Effectiveness of dinoprostone gel, misoprostol vaginal insert and dinoprostone vaginal insert for induction of labour in twin pregnancies.

OBJECTIVES: To compare the effectiveness and safety of Dinoprostone Gel (DG), Misoprostol Vaginal Insert (MVI) and Dinoprostone Vaginal Insert (DVI) for induction of labour (IOL) in twin pregnancies. STUDY DESIGN: Retrospective cohort study of twin pregnancies > 34 + 0 weeks gestation that underwent induction of labour (IOL) with DG, MVI or DVI between December 2016 and November 2019 in a Tertiary NHS hospital, North West England, UK. Delivery characteristics, maternal complications and neonatal outcomes were compared between the three groups. RESULTS: A total of 87 twin pregnancies were included for analysis. 27 women received DG, 34 received MVI and 26 DVI. The MVI cohort had a higher proportion of nulliparous women (55.9%) compared to the DG and DVI cohorts, 29.6% and 38.5% respectively. No other differences amongst demographic characteristics were considered clinically significant. DG demonstrated a significantly quicker time to delivery (minutes) compared to DVI (1021 ± 556 versus 1649 ± 852; P = 0.0026). Significantly fewer women required terbutaline for hyperstimulation/tachysystole in the DG group compared to MVI (0% vs 32%; RR 0.05; 95% CI 0.003-0.88). Both DG and MVI groups required significantly less oxytocin following artificial rupture of membranes compared to DVI (33% vs 65%; RR 0.51; 95% CI 0.28-0.93) and (29% vs 65%; RR 0.45; 95% CI 0.25-0.81). There were no significant differences in mode of delivery, maternal complications and neonatal outcomes. CONCLUSION: Our data suggests that for women with a twin pregnancy considering a planned labour that induction with DG, MVI and DVI appear to be equally safe and effective IOL methods. These results should be interpreted with caution due to the study being underpowered to detect significant adverse outcomes. In order to determine the optimal method of IOL in twins, direct randomised comparison is needed.

Using dinoprostone slow release vaginal insert for cervical ripening in term-pregnancy with oligohydramnios.

AIMS: The study purposed to evaluate the success rate of cervical ripening using dinoprostone controlled-release vaginal insert and reveal some factors relating to successful cervical ripening. METHODS: This cross-sectional study was conducted at Tu Du Hospital in Vietnam from December 2021 to August 2022. The study enrolled 200 pregnant women with gestational age ≥37 weeks diagnosed with oligohydramnios. These candidates underwent dinoprostone cervical ripening (DCR) according to the local protocol. The Bishop score ≥7 after 24 h was determined for the successful cervical ripening (SCR). RESULTS: In total, the success rate of DCR achieved at 57.5% and the cesarean delivery rate was 46.5%. None of the severe side-effects and complications was present. Using multivariable logistic regression, the study found that the body mass index ≥25 kg/m2 and oxytocin infusion drip related to SCR with adjusted odds ratio (aOR): 3.67 (95% confidence intervals [CI]: 1.78-7.57) and aOR: 4.68 (95% CI: 1.84-11.93), p < 0.001. Using the Kaplan-Meier curve, the present study revealed a significant difference between Bishop <3 and ≥3 following the duration time of cervical ripening, with hazard ratio: 1.38 (95% CI: 1.19-1.59), p < 0.001. The time duration of cervical ripening was not significantly different following amniotic fluid index from 3 to 5 cm. CONCLUSIONS: Cervical ripening using a dinoprostone vaginal insert is a potentially acceptable method in term pregnancy accompanying with oligohydramnios. The probability of SCR can be predicted on a careful assessment of relative factors by obstetricians. Further studies are required to strengthen these findings.

Clinical significances of Bishop score and vaginal bleeding to controlled-release dinoprostone delivery system (PROPESS) efficacy for cervical ripening: A retrospective single-center study in Japan.

AIMS: To evaluate the effect of vaginal bleeding on the efficacy of controlled-release dinoprostone delivery system (PROPESS) for cervical ripening and the factors affecting the PROPESS efficacy in a Japanese clinical setting. METHODS: A total of 100 term pregnant women in whom PROPESS was used due to an unfavorable cervix (Bishop score ≤ 6) were enrolled. We retrospectively investigated which factors, including vaginal bleeding, were associated with the success of cervical ripening using logistic regression analysis. Moreover, the effect of vaginal bleeding on vaginal acidity was examined in 24 selected cases (control, 11; rupture of membrane, 4; and vaginal bleeding, 8). RESULTS: A 25 women successfully ripened the cervix (effective group), and 75 were unsuccessful (noneffective group). Bishop score at insertion (adjusted odds ratio: 1.87; 95% confidence interval: 1.23-2.86; p = 0.004), and vaginal bleeding at PROPESS insertion (adjusted odds ratio 6.63; 95% confidence interval 1.21-36.36; p = 0.029) affected cervical ripening success. The cases with vaginal bleeding showed a significantly higher vaginal pH than the control cases (median value: 6.75 and 5.0, respectively). We identified no obvious adverse outcomes, such as tachysystole, fetal heart rate abnormality, or low Apgar/pH, associated with vaginal bleeding at insertion. CONCLUSIONS: Our findings suggest that the PROPESS efficacy depends on Bishop score at insertion and that vaginal bleeding at PROPESS insertion might have a significantly positive effect on cervical ripening in term pregnant women.

