http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1–6 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.883375
ORIGINAL ARTICLE
Pre-induction cervical ripening: comparing between two vaginal preparations of dinoprostone in women with an unfavorable cervix J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Universidad del Rosario on 09/10/14 For personal use only.
Eran Ashwal1,2, Liran Hiersch1,2, Nir Melamed1,2, Yaara Manor1,2, Arnon Wiznitzer1,2, Moshe Hod1,2, and Yariv Yogev1,2 1
Department of Obstetrics and Gynecology, Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tiqwa, Israel and 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract
Keywords
Objective: Prostaglandin E2 (PGE2-Dinoprostone) is accepted for both ripening of the cervix and induction of labor. As conflicting data exist concerning the efficiency and safety of different treatment modalities, we aimed to compare slow-release vaginal insert PGE2 with serial vaginal tablets of PGE2 for cervical ripening and induction of labor. Methods: A retrospective cohort study comparing all pregnancies who underwent induction of labor by either a single slow-release vaginal insert of 10 mg PGE2 (study group) to a historical control group of women who were treated with serial administration of 3 mg vaginal PGE2 tablets in a 2:1 ratio, matched by parity. Results: Overall, 639 women were enrolled (213 treated with PGE2 tablets and 426 with slowrelease vaginal inserts). Vaginal insert was associated with shorter initiation-to-ripening interval (12.4 ± 7.7 versus 18.6 ± 15.2 h, p50.001) and a higher rate of delivery within 24 h (61.5 versus 51.6%, p ¼ 0.018). Vaginal insert was associated with an increased rate of tachysystole (8.0 versus 3.1%, p50.01); however, the rates of cesarean section or operative delivery due to non-reassuring fetal heart rate (NRFHR) were similar. On multivariable analysis, slow-release vaginal insert was independently associated with a higher rate of delivery within 24 h (OR 1.50, 95% CI 1.04–2.18). Conclusion: Slow-release PGE2 vaginal insert achieves cervical ripening and subsequently delivery over a shorter time period than PGE2 tablets, without increasing uterine hyperstimulation rate.
Cervical ripening, dinoprostone, induction of labor, vaginal insert
Introduction Induction of labor is one of the most common obstetrical procedures performed, involving approximately 20% of all parturient women. As much as half of them are induced in the presence of an unfavorable cervix [1]. Cervical conditions at initiation of induction of labor greatly affect the success rate of labor induction. It is well established that an unfavorable cervix is associated with a higher rate of induction failure and increased rate of operative vaginal delivery and cesarean delivery [1,2]. Dinoprostone (PGE2) is one of the synthetic prostaglandin compounds most commonly applied in order to achieve cervical ripening and induction of labor. Numerous administration regimens have been used, such as tablets, suppositories, gel (either vaginal or intra-cervical) or as a slow-release vaginal insert. The slow-release vaginal insert has several potential advantages relative to other mentioned
Address for correspondence: Yariv Yogev, MD, Department of Obstetrics and Gynecology, Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tiqwa 49100, Israel. Tel: +972-3-9377400. Fax: +972-3-9377409. E-mail: [email protected]
History Received 27 December 2013 Revised 5 January 2014 Accepted 10 January 2014 Published online 4 February 2014
regimens. It is applied as a single application, the insertion is relatively easy and termination of drug effect can be achieved by removing it if uterine hyperstimulation and\or abnormal fetal heart rate changes occur during the ripening process. Previous studies comparing PGE2 vaginal insert to other prostaglandin formulations showed variable results [3,4]. These contrasting conclusions could be due to the heterogeneity in terms of inclusion criteria, indications for induction of labor, pre-induction Bishop score, different primary outcome measures and various drug administration regimens. As conflicting data exists concerning the most efficient and safe method, we aimed to compare slow-release PGE2 vaginal insert versus serial PGE2 vaginal tablets for cervical ripening and induction of labor.
Methods Study population We conducted a retrospective cohort study. The study group included women admitted for pre-induction cervical ripening between 34 and 41 weeks’ gestation using 10 mg vaginal dinoprostone insert (Propess, Ferring, Germany), between January to June 2013, in a university-affiliated tertiary
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hospital. Data were compared with historical control women who underwent pre-induction cervical ripening using vaginal tablets (Dinoprostone 3 mg, Pharmacia Upjohn, Puurf, Belgium) during the period 2011–2012 in a 1:2 ratio matched by parity (historical control). Both women had a Bishop score of 4 at admission. The reason for the difference in the time periods between the two studied groups was derived from a change in our pre-induction cervical ripening policy since 1 January 2013. Since then, slow-release vaginal PGE2 insert was suggested to all women who underwent cervical ripening and/or induction of labor. Pregnancies complicated by non-vertex presentation, multiple gestations, previous cesarean section (CS), known chromosomal or structural anomalies or any contraindication for vaginal delivery were excluded from both the study and control groups.
J Matern Fetal Neonatal Med, Early Online: 1–6
Other outcome variables were mode of delivery, uterine hyperstimulation rate, operative or cesarean delivery due to non-reassuring fetal heart rate, time interval from initiation of cervical ripening to achieving cervical ripening and time interval from initiation of cervical ripening to delivery. Data collection Data were obtained for both groups retrospectively from our departmental electronic health records. The following demographic and obstetrical variables were recorded: maternal age, gravidity, parity, indication for labor induction, gestational age at delivery, intra-partum characteristics, such as NRFHR and mode of delivery and indication for operative or cesarean delivery. The following perinatal outcomes were assessed: Apgar scores at 1 and 5 min and birthweight. Definitions
Labor induction protocol for the study and control groups According to our department protocol, 10 mg PGE2 slowrelease vaginal insert (Propess, Ferring, Germany) was administrated to the posterior fornix until cervical ripening was achieved (Bishop score 47). Fetal heart rate monitoring was performed prior to and one hour after the insertion of the vaginal PGE2 insert and again at 12 and 24 h or in the presence of painful uterine contractions or suspected ruptured membranes. The vaginal insert was removed in the presence of painful uterine contractions, uterine hyperstimulation, nonreassuring fetal heart rate (NRFHR), successful ripening (Bishop score 47) or after 24 h from insertion regardless the Bishop score. Ripening failure was defined as Bishop score 7 after 24 h from insertion. Serial PGE2 vaginal tablets (Dinoprostone 3 mg, Pharmacia Upjohn, Puurf, Belgium) were administrated to the posterior fornix at 6–8 h intervals until cervical ripening was achieved (Bishop score 47). Fetal heart rate monitoring was performed prior and after each application. In the presence of painful uterine contractions or uterine tachysystole, the administration of PGE2 was delayed until contractions subsided. According to our protocol up to five tablets administration were given (maximal cumulative dose of 15 mg). Following instillation of PGE2, the woman was advised to lie down for at least 60 min. Ripening failure was defined as a Bishop score 7 after 5 PGE2 tablets. Cervical ripening process was terminated if uterine hyperstimulation or NRFHR occurred without achieving adequate fetal heart rate reassuring. Women in whom cervical ripening was achieved were transferred to delivery room, and if necessary, augmentation of labor with oxytocin and/or artificial rupture of membranes (ARM) were used, under continuous electronic fetal monitoring. In general, upon failure of cervical ripening with PGE2 (regardless the regimen administrated), a subsequent trial of either labor induction with oxytocin or cervical ripening using extra-amniotic balloon was undertaken. The decision was made according to the Bishop score, uterine contractions patterns and physician’s preference. The primary outcome measure was achieving a delivery within 24 h from the initiation of the cervical ripening.
