|Year : 2021 | Volume
| Issue : 1 | Page : 52-57
Comparison of Dinoprostone Controlled Release Vaginal Pessary with Dinoprostone Intracervical Gel for Preinduction Cervical Ripening and Induction of Labor at Term
Anjali Tempe, Sonia Sindher, Niharika Dhiman, Devender Kumar, Pushpa Mishra
Department of Obstetrics and Gynecology, Maulana Azad Medical College, New Delhi, India
|Date of Submission||05-Oct-2020|
|Date of Acceptance||02-Apr-2021|
|Date of Web Publication||28-Apr-2021|
MS Niharika Dhiman
Associate Professor, Department of Obstetrics and Gynecology, Maulana Azad Medical College, New Delhi
Source of Support: None, Conflict of Interest: None
Context: There is limited experience of use of dinoprostone controlled release vaginal pessary in Indian scenario. Hence, we aim to find its efficacy for induction of labor (IOL). Aims: To compare two formulations of dinoprostone: intracervical gel and controlled release vaginal pessary for IOL. Settings and Design: Randomized controlled study in a tertiary care center. Methods: A double-blinded randomized controlled study was done on 106 women with singleton pregnancy, 37 to 41 weeks with vertex presentation, no obvious fetal compromise, and planned for IOL. They were randomly divided into equal groups to receive either dinoprostone intracervical gel (Group A) or dinoprostone controlled release vaginal pessary (Group B). The main outcome measures: change in Bishop score (using simplified Bishop score) at 0 to 6 hours and 6 to 12 hours after application and success to initiate active labor. The secondary outcome measures: maternal adverse effect, induction to delivery time, requirement of oxytocin infusion, cesarean section rate, APGAR score, and neonatal intensive care unit admission. Statistical Analysis: Statistical Package for Social Sciences (SPSS) version 17.0. Results: Increase in Bishop score and women achieving active labor were more in Group B (90.6% vs. 41.5%; P < 0.01). Mean time from induction to delivery was higher in Group A (19.72 hours vs. 12.53 hours; P < 0.01). Requirement of oxytocin was lesser in Group B (35.8% vs. 75.5%; P < 0.001). No adverse maternal or fetal outcome was noted in either of the groups. Conclusions: Dinoprostone controlled release vaginal pessary has significantly better outcomes than intracervical gel for IOL.
Keywords: Cervical ripening, dinoprostone (PGE2) controlled release vaginal pessary, dinoprostone (PGE2) intracervical gel, IOL, simplified Bishop score
|How to cite this article:|
Tempe A, Sindher S, Dhiman N, Kumar D, Mishra P. Comparison of Dinoprostone Controlled Release Vaginal Pessary with Dinoprostone Intracervical Gel for Preinduction Cervical Ripening and Induction of Labor at Term. MAMC J Med Sci 2021;7:52-7
|How to cite this URL:|
Tempe A, Sindher S, Dhiman N, Kumar D, Mishra P. Comparison of Dinoprostone Controlled Release Vaginal Pessary with Dinoprostone Intracervical Gel for Preinduction Cervical Ripening and Induction of Labor at Term. MAMC J Med Sci [serial online] 2021 [cited 2021 Jun 13];7:52-7. Available from: https://www.mamcjms.in/text.asp?2021/7/1/52/314872
Key Messages: Increase in Bishop score, shorter induction to delivery time, more women achieving active labor, and lesser requirement of oxytocin were observed with dinoprostone controlled release pessary. Dinoprostone controlled release vaginal pessary has better maternal outcomes than intracervical gel for IOL.
| Introduction|| |
Induction of labor (IOL) is defined as an artificial initiation of labor before its spontaneous onset. Labor induction is the most commonly used practice in obstetrics. Over the past decades, a rise has been observed in the rate of IOL. In developing countries, the rates are generally lower, but in some settings, they have been found to be as high as 30%.
Labor is induced due to various fetal–maternal conditions, using different methods and drug formulations. There are various prostaglandin E2 (PGE2)/Dinoprostone preparations available, which have been used since 1972 for IOL. Dinoprostone is the only preparation approved by food and drug administration (FDA) for use. Bishop pelvic scoring system is most commonly used for cervical assessment prior to IOL. A recent study examining over 5600 nulliparous women undergoing IOL found that a simplified Bishop score was equally as predictive as the traditional Bishop score in predicting vaginal delivery.
