# Uterine hyperstimulation in cervical ripening with oral misoprostol versus dinoprostone vaginal pessary: A real-life single-center descriptive study

Amélie Pieux, Benoit de la Fournière, Aurélie Lépée, Emmanuel Rault

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Amélie Pieux, Benoit de la Fournière, Aurélie Lépée, Emmanuel Rault. Uterine hyperstimulation in cervical ripening with oral misoprostol versus dinoprostone vaginal pessary: A real-life single-center descriptive study. Journal of Gynecology Obstetrics and Human Reproduction, 2025, 54 (5), pp.102944. 10.1016/j.jogoh.2025.102944. hal-05110065

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Original Article

# Uterine hyperstimulation in cervical ripening with oral misoprostol versus dinoprostone vaginal pessary: A real-life single-center descriptive study

<figure><img src="image_3.png" /></figure>

Amélie Pieux<sup>a</sup>, Benoit de la Fournière<sup>b,c</sup>, Aurélie Lépée<sup>a</sup>, Emmanuel Rault<sup>a,d,*</sup>

ARTICLE INFO

Keywords:

Cervical ripening

Induction of labor

Oral misoprostol

Dinoprostone vaginal pessary

Uterine tachysystole

Uterine hyperstimulation syndrome

ABSTRACT

**Introduction:** Cervical ripening is recommended in the event of an unfavorable cervix but carries a risk of uterine hyperstimulation, a serious complication of induction associated with maternal and fetal morbidity. To evaluate the incidence of uterine hyperstimulation following cervical ripening with oral misoprostol versus dinoprostone vaginal pessary.

**Materials and methods:** We conducted a retrospective cohort study of all deliveries in 2020 in the maternity department of a tertiary hospital involving women with a singleton cephalic presentation who underwent labor induction with cervical ripening by oral misoprostol or dinoprostone vaginal pessary.

**Results:** Four hundred and thirty-nine cervical ripening procedures were included in the study, 285 with oral misoprostol and 154 with dinoprostone vaginal pessary. In univariate analysis, uterine tachysystole was significantly less frequent with oral misoprostol (15/285 cases, 5.3 %) than with dinoprostone pessary (26/154 cases, 17.2 %; *p* < 0.01), as was uterine tachysystole with fetal heart rate abnormalities (3/285 cases, 1.1 % versus 8/154 cases, 5.2 %; *p* = 0.02). Using multivariable analysis, the odds of uterine tachysystole were significantly lower in the oral misoprostol group than in the dinoprostone pessary group (odds ratio (OR), 0.28; 95 % confidence interval (CI) [0.13; 0.55]; *p* < 0.01), as were the odds of uterine tachysystole with fetal heart rate abnormalities (OR, 0.19, 95 % CI [0.04; 0.68], *p* < 0.01).

**Conclusion:** In this group of women, uterine tachysystole and uterine tachysystole with fetal heart rate abnormalities occurred less frequently after cervical ripening with oral misoprostol than after ripening with a dinoprostone pessary.

Introduction

Labor induction is a common medical procedure designed to achieve vaginal delivery [1]. According to the last French national perinatal survey in 2021, it is performed in 26 % of deliveries [2]. When the cervix is unfavorable, typically characterized by a Bishop score <7, cervical ripening is recommended; however no international or national recommendations regarding which method to use are available [3–5]. Many studies have been conducted to compare maternal and neonatal morbidity between methods of induction, but no significant differences have been found [6–8].

