• Users Online: 432
  • Print this page
  • Email this page


 
 
Table of Contents
ORIGINAL ARTICLE
Year : 2023  |  Volume : 28  |  Issue : 1  |  Page : 31-38

Effectiveness and safety of vaginal versus sublingual misoprostol for cervical ripening and induction of labor: A randomized controlled trial


1 Department of Obstetrics and Gynaecology, Federal Medical Centre, Owerri, Nigeria
2 Department of Obstetrics and Gynaecology, Federal Medical Centre, Owerri, Nigeria; Department of Obstetrics and Gynaecology, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria
3 Department of Obstetrics and Gynaecology, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria; Department of Obstetrics and Gynaecology, College of Medicine, University of Nigeria, Ituku-Ozalla Campus, Enugu, Enugu State, Nigeria
4 Department of Paediatrics, Enugu State University Teaching Hospital-Parklane, Enugu, Nigeria
5 Department of Paediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria

Date of Submission14-Jul-2022
Date of Decision09-Sep-2022
Date of Acceptance28-Oct-2022
Date of Web Publication13-Dec-2022

Correspondence Address:
Emmanuel O Izuka
Department of Obstetrics and Gynaecology, Faculty of Medical Sciences, College of Medicine, University of Nigeria, Ituku-Ozalla, Enugu/University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu
Nigeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmh.IJMH_59_22

Rights and Permissions
  Abstract 

Background: Vaginal misoprostol is a highly effective method of cervical ripening and induction of labor; however, it is associated with some complications. Therefore, there is need to explore other routes of administration that may be safer, acceptable, and also effective. Objective: The aim of this study was to compare the effectiveness and safety of vaginal versus sublingual misoprostol for cervical ripening and induction of labor. Materials and Methods: This was a randomized controlled trial conducted among booked antenatal women in Owerri, South-East Nigeria. The eligible participants were randomized to receive either 25 μg of misoprostol vaginally (n = 90) or 25 μg sublingually (n = 90). Outcome measures included delivery within 24 h, induction to delivery interval, cesarean section rate, side effects of misoprostol, Apgar Score at birth, and admission into the Neonatal Intensive Care Unit. Results: There was no significant difference in the effectiveness and side effects of both routes of administration (p > 0.05). The results were comparable in both groups, except for the time to reach the active phase of labor (vaginal route 16.64 ± 9.12 vs. sublingual route 13.78 ± 7.47, P = 0.023) and the number of doses of misoprostol used (vaginal route 2.81 ± 1.53 vs. sublingual route 2.34 ± 1.49, P = 0.040). Conclusion: The effectiveness of cervical ripening and induction of labor is comparable in both groups and the side effect profile is also similar. Hence, the sublingual route is as effective and as safe as the vaginal route but with added advantage of shortening the duration of active phase of labor and requiring less doses for induction of labor.

Keywords: Cervical ripening, induction of labor, sublingual misoprostol, vaginal misoprostol


How to cite this article:
Okonkwo RI, Onyeabochukwu AD, Izuka EO, Onyegbule OA, Duke-Onyeabo CP, Obiora-Izuka CE, Nwagha UI. Effectiveness and safety of vaginal versus sublingual misoprostol for cervical ripening and induction of labor: A randomized controlled trial. Int J Med Health Dev 2023;28:31-8

How to cite this URL:
Okonkwo RI, Onyeabochukwu AD, Izuka EO, Onyegbule OA, Duke-Onyeabo CP, Obiora-Izuka CE, Nwagha UI. Effectiveness and safety of vaginal versus sublingual misoprostol for cervical ripening and induction of labor: A randomized controlled trial. Int J Med Health Dev [serial online] 2023 [cited 2023 Feb 1];28:31-8. Available from: https://www.ijmhdev.com/text.asp?2023/28/1/31/363258




  Introduction Top


Induction of labor is defined as the process of artificially stimulating the uterus to start labor after the age of viability and before the spontaneous onset of labor to achieve vaginal delivery.[1] It is a common obstetric procedure that is indicated when the benefits for the mother or fetus outweigh the benefits of continuing pregnancy,[1],[2] thereby reducing the incidence of maternal and perinatal morbidity and mortality. The rate of labor induction varies by location and institution. According to studies in the United States, the rate varies from 9.5% to 33.7% of all pregnancies annually.[2] In Nigeria, a rate of 6.6% was reported in Maiduguri[3] and 11.5% in Cross-River State.[4] There are several effective methods of induction of labor, such as a mechanical method using osmotic dilators or balloon catheters and biochemical method using prostaglandins, antiprogesterone, nitric oxide donors, and oxytocin.[2]

