Comparison of Efficacy and Safety Between Vaginal Misoprostol Tablets and Dinoprostone Insert for Labor Induction in a Pilot Study

Summary

This pilot study compares vaginal misoprostol and dinoprostone insert for labor induction in multiparous women with an unfavorable cervix. 24 h vaginal delivery rates were comparable, while misoprostol showed lower tocolytic use and meconium-stained amniotic fluid rate with similar safety.

Abstract

To compare the efficacy and safety of vaginal misoprostol 25 µg tablets vs dinoprostone controlled-release insert for labor induction in multiparous women with an unfavorable cervix. This single-center pilot cohort study included a prospective misoprostol cohort (n = 23) and a retrospective historical dinoprostone control (n = 26). Participants were term multiparous women with singleton pregnancies, cephalic presentation, Bishop score < 6, and no contraindications for vaginal delivery. Primary outcomes were the 24 h vaginal delivery rate and clinician-determined tocolytic use for uterine tachysystole. Secondary outcomes included cesarean section rate, meconium-stained amniotic fluid, postpartum hemorrhage, and neonatal outcomes. The 24 h vaginal delivery rates were similar between groups (82.6% vs 80.8%, p = 0.840). The misoprostol group had significantly lower tocolytic use (8.7% vs 38.5%, p = 0.037) and lower meconium-stained amniotic fluid incidence (4.3% vs 23.1%, p = 0.037). Cesarean section rates were <5% in both groups (4.3% vs 3.8%, p = 1.000). No significant differences were seen in postpartum hemorrhage or neonatal outcomes. Misoprostol 25 µg vaginal tablets achieved comparable 24 h vaginal delivery rates to dinoprostone, with reduced tocolytic use in this pilot cohort.

Introduction

Third-trimester induction of labor refers to the initiation of uterine contractions before the spontaneous onset of labor through pharmacological or other interventions to achieve delivery. According to statistics from the World Health Organization (WHO), approximately 20–25% of pregnant women worldwide require induced labor to complete childbirth^1,2. A critical determinant of successful induction is the degree of cervical ripeness. More than 50% of pregnant women undergoing induction present with an unfavorable cervix, defined as a Bishop score below 6, necessitating interventions to promote cervical maturation³. Internationally, the most commonly used approaches for cervical ripening include vaginal preparations of prostaglandins (e.g., misoprostol, dinoprostone) and mechanical methods like cervical balloon catheters and Foley catheter^4,5. The Foley catheter balloon is a widely used mechanical cervical ripening method with a favorable safety profile and has been compared with dinoprostone in several clinical studies⁶.

Following the implementation of the two‑child and three‑child policies, multiparous women now account for approximately 53.9% of pregnancies in China⁷. This population often presents with higher obstetric risks, including a higher prevalence of comorbidities and previous birth trauma. Although the 2024 Chinese guideline on cervical ripening and labor induction endorses 25 µg misoprostol vaginal tablets, it only advises that ‘caution should be exercised before administration’ in multiparous women and does not provide specific parity-tailored recommendations. This gap underscores the need for evidence focused on multiparous women in the Chinese context.

Prostaglandins facilitate labor through dual mechanisms. First, collagen fiber degradation and cervical softening were achieved by stimulating cervical connective tissue to release collagenase and elastase. Second, uterine contractions were induced by enhancing myosin light-chain kinase activity through increased intracellular free calcium concentrations in uterine myocytes⁸. Misoprostol is a synthetic analog of prostaglandin E1 (PGE1), whereas dinoprostone is a naturally occurring prostaglandin E2 (PGE2). A recent Cochrane systematic review, which included 39 randomized controlled trials involving over 8000 participants, found no significant difference between the two agents in terms of cesarean section rates (odds ratio OR] = 0.94; 95% confidence interval [CI]: 0.84–1.05) or the incidence of uterine tachysystole (OR = 1.21; 95% CI: 0.91–1.60)⁹.