Prospective observational study investigating the effectiveness, safety, women's experiences and quality of life at 3 months regarding cervical ripening methods for induction of labor at term-The MATUCOL study protocol.

BACKGROUND: The purposes of successful induction of labor (IOL) are to shorten the time for IOL to delivery, increase the vaginal delivery rate, and reduce the rate of maternal and neonatal morbidity. In cases of unfavorable cervix (Bishop score <6), cervical ripening is advised to improve vaginal delivery rate. It may be initiated by mechanical (double balloon catheter (DBC), synthetic osmotic dilator) or pharmacologic (prostaglandins) methods, and the problem is complex due to the multitude of cervical ripening methods. We are constantly looking for the optimal protocol of cervical ripening for each woman. The present study aims to elucidate whether cervical ripening method is associated with increase rate of vaginal delivery, good women's experience and unaltered long-term quality of life after cervical ripening at term regarding maternal and obstetric characteristics. METHODS AND DESIGN: The MATUCOL study is a monocentric, prospective, observational study of all consecutive women who required cervical ripening (Bishop score <6) using different methods (DBC, vaginal dinoprostone, oral misoprostol) with a live fetus at term (≥37 weeks) between January 2020 and August 2021. The outcomes will be mode of delivery, maternal and neonatal morbidity, discomfort/pain assessments during cervical ripening, women's experience and satisfaction, and the impact of cervical ripening on the health-related quality of life at 3 months. If it reports a significant efficacy/safety/perinatal morbidity/women's satisfaction/quality of life at 3 months post-delivery associated with a method of cervical ripening in a specific situation (gestational and/or fetal disease) using a multivariate analysis, its use should be reconsidered in clinical practice. DISCUSSION: This study will reveal that some cervical ripening methods will be more effectiveness, safe, with good women's experiences and QOL at 3 months compared to others regarding maternal and obstetric characteristics. TRIAL REGISTRATION: This study is being performed at La Roche sur Yon Hospital following registration as GNEDS on January 8, 2020.

Clinical predictive factors for vaginal delivery following induction of labour among pregnant women in Jordan.

BACKGROUND: Induction of labour (IOL) is an important and common clinical procedure in obstetrics. In the current study, we evaluate predictors of vaginal delivery in both nulliparous and multiparous women in north Jordan who were induced with vaginal prostaglandins. METHOD: A prospective study was conducted on 530 pregnant women at King Abdullah University Hospital (KAUH) in north Jordan. All pregnant mothers with singleton live fetuses, who had induction of labour (IOL) between July 2017 and June 2019, were included in the study. Mode of delivery, whether vaginal or caesarean, was the primary outcome. Several maternal and fetal variables were investigated. The safety and benefit of repeated dosage of vaginal prostaglandin E2 (PGE2) tablets, neonatal outcomes and factors that affect duration of labour were also evaluated. Pearson χ2 test was used to investigate the significance of association between categorical variables, while student's t-test and ANOVA were applied to examine the mean differences between categorical and numerical variables. Linear regression analysis was utilized to study the relation between two continuous variables. A multivariate regression analysis was then performed. Significance level was considered at alpha less than 0.05. RESULTS: Nulliparous women (N = 254) had significantly higher cesarean delivery rate (58.7% vs. 17.8%, p < 0.001) and longer duration of labour (16.1 ± 0.74 h vs. 11.0 ± 0.43 h, p < 0.001) than multiparous women (N = 276). In nulliparous women, the rate of vaginal delivery was significantly higher in women with higher Bishop score; the mean Bishop score was 3.47 ± 0.12 in nulliparous women who had vaginal delivery vs. 3.06 ± 0.10 in women who had cesarean delivery (Adjusted odds ratio (AOR) = 1.2, 95% CI: 1.03-1.28, p = 0.03). In multiparous women, the rate of vaginal delivery was significantly higher in women with higher Bishop scores and lower in women with higher body mass index (BMI). The mean Bishop score was 3.97 ± 0.07 in multiparous women who had vaginal delivery vs. 3.56 ± 0.16 in women who had cesarean delivery (AOR = 1.5, 95% CI: 1.1-2.1, p = 0.01). The mean BMI was 30.24 ± 0.28 kg/m2 in multiparous women who had vaginal delivery vs. 32.36 ± 0.73 kg/m2 in women who had cesarean delivery (AOR = 0.89, 95% CI: 0.84-0.96, p = 0.005). 27% of nulliparous women who received more than two PGE2 tablets and 50% of multiparous women who received more than two PGE2 tablets had vaginal delivery with no significant increase in neonatal morbidity. CONCLUSION: Parity and cervical status are the main predictors of successful labour induction. Further studies are required to investigate the benefit of the use of additional doses of vaginal PGE2 above the recommended dose for IOL.

8-iso-prostaglandin E2 induces nasal obstruction via thromboxane receptor in murine model of allergic rhinitis.