One of the most serious complications of labor induction is uterine hyperstimulation leading to increase the risk of cesarean delivery and

maternal or neonatal morbidity [9,10]. A recent Cochrane review concludes that low-dose oral misoprostol probably reduces the rate of cesarean sections and uterine hyperstimulation compared with vaginal dinoprostone and it highlights perspectives for establish the optimal oral misoprostol regimen [11]. Low-dose (25 µg) oral misoprostol tablets have recently been introduced in this context for more progressive administration, allowing doses to be adjusted according to woman's response and tolerance. Our hypothesis was that ripening with 25 µg oral misoprostol every 2 h reduces the risk of uterine hyperstimulation (uterine tachysystole, uterine hypertonus and uterine hyperstimulation syndrome) compared with dinoprostone vaginal pessary, particularly in fetuses at risk of hypoxia who are more susceptible to fetal heart rate abnormalities related to uterine hyperstimulation. The primary

<footnote><sup>a</sup> Service de gynécologie-obstétrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, France</footnote>

<footnote><sup>b</sup> Service de gynécologie-obstétrique, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Université Lyon 1 Claude Bernard, Lyon, France</footnote>

<footnote><sup>c</sup> LabTAU (INSERM 1032), Cours Albert Thomas Lyon, France</footnote>

<footnote><sup>d</sup> CRESS Laboratory (INSERM 1153), Epope, Paris, France</footnote>

<footnote>* Corresponding author at: Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Obstétrique, 59 Bld Pinel 69500 BRON.</footnote>

<footnote>E-mail address: Emmanuel.rault@chu-lyon.fr (E. Rault).</footnote>
objective was to compare the incidence of uterine hyperstimulation between two methods of cervical ripening: oral misoprostol and vaginal dinoprostone pessary in the overall population and in a subgroup of fetuses at risk of acidosis. The secondary objectives were to evaluate neonatal and maternal morbidity in the two groups.

## Methods

We conducted a retrospective study of all deliveries with ripening by oral misoprostol or dinoprostone vaginal pessary from January 1 to December 31, 2020 in the maternity department of the Hôpital Femme Mère Enfant (Lyon, France).

Deliveries were included if they involved a singleton fetus in cephalic presentation with an unscarred uterus requiring cervical ripening with oral misoprostol or dinoprostone pessary for labor induction. The exclusion criteria were breech presentation, multiple pregnancies, a history of caesarian section, fetal death, termination of pregnancy, and absence of cardiotocographic monitoring during induction.

Included women received either a 10 mg dinoprostone pessary (Propess®, Ferring) left in place for 24 h, or 25 µg misoprostol tablets (Angusta®, Azanta) administered orally every 2 h, with a maximum of eight tablets per 24 h. The choice of cervical ripening method was based on a shared decision between the obstetrician and the woman, considering her preference for an oral or vaginal route and the ripening methods previously used. Fetal heart rate (FHR) monitoring was performed prior to induction and immediately thereafter, for a duration that depended on the method used, and was extended in the event of FHR abnormalities or uterine hyperstimulation. In the event of cervical ripening failure, some women received multiple administrations.

The primary outcome was the occurrence of uterine hyperstimulation, namely uterine tachysystole, uterine hypertonus or uterine hyperstimulation syndrome. Uterine tachysystole was defined as five contractions or more per 10 min for at least 20 consecutive minutes. Uterine hypertonus was defined as at least one contraction lasting more than two minutes. Uterine hyperstimulation syndrome was defined as uterine tachysystole or uterine hypertonia with FHR abnormalities. The FHR abnormalities considered were those suggestive of fetal hypoxia, namely deceleration, tachycardia or decreased FHR variability. Outcomes of FHR in cases of uterine hyperstimulation were classified as continuation of induction, early transfer to the delivery room, emergency caesarean section or discontinuation of induction. The secondary outcomes were neonatal and maternal morbidity defined with composite outcomes. Neonatal morbidity was evaluated based on the following criteria, assessed individually: 5-minute Apgar score below 7, arterial cord pH below 7.1, and admission to neonatal intensive care. Maternal morbidity was defined by the occurrence of postpartum hemorrhage, defined as blood loss greater than 500 cc. Each cervical ripening procedure was analyzed independently and grouped according to the ripening method used (oral misoprostol or dinoprostone vaginal pessary).