Literature supports the use of two intra-vaginal prostaglandin preparations for induction of labor, including dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1 analog).[5]

Although not registered for such use, misoprostol is rapidly gaining ground as an effective labor induction agent. Tachysystole, hypertonus, uterine hyperstimulation, and uterine rupture are some of the complications associated with its use.[6]

Studies from different works of literature stated that the incidences of tachysystole, uterine hypertonus, and hyperstimulation were related to the dosage, dose interval, and route of administration of misoprostol.[7],[8],[9] Misoprostol can be administered through several routes, including oral, vaginal, sublingual, or rectal routes. Vaginal misoprostol appears to be more effective than the equivalent dose administered orally but is associated with a higher risk of tachysystole and hyperstimulation.[10],[11] This could be explained by the avoidance of the first-pass effects of the gastrointestinal and hepatic system and its direct effect on the cervix and uterus.[12]

Studies by Zahran et al.,[13] Jahrom et al.,[14] Feitosa et al.,[15] and Caliskan et al.[16] showed conflicting results. However, Jahrom study showed comparable efficacy among women in both groups in terms of delivery within 24 h. Zahran et al.[13]found that more subjects in the sublingual group achieved vaginal delivery within 24 h of induction than those in the vaginal group, although this was not statistically significant. Zahran et al.[13] also found that the rate of hyperstimulation and cesarean section was higher with vaginal misoprostol than with sublingual misoprostol. However, other studies[14],[15] showed higher rates of tachysystole, meconium-stained liquor, hyperstimulation, and cesarean section with the sublingual route compared to the vaginal route. In the study by Zahran et al.[13] the use of 50 µg of misoprostol may have explained the complications resulting from vaginal misoprostol. More research needs to be done using a dose of 25 µg so that the results can be compared. On the other hand, Feitosa et al.,[15] in their study, had a sample size of 150 and did not perform a preinduction CTG (cardiotocography). This could have affected the result of the study as fetuses who were already compromised were subjected to labor induction and thus, had a poor neonatal outcome which could erroneously be attributed to the route of misoprostol used. Caliskan et al.[16] used a dosing interval of 4 h and a 50 µg dose of misoprostol. This may explain the high rates of adverse maternal and neonatal outcomes found in that study. More studies are needed to administer misoprostol at a dosing interval of 6 h.

The quest for the ideal route of administration of misoprostol for cervical ripening and induction of labor is still a work in progress. Vaginal misoprostol is more effective than oral misoprostol in the induction of labor.[10],[11] However, vaginal misoprostol is associated with higher complications compared to oral misoprostol.[12] It is not clear whether there is another effective route with fewer complications. Therefore, it is necessary to advocate for another route of administration with an efficacy comparable to the vaginal route, which is more acceptable and has a better safety profile.

Some studies comparing sublingual and vaginal misoprostol for cervical ripening and labor induction at term showed conflicting reports in terms of efficacy, safety, and patient satisfaction.[13],[14],[15],[16] These randomized controlled trials had included in their studies, cases with complicated pregnancies as well as postdates as indications for labor induction.[13],[14],[15],[16] These complicated pregnancies may have adversely affected intrauterine fetal well-being which lead to poor outcomes during labor induction.

To limit these possible confounders, we studied pregnancies with postdates as an indication of labor induction. Therefore, the need to compare the effectiveness and safety of vaginal versus sublingual misoprostol for cervical ripening and labor induction is identified.


  Materials and Methods Top


Study area

The study was carried out in the labor ward of the Federal Medical Centre, Owerri, Imo State, South-East Nigeria. Imo State has an estimated population of about 4.6 million people with about 470,000 of these, residing in Owerri municipal area.[17] An estimated 130,000 (26.87%) of these are women of reproductive age.[17] Federal Medical Centre Owerri, is a tertiary health facility that provides health care to the people in the city of Owerri as well as neighboring towns and semi-urban settlements. It also caters to the needs of patients in other big cities such as Aba and Umuahia in Abia State, and Port-Harcourt in Rivers State. An average of 240 deliveries take place every month in its labor ward. An average of 20 women undergo labor induction every month.