Indications for labor induction were categorized into maternal of fetal indications. Maternal indications included any of the following: hypertensive disorders, diabetes or maternal morbidity. Fetal indication included any of the following: prolonged pregnancy (41+6 weeks’ gestation or more), premature rupture of membranes, fetal growth restriction (defined as sonographically estimated fetal weight below the 10th percentile according to local reference curves [5]), large for gestational age (defined as sonographically estimated fetal weight above the 90th percentile according to local reference curves [5]), amniotic fluid volume disorders, cholestasis of pregnancy, non-reassuring fetal heart rate, reduced perception of fetal movements or unstable lie. Uterine hyperstimulation was defined as fetal heart rate decelerations or fetal bradycardia in the presence of more than five uterine contractions in 10 min or a contraction lasting more than 2 min [1]. Tachysystole was defined as more than five uterine contractions in 10 min or a contraction lasting more than 2 min in the presence of reassuring fetal heart rate [1]. NRFHR was defined as fetal heart rate patterns which were classified as either Category II (without achieving adequate reassurance) or Category III, according to National institute of Child Health and Human Development workshop report [6]. Failed induction was defined as a failure to achieve active phase of labor (dilatation of 4 cm or more in the presence of regular uterine contractions) after at least 12 h have elapsed from the initiation of oxytocin infusion in the presence of artificial rupture of membranes. Maternal comorbidities include one or more of the following: asthma, hypothyroidism, pre-gestational diabetes mellitus, either inherited or acquired thrombophilia and inflammatory bowel disease. Statistical analysis Data analysis was performed with the SPSS v19.0 package (SPSS Inc., Chicago, IL). Student’s t test and Mann–Whitney U test were used to compare continuous variables with and without normal distribution between the groups, respectively. The chi-square and Fisher’s exact tests were used for
PGE2 (dinoprostone) for cervical ripening
DOI: 10.3109/14767058.2014.883375
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Table 1. Demographics and obstetrical characteristics for the study and control groups.
Maternal age Ethnicity Jewish Arabic Gravidity Parity Nulliparity Pre-gestational BMI Smoking Previous abortion Maternal Co-morbidities
Slow-release vaginal insert group N ¼ 213
PGE2 tablets group N ¼ 426
30.0 ± 5.0
30.7 ± 5.0
187 (92.1) 386 (93.5) 2 (1–3) 0 (0–2) 107 (50.2) 25.2 ± 4.8 7 (3.3) 20 (10.3) 56 (26.3)
16 (7.9) 27 (6.5) 2 (1–3) 0 (0–2) 216 (50.7) 25.1 ± 5.6 22 (5.2) 45 (9.9) 112 (26.3)
p Value 0.53 0.32 0.99 0.88 0.94 0.99 0.19 0.38 0.48
Values are presented as mean ± SD, median (interquartile range) or n (%). BMI – body mass index; CS – cesarean section.
categorical variables. Variables that were found to be different between the groups (p50.05) in the bivariate analysis as well as variables that were hypothesized to potentially affect the likelihood of adverse outcome based on clinical grounds were entered to the multivariable logistic regression model. Differences were considered significant when p value was less than 0.05.
Results A total of 639 women were included in the study, of them 213 and 426 underwent cervical ripening and induction of labor with a single slow-release vaginal PGE2 insert or serial vaginal PGE2 (dinoprostone) tablets, respectively. The demographic and obstetrical characteristics of the study and control groups are shown in Table 1. There were no differences between the groups with regard to maternal age, gravidity, parity and pre-gestational BMI. With respect to pregnancy and delivery characteristics, the rates of fertility treatments, hypertension disorders, diabetes, estimation of fetal weight, gestational age at delivery and the rate of preterm delivery were similar between the groups (Table 2). There were no differences in the indications for labor induction between the groups (Table 3). Cervical conditions were significantly more unfavorable in the slow-release PGE2 vaginal insert group in comparison with the serial vaginal PGE2 tablets group (closed cervix at enrollment 45.5 versus 27.0%, p50.001, respectively) (Table 4). During cervical ripening and induction of labor process, there was a higher rate of tachysystole in the vaginal insert group (8.0 versus 3.1%, p50.01). The rate of uterine hyperstimulation, NRFHR or painful contractions necessitating termination of the cervical ripening and induction of labor process was similar between the groups. Likewise, the rate of rupture of amniotic membranes during ripening was similar between the groups (Table 4). The time interval from administration of the different PGE2 agent for achieving cervical ripening was shorter in the vaginal insert group (11.01 ± 6.5 versus 16.9 ± 12.9 h,
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Table 2. Pregnancy characteristics for the study and control groups.
Fertility treatment Gestational age at delivery (weeks) Preterm birth (537 weeks) Hypertensive complications GDM IUGR EFW (g) Mode of delivery NVD Operative vaginal delivery Dystocia NRFHR Other CS Failed induction Dystocia NRFHR Other Intra-partum fever Meconium PPH Post-partum fever Birthweight (g) Birthweight 44000 g Blood transfusion
Slow-release vaginal insert group N ¼ 213
PGE2 tablets group N ¼ 426
p Value
16 (7.5) 39.0 ± 1.7
17 (4.0) 39.0 ± 1.8
0.08 0.59
12 (5.6) 16 (7.5) 42 (19.7) 13 (6.1) 3425 ± 347 0.36 155 (74.2) 22 (10.5) 6 (2.8) 15 (7.0) 1 (0.4) 32 (15.3) 13 (6.1) 5 (2.3) 10 (4.7) 4 (1.8) 4 (2.2) 20 (10.5) 8 (4.5) 1 (0.6) 3268 ± 483 12 (5.6) 3 (1.7)
22 (5.2) 41 (9.6) 79 (18.5) 23 (5.4) 3406 ± 372
0.85 0.23 0.39 0.42 0.62
322 (75.8) 54 (12.7) 19 (4.5) 33 (7.7) 2 (0.4) 49 (11.6) 12 (2.8) 7 (1.6) 23 (5.4) 7 (1.6) 11 (2.7) 55 (13.3) 12 (3.1) 3 (0.8) 3259 ± 478 31 (7.3) 2 (0.5)
0.24 0.23 0.39 0.87 NA 0.21 0.05 0.54 0.85 0.89 0.48 0.14 0.28 0.62 0.82 0.50 0.19
Values are presented as mean ± SD or n (%). CS – cesarean section; EFW – estimated fetal weight; GDM – gestational diabetes; MOD – mode of delivery; NA – not applicable; NRFHR – non-reassuring fetal heart rate; NVD – normal vaginal delivery; PPH – post-partum hemorrhage.