Data were collected by a single investigator from electronic medical records (Easily®; Hospices Civils de Lyon, Lyon, France). The following maternal characteristics were recorded: age, body mass index, parity, gestational age, initial Bishop score, indication for labor induction, and membrane status. All fetal cardiotocography recordings, maternal tocography recordings, and medical reports during ripening were reviewed to assess uterine contraction abnormalities and their management in case of anomalies. Induction duration, mode of delivery, and neonatal and maternal characteristics were also collected.

Univariate analysis was used to compare uterine hyperstimulation variables between the two groups. Sensitivity analysis in a subgroup of fetuses at risk of hypoxia was performed. Fetuses were classified as at risk of hypoxia in case of prematurity (< 37 weeks of gestation), late-term pregnancy (> 41 weeks of gestation), maternal diabetes, gestational diabetes, intrauterine growth restriction, pre-eclampsia or maternal hypertension, or maternal autoimmune disease. Multivariable

analysis was then performed included variables known to be associated with the considered outcomes, namely number of previous ripening procedures, nulliparity, rupture of membranes. Secondary outcomes were evaluated in univariate analysis. Quantitative variables were described as frequency and percentage, and compared in univariate analysis with chi square or Fisher exact tests as appropriate. Qualitative variables were described as mean and standard deviation and compared using Mann Whitney or Student t tests as appropriate. Multivariable analysis was performed using logistic regression model. Statistical analyses were performed using a web interface (https://www.pvalue.io/fr) for R statistical analysis software [12]. Ethical approval was obtained from the institutional review board (Comité scientifique et éthique des Hospices Civils de Lyon, n°21_537).

## Results

Among the 4601 births in our maternity unit during the study period, 1182 were induced (25.7 %), with 726 requiring cervical ripening (15.8 %). Among women with cervical ripening, 109 (15.0 %) underwent multiple ripening procedures. In total, 439 cervical ripening procedures met the inclusion criteria, including 154 (35.1 %) with dinoprostone vaginal pessary and 285 (64.9 %) with oral misoprostol (Fig. 1).

Maternal characteristics are summarized in Table 1. Nulliparity was significantly more frequent in the dinoprostone pessary group and previous ripening procedures were significantly more frequent in the oral misoprostol group (Table 1).

Univariate comparisons of uterine hyperstimulation variables are summarized in Table 2. Uterine tachysystole was significantly less frequent with oral misoprostol than with dinoprostone pessary (15/285 cases, 5.3 % versus 26/154 cases, 17.2 %; *p* < 0.01), as was uterine tachysystole with fetal heart rate abnormalities (3/285 cases, 1.1 % versus 8/154 cases, 5.2 %; *p* = 0.02). Ripening was significantly likelier to be continued following uterine tachysystole in the oral misoprostol group (9/14 cases, 64 %) than in the vaginal pessary group (7/26 cases, 27 %; *p* = 0.02). None of the three other uterine tachysystole outcomes differed significantly between the two groups. The only emergency cesarean section was performed after cervical ripening with dinoprostone pessary. The incidence of uterine hypertonus did not differ significantly between the two groups, with or without associated FHR abnormalities, and none of the considered outcomes in the case of hypertonus differed between the two ripening methods. The incidence of uterine hyperstimulation syndrome was non-significantly lower with oral misoprostol (17/285 cases, 5.9 %) than with dinoprostone pessary (16/154 cases, 10 %, *p* = 0.09).

Among fetuses at risk of hypoxia (Table 3), uterine tachysystole was significantly less frequent with oral misoprostol (9/211 cases, 4.3 %) than with dinoprostone pessary (18/118 cases, 15 %; *p* = 0.01) and uterine tachysystole with FHR abnormalities was significantly less frequent with oral misoprostol (2/211 cases, 1.0 %) than with dinoprostone pessary (6/118, 5.1 %; *p* = 0.03). The incidence of uterine hypertonus did not differ significantly between the two groups. The incidence of uterine hyperstimulation syndrome was non-significantly lower with oral misoprostol (14/211 cases, 6.6 %) than with dinoprostone pessary (13/118 cases, 11 %, *p* = 0.16).