Ethical consideration

Ethics clearance and permission to conduct this study were obtained from the ethics committee of the Federal Medical Center (FMC) Owerri (certificate no: FMC/OW/HREC/174). A written informed consent was also obtained from all participants. Excluded patients and all participants received treatment according to existing protocols. The results of this study were communicated to participants during subsequent visits.

Study design

This was a randomized controlled trial involving 180 participants divided into 90 participants per group. The study population consisted of eligible women in the labor ward of FMC Owerri scheduled for labor induction from April 2018 to February 2019.

After informed written consent was obtained, two sets of random numbers (1 to 180), corresponding to the two distinct groups, were developed by a statistician using a computer-based random sequence generator (RANDOM.ORG). The sealed opaque envelopes were sequentially labeled from 1 to 180 by the statistician. Each numbered envelope contained a 5 cm × 5 cm white paper labeled “A” for the vaginal group or “B” for the sublingual group, corresponding to the set of appropriate numbers described above. The envelopes were kept by a medical intern (third party), blinded to the study objectives. Furthermore, eligible women were consecutively recruited and randomized until the sample size was achieved.

Inclusion criteria

The inclusion criteria of the study included viable singleton pregnancy with a cephalic presentation at a gestation age of >40 weeks to <42 weeks calculated from the last menstrual period (LMP) or first-trimester ultrasound, Bishop score of <6, normal fetal heart rate and postdatism.

Exclusion criteria

The exclusion criteria of the study included multiple gestations, fetal malformation, fetal malpresentation, abnormal fetal heart rate, fetal macrosomia, cephalopelvic disproportion, placenta previa, unexplained vaginal bleeding, active genital infection (herpes), known allergy to prostaglandin preparation, grand multiparity, previous cesarean section delivery or uterine surgery, rupture of membranes, certain medical conditions in pregnancy such as preexisting cardiovascular disease, renal disease, hepatic dysfunction, or clotting disorder.

Sample size estimation

The sample size calculation was performed for a two-sided level of significance (1–a) = 95% with a power of 90%. For this study, the standard deviation of the mean induction delivery interval of 4.0 and 3.9 was used for the sublingual and vaginal groups, respectively[12] and an assumed expected difference of 4.0.

The minimum sample size required for this study was calculated using the formula for clinical noninferiority randomized control trial (RCT) when the outcome is a continuous variable.[18]

The minimum desired sample size for this study was calculated to be 82 participants per group. However, a 10% attrition (8.0) was added to account for incompletely filled questionnaires or nonresponse, bringing the sample size to 90 per group.

Data collection and methods

Following recruitment, the investigator or a trained assistant obtains the personal information including the LMP, parity, sociodemographic data, previous obstetric and medical history, and previous history of uterine surgeries. The antenatal records were reviewed for contraindications to vaginal delivery and use of prostaglandin. Weight and height were measured using an RGZ 160 model weighing scale and stadiometer manufactured in 2017 by Pyrochy Medical UK.

A 25-µg dose of misoprostol with the brand name Eprostol manufactured by Lincoln Pharmaceuticals Ltd, India was used. Participants underwent a preinduction cardiotocograph and an obstetric scan was performed to estimate fetal weight and to exclude any contraindication to vaginal delivery before enrolling in the study. A general physical examination and obstetric examination were done to ascertain fundal height, lie and presentation of the fetus and the Bishop’s score. The study drug was administered only when the Bishop score was <6 and the cardiotocograph was reassuring.

Participants in the vaginal misoprostol group received intermittent doses of 25 ug of misoprostol passed through the posterior fornix of the vagina under aseptic conditions. Participants in the sublingual group also had intermittent doses of 25 µg of misoprostol inserted under the tongue. Repeat doses of misoprostol for both groups were given every 6 h. All insertions were done by the residents in the department of Obstetrics and Gynaecology. A maximum of four doses was given. The decision to insert subsequent doses of misoprostol was made by a senior registra assessing uterine contractions and the pattern of fetal heart rate. Further doses of misoprostol were withheld if the participant started having regular uterine contractions of approximately 3 in 10 min, lasting for 35–40 s with cervical effacement and dilatation of up to 4centimeters or if there was evidence of fetal distress, or if she has received the maximum of four doses.