Table 3. Indications for labor induction in the study and control group.
Induction indication Fetal Maternal Fetal Post-term PROM Oligohydramnios Polyhydramnios GDM Macrosomia IUGR Cholestasis of pregnancy NRFHR Reduced fetal movements Unstable lie Others* Maternal HTN disorders Maternal morbidity
Slow-release vaginal insert group N ¼ 213
PGE2 tablets group N ¼ 426
113 (53.1) 100 (46.9)
229 (53.8) 197 (46.2)
p Value 0.47 0.29
50 27 2 12 37 8 13 8 5 12 3 0
(23.5) (13.6) (0.9) (5.6) (17.4) (3.8) (6.1) (3.8) (2.3) (5.6) (1.4) (0)
77 62 7 22 66 6 18 9 14 22 2 5
(18.1) (14.5) (1.6) (5.2) (15.5) (1.4) (4.2) (2.1) (3.3) (5.2) (0.5) (1.2) 0.25
17 (8) 7 (3.3)
39 (9.2) 16 (3.8)
Values are presented as mean ± SD or n (%). HTN – hypertension; IUGR – intrauterine growth restriction; GDM – gestational diabetes; NRFHR – non-reassuring fetal heart rate; PROM – premature rupture of membranes. Others* – umbilical cord varix, asymmetric fetal ventricles, unilateral fetal ventriculomegaly.
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Table 4. Induction characteristics for the study and control groups.
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Slow-release vaginal insert group N ¼ 213 Cervical condition – At PGE2 administration Closed cervix Dilatation 1 cm Effacement 50% Tachysystole Hyperstimulation NRFHR SROM Termination of ripening process* Additional induction Oxytocin EAB Initiation to ripening interval** (h) Time interval from ripening initiation to full cervical dilatation (h) Time interval from ripening initiation delivery (h) Delivery within 12 h Delivery within 24 h
97 170 108 17 6 8 14 21
(45.5) (79.8) (50.7) (8.0) (2.8) (3.8) (6.6) (9.9)
24 (11.2) 17 (7.9) 12.41 ± 7.79 22.17 ± 14.52 23.59 ± 15.82 54 (25.4) 131 (61.5)
PGE2 tablets group N ¼ 426 115 314 202 13 4 30 20 40
p Value 50.001 0.09 0.45 50.01 0.09 0.11 0.21 0.48
(27.0) (73.7) (47.4) (3.1) (0.9) (7.0) (4.7) (9.4)
36 (8.4) 12 (2.8) 18.64 ± 15.21 27.44 ± 19.75 28.41 ± 20.06 86 (20.2) 220 (51.6)
0.24 50.001 50.001 0.001 0.003 0.15 0.018
Values are presented as mean ± SD or n (%). EAB – extra amniotic balloon; NRFHR – non-reassuring fetal heart rate; SROM – spontaneous rupture of membranes. *As defined in the ‘‘Methods’’ section. **Time interval from PGE2 administration to achieving a Bishop score 4 7.
Table 5. Multivariable analysis for vaginal delivery within 24 h. OR Vaginal insert Maternal age Nulliparity Preterm delivery Closed cervix at insertion Cervical effacement 50% at insertion Tachysystole Birthweight
Figure 1. Time intervals between PGE2 administration and delivery for the study and control group. Time intervals in hours of cervical ripening process and time intervals in hours between PGE2 administration to full dilatation and delivery in study and control groups. Values are presented as mean ± SD. All interval are significant (p50.01).
p50.001) (Figure 1). No significant difference was found in the use of oxytocin augmentation between the groups. Likewise, time interval from administration of the PGE2 agent to full dilatation of the cervix was significantly shorter in the vaginal insert regimen (22.1 ± 14.5 versus 27.4 ± 19.7 h, p ¼ 0.001). There was approximately 5-h difference in the mean duration from ripening initiation to achieving vaginal delivery in the vaginal insert group versus the serial vaginal tablets group (23.5 ± 15.8 versus 28.4 ± 20.0 h, p ¼ 0.003, respectively) (Figure 1).
1.50 0.98 0.24 0.16 0.58 0.75 0.71 1.00
(1.04–2.18) (0.95–1.02) (0.17–0.36) (0.01–1.84) (0.39–0.86) (0.52–1.08) (0.42–1.78) (0.99–1.00)
p Value 0.02 0.50 50.001 0.14 50.01 0.12 0.87 0.06
Women in the vaginal insert group had a higher rate of delivery within 24 h from cervical ripening initiation (61.5 versus 51.6%, p ¼ 0.01), but not within 12 h (Table 4). The rates of operative vaginal delivery or cesarean section were similar between the groups, as the indications for cesarean delivery (Table 2). On multivariable logistic regression analysis, after controlling for other possible factors affecting time interval from pre-induction cervical ripening to delivery, such as maternal age, nulliparity, gestational age at enrollment, cervical dilatation and effacement at admission, tachysystole and birthweight, slow-release PGE2 vaginal insert was found to be significantly associated with increased chance for vaginal delivery within 24 h in comparison to serial PGE2 vaginal tablets (OR 1.50, 95% CI 1.04–2.18, p ¼ 0.02) (Table 5).