However, previous studies have often failed to stratify outcomes by parity, and in China, misoprostol has been routinely administered intravaginally by subdividing 200 µg oral tablets to obtain a lower dose. This off-label use is associated with challenges in dose accuracy and compromised drug stability¹⁰. With the recent introduction of domestically produced 25 µg misoprostol vaginal tablets in China, a standardized obstetric-specific formulation is now available. Approval of an on-label formulation does not inherently confer superior efficacy or safety compared with appropriately dosed off-label use, and comparative data are needed to confirm clinical advantages. Leading international guidelines, including those from the American College of Obstetricians and Gynecologists (ACOG), the International Federation of Gynecology and Obstetrics, and the WHO Model List of Essential Medicines, all recommend a 25 µg intravaginal dose of misoprostol as the preferred regimen for term labor induction^11,12. The Guideline of Cervical Ripening and Labor Induction During the Third Trimester Pregnancy (2024), issued by the Chinese Medical Association, also endorses the use of 25 µg misoprostol vaginal tablets. However, for multiparous women, the guideline only states that ‘caution should be exercised before administration’, without providing specific clinical recommendations⁵. Although multiple randomized trials and meta‑analyses have compared misoprostol and dinoprostone for labor induction in general obstetric populations, few studies have specifically focused on multiparous women with an unfavorable cervix, and parity‑stratified outcomes are rarely reported. In addition, there is a paucity of real‑world data on the newly introduced obstetric‑specific 25 µg misoprostol vaginal tablet in Chinese multiparous women.

Accordingly, the study aims to address this gap by providing preliminary comparative data on efficacy and safety in this understudied but increasingly common subgroup. These data are pilot and hypothesis-generating and aim to inform future, larger, randomized evaluations. The study aims to compare the efficacy and safety of 25 µg misoprostol vaginal tablets vs dinoprostone vaginal suppositories for cervical ripening in term multiparous women with singleton pregnancies and an unfavorable cervix, thereby providing a reference for clinical practice.

Protocol

This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of New Century Women’s and Children’s Hospital (Approval No.: 2024LLSC2106). Written informed consent was obtained from all participants. A study flowchart is presented in Figure 1. All materials, equipment, and software used in this study are detailed in the Table of Materials.

Novelty statement of study findings
This pilot study is the first real-world clinical study focusing on domestically produced 25 µg misoprostol vaginal tablets specifically for multiparous women with an unfavorable cervix in China. It fills the guideline evidence gap, which only provides vague caution for multiparas without targeted recommendations. It further verified that standardized 25 µg misoprostol vaginal tablets achieve a comparable 24 h vaginal delivery rate to dinoprostone, while significantly reducing the need for tocolysis and the incidence of meconium-stained amniotic fluid, providing new high-level clinical evidence for an individualized labor induction strategy in the multiparous population. Besides, it avoids the risk of dose inaccuracy associated with off-label tablet splitting and provides a practical reference for domestic obstetric clinical practice and subsequent large-scale randomized trials.

Study population
This was a single-center pilot cohort study incorporating both prospective and retrospective data. The prospective cohort included 23 term multiparous women with singleton pregnancies, indications for labor induction, and an unfavorable cervix, who were admitted to the Department of Obstetrics at Beijing New Century Women’s and Children’s Hospital between May 2024 and May 2025. These patients received 25 µg misoprostol vaginal tablets for cervical ripening and comprised the experimental group. The control group was retrospectively selected and included 26 multiparous women who had undergone labor induction using sustained-release dinoprostone vaginal suppositories at the same hospital during the corresponding period in 2023. Within each time period, patients who met the inclusion and exclusion criteria were included consecutively. No major changes in hospital protocols occurred between 2023 and 2024–2025, as confirmed by institutional records. The decision not to use a concurrent dinoprostone control group was driven by the change in institutional practice following the introduction of the 25 µg misoprostol vaginal tablet and its endorsement in national guidelines, which made routine dinoprostone use uncommon in comparable patients. This study was approved by the hospital’s ethics committee. All participants in the prospective misoprostol cohort provided written informed consent after receiving detailed information about the medical procedures involved in labor induction. For the retrospective dinoprostone cohort, the ethics committee granted a waiver of informed consent because the study involved anonymized analysis of existing medical records and posed minimal risk to participants. All analyses were performed using complete-case analysis due to the observational cohort design and the absence of missing key data.

