Department of Obstetrics and Gynaecology, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China
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Abstract |
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Key words: abortion/medical/misoprostol
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Introduction |
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Medical abortion had been available in Europe since 1990. Women can avoid the risks of surgery and anaesthesia. Mifepristone in combination with misoprostol is highly effective for first trimester medical abortion (Norman et al., 1991). Alternative regimens had been explored because mifepristone was not readily available in many countries. Methotrexate followed by misoprostol has also been shown to be effective (Creinin et al., 1995
). However, side-effects related to methotrexate and the possibility of teratogenicity limit its popularity.
Misoprostol is a synthetic prostaglandin E1 analogue that was initially used for the treatment of gastric ulcer. We have shown that it is a safe and effective cervical priming agent prior to vacuum aspirations in first trimester abortion (Ngai et al., 1995, 1996
). It is also an effective abortifacient when given in repeated doses in second trimester abortion (Ho et al., 1997
). The results of misoprostol alone in first trimester medical abortion were disappointing. The complete abortion rates were only 6166% (Bugalho et al., 1996
; Koopersmith and Mishel, 1996
). A 92% complete abortion rate in first trimester medical abortion (amenorrhoea <70 days) has been achieved simply by adding water to the misoprostol tablets prior to vaginal insertion (Carbonell et al., 1997
). This was, however, the only published series that showed a satisfactory result. We decided to perform this prospective study to find out whether addition of water onto misoprostol tablets before insertion can improve the efficacy of misoprostol alone on first trimester medical abortion.
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Materials and methods |
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The subjects were between 16 and 42 years of age. All women satisfied the following criteria: (i) normal general and gynaecological examination; (ii) 9 weeks of gestation (as calculated from the date when the missed menstrual period should have started) on day 1 of the study; (iii) the size of the uterus on pelvic examination was compatible with the estimated duration of pregnancy. Exclusion criteria included: (i) history or evidence of disorders that represent a contraindication to the use of misoprostol (mitral stenosis, glaucoma, sickle cell anaemia, diastolic pressure >100 mm Hg, bronchial asthma); (ii) history or evidence of thrombo-embolism, severe or recurrent liver disease or pruritus of pregnancy; (iii) presence of intrauterine contraceptive device (IUCD) in utero; (iv) suspect or proven ectopic pregnancy; (v) heavy smoker (smoking >10 cigarettes daily in the past 2 years) or had another risk factor for cardiovascular disease.
Women were randomized into two groups: group 1, misoprostol with 3 drops of water per tablet (water group) and group 2, misoprostol only (no water group). On day 1, women in group 1 received vaginal misoprostol 800 µg with 3 drops of water added onto each tablet; women in group 2 received vaginal misoprostol 800 µg without water. They stayed in the day ward for a 4 h clinical observation period (hourly recordings of blood pressure and pulse rate). The time of misoprostol administration and expulsion of gestational products, if it occurred, were recorded on the data forms. They were assessed by one of the investigators at the end of the 4 h period. Women were asked to bring back the tissue mass if it was passed at home. They were advised to come back if excessive bleeding or abdominal pain was noted. On days 3 and 5, vaginal misoprostol (same treatment as that on day 1) was inserted and the observations were repeated. They were followed up again on days 15 and 43. Transvaginal ultrasound scan was performed in all women on day 15. Patients were examined and the bleeding patterns were checked on day 43. For those presenting with persistent bleeding or when menstruation had not returned, a further follow-up appointment was made.
The outcome of treatment was classified as: (i) complete abortion; (ii) incomplete abortion; (iii) missed abortion; and (iv) live pregnancy. The initial judgement about the outcome of therapy was made at the follow-up visit on day 15. If the ultrasound findings showed a live pregnancy (i.e. fetal heart activity present) on day 15, vacuum aspiration would be performed and the aspirates were sent for histological examination. If the ultrasound findings on day 15 were compatible with missed abortion (identifiable gestational sac without fetal heart activity), the investigator had the option of either termination of the pregnancy by vacuum aspiration or awaiting spontaneous expulsion of the products of conception. The choice between these two alternatives was left to the principal investigator after discussion with the subject. If the ultrasound findings were compatible with complete or incomplete abortion, no further action would be taken unless there was heavy bleeding or signs of pelvic infection. In these women the final judgement would be made on day 43. If no emergency or elective vacuum aspiration was necessary during the period up to the first menstruation, the outcome was classified as complete abortion. Tissues removed by vacuum aspiration were sent for histological confirmation.