Thromboxane receptor (TP) mediates nasal obstruction, a typical symptom of allergic rhinitis. Since it has been reported that several types of eicosanoids, such as non-enzymatic oxidation product of arachidonic acid isoprostane, act as a TP ligand, there is a possibility that some other eicosanoids contribute to the TP-mediated nasal obstruction. The aim of this study is to investigate the mechanisms of TP-mediated nasal obstruction. Intranasal challenges of ovalbumin (OVA) induced nasal obstruction in mice. Pharmacological blockade of TP receptor but not thromboxane A2 synthase inhibited OVA-induced nasal obstruction. Simultaneous analysis of eicosanoids in nasal lavage fluid and the responses in trans-endothelial resistance suggested that 8-iso-prostaglandin E2 (PGE2 ) can be a candidate for TP ligand. Intranasal challenge of 8-iso-PGE2 induced vascular hyperpermeability and nasal obstruction in TP receptor-dependent manner. Wholemount immunostaining of nasal septum mucosa revealed that 8-iso-PGE2 increased plasma leakage accompanied by distention of venous sinusoids. This study shows that 8-iso-PGE2 is a contributor in TP-mediated nasal obstruction in mice.

Caffeine-induced inversion of prostaglandin E2 effects on hepatic stellate cell activation.

BACKGROUND AND AIMS: Liver inflammation leads to the activation of hepatic stellate cells (HSCs), resulting in the development of liver fibrosis. The present study aimed to investigate the effects of prostaglandin E2 (PGE2), which is biosynthesized by Kupffer cells, hepatocytes, and HSCs during inflammation, on HSC activation, including its combinatory effect with caffeine. METHODS: HSCs isolated from mice were activated by culturing in a medium supplemented with 10% fetal bovine serum for 7 days on plastic plates. The activation of HSCs was evaluated by immunofluorescence of α-smooth muscle actin in HSCs. Comprehensive gene expression analysis was performed using mRNA-sequencing to compare HSCs cultured for 1 or 7 days, with or without PGE2, caffeine, or both. RESULTS: PGE2 (1 µM) facilitated the activation of HSCs but inhibited the HSC activation in the presence of caffeine (3 mM). Comprehensive gene expression analysis revealed that HSCs treated with PGE2 in the presence of caffeine were classified in the same class as HSCs cultured for 1 day, i.e., quiescent HSCs. In contrast, PGE2 did not exhibit an inhibitory effect on HSC activation when co-treated with any isoform-specific phosphodiesterase inhibitors. Although the adenylate cyclase inhibitor 2',5'-dideoxyadenosine suppressed the elevation of intracellular cAMP level induced by PGE2 in the presence of caffeine, it had no effect on the inhibition of HSC activation by PGE2 plus caffeine. CONCLUSION: The effect of PGE2 on HSC activation is changed from facilitatory to inhibitory when combined with caffeine, suggesting that caffeine may effectively suppress liver fibrosis during inflammation.

Low-dose oral misoprostol for induction of labour.

