2025 Volume 13 Issue 1 Pages 17-22
Aim: This retrospective study compared PROPESS and intravenous dinoprost administration in labor induction to determine whether PROPESS use reduced the percentage of women who underwent amniotomy in induced labor under epidural analgesia (the amniotomy rate).
Methods: Of the women who underwent induced labor under epidural analgesia at our hospital, 131 primiparous women with a Bishop score ≤6 were included in this study. The participants were divided into the following two groups to compare the amniotomy rates: (1) PROPESS group (n=72), cases in which labor was induced using PROPESS (between June 2022 and May 2024). (2) Dinoprost group (n=59), cases in which labor was induced using intravenous dinoprost (between June 2019 and May 2022).
Results: Amniotomy rates did not differ between the PROPESS and dinoprost groups. However, amniotomy before the onset of effective labor contractions was significantly less frequent in the PROPESS group than in the dinoprost group (8.8 vs. 44.4%; P<0.001).
Conclusions: The results indicate that the use of PROPESS in induced labor under epidural analgesia may reduce the number of women who undergo amniotomy during the latent phase of the first stage of labor.
According to a report from the Ministry of Health, Labour and Welfare in 2020, painless delivery in medical institutions offering painless delivery and women undergoing painless delivery are still limited in Japan, accounting for 26.0% of all delivery facilities and 8.6% of all deliveries.1) Painless delivery is provided in two methods: “24-hour available painless delivery”, in which anesthetics are started after the onset of spontaneous labor, and “induced labor under epidural analgesia”, in which labor contractions are induced before the onset of spontaneous labor.
The success rate of labor induction depends on the status of cervical ripening. A prospective cohort study has shown that insufficient cervical ripening was associated with increased cesarean delivery rates, particularly in primiparous women.2) Therefore, Japanese guidelines recommend cervical ripening or dilation when inducing labor in women with insufficient cervical ripening.3)
Traditionally, mechanical devices, such as metreurynter and laminaria tent, have mainly been used for cervical ripening and dilation in Japan. Meanwhile, intravaginal prostaglandin administration for cervical ripening is the standard treatment recommended in guidelines in other countries, and the clinical use of dinoprostone vaginal inserts (PROPESS) has been approved in Japan in April 2020.
The conventional labor induction method at our hospital involved the use of intravenous dinoprost without mechanical dilation, considering the risk of umbilical cord prolapse and intrauterine infection due to metreurynter and laminaria tent use, respectively.4,5) Although intravenous dinoprost is suggested to be involved in cervical ripening,6) its exact effect is unclear. However, in clinical practice in Japan, intravenous dinoprost is often used in cases of insufficient cervical ripening. Furthermore, it is challenging to induce labor under epidural analgesia without cervical dilation and ripening at our hospital, and amniotomy for labor induction has been frequently performed.7)
Regarding amniotomy, a meta-analysis in 2013 has reported that “routine introduction of amniotomy is not recommendable because it did not significantly shorten the duration of the first stage of labor and was associated with an increased incidence of cesarean section, although the increase was not significant”.8) World Health Organization does not recommend the routine use of amniotomy in the first stage of labor to prevent prolonged labor.9) Accordingly, PROPESS has been used instead of intravenous dinoprost at our hospital since June 2022 for labor induction in women to adequately ripen the cervix before labor induction. This retrospective study compared PROPESS and intravenous dinoprost in labor induction to determine whether the use of PROPESS, which promotes cervical ripening, reduced the percentage of women who underwent amniotomy in induced labor under epidural analgesia (the amniotomy rate) at our hospital.
Of the women who underwent induced labor under epidural analgesia at our hospital during a 5-year period from June 2019 to May 2024, 131 primiparous women with a singleton pregnancy in the vertex position in the 37th to 41st week of pregnancy and a Bishop score ≤6 in whom PROPESS (Ferring Pharmaceuticals, Saint-Prex, Switzerland) (Period: June 2022 to May 2024) or intravenous dinoprost (period: June 2019 to May 2022) was used for labor induction were included in this study. Women with premature rupture of membrane were excluded. Mechanical dilatation of the cervix using metreurynter, laminaria tent, or other devices was not performed.
The participants were divided into two following groups:
PROPESS group (n=72): Cases in which labor was induced using PROPESS (between June 2022 and May 2024).
Dinoprost group (n=59): Cases in which labor was induced using intravenous dinoprost (between June 2019 and May 2022).
The percentage of women in whom effective labor contractions were induced (the rate of successful labor induction), perinatal events, and use/nonuse of amniotomy were compared between the two groups.
