European Journal of Cardiovascular Medicine

Induction of labour is artificial initiation of labor before its spontaneous onset for the purpose of delivery of the fetoplacental unit, after age of viability using mechanical or pharmacological method. [1] Induction of labor is indicated in cases where the benefit to the mother and fetus outweigh the once of continued pregnancy. [2] Goal of successful induction of labor is to bring out adequate uterine activity sufficient for cervical changes and fetal descent without causing uterine hyperstimulation or fetal compromise. [3] The success of labour induction depends on cervical status at the time of induction. It is generally predicted that women with poor bishop’s scores have an unacceptably higher rate of failure of induction. [4] Induction of labour with prostaglandins offer the advantage of cervical ripening with stimulation of myometrial contractility. Dinoprostone (PGE2) is available only in vaginal form. It is expensive and needs to be kept in the refrigerator. [5] In comparison misoprostol is a synthetic analog of prostaglandin E1 used in the treatment and prevention of gastric ulcers and is widely used today in gynaecology and obstetrics. [6] Misoprostol (PGE1) is functional in both oral and vaginal forms and widely used to induce labor for its high efficacy, considerable safety, reasonable cost, easy to use and easy to store at room temperature. [7] In addition, unlike other prostaglandins, misoprostol has selective effect on the uterus and cervix and has no inconvenient effect on the bronchi and blood vessels. [8] Absorption by oral route is more rapid than vaginal route. Oral Misoprostol reaches peak serum concentration within 30 minutes compared to 1 hour with the vaginal route. Oral misoprostol is eliminated more rapidly than the vaginal route. [9]

Aims and objective:

The objective of our study was to compare the efficacy and safety of oral route and intravaginal route of misoprostol for induction of labour. 

This was a prospective comparative study carried out at the Department of Obstetrics and Gynaecology, Gandhi Medical College and Sultania Zanana Hospital. Approval from the institutional ethical committee was taken.

Selection of cases: The methods were explained to the pregnant women who underwent induction of labor, between 37 to 42 weeks of gestation with singleton pregnancy and cephalic presentation who volunteered and fit the inclusion criteria were selected for the study. Informed consent was taken from every participant. The study consisted of 200 pregnant women of which 100 were of study group 1 and 100 were of study group 2. Pregnant women were randomly assigned to one of the two groups. The study group 1 received 50 micrograms of misoprostol by oral route and repeated four hourly if required for a maximum of four doses. In study group 2, 50 micrograms of misoprostol was inserted in the posterior vaginal fornix and repeated four hourly if required and maximum 4 doses were inserted.

Inclusion Criteria: The study group 1 and study group 2 included patients who fulfilled the following inclusion criteria:

1. Bishop score less than 6
2. Had no contraindications for vaginal delivery.
3. Labour induction indicated for one or more of the following medical/ obstetric reasons:

• Pregnancy induced hypertension (PIH)
• Premature rupture of membranes (PROM)
• Post-term pregnancy
• Rh isoimmunization
• Oligohydramnios
• Intrauterine growth retardation (IUGR)

Exclusion Criteria: Following cases were excluded from this study:

• Cervical dilatation more than 3 cm.
• Uterine contractions at rate of 3 per 10 min. lasting for 30-45 seconds.
• A scar on the uterus (caesarean section, history of other uterine surgeries like hysterotomy, or myomectomy).
• Cephalo-Pelvic disproportion.
• Malpresentations
• history of asthma, epilepsy, glaucoma, sickle cell disease
• Unexplained vaginal bleeding
• Preexisting foetal distress
• Grand multiparity
• Medical disorders like heart disease and chronic renal failure.
• Pyrexia

Initial assessment of patients: A detailed history of cases were taken with special reference to their obstetric history of present & past pregnancies, duration of gestation & any associated complaints. General examination was performed which was followed by systemic examination. A detailed abdominal examination was done to note the fundal height, lie, presentation, position of presenting part, attitude of fetus & uterine activity. Foetal heart was auscultated to note rate; rhythm & regularity. Then a per vaginum examination was done to note the consistency, position, dilatation & effacement of cervix, station of head, presence/absence of membranes.

All baseline blood and urine investigations were carried out and USG was done.