Inclusion criteria
Participants were eligible for inclusion if they met the following criteria: singleton pregnancy with cephalic presentation; multiparous women with a history of 1–2 prior deliveries; gestational age ≥37 weeks; indication for labor induction without the onset of spontaneous labor and a Bishop score <6; absence of contraindications to labor induction or vaginal delivery; and availability of complete clinical data. Based on the Guideline of Cervical Ripening and Labor Induction During the Third Trimester Pregnancy (2024)⁵, indications for labor induction included post-term pregnancy (≥41 weeks), abnormal amniotic fluid volume (oligohydramnios or polyhydramnios), abnormal fetal movement, gestational diabetes mellitus, hypertensive disorders of pregnancy, fetal growth restriction, and intrahepatic cholestasis of pregnancy.

Exclusion criteria
The exclusion criteria included intrauterine fetal demise, labor induction for lethal fetal anomalies, maternal comorbidities or complications precluding vaginal delivery, history of uterine scarring or cervical laceration, genital tract infections such as vaginitis, Bishop score ≥ 6, asthma, glaucoma, use of cervical balloon catheters (alone or in combination) for cervical ripening, and a history of 3 or more prior deliveries.

Sample size calculation
According to previous literature, the 24 h vaginal delivery rate with dinoprostone is approximately 75–85%¹³. Assuming a comparable rate in the misoprostol group and employing a non-inferiority design with a one-sided α of 0.05, a β of 0.20, and a non-inferiority margin of −15%, the required minimum sample size per group was calculated to be 20 using PASS 15.0. Allowing for a 10% attrition rate, at least 22 participants were planned for inclusion in each group. The non-inferiority margin of −15% was chosen pragmatically, based on prior reports of 75–85%¹³, and the judgment of clinicians at the institution regarding the largest clinically acceptable difference that would still support the use of misoprostol if other advantages (e.g., cost and availability) were present. It is acknowledged that this margin was not derived from formal consensus and should be interpreted cautiously. The sample size calculation was based on the primary efficacy endpoint (24 h vaginal delivery rate). This study was designed as a pilot study with a small sample size to generate a hypothesis for future large-scale research.

Misoprostol group
Participants in the experimental group received 25 µg misoprostol vaginal tablets for cervical ripening. The administration protocol followed the recommendations of the ACOG guidelines¹¹ and the “Guideline of Cervical Ripening and Labor Induction During the Third Trimester Pregnancy (2024)”⁵. Prior to administration, reactive fetal heart-rate monitoring was confirmed, the bladder was emptied, and perineal disinfection was performed. A 25 µg misoprostol tablet was then placed in the posterior vaginal fornix. Based on uterine activity, repeat doses of 25 µg were permitted every 6 h, with a maximum of 3 doses (total dose < 75 µg). If spontaneous labor did not occur after 3 doses, in cases of premature rupture of membranes during administration, or when the Bishop score reached ≥ 6, labor was induced with intravenous oxytocin. A minimum interval of more than 4 h between the final misoprostol dose and oxytocin initiation was maintained.

Dinoprostone group
Participants in the control group received sustained-release dinoprostone vaginal suppositories (detailed in Table of Materials). Administration was carried out according to the “Guideline of Cervical Ripening and Labor Induction During the Third Trimester Pregnancy (2024)”⁵. Following perineal disinfection, the suppository was placed deeply in the posterior vaginal fornix and rotated 90° to a transverse position. The suppository was retained for up to 24 h. If spontaneous labor had not commenced after removal, or if premature rupture of membranes occurred during treatment without the onset of regular contractions, labor induction was initiated using intravenous oxytocin. A minimum interval of 30 min was ensured between insert removal and oxytocin administration.

Oxytocin administration protocol
Oxytocin was administered in accordance with ACOG guidelines¹¹: the initial infusion rate was 2 mU/min, with incremental increases of 2 mU/min every 30 min, up to a maximum of 20 mU/min. If labor did not commence within 12 h of oxytocin infusion, the induction attempt was terminated.

Management of uterine tachysystole
Uterine tachysystole was defined as more than 5 contractions within a 10 min window, persisting for more than 20 min. Management procedures included immediate fetal heart-rate monitoring and vaginal examination. In the prospective misoprostol cohort, uterine activity tracings were reviewed per protocol to identify tachysystole. In the retrospective dinoprostone group, standardized tracings were not uniformly archived; therefore, tocolytic administration recorded in the chart is reported as a pragmatic clinical outcome rather than an objective measurement of tachysystole frequency. There was no systematic electronic or paper record of objectively defined uterine tachysystole (>5 contractions/10 min for >20 min) for all participants in both cohorts. Therefore, uterine hyperstimulation was assessed using the proxy of clinical requirement for tocolytic administration combined with the fulfillment of the tachysystole definition. In the dinoprostone group, the vaginal suppository was removed; in the misoprostol group, any residual drug fragments were removed manually. If tachysystole persisted, 2.5 g of magnesium sulfate was administered as a slow intravenous push over longer than 10 min. If necessary, oral nifedipine (10 mg) was added to further suppress uterine activity. The timing of tocolytic administration was not systematically documented in the retrospective cohort, so the between-group comparison of tachysystole onset time was not feasible.

