Oral versus Vaginal Misoprostol for Termination …. Zanco J. Med. Sci., Vol. 14, (Special issue 3), 2010
Oral versus Vaginal Misoprostol for Termination of Second
Trimester Missed Abortion
Dr. kajal abdulkareem salem* Dr. ghada saadullah al-sakkal**
Background and Objectives: Misoprostol is a synthetic analogue of prostaglandin E1. It
became an important drug in obstetric practice because of its uterotonic and cervical
ripening effects. This study was done to compare the effectiveness of it in oral versus
vaginal route for termination of second trimester missed abortion.
Methods: From 1st of October 2008 to the end of June 2009 at maternity teaching hospital
in Erbil, a clinical comparative study was done on 90 patients who had second trimester
missed abortion, They were randomly assigned to receive either oral misoprostol tablets
(45 patients) in dose of 200 microgram every 4 hours or vaginal misoprostol tablets (45
patients) in dose of 200 microgram every 4 hours. The patients were followed for 48 hours.
Results: The mean induction to abortion interval was significantly shorter for vaginal group
(9.98±4.56hours versus 13.30±6.24hours, P=0.005). More patients in vaginal group
aborted within 24 hours (95.6% versus 82.22%, P-value=0.045) .The vaginal group
required less number of doses than the oral group (2.09±0.90 versus 2.84±1.24, P=0.001).
Gastrointestinal side effects of misoprostol were significantly more in the oral group.
Conclusions: Misoprostol was effective drug for termination of second trimester abortion.
Vaginal misoprostol resulted in shorter induction to abortion interval, less doses required
and fewer side effects than oral misoprostol.
Key words: Misoprostol, missed abortion, uterine hyper stimulation.
of termination of pregnancy in the second
trimester. 6 Different doses, routes and
Second trimester miscarriage occurs regimens of misoprostol for medical between 13 and 24 weeks of gestation and complicates approximately 1% o f trimester have been studied with the aim to
pregnancies 1. Missed abortion is defined
as a gestational sac containing dead administration for effective termination i.e.
embryo or fetus before 24 weeks of acceptable success rate, short induction –
gestation without clinical symptom of termination interval and minimum side
expulsion 2,3. Various management effects 7- 9 . Misoprostol has the
protocols have been used for second advantages of being cheap, widely
trimester pregnancy termination, these available, stable at room temperature and
includes: surgical technique (dilatation and
as intra-amniotic prostaglandin F2alpha sublingually ,rectaly and vaginally 10.
instillation, prostaglandin E2 vaginal The aims of the study were:
suppositories, Prostaglandin E1 and high dose oxytocin. 4,5. The introduction of equivalent doses of oral misoprostol versus
Prostaglandin analogues in the late 1970 vaginal misoprostol in terms of the time *D.G.O. Maternity Teaching Hospital
** C.A.B.O.G. Lecturer in Obstetrics and Gynecological Department. College of Medicine, HMU

Oral versus Vaginal Misoprostol for Termination …. Zanco J. Med. Sci., Vol. 14, (Special issue 3), 2010
each tablet contains 200mc) 200microgram 3. To compare the number of doses Second group was arranged to receive
required for each route.
4. To determine the severity of side effects microgram (one tablet) vaginally every 4 hours up to 5 doses per day, if there was 5. To compare the rate of satisfaction of next day. The misoprostol tablet was placed in the PATIENTS AND METHODS:
posterior fornix of the vagina; the tablet was moistened with few drops of normal saline as lubricant at the time of insertion. comparative study from first October, 2008 At time of placement of subsequent doses, Teaching Hospitals in Erbil city / Kurdistan removed before next tablet was inserted. region /North of Iraq. Among patients who All patients were followed in the ward every attended the Hospital, one hundred and ten four hours with observation of pulse rate, cases of second trimester missed abortion Exclusion criteria:-
2. History of previous 2 or more Caesarean additional misoprostol dose was repeated if abortion is immenant (patient had at least opening). The induction considered to be started when the patient received the first 4. Known hypersensitivity to misoprostol. dose of misoprostol and abortion defined 6. Patients with abnormal results of (incomplete abortion) although in some cases placenta delivered at the same time 7. Patients with cervical changes (dilated ultrasonographic examination was done to All patients were cases of second trimester (fetus and placenta) had been successfully missed abortion with gestational age of (13 removed to establish that the abortion was -24) weeks .They were diagnosed by complete. Any retained products of the ultrasound and were admitted to hospital placenta (not delivered spontaneously one All patients had detailed history with full removed by soft sponging. In this study, failure of induction is considered if the investigations were done for all including The patients were randomized in two