Adjusting for nulliparity, number of previous ripening procedures, and rupture of membranes before ripening, the odds of uterine tachysystole were significantly lower in the oral misoprostol group than in the dinoprostone pessary group (adjusted odds ratio (aOR) [95 % confidence interval], 0.28 [0.13; 0.55]; *p* < 0.01). The odds of uterine tachysystole with FHR abnormalities was also lower with oral misoprostol than with dinoprostone pessary (aOR, 0.19 [0.04; 0.68]; *p* < 0.01). The odds of uterine hypertonus were non-significantly higher with oral misoprostol than with dinoprostone pessary (aOR 1.86, [0.92; 4.02]; *p* = 0.10). Labor induction outcomes are compared by ripening method in Table 4. The median time from induction to delivery was >8 h longer in the oral misoprostol group than in the dinoprostone pessary
<figure><img src="image_4.png" /><figcaption>**Fig. 1.** Flow chart GA, gestational age.</figcaption></figure>

group (35.0 vs 26.5 h; *p* = 0.03), with significantly more deliveries occurring within 24 h of initiation in the dinoprostone pessary group (73/154, 47.4% versus 102/285, 35.7% in the oral misoprostol group; *p* = 0.02). The caesarean section rate was non-significantly higher in the dinoprostone pessary group (41/154 cases, 26.6% versus 57/285 cases, 20.0%; *p* = 0.11).

Table 5 compares maternal and neonatal complications by cervical ripening method. The incidence of post-partum hemorrhage was the same in the two groups (17/154, 11.0% and 32/285, 11.2%; *p* = 0.94), and there were no significant differences either in neonatal morbidity.

## Discussion

In this group of women, uterine tachysystole occurred less frequently after cervical ripening using oral misoprostol than after ripening with dinoprostone vaginal pessary, and dinoprostone pessary was more frequently associated with uterine tachysystole with FHR abnormalities in univariate analysis and after adjusting for potential confounding factors. The incidence of hyperstimulation syndrome was lower with oral misoprostol than with dinoprostone pessary, but not statistically significantly. The incidence of uterine hypertonus did not differ significantly between the two groups. No significant differences were observed in the mode of delivery, maternal morbidity, or neonatal morbidity.

The rate of induction in our study is comparable to the one reported by a 2021 French national perinatal survey [2]. In a multicenter randomized trial conducted in 2001 to assess the efficacy and safety of oral misoprostol versus vaginal dinoprostone, Hofmeer et al. found rates of uterine tachysystole and of uterine hyperstimulation syndrome of 7%

and 4% respectively, compared with 5% and 6% in our study [13]. Meanwhile, Eriksson et al. found that the rate of uterine tachysystole with FHR abnormalities after oral misoprostol ripening was 1.1%, the same value as in our study (1.1%)[14].

The reduced risk of uterine tachysystole and hyperstimulation syndrome with oral misoprostol could be explained by its more gradual administration and by the fact that it can readily be interrupted in the event of hyperstimulation and/or FHR abnormalities, as well as by its pharmacological properties. The route of delivery did not differ significantly between the two methods. The caesarean section rate with oral misoprostol was 20%, slightly lower than observed by Levine et al. (24%) in their study [15].

As reported previously, the median time to delivery was considerably longer with oral misoprostol than with dinoprostone pessary [11]. The proportion of deliveries within 24 h of induction was 47% with dinoprostone pessary and 36% with oral misoprostol, both of which are substantially lower than the 75% reported by Levine et al. [16]. One possible explanation, since the probability of delivery within 24 h is higher in the case of rupture of the membranes, is that only 14% of women in our study had ruptured membranes before cervical ripening was initiated.

