The Role of the NLRP3 Inflammasome in the Molecular and Biochemical Mechanisms of Cervical Ripening: A Comprehensive Review.

The uterine cervix is one of the key factors involved in ensuring a proper track of gestation and labor. At the end of the gestational period, the cervix undergoes extensive changes, which can be summarized as a transformation from a non-favorable cervix to one that is soft and prone to dilation. During a process called cervical ripening, fundamental remodeling of the cervical extracellular matrix (ECM) occurs. The cervical ripening process is a derivative of many interlocking and mutually driving biochemical and molecular pathways under the strict control of mediators such as inflammatory cytokines, nitric oxide, prostaglandins, and reactive oxygen species. A thorough understanding of all these pathways and learning about possible triggering factors will allow us to develop new, better treatment algorithms and therapeutic goals that could protect women from both dysfunctional childbirth and premature birth. This review aims to present the possible role of the NLRP3 inflammasome in the cervical ripening process, emphasizing possible mechanisms of action and regulatory factors.

Association of the key immunological and hemodynamic determinants with cervix ripening in pregnant women.

OBJECTIVE: Aim: To investigate a correlation between cervical ripening, the immunological features and the hemodynamic characteristics of the cervix during the preparation for vaginal labor. PATIENTS AND METHODS: Materials and Methods: We examined 75 pregnant women at different gestational age. General clinical and immunological studies were conducted in order to check serum concentration of cytokines IL-6, IL-1ß, and TNF-α. Ultrasound and Doppler study were used to determine resistance index and systolic-diastolic ratio of blood flow in the common uterine artery as well as the descending and ascending parts and cervical stromal arteries. RESULTS: Results: Pregnant women with high cervical ripening score had high concentrations of the major proinflammatory cytokines (IL-1ß, IL-6, and TNF-α). Analysis of the of the cervical blood flow indicators of the studied groups showed significant differences in the indices of vascular resistance in the vessels that feed the cervix. Our data showed a significant correlation between the cervix ripening and both the serum levels of the studied cytokines and the level of peripheral vascular resistance indices in the common uterine arteries of the cervix, and the blood flow indices in the cervical stromal vessels. CONCLUSION: Conclusions: Our study shows that the process of preparing the woman's body for labor is associated with immunological adjustment and increased hemodynamics of the cervix. We report that cervical ripening is associated with the immunological components and hemodynamic parameters of the cervix at late-stage pregnancy. Measuring cervix ripening and the accompanied changes in cytokine levels and hemodynamic parameters will form a more accurate assessment of birth preparedness and labor complications.

Routine vaginal examination to assess labor progress at 8 compared to 4 hours after early amniotomy following Foley balloon ripening in the labor induction of multiparas: a randomized trial.

BACKGROUND: Vaginal examination to monitor labor progress is recommended at least every 4 hours, but it can cause pain and embarrassment to women. Trial data are limited on the best intensity for vaginal examination. Vaginal examination is not needed for oxytocin dose titration after an amniotomy has been performed and oxytocin infusion started. The Foley balloon commonly ripens the cervix without strong contractions. Amniotomy and oxytocin infusion are usually required to drive labor. OBJECTIVE: This study aimed to evaluate the first vaginal examination at 8 vs 4 hours after amniotomy-oxytocin after Foley ripening in multiparous labor induction. STUDY DESIGN: A randomized controlled trial was conducted from October 2021 to September 2022 at the University Malaya Medical Center, Kuala Lumpur, Malaysia. Multiparas at term were recruited at admission for labor induction. Participants were randomized to a first routine vaginal examination at 8 or 4 hours after Foley balloon ripening and amniotomy. Titrated oxytocin infusion was routinely commenced after amniotomy to initiate contractions. The 2 primary outcomes were the time from amniotomy to delivery (noninferiority hypothesis) and maternal satisfaction (superiority hypothesis). Data were analyzed using the Student t test, Mann-Whitney U test, and chi-square test (or Fisher exact test), as suitable for the data. RESULTS: A total of 204 women were randomized, 102 to each arm. Amniotomy to birth intervals were 4.97±2.47 hours in the 8-hour arm and 5.79±3.17 hours in the 4-hour arm (mean difference, -0.82; 97.5% confidence interval, -1.72 to 0.08; P=.041; Bonferroni correction), which were noninferior within the prespecified 2-hour upper margin, and the maternal satisfaction scores (11-point 0-10 numerical rating scale) with allocated labor care were 9 (interquartile range, 8-9) in the 8-hour arm and 8 (interquartile range, 7-9) in the 4-hour arm (P=.814). In addition, oxytocin infusion to birth interval difference was noninferior within the 97.5% confidence interval (-1.59 to 0.23) margin of 1.3 hours. Of the maternal outcomes, the amniotomy to first vaginal examination intervals were 3.9±1.8 hours in the 8-hour arm and 3.4±1.3 hours in the 4-hour arm (P=.026), and the numbers of vaginal examinations were 2.00 (interquartile range, 2.00-3.00) in the 8-hour arm and 3.00 (interquratile range, 2.00-3.25) in the 4-hour arm (P<.001). For the 8-hour arm, the first vaginal examination was less likely to be as scheduled and more likely to be indicated by sensation to bear down (P<.001), and the epidural analgesia rates were lower (13/102 participants [12.7%] in the 8-hour arm vs 28/102 participants [27.5%] in the 4-hour arm; relative risk, 0.46; 95% confidence interval, 0.26-0.84; P=.009). Other outcomes of the mode of delivery, indications for cesarean delivery, and delivery blood loss were not different. Neonatal outcomes were not different. CONCLUSION: Routine first vaginal examination at 8 hours compared with that at 4 hours was noninferior for the time to birth but did not improve maternal satisfaction.

