Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China
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Abstract |
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Key words: measured blood loss/mifepristone/misoprostol
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Introduction |
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Materials and methods |
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All women had a transvaginal ultrasound examination to confirm the gestational age. Women who were eligible for the study were allocated randomly to one of three treatment groups using a computer-generated random table. The study was a double-blind, placebo-controlled trial. All women received a single dose of 200 mg mifepristone (Mifegyne; Roussel UCLAF, Romainville, France) on day 1 of the study. On day 3, 48 h after the administration of mifepristone, women in group A were administered 0.8 mg misoprostol (Cytotec; Searle Pharmaceutical, Skokie, IL, USA) orally, and placebo tablets vaginally; women in groups B and C were given 0.8 mg of misoprostol vaginally and placebo tablets orally. They stayed in the hospital for 4 h, and blood pressure and pulse rates were recorded hourly. Vaginal examination was performed at the end of the 4 h observation period.
In groups A and B, the women continued with oral misoprostol 0.4 mg twice daily on days 410 and the women in group C took placebo tablets (Table I). All women were asked to return to the hospital on days 14 and 43 for follow-up. All women were asked to save all the sanitary towels used from day 1 until vaginal bleeding had stopped and to bring them at each follow-up visit. They were given the same brand of sanitary towels so that the results could be standardized. The women were given a diary card to record the days and amount of vaginal bleeding (in comparison with their usual menstrual periods) and any side-effects. The women then returned to the hospital on day 14 (after mifepristone) and vaginal examination, measurement of blood pressure and pulse, ultrasound of pelvis and measurement of haemoglobin level were carried out. An extra sample of venous blood was taken at each visit as the standard for the laboratory to determine the volume of blood loss. If pelvic ultrasound showed the presence of an ongoing pregnancy, vacuum aspiration was arranged. If pelvic ultrasound examination showed that there was an incomplete or missed abortion, the women were observed unless there was heavy bleeding.
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The primary outcome measure was the total amount of blood loss. The complete abortion rate, haemoglobin level, duration of vaginal bleeding and side-effects of treatment were also studied. The total amount of blood loss was used for calculation of the sample size required. In the literature, the mean measured blood loss in medical abortion was 130 ml with a SD of 100 ml (Chan et al., 1993
; Prasad et al., 1995
). It would be of clinical significance if the use of an additional 1 week course of misoprostol could reduce the amount of blood loss by 50%. Therefore, a sample size of 38 in each group was required to detect such a difference in blood loss. Assuming a 10% default rate, a total of 150 women were required.
SPSS 10.0 for Windows statistical package was used for data analysis. Continuous variables were compared by one-way analysis of variance and post-hoc (Tukey) test for multiple comparison if the data were normally distributed. KruskalWallis test was used if the data were skewed. KolgoromovSmirnov test was used to determine the distribution of samples. Paired data were compared by paired t-test. Categorical data were compared by 2-test. A P-value (two-tailed) of < 0.05 was taken as statistically significant.
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Results |
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Discussion |
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In this study, the incomplete abortion rate was not decreased by an additional 1 week course of misoprostol. There was also no significant difference in the bleeding pattern among the three groups of women. The duration of bleeding was the same for the three groups and was comparable with previous studies in the same population of women (Tang et al., 1999). The median amount of blood loss ranged from 83 to 95 ml in the three groups and the findings were comparable with two previous similar studies. Both of these studies used the same alkaline haematin method to measure blood loss as in this study. They reported a median blood loss of 84.1 (Chan et al., 1993
) and 91.5 ml (Prasad et al., 1995
). There was no significance difference among the three groups in the amount of blood loss, indicating that an additional 1 week course of oral misoprostol is not effective in reducing the amount of blood loss.
It has been postulated that incomplete abortion accounts for some of the failures of medical abortion and that it also causes the prolonged vaginal bleeding after treatment. Oral misoprostol has been shown to be less effective than vaginal misoprostol when combined with mifepristone in medical termination of pregnancy of <9 weeks gestation (El-Refaey et al., 1995). In the present study, the complete abortion rate in group A (oral misoprostol) was comparable with group C (vaginal misoprostol), indicating that the use of an additional 1 week course of misoprostol might have improved the complete abortion rate. However, the use of an additional 1 week course of oral misoprostol could not further improve the complete abortion rate of vaginal misoprostol (group B). The present study did not have enough power to confirm the above findings and a larger sample size is required to assess the difference in complete abortion rate among the three regimens.
In our previous pilot study, 50% of women complained of mild diarrhoea during treatment with misoprostol (Tang et al., 1998). This was confirmed in this randomized trial; the incidence of diarrhoea in the two groups taking an additional course of misoprostol was significantly higher than the group without an additional course. The incidence of diarrhoea was also similar to the previous pilot study (5566%). The other side-effects were similar among the three groups.
In conclusion, an additional 1 week course of oral misoprostol (0.4 mg twice daily) did not decrease the duration and amount of vaginal bleeding after medical abortion. It also increased the side-effects of treatment and therefore is not recommended for the purpose of decreasing the amount of blood loss. A larger sample size is required to assess its effect on the complete abortion rate.
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Acknowledgements |
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Notes |
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References |
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Submitted on April 15, 2002; accepted on July 1, 2002.