Discussion The present study was conducted in order to compare the efficacy and safety of two PGE2 regimens for cervical ripening and induction of labor. We aimed to compare slowrelease PGE2 vaginal insert with serial PGE2 vaginal tablets. Our main findings were: (1) slow-release PGE2 vaginal insert was associated with shorter mean time interval from cervical
PGE2 (dinoprostone) for cervical ripening
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DOI: 10.3109/14767058.2014.883375
ripening to delivery in comparison to serial vaginal inserts. (2) Slow-release PGE2 vaginal insert was associated with a higher rate of tachysystole without increasing the rate uterine hyperstimulation or the rate of cesarean delivery due to NRFHR. In the current study, we demonstrated that induction of labor with a vaginal PGE2 insert achieved a significantly higher rate of vaginal delivery within 24 h. Of interest, cervical conditions (cervical dilatation and effacement at the beginning of the ripening process) were significantly less favorable for ripening merely in the vaginal insert group. Although low Bishop score prior to induction of labor was associated with significantly higher rates of failed induction and of cesarean delivery [7], women treated with vaginal insert had the same CS rate as controls, and had a higher rate of delivery within 24 h. This difference emphasized the superior benefit of vaginal insert upon serial PGE2 tablets. The overall rates of vaginal delivery within 24 h but not within 12-h were higher for vaginal insert in comparison to serial vaginal tablets. Our results are in concordance with previous studies which showed that induction to delivery interval was significantly shorter with the 12-h PGE2 vaginal pessary in comparison to 0.5 mg dinoprostone cervical gel, with a mean difference of about 5.5 h between the groups [8]. 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 h [3], whereas others, demonstrated that slow-release PGE2 vaginal insert was as equally effective as other prostaglandin in terms of delivery by 24 h [4]. Reasons for these contrasting conclusions could be the heterogeneity in terms of inclusion criteria, pre-induction Bishop score, primary outcome measures and varying protocols of induction. Our vaginal insert protocol applied it for 24 h, whereas the majority of previous vaginal insert protocols applied it to not longer than 12 h [9–12]. Indeed, a linear fashion of releasing prostaglandins for 24 h was also reported for vaginal insert [13,14]. A potential benefit of continuing the use of slowrelease PGE2 for 24 h when first 12 h exposure had not resulted the onset of labor was demonstrated [15]. Noteworthy, when considering the overall rate of delivery within 12 h in the current study, a higher rate was noted in the vaginal insert group, however, not statistically significant (25.4 versus 20.2%, p ¼ 0.15, respectively). As previously discussed, the heterogeneity in terms of pre-induction Bishop score and varying protocols of induction can explain the contradictory findings. Additionally, our cohort included both term and preterm pregnancies while previous studies evaluated pre-induction cervical ripening vaginal insert merely at term pregnancies [10,11,16,17]. In terms of safety, our data showed that slow-release PGE2 vaginal insert was associated with a higher rate of uterine tachysystole. Likewise, previous reports showed that patients who were treated with vaginal insert of PGE2 showed a trend for an increased rate of abnormal fetal heart rate; however, the incidence of cesarean section for fetal distress and an umbilical artery pH 57.10 was comparable between the studied groups [4,8,18,19]. In a recent randomized study
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comparing the efficacy of 24-h vaginal insert of PGE2 in comparison to vaginal gel of PGE2, a similar rate of uterine hyperstimulation and cesarean section was found between the groups [16]. A higher rate of utilizing extra-amniotic balloon catheter as an additional agent of cervical ripening was demonstrated in the slow-release group. This difference can probably be explained by the higher rate of uterine tachysystole in the slow-release group and additionally by a priori less favorable cervical conditions in that specific group. Our study offered several strengths. The current study is one of the largest studies to date regarding this issue. In addition, as the study was conducted in a single center, the same obstetrical protocols were used. Moreover, the two groups were similar in their demographics and obstetrical characteristics, as well for the indications for induction of labor. Moreover, our study should be considered the first study testing 24-h slow-release PGE2 vaginal insert versus vaginal serial PGE2 tablets administered in patients admitted for induction of labor with an unfavorable cervix. However, our study is limited by its retrospective design and the potential lack of data such as the dose of oxytocin during delivery. In summary, both the 24-h PGE2 vaginal insert and the vaginal PGE2 tablets appear to be safe for ripening and induction of labor. However, cervical ripening and induction of labor using slow-release PGE2 vaginal insert had a significantly higher rate of spontaneous vaginal delivery within 24 h. This superior effectiveness was not accompanied with either a higher rate of uterine hyperstimulation or a higher rate of operative or cesarean deliveries.
Declaration of interest The authors report no conflict of interest.
References 1. American College of Obstetricians and Gynecologists. Induction of labor. ACOG Practice Bulletin N. 107. Obstet Gynecol 2009; 114:386–97. 2. Chyu JK, Strassner HT. Prostaglandin E2 for cervical ripening: a randomized comparison of Cervidil versus Prepidil. Am J Obstet Gynecol 1997;177:606–11. 3. Sanchez-Ramos L, Kaunitz AM, Delke I, Gaudier FL. Cervical ripening and labor induction with a controlled-release dinoprostone vaginal insert: a meta-analysis. Obstet Gynecol 1999;94:878–83. 4. Hughes EG, Kelly AJ, Kavanagh J. Dinoprostone vaginal insert for cervical ripening and labor induction: a meta-analysis. Obstet Gynecol 2001;97:847–55. 5. Dollberg S, Haklai Z, Mimouni FB, et al. Birth weight standards in the live-born population in Israel. Isr Med Assoc J 2005;7:311–14. 6. Macones GA, Hankins GD, Spong CY, et al. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. Obstet Gynecol 2008;112:661–6. 7. Xenakis EM, Piper JM, Conway DL, Langer O. Induction of labor in the nineties: conquering the unfavorable cervix. Obstet Gynecol 1997;90:235–9. 8. Strobelt N, Meregalli V, Ratti M, et al. Randomized study on removable PGE2 vaginal insert versus PGE2 cervical gel for cervical priming and labor induction in low-Bishop-score pregnancy. Acta Obstet Gynecol Scand 2006;85:302–5. 9. Smith CV, Rayburn WF, Miller AM. Intravaginal prostaglandin E2 for cervical ripening and initiation of labor. Comparison of a multidose gel and single, controlled-release pessary. J Reprod Med 1994;39:381–4.
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10. Facchinetti F, Venturini P, Verocchi G, Volpe A. Comparison of two preparations of dinoprostone for pre-induction of labour in nulliparous women with very unfavourable cervical condition: a randomised clinical trial. Eur J Obstet Gynecol Reprod Biol 2005; 119:189–93. 11. Facchinetti F, Venturini P, Fazzio M, Volpe A. Elective cervical ripening in women beyond the 290th day of pregnancy: a randomized trial comparing 2 dinoprostone preparations. J Reprod Med 2007;52:945–9. 12. Ferraiolo A, Dellacasa I, Bentivoglio G, et al. Evaluation of patients’ satisfaction of cervical ripening using dinoprostone by either intravaginal gel or pessary: an open-label, randomized, prospective study. J Reprod Med 2010;55:423–9. 13. Goharkhay N, Stanczyk FZ, Gentzschein E, Wing DA. Plasma prostaglandin E(2) metabolite levels during labor induction with a sustained-release prostaglandin E(2) vaginal insert. J Soc Gynecol Investig 2000;7:338–42. 14. Lyrena¨s S, Clason I, Ulmsten U. In vivo controlled release of PGE2 from a vaginal insert (0.8 mm, 10 mg) during induction of labour. BJOG 2001;108:169–78.
