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 > 0.05), indicating good baseline comparability between the two groups (Table 1).

Primary outcomes
The 24 h vaginal delivery rates were high and comparable between the two groups: 82.61% in the misoprostol group and 80.77% in the dinoprostone group (risk difference 1.8%, 95% CI -16.4% to 20.1%, p = 0.840). However, the use of uterine tocolytics was significantly lower in the misoprostol group compared with the dinoprostone group (8.70% vs 38.46%, risk difference -29.8%, 95% CI -54.7% to -4.9%, p = 0.037). Notably, no participants in the misoprostol group required the combined use of magnesium sulfate and nifedipine, whereas 19.23% of those in the dinoprostone group did (p = 0.053) (Table 2).

Secondary outcomes
Mode of delivery and labor duration
Cesarean section rates were similarly low in both groups (4.35% in the misoprostol group vs 3.85% in the dinoprostone group, p = 1.000). One case in each group required an intrapartum cesarean section: a patient with an intrauterine infection in the misoprostol group and recurrent fetal heart decelerations in a patient in the dinoprostone group. There were no statistically significant between-group differences in the time from drug administration to onset of active labor (9.09 ± 6.63 vs 7.87 ± 7.14 h; p = 0.540), time from drug administration to delivery (14.69 ± 7.81 vs 12.98 ± 8.26 h; p = 0.476), or duration from onset of active labor to delivery (5.40 ± 3.67 vs 5.56 ± 3.69 h; p = 0.880). Oxytocin augmentation was required in 4.35% (n = 1) of women in the misoprostol group and 11.54% (n = 3) in the dinoprostone group (Fisher’s exact test; p = 0.612) (Table 2). Among the 22 vaginal deliveries in the misoprostol group, 50.00% occurred between 12–24 h post-administration, and 27.27% occurred between 6–12 h, totalling 77.27% within 6–24 h. In contrast, vaginal delivery time in the dinoprostone group (n = 25) was more variably distributed (Supplementary Table 1).

Drug administration
In the misoprostol group, 14 participants (60.87%) required only a single dose, while 9 participants (39.13%) required 2 doses. No patients required a third dose. In contrast, all patients in the dinoprostone group received a single sustained-release suppository.

Maternal and neonatal outcomes
In this pilot cohort, the observed incidence of meconium-stained amniotic fluid was lower in the misoprostol group compared with the dinoprostone group (4.35% vs 23.08%, risk difference -18.8%, 95% CI -35.9% to -1.6%, p = 0.037); however, this difference is based on small absolute event numbers (1 vs 6 cases) and may be due to chance, variation in clinical practice, or documentation, so it should be interpreted with extreme caution. The two groups showed no significant differences in postpartum blood loss (median [IQR]: misoprostol group 300 [250–380] mL vs dinoprostone group 300 [220–300] mL; p = 0.446, Mann–Whitney U test), neonatal birth weight (3500.87 ± 330.63 g vs 3513.08 ± 402.50 g; p = 0.909), or umbilical artery blood gas parameters, including pH, base excess, and lactate levels. Additionally, there were no cases of severe perineal trauma, placental abruption, neonatal asphyxia, Apgar scores < 7 at 1 min, or NICU admissions in either group (Table 3).

Analysis of factors associated with uterine tocolytic use
A binary logistic regression analysis was performed as an exploratory analysis to identify factors influencing the use of uterine tocolytics. The dependent variable was tocolytic use (yes/no), and the following independent variables were included: maternal age, gestational age, pre-pregnancy BMI, pre-delivery BMI, indication for induction, initial Bishop score, and type of induction agent. The analysis revealed that only the type of induction agent was significantly associated with tocolytic use. Specifically, participants in the dinoprostone group were 6.56 times more likely to require tocolytics compared with those in the misoprostol group (OR = 6.56; 95% CI = 1.27–33.92, p = 0.025). The logistic regression model demonstrated acceptable calibration according to the Hosmer–Lemeshow test (χ² = 3.476; df = 8; p = 0.9011). However, the omnibus test of model coefficients was not statistically significant (χ² = 11.234; df = 6; p = 0.081). The model had a Cox & Snell R² of 0.215 and a Nagelkerke R² of 0.329, indicating moderate explanatory power. However, because only 2 tocolytic administrations occurred in the misoprostol group, the logistic regression estimates are highly unstable and imprecise, and this analysis should be interpreted as exploratory only (Table 4).

DATA AVAILABILITY:
All data generated or analyzed during this study are included in this article as supplementary files named Raw Data 1 and Raw Data 2.

Figure 1: The flow chart. This flowchart illustrates the study design, participant enrollment, grouping, interventions, and outcome assessments for the pilot study comparing vaginal misoprostol 25 µg tablets and dinoprostone insert for labor induction. The notation “q6h” denotes “every 6 h”. Please click here to view a larger version of this figure.