Those who did not require vacuum aspiration were defined as successful cases. Failure was defined as the recourse to surgical abortion either due to method failure or change of patients' decision. The incidence of side-effects, duration of vaginal bleeding, dosage of analgesic requirement and infection rate between the two groups were also compared. A standardized questionnaire was given to patients during and after the abortion in order to assess acceptability to the patients. The differences in the discontinuous variables were analysed by 2 test or Fisher's exact test. The differences of continuous variables were analysed by Student's t-test for normally distributed data and the MannWhitney test for skewed data.
The calculation of sample error was based on the following assumptions: (i) type 1 error of 0.05 and power of 0.8 were acceptable; (ii) the `water group' and `no water group' would lead to complete abortion rates of 90 and 60% respectively. The sample size in each group should have been 38. Allowing for ~5% of the data not being available for use, the number in each group was 40. Therefore, the total sample size was 80.
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Results |
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Seven women withdrew from the study. They all belonged to group 2, the no water group. Three of them withdrew on day 3 and four of them withdrew on day 5. All of them had suction evacuation with no complication.
The reasons for choosing medical abortion are listed in Table IV. It was noticed that worry about risks and complications of surgery was the major reason. Other factors that contributed to the decision making included the possible adverse effect on future pregnancy and the confidence about new medical technology.
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Discussion |
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The efficacy of vaginal misoprostol alone for first trimester medical abortion varies widely, from 47 to 94% (Creinin et al., 1994; Carbonell et al., 1997). The latter group (Carbonell et al., 1997
) used three doses of 800 µg every 48 h in women with pregnancy length <70 days. He modified the administrative procedure by adding 3 drops of water with misoprostol. The complete abortion rate in his study was 92%, which was comparable to that obtained from using mifepristone together with misoprostol (Normal et al., 1991). However, the size of the study was small and no control group was included. We therefore conducted a randomized trial to evaluate the use of misoprostol (with and without water) in medical abortion up to 9 weeks of gestation.
We showed that there was an apparent but not significant trend towards achieving higher complete abortion rate when water was added to misoprostol in medical abortion up to 9 weeks of pregnancy. However, this did not reach statistical significance and the difference was less than that estimated from previous results (Carbonell et al., 1997). With the overall complete abortion rate of 85%, it is probably not a clinically acceptable method even if the addition of water can improve the results. Moreover, the inconvenience of repeated administration of vaginal misoprostol compares unfavourably with the mifepristonemisoprostol regimen. However, the complete abortion rate with addition of water appears reasonable (94%) in pregnancies with menstrual delay of
7 weeks. Further studies may be worthwhile in this group of women.
All the women who withdrew from the study did so after the second dose of misoprostol. This was probably related to the relatively long treatment protocol. Patients became more anxious and the worry of treatment failure grew if they were not responding after `repeated medication'. From our results, we noted that ~70% in both groups passed the tissue mass after the second dose and a further 10% passed the tissue mass after the third dose. This information is useful in counselling in the future.
There is an increasing awareness among both the general public and the medical profession of the need to incorporate patients' preferences into medical decision making. The acceptability of any method of treatment will influence the degree to which it is used by consumers, with important implications for health care planners (McNeil et al., 1982). Therefore, we included the patients' views on acceptability in this study. A similar study had been performed in our department using RU486 and ONO802 in first trimester abortion (Tang et al., 1992). The reasons for patients choosing medical abortion in this study were very similar to those of the previous study. The worry about surgical complications remained the major concern prompting patients to choose a medical rather than a surgical method of abortion. The side-effects produced by misoprostol were minimal, transitory and comparable between the treatment groups. Pain was the most common physical symptom and was well tolerated. There was no difference in the incidence and intensity of pain between treatment groups. In the previous study (Tang et al., 1993
), 80% of women would have chosen the same medical regimen again in future. In our study, we considered that the acceptability of the misoprostol regimen with or without water was low because 40% of women would not choose this regimen again. This was largely due to the high failure rate and inconvenience related to frequent visits. Overall, about one-fifth of the patients commented that the frequency of visits was higher than expected. Unacceptable side-effects, including prolonged bleeding and pain, also contributed to the preference for a surgical method in the future, if necessary.
We conclude that the use of misoprostol alone (either with or without water added) is not recommended for medical abortion up to 9 weeks of pregnancy because of the high failure rate and low acceptability by patients. Further study focusing on the medical abortion up to 7 weeks may be worthwhile.
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Notes |
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References |
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Submitted on September 16, 1999; accepted on February 8, 2000.