In both the groups meticulous maternal and foetal monitoring was done. Trial interruption followed by active intervention was done whenever there were signs of:

1. Foetal distress
2. Inco-ordinate uterine activity
3. Maternal exhaustion
4. Signs of chorioamnionitis
5. Cervical dystocia

Outcomes Measured:

1. Induction-delivery interval
2. Incidence of uterine tachysystole or uterine hyperstimulation syndrome
3. Incidence of foetal distress & passage of meconium
4. Mode of delivery
5. Apgar scores at 1 min & 5 minutes after birth.
6. Admission to neonatal intensive care unit
7. Incidence of vaginal lacerations
8. Incidence of cervical tears & lacerations
9. Incidence of postpartum atonic bleeding
10. Systemic side effects in mother.

The mother and babies were followed up for a period of 72 hrs to look for postpartum haemorrhage and signs of morbidity in mother and baby.

The range of age of patients was from 18 years to 35 years and maximum patients were from the age group 21-25 years. In each study group, 50 out of 100 patients were primigravida and 50 were multipara. In both study groups 1 and 2, the commonest indications for induction were PROM and PIH (Table 1). The mean pre-induction Bishop’s scores in study group 1 and 2 were 2.31 and 2.46, respectively. In study group 1, maximum primigravida patients (64%) required 100 micrograms of drug and maximum multipara patients (82%) required 50 micrograms of drug. In study group 2 also, maximum primigravida patients (58%) required 100 micrograms of drug and maximum multipara patients (88%) required 50 micrograms of drug (Table 2). In study group 1, maximum primigravida patients (44%) delivered within 6-9 hours and maximum multipara patients (84%) delivered within 3-6 hours. In study group 2 also, maximum primigravida patients (48%) delivered within 6-9 hours and maximum multipara patients (80%) delivered within 3-6 hours (Table 3). In study group 1 and 2, 91% and 90% cases delivered vaginally, respectively (Table 4). In both study groups, maximum indications for caesarean section were fetal distress. In study group 1, 72% patients had no side effects and the most common side effects and complications were fetal distress (8%), gastrointestinal side effects (7%) and hypertonic uterine contractions (6%). In study group 2, 68% patients had no side effects and the most common side effects and complications were fetal distress (10%), hypertonic uterine contractions (10%) and vaginal lacerations and tears (9%) (Table 5). APGAR scores at 1 and 5 minutes in both study groups revealed that misoprostol given either by oral or vaginal route is not associated with significant adverse neonatal outcomes.

Table 1: Distribution of cases according to indications for induction

Table 2: Distribution of cases according to amount of drug required

Table 3: Distribution of cases according to induction-delivery interval

Table 4: Distribution of cases according to mode of delivery

Table 5: Distribution of cases according to side effects and complications

The study comparing the efficacy and safety of oral and intravaginal misoprostol for labor induction revealed that both routes are effective, with no significant differences in drug quantity, induction-delivery interval, delivery mode, or neonatal outcomes. However, variations were observed in maternal side effects, with gastrointestinal issues more common in the oral group and vaginal lacerations and cervical tears more frequent in the vaginal group. These findings are consistent with the known pharmacokinetics and pharmacodynamics of misoprostol. 

Our results align with a study conducted by Hofmeyr et al. [10], which demonstrated that both oral and vaginal misoprostol are effective for labor induction but differ in side effect profiles. The oral route has a faster systemic absorption rate, leading to more pronounced gastrointestinal side effects, while the vaginal route is associated with localized effects like lacerations due to prolonged contact with cervical tissues. 

The induction-delivery interval in our study was comparable between the two groups, with primigravida patients generally requiring more time and higher drug doses than multiparous patients. A similar pattern was observed in a study by Shetty et al. [11], where oral and vaginal misoprostol showed equivalent efficacy, though the oral route was slightly favored for its patient comfort and ease of administration. 

Regarding delivery outcomes, both groups showed a high rate of vaginal deliveries, with cesarean sections primarily due to fetal distress. These findings echo the conclusions of Tang et al. [12], who also reported no significant differences in cesarean rates between the two routes of administration. However, our study noted a marginally higher rate of fetal distress in the vaginal group, potentially attributable to localized hyperstimulation effects on the uterus, as previously hypothesized by Sanchez-Ramos et al. [4] 

The safety profile in our study indicates that oral misoprostol may be preferred in settings where gastrointestinal side effects are manageable, while vaginal misoprostol could be reserved for cases where local effects are advantageous. This is supported by a meta-analysis by Alfirevic et al. [13], which emphasized the need for tailored misoprostol administration based on individual patient characteristics and clinical scenarios. 