In Indian scenario, experience of use of pessary is limited. This study may be beneficial in Indian population which is demographically different from western world where most of the studies are carried out.
| Subjects and Methods|| |
Aim of our study was to evaluate the efficiency of dinoprostone controlled release vaginal pessary compared with dinoprostone intracervical gel for cervical ripening and IOL. This randomized controlled study was conducted over a period of 16 months, from November 2017 to March 2019 in a tertiary care center. The study was approved by Institutional Ethics Committee of the hospital (IEC/MAMC/2017/OBG/15).
Eligibility criteria for participants were: singleton pregnancy, gestational age 37 to 41 weeks (calculated by last menstrual period and confirmed by first trimester ultrasonography), fetal vertex presentation, and no obvious fetal compromise. Exclusion criteria were: contraindications to use of prostaglandins, previous uterine surgeries or repeated dilatation and currettage (D&C), severe medical disorders, and critically ill patients.
All pregnant women (n = 139) received in labor room of our hospital requiring IOL were assessed for the eligibility criteria for enrolment in our study. A total of 106 pregnant women fulfilling above criteria were recruited; excluding all noneligible candidates (n = 28) and participants who were not willing for enrolment into the study (n = 5). The participants were explained about the two possible methods to be allocated at the time of taking consent for study. Informed written consent for participation into this study and for IOL was taken.
All participants (n = 106) were randomly divided into two equal groups using simple randomization method (envelope method). Total 106 envelopes were made; 53 envelopes were assigned as alphabet A and the remaining 53 with alphabet B, ensuring even distribution of participants in the two treatment groups. Each of the eligible participants was asked to take one envelope and method was allocated as per alphabet assigned in the envelope. Double blinding was done for both participant and researcher; however, resident in charge of labor room was aware about the allocated method. A preprocedural assessment of all the participants in terms of uterine activity, simplified Bishop score [Table 1], and fetal heart rate was done by the resident in charge who also applied the method allocated as per the randomization to either of the groups.
Group A (n = 53): Dinoprostone intracervical gel (0.5 mg)
Group B (n = 53): Dinoprostone controlled release vaginal pessary
Dinoprostone preparations used:
- Intracervical gel: It contains 0.5 mg of PGE2 which is incorporated into a viscous hydroxyl methyl cellulose gel.
- Controlled release vaginal pessary: It is a thin, flat, polymer wrapped in polyester net to enable its removal by a 30 cm thread. It contains 10 mg of PGE2 which is released at a rate of 0.3 to 0.4 mg/hour. It was designed to minimize or correct the deficiencies of gel formulation. It delivers drug at a controlled and predictable rate. Furthermore, pessary can be removed in the event of adverse drug reaction.
All the participants were monitored for uterine activity, progress of labor, and fetal heart rate (using intermittent auscultation or Doppler or cardiotocography) as per the standard protocol. Simplified Bishop score was noted at 6th hour and 12th hour following IOL or prior if signs of active labor were present. Women in Group A received second dose of 0.5 mg dinoprostone gel if Bishop score at 6 hours assessment was found to be <4; with maximum two doses given 6 hours apart. While Group B received single dinoprostone controlled release pessary which was removed after 12 hours or before − in cases of either spontaneous rupture of membranes or if active labor ensued. Augmentation of labor with artificial rupture of membranes (with at least 5 cm cervical dilatation) and/or oxytocin infusion (if ≤2 contractions in 10 minutes at the end of 12 hours in both the groups) was done with the aim of delivery within 24 to 48 hours. Active labor was considered to be established when there were at least three regular uterine contractions during a 10-minutes period and the cervix was at least 4 cm cervical dilatation.
The primary outcomes were:
- Change in Bishop score at 0 to 6 hours and 6 to 12 hours after application.
- Success to initiate active labor.
The secondary outcomes were:
- Induction to delivery time.
- Number of patients requiring augmentation of labor using oxytocin.
- Mode of delivery.
- Maternal adverse effects.
- Fetal outcome: Apgar score and neonatal intensive care unit (NICU) admission.
