During pregnancy, initiating labor before its spontaneous onset is called the induction of labor. To offer better care for both the fetus and mother, it is an increasingly common practice in modern obstetrics [1] . The ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management) reported a significantly lower risk of cesarean section and no significant difference in composite neonatal complications after elective induction at 39 weeks and 0 - 4 days of gestation, compared with expectant management [2] . To achieve the successful induction of labor, cervical ripening is a key step in the initiation, following which adequate and powerful uterine contractions at a regular frequency are required. Drugs are often used to induce cervical ripening and uterine contractions. The two main methods of cervical ripening for labor induction are mechanical dilation using absorbable cervical dilators or balloon catheters and pharmacological methods such as oral and vaginal PGE2 (dinoprostone) and PGE1 (misoprostol). Cervical ripening at the appropriate time is required for women who need induction of labor and have a cervix with a Bishop score of <6; induction of labor with oxytocin has a risk of failure when the Bishop score is <6.

PROPESS is the commercial name of PG2, also known as dinoprostone, a vaginal release drug. In Japan, until the approval of PROPESS in January 2020, only an intravenous formulation of prasterone sulfate sodium hydrate was approved as a pharmacological cervical maturation preparation. Therefore, mechanical cervical ripening methods were more commonly used. Controlled-release dinoprostone vaginal insert (PROPESS Vaginal Delivery System 10 mg) promotes cervical ripening in pregnant women. PROPESS is composed of a thin, flat, hydrogel polymer containing 10 mg of dinoprostone enclosed within a mesh-knitted thread for retrieval [3] .

In a previous randomized, double-blind, placebo-controlled study in Japan, a controlled-release dinoprostone vaginal delivery system for PROPESS or placebo was used in 113 women at 41 weeks of gestation with a Bishop score < 4. The time from insertion to vaginal delivery was 26.2 vs. 33.0 h (p < 0.0001), which was significantly shorter in the PROPESS group [3] . In a study comparing Foley catheters and PGE2, no significant differences were observed in the rate of vaginal delivery, the incidence of fetal dysfunction, time to delivery, or maternal complications, although oxytocin was more frequently used in the balloon catheter group [4] . Particularly in primiparas, mechanical cervical dilation causes more intense pain. Achieving cervical dilation without causing pain is advantageous in these patients. PROPESS comprises a hydrophilic polymer containing PGE2 and a net with an extraction cord. It is inserted into the posterior vaginal canal, where it remains for up to 12 h to promote painless cervical ripening with a low risk of intrauterine infection. Predicting the success of labor induction is challenging in clinical practice, especially in primiparas with unruptured membranes, necessitating a painless cervical ripening method without the risk of infection. Previous studies have focused on pregnant women with unruptured membranes, but none specifically targeted primiparas. This study aimed to evaluate the effectiveness and safety of PROPESS compared with conventional mechanical cervical ripening methods in primiparas with unruptured membranes.

We retrospectively analyzed 90 primiparas with intact membranes, including 41 in the PROPESS group (between May 2020 and December 2021) and 49 in the mechanical dilation group (between January 2017 and October 2019).

The mechanical ripening devices used in our department were Dylapan S^® (TKB Corporation, Japan) and Obatametro^® (Fuji Latex Co. Ltd., Japan). Dylapan S^® was used if the cervix was dilated less than 3 cm. Obatametro^® was used if the cervix was dilated more than 3 cm. For cervical dilation with Obatametro^®, less than 40 mL of sterile water must be injected after insertion. Of the 49 patients in the mechanical dilation group, 24 underwent initial dilation using Dylapan S^®, while 25 received dilation using Obatametro^®. Cervical dilation was repeated the following day until the Bishop score was ≥6; oxytocin was administered thereafter. Since May 2020, our first choice for cervical ripening has been PROPESS. PROPESS was inserted into the posterior vaginal canal and remained there for up to 12 h to promote cervical ripening. If labor did not start after using PROPESS, the Bishop score was checked the following day to determine whether mechanical cervical dilation or oxytocin should be used. The adverse effects of PROPESS include uterine hyperstimulation, non-reassuring fetal status (NRFS), fever, elevated blood pressure, and nausea. If adverse effects occur, the cord can be pulled to readily and quickly withdraw the device. Continuous fetal heart rate monitoring should be performed during PROPESS insertion. The criteria for removing PROPESS included 30 min of regular (3-min intervals) and painful contractions, artificial membrane rupture, onset of uterine hyperstimulation (>5 per 10 min), NRFS, and systemic side effects such as vomiting, nausea, and hypotension.

