JRHS 2008; 8(2): 51-54

Copyright © Journal of Research in Health Sciences

Comparison between Intravenous and Intramuscular Administration of Prostaglandin E2 on Management of Missed Abortion

Nasrollahi Sh (MD)a, Arab M (MD)b,  Zamani M (MD)c,  Ghafeleh-bashi MS (MD)d

a Department  of Obstetrics & Gynecology, Fatemiyeh Hospital, Hamedan University of Medical Sciences, Iran

b Department  of Oncology, Shaheed Beheshti, University of Medical Science, Tehran, Iran

c Department  of Obstetrics & Gynecology, Fatemiyeh Hospital, Hamedan University of Medical Sciences, Iran

d Department  of Gynecologist, Obstetrics & Gynecologyt, Fatemiyeh Hospital, Hamedan University of Medical Sciences, Iran

*Corresponding to author: Dr Shahla Nasrollahi ,  E-mail: sh_nasrolahi@yahoo.com

Received: 11 July 2008; Accepted: 10 October 2008


Background: To compare the efficacy of two routes of prostaglandin E2 administration (Intravenous and Intramuscular) for treatment of missed abortion this study was conducted. Regarding the pilot cases of missed abortion admitted for termination of pregnancy intravenous administration of PGE2 that had higher efficacy compare to intramuscular route, investigators designed this study.

Methods: In a randomized clinical trail, 50 women with confirmed missed abortion received 250-500 μg prostaglandins E2 either intravenously or intramuscularly. Evacuation time set from drug injection to complete empting of uterus. Complete uterine evacuation was defined as empting of uterus from preg­nancy materials without the need for surgical intervention and partial evacuation defined as incomplete empting of uterus that need further surgical management. Data were analyzed using SPSS, version 13. All the data extracted with a checklist and compare by descriptive statistics and X2 and t-tests.

Results: There was no statistically difference between the results of two administration routes. The mean of evacuation time in intravenous administration routes was significantly lower in compare to in­tramuscular administration routes (P< 0.5). There was no statistically significant difference in the demographic data in two groups.

Conclusions: There was no preference between two administration routes except for evacuation time that occurred more rapidly in intravenous administration of PG E2.

Keywords: Missed abortion, Prostaglandin e2, intramuscular administration, Intravenous administra­tion, Iran


Missed abortion also named early pregnancy failure occurs in 15-20% of all pregnancies (1) and defined as a nonviable pregnancy that retained in the uterus without spontane­ous passage for at least 8 weeks since the demise (2). Traditionally, it is treated with surgical dilatation and curettage but waiting

for spontaneous abortion or medically in­duc­ing abortion are alternative procedures. For a long time, dilation and curettage has been a standard of care for early pregnancy failure. Complications associated with sur­gery are infrequent but can be serious and uterine adhesions, perforation, cervical tears, intra-abdominal trauma, hemorrhage, post-proce­dural infection, incomplete evacuation and anesthetic complication can occur in this con­text (3-4). Expectant management has 96% success rate in cases of incomplete miscar­riage. However, in missed abortions, the complete expulsion rate by the end of the third week is in the range of 60% (5).

In recent decades, medical abortion was in­troduced successfully. It has some advan­tages like patients preference, the avoidance of general anesthesia and surgical interven­tion and its lesser cost. The disadvantages of medical abortion in the first trimester are a longer duration of and significantly higher volume of bleeding compared with that fol­lowing surgical termination (6).

Prostaglandin analogues constitute the cor­nerstone of medical treatment for missed abor­tion. In studies evaluating medical treatment of missed abortion, success rates ranging be­tween 25 and 94% are reported (7-8). These studies are difficult to compare, as differ­ences in inclusion criteria, defini­tions of success, dosing intervals and routes of administration can be found. However, despite so many stud­ies, a wide variety of prostaglandin regi­mens have been used, with varying routes of administration. The present study was con­ducted among women to com­pare intrave­nous and intramuscular admini­stration routes of prostaglandin E2 in the management of missed abortion.


In a randomized clinical trail, 50 women presenting with a confirmed missed abortion (non-viable pregnancy) aged less than 20 weeks of gestation, enrolled in the trail based on investigator observation and this formula:

N= (Z1-α+Z1-β)2 (p1-p2)   (P1-P2)2

P1-p2=20 %  α =5%   β =20%   N=25

The Ethical Committee of the Hamadan Uni­versity of Medical Science approved the study protocol, and informed consent was obtained from all participating patients. Pa­tients were divided randomly in two groups equally, the first group received pros­taglandin E2 intra­muscularly (Prostadin, Sherkat-sahami-darou, Tehran, Iran) and the second group received it intravenously (Di­noprostone, Sherkat-sa­hami-darou, Tehran, Iran). Patients were blin­ded for their chosen protocol. This trail took place at Fatemiyeh referral University Hos­pital, in Hamedan, west of Iran in 2006.