BACKGROUND: Misoprostol given orally is a commonly used labour induction method. Our Cochrane Review is restricted to studies with low-dose misoprostol (initially ≤ 50 µg), as higher doses pose unacceptably high risks of uterine hyperstimulation. OBJECTIVES: To assess the efficacy and safety of low-dose oral misoprostol for labour induction in women with a viable fetus in the third trimester of pregnancy. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov,  the WHO International Clinical Trials Registry Platform (14 February 2021) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing low-dose oral misoprostol (initial dose ≤ 50 µg) versus placebo, vaginal dinoprostone, vaginal misoprostol, oxytocin, or mechanical methods; or comparing oral misoprostol protocols (one- to two-hourly versus four- to six-hourly; 20 µg to 25 µg versus 50 µg; or 20 µg hourly titrated versus 25 µg two-hourly static). DATA COLLECTION AND ANALYSIS: Using Covidence, two review authors independently screened reports, extracted trial data, and performed quality assessments. Our primary outcomes were vaginal birth within 24 hours, caesarean section, and hyperstimulation with foetal heart changes. MAIN RESULTS: We included 61 trials involving 20,026 women. GRADE assessments ranged from moderate- to very low-certainty evidence, with downgrading decisions based on imprecision, inconsistency, and study limitations. Oral misoprostol versus placebo/no treatment (four trials; 594 women) Oral misoprostol may make little to no difference in the rate of caesarean section (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.59 to 1.11; 4 trials; 594 women; moderate-certainty evidence), while its effect on uterine hyperstimulation with foetal heart rate changes is uncertain (RR 5.15, 95% CI 0.25 to 105.31; 3 trials; 495 women; very low-certainty evidence). Vaginal births within 24 hours was not reported. In all trials, oxytocin could be commenced after 12 to 24 hours and all women had pre-labour ruptured membranes. Oral misoprostol versus vaginal dinoprostone (13 trials; 9676 women) Oral misoprostol probably results in fewer caesarean sections (RR 0.84, 95% CI 0.78 to 0.90; 13 trials, 9676 women; moderate-certainty evidence). Subgroup analysis indicated that 10 µg to 25 µg (RR 0.80, 95% CI 0.74 to 0.87; 9 trials; 8652 women) may differ from 50 µg (RR 1.10, 95% CI 0.91 to 1.34; 4 trials; 1024 women) for caesarean section. Oral misoprostol may decrease vaginal births within 24 hours (RR 0.93, 95% CI 0.87 to 1.00; 10 trials; 8983 women; low-certainty evidence) and hyperstimulation with foetal heart rate changes (RR 0.49, 95% CI 0.40 to 0.59; 11 trials; 9084 women; low-certainty evidence). Oral misoprostol versus vaginal misoprostol (33 trials; 6110 women) Oral use may result in fewer vaginal births within 24 hours (average RR 0.81, 95% CI 0.68 to 0.95; 16 trials, 3451 women; low-certainty evidence), and less hyperstimulation with foetal heart rate changes (RR 0.69, 95% CI 0.53 to 0.92, 25 trials, 4857 women, low-certainty evidence), with subgroup analysis suggesting that 10 µg to 25 µg orally (RR 0.28, 95% CI 0.14 to 0.57; 6 trials, 957 women) may be superior to 50 µg orally (RR 0.82, 95% CI 0.61 to 1.11; 19 trials; 3900 women). Oral misoprostol probably does not increase caesarean sections overall (average RR 1.00, 95% CI 0.86 to 1.16; 32 trials; 5914 women; low-certainty evidence) but likely results in fewer caesareans for foetal distress (RR 0.74, 95% CI 0.55 to 0.99; 24 trials, 4775 women). Oral misoprostol versus intravenous oxytocin (6 trials; 737 women, 200 with ruptured membranes) Misoprostol may make little or no difference to vaginal births within 24 hours (RR 1.12, 95% CI 0.95 to 1.33; 3 trials; 466 women; low-certainty evidence), but probably results in fewer caesarean sections (RR 0.67, 95% CI 0.50 to 0.90; 6 trials; 737 women; moderate-certainty evidence). The effect on hyperstimulation with foetal heart rate changes is uncertain (RR 0.66, 95% CI 0.19 to 2.26; 3 trials, 331 women; very low-certainty evidence). Oral misoprostol versus mechanical methods (6 trials; 2993 women) Six trials compared oral misoprostol to transcervical Foley catheter. Misoprostol may increase vaginal birth within 24 hours (RR 1.32, 95% CI 0.98 to 1.79; 4 trials; 1044 women; low-certainty evidence), and probably reduces the risk of caesarean section (RR 0.84, 95% CI 0.75 to 0.95; 6 trials; 2993 women; moderate-certainty evidence). There may be little or no difference in hyperstimulation with foetal heart rate changes (RR 1.31, 95% CI 0.78 to 2.21; 4 trials; 2828 women; low-certainty evidence). Oral misoprostol one- to two-hourly versus four- to six-hourly (1 trial; 64 women) The evidence on hourly titration was very uncertain due to the low numbers reported. Oral misoprostol 20 µg hourly titrated versus 25 µg two-hourly static (2 trials; 296 women) The difference in regimen may have little or no effect on the rate of vaginal births in 24 hours (RR 0.97, 95% CI 0.80 to 1.16; low-certainty evidence). The evidence is of very low certainty for all other reported outcomes. AUTHORS' CONCLUSIONS: Low-dose oral misoprostol is probably associated with fewer caesarean sections (and therefore more vaginal births) than vaginal dinoprostone, and lower rates of hyperstimulation with foetal heart rate changes. However, time to birth may be increased, as seen by a reduced number of vaginal births within 24 hours. Compared to transcervical Foley catheter, low-dose oral misoprostol is associated with fewer caesarean sections, but equivalent rates of hyperstimulation. Low-dose misoprostol given orally rather than vaginally is probably associated with similar rates of vaginal birth, although rates may be lower within the first 24 hours. However, there is likely less hyperstimulation with foetal heart changes, and fewer caesarean sections performed due to foetal distress. The best available evidence suggests that low-dose oral misoprostol probably has many benefits over other methods for labour induction. This review supports the use of low-dose oral misoprostol for induction of labour, and demonstrates the lower risks of hyperstimulation than when misoprostol is given vaginally. More trials are needed to establish the optimum oral misoprostol regimen, but these findings suggest that a starting dose of 25 µg may offer a good balance of efficacy and safety.

Chorioamnionitis after premature rupture of membranes in nulliparas undergoing labor induction: prostaglandin E2 vs. oxytocin.