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15. Rath W. A clinical evaluation of controlled-release dinoprostone for cervical ripening – a review of current evidence in hospital and outpatient settings. J Perinat Med 2005;33:491–9. 16. Triglia MT, Palamara F, Lojacono A, et al. A randomized controlled trial of 24-hour vaginal dinoprostone pessary compared to gel for induction of labor in term pregnancies with a Bishop score 5 or ¼ 4. Acta Obstet Gynecol Scand 2010;89: 651–7. 17. Zanconato G, Bergamini V, Mantovani E, et al. Induction of labor and pain: a randomized trial between two vaginal preparations of dinoprostone in nulliparous women with an unfavorable cervix. J Matern Fetal Neonatal Med 2011;24:728–31. 18. Sanchez-Ramos L, Peterson DE, Delke I, et al. Labor induction with prostaglandin E1 misoprostol compared with dinoprostone vaginal insert: a randomized trial. Obstet Gynecol 1998;91: 401–5. 19. Kelly AJ, Malik S, Smith L, et al. Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term. Cochrane Database Syst Rev 2009;(4):CD003101. DOI: 10.1002/14651858. CD003101.pub2.
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ORIGINAL ARTICLE
Pre-induction cervical ripening: comparing between two vaginal preparations of dinoprostone in women with an unfavorable cervix J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Universidad del Rosario on 09/10/14 For personal use only.
Eran Ashwal1,2, Liran Hiersch1,2, Nir Melamed1,2, Yaara Manor1,2, Arnon Wiznitzer1,2, Moshe Hod1,2, and Yariv Yogev1,2 1
Department of Obstetrics and Gynecology, Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tiqwa, Israel and 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract
Keywords
Objective: Prostaglandin E2 (PGE2-Dinoprostone) is accepted for both ripening of the cervix and induction of labor. As conflicting data exist concerning the efficiency and safety of different treatment modalities, we aimed to compare slow-release vaginal insert PGE2 with serial vaginal tablets of PGE2 for cervical ripening and induction of labor. Methods: A retrospective cohort study comparing all pregnancies who underwent induction of labor by either a single slow-release vaginal insert of 10 mg PGE2 (study group) to a historical control group of women who were treated with serial administration of 3 mg vaginal PGE2 tablets in a 2:1 ratio, matched by parity. Results: Overall, 639 women were enrolled (213 treated with PGE2 tablets and 426 with slowrelease vaginal inserts). Vaginal insert was associated with shorter initiation-to-ripening interval (12.4 ± 7.7 versus 18.6 ± 15.2 h, p50.001) and a higher rate of delivery within 24 h (61.5 versus 51.6%, p ¼ 0.018). Vaginal insert was associated with an increased rate of tachysystole (8.0 versus 3.1%, p50.01); however, the rates of cesarean section or operative delivery due to non-reassuring fetal heart rate (NRFHR) were similar. On multivariable analysis, slow-release vaginal insert was independently associated with a higher rate of delivery within 24 h (OR 1.50, 95% CI 1.04–2.18). Conclusion: Slow-release PGE2 vaginal insert achieves cervical ripening and subsequently delivery over a shorter time period than PGE2 tablets, without increasing uterine hyperstimulation rate.
Cervical ripening, dinoprostone, induction of labor, vaginal insert
Introduction Induction of labor is one of the most common obstetrical procedures performed, involving approximately 20% of all parturient women. As much as half of them are induced in the presence of an unfavorable cervix [1]. Cervical conditions at initiation of induction of labor greatly affect the success rate of labor induction. It is well established that an unfavorable cervix is associated with a higher rate of induction failure and increased rate of operative vaginal delivery and cesarean delivery [1,2]. Dinoprostone (PGE2) is one of the synthetic prostaglandin compounds most commonly applied in order to achieve cervical ripening and induction of labor. Numerous administration regimens have been used, such as tablets, suppositories, gel (either vaginal or intra-cervical) or as a slow-release vaginal insert. The slow-release vaginal insert has several potential advantages relative to other mentioned
Address for correspondence: Yariv Yogev, MD, Department of Obstetrics and Gynecology, Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tiqwa 49100, Israel. Tel: +972-3-9377400. Fax: +972-3-9377409. E-mail: [email protected]
History Received 27 December 2013 Revised 5 January 2014 Accepted 10 January 2014 Published online 4 February 2014
regimens. It is applied as a single application, the insertion is relatively easy and termination of drug effect can be achieved by removing it if uterine hyperstimulation and\or abnormal fetal heart rate changes occur during the ripening process. Previous studies comparing PGE2 vaginal insert to other prostaglandin formulations showed variable results [3,4]. These contrasting conclusions could be due to the heterogeneity in terms of inclusion criteria, indications for induction of labor, pre-induction Bishop score, different primary outcome measures and various drug administration regimens. As conflicting data exists concerning the most efficient and safe method, we aimed to compare slow-release PGE2 vaginal insert versus serial PGE2 vaginal tablets for cervical ripening and induction of labor.
Methods Study population We conducted a retrospective cohort study. The study group included women admitted for pre-induction cervical ripening between 34 and 41 weeks’ gestation using 10 mg vaginal dinoprostone insert (Propess, Ferring, Germany), between January to June 2013, in a university-affiliated tertiary
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hospital. Data were compared with historical control women who underwent pre-induction cervical ripening using vaginal tablets (Dinoprostone 3 mg, Pharmacia Upjohn, Puurf, Belgium) during the period 2011–2012 in a 1:2 ratio matched by parity (historical control). Both women had a Bishop score of 4 at admission. The reason for the difference in the time periods between the two studied groups was derived from a change in our pre-induction cervical ripening policy since 1 January 2013. Since then, slow-release vaginal PGE2 insert was suggested to all women who underwent cervical ripening and/or induction of labor. Pregnancies complicated by non-vertex presentation, multiple gestations, previous cesarean section (CS), known chromosomal or structural anomalies or any contraindication for vaginal delivery were excluded from both the study and control groups.