At the beginning of the active phase of labor, the resident doctors on duty moved the parturient to labor ward and commenced partograhic recording. The time of administration of misoprostol and the time at the onset of labor were recorded. Artificial rupture of the fetal membrane was performed in the active phase. When indicated, oxytocin infusion was delayed for 6 h from the last dose of misoprostol. Oxytocin was administered by adding 10 IU of oxytocin to 1 liter of infusion and titration commenced at 10 drops per minute and increased by 10 drops per minute every 30 min till 60 drops per minute is reached or strong uterine contractions of up to 3–4 in 10 min is generated.

The fetal heart rate was monitored quarter-hourly by intermittent auscultation using a handheld Doppler (Sonicaid). At intervals of 30 min, there was an evaluation of uterine contraction pattern and frequency over 10 min along with the duration and intensity of each contraction. The maternal vital signs were assessed half-hourly. The monitoring was carried out by the principal investigator and three assistants. Abnormalities in labor were appropriately managed in line with standard obstetric interventions. Inability to attain active phase labor after 24 h (four doses) of commencement of treatment was deemed method failure and required the method to be changed emergency cesarean section to be performed.

The only participant that developed tachysystole and/or hyperstimulation in the vaginal misoprostol group, had immediate discontinuation of oxytocin infusion, had infusion of normal saline, change in maternal position (left lateral positioning), and intranasal oxygen was administered. An injection of salbutamol, 10 mg, was added to 1 liter of normal saline and titrated against uterine contraction. She also had irrigation of the vagina using normal saline via a 50-mL syringe without a needle, repeated several times, until the pill fragments were completely dissolved. Furthermore, she also had 4 g of magnesium sulfate administered intravenously for 20 min followed by a 2 g/h infusion, as well as close feto-maternal monitoring.

Outcome measures

The primary outcome measure was the vaginal birth achieved within 24 h of induction. (This defines the effectiveness of each route)

The secondary outcome measures include rate of cesarean section and its indication, induction to delivery interval, number of misoprostol doses administered, time from the first dose to active labor, need for augmentation of labor with oxytocin, uterine hyperstimulation, hypertonus, uterine rupture, neonatal outcomes include Apgar score at birth, intrapartum fetal death, admission into Neonatal Intensive Care Unit and use of additional uterotonic like oxytocin.

Induction to delivery interval is defined as the interval between the time of the first insertion of misoprostol and delivery of the baby. Tachysystole is described as more than 5 uterine contractions in two consecutive 10-min periods. Hypertonus is characterized by a uterine contraction that lasts more than or equal to 2 min. Hyperstimulation syndrome is identified as tachysystole and/or hypertonus with fetal heart irregularity. Changes in fetal heart rate that were considered abnormal: fetal tachycardia (heart rate >160 bpm) and fetal bradycardia (FHR <110 bpm).

Standardization of research team/ pretesting of the questionnaire

Three junior resident physicians were trained and used as research assistants. All interviews and measurements were made by the researcher with the help of the three research assistants. The research questionnaire was pre-tested at General Hospital Umuguma, Imo State, and standardized before the main study to assess its challenges or ambiguity. At the end of the survey, all ambiguous questions were corrected.

Statistical analysis

The data was analyzed using International Business Machine Statistical Product for Service Solutions (IBM SPSS) 21.0 (Chicago, Illinois). Demographic and baseline variables were compared using the Chi-square test. Continuous variables were compared using the student’s t test. The categorical variables were contrasted using the Chi-square. A value of P < 0.05 was considered significant.


  Results Top


A total of 180 participants were recruited; the vaginal group consisted of 90 respondents and the sublingual group consisted of 90 respondents.

The sociodemographic characteristics of the vaginal route were not statistically significantly different from those of the sublingual route [Table 1].
Table 1: Sociodemographic characteristics of study respondent

Click here to view


There was no statistically significant difference between effectiveness in both groups (P = 0.262), as shown in [Table 2].
Table 2: Comparison of effectiveness of the route of administration of misoprostol

Click here to view


There was a statistically significant difference between both routes of administration and the time it took to attain active phase labor (P = 0.023). There was also a statistically significant difference between both routes of administration and the number of doses of misoprostol used (P = 0.040) as represented in [Table 3]
Table 3: Comparison of clinical results of the route of administering misoprostol

Click here to view


There was no statistically significant difference in the side effects in both routes of administration [Table 4].
Table 4: Comparison of misoprostol administration side effects of routes

Click here to view



  Discussion Top


The present study clearly showed that there was no statistically significant difference in the number of women who achieved vaginal delivery within 24 h between the vaginal route and sublingual route. Hence, the two routes of misoprostol share comparable effectiveness. This finding is similar to the study that was conducted in Iran by Jahrom et al.[14] This could be because the same dose of misoprostol was used. However, the work done in Turkey by Caliskan et al.[13] showed that more subjects in the sublingual group achieved vaginal delivery in 24 h compared to the vaginal group. This could be explained by the difference in the methodology, as they used a different dose of misoprostol as well as dosage interval.