Digital versus speculum insertion of Foley catheter for labor induction: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To compare Foley catheter insertion by digital blind method to its placement with a sterile speculum in women with unripe cervix for induction of labor. METHODS: A systematic search was conducted in Cochrane Library, PubMed, Web of Science, and Scopus databases for randomized clinical trials (RCTs) from inception to July 2023. Included studies compared digital to speculum placement of the Foley catheter for labor induction. Data from the included studies were extracted and pooled using RevMan software for meta-analysis. The primary outcome was pain score during the procedure measured by the Visual Analog Scale (VAS). Secondary outcomes included Foley catheter insertion duration, cesarean delivery rate, induction to delivery interval, Bishop score, need for other cervical ripening methods, maternal satisfaction, and maternal fever. RESULTS: Four RCTs involving a total of 600 patients met the inclusion criteria. Pain during the procedure and Foley catheter insertion duration were significantly reduced in the digital insertion group compared to the speculum-guided group (p < 0.05). The Bishop score showed a significant improvement in the digital Foley catheter placement group. However, there were no statistically significant differences in the cesarean delivery rate or the requirement for additional cervical ripening methods between the two groups. Maternal satisfaction with the delivery process was significantly improved in the digital insertion group (p < 0.001). Induction to delivery interval and maternal fever were comparable between both groups. CONCLUSIONS: Digital placement of Foley catheter can be considered as an alternative to the sterile speculum method for pre-induction cervical ripening. More trials are required to confirm our findings.

Just Pop It: Early AROM After Cervical Ripening Reduces the Time to Delivery.

In pregnant patients at term undergoing induction of labor, early time-based artificial rupture of membranes (AROM) within 1 hour of Foley bulb expulsion results in a shorter duration of labor by nearly 9 hours with no significant difference in cesarean delivery rates or maternal or neonatal adverse outcomes.1.

Methods for the induction of labor: efficacy and safety.

This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 µg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygroscopic cervical dilator has been found to be effective for preinduction cervical ripening. Although a pharmacologic agent may be administered after the use of the synthetic hygroscopic dilator, in an attempt to reduce the interval to vaginal delivery, concomitant use of mechanical and pharmacologic methods is being explored. Combining the use of a single-balloon catheter with dinoprostone, misoprostol, or oxytocin enhances the efficacy of these pharmacologic agents in cervical ripening and labor induction. The efficacy of single- and double-balloon catheters in cervical ripening and labor induction seems similar. To date, the combination of misoprostol with an intracervical catheter seems to be the best approach when balancing delivery times with safety. Although complementary methods are occasionally used by patients, given the lack of data documenting their efficacy and safety, these methods are rarely used in hospital settings.

Comparison of digital and speculum-guided methods of transcervical Foley catheter insertion in primigravida undergoing cervical ripening at term gestation: a noninferiority randomized clinical trial.