The safety and efficacy of oral misoprostol for cervical ripening has been widely studied. In a French study published in 2021, Bagory et al. found, similar to us, that the rate of uterine tachysystole was significantly lower with oral misoprostol (9.3%) than with dinoprostone vaginal gel or pessary (16.9%), and that the rate of uterine hyperstimulation syndrome was non-significantly lower with oral misoprostol (3.8%) versus vaginal dinoprostone (5.8%), while uterine hypertonus rates were comparable in the two groups (4.4% versus 4.2%)[17].
<table><caption>**Table 1**
Maternal and induction characteristics by cervical ripening method.</caption><thead><tr><th></th><th>Dinoprostone<br>pessary<br>(n = 154)</th><th>Oral<br>misoprostol<br>(n = 285)</th><th>p</th></tr></thead><tbody><tr><td>Age (years)</td><td>29.5 ± 5.4</td><td>30.2 ± 5.1</td><td>0.24</td></tr><tr><td>BMI</td><td>26.6 ± 5.5</td><td>25.9 ± 5.7</td><td>0.20</td></tr><tr><td>Nulliparity</td><td>109 (70.8 %)</td><td>168 (58.9 %)</td><td>0.01</td></tr><tr><td>Gestational age (weeks)</td><td>39.0 ± 1.8</td><td>39.1 ± 1.5</td><td>0.79</td></tr><tr><td>Initial Bishop score</td><td></td><td></td><td>0.08</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;&lt;2</td><td>22 (14.3 %)</td><td>28 (9.8 %)</td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;2-4</td><td>108 (70.1 %)</td><td>193 (67.7 %)</td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;5-6</td><td>23 (14.9 %)</td><td>64 (22.4 %)</td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;&gt; 6</td><td>1 (0.7 %)</td><td>0 (0 %)</td><td></td></tr><tr><td>Indication for labor induction</td><td></td><td></td><td>0.26</td></tr><tr><td>Late-term pregnancy</td><td>23 (14.9 %)</td><td>35 (12.3 %)</td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;PROM</td><td>13 (8.4 %)</td><td>40 (14.0 %)</td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Diabetes</td><td>37 (24.0 %)</td><td>70 (24.6 %)</td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Blood pressure disorders</td><td>11 (7.1 %)</td><td>15 (5.3 %)</td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Other maternal<br>pathologies</td><td>10 (6.5 %)</td><td>30 (10.5 %)</td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Other fetal pathologies</td><td>60 (38.9 %)</td><td>95 (33.3 %)</td><td></td></tr><tr><td>Contractions before induction</td><td>71 (46.1 %)</td><td>156 (54.7 %)</td><td>0.08</td></tr><tr><td>Rupture of membranes before<br>ripening</td><td>17 (11.0 %)</td><td>45 (15.8 %)</td><td>0.17</td></tr><tr><td>Number of previous cervical<br>ripening*</td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;0</td><td>134 (87.0 %)</td><td>208 (73.0 %)</td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;1</td><td>12 (7.8 %)</td><td>66 (23.2 %)</td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;2</td><td>5 (3.2 %)</td><td>10 (3.5 %)</td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;3</td><td>3 (1.9 %)</td><td>1 (0.4 %)</td><td></td></tr><tr><td>Fetus at risk of hypoxia</td><td>118 (76.6 %)</td><td>211 (74.0 %)</td><td>0.55</td></tr></tbody></table>

Values are reported as mean (standard deviation) or frequency (percentage). BMI: body mass index; PROM: prelabor rupture of membranes.

* previous cervical ripening with potential additional methods such as intra-cervical ballon or dinoprostone vaginal gel 1mg.