The indications for cervical ripening were defined as follows: singleton pregnancy from 37 weeks 0 days to 41 weeks 6 days gestation, cephalic position, cervical findings with a Bishop score ≤ 6, no history of CS, and consent for PROPESS or mechanical cervical ripening. Patients were not eligible for labor induction if they met any of the following criteria: already in labor, had undergone surgery involving myomectomy or uterine rupture, fetal dysfunction, placenta previa, placental abruption, cephalopelvic disproportion, breech positioning, or use of another cervical ripening or dilatation agent. The primary outcome was the CS rate in both groups. The secondary outcomes were the rate of delivery within 12 or 24 h after insertion, time required for delivery, CS rate owing to induction failure, prevalence of NRFS and chorioamnionitis, oxytocin use rate, neonatal outcomes, and additional use of mechanical dilation in the PROPESS group. Medical records were reviewed retrospectively; data are presented as the mean and standard deviation (SD) for continuous variables, and the number and percentage for categorical variables. Pearson’s chi-square tests were used for categorical variables. All statistical analyses were conducted using JMP Pro 15. P values < 0.05 were considered statistically significant. This study adhered to the relevant ethical considerations. Ethical approval was obtained from the ethics committee of our university (approval no. 1959, registered on 06/17/2022), and informed consent was obtained from all participants.

Table 1 shows patient characteristics and reasons for labor induction in the PROPESS and mechanical dilation groups. No significant differences were observed in the maternal age, gestational age at induction, baseline Bishop score, or frequency of maternal complications between the two groups. However, the PROPESS group had a significantly higher incidence of diabetes mellitus (DM) or gestational diabetes mellitus (GDM). Figure 1 shows the outcomes of the PROPESS and mechanical dilation groups. Of the individuals who received PROPESS alone, 15 (36.6%) individuals delivered transvaginally, of whom three delivered within 12 h and six within 24 h. Conversely, vaginal delivery was successful in two (4.1%) individuals in the mechanical dilatation group, with none occurring within 12 h and two within 24 h. The PROPESS group had significantly fewer patients requiring additional oxytocin compared to the mechanical dilation group (65.9% vs. 91.8%; p = 0.003). The addition of oxytocin resulted in 13 vaginal deliveries in the PROPESS group and 15 deliveries in the mechanical dilatation group, with significantly higher rates in the PROPESS group (63.4% and 38.8%, respectively; p = 0.02). After using PROPESS, 14 patients (34%) required additional mechanical cervical dilation, 2 with Dylapan^®, and 12 with Obatametro^®. Table 2 presents the delivery outcomes of both groups. The CS rate was significantly lower in the PROPESS group (36.6% vs. 61.2%, p = 0.02), and the delivery rates within 12 and 24 h after administration were higher in the PROPESS group than in the mechanical dilation group. However, no significant differences were observed in the overall delivery times between the two groups. We compared the delivery time between cases of failed cervical ripening with PROPESS requiring additional mechanical dilation (n = 14) and those in the mechanical dilation group (n = 49). The PROPESS group had a delivery time of 108 ± 54.7 h, while the mechanical dilatation group had a delivery time of 54 ± 8 h, indicating a shorter delivery time in the mechanical dilatation group (p = 0.01). To identify predictors of response to PROPESS, we compared patient backgrounds between cases in which vaginal delivery was achieved with a Bishop score ≥7 at the time of PROPESS removal (effective group; n = 19) and cases requiring additional mechanical dilation with PROPESS (ineffective group; n = 14) ( Table 3 ). However, we found no significant differences between the two groups in terms of maternal age, history of fertility treatment, pre-pregnancy body mass index, body mass index at delivery, gestational age at induction, or Bishop score at insertion. Additionally, multivariate analysis revealed no significant differences. No significant difference was observed between the two groups in the incidence of NRFS, chorioamnionitis, or neonatal outcomes.

DM, diabetes mellitus; GDM, gestational diabetes mellitus; HDP, hypertensive disorders of pregnancy; FGR, fetal growth restriction.

CS, cesarean section. * Cases requiring additional mechanical dilation for PROPESS included Dylapan S^® (n = 2) and Obatametro^® (n = 12), ** Comparison of delivery times in cases where cervical dilation was unsuccessful with PROPESS requiring additional mechanical dilation versus those in the mechanical dilation group.

Effective group: patients with a BS > 7 at the time of PROPESS extraction, resulting in vaginal delivery. Non-effective group: patients requiring additional mechanical dilation for PROPESS included Dylapan S® (n = 2) and Obatametro® (n = 12).

Avoid the authors thank Editage ( https://www.editage.jp ) for the English language review of this article.

Ethical approval was obtained from the ethics committee of the University of Ryukyus (Approval no. 1959, registered on 06/17/2022).

The datasets created and analyzed in this study are available from the corresponding author upon reasonable request.

All authors collaborated in this study. YK and KM contributed substantially to the study concepts and design. YC and TK made substantial contributions to the acquisition of data.