Methods of labor induction in the two groups were as follows:
PROPESS group: After confirming that the fetal heart rate was normal using a fetal heart rate monitor and that the woman had not yet gone into labor, PROPESS was inserted into the posterior vaginal fornix in the morning and left there for up to 12 h. PROPESS was removed immediately when (i) regular uterine contractions with pain at intervals of ≤3 min, (ii) a spontaneous rupture of membrane, (iii) non-reassuring fetal status (NRFS), (iv) hypertonic uterine contractions, or (v) a maternal adverse event was noted. PROPESS was also removed when the attending obstetrician considered that effective labor contractions were not occurring and performed amniotomy. After removal of PROPESS, the administration of anesthetics was started when the obstetrician considered that effective labor contractions had occurred. When uterine inertia was noted after the administration of anesthetics, intravenous oxytocin was started and used until delivery.
Dinoprost group: After confirming that the fetal heart rate was normal using a fetal heart rate monitor and that the woman had not yet gone into labor, intravenous dinoprost infusion was started in the morning. If no effective labor contractions were observed even after intravenous dinoprost was used, dinoprost was administered for a maximum duration of 12 h. If effective labor contractions started during the intravenous infusion of dinoprost, administration of anesthetics was initiated and continued until delivery. Because dilatation of the cervix was not performed, attention was paid to any findings on the fetal heart rate monitor suggestive of hypertonic uterine contractions or uterine rupture during labor induction.
When effective labor contractions were not noted during the day of administration of PROPESS or dinoprost, drug administration was discontinued during the night, and labor induction was initiated again next morning with intravenous oxytocin in all cases.
The intravenous administration of dinoprost and oxytocin infusions was performed according to the Guidelines for Obstetrical Practice in Japan 2020 edition,10) as follows:
Intravenous dinoprost infusion: 3,000 μg of dinoprost dissolved in 500 ml of 5% glucose solution was administered at a starting dose of 3.0 μg/min. The maximum dose was 25.0 μg/min, and the dose was increased by 1.5 μg/min at intervals of at least 40 min until the onset of effective contractions.
Intravenous oxytocin infusion: 5 IU of oxytocin dissolved in 500 ml of 5% glucose solution was administered at a starting dose of 2 mIU/min. The maximum dose was 20 mIU/min, which was increased by 2 mIU/min at intervals of at least 40 min until the onset of effective labor contractions.
Painless delivery was performed using epidural anesthesia, and anesthetic administration was started at the onset of effective labor contractions. Anesthesia was induced by injecting 10 ml of ropivacaine hydrochloride hydrate (0.1%) and 2 ml (100 μg) of fentanyl through the epidural catheter, followed by a continuous infusion of 58 ml of ropivacaine hydrochloride hydrate (0.1%) and 2 ml (100 μg) of fentanyl at a rate of 8 ml/h.
Amniotomy was performed in the following cases: (i) no effective labor contractions: uterine contractions at 3-min intervals were noted after uterotonic administration but were not associated with pain; and (ii) uterine inertia: no more widening of the cervix occurred for at least 2 h after the onset of painful contractions. Amniotomy was performed when the fetal head position was at station −3 cm or lower. Amniotomy before the initiation of anesthetics was defined as “amniotomy for inducing effective labor contractions”.
Stages of labor were evaluated according to a report by the Japan Society of Obstetrics and Gynecology, and dilation of the cervix to <5 cm and ≥5 cm was defined as the latent and active phases, respectively.11)
Determination of Bishop scores and delivery management in all cases were performed by a single obstetrician-gynecologist.
This study was approved by the Ethics Committee of Nakabayashi hospital (Approval No. 23-N001), Tokyo, Japan, and was performed in compliance with the Declaration of Helsinki. Although consent was not obtained from the patients because this is a retrospective observational study, we used the opt-out method. The presented data were anonymized to prevent the risk of identification.
Statistical analyses were performed using the χ2 test and Mann–Whitney U test. Bell Curve for Excel (Social Survey Research Information Co., Ltd.) was used for the analyses. Differences were considered statistically significant when P-value was <0.05.
There were no differences in age, height, prepregnant body mass index (BMI), gestational age in weeks at delivery, birth weight, umbilical cord arterial pH, duration of PROPESS or dinoprost use, analgesia use time, Bishop score at labor induction, cesarean delivery rate, and indications for cesarean delivery between the two groups (Table 1). No cases of umbilical cord prolapse or intrauterine infection were observed in either group.
