Unsuccessful misoprostol induction in pregnant women: an integrative review

This is an integrative review, carried out between January and November 2022, whose research question and descriptors were outlined using the PECO strategy. The searches were carried out in the MEDLINE, Web of Science, CINAHL, EMBASE and Scopus databases by two researchers independently as well as assessment. For the study selection and identification phase, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used. The risk of bias assessment of included articles was carried out using the Newcastle-Ottawa Scale.

Results

A total of 3,674 articles were identified, and 84 were read in full, of which 11 comprised the review (n=9,010 pregnant women), published between 2005 and 2021, with the majority in the United States. Regarding the level of evidence, all articles were classified as 2b, assessed according to the design of each study. The study showed evidence regarding the following factors: High BMI (greater than 30 kg/m2), nulliparity, immature bishop, cervical length (greater than 30 mm), height, ethnicity (non-Caucasians from southern Europe) and fetal weight (greater equal to 4 kg).

Conclusion

The objective study was achieved, having demonstrated six maternal factors and one fetal factor that can lead to unsuccessful induction. It is worth highlighting the need for evidence that incorporates the individuality of each characteristic and the contribution of this study to support the choice of the best conduct for each pregnancy on an individual basis stands out.

Misoprostol; Labor, induced; Delivery, obstetric; Pregnancy; Cesarean section; Pregnant women

Article	Country/year	Objective	Design and LoE	Population	Risk of bias
Ferrazzi et al.⁽⁷⁾	Italy 2019	To investigate the impact of maternal age and BMI on the risk of late induction, prolonged induction time and the need for cesarean section after induction.	Retrospective cohort 2b	4618 pregnant women G1 n=4006 spontaneous labor G2 n=612 induced labor	7
Drakopoulos et al.⁽²¹⁾	Geneva 2017	To assess the number of doses of misoprostol necessary for cervical maturation and risk factors for cesarean section.	Retrospective cohort 2b	1295 pregnant women induced with misoprostol, dinoprostone or oxytocin.	7
Kehl et al.⁽²²⁾	Germany 2016	To assess the effectiveness of labor induction with a double balloon catheter and oral misoprostol after catheter removal, when necessary, compared to oral misoprostol alone.	Retrospective cohort 2b	1032 pregnant women at term. 830 were induced with oral misoprostol alone and 202 began induction with a double balloon catheter and continued with oral misoprostol.	7
El-Maghraby.⁽²³⁾	Egypt 2021	To compare cervical length measurement on pre-induction ultrasound and detection of insulin-like growth factor binding protein 1 (IGFBP-1) in cervical secretions by the Actim Partus test in predicting successful induction.	Retrospective cohort 2b	140 pregnant women	8
Lassiter et al.⁽²⁴⁾	USA 2015	To assess the impact of BMI index on labor induction with misoprostol.	Retrospective cohort 2b	329 pregnant women G1 (BMI <30 kg/m2) n=103 G2 (BMI 30-40 kg/m2) n=151 G3 (BMI >40 kg/m2) n=75	7
Ware et al.⁽²⁵⁾	USA 2000	To compare transvaginal cervical measurement and Bishop score as indicators of labor duration and successful induction.	Prospective cohort 2b	77 pregnant women G1 nulliparous (n=32) G2 multiparous (n=45)	6
Batool S.⁽²⁶⁾	South Africa 2013	To compare the effectiveness of oral misoprostol in primigravida and multigravida for labor induction.	Prospective cohort 2b	100 pregnant women G1 primigravida (n=50) G2 multigravida (n=50)	6
Beckwith et al.⁽²⁷⁾	USA 2017	To investigate the effect of maternal obesity on the effectiveness of cervical ripening using misoprostol at the same dose in obese versus non-obese women compared to the effect of maternal obesity on mechanical ripening using oxytocin and a Foley catheter.	Prospective cohort 2b	709 pregnant women G1 misoprostol (n=515) G2 Oxy/Foley (n=194)	7
Caliskan et al.⁽²⁸⁾	Turkey 2006	To assess cervical length measurement by transvaginal ultrasound to predict the success of labor induction in women with an unfavorable cervix.	Prospective cohort 2b	74 pregnant women G1 nulliparous (n=38) G2 multiparous (n=36)	6
Maged et al.⁽²⁹⁾	Egypt 2018	To test the hypothesis that there is a higher rate of unsuccessful labor induction in post-term obese pregnant women compared to non-obese women.	Prospective cohort 2b	288 pregnant women G1 obese (n=144) G2 non-obese (n=144)	8
Rijal P.⁽³⁰⁾	Nepal 2014	To increase knowledge of factors that increase the risk of cesarean section when labor is induced.	Prospective cohort 2b	348 pregnant women G1 vaginal birth (n= 174) G2 cesarean section (n= 174)	6