OBJECTIVES: To assess the risk of chorioamnionitis in nulliparous, term, singleton, vertex (NTSV) pregnancies with premature rupture of membranes (PROM) and an unfavorable cervix undergoing labor induction with either prostaglandin E2 (PGE2) or oxytocin only. METHODS: Retrospective cohort of NTSV pregnancies presenting with PROM who underwent labor induction with either PGE2 (n=94) or oxytocin (n=181) between October 2015 and March 2019. The primary outcome of chorioamnionitis was compared between the two groups. Statistical analysis included Chi-squared and Wilcoxon rank-sum tests, as well as logistic regression. For time to delivery, a Cox proportional hazard regression was used to determine the hazard ratio (HR) and adjusted HR (aHR). RESULTS: Baseline characteristics were similar between the two groups. Cervical ripening with PGE2 was associated with an increased rate of chorioamnionitis (18.1 vs. 6.1%; aOR 4.14, p=0.001), increased neonatal intensive care unit admissions (20.2 vs. 9.9%; aOR 2.4, p=0.02), longer time interval from PROM to delivery (24.4 vs. 17.9 h; aHR 0.56, p=<0.0001), and lower incidence of meconium (7.4 vs. 14.4%; aOR 0.26, p=0.01), compared to the oxytocin group. CONCLUSIONS: Based on our data, the use of oxytocin appears both superior and safer compared to PGE2 in NTSV pregnancies with PROM undergoing labor induction.

Comparative Evaluation of Efficacy and Safety of Tacrolimus and Dinoprostone Following Dermabrasion in Stable Vitiligo.

BACKGROUND: Dinoprostone (DNP), a prostaglandin E2 (PGE2) analogue, has been found to cause repigmenation in vitiliginous lesions. Combined medical and surgical therapy might be more useful for successful treatment of vitiligo. OBJECTIVES: In this study, we aimed to evaluate the efficacy and safety of dermabrasion followed by dinoprostone gel and to compare it with tacrolimus ointment following the same procedure in the treatment of localized stable vitiligo. METHODS: 40 patients of stable vitiligo were enrolled which were divided in two groups of 20 patients each. In group 1, dermabrasion followed by tacrolimus 0.1% ointment was done and in group 2, dermabrasion followed by dinoprostone gel was done. RESULTS: Group 1 patients showed slightly better response (P=0.039), whereas the side effect profile was better for group 2. CONCLUSION: DNP and tacrolimus have immunomodulatory and melanocyte stimulating effect and are well tolerated when combined with dermabrasion. Their effect on skin pigmentation could be enhanced by dermabrasion. J Drugs Dermatol. 2021;20(5):519-522. doi:10.36849/JDD.5751.

Change in prostaglandin signaling during sickness syndrome hyperalgesia after ovariectomy in female rats.

The present study investigated hyperalgesia during sickness syndrome in female rats. Hyperalgesia was induced by an intraperitoneal injection of lipopolysaccharide (LPS) or an intracerebroventricular injection of prostaglandin E2 (PGE2). No differences were found in basal mechanical and thermal thresholds or in LPS-induced hyperalgesia in sham-operated animals in the diestrus or proestrus phase or in ovariectomized (OVX) animals. However, higher levels of PGE2 where found in the cerebrospinal fluid of OVX animals compared to sham-operated females. Intracerebroventricular injection of PGE2 produced rapid mechanical hyperalgesia in sham-operated rats while these responses were observed at later times in OVX animals. The protein kinase A (PKA) inhibitor H-89 reduced mechanical PGE2-induced hyperalgesia in OVX female rats, whereas no effect was observed in sham-operated animals. In contrast, the exchange protein activated by cyclic adenosine monophosphate (cAMP; Epac) inhibitor ESI-09 reduced mechanical PGE2-induced hyperalgesia, whereas no effect was observed in OVX animals. PGE2 also induced thermal hyperalgesia in sham-operated and OVX female rats and a similar effect of ESI-09 was observed. These results suggest that PGE2-induced hyperalgesia that is observed during sickness syndrome has different signaling mechanisms in cycling and OVX female rats involving the activation of the cAMP-Epac or cAMP-PKA pathways, respectively.

Misoprostol vs dinoprostone vaginal insert in labour induction: comparison of obstetrical outcome.

Induction of labour (IOL) is increasingly used in obstetric practice. For patients with unfavourable cervix, we are constantly looking for an optimal, in terms of effectiveness and safety, ripening of cervix protocol. It was retrospective cohort study. We analyzed obstetrical results in 481 patients undergoing IOL in one center using two different vaginal inserts that release prostaglandins at a constant rate for 24 h-misoprostol vaginal insert (MVI) with 200 µg of misoprostol (n = 367) and dinoprostone vaginal insert (DVI) with 10 mg of dinoprostone (n = 114). Full-term, single pregnancy patients with intact fetal membranes and the cervix evaluated in Bishop score ≤ 6 were included in the analysis. In the group of MVI patients, the labour ended with caesarean section more often (OR 2.71 95% CI 1.63-4.47) and more frequent unreassuring cardiotocographic trace indicating the surgical delivery occurred (OR 2.38 95% CI 1.10-5.17). We did not notice any differences in the percentage of vacuum extraction and patients in whom the use of oxytocin was necessary during labour induction. The clinical status of newborns after birth and the pH of cord blood did not differ between groups.The use of MVI 200 µg in patients with an unriped cervix is associated with a greater chance of completing delivery by caesarean section and increased chance of abnormal intrapartum CTG trace compared to the use of DVI 10 mg. These differences do not affect the clinical and biochemical status of the newborn.

Induction of labor at term with vaginal misoprostol or a prostaglandin E2 pessary: a noninferiority randomized controlled trial.

