J Gandhara Med Dent Sci

January - March 2025

ORIGINAL ARTICLE

COMPARISON OF VAGINAL VERSUS SUBLINGUAL MISOPROSTOL IN THE TREATMENT OF

FIRST-TRIMESTER MISSED MISCARRIAGES

Maimoona Qadir1

ABSTRACT

OBJECTIVES

To evaluate the ecacy of sublingual versus vaginal misoprostol for the

treatment of missed miscarriages in the rst trimester of pregnancy.

METHODOLOGY

The gynecology and obstetrics department of Khyber Teaching Hospital in

Peshawar conducted this Randomized Controlled Trial investigation from

January 2021 to December 2023. Two groups of patients were formed,

according to the FIGO procedure, based on whether misoprostol was given

vaginally or orally. The dosages of 800 micrograms were administered

vaginally to the rst group and sublingually to the second group every three

hours. Patients were observed for vaginal bleeding and evacuation after 24

hours; if neither happened, the dose was repeated.

RESULTS

The groups did not dier statistically (P-value > 0.05). The mean age of the

patients (26.56 ± 5.73 versus 25.45 ± 5.63), parity of the patients (3.31 ± 0.56

versus 3.22 ± 0.54), period of gestation (8.85 ± 1.63 versus 9.37 ± 1.48), and

time from initiation of induction till expulsion (13.68 ± 3.52 versus 12.94 ±

3.45) were similar in both groups. For a complete miscarriage in the vaginal

misoprostol group, more doses (4.28 ± 0.65 vs 3.26 ± 1.23, P-value < 0.05)

were needed. In comparison to the vaginal misoprostol group (56%), the

sublingual group (91.6%) reported feeling more comfortable (P-value <

0.05) throughout the drug’s administration. The sublingual misoprostol

group had a considerably (P-value < 0.05) better success rate (77.66%)

compared to the vaginal misoprostol group (56.32%). Such adverse eects as

bleeding during menstruation (68.33% versus 93.33%), vaginal bleeding

(31.66% versus 84%), and diarrhoea (30.57% vs 59%) had signicant (P-

value < 0.05) association with sublingual misoprostol.

CONCLUSION

The ecacy of sublingual misoprostol surpasses vaginal misoprostol.

Patients are more satised and respond more favourably to the sublingual

approach.

KEYWORDS: Miscarriage, Misoprostol, Mifepristone, Uterine Evacuation,

Manual Vacuum Aspiration, Gestational Age

How to cite this article

Qadir M. Comparison of Vaginal

Versus Sublingual Misoprostol in the

Treatment of First-Trimester Missed

Miscarriages. J Gandhara Med Dent

Sci. 2025;12(1):11-14.doi:10.37762

/jgmds.12-1.614

Date of Su bmission: 28-09-2024

Date Revised: 20-11-2024

Date Acceptance: 21-11-2024

Correspondence

1Maimoona Qadir, Assistant Professor,

Department of Gynae B Unit, Khyber

Teaching Hospital, Peshawar

+92-346-9196731

dr.maimoona1983@gmail.com

INTRODUCTION

A missed abortion occurs when an embryo or fetus dies

within the uterus.1 Any therapy, including induced

abortion, should meet the highest criteria of

accessibility, aordability, safety, and patient

acceptance. A synthetic prostaglandin E1 analogue

called misoprostol encourages the ripening of the cervix

and the contraction of the uterine smooth muscle. There

are three routes of administration available: sublingual,

vaginal, and oral.2Previous studies have looked at the

consequences of giving misoprostol and have identied

advantages and disadvantages related to each

approach.3 While no appreciable dierence in the

results of oral and vaginal methods was noted, other

studies showed that the vaginal route was more

successful.4 The vaginal and sublingual methods were

almost equivalent in treatment success rates;

nevertheless, sublingual delivery is linked to a greater

prevalence of adverse drug reactions, such as fatigue

and diarrhea.5 Miscarriages may happen on their own or

be induced. Miscarriage complicates around 10% of

pregnancies and creates severe psychological distress

for the couple. According to WHO estimates, unsafe

abortions are responsible for signicant maternal

mortality, the vast majority of which take place in

developing countries where access to safe abortion

services is limited Missed miscarriage, sometimes

called early foetal demise, is a type when the fetus is

seen on USG but shows no fetal heart activity.6,7

Missed miscarriages may be treated surgically, which

12 J Gandhara Med Dent Sci

January - March 2025

Comparison of Vaginal Versus Sublingual Misoprostol in the Treatment

involves removing the products of conception from the

uterus while under anaesthesia, with the administration

of misoprostol, and expectantly, which consists in

waiting for spontaneous ejection.8 The psychological

effect of having a dead fetus is associated with the

unsuccessful expectant management.10 Although

surgical evacuation is a popular and eective therapy,

there is an association with postprocedure heavy

bleeding, infection, damage to the cervical region, and

Asherman‟s syndrome.9 The recommended course of

treatment for miscarriages used to be surgical uterine

evacuation. However, things have evolved dramatically

in the last several years. Misoprostol is the most current

treatment modality. Misoprostol is a prostaglandin E

that is often administered for termination of

miscarriages. This is used sublingually, via the vaginal

route, and orally.8,9 Although misoprostol can be used

with dierent roots, including oral, sublingual and

vaginal, however, a few evidences are available on drug

effectiveness as well as its related side eects when

used in dierent roots. Hence, the present study aimed

to compare the ecacy of misoprostol in rst -trimester

abortion through two sublingual and vaginal routes of

administration.