| PROPESS group (n=72) | Dinoprost group (n=59) | P | |
|---|---|---|---|
| Age (Years)† | 31.0 (25–44) | 32.0 (25–41) | 0.441 |
| Height (cm)† | 160 (148–172) | 158 (145–174) | 0.165 |
| Prepregnant BMI (kg/m2)† | 20.9 (15.6–27.9) | 20.4 (16.5–26.0) | 0.358 |
| Gestational age at delivery (weeks)† | 39.0 (37.0–41.0) | 39.0 (37.0–41.0) | 0.483 |
| Birth weight (g)† | 3,052 (2,468–4,036) | 3,068 (2,432–4,002) | 0.410 |
| Umbilical cord arterial pH† | 7.32 (7.08–7.43) | 7.29 (7.14–7.41) | 0.260 |
| Duration of PROPESS/dinoprost use (h)† | 6 (1–11) | 6 (2–13) | 0.489 |
| Analgesia use time (h)† | 5 (1–24) | 5 (1–23) | 0.250 |
| Bishop score at labor induction† | 4.0 (2.0–6.0) | 4.0 (1.0–6.0) | 0.504 |
| Cesarean delivery rate (%) | 20.8 | 23.7 | 0.853 |
| Indication : | |||
| · Arrest of labor (%) | 60 | 57.1 | 1.000 |
| · NRFS‡ (%) | 40 | 42.3 | 1.000 |
The reasons for removal of PROPESS were “regular uterine contractions with pain at intervals ≤3 min” in 57.0%, “no signs of labor onset” in 28.0%, “spontaneous rupture of membrane” in 10.0%, “NRFS” in 4.0%, and “maternal adverse events” in 1.4%. There were no cases in which PROPESS was removed due to uterine tachysystole or for amniotomy purposes.
Among women who underwent vaginal delivery in the PROPESS and dinoprost groups, there were no differences in age, height, prepregnant BMI, gestational age in weeks at delivery, birth weight, umbilical cord arterial pH, duration of PROPESS or dinoprost use, analgesia use time, Bishop score at labor induction, duration of labor, vacuum extraction, cervical laceration, intrapartum blood loss between the two groups (Table 2). There were no blood transfusion cases in all subjets. The number of days of labor induction was significantly lower in the PROPESS group than in the dinoprost group (one day of labor induction: 40.4% vs. 13.3%; P<0.005) (Table 2). On the first day of labor induction, intravenous oxytocin was used in 28.1% of cases after the removal of PROPESS. Intravenous oxytocin was started approximately 1.5 hours after the initiation of analgesia or when the cervical dilation was about 4.5 cm.
| PROPESS group (n=57) | Dinoprost group (n=45) | P | |
|---|---|---|---|
| Age (Years)† | 30.0 (25–44) | 32.0 (25–41) | 0.120 |
| Height (cm)† | 160 (148–172) | 158 (145–174) | 0.160 |
| Prepregnant BMI (kg/m2)† | 20.8 (15.6–26.4) | 20.0 (16.5–25.5) | 0.222 |
| Gestational age at delivery (weeks)† | 39.0 (37.0–41.0) | 39.0 (37.0–41.0) | 0.337 |
| Birth weight (g)† | 3,054 (2,468–4,036) | 3,062 (2,432–3,818) | 0.578 |
| Umbilical cord arterial pH† | 7.33 (7.15–7.43) | 7.29 (7.14–7.41) | 0.220 |
| Duration of PROPESS/dinoprost use (h)† | 5 (1–11) | 6 (2–13) | 0.279 |
| Analgesia use time (h)† | 5 (1–24) | 4 (1–23) | 0.216 |
| Bishop score at labor induction† | 4.0 (2.0–6.0) | 4.0 (2.0–6.0) | 0.766 |
| Number of days of labor induction | |||
| 1 day (%) | 40.4 | 13.3 | <0.005 |
| 2 days (%) | 59.6 | 86.7 | <0.005 |
| Duration of labor (h)† | 6 (2–25) | 6 (2–25) | 0.474 |
| Duration of the 2nd stage of labor (min)† | 65 (5.0–179) | 49 (3.0–268) | 0.422 |
| Used oxytocin at 1st day on the labor induction (%) | 28.1 | 0.0 | |
| Duration from start of anesthesia to start of oxytocin (h)† | 1.5 (1–6) | ||
| Cervical dilation when oxytocin was started at 1st day of labor induction (cm)† | 4.5 (3–10) | ||
| Amniotomy (%) | 52.6 | 68.9 | 0.144 |
| Amniotomy for labor inducing effective labor contractions (%) | 8.8 | 44.4 | <0.001 |
| Vacuum extraction (%) | 54.4 | 71.1 | 0.128 |
| Cervical laceration (%) | 15.8 | 8.9 | 0.460 |
| Intrapartum blood loss (g)† | 437 (74–2,104) | 346 (134–977) | 0.352 |
| Blood transfusion rate (%) | 0 | 0 | — |
There were no significant differences in amniotomy rates between the PROPESS and dinoprost groups (Table 2). Meanwhile, amniotomy for inducing effective labor contractions was significantly less common in the PROPESS group than in the dinoprost group (8.8% vs. 44.4%; P<0.001) (Table 2). Fewer women tended to undergo amniotomy with a cervical opening <5 cm in the PROPESS group than in the dinoprost group, albeit the difference was not significant (73.3% vs. 93.5%; P=0.07) (Table 3).