BACKGROUND: Foley catheter insertion is frequently used for cervical ripening during the induction of labor. However, the insertion failure, safety, maternal side effects, complications, and satisfaction of digital compared with speculum-guided Foley catheter placement have not been evaluated in a large trial involving primigravida. OBJECTIVE: The study aimed to compare the insertion failure rate of digital and speculum-based transcervical Foley catheter placement in primigravida. The co-primary outcome was insertion-associated pain. The secondary outcomes were the time required for successful insertion, maternal satisfaction, and maternal complications within 24 hours of Foley insertion. STUDY DESIGN: This randomized, open-label, parallel-arm, noninferiority clinical trial was performed in a large tertiary care university hospital. Primigravida aged >18 years with term gestation (≥37 weeks) were included in this study. Additional inclusion criteria for enrollment in this study were singleton pregnancy with a cephalic presentation, intact membrane, a Bishop score of ≤5, and reassuring preinduction fetal heart rate tracing. All women planned for cervical ripening were assessed for eligibility and were randomized into digital or speculum arms. Foley catheter insertion was performed in a supine lithotomy position. Vaginal and cervical cleaning were performed before insertion. A 22-French Foley balloon catheter was guided digitally or via speculum to position the bulb at the level of the internal os using water-soluble lubricant. Insertion-associated pain was measured using a visual numeric rating scale, and maternal satisfaction was assessed using a set of questions. RESULTS: Four hundred and sixty-nine pregnant women were assessed for eligibility, and 446 patients were enrolled and randomized. The median age of the parturients was 24 (19-40) and 24 (18-38) years, respectively. The body mass index, gestational age at randomization, the incidence of postdated pregnancy, and prerandomization Bishop scores were comparable. Insertion failure was observed in 24 (10.8%) and 17 (7.6%) women in digital and speculum arms, respectively (relative risk=1.41 [95% confidence interval, 0.78-2.55]; P=.25). Requirements of >1 attempt (5.4% vs 3.6%) followed by the change in hands (3.6% vs 2.7%) were the most common reasons for insertion failure. The median (interquartile range) visual numeric rating scale was comparable (6 [2-9] vs 5 [2-10]; P=.15). The time taken for successful insertion was similar (58 [12-241] vs 54 [10-281]; P=.30). 9.4% and 10.8% of women required additional methods of cervical ripening. More women in the speculum group (41.7% vs 33.2%; P=.06) felt a medium level of discomfort than the digital group. CONCLUSION: Insertion failure and insertion-related pain in the digital approach were comparable to the speculum-guided approach for transcervical Foley catheter insertion in primigravida for cervical ripening. Nevertheless, maternal satisfaction was higher in the digital group because of a lesser level of discomfort.

Outpatient cervical ripening and labor induction with low-dose vaginal misoprostol reduces the interval to delivery: a systematic review and network meta-analysis.

OBJECTIVE: Several systematic reviews and meta-analyses have summarized the evidence on the efficacy and safety of various outpatient cervical ripening methods. However, the method with the highest efficacy and safety profile has not been determined conclusively. We performed a systematic review and network meta-analysis of published randomized controlled trials to assess the efficacy and safety of cervical ripening methods currently employed in the outpatient setting. DATA SOURCES: With the assistance of an experienced medical librarian, we performed a systematic search of the literature using MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. We systematically searched electronic databases from inception to January 14, 2020. STUDY ELIGIBILITY CRITERIA: We considered randomized controlled trials comparing a variety of methods for outpatient cervical ripening. METHODS: We conducted a frequentist random effects network meta-analysis employing data from randomized controlled trials. We performed a direct, pairwise meta-analysis to compare the efficacy of various outpatient cervical ripening methods, including placebo. We employed ranking strategies to determine the most efficacious method using the surface under the cumulative ranking curve; a higher surface under the cumulative ranking curve value implied a more efficacious method. We assessed the following outcomes: time from intervention to delivery, cesarean delivery rates, changes in the Bishop score, need for additional ripening methods, incidence of Apgar scores <7 at 5 minutes, and uterine hyperstimulation. RESULTS: We included data from 42 randomized controlled trials including 6093 participants. When assessing the efficacy of all methods, 25 µg vaginal misoprostol was the most efficacious in reducing the time from intervention to delivery (surface under the cumulative ranking curve of 1.0) without increasing the odds of cesarean delivery, the need for additional ripening methods, the incidence of a low Apgar score, or uterine hyperstimulation. Acupressure (surface under the cumulative ranking curve of 0.3) and primrose oil (surface under the cumulative ranking curve of 0.2) were the least effective methods in reducing the time to delivery interval. Among effective methods, 50 mg oral mifepristone was associated with the lowest odds of cesarean delivery (surface under the cumulative ranking curve of 0.9). CONCLUSION: When balancing efficacy and safety, vaginal misoprostol 25 µg represents the best method for outpatient cervical ripening.

Tafoxiparin, a novel drug candidate for cervical ripening and labor augmentation: results from 2 randomized, placebo-controlled studies.

