scores, and neonatal intensive care unit admission. Analysis followed the intention-to-treat principle. RESULTS: The mean induction-to-delivery time was shorter with the combination of the Foley bulb and vaginal misoprostol when compared with vaginal misoprostol alone (15.3±6.5 compared with 18.3±8.7 hours, difference -3.1 hours, 95% confidence interval [CI] -5.9 to -0.30). The combination also resulted in shorter induction to complete cervical dilation time (13.7±5.9 compared with 17.1±8.7 hours, difference -3.5 hours, 95% CI -6.7 to -0.4). There were no differences in labor complications or adverse neonatal and maternal outcomes. CONCLUSION: A combination of the Foley bulb and vaginal misoprostol resulted in a shorter induction-to-delivery time when compared with vaginal misoprostol alone without increasing labor complications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01279343. LEVEL OF EVIDENCE: I.

Misoprostol for cervical ripening prior to manual vacuum aspiration (MVA) in abnormal uterine bleeding: double blinded randomized controlled trialt.

OBJECTIVE: To study the effectiveness of sublingual misoprostol for cervical ripening before MVA in women aged between 35 and 55 years old. MATERIAL AND METHOD: Women aged between 35 and 55 years old who had indications for endometrial sampling were recruited. Exclusion criteria were gross pathology of cervix, pregnancy, allergy to misoprostol, and abnormal coagulopathy. Eighty women who had indication for MVA were then assigned by randomization (block of four). Participants were treated with either sublingual 200 microg of misoprostol (study group) or placebo (controlled group) for cervical priming at two hours before procedure. The largest diameter of the Hegar's dilator through internal so without any resistance before MVA was the primary collected data. Secondary data were operating time, immediate pain score, satisfactory score, complications, and side effects. RESULTS: Mean age of misoprostol and controlled group were 44.8 +/- 5.2 and 45.5 +/- 5.0 years old, respectively. One third of both groups had previously experienced uterine curettage. The initial cervical diameter before MVA of individuals receiving misoprostol and controlled group were 6.9 +/- 2.0 and 5.5 +/- 2.4 mm, respectively. The MVA time in misoprostol group was significantly shorter than controlled group (5.1 +/- 1.7 vs. 8.0 +/- 3.9 min, p < 0.001). The additional analgesia was not different in both groups. Side effect before MVA were more significantly found in misoprostol group (p = 0.001). Lower post MVA pain and satisfactory score were better reported in misoprostol group than placebo's (p < 0.001). CONCLUSION: Two hundred micrograms of sublingual misoprostol administration prior to MVA gave significantly effective result of cervical priming. Satisfactory and pain scores were more favorable in misoprostol group with manageable side effects.