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Other outcome variables were mode of delivery, uterine hyperstimulation rate, operative or cesarean delivery due to non-reassuring fetal heart rate, time interval from initiation of cervical ripening to achieving cervical ripening and time interval from initiation of cervical ripening to delivery. Data collection Data were obtained for both groups retrospectively from our departmental electronic health records. The following demographic and obstetrical variables were recorded: maternal age, gravidity, parity, indication for labor induction, gestational age at delivery, intra-partum characteristics, such as NRFHR and mode of delivery and indication for operative or cesarean delivery. The following perinatal outcomes were assessed: Apgar scores at 1 and 5 min and birthweight. Definitions
Labor induction protocol for the study and control groups According to our department protocol, 10 mg PGE2 slowrelease vaginal insert (Propess, Ferring, Germany) was administrated to the posterior fornix until cervical ripening was achieved (Bishop score 47). Fetal heart rate monitoring was performed prior to and one hour after the insertion of the vaginal PGE2 insert and again at 12 and 24 h or in the presence of painful uterine contractions or suspected ruptured membranes. The vaginal insert was removed in the presence of painful uterine contractions, uterine hyperstimulation, nonreassuring fetal heart rate (NRFHR), successful ripening (Bishop score 47) or after 24 h from insertion regardless the Bishop score. Ripening failure was defined as Bishop score 7 after 24 h from insertion. Serial PGE2 vaginal tablets (Dinoprostone 3 mg, Pharmacia Upjohn, Puurf, Belgium) were administrated to the posterior fornix at 6–8 h intervals until cervical ripening was achieved (Bishop score 47). Fetal heart rate monitoring was performed prior and after each application. In the presence of painful uterine contractions or uterine tachysystole, the administration of PGE2 was delayed until contractions subsided. According to our protocol up to five tablets administration were given (maximal cumulative dose of 15 mg). Following instillation of PGE2, the woman was advised to lie down for at least 60 min. Ripening failure was defined as a Bishop score 7 after 5 PGE2 tablets. Cervical ripening process was terminated if uterine hyperstimulation or NRFHR occurred without achieving adequate fetal heart rate reassuring. Women in whom cervical ripening was achieved were transferred to delivery room, and if necessary, augmentation of labor with oxytocin and/or artificial rupture of membranes (ARM) were used, under continuous electronic fetal monitoring. In general, upon failure of cervical ripening with PGE2 (regardless the regimen administrated), a subsequent trial of either labor induction with oxytocin or cervical ripening using extra-amniotic balloon was undertaken. The decision was made according to the Bishop score, uterine contractions patterns and physician’s preference. The primary outcome measure was achieving a delivery within 24 h from the initiation of the cervical ripening.
Indications for labor induction were categorized into maternal of fetal indications. Maternal indications included any of the following: hypertensive disorders, diabetes or maternal morbidity. Fetal indication included any of the following: prolonged pregnancy (41+6 weeks’ gestation or more), premature rupture of membranes, fetal growth restriction (defined as sonographically estimated fetal weight below the 10th percentile according to local reference curves [5]), large for gestational age (defined as sonographically estimated fetal weight above the 90th percentile according to local reference curves [5]), amniotic fluid volume disorders, cholestasis of pregnancy, non-reassuring fetal heart rate, reduced perception of fetal movements or unstable lie. Uterine hyperstimulation was defined as fetal heart rate decelerations or fetal bradycardia in the presence of more than five uterine contractions in 10 min or a contraction lasting more than 2 min [1]. Tachysystole was defined as more than five uterine contractions in 10 min or a contraction lasting more than 2 min in the presence of reassuring fetal heart rate [1]. NRFHR was defined as fetal heart rate patterns which were classified as either Category II (without achieving adequate reassurance) or Category III, according to National institute of Child Health and Human Development workshop report [6]. Failed induction was defined as a failure to achieve active phase of labor (dilatation of 4 cm or more in the presence of regular uterine contractions) after at least 12 h have elapsed from the initiation of oxytocin infusion in the presence of artificial rupture of membranes. Maternal comorbidities include one or more of the following: asthma, hypothyroidism, pre-gestational diabetes mellitus, either inherited or acquired thrombophilia and inflammatory bowel disease. Statistical analysis Data analysis was performed with the SPSS v19.0 package (SPSS Inc., Chicago, IL). Student’s t test and Mann–Whitney U test were used to compare continuous variables with and without normal distribution between the groups, respectively. The chi-square and Fisher’s exact tests were used for
PGE2 (dinoprostone) for cervical ripening
DOI: 10.3109/14767058.2014.883375
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Table 1. Demographics and obstetrical characteristics for the study and control groups.
Maternal age Ethnicity Jewish Arabic Gravidity Parity Nulliparity Pre-gestational BMI Smoking Previous abortion Maternal Co-morbidities
Slow-release vaginal insert group N ¼ 213
PGE2 tablets group N ¼ 426
30.0 ± 5.0
30.7 ± 5.0
187 (92.1) 386 (93.5) 2 (1–3) 0 (0–2) 107 (50.2) 25.2 ± 4.8 7 (3.3) 20 (10.3) 56 (26.3)
16 (7.9) 27 (6.5) 2 (1–3) 0 (0–2) 216 (50.7) 25.1 ± 5.6 22 (5.2) 45 (9.9) 112 (26.3)
p Value 0.53 0.32 0.99 0.88 0.94 0.99 0.19 0.38 0.48
Values are presented as mean ± SD, median (interquartile range) or n (%). BMI – body mass index; CS – cesarean section.
categorical variables. Variables that were found to be different between the groups (p50.05) in the bivariate analysis as well as variables that were hypothesized to potentially affect the likelihood of adverse outcome based on clinical grounds were entered to the multivariable logistic regression model. Differences were considered significant when p value was less than 0.05.
Results A total of 639 women were included in the study, of them 213 and 426 underwent cervical ripening and induction of labor with a single slow-release vaginal PGE2 insert or serial vaginal PGE2 (dinoprostone) tablets, respectively. The demographic and obstetrical characteristics of the study and control groups are shown in Table 1. There were no differences between the groups with regard to maternal age, gravidity, parity and pre-gestational BMI. With respect to pregnancy and delivery characteristics, the rates of fertility treatments, hypertension disorders, diabetes, estimation of fetal weight, gestational age at delivery and the rate of preterm delivery were similar between the groups (Table 2). There were no differences in the indications for labor induction between the groups (Table 3). Cervical conditions were significantly more unfavorable in the slow-release PGE2 vaginal insert group in comparison with the serial vaginal PGE2 tablets group (closed cervix at enrollment 45.5 versus 27.0%, p50.001, respectively) (Table 4). During cervical ripening and induction of labor process, there was a higher rate of tachysystole in the vaginal insert group (8.0 versus 3.1%, p50.01). The rate of uterine hyperstimulation, NRFHR or painful contractions necessitating termination of the cervical ripening and induction of labor process was similar between the groups. Likewise, the rate of rupture of amniotic membranes during ripening was similar between the groups (Table 4). The time interval from administration of the different PGE2 agent for achieving cervical ripening was shorter in the vaginal insert group (11.01 ± 6.5 versus 16.9 ± 12.9 h,
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Table 2. Pregnancy characteristics for the study and control groups.