<table><caption>**Table 2**
Univariate comparison of uterine hyperstimulation variables by cervical ripening method.</caption><thead><tr><th></th><th>Dinoprostone<br>pessary<br>(n = 154)</th><th>Oral<br>misoprostol<br>(n = 285)</th><th>p</th></tr></thead><tbody><tr><td>Uterine tachysystole</td><td>26 (17.2 %)</td><td>14 (5 %)</td><td>&lt; 0.01</td></tr><tr><td>Without FHR abnormalities</td><td>18 (11.6 %)</td><td>11 (3.9 %)</td><td>&lt; 0.01</td></tr><tr><td>With FHR abnormalities</td><td>8 (5.2 %)</td><td>3 (1.1 %)</td><td>0.02</td></tr><tr><td>Management if uterine<br>tachysystole</td><td></td><td></td><td>0.09</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Further cervical ripening</td><td>7 (27 %)</td><td>9 (64 %)</td><td>0.02</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Early transfer to delivery<br>room</td><td>3 (12 %)</td><td>0 (0 %)</td><td>0.54</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Emergency caesarean<br>section</td><td>1 (4 %)</td><td>0 (0 %)</td><td>1</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Discontinuation of cervical<br>ripening</td><td>15 (58 %)</td><td>5 (36 %)</td><td>0.18</td></tr><tr><td>Uterine hypertonus</td><td>21 (13.6 %)</td><td>40 (14.0 %)</td><td>0.83</td></tr><tr><td>Without FHR abnormalities</td><td>12 (7.8 %)</td><td>26 (9.1 %)</td><td>0.64</td></tr><tr><td>With FHR abnormalities</td><td>9 (5.8 %)</td><td>14 (4.9 %)</td><td>0.68</td></tr><tr><td>Management if uterine<br>hypertonus</td><td></td><td></td><td>0.46</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Further cervical ripening</td><td>14 (67 %)</td><td>32 (80 %)</td><td>0.25</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Early transfer to delivery<br>room</td><td>1 (5 %)</td><td>3 (7.5 %)</td><td>1</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Emergency caesarean<br>section</td><td>1 (5 %)</td><td>1 (2.5 %)</td><td>1</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Discontinuation of cervical<br>ripening</td><td>5 (24 %)</td><td>4 (10 %)</td><td>0.25</td></tr><tr><td>Uterine hyperstimulation<br>syndrome</td><td>16 (10.4 %)</td><td>17 (5.9 %)</td><td>0.09</td></tr></tbody></table>

Values are reported as frequency (percentage). FHR: fetal heart rate.

<table><caption>**Table 3**
Subgroup analysis of uterine contractility abnormalities according to ripening method among fetuses at risk of hypoxia.</caption><thead><tr><th></th><th>Dinoprostone<br>pessary<br>(n = 118)</th><th>Oral<br>misoprostol<br>(n = 211)</th><th>p</th></tr></thead><tbody><tr><td>Uterine tachysystole</td><td>18 (15 %)</td><td>9 (4.3 %)</td><td>0.01</td></tr><tr><td>with FHR abnormalities</td><td>6 (5 %)</td><td>2 (1.0 %)</td><td>0.03</td></tr><tr><td>Uterine hypertonus</td><td>16 (15 %)</td><td>29 (13.7 %)</td><td>0.83</td></tr><tr><td>Uterine hyperstimulation<br>syndrome</td><td>13 (11 %)</td><td>14 (6.6 %)</td><td>0.16</td></tr></tbody></table>

<table><caption>**Table 4**
Induced labor outcomes by cervical ripening method.</caption><thead><tr><th></th><th>Dinoprostone<br>pessary<br>(n = 154)</th><th>Oral<br>misoprostol<br>(n = 285)</th><th>p</th></tr></thead><tbody><tr><td>Time from induction to delivery<br>(h)</td><td>26.5 [14.0; 50.8]</td><td>35.0 [18.0; 54.0]</td><td>0.03</td></tr><tr><td>Time from induction to delivery<br>&lt;24 h</td><td>73 (47.4 %)</td><td>102 (35.7 %)</td><td>0.02</td></tr><tr><td>Oxytocin required during labor</td><td>76 (49.4 %)</td><td>147 (51.6 %)</td><td>0.74</td></tr><tr><td>Mode of delivery</td><td></td><td></td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Vaginal</td><td>113 (73.4 %)</td><td>228 (80.0 %)</td><td>0.28</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Caesarean section</td><td>41 (26.6 %)</td><td>57 (20.0 %)</td><td>0.11</td></tr></tbody></table>

Values are reported as median [interquartile range] or frequency (percentage).