Statistical analysis: Data in the literature reported the mean change in Bishop score for patients using PGE2 intracervical gel was 1.8 ± 1.9 as against 3.2 ± 3.1 in the PGE2 vaginal pessary (William et al., 1998). Assuming these as reference values, the minimum required sample size at 5% level of significance and 80% power is obtained as at least 53 patients in each group.
Formula used for sample size calculation: n = 2σ2 (Zα/2 + Zβ)2/Δ2, where n is the number of subjects required in each group; Δ is the expected difference, and σ2 is the standard deviation of the difference. Zα/2 is cumulative normal distribution at α/2 level of significance. Zβ is cumulative normal distribution at β value (where, power = 1 − β).
Sample size calculation: Δ = 1.4; σ2 = 6.61; Z2.5% = 1.96 at α = 5% level of significance; Zβ = 0.842 at β = 20% value (where, power = 1 − β = 80%).
The quantitative variables in both groups were expressed as mean ± SD and compared using unpaired t test between groups and paired t test within each group at various follow-ups. The qualitative variables were expressed as frequencies/percentages and compared using chi-square test. A P-value < 0.05 was considered statistically significant. Statistical Package for Social Sciences (SPSS) version 17.0 (IBM SPSS Statistics) was used for statistical analysis.
| Results|| |
A total of 106 pregnant women were randomized. [Table 2] represents the maternal age, period of gestation, and parity in the two study groups. Both the groups were comparable in terms of demographic profile. The maternal age of the studied group varied from 19 years to 36 years in Group A and from 20 years to 34 years in Group B.
Indication of IOL
Various indications of IOL were used. Postdatism was the most common indication for IOL in both the groups (50.9% in Group A and 66% in Group B). Other indications of IOL In Group A were: Gestational Diabetes Mellitus (15.1%), decreased fetal movements (13.2%), Fetal growth restriction (7.5%) Intrahepatic Cholestasis Of Pregnancy (7.5%), Gestational Hypertension (3.8%), and oligohydramnios (1.9%), while in Group B were: decreased fetal Movements (9.4%), gestational hypertension (9.4%), Fetal Growth Restriction (7.5%), Oligohydramnios (3.8%), Gestational Diabetes Mellitus (1.9%) and intrahepatic Cholestasis of pregnancy (1.9%).
Bishop score at 0, 6, and 12 hours
Bishop score was calculated manually at 0, 6, and 12 hours using three parameters (cervical dilatation, cervical effacement, and cervical consistency). In our study, both the groups had comparable Bishop score at 0 hours (i.e., preinduction Bishop score) (2.42 ± 0.95 in Group A and 2.68 ± 1.05 in Group B; P-value = 0.178). According to the data, there was statistically significant difference between the two groups at 6 hours (3.78 ± 1.54 in Group A and 5.22 ± 1.58 in Group B) and 12 hours (4.49 ± 1.69 in Group A and 6.00 ± 1.41 in Group B) with P-value < 0.001.
In Group A, total two out of 53 patients delivered in ≤6 hours (but none of them had precipitate labor, i.e., delivery in <3 hours). Therefore, mean Bishop score at 6 hours was calculated for 51 patients. In Group A, total 16 out of 53 patients delivered in ≤12 hours. Therefore, mean Bishop score at 12 hours was calculated for 37 patients.
In Group B, total seven out of 53 patients delivered in ≤6 hours (but none of them had precipitate labor, i.e., delivery in <3 hours). Therefore, mean Bishop score at 6 hours was calculated for 46 patients. In Group B, total 27 out of 53 patients delivered in ≤12 hours. Therefore, mean Bishop score at 12 hours was calculated for 26 patients.
Change in Bishop score from 0 to 6 hours, 6 to 12 hours, and 0 to 12 hours: Simplified Bishop score noted during assessment at 0, 6, and 12 hours was analyzed and change in Bishop score was calculated from 0 to 6 hours, 6 to 12 hours, and 0 to 12 hours [Table 3]. Increase in Bishop score was more in Group B which was statistically significant [Figure 1].
|Figure 1 Comparison of dinoprostone controlled release vaginal pessary with dinoprostone intracervical gel for change in Bishop score (simplified)|
Click here to view
Success to initiate active labor: In Group B (90.6%, n = 48), a greater number of patients achieved active labor as compared to Group A (41.5%, n = 22) (P < 0.01) [Table 3].
