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Evacuation Interval After Vaginal Misoprostol for Preabortion Cervical Priming

A Randomized Trial


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Preabortion cervical priming is recommended routinely in nulliparas seeking termination of first-trimester pregnancies1 because it reduces the risk of cervical damage and uterine perforation.2,3 Misoprostol, a synthetic analogue of naturally occurring prostaglandin El has been used more often for preabortion cervical priming.4–6 The optimal dose of vaginal misoprostol for preabortion cervical priming in first-trimester nulliparas appears to be 400 μg administered 3 to 4 hours before vacuum aspiration.7

In Singapore, most nulliparas seeking termination of unwanted pregnancies are unmarried. Thus, for social and personal reasons, vacuum aspiration is done more often as outpatient surgery. A shorter evacuation interval for cervical priming would ensure that vacuum aspiration could be done earlier, and women could be observed for a reasonable time before going home. Whether giving a higher dose of misoprostol with a shorter evacuation time increases benefit or risk is unknown.8 The aim of this randomized study was to compare efficacy of higher doses of vaginal misoprostol given with shorter interval to evacuation with the established standard dose and interval to determine the minimum optimal interval between application of misoprostol and evacuation.

Materials and Methods

One hundred eighty nulliparas between 6 and 11 weeks' gestation who requested legal termination of first-trimester pregnancies were recruited for the study. Gestational ages were determined by reliable menstrual history and confirmed by pelvic examination or ultrasound. Only women with estimated preoperative hemoglobin of more than 10 g/dL were recruited. Informed consent was obtained from all women.

The study was double-masked and women were randomly assigned to one of three dosage groups (400, 600, and 800 μg of misoprostol) by opening one of 180 sequentially numbered, sealed envelopes prepared using random number tables. Termination of pregnancy was done as day surgery, so women were admitted on the morning of the procedure, having fasted overnight. During vaginal examination on the morning of surgery, the appropriate prepacked dose of misoprostol was inserted into the posterior vaginal fornix by a doctor who was not one of the surgeons assessing the treatment outcome. No preoperative medication was given, but women were told that analgesics were available should they experience pain. Blood pressure, pulse rate, temperature, and side effects, such as abdominal pain, vaginal bleeding, nausea, vomiting, fever, and diarrhea, were recorded. Severity of abdominal pain was assessed using the following three-point response scale: no pain, minimal or moderate pain requiring no analgesics, and severe abdominal pain requiring analgesics. Preoperative blood loss was estimated by measuring blood from the vagina in a measuring cylinder. The degree of soaking of sanitary pads was also noted.

Vacuum aspiration was done under general anesthesia after 2 hours when the 600-μg or 800-μg doses were given and after 3 hours when the dose was 400 μg. It was not possible to do every operation exactly on the hour, so arrangements were made to do every vacuum aspiration within 15 minutes of scheduled time. Vacuum aspirations were done in all women by one of two designated surgeons (KS or YFF) to reduce individual variation. The randomization schedule was unknown to the surgeons and their first contact with subjects was when the subjects were under general anesthesia. Preoperative douching of the vagina with water to clear out any particulate remains of the misoprostol tablets helped minimize any knowledge by the surgeons of the applied dosage. The degree of cervical dilatation before vacuum aspiration was measured by passing Hegar dilators in descending order starting with Hegar 12. The size of the largest Hegar dilator that could be passed into the cervical os without resistance was recorded as the cervical dilatation achieved. Other characteristics assessed during the operation included the intraoperative blood loss and amount of further dilatation required (if less than Hegar 8) to permit passage of the suction vacurette. Intraoperative blood loss was recorded as the volume of total uterine aspirate, after sieving away the products of conception. At the end of the procedure, women were kept in the hospital for 3 to 4 hours before discharge. Products of conception were confirmed histologically for all women. The women attended follow-up appointments 6 weeks later, when pelvic examinations were done and their hemoglobin levels were measured.

The sample size was estimated on the basis of successful cervical dilatation of at least 8 mm and differences in side effects between the three groups. For a 50% difference in successful cervical dilatation, with a type 1 error of 0.05 and a power of 0.95, the sample size for each dosage group would only be 27 women. For adequate power to detect differences in side effects, a larger sample size was needed, with a type 1 error of 0.05, power of 0.80, and a 25% difference in side effects. Using the method described by Fisher and Van Belle,9 the sample for each group was estimated at 51. Assuming a 10% loss to follow-up, the number chosen for each group was 60; therefore, the total sample was 180 women.