in hospital for eight hours, and advised for groups (45 patients for each):
First group was arranged to receive oral
protocol of Misoprostol (misotac) (Sigma (SPSS version 17) was used for data entry pharmaceutical Industries, SAE, Egypt, and analysis. Chi square test of Oral versus Vaginal Misoprostol for Termination …. Zanco J. Med. Sci., Vol. 14, (Special issue 3), 2010
frequencies. T-test was used to associate the difference between 2 means of abortion ,Within the vaginal group 73.33% variables. Contingency Coefficient used for nominal variable. P-value of less than 0.05 was considered statistically significant (P=0.049) which is statistically significant, as shown in (Table 3). Regarding the mean The mean maternal age for the oral group for termination of pregnancy ,we found that vaginal group required significantly less the vaginal group (29.0 ± 5.90 years), with no statistical significant difference between them (p value 0.970).The mean gestational age(in weeks) according to last menstrual statistically significant, Regarding the period and gestational age according to the frequency of side effects after misoprostol new ultrasound assessment in the oral administration, orally treated group group were(17.95±2.64and 16.57±2.34 reported more gastrointestinal side effects respectively) compared with than vaginally treated group, as shown in (18.42±2.72and16.64±2.28 respectively) (Table 4). Other for vaginal group with no statistical reported side effects show no statistical significant difference between them (p difference between the two groups as value 0.41and 0.89 respectively). abdominal pain requiring analgesia, fever, Regarding the mean induction to abortion interval (in hours) in the vaginal group was significantly less than in the oral group (9.98±4.56hours versus 13.30±6.24hours, group showed complete satisfaction to the P=0.005), as shown in (Table 1). treatment compared with 15 women Regarding the number of successful (33.3%) women in the vaginal misoprostol abortions within 24 hours after the initial group, with highly statistical significant drug administration was higher in the difference (p value=0.0001 ). While 9 vaginal group(95.6% versus 82.22%,P- value=0.045) which is statistically were not satisfied to the treatment significant .However, all abortions compared with 30 women (66.7 %) they happened within 48 hours after the initial Table 1: Comparison in mean induction to abortion interval, in oral and vaginal groups
Vaginal group
Oral group N=45
P – Value
P value of less than 0.05 is of statistical significance Oral versus Vaginal Misoprostol for Termination …. Zanco J. Med. Sci., Vol. 14, (Special issue 3), 2010
Table 2: Comparison of successful abortion within 24 Hours, in oral and vaginal groups
Oral group N=45
Vaginal group
(No. and %)
P – Value
(No. and %)
P value of less than 0.05 is of statistical significance

Table 3:
Comparison of type of abortion, in oral and vaginal groups
Type of Abortion
Oral group (No.
Vaginal group
P – Value
(No. and %)
P value of less than 0.05 is of statistical significance Table 4: The frequency of side effects, in oral and vaginal groups
Oral Method
Vaginal Method
Side effect
P – Value
Fever(temp ≥38C) 2(4.44%) 4(8.89%) 6(6.67%) P value of less than 0.05 is of statistical significance DISCUSSION :
prostaglandins .Being highly active organic The development of safe and effective chemical compounds; they not only affect
technique for second trimester missed myometrial contractility, but also accelerate
abortion and intrauterine fetal death physiological ripening of the cervix 11 There
termination become a major clinical was no significant difference between both
challenge. Different management protocols
are continuously revised to achieve mean gestational age. This result was in improved success rate and reduced agreement with a study done by Gilbert discomfort for the patients. The practice of and Reid, 2001 12, because these factors
do not affect the route of administration. Oral versus Vaginal Misoprostol for Termination …. Zanco J. Med. Sci., Vol. 14, (Special issue 3), 2010
Regarding the mean induction to abortion interval, it was slightly shorter in our study than a study done by Fadalla et al, 2004 (13). This is may be due to the dosage we (2005) 18. In the current study, we noticed that the satisfaction rate was more in the oral group. As there is less invasiveness, induction to abortion interval and hospital self administration, and may result in the stay were slightly shorter for the oral group same effects as vaginal approach. On the than vaginal group 9, because Feldman et preferred vaginal application if they need misoprostol, he added vaginal tablet with the oral group; therefore it is difficult to accept the higher incidence of nausea and those patients thought the drug near the uterus, the better it works. Our finding disagrees with Dickinson and Evans, 2003 studied the effect of misoprostol on the results, in which they found similar route uterine contractility following different routes of administration (Oral, vaginal and CONCLUSION:
sublingual), they found that the first effect observed was an increase in uterine tone which occur significantly in a shorter time 1-Misoprostol alone is very effective agent for termination of second trimester missed (10.7 min) than after vaginal (19.4 min). Regular uterine contraction developed in all 2-Vaginal administration of misoprostol is subjects following sublingual and vaginal more effective than oral administration in increase in uterine activity was significantly higher after two hours and thereafter for 3-Oral preparation of misoprostol can be sublingual and vaginal treatment than oral used vaginally, by this way the effect of misoprostol 14. This may explain the more NDATIONS:
agreement with the study of Dickinson and 2008 16. Our finding disagree with study 1-Further studies are required to asses the done by Saha et al,2006, because they misoprostol ;therefore it is difficult to 2-Trials needed to optimize the dose and vaginal route 17. In regarding to frequency of maternal misoprostol side effects as in 3-Since oral preparations do not dissolve with Dickinson and Evans, 2003 results 15. Regarding the side effects of misoprostol, Bebbington et al ,(2002) found that there Oral versus Vaginal Misoprostol for Termination …. Zanco J. Med. Sci., Vol. 14, (Special issue 3), 2010
Danielsson K. Effects of misoprostol on uterine 1. Baker PN, Johnson I., Jones G, Kean L, Kenny contractility following different routes of LC, Mires G et al. Second trimester miscarriage. administration. Hum Reprod. 2004; 19(1):pp81– Baker PN. Obstetrics by ten teachers. London. Edward Arnold. 2006. 18th edition. pp116-124. 15. Dickinson JE, Evans SF . A comparison of oral 2. Grudzinskas JG. Miscarriage, ectopic pregnancy and trophoblast disease. In: Dewhurst's text book administration in second-trimester pregnancy of Obstetrics and Gynecology for postgraduates. t e r m i n a t i o n f o r f et al a b n o r m a l i t y. J London, Black well science Ltd; 1999. sixth 16. Behrashi M, Mahdian M . Vaginal versus oral 3. Edmonds K, Gebbie AE, Hay P, Ingamells S, Misoprostol for second-trimester pregnancy Monga A, Norman J et al .Disorders of early termination .J. Biolog. Scien. 2008; 11(21): teachers, London. Edward Arnold. 2006. 18th 17. Saha S, Bal RS, Ghosh P .Medical abortion in the late second trimester. A comparative study 4. Ramsey PS, Savage K, Lincoln T, Owen J . with misoprostol through vaginal versus oral Vaginal misoprostol versus concentrated oxytocin followed by vaginal route.J.Indian Med. Assoc. and vaginal PGE2 for second-trimester labor induction.J Obstet Gynecol. 2004; 104:138–45. 18. Dickinson JE. Misoprostol for second-trimester 5.Cunningham FG ,Leveno KJ ,Bloom SL ,Hauth pregnancy termination in women with a prior JC ,Gilstrap L .Williams Obstetrics. Mc Graw Hill. cesarean delivery. J Obstet Gynecol. 2005; 105 6. Ramos LS, Delke I .Induction of labor and pregnancy termination for fetal abnormality. In: James DK, Steer PhJ, Weiner CP and Conik B. (ed).High risk pregnancy (management options). USA. 2006. 3rd edition. pp1404- 1418. 7. Dickinson JE, Evans SF .The optimization of intravaginal misoprostol dosing schedules in second-trimester pregnancy termination. Is J Obstet Gynecol. 2002; 186; 470–4. 8. Bebbington MW, Kent N, Lim K, Gagnon A, Delisle MF. A randomized controlled trial comparing two protocols for the use of misoprostol in midtrimester pregnancy termination. Am J.Obstet Gynecol. 2002 ; 187:853–857. 9. Feldman DM, Borgida AF, Rodis JF, Leo MV, and Campbell WA. A randomized comparison of two regimens of misoprostol for second-trimester pregnancy termination. Am.J.Obstet.Gynecol. 2003 ; 189: 710-3. 10.Tang OS, Schweer H, Seyberth HW, Lee SW and Ho PC .Pharmacokinetics of different routes of administration of misoprostol. Hum Reprod. 2002 ;17:332–336. 11. Scheepers HCJ, van Erp EJM, van den Bergh AS. Use of misoprostol in first and second trimester abortion: a review. Obstet Gynecol Survey. 1999. ;54(9) pp592-600. 12. Gilbert A, Reid R .A randomized trial of oral versus vaginal administration of misoprostol for the purpose of mid-trimester termination of pregnancy. Aust. N.Z.J. obstetr.Gynecol; 2001. 41:407-410. 13. Fadalla FA, Mirghani OA, Adam I. Oral misoprostol versus vaginal misoprostol for termination of pregnancy with intrauterine fetal demise in the second-trimester. International J. Obstet Gynecol. 2004; 86:pp52-53.

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