- Mean time from IOL to delivery: Overall Group B had a shorter time from induction to delivery (12.53 ± 6.565 hours vs. 19.72 ± 11.185 hours; P < 0.001). In Group B, more number of patients delivered within 12 hours from induction (50.9%) compared to Group A (30.2%). And none of these patients had precipitate labor, that is, delivery in <3 hours. Only one patient in Group A was delivered after 48 hours of induction while rest all of the patients were delivered within 48 hours in both the groups [Table 4].
- Need for augmentation of labor using oxytocin: More number of patients in Group A required augmentation of labor using oxytocin as compared to Group B (75.5% vs. 35.8%; P < 0.01) [Table 4].
- Mode of delivery: In terms of mode of delivery, Group B had more vaginal deliveries as compared to Group A (83% vs. 67.9%) but this difference was not found to be statistically significant (P = 0.088). There were only two out of 53 patients (3.8%) in each group who had instrumental delivery. In Group A, there was one instrumental delivery in the form of forceps application due to fetal bradycardia with caput at +3 station while another in the form of vacuum extraction due to meconium stained liquor with poor maternal bearing down efforts. In Group B, two instrumental deliveries were in the form of forceps application due to fetal bradycardia with poor maternal bearing down efforts. Rate of cesarean section was comparatively more in Group A but difference was not statistically significant (28.3% vs. 13.2%; P-value 0.088). Most common indication of cesarean section in Group A was failed induction (33.3%) followed by fetal bradycardia (26.7%), meconium staining of amniotic fluid (20%), nonprogress of labor (13.3%), and second stage arrest of labor (6.7%). Most common indication of cesarean section in Group B was nonprogress of labor (42.8%) followed by meconium staining of liquor (28.6%), failed induction (14.3%), and fetal bradycardia (14.3%) [Table 4].
- Maternal adverse effects: In Group A, none of the patients had any maternal adverse effect. All the participants received injection drotaverine 40 mg intravenous during active phase but still in Group B two patients out of total 53 patients developed unbearable pain. However, uterus was not hypertonus and it was not associated with any fetal heart rate abnormalities. Pessary was removed in these patients and both patients became normal immediately within 15 to 20 minutes of pessary removal. They did not have precipitate labor. This difference was not statistically significant (P = 0.153) [Table 4].
- Fetal outcome: Fetal outcome was same in both the groups with respect to NICU admission and APGAR score. No neonatal adverse outcome was observed in any of the two groups [Table 4].
| Discussion|| |
Our study demonstrates that the preinduction cervical ripening with the dinoprostone controlled release vaginal pessary is associated with a very high rate of women entering into active labor. Thus, the vaginal insert was associated with more vaginal deliveries within 12 and 24 hours than with the intracervical gel. Moreover, there was a decreased need for oxytocin induction together with a trend toward reduced rate of cesarean section. These performances of dinoprostone controlled release vaginal pessary are relevant since they apply to women undergoing labor induction mainly because of postdated pregnancy. [Table 5] shows comparison of results of our study with previous studies done in past. Our results are in concordance with previous studies which showed that induction to delivery interval was significantly shorter with PGE2 vaginal pessary in comparison to dinoprostone cervical gel.,,, Of note, other authors demonstrated contradicting results. Some concluded that the vaginal insert was less effective than other prostaglandins for cervical ripening in terms of longer time interval from induction to vaginal delivery and in terms of achieving vaginal delivery within 12 hours,, whereas others, demonstrated that slow-release PGE2 vaginal insert was as equally effective as other prostaglandins in terms of delivery by 24 hours. Reasons for these contrasting conclusions could be the heterogeneity in terms of inclusion criteria, preinduction Bishop score, primary outcome measures, and varying protocols of induction.
| Conclusion|| |
In our randomized controlled study, we conclude that dinoprostone controlled release vaginal pessary has significantly better outcomes in terms of achieving favorable Bishop score, greater success to initiate active labor, and shorter induction to delivery time with lesser requirement of oxytocin for augmentation after induction. However, the rate of cesarean section did not decrease significantly. Both the preparations of dinoprostone were found to be effective for IOL and can be used as per standard guidelines for their use.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]