Statistical analyses included analysis of variance, Fisher exact test, and Dunnett T3 test. Variables that were normally distributed were presented as mean and standard error of the mean. Differences in maternal age, gestational age, preoperative and postoperative hemoglobin level, and mean cervical dilatation were compared using analyses of variance. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated for successful cervical dilatation (at least 8 mm after cervical priming) for the 600- and 800-μg doses, using the 400-μg group as a comparison. Preoperative and intraoperative blood loss in the three groups were compared using the Dunnett T3 test because those data had no homogeneity of variances. Frequencies of preoperative side effects were compared with the Fisher two-tailed exact test. The study was approved by the local ethics committee.


The three groups were similar in maternal and gestational ages (Table 1). None of the women aborted during the interval between misoprostol administration and the scheduled time of evacuation of the uterus. Eleven (18.3%) and 15 (25.0%) of the women who received 600 and 800 μg of misoprostol, respectively, for an interval of 2 hours, achieved successful cervical dilatation of at least 8 mm, compared with 55 (91.7%) women who received 400 μg of misoprostol for an interval of 3 hours. When the 400-μg dose was considered the standard, the OR was 0.02 (95% CI 0.01, 0.06) for 600 μg and 0.03 (95% CI 0.01, 0.09) for 800 μg for successful dilatation of at least 8 mm (P < .001). The mean cervical dilatations of 6.7 and 6.8 mm, respectively, for 600- and 800-μg doses were also significantly less than the mean of 8.1 for the 400-μg dose (P < .001). There was no statistically significant difference in successful dilatation and mean cervical dilatation between the 600- and 800-μg groups. The mean preoperative and intraoperative blood losses in the 800-μg group were both significantly greater than those of the 400-μg group. There was no statistical difference in those two indices when compared between the 600- and 400-μg groups and the 600- and 800-μg groups (Table 2).

Table 1
Table 1:
Patient Characteristics
Table 2
Table 2:
Cervical Dilatation and Intraoperative Findings

Thirty (50.0%) and 48 (80.0%) of the women in the 600-μg and 800-μg groups, respectively, had abdominal pain, compared with eight (13.3%) in the 400-μg group (Table 3). Although that difference among the three groups was statistically significant (P < .001), none of the women required analgesics. A significantly higher number of women in the 600- and 800-μg groups had a fever higher than 38.0C (Table 3). In all those women, the fever subsided postoperatively over 3 hours without the need for antipyretics. There was no statistical difference in the number of women in the three groups who had preoperative vaginal bleeding.

Table 3
Table 3:
Side Effects in Treatment Groups

At the 6-week follow-up visits, all women in the study had resumed menses. None had any persistent or delayed side effects, and there were no significant differences in hemoglobin levels preoperatively and postoperatively in any group (Table 1).


In our previous shady,7 we showed that 400 μg of intravaginal misoprostol was the optimal dose for pre-abortion cervical priming 3 to 4 hours before vacuum aspiration in first-trimester nulliparas. Increasing the dose further with the same interval of 3 to 4 hours was not associated with any significant difference in successful cervical dilatation of 8 mm or more, but was associated with significantly more intraoperative blood loss and side effects.

In the present study, higher doses of misoprostol (600 and 800 μg) with a shorter evacuation interval of 2 hours failed to achieve the desired successful cervical dilation of 8 mm or more, compared with 400 μg of misoprostol and an interval of 3 hours. Despite the shorter interval, the 600- and 800-μg doses were associated with significantly more abdominal pain and fever of over 38.0C compared with 400 μg and an evacuation interval of 3 hours. The incidence of those side effects was less than that in the previous study7 when the same higher doses were used with an interval of 3 to 4 hours.

Zieman et al10 studied absorption pharmacokinetics of misoprostol and found that with intravaginal misoprostol, peak plasma levels were reached 1 to 2 hours after administering the dose. Plasma levels were sustained to up to 4 hours, and systemic bioavailability of vaginal misoprostol was three times higher than oral misoprostol, which probably indicates that there is a relationship between plasma levels of misoprostol and its therapeutic effect.


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4. el-Refaey H, Calder L, Wheatley DN, Templeton A. Cervical priming with prostaglandin E, analogues, misoprostol and gemeprost. Lancet 1994;343:1207–9.
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Cited By

This article has been cited 1 time(s).

Obstetrics & Gynecology
Gemeprost Versus Misoprostol for Cervical Priming Before First-Trimester Abortion: A Randomized Controlled Trial
Ekerhovd, E; Radulovic, N; Norström, A
Obstetrics & Gynecology, 101(4): 722-725.

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© 1999 The American College of Obstetricians and Gynecologists