METHODOLOGY

This randomized controlled trial was conducted in the

Gynae department of Khyber Teaching Hospital in

Peshawar between January 2021 and December 2023.

Written informed consent for medical intervention was

taken. Patients attending the Outpatient Department

with a nal diagnosis of missed miscarriage presenting

in the rst trimester of pregnancy were the inclusion

criteria. The research did not include any patients with

co-morbidities, a gestational age higher than 13 weeks,

or who chose surgical or expectant therapy. Because of

the small sample size, block randomization was

performed according to the time of admission. Single

blind allocation and intervention were conducted by a

medical ocer working in the gynae A unit. A non-

probability consecutive sampling technique was used,

and a sample of 120 women was taken, further

classified into two groups of 60 women each. The

sample size was calculated, taking a total complication

rate of 48% as compared to 20% in the sublingual and

vaginal misoprostol groups. 90% condence interval

and a 5% margin of error were observed. Depending on

whether misoprostol was given sublingually or

vaginally, patients were randomly divided into two

groups per the FIGO technique. The dosages of 800

micrograms 3 hours vaginally and 800 micrograms 3

hours sublingually were used. After 24 hours, all the

women were evaluated for bleeding per vaginum and,

therefore, evacuation. In case none of these occurred,

the dosage was administered again. When after

completion of two cycles of misoprostol, the bleeding

continued to appear, evacuation was performed. For

confirmation, a pelvic sonogram was performed. After

admitting the patient, baseline evaluation and

coagulation tests were conducted. Demographic

information was recorded. The patients were evaluated

from the time of initiation of administration of

misoprostol till complete evacuation of the uterus was

done, which was conrmed by doing pelvic ultrasound

for retained products. Total misoprostol doses, bleeding

per vaginum in excess or less than menses, evacuation

of the uterus, and misoprostol side eects - such as

chills, pain, fever and diarrhoea were recorded. The

mean and standard deviation were calculated for the

quantitative data. The age and gestation period were

compared between the two groups, and an independent

sample t-test was performed. Percentages were used to

determine the frequency of qualitative data, and the chi-

square test was performed to compare the qualitative

variables among the two groups. P values were -

significant if < 0.05.

RESULTS

Table 1: Demographic Characteristics

Characteristics

Vaginal

Misoprostol

Sublingual

Misoprostol

P- Value

Age of the women

Mean ± SD 26.56 ± 5.73 25.45 ± 5.63 0.384

Parity

Mean ± SD 3.31 ± 0.56 3.22 ± 0.54 0.057

Period of Gestation

Mean ± SD 8.85 ± 1.63 9.37 ± 1.48 0.283

Table 2: Comparison of Initiation of Termination to Miscarriage

Duration, Doses Needed and Satisfaction Level among both

Groups

Characteristics

Vaginal

Misoprostol

Sublingual

Misoprostol

P- Value

Initiation of termination to miscarriage duration

Mean ± SD 13.68 ± 3.52 12.94 ± 3.45 0.124

Doses needed for complete abortion

Mean ± SD 4.28 ± 0.65 3.26 ± 1.23 0.000*

Level of satisfaction regarding the route of administration

Comfortable 34 (56%) 55 (91.6%) 0.000*

Uncomfortable 26(44%) 05(8.3%)

* Significant at a 5% level of signicance

Table 3: Comparison of Eﬃcacy of both Groups

Complete

Miscarriage

Successful

Unsuccessful

Total

Vaginal

Misoprostol

Sublingual

Misoprostol

Total

P-

Value

34 (56.32%)

47 (77.66%)

(67.5%)

0.032*

26 (42%)

13 (22.33%)

(32.5%)

60 (100%)

120

J Gandhara Med Dent Sci

January - March 2025

Comparison of Vaginal Versus Sublingual Misoprostol in the Treatment

Table 4: Comparison of Adverse Eects in Both Groups

Adverse eects

Vaginal

Misoprostol

Sublingual

Misoprostol

P-Value

Vaginal

bleeding

42 (68.33%) 56 (93.33%)

0.000*

P/v bleeding more

than menses

19 (31.66%) 50 (84%) 0.000*

P/v bleeding less

than menses

42 (68.32%) 10 (15.66%)

