Vol. 7(20), pp.

1339-1342, 29 May, 2013

DOI 10.5897/AJPP12.1292
ISSN 1996-0816 2013 Academic Journals
http://www.academicjournals.org/AJPP

African Journal of Pharmacy and

Pharmacology

Full Length Research Paper

Comparison of vaginal misoprostol application versus

curettage in treatment of early pregnancy failure: A
randomization clinical trial study
Zoleikha Atarod1, Fatemeh Talebi1, Seyyed Abbas Hashemi2* and Ali Kheradmand2
1

Department of Obstetrics and Gynecology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
2
Faculty of Medicine, Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Accepted 15 May, 2013

In this study, we examined the impacts of vaginal misoprostol versus curettage in treatment of early
pregnancy failure in women with first time pregnancy. Sixty (60) pregnant women (30 women in
misoprostol and 30 subjects in curettage group) with mean age of 25.8 5.3 were enrolled in the
research. Early pregnancy failure (less than 12 weeks) was confirmed by trans-vaginal sonography.
Eight hundred (800 g) of misoprostol was applied in posterior fornix of vagina and if there was failure
to first prescription, second dose of misoprostol was applied after 24 h. Data were analyzed by chi
square and T-test. In misoprostol group; 5 women (17.2%) in first 24 h, 14 subjects (48.2%) in 48 h and 3
participants (10.3%) in 7 days had complete treatment. Seven women (24.1%) had failure to misoprostol
application. In curettage group, all of the patients received successful treatment. Hematocrit (HCT)
before and after treatment in curettage group was 37.8 1.4 and 35.6 1.3, respectively while in
misoprostol group, the HCT before treatment was 38.5 1.5 and changed to 36.1 1.6 after treatment.
With considering type of therapy, there was significant differences between HCT level before and after
treatment (p = 0.02). Negative hCG was observed after 3.3 0.5 weeks in the curettage group while it
was 3.5 0.5 weeks for misoprostol group. There was no significant change in this regard (p = 0.3).
Application of vaginal misoprostol can be used as treatment in early pregnancy failure but curettage is
superior.
Key words: Early pregnancy failure, misoprostol, curettage.

INTRODUCTION
Early pregnancy failure is a common complication, and
about one of every four women experiences it. The standard method of encounter with early pregnancy failure
has been dilatation and curettage Graziosi et al., 2004;
McNamee et al., 2012; Kulier et al., 2011). In the past,
considering the speed and effectiveness of surgical treatment, surgery was considered a standard treatment for
miscarriage. But due to complications such as bleeding,
damage to the uterus (uterine perforation) and cervical

injury or Asherman's syndrome, it seems non-surgical

treatment for miscarriage is more appropriate (Tang and
Ho, 2006).
Misoprostol is a synthetic analog of prostaglandin E1. It
has been widely used for medical abortion, cervical preparation before surgical abortion, induction of labor and is
also used to terminate pregnancy (Graziosi et al., 2005).
Misoprostol was considered as a cheap, easy, available
and noninvasive alternative for abortion (Wood and Brain,

*Corresponding author. E-mail: [email protected]. Tel: 00989112581083. Fax: 00981513543248.

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Afr. J. Pharm. Pharmacol.

2002). According to these advantages, misoprostol has

been considered as a well treatment option for early
pregnancy failure (Ngai et al., 2001). In 50 to 99% of
women with early pregnancy failure, treatment with
misoprostol as an alternative to abortion, lead to withdrawal of gestation contents to 14 weeks of pregnancy
(Carbonell et al., 2001; Carbonell et al., 1998; Creinin et
al., 1997).
In many countries, recommended dose of misoprostol
for termination of early pregnancy failure is 800 to 1000
g (Sahin et al., 2001; Muffley et al., 2002; Kovavisarach
and Sathapanachai, 2002; Herabutya and OPrasertsawat, 1997; Wood and Brain, 2002; Jain et al.,
1999; Barcel et al., 2012). But they have reported many
dose-related side effects such as nausea, vomiting, diarrhea, abdominal pain, chills and fever (Prasartsakulchai
and Tannirandorn, 2004). However, drug therapies can
reduce complications, hospitalization time and costs. The
aim of this study was to compare vaginal misoprostol with
curettage in the treatment of early pregnancy failure.