BACKGROUND: Induction of labor is among the most common procedures for pregnant women. Only a few randomized clinical trials with relatively small samples have compared misoprostol with dinoprostone. Although their efficacy seems similar, their safety profiles have not been adequately evaluated, and economic data are sparse. OBJECTIVE: This study aimed to test the noninferiority of vaginal misoprostol (prostaglandin E1) (25 µg) to a slow-release dinoprostone (prostaglandin E2) pessary (10 µg) for induction of labor with an unfavorable cervix at term. STUDY DESIGN: This was an open-label multicenter randomized noninferiority trial at 4 university hospitals of the Research Group in Obstetrics and Gynecology between 2012 and 2015. We recruited women who underwent induction of labor for medical reasons, those with a Bishop score of ≤5 at ≥36 weeks' gestation, and those with a cephalic-presenting singleton pregnancy with no previous cesarean delivery. Women were randomly allocated to receive either vaginal misoprostol at 4-hour intervals (25 µg) or a 10-mg slow-release dinoprostone pessary. The primary outcome was the total cesarean delivery rate. Noninferiority was defined as a difference in the cesarean delivery rates between the groups of no more than 5%. Secondary outcomes included neonatal and maternal morbidity, vaginal delivery at <24 hours after starting the induction of labor process, and maternal satisfaction. RESULTS: The study included 1674 randomized women. The per-protocol analysis included 790 women in each group. The total cesarean delivery rates were 22.1% (n=175) in the misoprostol group and 19.9% (n=157) in the dinoprostone group, a difference of 2.2% (with an upper-bound 95% confidence limit of 5.6%) (P=.092). Results in the intention-to-treat analysis were similar. Neonatal and maternal morbidity rates were similar between groups. Vaginal delivery within 24 hours was significantly higher in the misoprostol group (59.3% vs 45.7%; P<.001) as was maternal satisfaction, assessed in the postpartum period by a visual analog scale (mean score, 7.1±2.4 vs 5.8±3.1; P<.001). CONCLUSION: The noninferiority of a 25-µg dose of vaginal misoprostol every 4 hours to the dinoprostone pessary for cesarean delivery rates after induction of labor at term could not be demonstrated, although the confidence limit of the difference barely exceeded the noninferiority margin. Nonetheless, given the small difference between these cesarean delivery rates and the similarity of neonatal and maternal morbidity rates in this large study, the clinical risk-to-benefit ratio justifies the use of both drugs.

Vaginal dinoprostone versus placebo for pain relief during intrauterine device insertion: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To systematically and meta-analytically investigate the efficacy and safety of vaginal dinoprostone versus placebo in pain relief during intrauterine device (IUD) insertion. METHODS: PubMed, Scopus, Web of Science, and Cochrane Library were screened till 1 October 2020. Only randomised placebo-controlled studies were included and assessed for risk of bias. Main outcomes included IUD insertion related pain, patient satisfaction, provider ease of IUD insertion, and side effects. Pooled outcomes were summarised as standardised mean difference (SMD), weighted mean difference (WMD), or risk ratio (RR) with 95% confidence interval (95% CI). RESULTS: Five studies were included, comprising 862 patients; equally 431 patients received vaginal dinoprostone and placebo. All studies showed an overall low risk of bias. When compared to placebo, dinoprostone significantly correlated with decreased pain at tenaculum placement (SMD = -0.79, 95% CI [-1.43, -0.16], p = 0.01), decreased pain at uterine sounding (SMD = -0.88, 95% CI [-1.54, -0.22], p = 0.009), decreased pain at IUD insertion (SMD = -1.18, 95% CI [-1.74, -0.61], p < 0.001), decreased need for additional analgesia (RR = 0.34, 95% CI [0.22, 0.53], p < 0.001), increased patient satisfaction (SMD = 1.41, 95% CI [0.62, 2.20], p < 0.001), and increased provider ease of IUD insertion (SMD = -1.17, 95% CI [-1.62, -0.73], p < 0.001). Fever was statistically significantly higher in dinoprostone versus placebo group (RR = 3.73, 95% CI [1.47, 9.44], p = 0.006). All other side effects-including nausea, vomiting, shivering, diarrhoea, abdominal cramps, vasovagal attack, uterine perforation, and postprocedural bleeding-did not substantially differ between both groups. CONCLUSIONS: This first ever meta-analysis advocates that dinoprostone compared with placebo is safe, effective, and yields favourable analgesic outcomes during IUD insertion.

Cervical ripening in prolonged pregnancies by silicone double balloon catheter versus vaginal dinoprostone slow release system: The MAGPOP randomised controlled trial.

