Dr. Suyash S. Bhandekar completed his MS in Obstetrics and Gynecology from Seth G.S. Medical College and K.E.M. Hospital in Mumbai, India. During his residency, he presented papers at local and national conferences and won prizes for the same. He is interested in high-risk pregnancy and endoscopy and is currently busy setting up his practice in Mumbai.
Background: Various medical methods for second-trimester medical termination of pregnancy (MTP) exist. Misoprostol alone has been used with myriad variations in route and dosage. Comparison between oral and vaginal routes of misoprostol forms the basis of this study.
Methods This was a prospective comparative study of misoprostol for second-trimester (14–20 weeks) MTP, comparing oral versus vaginal routes. Sixty patients were randomly allotted to two groups; 30 received oral misoprostol 400 lg 4 h up to a maximum of five doses (2000 lg), and 30 received vaginal misoprostol in the same dose and duration. In both groups, oxytocin infusion was started if abortion did not occur. Efficacy of oral versus vaginal misoprostol, induction–abortion interval (AI) and need for surgical intervention were analyzed.
Results: Both groups were well matched in terms of age, parity, previous LSCS, mean gestational age and indication for MTP. Overall mean induction–abortion interval was 19.59 h (21.66 vs. 18.57 h, oral vs. vaginal, respectively), with vaginal group taking lesser time (p 0.09). Sixty percentage in oral group required five doses, while 70% in vaginal group required 3–4 doses of misoprostol (p 0.010). 23.7 versus 6.7% in oral versus vaginal group required check curettage (p 0.038). There were no major complications, and there was only one failure in oral group. Conclusions Though both oral and vaginal misoprostol are safe, vaginal route appears to be more efficacious for second-trimester MTP.
Keywords : Misoprostol Abortion interval Second-trimester MTP Curettage
Worldwide, about a million abortions are estimated to take
place annually and approximately half may be unsafe.
Though the Medical Termination of Pregnancy (MTP) Act
has liberalized indications for which abortion is legal in India
and incidence of abortion has declined due to improved
access to contraception, the availability of ultrasonographic
diagnosis of fetal abnormalities tends to increase the incidence
of abortion in the second trimester. Though secondtrimester
MTPs account for 20% of all MTPs, they are
responsible for two-thirds of abortion-related complications
and a threefold higher morbidity. Because of the potential for
bleeding and complications, it is advisable that second-trimester
terminations take place in a health-care facility where
blood transfusion and emergency surgery are available [1].
In this context, finding the optimum method for termination
of second-trimester pregnancy is critical. Ethacridine
lactate which was used previously is not available;
numerous studies have elucidated the safety and efficacy of
mifepristone–misoprostol, or misoprostol alone, in various
dose combinations. Misoprostol, a synthetic prostaglandin
analogue with good uterotonic potential, is used for cervical
ripening and induction of abortion in different doses
and by different routes; a comparison between oral and
vaginal routes forms the basis of this study.
This was a prospective comparative study carried out at a tertiary care hospital, initiated after Institutional Ethics Committee approval. Sixty cases requiring second-trimester MTP for any indication and fulfilling inclusion criteria were selected. Aims of the study were to determine:
A total of 60 patients (30 in each group) were studied.
Maternal characteristics are shown in Table 1. Majority of
cases were seen between 26 and 30 years in both groups;
mean age was 26.67 and 26.9 years in oral and vaginal
group, respectively. Forty percentage of patients in oral
group were primigravidae; only 16% in vaginal group were
primigravidae. Majority of patients did not have a prior
abortion. There were six cases of previous 1 LSCS, two in
oral and four in vaginal group, as well as one case of
previous 2 LSCS in oral group. The mean gestational age
in both groups was 16 weeks 5 days. 46.66% of cases in
oral group were between 14 and 16 weeks of gestation,
while 50% of cases in vaginal group were between 16 and
18 weeks. There was no statistical difference noted in any of these parameters (age, parity, previous abortion or
LSCS, mean gestational age) between the two groups.
Failure of contraception was the major indication for
MTP in both groups (50% each), followed by congenital
malformations (23.3 and 26.7% in oral and vaginal group,
respectively) and social reasons mainly unmarried status
(20 and 3.3% cases in oral and vaginal group, respectively).
The mean hemoglobin was 10.51 g%, and no patients
required blood transfusion.