First trimester missed abortion was defined as ultrasound evidence of an intact gesta­tional sac, no evidence of fetal cardiac ac­tivity (after 6 weeks LMP), a closed cervical os, and a history of no or minimal bleeding (9). Otherwise healthy patients with con­firmed diagnosis of missed abortion that had no contraindications to prostaglandin E2 and had no history of herbal or chemical drug use for abortion, were included in this trail. Pa­tients were excluded if had massive bleeding and dilated cervix with forceful contraction or severe drug side effect oc­curred. Com­plete uterine evacuation was defined as empting of uterus from pregnancy materials without the need for surgical inter­vention and partial evacuation defined as incomplete empting of uterus that need fur­ther surgical manage­ment.

Women then received 250 μg prostaglandin E2 intramuscularly or 500 μg intravenously. In intramuscular administration group, dos­age repeated if we did not receive proper re­sponse after 4 h. In intravenous group 500 μg prostaglandin E2 was diluted by 500 ml nor­mal saline 0.9% and trans­fused in 30 min (10, 11). Vital sings and symptoms were re­corded every 30 min. Evacuation time was set from drug admini­stration to complete empt­ing of uterus. The complete evacuation con­firmed by ultra­sono­graphy in 24 h after the termination of preg­nancy. Both sonographies were done by a same sinologist and one sono­graphic device in a case of medical manage­ment fail­ure patients underwent dilation and cu­rettage promptly. Patients with complete eva­cuation were dis­charged after 36 h without any medi­cation but patients underwent Dila­tation and Curettage (D&C) received 200 mg doxycy­cline qid for 7 d after hospital discharge.

Data were analyzed using SPSS, Version 13. Non-parametric was used for correlation be­tween classified variables, fisher exact test and chi-square tests, and t-tests were used for pa­rametric data. Differences were con­sidered statistically significant if P< 0.05.


Fifty patients completed the trail success­fully. The age range was 16 to 40 yr. 38% of the women were primiparous and 62% were reported as mul­tiparous. As shown in Table 1, there was no statistically significant differ­ence in the demographic data in two groups.

Table 1: Demographic data in both intravenous (IV) and intramuscular (IM) administration groups

Demographic Item



P value

Maternal age (Year) mean±SD




Gestational age (Week) mean±SD




No (%)








*Student t-test, **fishers exact

There was no statistically difference between the results of two administration routes with chi square test. The mean of evacuation time were 17.91±11.39 and 9.65±7.91 h in intra­mus­cular and intravenous administra­tion routes, respectively (P= 0.010). Table 2 shows pa­tients characteristics and complica­tions in both groups. Vomiting was not re­ported by any of the women participating in this study but dy­sp­nea and diarrhea were re­ported by 3 patients.

Table 2: Patients characteristics and complications in intravenous (IV) and intramuscular (IM) administration groups


n (%)


n (%)

P value

Active Bleeding

7 (28)

7 (28)


Uterus cramp

0 (0)

3 (12)


Complete evacuation

8 (32)

6 (24)


Partial evacuation

14 (56)

14 (56)

Failure of evacuation

3 (12)

5 (20)

Dilatation and curettage

8 (32)

6 (24)



2 (8)

1 (4)




5 (20)

7 (28)



20 (80)

18 (72)

NS= not significant, *Fishers exact test, **chi square test


Nonsurgical treatment options are becoming increasingly popular among women needing to terminate a pregnancy and their physi­cians. Pregnant women are interested in noninva­sive options to avoid complications that may adversely affect their fertility (3). In the pre­sent study, there was no significant differ­ence between intravenous and intramuscular administration routes. Also we could not find any significant difference between the two groups with respect to vaginal bleeding, side effect, surgical intervention need, uterus cramp, dosage of the drugs except for evacuation time.

Several clinical trials have evaluated the use of prostaglandin E2 and other prostaglandins for the termination of early pregnancy failure and their administration routes (3-8).

As mentioned by Ratnam several administra­tion routes of prostaglandins are acceptable and have similar effectiveness (10). The most eva­luate route of prostaglandin administra­tion was evaluated in PG E1especially orally and vaginally (11). We faced with a paucity of data about the evaluation of administra­tion routes for prostaglandin E2 in published articles.

Various routes of administration e.g. intrave­nous, intramuscular, intra-amniotic, extra-am­niotic and vaginal for terminating preg­nancies of varying gestations have been ex­amined. Intravenous infusion causes severe side effects such as fever, vomiting and diar­rhea (5-7). In this study we faced with limited number of complications (three patients).

Some few studies evaluate IM route and vagi­nal application of PG E2 (11) and another route of administration that administered sul­prostone by extraamniotic instillation (12).

In conclusions, there was no preference be­tween two administration routes except for evacuation time that occurred more rapidly in intravenous administration of PG E2.


This project financially was supported by Research Deputy of Hamadan University of Medical Science and Health Services.


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