BACKGROUND: Prolonged pregnancies are a frequent indication for induction of labour. When the cervix is unfavourable, cervical ripening before oxytocin administration is recommended to increase the likelihood of vaginal delivery, but no particular method is currently recommended for cervical ripening of prolonged pregnancies. This trial evaluates whether the use of mechanical cervical ripening with a silicone double balloon catheter for induction of labour in prolonged pregnancies reduces the cesarean section rate for nonreassuring fetal status compared with pharmacological cervical ripening by a vaginal pessary for the slow release of dinoprostone (prostaglandin E2). METHODS AND FINDINGS: This is a multicentre, superiority, open-label, parallel-group, randomised controlled trial conducted in 15 French maternity units. Women with singleton pregnancies, a vertex presentation, ≥41+0 and ≤42+0 weeks' gestation, a Bishop score <6, intact membranes, and no history of cesarean delivery for whom induction of labour was decided were randomised to either mechanical cervical ripening with a Cook Cervical Ripening Balloon or pharmacological cervical ripening by a Propess vaginal pessary serving as a prostaglandin E2 slow-release system. The primary outcome was the rate of cesarean for nonreassuring fetal status, with an independent endpoint adjudication committee determining whether the fetal heart rate was nonreassuring. Secondary outcomes included delivery (time from cervical ripening to delivery, number of patients requiring analgesics), maternal and neonatal outcomes. Between January 2017 and December 2018, 1,220 women were randomised in a 1:1 ratio, 610 allocated to a silicone double balloon catheter, and 610 to the Propess vaginal pessary for the slow release of dinoprostone. The mean age of women was 31 years old, and 80% of them were of white ethnicity. The cesarean rates for nonreassuring fetal status were 5.8% (35/607) in the mechanical ripening group and 5.3% (32/609) in the pharmacological ripening group (proportion difference: 0.5%; 95% confidence interval (CI) -2.1% to 3.1%, p = 0.70). Time from cervical ripening to delivery was shorter in the pharmacological ripening group (23 hours versus 32 hours, median difference 6.5 95% CI 5.0 to 7.9, p < 0.001), and fewer women required analgesics in the mechanical ripening group (27.5% versus 35.4%, difference in proportion -7.9%, 95% CI -13.2% to -2.7%, p = 0.003). There were no statistically significant differences between the 2 groups for other delivery, maternal, and neonatal outcomes. A limitation was a low observed rate of cesarean section. CONCLUSIONS: In this study, we observed no difference in the rates of cesarean deliveries for nonreassuring fetal status between mechanical ripening with a silicone double balloon catheter and pharmacological cervical ripening with a pessary for the slow release of dinoprostone. TRIAL REGISTRATION: ClinicalTrials.gov NCT02907060.

Prostaglandin E2 stimulates cAMP signaling and resensitizes human leukemia cells to glucocorticoid-induced cell death.

Glucocorticoid (GC) resistance remains a clinical challenge in pediatric acute lymphoblastic leukemia where response to GC is a reliable prognostic indicator. To identify GC resistance pathways, we conducted a genome-wide, survival-based, short hairpin RNA screen in murine T-cell acute lymphoblastic leukemia (T-ALL) cells. Genes identified in the screen interfere with cyclic adenosine monophosphate (cAMP) signaling and are underexpressed in GC-resistant or relapsed ALL patients. Silencing of the cAMP-activating Gnas gene interfered with GC-induced gene expression, resulting in dexamethasone resistance in vitro and in vivo. We demonstrate that cAMP signaling synergizes with dexamethasone to enhance cell death in GC-resistant human T-ALL cells. We find the E prostanoid receptor 4 expressed in T-ALL samples and demonstrate that prostaglandin E2 (PGE2) increases intracellular cAMP, potentiates GC-induced gene expression, and sensitizes human T-ALL samples to dexamethasone in vitro and in vivo. These findings identify PGE2 as a target for GC resensitization in relapsed pediatric T-ALL.

Controlled Release Dinoprostone Insert and Foley Compared to Foley Alone: A Randomized Pilot Trial.

OBJECTIVE: The aim of study is to compare, in a pilot study, combined dinoprostone vaginal insert and Foley catheter (DVI + Foley) with Foley alone (Foley) for cervical ripening and labor induction at term. STUDY DESIGN: In this open-label pilot randomized controlled trial, women not in labor, with intact membranes, no prior uterine incision, an unfavorable cervix, gestational age ≥37 weeks, and a live, nonanomalous singleton fetus in cephalic presentation were randomly assigned, stratified by parity, to DVI + Foley or Foley. Oxytocin was used in both groups after cervical ripening. Primary outcome was time to vaginal delivery. RESULTS: From April 2017 to January 2018, 100 women were randomized. Median (25-75th percentile) time to vaginal delivery for nulliparous women was 21.2 (16.6-38.0) hours with DVI + Foley (n = 26) compared with 31.3 (23.3-46.9) hours with Foley (n = 24) (Wilcoxon p = 0.05). Median time to vaginal delivery for parous women was 17.1 (13.6-21.9) hours with DVI + Foley (n = 25) compared with 14.8 (12.7-19.5) hours with Foley (n = 25) (Wilcoxon p = 0.21). Results were also analyzed to consider the competing risk of cesarean using cumulative incidence functions. CONCLUSION: Compared with Foley alone, combined use of the dinoprostone vaginal insert and Foley for cervical ripening may shorten time to vaginal delivery for nulliparous but not parous women.

Effects of intravesical prostaglandin E2 on bladder function are preserved in capsaicin-desensitized rats.