Fertility treatment Gestational age at delivery (weeks) Preterm birth (537 weeks) Hypertensive complications GDM IUGR EFW (g) Mode of delivery NVD Operative vaginal delivery Dystocia NRFHR Other CS Failed induction Dystocia NRFHR Other Intra-partum fever Meconium PPH Post-partum fever Birthweight (g) Birthweight 44000 g Blood transfusion
Slow-release vaginal insert group N ¼ 213
PGE2 tablets group N ¼ 426
p Value
16 (7.5) 39.0 ± 1.7
17 (4.0) 39.0 ± 1.8
0.08 0.59
12 (5.6) 16 (7.5) 42 (19.7) 13 (6.1) 3425 ± 347 0.36 155 (74.2) 22 (10.5) 6 (2.8) 15 (7.0) 1 (0.4) 32 (15.3) 13 (6.1) 5 (2.3) 10 (4.7) 4 (1.8) 4 (2.2) 20 (10.5) 8 (4.5) 1 (0.6) 3268 ± 483 12 (5.6) 3 (1.7)
22 (5.2) 41 (9.6) 79 (18.5) 23 (5.4) 3406 ± 372
0.85 0.23 0.39 0.42 0.62
322 (75.8) 54 (12.7) 19 (4.5) 33 (7.7) 2 (0.4) 49 (11.6) 12 (2.8) 7 (1.6) 23 (5.4) 7 (1.6) 11 (2.7) 55 (13.3) 12 (3.1) 3 (0.8) 3259 ± 478 31 (7.3) 2 (0.5)
0.24 0.23 0.39 0.87 NA 0.21 0.05 0.54 0.85 0.89 0.48 0.14 0.28 0.62 0.82 0.50 0.19
Values are presented as mean ± SD or n (%). CS – cesarean section; EFW – estimated fetal weight; GDM – gestational diabetes; MOD – mode of delivery; NA – not applicable; NRFHR – non-reassuring fetal heart rate; NVD – normal vaginal delivery; PPH – post-partum hemorrhage.
Table 3. Indications for labor induction in the study and control group.
Induction indication Fetal Maternal Fetal Post-term PROM Oligohydramnios Polyhydramnios GDM Macrosomia IUGR Cholestasis of pregnancy NRFHR Reduced fetal movements Unstable lie Others* Maternal HTN disorders Maternal morbidity
Slow-release vaginal insert group N ¼ 213
PGE2 tablets group N ¼ 426
113 (53.1) 100 (46.9)
229 (53.8) 197 (46.2)
p Value 0.47 0.29
50 27 2 12 37 8 13 8 5 12 3 0
(23.5) (13.6) (0.9) (5.6) (17.4) (3.8) (6.1) (3.8) (2.3) (5.6) (1.4) (0)
77 62 7 22 66 6 18 9 14 22 2 5
(18.1) (14.5) (1.6) (5.2) (15.5) (1.4) (4.2) (2.1) (3.3) (5.2) (0.5) (1.2) 0.25
17 (8) 7 (3.3)
39 (9.2) 16 (3.8)
Values are presented as mean ± SD or n (%). HTN – hypertension; IUGR – intrauterine growth restriction; GDM – gestational diabetes; NRFHR – non-reassuring fetal heart rate; PROM – premature rupture of membranes. Others* – umbilical cord varix, asymmetric fetal ventricles, unilateral fetal ventriculomegaly.
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Table 4. Induction characteristics for the study and control groups.
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Slow-release vaginal insert group N ¼ 213 Cervical condition – At PGE2 administration Closed cervix Dilatation 1 cm Effacement 50% Tachysystole Hyperstimulation NRFHR SROM Termination of ripening process* Additional induction Oxytocin EAB Initiation to ripening interval** (h) Time interval from ripening initiation to full cervical dilatation (h) Time interval from ripening initiation delivery (h) Delivery within 12 h Delivery within 24 h
97 170 108 17 6 8 14 21
(45.5) (79.8) (50.7) (8.0) (2.8) (3.8) (6.6) (9.9)
24 (11.2) 17 (7.9) 12.41 ± 7.79 22.17 ± 14.52 23.59 ± 15.82 54 (25.4) 131 (61.5)
PGE2 tablets group N ¼ 426 115 314 202 13 4 30 20 40
p Value 50.001 0.09 0.45 50.01 0.09 0.11 0.21 0.48
(27.0) (73.7) (47.4) (3.1) (0.9) (7.0) (4.7) (9.4)
36 (8.4) 12 (2.8) 18.64 ± 15.21 27.44 ± 19.75 28.41 ± 20.06 86 (20.2) 220 (51.6)
0.24 50.001 50.001 0.001 0.003 0.15 0.018
Values are presented as mean ± SD or n (%). EAB – extra amniotic balloon; NRFHR – non-reassuring fetal heart rate; SROM – spontaneous rupture of membranes. *As defined in the ‘‘Methods’’ section. **Time interval from PGE2 administration to achieving a Bishop score 4 7.
Table 5. Multivariable analysis for vaginal delivery within 24 h. OR Vaginal insert Maternal age Nulliparity Preterm delivery Closed cervix at insertion Cervical effacement 50% at insertion Tachysystole Birthweight
Figure 1. Time intervals between PGE2 administration and delivery for the study and control group. Time intervals in hours of cervical ripening process and time intervals in hours between PGE2 administration to full dilatation and delivery in study and control groups. Values are presented as mean ± SD. All interval are significant (p50.01).
p50.001) (Figure 1). No significant difference was found in the use of oxytocin augmentation between the groups. Likewise, time interval from administration of the PGE2 agent to full dilatation of the cervix was significantly shorter in the vaginal insert regimen (22.1 ± 14.5 versus 27.4 ± 19.7 h, p ¼ 0.001). There was approximately 5-h difference in the mean duration from ripening initiation to achieving vaginal delivery in the vaginal insert group versus the serial vaginal tablets group (23.5 ± 15.8 versus 28.4 ± 20.0 h, p ¼ 0.003, respectively) (Figure 1).