One important finding in the present study is the statistically significant difference in time to attain the active phase of labor between the sublingual misoprostol group and vaginal misoprostol group. This could be a result of the shorter time it takes for sublingual misoprostol to reach its maximum concentration than the vaginal route. This finding was in contrast to the study that was done in Iran by Ayati et al.,[19] where the vaginal misoprostol group had less time to attain the active phase of labor compared to the sublingual misoprostol group though this was not statistically significant. The disparity in results could be due to racial differences in the study populations (Africa and Asia). More so, there was no statistically significant difference in the induction delivery interval between the study groups. The induction delivery interval was minimally decreased in the vaginal misoprostol group compared to the sublingual misoprostol group. This result is at variance with the findings of a study that was conducted by Kattan et al.[20] in Egypt, where the induction delivery interval was found to be less in the sublingual group compared with the vaginal group this was not statistically significant. The difference in results could be due to the small sample size (50) employed in the Egyptian study,[20] which could have affected the power of the study.

Furthermore, there was a statistically significant difference in the number of doses of misoprostol required to achieve delivery between the sublingual misoprostol group and the vaginal misoprostol group. This is similar to the findings of the study conducted by Kattan et al.[20] in Egypt, where the number of doses of misoprostol used was lower with the sublingual route than with the vaginal route. However, this contradicts the result of the study conducted by Siwatch et al.[21] in India. In their study, the number of doses of misoprostol was to a slight extent, reduced in the vaginal route compared to the sublingual route. This could be explained by the difference in their methodology where 100 mcg of misoprostol was divided into 25 mcg and a dosing interval of 4 h was used.

In this study, a smaller proportion of sublingual misoprostol users needed augmentation, compared to vaginal misoprostol users who required augmentation to facilitate their delivery, although this disparity was not shown to be statistically significant. This is similar to the study by Zahran et al.[13] in Egypt, possibly due to the same dosage interval that was used in both studies. In contrast, equal proportions of both vaginal and sublingual misoprostol needed augmentation, in the study by Bartusevicius et al.[12] in Lithuania. This may be due to the disparity in the dosage of misoprostol administered to both groups.

In terms of maternal complications, nausea, vomiting, flushing and hyperpyrexia, to a slight extent, were found to be slightly higher in the vaginal misoprostol group than in the sublingual group, although this was not statistically significant. This is similar to the finding of Souza et al.,[22] in Brazil. This may be because vaginal misoprostol has a higher bioavailability than sublingual misoprostol. This was not in keeping with the result of Ayati et al.,[19] in Iran. This may be explained by the racial differences in the study population. More women in the vaginal group had uterine hyperstimulation and tachysystole compared to the sublingual group, although the difference was not statistically significant. This conflicted with the study by Zahran et al.[13] in Egypt, where more people in the sublingual group had hyperstimulation and tachysystole. This could be explained by the fact that their study had a larger sample size.

There were no statistically significant differences in caesarean section in the vaginal misoprostol group and sublingual misoprostol, although more women in the vaginal group had a caesarean section. Comparable results (14 vaginal versus sublingual 12) were obtained by the study that was conducted by Bartusevicius et al.[12] in Lithuania. This may be due to the higher uterotonic potency of misoprostol via the vaginal route, as seen in this study, which may cause changes in fetal heart rate, a major indication for caesarean section in the present study. However, this observation conflicts with the study by Jahromi et al.[14] in Iran, where a 4-h dose interval was used.