Prostaglandin E2 (PGE2) instilled into the bladder generates symptoms of urinary urgency in healthy women and reduces bladder capacity and urethral pressure in both humans and female rats. Systemic capsaicin desensitization, which causes degeneration of C-fibers, prevented PGE2-mediated reductions in bladder capacity, suggesting that PGE2 acts as an irritant (Maggi CA, Giuliani S, Conte B, Furio M, Santicioli P, Meli P, Gragnani L, Meli A. Eur J Pharmacol 145: 105-112, 1988). In the present study, we instilled PGE2 in female rats after capsaicin desensitization but without the hypogastric nerve transection that was conducted in the Maggi et al. study. One week after capsaicin injection (125 mg/kg sc), rats underwent cystometric and urethral perfusion testing under urethane anesthesia with saline and 100 µM PGE2. Similar to naïve rats, capsaicin-desensitized rats exhibited a reduction in bladder capacity from 1.23 ± 0.08 mL to 0.70 ± 0.10 mL (P = 0.002, n = 9), a reduction in urethral perfusion pressure from 19.3 ± 2.1 cmH2O to 10.9 ± 1.2 cmH2O (P = 0.004, n = 9), and a reduction in bladder compliance from 0.13 ± 0.020 mL/cmH2O to 0.090 ± 0.014 mL/cmH2O (P = 0.011, n = 9). Thus, changes in bladder function following the instillation of PGE2 were not dependent on capsaicin-sensitive pathways. Further, these results suggest that urethral relaxation/weakness and/or increased detrusor pressure as a result of decreased compliance may contribute to urinary urgency and highlight potential targets for new therapies for overactive bladder.

Effect of intramuscular and intravaginal PGE-2 treatment compared to intramuscular oxytocin treatment in eutocic sows on the farrowing performance in a free farrowing system.

A duration of parturition beyond 300 min negatively impacts the health of the sow and the survival of piglets during parturition. Hence, oxytocin is widely used to speed up the parturition. However, oxytocin's negative side effects raise the need of finding alternative treatments such as those already implemented in human medicine. The aim of this study was to evaluate the efficacy of Prostaglandin E2 (PGE2) applied intravaginally (PGE2-V) (1.0 mg) or intramuscularly (PGE2-M) (2.5 mg) to improve the parturition process after expulsion of the fourth piglet compared to a placebo (P-V), which was sterile intravaginal gel or intramuscular oxytocin application (OXY-M) (20 iu) in free farrowing systems.In total, 201 eutocic sows were examined after stratification by parity and random allocation into groups: 54 (P-V), 48 (OXY-M), 50 (PGE2-V), 49 (PGE2-M). Farrowing duration (time between first piglet and last piglet), piglet interval and placenta expulsion duration (time between first and last placenta) were recorded, and each piglet was scored for meconium staining and vitality. Furthermore, stillborn piglets were categorized into ante-partum and intra-partum deaths.Under the present conditions, neither administration of PGE2 nor oxytocin revealed a significant effect on the farrowing process or the vitality of the piglets when compared to untreated sows. Nonetheless, significant differences could be detected between PGE-2 and oxytocin treatments. The duration of farrowing was significantly shorter in oxytocin-treated sows (156 min) compared to sows treated intramuscularly with PGE2 (238 min). Furthermore, the placenta expulsion duration in the OXY-M group (130 min) significantly differed from PGE2-V (198 min) and PGE2-M group (218 min). Although these accelerations of parturition might be considered as a beneficial effect, routine treatment with uterotonic agents after birth of the fourth piglet in free farrowing eutocic sows cannot be recommended, because an overall benefit when compared to untreated sows was not approved.

Effectiveness of Dinoprostone and Cook's Balloon for Labor Induction in Primipara Women at Term.

Labor induction is commonly used for achieving successful vaginal delivery. This study aimed to compare the effectiveness of dinoprostone and Cook's balloon as labor-inducing agents in primipara women at term. A retrospective cohort study among primipara women was conducted in Hubei Maternity and Child Health Hospital. Basic clinical characteristics were collected. The main outcomes were vaginal delivery rate, cesarean section rate and forceps delivery rate. Obstetric and perinatal outcomes were also compared. Univariate and multivariate analyses were further performed to evaluate the predictors for vaginal delivery within 24 h. A total of 845 eligible primipara women undergoing labor induction were recruited. Of them, 141 women were induced with dinoprostone (dinoprostone group, DG), and 704 with Cook's balloon (Cook's balloon group, CG). Groups were homogeneous except more women with premature rupture of membranes in DG, with gestational hypertension in CG (P<0.05). The vaginal delivery rate within 12 h was 1.98% and 16.52% in CG and DG respectively (P=0.0001). Besides, the vaginal delivery rate within 24 h was 37.62% and 52.26% in CG and DG respectively (P=0.0079). DG showed the lower rate of oxytocin augmentation, artificial rupture of membrane and postpartum hemorrhage and the shorter interval from insertion to active labor than CG (P<0.05). Multivariate regression analysis revealed that abortion history, oxytocin augmentation, artificial rupture of membrane, and obstetric analgesia were independent predictors for vaginal delivery within 24 h. In conclusion, dinoprostone was more effective than Cook's balloon to induce labor and achieve vaginal birth in the sample of primipara women at term.