BACKGROUND: Slow progression of labor is a common obstetrical problem with multiple associated complications. Tafoxiparin is a depolymerized form of heparin with a molecular structure that eliminates the anticoagulant effects of heparin. We report on 2 phase II clinical studies of tafoxiparin in primiparas. Study 1 was an exploratory, first-in-pregnant-women study and study 2 was a dose-finding study. OBJECTIVE: Study 1 was performed to explore the effects on labor time of subcutaneous administration of tafoxiparin before onset of labor. Study 2 was performed to test the hypothesis that intravenous treatment with tafoxiparin reduces the risk for prolonged labor after spontaneous labor onset in situations requiring oxytocin stimulation because of dystocia. STUDY DESIGN: Both studies were randomized, double-blind, and placebo-controlled. Participants were healthy, nulliparous females aged 18 to 45 years with a normal singleton pregnancy and gestational age confirmed by ultrasound. The primary endpoints were time from onset of established labor (cervical dilation of 4 cm) until delivery (study 1) and time from start of study treatment infusion until delivery (study 2). In study 1, patients at 38 to 40 weeks of gestation received 60 mg tafoxiparin or placebo daily as 0.4 mL subcutaneous injections until labor onset (maximum 28 days). In study 2, patients experiencing slow progression of labor, a prolonged latent phase, or labor arrest received a placebo or 1 of 3 short-term tafoxiparin regimens (initial bolus 7, 21, or 35 mg followed by continuous infusion at 5, 15, or 25 mg/hour until delivery; maximum duration, 36 hours) in conjunction with oxytocin. RESULTS: The number of participants randomized in study 1 was 263, and 361 were randomized in study 2. There were no statistically significant differences in the primary endpoints between those receiving tafoxiparin and those receiving the placebo in both studies. However, in study 1, the risk for having a labor time exceeding 12 hours was significantly reduced by tafoxiparin (tafoxiparin 6/114 [5%] vs placebo 18/101 [18%]; P=.0045). Post hoc analyses showed that women who underwent labor induction had a median (range) labor time of 4.44 (1.2-8.5) hours with tafoxiparin and 7.03 (1.5-14.3) hours with the placebo (P=.0041) and that co-administration of tafoxiparin potentiates the effect of oxytocin and facilitates a shorter labor time among women with a labor time exceeding 6 to 8 hours (P=.016). Among women induced into labor, tafoxiparin had a positive effect on cervical ripening in 11 of 13 cases (85%) compared with 3 of 13 participants (23%) who received the placebo (P=.004). For women requiring oxytocin because of slow progression of labor, the corresponding results were 34 of 51 participants (66%) vs 16 of 40 participants (40%) (P=.004). In study 2, tafoxiparin had no positive effects on the secondary endpoints when compared with the placebo. Except for injection-site reactions in study 1, adverse events were no more common for tafoxiparin than for the placebo among either mothers or infants. There were few serious or treatment-related adverse events. CONCLUSION: Subcutaneous treatment with tafoxiparin before labor onset (study 1) may be effective in reducing the labor time among women undergoing labor induction and among those requiring oxytocin for slow progression of labor. Moreover, tafoxiparin may have a positive effect on cervical ripening. Short-term, intravenous treatment with tafoxiparin as an adjunct to oxytocin in patients with labor arrest (study 2) did not affect labor time or other endpoints. Both studies suggest that tafoxiparin has a favorable safety profile in mothers and their infants.

Randomized control trial comparing hygroscopic cervical dilators to cervical ripening balloon for outpatient cervical ripening.

BACKGROUND: Outpatient term preinduction cervical ripening with mechanical agents has been associated with reduced length of stay, decreased cesarean delivery rates, low maternal and neonatal complications, and increased incidence of vaginal delivery within 24 hours. OBJECTIVE: This study aimed to demonstrate equivalent efficacy between synthetic hygroscopic dilators and the single-balloon catheter for outpatient cervical ripening. STUDY DESIGN: This randomized control equivalence trial compared synthetic hygroscopic dilators with the 30-mL silicone single-balloon catheter in primiparous and multiparous patients undergoing labor induction. The primary outcome was time from admission to delivery, with a prespecified 3-hour margin of equivalence. The secondary objectives were patient outcomes and perspectives. RESULTS: Between March 1, 2019, and May 31, 2021, 1605 patients met the screening criteria, and 174 patients completed the study. The mean admission-to-delivery time was equivalent at 18.01 hours for the dilator group vs 17.55 hours for the balloon group (P=.04). The cesarean delivery rate of primiparous patients was similar at 28.1% with dilators vs 29.7% with the balloon. The groups had similar median cervical dilation and pain scores on insertion and admission. Overall patient satisfaction was high, 92.8% with dilators vs 96.2% with the balloon. The balloon group had significantly higher rates of early admission and device expulsion. CONCLUSION: Although the enrollment goal was not met, our study suggests that synthetic hygroscopic dilators and the single-balloon catheter for outpatient cervical ripening are both efficacious with similar time from admission to delivery, pain scores, and patient satisfaction with the procedure.

Effect of epidural analgesia on cervical ripening using dinoprostone vaginal inserts.