Variable	Misoprostol group (n = 23)	Dinoprostone group (n = 26)	t/χ² value	p-value
Age (years)	33.39 ± 3.66	34.23 ± 3.41	0.826	0.42
Gravidity	2.74 ± 0.94	2.85 ± 1.06	0.381	0.7
Parity	1.09 ± 0.28	1.08 ± 0.27	0.127	0.89
Pre-pregnancy BMI (kg/m²)	21.74 ± 3.90	22.21 ± 3.64	0.434	0.66
Pre-delivery BMI (kg/m²)	27.01 ± 3.48	27.45 ± 3.08	0.467	0.64
Interval since last delivery (years)	6.24 ± 3.51	5.42 ± 2.34	0.97	0.34
Gestational age at delivery (weeks)	39.59 ± 1.14	39.95 ± 0.93	1.231	0.22
Birth weight of previous neonate (g)	3425.87 ± 291.71	3347.69 ± 320.43	0.891	0.44
Pre-induction Bishop score	3.43 ± 0.92	3.08 ± 0.83	1.404	0.15

Table 1: Baseline characteristics of the two groups. This table presents the baseline demographic and clinical characteristics of participants in the misoprostol group (n = 23) and dinoprostone group (n = 26), including maternal age, gestational age, BMI, prior delivery count, Bishop score, and labor induction indications. Data are presented as mean ± SD or n (%). Between-group comparisons were performed using an independent samples t-test or a chi-square test. A p-value > 0.05 was considered not statistically significant. Abbreviations; BMI = body mass index; SD = standard deviation.

Variable	Misoprostol Group	Dinoprostone Group	Statistic	p-value
Time from administration to active labor (h)	9.09 ± 6.63	7.87 ± 7.14	t = 0.615	0.540
Time from administration to delivery (h)	14.69 ± 7.81	12.98 ± 8.26	t = 0.741	0.476
Time from active labor to delivery (h)	5.40 ± 3.67	5.56 ± 3.69	t = 0.151	0.880
Vaginal delivery within 24 h (n[%])	19 (82.61)	21 (80.77)	χ² = 0.027	0.840
RD (95% CI)	1.8% (-16.4% to 20.1%)	—	—	—
Use of uterine tocolytics (n[%])	2 (8.70)	10 (38.46)	χ² = 5.831	0.037
RD (95% CI)	-29.8% (-54.7% to -4.9%)	—	—	—
Magnesium sulfate use as monotherapy (n[%])	2 (8.70)	5 (19.23)	—	0.424*
Combined use of magnesium sulfate and nifedipine (n[%])	0 (0.00)	5 (19.23)	—	0.053*
Oxytocin use (n[%])	1 (4.35)	3 (11.54)	—	0.612*

Table 2: Comparison of labor duration and uterine activity interventions between the misoprostol and dinoprostone groups. This table displays the primary study outcomes, including 24 h vaginal delivery rate and tocolytic use rate, for the misoprostol group and dinoprostone group, with between-group statistical comparisons. Data are presented as mean ± SD or n (%). *p-values were calculated using Fisher’s exact test. Between-group comparisons were performed using an independent samples t-test or a chi-square test. Abbreviations; SD = standard deviation; h = hours.

Variable	Misoprostol group n = 23 Mean ± SD (95% CI)	Dinoprostone group n = 26 Mean ± SD (95% CI)	Statistic	p-value
Postpartum blood loss (mL)	300 (250–380) [median (IQR)]	300 (220–350) [median (IQR)]	Z = 0.77	0.446#
Umbilical artery pH	7.32 ± 0.05 (7.30–7.34)	7.33 ± 0.09 (7.30–7.36)	t = 0.493	0.327
Umbilical artery BE (mmol/L)	1 (4.35)	-3.58 ± 2.29 (-4.46–2.70)	t = 0.436	0.663
Umbilical artery lactate (mmol/L)	2.82 ± 0.88 (2.46–3.18)	2.93 ± 1.54 (2.34–3.52)	t = 0.307	0.758
Neonatal birth weight (g)	3500.87 ± 330.63 (3365.75–3635.99)	3513.08 ± 402.50 (3358.36–3667.80)	t = 0.115	0.909
Meconium-stained amniotic fluid (n[%])	1 (4.35)	6 (23.08)	—	0.037*
RD (95% CI)	-18.8% (-35.9% to -1.6%)	—	—	—
Severe perineal laceration (n[%])	0 (0.00)	0 (0.00)	—	—
Placental abruption (n[%])	0 (0.00)	0 (0.00)	—	—
Neonatal asphyxia (n[%])	0 (0.00)	0 (0.00)	—	—
1-min Apgar <7 (n[%])	0 (0.00)	0 (0.00)	—	—
NICU admission (n[%])	0 (0.00)	0 (0.00)	—	—