There was no statistically significant difference in the Apgar score of <7 at 1-min, abnormal fetal heart rate changes in vaginal misoprostol and sublingual misoprostol. However, more fetuses whose mothers were in the vaginal group had fetal heart rate changes. This could be explained by the greater uterotonic effect with vaginal administration of misoprostol. This result is similar to the findings in the study that was done in Morroco by Meldi et al.,[23] probably due to similarity in sample size. In contrast, Feitosa et al.[15] observed that more abnormal changes in fetal heart rate occurred in the sublingual group. This may be due to the difference in methodology, as that study took place in two centers. In the study by Jahromi et al.,[14] more newborns were admitted to the sublingual group in the Neonatal Intensive Care Unit. In the present study, 4.4% of neonates in the vaginal group and 2.2% in the sublingual group were admitted to the Neonatal Intensive Care Unit. The difference was not statistically significant. This result corroborated the finding by Zahran et al.,[13] which is more likely due to a longer dosing interval of 6 h that was employed by both studies. In the present study, there was no maternal death, uterine rupture, fetal death, or neonatal death. This is most likely because the dose of misoprostol approved by American College of Obstetrician and Gynecologists (ACOG) for induction of labor (25mcg) was used and a 6-h dosing interval was also employed.

Another important finding in this study is the low rate of caesarean section (4.4%), probably due to the strict selection criteria where unbooked cases and complicated pregnancies were excluded.

This study is not without limitations. It is a hospital-based study and may not be a true representation of the general population. A continuous cardiotocometer (CTG) would have been the preferred choice to monitor maternal complications because it is an objective way to measure uterine contraction. However, diligent, and meticulous manual monitoring of the delivery helped minimize this limitation. Despite these limitations, some strengths could be drawn from this study. The randomization used in this study helped minimize bias. Using premade 25 mcg of misoprostol also limited confounding variables. Postdates were strictly selected as the only criterion for cervical ripening and labor induction in the present study, because other indications of labor induction, such as gestational diabetes and hypertensive disorders of pregnancy, can inadvertently affect neonatal outcomes.

The findings in this study gave valuable information that could guide the protocol for labor induction in the future. The recommendations made are that the sublingual route should be considered as an alternative to the vaginal route for cervical ripening and labor induction using misoprostol since it was found to be as effective and as safe as the vaginal route. Second, there is a reduction in the frequency of vaginal examinations when the sublingual route is used, and this is of immense importance in the cases of premature rupture of membranes (PROM) when reduced or no digital vaginal examination is recommended to prevent chorioamnionitis. And finally, a large multicenter randomized double-blind study should be conducted to further assess how effective and safe vaginal and sublingual misoprostol is for cervical ripening and induction of labor, as this will further increase external validity.


  Conclusion Top


This study showed that the vaginal and sublingual routes of misoprostol administration shared comparable efficacy. The majority of clinical outcomes were similar in both groups, except for the time to attain active phase labor which was significantly shorter with the sublingual misoprostol group than with the vaginal misoprostol group. The number of doses of misoprostol required to achieve vaginal delivery was also significantly smaller with sublingual misoprostol. The side effects were also similar on both routes of misoprostol administration. Therefore, the sublingual route appears to be as safe as the vaginal route.

Acknowledgement

The authors acknowledge the entire nursing staff and resident doctors at the labor ward of Federal Medical Centre, Owerri for their contribution and support towards the successful conclusion of this research project.

Financial support and sponsorship

Not applicable.

Conflict of interest

There are no conflicts of interest.



 
  References Top

1.
Orhue AAE Induction of labor. Tropical J Obstet Gynaecol 1997;14:1-4.  Back to cited text no. 1
    
2.
Tenore JL Methods for cervical ripening and induction of labor. Am Fam Physician 2003;67:2123-8.  Back to cited text no. 2
    
3.
Bako BG, Obed JY, Sanusi I Methods of induction of labor at The University of Maiduguri Teaching Hospital, Maiduguri: A 4-year review. Niger J Med 2008;17:139-42.  Back to cited text no. 3
    
4.
Osaheni LL, Azubuike KO, Chukwuemeka AI, Chikezie NO, Leonard OA Obstetric outcome and significance of labor induction in a poor health resource setting. Obstet Gynecol Int 2014;2014:419621.  Back to cited text no. 4
    
5.
Sudan RS, Rondon KC, Apuzzio JJ, Williams SF Labor outcomes of obese patients who underwent induction of labor with Misoprostol compared to dinoprostone. Am J Peritonatol 2015;30:187-92.  Back to cited text no. 5
    
6.
Bushra I, Shehla MB Dinoprostone and misoprostol for induction of labor at term pregnancy. Pak Armed Forces Med J 2016;66:631-36.  Back to cited text no. 6
    