Differences in maternal side effects between the two groups highlight the need for personalized treatment plans. The higher prevalence of nausea, vomiting, and diarrhea with oral misoprostol aligns with its systemic absorption and metabolism, as reported in the pharmacokinetic studies by Zieman et al. [14] In contrast, the localized effects of vaginal misoprostol, including cervical tears and lacerations, are consistent with its slower systemic clearance and higher tissue concentration. 

In conclusion, both oral and intravaginal misoprostol are effective and safe for labor induction, with distinct side effect profiles. The choice of route should consider patient preferences, clinical indications, and the availability of monitoring facilities. Future studies focusing on optimizing dosing schedules and exploring alternative administration routes, such as sublingual or buccal, could provide further insights into enhancing labor induction outcomes.

This study demonstrates that both oral and intravaginal misoprostol are effective and safe options for labor induction, with no significant differences in efficacy or neonatal outcomes. The oral route is associated with more systemic side effects, while the vaginal route has localized complications. The choice of route should be individualized, considering patient needs, clinical scenarios, and available monitoring. Further research is warranted to refine dosing strategies and improve maternal and neonatal outcomes.

1. Rayburn WF. Preinduction cervical ripening: basis and methods of current practice. Obstet Gynecol Surv. 2002;57(10):683-692. doi:10.1097/00006254-200210000-00022
2. Ghasemi, V., Rashidi Fakari, F., Ebadi, A., Ozgoli, G., Kariman, N., Saei Gharenaz, M. Effective interventions for the induction of labor: A systematic review. The Iranian Journal of Obstetrics, Gynecology and Infertility, 2018; 21(1): 90-104. doi: 10.22038/ijogi.2018.10586
3. Penna LK. The management of labour. 2nd edition. Chennai: Orient Longman publisher; 2005. Induction of labour. In: Arulkumaran S, Penna LK, Rao KB, editors; pp. 1–25.
4. Sanchez-Ramos L, Kaunitz AM, Wears RL, Delke I, Gaudier FL. Misoprostol for cervical ripening and labor induction: a meta-analysis. Obstet Gynecol. 1997;89(4):633-642. doi:10.1016/S0029-7844(96)00374-2
5. American College of Obstetrician and Gynecologists. Induction of labour with misoprostol. Int J Gynecol Obstet. 2000;69:77-8.
6. Lin, Monique G. MD1; Nuthalapaty, Francis S. MD1; Carver, Alissa R.1; Case, Ashley S. MD1; Ramsey, Patrick S. MD, MSPH1. Misoprostol for Labor Induction in Women With Term Premature Rupture of Membranes: A Meta-Analysis. Obstetrics & Gynecology 106(3):p 593-601, September 2005. | DOI: 10.1097/01.AOG.0000172425.56840.57
7. Hill JB, Thigpen BD, Bofill JA, Magann E, Moore LE, Martin JN Jr. A randomized clinical trial comparing vaginal misoprostol versus cervical Foley plus oral misoprostol for cervical ripening and labor induction. Am J Perinatol. 2009;26(1):33-38. doi:10.1055/s-0028-1091396.
8. Scheepers HC, van Erp EJ, van den Bergh AS. Use of misoprostol in first and second trimester abortion: a review. Obstet Gynecol Surv. 1999;54(9):592-600. doi:10.1097/00006254-199909000-00024.
9. More, B. Misoprostol: An Old Drug, New Indications. Journal of Postgraduate Medicine 48(4):p 336-339, Oct–Dec 2002.
10. Hofmeyr GJ, Gülmezoglu AM, Pileggi C. Vaginal misoprostol for cervical ripening and induction of labor. Cochrane Database Syst Rev.2010;(10):CD000941.
11. Shetty A, Danielian P, Templeton A. A comparison of oral and vaginal misoprostol tablets in induction of labor at term. BJOG. 2001;108(3):238-43.
12. Tang OS, Gemzell-Danielsson K, Ho PC. Misoprostol: pharmacokinetic profiles, effects on the uterus, and side-effects. Int J Gynaecol Obstet. 2007;99(Suppl 2):S160-7.
13. Alfirevic Z, Weeks A. Oral misoprostol for induction of labor. Cochrane Database Syst Rev. 2006;(2):CD001338.
14. Zieman M, Fong SK, Benowitz NL, Banskter D, Darney PD. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol. 1997;90(1):88-92.