<table><caption>**Table 5**
Maternal and neonatal complications according to induction method.</caption><thead><tr><th></th><th>Dinoprostone<br>pessary<br>(n = 154)</th><th>Oral misoprostol<br>(n = 285)</th><th>p</th></tr></thead><tbody><tr><td>Hemorrhage,</td><td>17 (11.0 %)</td><td>32 (11.2 %)</td><td>0.94</td></tr><tr><td>Severe hemorrhage,</td><td>6 (3.9 %)</td><td>9 (3.2 %)</td><td>0.69</td></tr><tr><td>Neonatal morbidity</td><td></td><td></td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Apgar &lt; 7 à 5 min,</td><td>5 (3.2 %)</td><td>11 (3.9 %)</td><td>0.74</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Arterial pH &lt; 7,10,</td><td>4 (2.9 %)</td><td>8 (3.2 %)</td><td>1</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Intensive care,</td><td>9 (5.8 %)</td><td>15 (5.3 %)</td><td>0.8</td></tr></tbody></table>

Contrary to Bagory et al., we did not include ripening procedures with dinoprostone gel, as this technique was mainly used in women with prelabor rupture of membranes, and could potentially have led to confounding.

Dodd et al.'s randomized trial comparing 25 µg oral misoprostol with dinoprostone vaginal gel found, like us, that the risk of uterine hyper-stimulation (uterine tachysystole and hypertonus) without FHR abnormalities was significantly lower with oral misoprostol, and that the risk of uterine hyperstimulation syndrome was non-significantly lower with oral misoprostol [18]. Kerr et al.'s recent Cochrane review found a significantly reduced risk of uterine hyperstimulation syndrome with oral misoprostol compared with vaginal dinoprostone, but, as in our study, a significantly lower rate of deliveries within 24 h [11]. In addition to safety considerations, studies also evaluate women's satisfaction with different methods of cervical ripening, as patient experience is a key component of obstetric care [19].

The strengths of this study include the fact that it was conducted in a tertiary maternity hospital with a large number of deliveries and that we adjusted for variables known to be associated with tachysystole and uterine hyperstimulation, namely rupture of membranes before cervical ripening, the presence of uterine contractions before ripening, and the risk of fetal hypoxia. Furthermore, we considered the particular case of fetuses at risk of acidosis in a sub-group analysis, who face an additional risk in the event of uterine contractility abnormalities.

The main limitations of this study are its retrospective and descriptive nature, allowing limited control of confounding. The primary
endpoint was assessed by a single investigator who was not blinded to
the method of ripening, which carries a risk of confirmation bias. The
available cardiotocography data were sometimes of poor quality. To
limit exclusions, these were complemented by a subjective analysis of
medical and paramedical observations during induction. Since all
ripening procedures were analyzed independently, some women were
analyzed more than once, and only the number of previous ripening
procedures were considered, not the method used in each case. The
criteria used to select the cervical ripening method may have introduced
selection bias. However, we compared the Bishop score and indications
for induction between the two groups and found no statistically signif-
icant differences. Additionally, we accounted for key factors that could
influence uterine contraction abnormalities, such as parity and the
number of previous ripening attempts, by including them in the multi-
variable analysis. Note finally that this study compared the safety of the
two methods of cervical ripening, not their efficacy.

Conclusion

In this group of women with an unscarred uterus who underwent
cervical ripening with either oral misoprostol or dinoprostone vaginal
pessary, uterine tachysystole and uterine tachysystole with FHR ab-
normalities were less frequent in those who received oral misoprostol.
Oral misoprostol therefore appears to be a safer molecule for labor in-
duction in these women. These results need to be confirmed by ran-
domized controlled studies. Further research is essential to improve the
efficacy and safety of labor induction methods.

Declaration of competing interests

The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.

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