OBJECTIVE: To clarify whether the duration from cervical ripening induction to labor onset is prolonged when epidural analgesia is administered following application of dinoprostone vaginal inserts vs. cervical ripening balloon. METHODS: This retrospective study included mothers with singleton deliveries at a single center between 2020-2021. Nulliparous women who underwent labor induction and requested epidural analgesia during labor after 37 weeks of gestation were included. The duration from cervical ripening induction to labor onset was compared between women using a dinoprostone vaginal insert and those using a cervical ripening balloon and between women who received epidural analgesia before and after labor onset. RESULTS: In the dinoprostone vaginal insert group, the duration was significantly shorter in the subgroup that received epidural analgesia after labor onset (estimated median, 545 [95% confidence interval: 229-861 min]) than the subgroup that received it before labor onset (estimated median, 1,570 [95% confidence interval: 1,226-1,914] min, p = 0.004). However, in the cervical ripening balloon group, the difference between subgroups was not significant. The length of labor among the groups was also not significantly different. CONCLUSION: Epidural analgesia as labor relaxant adversely affected the progression of uterine cervical ripening when dinoprostone vaginal inserts were used, whereas it did not affect cervical ripening when a mechanical cervical dilatation balloon was used. The present results are significant for choosing the appropriate ripening method.

Early vs delayed amniotomy following transcervical Foley balloon in the induction of labor: a randomized clinical trial.

BACKGROUND: The optimal timing of amniotomy during labor induction is a topic of ongoing debate due to the potential risks associated with both amniotomy and prolonged labor. As such, individuals in the field of obstetrics and gynecology must carefully evaluate the associated benefits and drawbacks of this procedure. While amniotomy can expedite the labor process, it may also lead to complications such as umbilical cord prolapse, fetal distress, and infection. Therefore, a careful and thorough examination of the risks and benefits of amniotomy during labor induction is essential in making an informed decision regarding the optimal timing of this procedure. OBJECTIVE: This study aimed to determine if an amniotomy within 2 hours after Foley balloon removal reduced the duration of active labor and time taken to achieve vaginal delivery when compared with an amniotomy ≥4 hours after balloon removal among term pregnant women who underwent labor induction. STUDY DESIGN: This was an open-label, randomized controlled trial that was conducted at a single academic center from October 2020 to March 2023. Term participants who were eligible for preinduction cervical ripening with a Foley balloon were randomized into 2 groups, namely the early amniotomy (rupture of membranes within 2 hours after Foley balloon removal) and delayed amniotomy (rupture of membranes performed more than 4 hours after Foley balloon removal) groups. Randomization was stratified by parity. The primary outcome was time from Foley balloon insertion to active phase of labor. Secondary outcomes, including time to delivery, cesarean delivery rates, and maternal and neonatal complications, were analyzed using intention-to-treat and per-protocol analyses. RESULTS: Of the 150 participants who consented and were enrolled, 149 were included in the analysis. In the intention-to-treat population, an early amniotomy did not significantly shorten the time between Foley balloon insertion and active labor when compared with a delayed amniotomy (885 vs 975 minutes; P=.08). An early amniotomy was associated with a significantly shorter time from Foley balloon placement to active labor in nulliparous individuals (1211; 584-2340 vs 1585; 683-2760; P=.02). When evaluating the secondary outcomes, an early amniotomy was associated with a significantly shorter time to active labor onset (312.5 vs 442.5 minutes; P=.02) and delivery (484 vs 587 minutes; P=.03) from Foley balloon removal with a higher rate of delivery within 36 hours (96% vs 85%; P=.03). Individuals in the early amniotomy group reached active labor 1.5 times faster after Foley balloon insertion than those in the delayed group (hazard ratio, 1.5; 95% confidence interval, 1.1-2.2; P=.02). Those with an early amniotomy also reached vaginal delivery 1.5 times faster after Foley balloon removal than those in the delayed group (hazard ratio, 1.5; 95% confidence interval, 1-2.2; P=.03). A delayed amniotomy was associated with a higher rate of postpartum hemorrhage (0% vs 9.5%; P=.01). No significant differences were observed in the cesarean delivery rates, length of hospital stay, maternal infection, or neonatal outcomes. CONCLUSION: Although an early amniotomy does not shorten the time from Foley balloon insertion to active labor, it shortens time from Foley balloon removal to active labor and delivery without increasing complications. The increased postpartum hemorrhage rate in the delayed amniotomy group suggests increased risks with delayed amniotomy.

