According to the American College of Obstetrics and Gynecology (ACOG) guidelines on labor induction, misoprostol can be used intravaginally, sublingually, or orally for cervical ripening or to induce labor. When compared to dinoprostone and oxytocin, intravaginal misoprostol is associated with a lower rate of need for epidural analgesia during labor and an increased rate of vaginal delivery within 24 hours. However, it is associated with more tachysystole with or without changes to the fetal heart rate (FHR). Additionally, misoprostol is associated with longer times to achieve active labor and delivery than oxytocin. [1]
It is stated that oxytocin is effective in labor induction and its time to effect is between three to five minutes. Dinoprostone is another suggested option for cervical ripening in term or near-term pregnancies. Dinoprostone can be used intravaginally or intracervically for labor induction. For comparative efficacy, however, it is stated intravaginal misoprostol is either superior or equally efficacious compared to the dinoprostone gel. Compared to placebo or no therapy, dinoprostone can result in an increased chance of delivery within 24 hours, but it does not reduce the incidence of cesarean delivery and is associated with an increased risk of uterine tachysystole with FHR changes. [1]
It is stated that the benefits of using oral misoprostol (Cytotec®) for labor induction are that it is low in cost, noninvasive, stable at room temperature, and is associated with lower cesarean rates than other induction methods. Additionally, it may lead to less uterine hyperstimulation with fetal heart rate (FHR) changes as compared to vaginal misoprostol. However, despite its benefits, it notes that the optimal dose for safety is yet to be determined. Compared to the oral route, the benefits of vaginal misoprostol (Cytotec®) are similar with additional benefit of achieving a higher plasma level. It is also stated to be more efficacious at cervical ripening and induction of labor compared to oxytocin and dinoprostone. However, it is noted that vaginal misoprostol is associated with more uterine hyperstimulation and meconium-stained fluid when compared to other vaginal induction methods. Furthermore, slow or erratic absorption can occur with vaginal misoprostol, which may result in inaccurate dosing. A stated advantage of using dinoprostone (Cervidil®) vaginal insert is that it is able to be removed quickly in the case of FHR changes, which may resolve within 15 minutes after removing the insert. It is noted, however, that vaginal dinoprostone is associated with a 5% chance of uterine hyperstimulation one hour after administration. [2]
A 2024 systematic review and meta-analysis encompassing 53 randomized controlled trials and 10,455 participants evaluated the efficacy and safety of oral and vaginal misoprostol compared to vaginal dinoprostone (prostaglandin E2) for labor induction. Randomized trials involving term pregnancies with live singleton fetuses in cephalic presentation were analyzed. The trials varied in their design, doses, and geographical distribution, with robust quality assessments revealing largely low-risk biases. Pooled results demonstrated that vaginal misoprostol was significantly more effective than dinoprostone in achieving vaginal delivery within 24 hours (risk ratio [RR] 1.14, 95% confidence interval [CI] 1.08 to 1.21, p<0.00001). However, it was associated with higher risks of adverse outcomes, including tachysystole (RR 1.64, 95% CI 1.26 to 2.15, p= 0.0003) and uterine hyperstimulation (RR 1.36, 95% CI 1.03 to 1.78, p= 0.03). Conversely, oral misoprostol demonstrated similar efficacy to vaginal dinoprostone with fewer maternal adverse effects but required more frequent dosing. Neonatal safety outcomes, including Apgar scores and NICU admission rates, showed no significant differences between groups, though vaginal misoprostol was linked to higher rates of abnormal cardiotocography and meconium-stained amniotic fluid. These findings highlight oral misoprostol as a less invasive and comparably safe alternative, while vaginal misoprostol offers greater efficacy but with a higher risk profile. [3]
A 2024 individual participant data meta-analysis of eight randomized controlled trials evaluated the comparative effectiveness and safety profiles of low-dose vaginal misoprostol and vaginal dinoprostone for cervical ripening and induction of labor. The analysis encompassed 4,180 participants, with 2,077 receiving vaginal misoprostol and 2,103 allocated to vaginal dinoprostone. Inclusion criteria spanned viable singleton pregnancies at various gestational ages, unripe cervices, and no history of prior cesarean sections. Notably, the meta-analysis demonstrated comparable vaginal birth rates between low-dose vaginal misoprostol and dinoprostone (adjusted odds ratio [aOR] 0.95, 95% CI 0.80 to 1.13). Perinatal safety outcomes, including adverse neonatal events, did not significantly differ between the two agents (aOR 0.96, 95% CI 0.74 to 1.25). However, maternal safety showed a favorable trend for low-dose vaginal misoprostol, with a significant reduction in adverse maternal outcomes (aOR 0.80, 95% CI 0.65 to 0.98). While uterine hyperstimulation, maternal infections, and ICU admissions exhibited numerically lower incidences with misoprostol, these differences were not individually statistically significant. The findings underscore the comparable efficacy yet greater maternal safety advantages of low-dose vaginal misoprostol, suggesting its use as a cost-effective and accessible alternative to dinoprostone, particularly in resource-limited settings. [4]
A 2023 systematic review and meta-analysis synthesized data from 39 randomized controlled trials involving 15,993 participants to evaluate the safety profiles of misoprostol (PGE1) and dinoprostone (PGE2) for labor induction in women with singleton pregnancies beyond 36 weeks' gestation. The meta-analysis identified no statistically significant differences between misoprostol and dinoprostone in the primary outcomes of cesarean delivery (OR 0.94; 95% CI 0.84 to 1.05) or instrumental delivery (OR 1.04; 95% CI 0.90 to 1.19). Rates of uterine tachysystole were comparable between groups overall (OR 1.21; 95% CI 0.91 to 1.60), though a subgroup analysis revealed heightened tachysystole with vaginal misoprostol compared to dinoprostone gel (OR 1.48; 95% CI 1.09–2.01). There was no significant difference in postpartum hemorrhage (OR 0.85; 95% CI 0.62–1.15), neonatal Apgar scores <7 (OR 0.83; 95% CI 0.61 to 1.12), or NICU admissions (OR 0.91; 95% CI 0.77 to1.09). The findings suggest a comparable safety profile between the two agents, with no clear superiority for either in any maternal or neonatal outcomes. The evidence highlights the potential advantages of oral over vaginal misoprostol while underscoring the need for tailored clinical decision-making based on local contexts and patient-specific factors. [5]
Another meta-analysis suggests that when comparing intravaginal misoprostol to intracervical dinoprostone in women with an unfavorable cervix at term, misoprostol was more efficacious at resulting in delivery within 24 hours (RR 1.27; 95% CI 1.10 to 1.48; p= 0.002; I2 = 0%;) and required less use of oxytocin as an augmentation strategy (RR 0.62; 95% CI 0.54 to 0.72; p<0.00001; I2= 40%). On the other hand, misoprostol use was associated with increased uterine hyperstimulation (RR 3.15; 95% CI 1.58 to 6.28; p= 0.001; I2= 0% ) and tachysystole (RR 2.02; 95% CI 1.28 to 3.19; p= 0.003; I2 = 44%). There was no significant difference in the rate of cesarean delivery (RR 0.95; 95% CI, 0.78 to 1.17; p= 0.66; I2= 23%), the incidence of neonatal intensive care unit (NICU) admission (RR 0.95; 95% CI 0.62 to 1.45; P = 0.80; I2= 0%), Apgar scores at 1 and 5 minutes (1 min: mean difference [MD] 0.03; 95% CI −0.38 to 0.43; p= 0.90; I2= 31%; 5 min: MD 0.02; 95% CI, −0.33 to 0.38; p= 0.89; I2= 56%). [6]