In both groups, approximately a third of patients aborted
within 12–16 h. However, the main difference was that
additionally 40% cases in the vaginal group aborted at
17–20 h of induction, as compared to only 10% in oral
group; cumulatively, 93.3 and 76.6% in vaginal and oral
group, respectively, aborted within 24 h. The overall mean
AI was 19.59 h, with 21.66 and 18.57 h in the oral and
vaginal groups, respectively; this difference was statistically
significant (p value 0.09), with vaginal group taking
lesser time. Majority of the cases in oral group (60%)
required five doses of misoprostol, while vaginal group
cases (70%) required only 3–4 doses of misoprostol. The
overall mean number of doses was 4.12, with 4.3 and 3.93
doses each in the oral and vaginal groups, respectively; this difference was also statistically significant (p value 0.010).
Mean dose of misoprostol required overall for our study
was 1648 ± 696 lg; requirement of oral dose was higher
(1720 ± 736 lg) as compared to vaginal dose
(1572 ± 696 lg). Oxytocin was required in 34.5% cases in
oral group, but only 10% in vaginal group; this difference
was statistically significant (p value 0.023). Induction time
and doses required are outlined in Table 2.
As shown in Fig. 1, overall efficacy of misoprostol in
achieving complete abortion was 83.3% (73.3 and 93.3% in
oral and vaginal group, respectively), with 15% incomplete
abortion and 1.7% failure. All cases of incomplete abortion
needed oxytocin, and 23.7% of cases in oral group compared
to only 6.7% of vaginal group required check
curettage; this difference was statistically significant
(p value 0.038). Only one case (1.7%) in oral group, second
gravida with no high risk factor, failed to abort despite
maximal doses of misoprostol and oxytocin for total of
36 h and was labeled as failure; she subsequently required
hysterotomy. Minor side effects like nausea, fever, shivering,
vomiting and diarrhea were seen in three and 4% of
oral and vaginal group, respectively.
Unsupervised and unsafe abortions continue to be a major cause of maternal morbidity worldwide [2]. In our country, the liberal MTP Act has unfortunately been misused for second-trimester termination of pregnancy following sex determination and has been intricately (and wrongly) related to the PC-PNDT Act. Due to legal implications and close monitoring by authorities, many practitioners may even refuse to perform second-trimester MTP, even when indicated [3]. Elsewhere in the world, second-trimester abortion has become a topic of feminist activism, enhancing the medical importance of this topic [4].
The introduction and availability of drugs which can
cause ‘‘mini-labor’’ have revolutionized the performance of
termination of pregnancy, and the emphasis is less on
surgical techniques and more on administration of drugs
like mifepristone and misoprostol. The rationale of not
priming with mifepristone prior to misoprostol is based on
evidence from studies that have evaluated the use of
misoprostol alone with good success rate for second-trimester
MTP in various routes, dosages and schedules.
Added advantages of reduced hospital stay, low cost and
higher bed turnover rate make misoprostol alone an
attractive option especially in low resource settings. In this
context, the present study was designed to compare oral
and vaginal routes for second-trimester MTP.
The average age of patients in our study was 26 years.
Lower maternal age has been specifically described as a
factor which reduces the likelihood of a patient seeking
abortion services early. We had five patients (12%) who were\20 years of age, with two being below 18 years
[5]. Majority of our patients were primigravidae. Though
increased parity may reduce time for expulsion of fetus in
MTP, we did not find this in our study [6].
A similar study by Bangal et al. analyzed 148 women
seeking MTP over a 3-year period. They used an initial
dose of 400 lg of misoprostol by vaginal route, followed
by 200 lg every 4 h till maximum of six doses. Overall
success rate was 92%; average induction–abortion interval
was 14 h, and average dose required for complete abortion
was 1200 lg. The overall success rate for vaginal group in
the present study was comparable at 93%, though the
average dose (1572 lg) and induction–abortion interval
were slightly higher at 18.57 h [7]. Tanha et al. compared
the efficacy of two routes of administration of misoprostol
(sublingual and vaginal) in 134 women desiring medical
termination of second-trimester pregnancies for various
indications. They found no differences between the vaginal
and sublingual groups in terms of efficacy. The mean dose
of misoprostol in both groups was around 1340 lg [8].
Ting compared two dose variations, 200 or 400 lg of
priming vaginal misoprostol, followed by 200 lg
of misoprostol orally at 6 h intervals in 101 patients and
found no significant difference in the abortion time (median
16.3 h) in groups that received different doses of
priming vaginal misoprostol [9]. Ting reported just one
failed case in their study, similar to the present study. With
the existing methods and dosage patterns of misoprostol,
failure is extremely uncommon.