PATIENTS AND METHODS

The ethics committee of Mazandaran University of Medical Sciences
approved this study (register number = 1200). The study population
voluntarily participated in this investigation. Written consent was
obtained from the participants for publication of the research
outcomes. All subjects signed consent forms in the presence of a
witness for all evaluations and treatments applied. Study
participants consisted of pregnant women less than 12 weeks who
have been visited in Imam Khomeini hospital (University hospital)
Sari, Iran. Inclusion criteria were nulligravid women aged 18 to 45
years, with confirmation of early pregnancy failure by trans-vaginal
sonography. All patients were divided in two groups (30 patients in
each study arm) based on randomization. One group received
vaginal misoprostol (medical therapy) and the patients in the other
group underwent dilation and curettage (surgical group).
Patients had stable vital signs without any infection or history of
asthma and allergy to misoprostol. They did not have any
contraindications for prostaglandins. Patients who had side effects
like nausea and severe vomiting (more than four times per day or
with dehydration), severe bleeding, diarrhea with dehydration were
withdrawn from the study and categorized as complication group.
For cases which had been selected for dilation and curettage,
complete blood count (CBC) and rhesus (Rh) were checked. If Rh
was negative, 300 g rhogam was injected and then dilation and
curettage were performed by researcher. CBC and trans-vaginal
sonography were checked 24 h after dilation and curettage again.
The same procedure was performed for misoprostol group
(checking CBC and Rh). If the Rh was negative, 300 g rhogam
was injected and then 800 g misoprostol was applied in posterior
fornix of vagina. All patients were controlled for signs such as
bleeding, nausea, vomiting, fever and chilling. If there were no
alarm signs, patients were discharged after teaching all alarm signs.
The day after treatment, patients were visited again and transvaginal sonography was done by sonographist. Treatment was
considered as successful if there were no residues (meaning if the
thickness of the uterine cavity was less than 30 mm, patients were
discharged and if the sac was still intact or the thickness of the
uterine cavity was more than 30 mm, they were offered an additional dosage of vaginal misoprostol or surgical uterine evacuation),

then hematocrit (HCT) was checked. If there were pregnancy

residue without bleeding, once more, 800 g misoprostol was
applied in posterior fornix. If patient did not have any signs, they
were discharged and after 24 h trans-vaginal sonography was
applied. If there were residues and failure to medical therapy after
one week, patients were prepared for dilatation and curettage in
operation room under general anesthesia.
Patients were referred to the Imam Khomeini Hospital Laboratory
in order to check HCT if medical therapy was successful, and HCT
level was compared in two groups. Then, hCG was controlled
every week and the time was needed for negative hCG compared
in the two groups. Data were presented as mean standard
deviation (SD). For statistical analysis, statistical package for social
sciences (SPSS) software (Version 16, Chicago, IL, USA) was
used. Quantitative variables were compared in two groups by T-test
and qualitative once by chi square test. P < 0.05 was defined as
statistically significant.

RESULTS
Study population included 30 patients in surgical therapy
group (the first group) and 30 people in medical therapy
group (treatment with misoprostol). The mean age for all
cases was 25.8 5.3; 26.3 5.4 in the medical therapy
and 25.3 5.3 in surgical group (p = 0.4) (Table1). There
were no history of diseases such as coagulation disorder,
sensibility with prostaglandins and history of asthma.
Baseline characteristics were 16 cases (26.7%) with
blighted ovum, 37 cases (61.6%) with missed abortion,
and the rest had pregnancy residue. In surgical group
with curettage, all cases had successful treatment which
was confirmed by trans-vaginal sonography, and we did
not see any pregnancy residue, whereas in medical
therapy, 7 cases (24.1%) had failure to therapy.
In medical therapy group, 5 cases (17.3%) received
just one dose (800 g) of misoprostol and 24 cases
(82.7%) received two time misoprostol with 24 h interval.
Successful treatment in medical group was observed in 5
cases (17.3%) within 24 h, 14 cases (48.2%) within 48 h
and 3 cases (10.3%) within 7 days. For 7 cases (who had
failure in medical therapy), dilatation and curettage was
prescribed and 1 case (3.4%) after the first dose of
misoprostol withdrawn out of study because of unstable
vital signs, and then was prepared for urgency dilatation
and curettage. In all, 75.9% cases medical therapy was
successful.
Uterus tissues existence and bleeding time after
medical therapy with misoprostol was 7.9 3.4 h after
treatment. HCT before and after treatment in surgical
group was 37.8 1.4 and 35.6 1.3, respectively whereas in medical group the HCT before treatment was 38.5
1.5 and decreased to 36.1 1.6 after therapy. Difference
between HCT level before and after treatment was significantly related with the kind of therapy (p = 0.02) (Table
2). After 3.3 0.5 weeks, we had negative hCG in the
surgical group while it was 3.5 0.5 weeks for medical
group. There were no significant differences between
these variables (p = 0.3) (Table 1).