7.
Girija S, Manjunath AP Comparison of two dosing regimens of vaginal misoprostol for labor induction: A randomised controlled trial. J Turk Ger Gynecol Assoc 2009;10:220-5.  Back to cited text no. 7
    
8.
Azubuike IJ, Bassey G, Okpani A Comparison of 25 and 50 microgram of misoprostol for induction of labor in nulliparous women with postdate pregnancy in Port Harcourt. Niger J Clin Pract 2015;18:263-7.  Back to cited text no. 8
    
9.
Ezechukwu PC, Ugwu EO, Obi SN, Chigbu CO Oral versus vaginal misoprostol for induction of labor in Enugu, Nigeria: A randomized controlled trial. Arch Gynecol Obstet 2015;291:537-44.  Back to cited text no. 9
    
10.
Bartusevicius A, Barcaite E, Nadisauskiene R Oral, vaginal and sublingual misoprostol for induction of labor. Int J Gynecol Obstet 2005;91:2-9.  Back to cited text no. 10
    
11.
Hofmeyr GJ, Gulmezoglu AM Vaginal misoprostol for cervical ripening and induction of labor. Cochrane Database Syst Rev 2010:CD000941. doi: 10.1002/14651858.CD000941.pub2.  Back to cited text no. 11
    
12.
Bartusevicius A, Barcaite E, Krikstolaitis R, Gintautas V, Nadisauskiene R Sublingual compared with vaginal misoprostol for labor induction at term: A randomised controlled trial. Bjog 2006;113:1431-7.  Back to cited text no. 12
    
13.
Zahran KM, Shalin AY, Abdellah MS, Elsayh KI Sublingual versus vaginal misoprostol for induction of labor at term: A randomized prospective placebo-controlled study. J Obstet Gynecol Res 2009;35:1054-60.  Back to cited text no. 13
    
14.
Jahrom BN, Poorgholan F, Yousefi G, Sahrian L Sublingual versus vaginal misoprostol for the induction of labor at term: A randomized, triple-blind placebo-controlled clinical trial. Iran J Med Sci 2016;41:79-85.  Back to cited text no. 14
    
15.
Feitosa FEL, Sampaio ZS, Alencar J, Amorim MMR, Passini J Sublingual vs. vaginal misoprostol for labor induction. Int Journal Gynecol Obstet 2006;94:91-5.  Back to cited text no. 15
    
16.
Caliskan E, Bodur H, Ozeren S, Corakci A, Ozkan S, Yucesoy I Misoprostol 50 microg sublingually versus vaginally for labor induction at term: A randomized study. Gynecol Obstet Invest 2005;59:155-61.  Back to cited text no. 16
    
17.
National Population Commission of Nigeria. Population and Housing Census of Federal Republic of Nigeria, 2006. Vol 1. Abj, Nig: NPC Press; 2009. p. 1-5.  Back to cited text no. 17
    
18.
Zhong B How to calculate the sample size in the randomized controlled trial? J Thorac Dis 2009;1:51-4.  Back to cited text no. 18
    
19.
Ayati S, Vahidroodsari F, Farshid F, Shabhabian M Vaginal versus sublingual misoprostol for labor induction at term and post-term: A randomized prospective study. IJPR 2014;13:299-304.  Back to cited text no. 19
    
20.
Kattan EL, Eman A, Abdel M, Ghada A, AbdElRahman A Sublingual versus vaginal misoprostol for induction of labor in term primigravidas: A randomized study. Evid Based Women Health J 2013;3:111-4.  Back to cited text no. 20
    
21.
Siwatch S, Kalra J, Bagga R, Jain V Sublingual vs vaginal misoprostol for labor induction. J Postgrad Med Edu Res 2012;46:138-43.  Back to cited text no. 21
    
22.
Souza AS, Amorim MM, Feitosa FE Comparison of sublingual versus vaginal misoprostol for the induction of labor: A systematic review. Bjog 2008;115:1340-9.  Back to cited text no. 22
    
23.
Meldi HE, Mohammed EK, Fawzi M, Mahjoub G Misoprostol sublingually versus vaginally for labor induction at term: A randomized study. Research in Obstetrics and Gynecology 2012;1:27-9.  Back to cited text no. 23
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed332    
    Printed16    
    Emailed0    
    PDF Downloaded34    
    Comments [Add]    

Recommend this journal