1.50 0.98 0.24 0.16 0.58 0.75 0.71 1.00
(1.04–2.18) (0.95–1.02) (0.17–0.36) (0.01–1.84) (0.39–0.86) (0.52–1.08) (0.42–1.78) (0.99–1.00)
p Value 0.02 0.50 50.001 0.14 50.01 0.12 0.87 0.06
Women in the vaginal insert group had a higher rate of delivery within 24 h from cervical ripening initiation (61.5 versus 51.6%, p ¼ 0.01), but not within 12 h (Table 4). The rates of operative vaginal delivery or cesarean section were similar between the groups, as the indications for cesarean delivery (Table 2). On multivariable logistic regression analysis, after controlling for other possible factors affecting time interval from pre-induction cervical ripening to delivery, such as maternal age, nulliparity, gestational age at enrollment, cervical dilatation and effacement at admission, tachysystole and birthweight, slow-release PGE2 vaginal insert was found to be significantly associated with increased chance for vaginal delivery within 24 h in comparison to serial PGE2 vaginal tablets (OR 1.50, 95% CI 1.04–2.18, p ¼ 0.02) (Table 5).
Discussion The present study was conducted in order to compare the efficacy and safety of two PGE2 regimens for cervical ripening and induction of labor. We aimed to compare slowrelease PGE2 vaginal insert with serial PGE2 vaginal tablets. Our main findings were: (1) slow-release PGE2 vaginal insert was associated with shorter mean time interval from cervical
PGE2 (dinoprostone) for cervical ripening
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DOI: 10.3109/14767058.2014.883375
ripening to delivery in comparison to serial vaginal inserts. (2) Slow-release PGE2 vaginal insert was associated with a higher rate of tachysystole without increasing the rate uterine hyperstimulation or the rate of cesarean delivery due to NRFHR. In the current study, we demonstrated that induction of labor with a vaginal PGE2 insert achieved a significantly higher rate of vaginal delivery within 24 h. Of interest, cervical conditions (cervical dilatation and effacement at the beginning of the ripening process) were significantly less favorable for ripening merely in the vaginal insert group. Although low Bishop score prior to induction of labor was associated with significantly higher rates of failed induction and of cesarean delivery [7], women treated with vaginal insert had the same CS rate as controls, and had a higher rate of delivery within 24 h. This difference emphasized the superior benefit of vaginal insert upon serial PGE2 tablets. The overall rates of vaginal delivery within 24 h but not within 12-h were higher for vaginal insert in comparison to serial vaginal tablets. Our results are in concordance with previous studies which showed that induction to delivery interval was significantly shorter with the 12-h PGE2 vaginal pessary in comparison to 0.5 mg dinoprostone cervical gel, with a mean difference of about 5.5 h between the groups [8]. 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 h [3], whereas others, demonstrated that slow-release PGE2 vaginal insert was as equally effective as other prostaglandin in terms of delivery by 24 h [4]. Reasons for these contrasting conclusions could be the heterogeneity in terms of inclusion criteria, pre-induction Bishop score, primary outcome measures and varying protocols of induction. Our vaginal insert protocol applied it for 24 h, whereas the majority of previous vaginal insert protocols applied it to not longer than 12 h [9–12]. Indeed, a linear fashion of releasing prostaglandins for 24 h was also reported for vaginal insert [13,14]. A potential benefit of continuing the use of slowrelease PGE2 for 24 h when first 12 h exposure had not resulted the onset of labor was demonstrated [15]. Noteworthy, when considering the overall rate of delivery within 12 h in the current study, a higher rate was noted in the vaginal insert group, however, not statistically significant (25.4 versus 20.2%, p ¼ 0.15, respectively). As previously discussed, the heterogeneity in terms of pre-induction Bishop score and varying protocols of induction can explain the contradictory findings. Additionally, our cohort included both term and preterm pregnancies while previous studies evaluated pre-induction cervical ripening vaginal insert merely at term pregnancies [10,11,16,17]. In terms of safety, our data showed that slow-release PGE2 vaginal insert was associated with a higher rate of uterine tachysystole. Likewise, previous reports showed that patients who were treated with vaginal insert of PGE2 showed a trend for an increased rate of abnormal fetal heart rate; however, the incidence of cesarean section for fetal distress and an umbilical artery pH 57.10 was comparable between the studied groups [4,8,18,19]. In a recent randomized study
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comparing the efficacy of 24-h vaginal insert of PGE2 in comparison to vaginal gel of PGE2, a similar rate of uterine hyperstimulation and cesarean section was found between the groups [16]. A higher rate of utilizing extra-amniotic balloon catheter as an additional agent of cervical ripening was demonstrated in the slow-release group. This difference can probably be explained by the higher rate of uterine tachysystole in the slow-release group and additionally by a priori less favorable cervical conditions in that specific group. Our study offered several strengths. The current study is one of the largest studies to date regarding this issue. In addition, as the study was conducted in a single center, the same obstetrical protocols were used. Moreover, the two groups were similar in their demographics and obstetrical characteristics, as well for the indications for induction of labor. Moreover, our study should be considered the first study testing 24-h slow-release PGE2 vaginal insert versus vaginal serial PGE2 tablets administered in patients admitted for induction of labor with an unfavorable cervix. However, our study is limited by its retrospective design and the potential lack of data such as the dose of oxytocin during delivery. In summary, both the 24-h PGE2 vaginal insert and the vaginal PGE2 tablets appear to be safe for ripening and induction of labor. However, cervical ripening and induction of labor using slow-release PGE2 vaginal insert had a significantly higher rate of spontaneous vaginal delivery within 24 h. This superior effectiveness was not accompanied with either a higher rate of uterine hyperstimulation or a higher rate of operative or cesarean deliveries.
Declaration of interest The authors report no conflict of interest.
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15. Rath W. A clinical evaluation of controlled-release dinoprostone for cervical ripening – a review of current evidence in hospital and outpatient settings. J Perinat Med 2005;33:491–9. 16. Triglia MT, Palamara F, Lojacono A, et al. A randomized controlled trial of 24-hour vaginal dinoprostone pessary compared to gel for induction of labor in term pregnancies with a Bishop score 5 or ¼ 4. Acta Obstet Gynecol Scand 2010;89: 651–7. 17. Zanconato G, Bergamini V, Mantovani E, et al. Induction of labor and pain: a randomized trial between two vaginal preparations of dinoprostone in nulliparous women with an unfavorable cervix. J Matern Fetal Neonatal Med 2011;24:728–31. 18. Sanchez-Ramos L, Peterson DE, Delke I, et al. Labor induction with prostaglandin E1 misoprostol compared with dinoprostone vaginal insert: a randomized trial. Obstet Gynecol 1998;91: 401–5. 19. Kelly AJ, Malik S, Smith L, et al. Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term. Cochrane Database Syst Rev 2009;(4):CD003101. DOI: 10.1002/14651858. CD003101.pub2.
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