Table 3: Comparison of maternal and neonatal outcomes between the misoprostol and dinoprostone groups. This table summarizes the secondary study outcomes, including cesarean section rate, meconium-stained amniotic fluid incidence, postpartum hemorrhage rate, and neonatal outcomes, for the two study groups. Data are presented as mean ± SD (95% CI) or n (%). *p-values were calculated using Fisher’s exact test. Postpartum blood loss is presented as median (interquartile range, IQR) and compared using the Mann–Whitney U test. Abbreviations; SD = standard deviation; CI = confidence interval; BE = base excess; NICU = neonatal intensive care unit.

Variable	B‐value	SE	Wald χ²	p‐value	OR	95% CI
Age	0.082	0.112	0.535	0.465	1.085	0.871–1.352
Gestational age	-0.241	0.385	0.392	0.531	0.786	0.370–1.670
Pre‐pregnancy BMI	0.098	0.124	0.624	0.43	1.103	0.865–1.406
Pre‐delivery BMI	-0.075	0.148	0.257	0.612	0.928	0.694–1.241
Initial Bishop score	-0.356	0.425	0.702	0.402	0.7	0.304–1.611
Induction agent (dinoprostone = 1)	1.881	0.842	4.991	0.025	6.56	1.268–33.920
Model Fit Statistics
Omnibus test of model coefficients			11.234	0.081		df = 6
Hosmer–Lemeshow test			3.476	0.9011		df = 8
Cox & Snell R²					0.215
Nagelkerke R²					0.329

Table 4: Exploratory multivariable logistic regression analysis of factors associated with uterine tocolytic use. This table presents the results of an exploratory multivariable logistic regression analysis evaluating factors associated with uterine tocolytic use. Odds ratios (ORs) with 95% confidence intervals (CIs) are shown. Because of the low number of tocolytic events, the regression estimates are unstable and should be interpreted as exploratory only.

Supplementary Table 1: Vaginal delivery timing of misoprostol and dinoprostone groups. Data are presented as n (%). Distribution of time from drug administration to vaginal delivery among women who achieved successful vaginal birth in each group. Abbreviations; h = hours.Please click here to download this file.

Raw Data 1: Raw data used in this study.

Raw Data 2: Raw data used in this study.

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 lower than the 38.5% observed in the dinoprostone group. Furthermore, no participants in the misoprostol group required combination tocolytic therapy, highlighting a potential safety advantage in this population. These preliminary findings are hypothesis-generating due to the small sample size and low event rates, and larger studies are required to confirm this signal.

A previous study compared the outcomes of labor induction with oral misoprostol in primiparas and multiparas¹³. The researchers found that 85.7% of multiparas achieved vaginal delivery within 12 h, significantly higher than the 42.9% observed in the primiparas¹³. This finding is consistent with the results of the present study, suggesting a greater responsiveness to prostaglandin-based induction agents in multiparous women. Regarding the efficacy of different prostaglandin formulations, a 2023 review noted that the vaginal administration of 50 µg misoprostol was associated with the highest probability of vaginal delivery within 24 h¹⁴. Another study on multiparous women concluded that misoprostol is a safe, cost-effective option for labor induction in this population¹⁵.

Additionally, a randomized controlled trial compared low-dose vaginal misoprostol with dinoprostone vaginal suppositories for induction in post-term pregnancies¹⁶. The results demonstrated that both agents were equally safe and effective for induction after 41 weeks of gestation¹⁶. Notably, this study used the same 25 µg dosage of vaginal misoprostol as in our investigation, thereby lending further support to the findings. Chinese scholars have also contributed to the evidence base on misoprostol use. A double-blind, prospective randomized controlled trial evaluated the efficacy of 25 µg vaginal misoprostol tablets in primiparous women, using the same domestically manufactured formulation as in the present study¹⁷. The trial highlighted the critical importance of precise dosing, a key advantage shared by this study.

Regarding differences between primiparous and multiparous women, a previous study reported that the oral administration of 50 µg misoprostol every 4 h significantly shortened the interval from the premature rupture of membranes to delivery in primiparas, but not in multiparas¹⁸. This finding suggests that the response to misoprostol may vary by parity, highlighting the need for individualized dosing strategies¹⁹. The ACOG website clearly defines the indications and criteria for labor induction²⁰. According to a large-scale national survey conducted in China, the induction rate between 2015 and 2016 was 18.4% among primiparous women and 10.2% among multiparous women²¹. By focusing specifically on multiparas, the present study addresses an understudied population and fills an important gap in the current literature.