| Women undergoing amniotomy | P | |||
|---|---|---|---|---|
| PROPESS group (n=30) | Dinoprost group (n=31) | |||
| Cervical dilatation | <5 cm (%) | 73.3 | 93.5 | 0.07 |
| ≥5 cm (%) | 26.7 | 6.5 | 0.07 | |
This study showed that the use of PROPESS in induced labor under epidural analgesia may reduce the amniotomy rate during the latent phase of the first stage of labor compared with that using intravenous dinoprost.
Bishop scores ≤6 are commonly considered to indicate “insufficient cervical ripening”.12) In this study, the use of PROPESS instead of intravenous dinoprost decreased the number of days required for labor induction and reduced the need for amniotomy to induce effective labor contractions during induced labor under epidural analgesia in primiparous women with insufficient cervical ripening. This may be because PROPESS facilitates uterine contractions and cervical ripening, resulting in labor onset in 57% of PROPESS users.
The first stage of labor is divided into the latent and active phases, and dilation of the cervix to 5 cm is a criterion for the active phase in Japan.11) In the women in whom PROPESS was not used, the majority underwent amniotomy in the latent phase, and the amniotomy rate tended to be higher than that in the women in whom PROPESS was used, although the difference was not significant. As mentioned above, amniotomy in the first stage of labor is not recommended based of the cesarean delivery rates.8,9) A review of Japanese cases has reported that amniotomy with a high fetal head position may cause local allergy-like reactions in the uterus and contribute to the development of amniotic fluid embolism because amniotic fluid components come into contact with the cervical tissue.13) Amniotomy with a high fetal head position may also pose a risk of umbilical cord prolapse.14) Therefore, amniotomy in the first stage of labor, particularly in the latent phase, should be avoided whenever possible. The results of this study indicate that labor induction using PROPESS can reduce the rate of amniotomy during the latent phase.
The overall number of women who underwent amniotomy did not differ depending on whether PROPESS was used or not. This was presumably because the participants of this study who underwent painless delivery developed uterine inertia as an effect of the anesthetics; thus, amniotomy was used to promote labor. A previous study reported that the cesarean section rate in the active labor management group, in which amniotomy and oxytocin were used for labor induction, was lower than that in the control group (waiting group).15) In painless delivery, amniotomy is used to promote labor in some cases because the anesthetics slow labor progression. However, our previous study reported that amniotomy during the use of a uterotonic agent (oxytocin) may be a risk factor for amniotic fluid embolism and obstetric disseminated intravascular coagulation, as it can cause hypertonic uterine contractions.16) Moreover, intravaginal administration of dinoprostone is prone to concurrent onset of cervical ripening and uterine contractions, resulting in a higher frequency of hypertonic contractions than mechanical methods for cervical ripening.17) Thus, attention should be paid to hypertonic uterine contractions even when amniotomy is used for inducing labor in women with uterine inertia.
As mentioned above, the adoption rate of painless delivery is low in Japan. However, the number of facilities offering painless delivery is expected to increase because many pregnant and parturient women prefer to have painless delivery. Because of the increase, more obstetric facilities are expected to provide labor induction during the daytime due to humanpower and other limitations. Therefore, the entire country should consider safe methods for induced labor under epidural analgesia.
The limitations of this study are as follows: the difference in the duration of PROPESS and intravenous dinoprost use. Therefore, it is necessary to conduct a randomized trial to confirm the result of this study. Regarding the number of days of labor induction, in the PROPESS group, there were cases where oxytocin was administered after the removal of PROPESS, while in the dinoprost group, the same drug was continued. This difference may have affected the results. Therefore, it is necessary to compare PROPESS without oxytocin to dinoprost.
The use of PROPESS in induced labor under epidural analgesia may reduce the number of women who undergo amniotomy during the latent phase of the first stage of labor and may reduce the above risks.
The authors thank Crimson Interactive Pvt. Ltd. (Ulatus) - www.ulatus.jp for their assistance in manuscript translation and editing.
The authors have no conflict of interests to declare.
Yasushi Nakabayasi wrote the paper and conceived and designed the analysis. Makiko Nakabayasi, Kiyomi Nakabayashi, Masayuki Santo contributed data collection. Masao Nakabayashi contributed performed the analysis. All authors have contributed significantly and agree with the content of the manuscript.