Applying Tension to the Transcervical Foley Balloon and Delivery Times in Term Nulliparous Women Undergoing Induction of Labor: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of applying tension to a transcervical Foley balloon on delivery time in term nulliparous patients undergoing labor induction. METHODS: This cluster randomized clinical trial included 279 term nulliparous women presenting for labor induction with a plan for cervical ripening through transcervical Foley balloon placement. Participants were assigned to either the tension group (n=138) or the no-tension group (n=141) on the basis of randomized, weekly clusters (26 total clusters). The primary outcome measured was the time from initial Foley balloon insertion to delivery. Secondary outcomes included cesarean delivery rates, peripartum infection, and neonatal intensive care unit (NICU) admission. Our prior data suggested that delivery time in the tension group would be about 1,053 minutes. We estimated a sample size of 260 (130 per group, 26 clusters) on the basis of a 25% difference, power of 80%, and two-sided α of 0.05. RESULTS: A total of 279 term nulliparous patients were included in the analysis. The median time from Foley placement to delivery was 1,596 minutes (range 430-3,438 minutes) for the tension group and 1,621 minutes (range 488-3,323 minutes) for the no-tension group ( P =.8); similar results were noted for time to vaginal delivery. No significant differences were observed in the secondary outcomes, including the rates of cesarean delivery (34.1% vs 29.8%, P =.7), peripartum infection, and NICU admission, between the two groups. CONCLUSION: Applying tension to a transcervical Foley balloon in term nulliparous women undergoing labor induction did not significantly reduce delivery time or improve secondary outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT05404776.

The effect of slow-release vaginal dinoprostone on maternal and fetal oxidative stress in term pregnancies complicated by oligohydramnios: Prospective cohort study.

BACKGROUND: To evaluate changes in oxidant status using thiol/disulfide homeostasis in mothers and fetuses after induction of labor with slow-release vaginal dinoprostone inserts. METHODS: A total of 70 pregnant women were divided into two groups. Thirty-five women in whom labor was induced with slow-release vaginal dinoprostone inserts (10 mg of prostaglandin E2, group A) were compared before and after the administration. The other 35 women, who were followed up spontaneously during labor (group B), were included as a control group. Both groups were diagnosed with isolated oligohydramnios without signs of placental insufficiency. The thiol/disulfide homeostasis parameters were calculated before medical induction and after removal of the insert at the beginning of the active phase of labor. Maternal and cord blood values were measured in both groups. RESULTS: Although the balance shifted to the antioxidant side after the slow-release vaginal dinoprostone insert was applied, there was no significant difference in maternal oxidative load compared to the pre-application status (5.32 ± 014/5.16 ± 0.15, p = 0.491). Despite the shift toward the antioxidant side, maternal antioxidants were still significantly lower in the group that received slow-release vaginal dinoprostone at the beginning of the active phase of labor than in the control group (295.98 ± 13.03/346.47 ± 12.04, respectively, p = 0.009). There was no statistically significant difference in terms of oxidative balance or newborn Apgar score ( p > 0.05). CONCLUSION: Induction of labor with slow-release vaginal dinoprostone inserts in pregnancies with isolated oligohydramnios does not cause further oxidative stress and is safe for both mothers and neonates in terms of oxidant load by thiol/disulfide homeostasis.

Evidence Based Management of Labor.

Importance: Induction of labor (IOL) is a common obstetric intervention. Augmentation of labor and active management of the second stage is frequently required in obstetric practice. However, techniques around labor and induction management vary widely. Evidence-based practice regarding induction and labor management can reduce birth complications such as infection and hemorrhage and decrease rates of cesarean delivery. Objective: To review existing evidence on IOL and labor management strategies with respect to preparing for induction, cervical ripening, induction and augmentation, and second stage of labor techniques. Evidence acquisition: Review of recent original research, review articles, and guidelines on IOL using PubMed (2000-2022). Results: Preinduction, pelvic floor training and perineal massage reduce postpartum urinary incontinence and perineal trauma, respectively. Timely membrane sweeping (38 weeks) can promote spontaneous labor and prevent postterm inductions. Outpatient Foley bulb placement in low-risk nulliparous patients with planned IOL reduces time to delivery. Inpatient Foley bulb use beyond 6 to 12 hours shows no benefit. When synthetic prostaglandins are indicated, vaginal misoprostol should be preferred. For nulliparous patients and those with obesity, oxytocin should be titrated using a high-dose protocol. Once cervical dilation is complete, pushing should begin immediately. Warm compresses and perineal massage decrease risk of perineal trauma. Conclusion and relevance: Several strategies exist to assist in successful IOL and promote vaginal delivery. Evidence-based strategies should be used to improve outcomes and decrease risk of complications and cesarean delivery. Recommendations should be shared across interdisciplinary team members, creating a model that promotes safe patient care.

Methods of induction of labor in women with obesity: A secondary analysis of two multicenter randomized controlled trials.