One possible explanation for the lower observed need for tocolytics in the misoprostol group is the pharmacological profile and formulation of misoprostol. According to the US Food and Drug Administration prescribing information for misoprostol, the drug has a relatively short half-life of approximately 4 h, and the 25 µg vaginal tablet formulation permits precise low-dose administration and discontinuation, which may allow clinicians to better titrate uterine activity compared with a sustained-release dinoprostone insert²². In contrast, dinoprostone vaginal suppositories are controlled-release formulations designed to deliver the drug continuously over a 24 h period, which may limit dose adjustability in response to uterine activity.

From a cost-effectiveness perspective, recent meta-analyses have shown that misoprostol offers substantial advantages over dinoprostone²³. Unlike dinoprostone, misoprostol is less expensive, easier to administer, does not require refrigeration, and is readily accessible even in resource-limited settings, making it a more practical option²³. A 2003 cost analysis study found that the average cost per patient in the misoprostol group was significantly lower than in the dinoprostone suppository group and gel group²⁴. Similarly, an earlier analysis reached the same conclusion: misoprostol was more cost-effective than commercially available dinoprostone formulations when used as an adjunct for labor induction in women with an unfavorable cervix²⁵. Given the rising proportion of multiparous women in China and the increasing emphasis on cost control within the national healthcare system, the promotion of 25 µg vaginal misoprostol tablets holds considerable public health significance. Notably, a comprehensive meta-analysis published in 2024 reported a statistically significant advantage in induction success rates for the misoprostol group compared with the PGE2 group. Formal cost‑effectiveness analysis was not performed in this investigation; thus, the cost-benefit of misoprostol remains hypothetical and warrants further pharmacoeconomic assessment. Approval of an on-label misoprostol formulation does not inherently mean it is superior to off-label use, and clinical benefits should be confirmed by rigorous comparative studies.

This study has several notable strengths: It specifically focuses on multiparous women with an unfavorable cervix, thus addressing a critical knowledge gap in existing guidelines. The use of a standardized 25 µg vaginal misoprostol tablet avoids the inaccuracies and risks associated with splitting tablets, which is common in off-label practices. Detailed documentation of uterine contraction management offers valuable guidance for clinical practice. However, this study has several limitations that should be considered when interpreting the results. First, this is a pilot study with a small sample size (23 vs 26 cases), and all statistically significant differences are based on very small absolute event numbers, so results are hypothesis-generating rather than confirmatory. Second, the study used a hybrid design, in which the misoprostol group comprised a prospective cohort (2024–2025) and the dinoprostone group included a retrospective historical cohort (2023). This non-concurrent design introduces significant temporal bias, including potential differences in clinical staff, CTG monitoring standards, tocolytic use thresholds, documentation practices, and overall obstetric management protocols between the two periods, which may independently affect outcomes.

Therefore, the observed differences in safety outcomes should be interpreted with caution. Third, the small sample size and low number of adverse events limited the statistical power to detect or exclude clinically meaningful differences in safety outcomes. Some statistically significant findings (e.g., tocolytic use, meconium-stained amniotic fluid) were based on small absolute numbers and should be interpreted as exploratory rather than definitive, and the study should be viewed as hypothesis-generating and preliminary. Fourth, the findings were based on data from a single center, which may limit their generalizability to other settings or populations. Fifth, retrospective data collection precluded the systematic assessment of drug-related adverse effects. Sixth, uterine tocolytic use was used as a pragmatic clinical endpoint rather than an objective measurement of tachysystole frequency, due to incomplete uterine contraction recording in the retrospective cohort. Future research should include multicentre, large-scale randomized controlled trials and formal cost-effectiveness analyses to validate and expand upon these findings. Seventh, the exploratory logistic regression model included multiple variables with very few tocolytic events, leading to highly imprecise OR estimates with wide CIs.

The use of 25 µg vaginal misoprostol tablets for labor induction in multiparas with an unfavorable cervix achieved a vaginal delivery rate exceeding 80% within 24 h, comparable to that of dinoprostone vaginal suppositories. More importantly, misoprostol was associated with a preliminary lower rate of tocolytic use (8.7% vs 38.5%) and a markedly reduced incidence of meconium-stained amniotic fluid, suggesting a lower observed need for uterine contraction inhibitors in this pilot cohort. These findings support extending the clinical indications for 25 µg vaginal misoprostol tablets to include multiparous women. Nonetheless, individualized risk assessment and close intrapartum monitoring remain essential to ensure optimal maternal and neonatal outcomes. These preliminary findings warrant confirmation in larger, adequately powered studies such as multicentre randomized controlled trials with larger samples before firm conclusions about comparative safety can be drawn.

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.