Abdominal

Cramping

37 (63.32%) 44 (72.67%) 0.949

Intolerable pain 09 (15.40%) 16 (25.00%) 0.171

V omiting 07 (13.33%) 14 (21.67%) 0.230

Diarrhea 18 (30.67%) 37 (59%) 0.002*

Pyrexia 12 (21.67%) 22 (35.00%) 0.105

DISCUSSION

In the present research, surgical curettage was not

necessary since induction resulted in a complete

abortion in most cases during the rst 24 hours of

therapy. The sublingual group had a greater success rate

for abortions than the vaginal group when the treatment

results of the two groups were compared. Research has

shown that taking drugs under the tongue increases

their eectiveness. Similar results regarding the

medication‟s eectiveness for two routes are seen,

according to research by Kapp N, as long as the dose

and interval of drug administration in the sublingual

and vaginal procedures are carried out correctly.11,12

According to Munn Z‟s study, there isn't any valuable

data that compares the eciency of the oral and vaginal

procedures between weeks 9 and 12 of pregnancy, yet,

the vaginal approach has generally been claimed to

have a higher success rate. Furthermore, the sublingual

technique reduces the pain that many women

experience while taking it vaginally. The results of the

study are consistent with those of other local studies,

according to Bracken H, who found that the sublingual

group had a success rate of 73.3% and the vaginal

group had a success rate of 66.7%, and Libei D, who

found that sublingual group had a success rate of 72%

and the vaginal group had a success rate of 63%.14,15

Chu JJ’s study indicates that sublingual administration

has higher success rates than oral and vaginal methods

in the rst 24 hours after induction. Treatment failure

was dened as the residual volume of retained products

more than 10 mm at the end of the rst induction week.

The oral group had the highest failure rate and the

highest requirement for surgical curettage. This is

pertinent in terms of medicine. Similar ndings were

reported in this aspect by the same research.16 The

vaginal group had the longest bleeding time, while the

sublingual group had the worst haemorrhage. This

might have signicant clinical implications. Between

the three groups, there was no appreciable variance in

haemoglobin levels. The sublingual group‟s

haemoglobin levels (less than 10 g/dl) decreased most.

When we examined the side eects of the two groups

the vaginal and sublingual misoprostol groups-we

found that several of the adverse eects were notably

more common in the former. Bleeding per vaginum

(68.33% vs 93.33%), excessive menstrual blood loss

(31.67% vs 83.33%), and lose motions (31.66% vs

84%) were among the adverse eects that were shown

to be substantially (P-value <0.05) related to the

misoprostol used sublingually. These results contrast

with previous studies, like one by Stanuloy J, which

showed that the sublingual group was more eective

than the vaginal group (sublingual 84.5%, vaginal

46.4%, P = 0.000), there was a higher incidence of

bleeding, pain intensity, fever, and diarrhoea in the

sublingual group.17 Schiavou JH also reported diarrhoea

(10% against 4%), vomiting (20 versus 10%), and

changed taste (62% versus 4%). This study suggests

that the vaginal method with the lowest rate of

complications was safer than the other routes, despite

some studies showing the same frequency of problems

for both oral and vaginal routes.18 Numerous studies

have reported diering rates of medication-related

issues; these dierences are probably due to dierences

in dosage, time between doses, number of doses, and

drug pharmacokinetics.19,20 The study‟s ndings

suggest that misoprostol is more eective in uterine

evacuation during the rst trimester of pregnancy when

compared to other pharmaceutical administration

strategies. Misoprostol is inexpensive, widely

accessible, and stable at room temperature. In terms of

pharmacokinetic characteristics, misoprostol delivered

vaginally has the lowest frequency of issues and the

most eective therapeutic ecacy within the rst 24

hours after induction. The biggest drawback of the

research was that the patient knew the treatment plan,

making it impossible to keep the inquiry blind.

However, the main advantage of this research was its

relatively large sample size, which produced more

precise and impactful ndings. Another interesting

aspect of this research that makes a variety of outcomes

in dierent ways is a comparison of the two methods of

misoprostol administration.

LIMITATIONS

This study has several limitations. First, the sample size

may not be large enough to generalize the ndings to

all populations. The study was conducted in a single

center, which could introduce institutional biases and

limit the external validity of the results. Additionally,

the trial only evaluated the immediate eects of

misoprostol, without considering long-term outcomes

or potential complications. The use of subjective

measures, such as patient comfort and satisfaction, may

be inuenced by individual perceptions, and the study

14 J Gandhara Med Dent Sci

Midterm Follow-up of Tlif in Single-Level Lumbar Disc

January - March 2025

did not account for potential confounding factors like

comorbidities or prior pregnancies.

CONCLUSIONS

Sublingual misoprostol is a more successful medication

than vaginal misoprostol for treating missed

miscarriages in the rst trimester. Patients reported

improved outcomes and higher levels of satisfaction

with the sublingual method. The sublingual approach

has been shown to have a more signicant possibility of

adverse eects, such as vaginal haemorrhage, blood

loss in excess of menses, and loose motions, but

patients react more positively and are more happy with

it. It oers safe, ecient, and socia lly acceptable

abortion treatment in environments with and without

resources.

CONFLICT OF INTEREST: None

FUNDING SOURCES: None

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CONTRIBUTORS

1. Maimoona Qadir - Concept & Design; Data Acquisition; Data

Analysis/Interpretation; Drafting Manuscript; Critical

Revision; Supervision; Final Approval

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