INTRODUCTION: Obesity is an increasing public health concern worldwide and can lead to more complications in pregnancy and childbirth. Women with obesity more often require induction of labor for various indications. The aim of this study is to assess which method of induction of labor is safest and most effective in women with obesity. MATERIAL AND METHODS: This is a secondary analysis of two randomized controlled trials about induction of labor. Women with a term singleton pregnancy in cephalic presentation, an unfavorable cervix, intact membranes and without a previous cesarean section were randomly allocated to cervical priming with a Foley catheter or vaginal prostaglandin-E2-gel (PROBAAT-I) or a Foley catheter or oral misoprostol (PROBAAT-II). The inclusion and exclusion criteria for the studies were identical. Induction methods were compared in women with obesity (body mass index ≥30.0). Main outcomes were cesarean section and postpartum hemorrhage (blood loss >1000 mL). RESULTS: A total of 2664 women, were included in the trials, 517 of whom were obese: 254 women with obesity received a Foley catheter, 176 oral misoprostol and 87 prostaglandin E2 (PGE2). A cesarean section was performed in 29.1% of women allocated to Foley vs 22.2% in the misoprostol and 23.0% in the PGE2 groups. Comparisons between groups revealed no statistically significant differences: the relative risk [RR] was 1.31 (95% confidence interval [CI] 0.94-1.84) in the Foley vs misoprostol group and 1.27 (95% CI 0.83-1.95) in the Foley vs PGE2 group. The rates of postpartum hemorrhage were comparable (10.6%, 11.4% and 6.9%, respectively; P = 0.512). In women with obesity, more often a switch to another method occurred in the Foley group, (20.1% vs 6.3% in misoprostol vs 1.1% in the PGE2 group; P < 0.001). The risk of a failed Foley placement was higher in women with obesity than in women without obesity (8.3% vs 3.2%; adjusted odds ratio 3.12, 95% CI 1.65-5.90). CONCLUSIONS: In women with obesity we found a nonsignificant trend towards an increased rate of cesarean sections in the group induced with a Foley catheter compared to oral misoprostol; however, the study lacked power for this subgroup analysis. The finding of a higher risk of failed placement of a Foley catheter in women with obesity can be used in shared decision making.

[Clinical analysis of 102 cases of labor induction in the third trimester on twin pregnancy].

Objective: To investigate the clinical characteristics of induced labor in twin pregnancy and the related factors of induced labor failure. Methods: The clinical data of twin pregnant women who underwent induced labor in Peking University Third Hospital from January 2016 to December 2022 were retrospectively analyzed. According to whether they had labor or not after induction, pregnant women were divided into the success group (pregnant women who had labor after induction, 72 cases) and the failure group (pregnant women who did not have labor after induction, 30 cases). Logistic regression was used to analyze the related factors of induction failure in twin pregnant women. Results: The parity and cervical Bishop score in the failure group were significantly lower than those in the success group, while the proportion of dichorionic diamniotic twins, assisted reproductive technology pregnancy and cervical Bishop score <6, postpartum hospital stay and total hospital stay in the failure group were significantly higher than those in the success group (all P<0.05). The proportion of induced labor by artificial rupture of membranes ± oxytocin intravenous infusion in the success group was 72.2% (52/72), which was significantly higher than that in the failure group (46.7%, 14/30; P=0.030). There were no significant differences between the two groups in the gestational age at delivery, the incidence of severe postpartum hemorrhage and blood transfusion, the amount of postpartum hemorrhage, the neonatal weight of two fetuses, the incidence of neonatal asphyxia, and the proportion of neonates admitted to the neonatal intensive care unit (all P>0.05). There were no severe perineal laceration and hysterectomy in all pregnant women. Multivariate logistic regression analysis showed that primipara (OR=3.064, 95%CI: 1.112-8.443; P=0.030) and cervical Bishop score <6 (OR=5.208, 95%CI: 2.008-13.508; P=0.001) were the independent risk factors for induction failure in twin pregnancy. Conclusions: Elective induction of labor in twin pregnancy is safe and feasible. It is helpful to improve the success rate of induction of labor by strictly grasping the timing and indications of termination of pregnancy, choosing the appropriate method of induction according to the condition of the cervix, and actively promoting cervical ripening.

Efficacy and safety of double balloon catheter and dinoprostone for labor induction in multipara at term.

PURPOSE: The aim of this study was to comparatively assess the efficacy and safety of double balloon catheter (DBC) and dinoprostone as labor-inducing agents just for multipara at term. METHODS: A retrospective cohort study was conducted among multipara at term with a Bishop score < 6 who needed planned labor induction from January 1, 2020, to December 30, 2020 in Maternal and Child Health Hospital of Hubei province, Tongji Medical College, Huazhong University of Science and Technology. They were divided into DBC group and dinoprostone group, respectively. Baseline maternal data, maternal and neonatal outcomes were recorded for statistical analysis. Total vaginal delivery rate, rate of vaginal delivery within 24 h, rate of uterine hyperstimulation combined with abnormal fetal heart rate(FHR) were regarded as the primary outcome variables. The difference between groups was considered statistically significant when p value < 0.05. RESULTS: A total of 202 multiparas was included for analysis (95 women in DBC group vs 107 women in dinoprostone group). There were no significant differences in total vaginal delivery rate and rate of vaginal delivery within 24 h between groups. Uterine hyperstimulation combined with abnormal FHR occurred exclusively in dinoprostone group. CONCLUSION: DBC and dinoprostone seem to be equally effective, while, DBC seems to be safer than dinoprostone.