Atarod et al.

1341

Table 1. Characteristics of study population and hCG level.

Treatment
Age
Negative hCG (weeks)

Curettage group
25.35.3
3.30.5

Misoprostol group
26.35.4
3.50.5

P value
0.4
0.3

Table 2. Mean values of HCT before and after treatment.

Treatment
Curettage group
Misoprostol group

HCT before therapy

37.81.4
38.51.5

None of the patients in curettage group had any

compliant such as anesthesia complications, perforation,
urethritis, bleeding and cervical injury. Patients vital signs
after surgery were stable in curettage group while
medical group 6 cases (19.8 %) had complications, including 1 case (3.3%) with severe bleeding and unstable
vital signs, 3 cases (10%) with nausea and mild vomiting
(1 to 2 times per day without dehydration ) and 2 cases
(6.6%) with mild diarrhea (1 to 2 time per day).
DISCUSSION
In this clinical trial study, we compared the effect of
application of vaginal misoprostol versus curettage in
treatment of early pregnancy failure in women with first
time pregnancy. In the current investigation, we showed,
in misoprostol group; 5 patients (17.2%) in first 24 h, 14
patients (48.2%) in 48 h and 3 participants (10.3%) in 7
days had complete evacuation of uterine content. In patients that underwent dilatation and curettage, all of them
received successful treatment. In this relation,
Kovavisarach and Sathapanachai (2002) compared the
effect of misoprostol and placebo in induction of abortion
in women in first trimester. They indicated that the
induction of abortion in misoprostol group was 63% and
in placebo 18.5%.
Graziosi et al. (2004) examined the effects of
misoprostol and curettage in 79 women with early
pregnancy failure. They reported in misoprostol and
curettage group; 53% and 96% had complete delivery
without the aid of surgery, respectively. In their research,
60% of women used misoprostol for second time. But in
contrast with our study, 77% of the participants used
misoprostol for second time which can be related to the
first pregnancy of these subjects. They indicated that
complications were observed in 25% of the misoprostol
group. Likewise in this study, complications were noted in
6 cases (19.8%) including severe bleeding and unstable
vital signs (3.3%), nausea and mild vomiting (10%) and
mild diarrhea (6.6%).

HCT after therapy

35.61.3
36.11.6

P value
0.02
0.02

Odeh et al. (2010) investigated 81 women with early

pregnancy failure, with the mean age of 29 years. They
revealed that those patients who received one dose of
misoprostol (800 g) had 88.9% achievement in therapy
and those who received second dose since failure to first
use had 66.7% success. In consistency with the current
study, 17.3% had successful treatment in their first experience. Carbonell et al. (1998, 2001) used misoprostol
(1000 g vaginal) in three consequent doses every 24 h
and elucidated that this could be accompanied with
complete abortion in 93% of the patients. The mean time
of uterus tissue extraction existence and bleeding was
8.1 h in their study but this time in our study was 7.9 h.
Conclusion
Our study revealed that vaginal misoprostol (800 g) can
be used for termination in treatment of early pregnancy
failure in pregnant women in the first trimester. Our
results showed that curettage is superior to vaginal
misoprostol in the evacuation of early pregnancy failure.
But vaginal misoprostol can be considerable since it
decreases the rate of curettage and has low complication
rate.
ACKNOWLEDGEMENT
We acknowledge Mazandaran University of medical
sciences for their support through grant.
REFERENCES
Graziosi GC, Mol BW, Reuwer PJ, Drogtrop A, Bruinse HW (2004).
Misoprostol versus curettage in women with early pregnancy failure
after initial expectant management: a randomized trial. Hum. Reprod.
19(8):1894-1899.
McNamee K, Dawood F, Farquharson RG (2012). Thrombophilia and
early pregnancy loss. Best Pract. Res. Clin. Obstet. Gynaecol.
26(1):91-102.
Kulier R, Kapp N, Glmezoglu AM, Hofmeyr GJ, Cheng L, Campana A