Outcome measures
Primary outcomes: vaginal delivery rate within 24 h of drug administration, and the use of uterine tocolytics (magnesium sulfate and/or nifedipine) as a pragmatic clinical proxy for significant uterine tachysystole. Uterine tachysystole was defined as more than 5 contractions within a 10 min window, persisting for more than 20 min. Due to incomplete retrospective documentation of this strict definition, however, tocolytic use was selected as the most consistently available indicator across both cohorts and is reported as a clinical outcome rather than a direct measure of tachysystole.

Secondary outcomes: caesarean delivery rate, time from drug administration to the onset of active labor (defined as cervical dilation ≥3 cm with regular uterine contractions), time from drug administration to delivery, duration from onset of active labor to delivery, use of uterine tocolytics (magnesium sulphate and/or nifedipine), use of oxytocin, estimated postpartum blood loss, incidence of meconium-stained amniotic fluid, and neonatal outcomes (including birth weight, umbilical artery blood gas parameters, Apgar scores, and neonatal intensive care unit [NICU] admission rate).

Bishop score assessment: The Bishop score was evaluated at 3 time points: baseline, 6 h post-administration, and 12 h post-administration.

Statistical analysis
All statistical analyses were performed using the SPSS 23.0 software (detailed in Table of Materials). For continuous variables with a normal distribution, data are presented as mean ± standard deviation (x̄ ± s), and between-group comparisons were conducted using the independent samples t-test. For non-normally distributed continuous data, results are expressed as median (interquartile range, IQR). Comparisons were made using the Mann–Whitney U test. Categorical variables are presented as frequencies and percentages (n [%]), with between-group comparisons conducted using the chi-square test (χ²) or Fisher’s exact test. Between-group differences are reported as risk differences with 95% CI for categorical outcomes. A binary logistic regression model was used as an exploratory analysis to identify factors associated with the use of uterine tocolytics, and ORs with 95% CI were calculated. A p-value <0.05 was considered statistically significant.

Results

Baseline characteristics
A total of 23 participants were prospectively enrolled in the misoprostol (experimental) group, and 26 participants were retrospectively included in the dinoprostone (control) group. There were no statistically significant between-group differences in maternal age, gravidity, parity, pre-pregnancy body mass index (BMI), pre-delivery BMI, interval since last delivery, gestational age at delivery, birth weight of the previous neonate, or pre-induction Bishop score (all p &g...

Discussion

This pilot study is the first to report real-world data on the use of domestically produced 25 µg misoprostol vaginal tablets in multiparous women in China. The findings demonstrate that the 24 h vaginal delivery rate in the misoprostol group reached 82.6%, comparable to the 80.8% rate observed in the dinoprostone group. Both rates exceeded the clinically expected benchmark of 80%, indicating favorable efficacy. More importantly, the incidence of tocolytic use in the misoprostol group was only 8.7%, significantly lo...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Dinoprostone	Controlled-release vaginal insert	0.1 mg/insert	Ferring Pharmaceuticals
Fetal heart rate monitor	Medical device	CTG series	Philips Healthcare
Misoprostol	Vaginal tablet	25 μg	Guangzhou Longsun Pharmaceutical Co., Ltd.
Nifedipine (Tocolytic agent)	Tablet	10 mg	Bayer Schering Pharma AG
Oxytocin	Injection	10 IU/ampoule	Shanghai No.1 Biochemical & Pharmaceutical Co., Ltd.
PASS	Software	Version 15.0	NCSS, LLC, Kaysville, UT, USA
SPSS Statistics	Software	Version 23.0	IBM Corp., Armonk, NY, USA
Sterile vaginal examination kit	Medical device	Single-use	Jiangsu Yuyue Medical Equipment & Supply Co., Ltd.