Article	Exhibition	Variables analyzed	Related factors	Conclusions
Drakopoulos et al.,2017⁽²¹⁾	Misoprostol 20 mg (2 doses) + 40 mg every 2 hours (maximum 320 mg in 18 h)/OR	Primary outcome = Obtaining Bishop ≥ 6. Secondary outcomes = Cervical change defined as an increase of at least 2 points in the BS and risk of cesarean section.	Nulliparity BMI ≥ 30 Bishop ≤ 2	Nulliparity, BMI ≥ 30 and Bishop ≤ 2 had a significant association with the risk of cesarean section after induction.
Ferrazzi et al., 2019⁽⁷⁾	Misoprostol 25 mcg 4/4 h (maximum 12 doses)/SL	Prolonged induction time (> 24h) and cesarean section rate.	BMI = 25 to 29.9 BMI > 30 Parity Non-Caucasian ethnicity	Overweight, obesity, nulliparity, and ethnicity (non-Caucasian) are significantly associated with cesarean section after induction.
Kehl et al., 2016⁽²²⁾	Double balloon catheter + misoprostol 50 mcg 4 and 8h/OR. After 48 h: 100 mcg 4, 8, 12 h/VA	Primary outcome = Cesarean section rate. Secondary outcome = Labor induction interval, rate of vaginal births between 24 and 48 hours, unsuccessful induction and neonatal parameters.	BMI Stature Nulliparity	Cesarean section rate significantly associated with BMI (p=0.031) and height (166.3±6.6 vs. 167.8±6.9 cm, p=0.004) and nulliparity (p=0.015). Cesarean section rate significantly lower in G2 (catheter + miso) (26.1 vs. 17.3%, p =0.021). Fewer cesarean sections in G2 (37.2% vs. 24.2%, p =0.015) in nulliparous.
El-Maghraby., 2021⁽²³⁾	Misoprostol* + amniotomy with oxytocin	Primary outcome = active phase of labor; dilation cervical ≥ 4 cm. Secondary outcome: Interval from induction to labor and newborns’ Apgar score.	Cervical length	Significantly greater cervical length in pregnant women who has cesarean section after induction than those who had vaginal birth. Successful induction was significantly correlated with iGFBP-1 detection in cervical secretions.
Lassiter et al., 2015⁽²⁴⁾	Misoprostol 25 mcg 4/4 h (max 06 doses)/VA + oxytocin IV	Primary outcome: Interval from induction to labor. Secondary outcomes: Number of misoprostol doses, duration of oxytocin and cesarean section.	BMI < 30 BMI 30–40 BMI > 40	Increased BMI is significantly associated with cesarean section after induction.
Ware et al., 2000⁽²⁵⁾	Misoprostol 50 mcg/VA	Primary outcome: Type of birth.	Cervical measurement ≥3cm Cervical measurement <3cm Bishop ≤ 4 Parity	Cervical measurement ≥3 cm and Bishop score ≤ 4 were statistically associated with the outcome of cesarean section. Increased cervical measurement and nulliparity are independent variables that were correlated with cesarean section.
Batool S., 2013⁽²⁶⁾	Misoprostol 25 mcg/OR	Outcomes: Number of misoprostol dose, labor induction interval and type of birth.	Parity	The cesarean section rate was higher in primiparous women.
Beckwith et al., 2017⁽²⁷⁾	Misoprostol 25 mcg/VA vs. Oxytocin with foley/VA catheter	Primary outcome: Failure to achieve active labor. Secondary outcomes: Cesarean section rate, number of misoprostol doses and need to use other methods (Pit/Fb or dinoprostone).	Obesity (BMI >30)	Pregnant women who are obese were statistically associated with higher cesarean section rates.
Caliskan et al., 2006⁽²⁸⁾	Misoprostol 50 mcg/SL	Outcomes: Unsuccessful induction (uterine contraction, Bishop less than 6 or birth not achieved in the first 24 hours after the start of induction), interval from induction to labor and the cesarean section rate.	Cervical length ≥ 30 mm Cervical length ≤ 30 mm	Cervical length ≥ 30 mm was statistically associated with higher cesarean section rates. The 30 mm cut-off point for cervical measurement demonstrated an accuracy of 68%.
Maged et al., 2018⁽²⁹⁾	Misoprostol 50 mcg/VA if Bishop > 6	Primary outcome: Cesarean section. Secondary outcome: Interval between labor and birth and the occurrence of postpartum hemorrhage (PPH).	Obesity (gestational BMI >29.9	Pregnant obese women with Bishop score > 6 showed a statistical association with cesarean section with a risk twice as high.
Rijal P., 2014⁽³⁰⁾	Misoprostol* 4/4 h (max 03 doses)	Primary outcome: Marital rate, duration of the latent and active phases of labor. Neonatal parameters.	Bishop ≤ 5 Fetal weight >4 kg	Fetal weight > 4 kg is statistically associated with cesarean section, with the risk being almost three times higher in newborns with this weight compared to those weighing less than 4 kg. Bishop score ≤ 5 was statistically associated with cesarean section.

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[1] Corresponding author: Juliana Oliveira Brito E-mail: enfajulianaoliveira@gmail.com