1342

Afr. J. Pharm. Pharmacol.

(2011). Medical methods for first trimester abortion. Cochrane

Database Syst. Rev. Nov 9;(11):CD002855.
Tang OS, Ho PC (2006). The use of misoprostol for early pregnancy
failure. Curr. Opin. Obstet. Gynecol. 18(6):581-586.
Graziosi GC, Bruinse HW, Reuwer PJ, van Kessel PH, Westerweel PE,
Mol BW (2005). Misoprostol versus curettage in women with early
pregnancy failure: impact on women's health-related quality of life. A
randomized controlled trial. Hum. Reprod. 20(8):2340-2347.
Wood SL, Brain PH (2002). Medical management of missed abortion: a
randomized clinical trial. Obstet Gynecol 99:563566.
Ngai SW, Chan YM, Tang OS, Ho PC (2001). Vaginal misoprostol as
medical treatment for first trimester spontaneous miscarriage. Hum.
Reprod. 16:1493-1496.
Carbonell JL, Rodriguez J, Aragon S (2001). Vaginal misoprostol 1000
microgram for early abortion. Contraception 63:131-136.
Carbonell JL, Varela L, Velazco A, Cabezas E, Tanda R, Sanchez C
(1998). Vaginal misoprostol for late first trimester abortion.
Contraception 57:329-333.
Creinin MD, Moyer R, Guido R (1997). Misoprostol for medical
evacuation of early pregnancy failure. Obstet. Gynecol. 89:768-762.
Sahin HG, Sahin HA and Kocer M (2001). Randomized outpatient
clinical trial of medical evacuation and surgical curettage in
incomplete miscarriage. Eur. J. Contracept. Reprod. Health Care
6:141-144.

Muffley PE, Stitely ML, Gherman RB (20020. Early intrauterine

pregnancy failure: a randomized trial of medical versus surgical
treatment. Am. J. Obstet. Gynecol. 187:321-325.
Kovavisarach E, Sathapanachai U (2002). Intravaginal 400 microg
misoprostol for pregnancy termination in cases of blighted ovum: a
randomized controlled trial. Aust. NZ. J. Obstet. Gynaecol. 42:161163.
Herabutya Y, O-Prasertsawat P (1997). Misoprostol in management
missed abortion. Int. J. Gynaecol. Obstet. 56:263-266.
Jain JK, Meckstroth KR, Mishell DR (1999). Early pregnancy termination with intravaginally administered sodium chloride solution moistened misoprostol tablet. Am. J. Obstet. Gynecol. 181:1386-1391.
Barcel F, De Paco C, Lpez-Espn JJ, Silva Y, Abad L, Parrilla JJ
(2012). The management of missed miscarriage in an outpatient
setting: 800 versus 600 g of vaginal misoprostol. Aust. NZ. J.
Obstet. Gynaecol. 52(1):39-43.
Prasartsakulchai C, Tannirandorn Y (2004). A Comparison of Vaginal
Misoprostol 800 g Versus 400 g in Early Pregnancy Failure: A
Randomized Controlled Trial. J. Med. Assoc. Thai 87:18-23.
Odeh M, Tendler R, Kais M, Maximovsky O, Ophir E, Bornstein J
(2010). Early pregnancy failure: factors affecting successful medical
treatment. Isr. Med. Assoc. J. 12(6):325-258.