The use of virtual reality during extra-amniotic balloon insertion for pain and anxiety relief-a randomized controlled trial.

BACKGROUND: Induction of labor with an extra-amniotic balloon catheter is a procedure commonly associated with maternal discomfort, pain, and anxiety. OBJECTIVE: We aimed to investigate the distractive effect of virtual reality technology on pain and anxiety among pregnant patients who underwent induction of labor with an extra-amniotic balloon catheter. STUDY DESIGN: In this randomized controlled trial, pregnant patients who were undergoing planned induction of labor using an extra-amniotic balloon catheter at term for various obstetrical indications were recruited and randomized in a 1:1 ratio into 2 groups. Patients in the virtual reality group were exposed to a virtual reality technology clip (using SootheVR All-In-One virtual reality care system for pain and anxiety) during the entire extra-amniotic balloon catheter insertion, whereas patients in the control group received the institutional standard care for extra-amniotic balloon catheter insertion. Pain scores, expressed as visual analog scale scores, and maternal hemodynamic parameters were obtained before, during, and after extra-amniotic balloon catheter insertion. Anxiety was evaluated using the validated State-Trait Anxiety Inventory Scale before and after the procedure. Maternal satisfaction with the virtual reality technology was also recorded. The primary outcome was the change in visual analog scale score before and during extra-amniotic balloon catheter insertion. Among the secondary outcomes was the change in anxiety levels before and after extra-amniotic balloon catheter insertion. The study was powered to detect a 25% decrease in the primary outcome. RESULTS: A total of 132 pregnant patients were recruited (66 in each group). There were no differences between groups in terms of age, body mass index, gestational age at enrollment, indication for induction of labor, and preprocedural visual analog scale score and anxiety levels. The change in visual analog scale score (maximal visual analog scale score during the procedure minus the initial visual analog scale score before the procedure, ie, the primary outcome) was significantly lower in the virtual reality group than in the control group (2.78±3.0 vs 4.09±2.99; P=.01). In addition, the virtual reality group experienced a higher rate of anxiety relief, expressed as the difference between the preprocedure and postprocedure State-Trait Anxiety Inventory Scale scores (-6.46±9.6 vs -2.01±9.11; P=.007). Patients in the virtual reality group reported a very high overall (94%) satisfaction score. CONCLUSION: In this randomized controlled trial, we demonstrated that the use of virtual reality technology among patients who underwent induction of labor using an extra-amniotic balloon catheter was associated with lower visual analog scale scores during the procedure and a significant reduction in anxiety than patients who received standard care. There was also a very high satisfaction rate with the use of virtual reality technology.

Two different regimens of outpatient Foley catheter induction of labor in nulliparas: A randomized trial.

OBJECTIVES: To evaluate expectant compared to immediate return to hospital upon outpatient Foley catheter expulsion predicated on maternal satisfaction and amniotomy-titrated oxytocin infusion to delivery interval. METHODS: This randomized trial was conducted in a tertiary university hospital in Malaysia from September 2020 to February 2022. A total of 330 nulliparous women at term with unripe cervices (Bishop score ≤5), singleton viable fetus in cephalic presentation, reassuring preinduction fetal heart rate tracing and intact membranes who underwent planned outpatient Foley catheter induction of labor (IOL) were included. Women were randomized to expectant or immediate return to hospital if the Foley was spontaneously expelled at home before their scheduled hospital admission the following day. Primary outcomes were amniotomy-titrated oxytocin infusion to delivery interval and maternal satisfaction on the induction process (assessed by 0-10 visual numerical rating scale [VNRS]). RESULTS: Amniotomy-titrated oxytocin infusion to delivery interval was 8.7 ± 4.1 versus 8.9 ± 3.9 h, P = 0.605 (mean difference - 0.228 95% CI: -1.1 to +0.6 h) and maternal satisfaction VNRS score was median (interquartile range) 8 (7-9) versus 8 (7-9), P = 0.782. Early return to hospital rates were 37/165 (22.4%) versus 72/165 (43.6%), RR 0.51 (95% CI: 0.37-0.72), P ≤ 0.001, Cesarean delivery rates were 80/165 (48.5%) versus 80/165 (48.5%), RR 1.00 (95% CI: 0.80-1.25), P = 1.00 and duration of hospital stay was 54.4 ± 22.9 versus 56.7 ± 22.8 h, P = 0.364 for the expectant versus immediate return groups respectively. CONCLUSION: In outpatient Foley catheter IOL, expectant compared to immediate return to hospital following Foley dislodgement results in similarly high maternal satisfaction. The amniotomy-titrated oxytocin to delivery duration is non-inferior with expectant management.