Rahimi-Sharbaf compared the effectiveness of misoprostol
via vaginal or sublingual administration versus a
combined vaginal and sublingual route in the termination
of 13–24 week pregnancies in 195 women. 400 lg misoprostol
was inserted in the posterior fornix every 4 h for
48 h in the vaginal group; the same dosage schedule was
given sublingually in the sublingual group. In the combination
group, initially 400 lg misoprostol was inserted in
the posterior fornix, followed by 400 lg sublingually every
4 h for 48 h. The overall success rate did not significantly
differ among the three groups, though the mean duration of
abortion (655 ± 46 min) and number of tablets required
were least in the sublingual group, and overall patient
satisfaction was also highest in this group [10]. While the
success rate of vaginal with sublingual routes of 400 lg
misoprostol was similar, Milani et al. [11] found that the
abortion interval was shorter with the sublingual route and
the patients preferred the sublingual route over the vaginal
route. In Indian setting, Garg et al. [12] have studied the
sublingual route and observed better outcomes over vaginal
administration, not only in second trimester, but also in
first-trimester abortions.
The mean induction abortion duration in the vaginal
group in our study was 18.57 h. This is in contrast to the study by Desai et al. [13] who reported a shorter induction–
abortion interval 7.9 h, though the route described by them
was a less common intracervical route. In a similar study
by Nautiyal et al., 400 lg misoprostol every 4 h for a
maximum of four doses was used sublingually, vaginally
and orally in 150 women between 12 and 20 weeks gestation.
Induction–abortion interval in sublingual
(9.8 ± 3.6 h) and vaginal (10.6 ± 2.9 h) groups was less
than that in oral group (14.3 ± 3.3 h), but there were no
significant differences in failure rate and need for surgical
intervention. Oral group was best tolerated by patients [14].
In our study, the same dosage of misoprostol (400 lg)
was used for patients with scarred uteri. However, Pluchon
and Winer [15] recommend that caution be exercised when
misoprostol is used for scarred uteri, with a reduction in
dosage. Clouqueur et al. [16] has recommended a dose of
100 lg in patients with previous cesarean scar.
None of our patients had fever. Rahimi-Sharbaf et al.
[10] had highlighted that use of combination (oral followed
by vaginal) can result in a higher chance of fever. Nautiyal
had observed that the chance of fever was higher with the
vaginal group than the oral group. Hyperpyrexia is a
problem even when administered in smaller doses for the
management of first-trimester abortions [14]. Sajjan et al.
have reported complete avulsion of cervix from the lower
part of the uterus, which is a rare complication with
intravaginal misoprostol. Though there were no local
complications in the present study, due diligence should be
exercised by clinicians [17].
When used by vaginal route, pre-moistened misoprostol
using saline is most popular, as in our study also. However,
Bhattacharjee compared vaginal administration of acetic
acid-moistened misoprostol tablets with those of dry tablets
and concluded that moistening misoprostol tablets with
acetic acid did not have any benefit [18]. Huang et al. have
studied a newer dosing pattern which is 800 lg initial
loading dose followed by sequential vaginal and sublingual
misoprostol dosages. They found that higher dosage per
administration resulted in an equally efficacious dosing
pattern and reduced the number of pelvic examinations in
the aborting woman [19].
A recent 2017 publication by FIGO on their updated
recommendations for misoprostol use alone recommends a
dose of 400 lg misoprostol (sublingual, buccal or vaginal)
every 3 h till expulsion (no maximum doses suggested), for
termination of pregnancy between 13 and 26 weeks. They
also concluded that misoprostol can be used for women
with previous cesarean or other transmural uterine scars in
the second trimester, as evidence from studies show that
the risk of uterine rupture is\0.3%, and there are no
significant differences in outcomes for women with previous
CS [20]. Our study and findings are in keeping with
these guidelines. To conclude, 400 lg misoprostol 4 h by both oral and vaginal routes are safe for second-trimester
MTP. Vaginal route appears to be more efficacious with an
overall induction–abortion interval of about 19 h, with less
need for oxytocin and surgical intervention.
Conflict of interest: The authors declare that they have no conflict of
interest.
Ethical Approval: All procedures followed were in accordance with
the ethical standards of the Institutional Ethics Committee and with
the Helsinki Declaration of 1975, as revised in 2008 (5).
Informed Consent Informed consent was obtained from all patients
for being included in the study.
