Department of Obstetrics and Gynecology, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China
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Abstract |
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Key words: expectant management/misoprostol/randomized trial/spontaneous miscarriage
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Introduction |
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Recently, alternative treatment approaches have been suggested. There is evidence that a substantial proportion of spontaneous miscarriage will resolve spontaneously (Letterie et al., 1991). Furthermore, medical treatment using prostaglandin analogues and antiprogesterone have been shown to be effective in the management of spontaneous miscarriage (Henshaw et al., 1993
; Chung et al., 1995
; Nielsen and Hahlin, 1995
). Medical management was also found to be effective and may be able to generate cost savings when compared with surgical management (Huges et al., 1996
). The need for routine suction evacuation is thus being questioned.
Misoprostol, a synthetic prostaglandin oestrone analogue, has been shown to be effective for cervical priming prior to suction evacuation in first trimester pregnancy terminations (Ngai et al., 1999). However, data from randomized trials comparing expectant versus repeated vaginal misoprostol for spontaneous abortion are lacking. We therefore performed a randomized study to investigate its role in the management of first trimester spontaneous miscarriage.
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Materials and methods |
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The randomization table was constructed as described by Meinert (Meinert, 1986). The grouping allocation number was put into an opaque envelope that was serially labelled. Each patient, with consent for randomization, was assigned to the latest numbered envelope. Women were randomized into two groups: group 1: misoprostol treatment; group 2: expectant treatment.
Medical treatment
In our previous study, we have shown that the vaginal route was more effective and the incidence of side-effects was lower when compared with the oral route in second trimester termination of pregnancy (Ho et al., 1997). Therefore the vaginal route was used in this study. As we were planning a protocol that could be managed in an out-patient setting, side-effects such as excessive vaginal bleeding and gastro-intestinal upset leading to emergency admission should be avoided. Chung et al. (1999) used the daily dose of 1200 µg misoprostol for the management of spontaneous miscarriage (Chung et al., 1999
). In order to minimize the incidence of side-effects, we decided to use a lower daily dose (400 µg) and give it every other day. The day of diagnosis and recruitment was defined as day 0. On day 1, women were given 400 µg vaginal misoprostol followed by a 4 h clinical observation period (hourly recording of blood pressure, pulse rate and the amount of oral analgesia given) in the day care centre. Expulsion of gestational products, where present, was recorded on the data forms. Side-effects such as nausea, vomiting and abdominal pain were also recorded. Patients were discharged if there was no excessive vaginal bleeding. Emergency suction evacuation was arranged where excessive blood loss or abdominal pain occurred. The decision for emergency suction evacuation was made by the on-call medical officer based on clinical judgement. The amount of blood loss was assessed clinically by the on-call doctor. Objective measurement of blood loss was not done. All women were advised to record and bring the tissue mass back if it was passed at home. Oral analgesia was given and the dosage and frequency of medication taken were recorded. Sexual intercourse was avoided in the following 2 weeks. The same procedure was repeated on day 3 and day 5.
Expectant management
On day 1, women were discharged if there was no excessive vaginal bleeding. They were advised to come back if excessive bleeding was noted. They were then followed up on day 3 and day 5. If they had passed tissue masses, transvaginal ultrasonography was performed to check for retained gestational product.
Outcome assessment
The initial judgement about the outcome was made on day 15. If the ultrasound findings were compatible with a missed miscarriage (identifiable gestational sac without fetal heart activity), suction evacuation was performed and the aspirates were sent for histological examination. If the ultrasound findings were compatible with complete or incomplete miscarriage, no further action was taken. All women were followed up on day 43. If menstruation did not return, an additional follow-up visit was arranged. Those who did not require suction evacuation up to the time of normal menstruation were classified as successful cases. Failure was defined as the recourse to surgical treatment either due to method failure or change of patients' decision. The incidences of side-effects, duration of vaginal bleeding, dosage of analgesic requirement and infection rate between the two groups were also compared. Standardized questionnaires were given to patients during and after the abortion in order to assess patients' acceptability and the incidence of side-effects.
The calculation of the sample size was based on the following assumptions: (i) type 1 error of 0.05 and power of 0.85 were acceptable; (ii) the use of misoprostol would achieve a complete abortion rate of 60% (Chung et al., 1995) so that it could be clinically useful as an alternative when compared with surgical intervention. The chance of spontaneous resolution in the expectant group was about 20%. Assuming that 10% of the data were retrospectively excluded due to incomplete data, the number was 29 in each group. Thus, the total required sample size was 58. The differences of discrete variables were analysed by
2 test or Fisher's exact test. The differences of continuous variables were analysed by the Student's t-test for normally distributed data and MannWhitney's U-test for skewed data.
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Results |
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The mean duration of vaginal bleeding was similar between the two groups (14.6 days in misoprostol group versus 15.0 days in expectant group). For those who required suction evacuation, prophylactic antibiotics were not given. No patient suffered from infection or operative complications. Four women in each group had not menstruated by day 42. Extra follow-up was arranged for these women until normal menstruation returned.
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Discussion |
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This is the first randomized study comparing repeated doses of vaginal misoprostol with expectant management for first trimester spontaneous miscarriage. Our results showed that outpatient treatment using vaginal misoprostol was more effective when compared with expectant management.
Nielsen et al. (1999) showed that the combination of mifepristone and oral misoprostol was effective for first trimester miscarriage (Nielsen et al., 1999). They used 400 mg oral mifepristone followed by a single dose of 400 µg oral misoprostol. A total of 82% of women had an empty uterine cavity after 5 days. However, mifepristone is only available in a few countries. The addition of mifepristone also added to the drug costs of the regimen. We demonstrated that by using vaginal misoprostol alone, the successful rate was comparable with the combination of mifepristone and misoprostol. Patients can have an option of medical treatment where mifepristone is not available.
Chung et al. (1999) had compared oral misoprostol versus surgical treatment in a randomized trial (Chung et al., 1999). In their study, women who presented with the clinical diagnosis of spontaneous miscarriage were recruited. Those who presented with ultrasound scan findings showing a choriodecidual reaction measuring <5 cm2 in transverse and <6 cm2 in the sagittal plane were considered to have an empty uterus and were excluded from the trial. In their study, the successful rate of misoprostol treatment was 50.4%. Women treated with misoprostol had significantly more blood loss and required more analgesia when compared with the surgical group. Seven subjects in the misoprostol group failed to complete the protocol because of excessive side-effects. In our study, all women considered the side-effects tolerable and transient. Only one patient in the misoprostol group underwent emergency suction evacuation because of excessive bleeding. Our complete miscarriage rate (83.3%) is also higher. This is probably due to the difference in administration route and the dosage of treatment protocol. They used oral misoprostol 400 µg every 4 h up to a total dose of 1200 µg, whereas in our study, we were using a lower daily dosage (400 µg) vaginally and the repeated medication was given on alternate days.
Although effective, our regimen required additional follow-up visits for drug administration. Patients considered it inconvenient and it was the major reason for withdrawal from the study. The cost was also increased if repeated follow-up was required. An optimal regimen should be acceptable to both health care consumers and providers. We suggest further comparative studies for different dosages and schedule to shorten the treatment regimen and decrease the number of follow-up visits.
In view of the high success rate in the misoprostol group, we support the use of repeated vaginal misoprostol in the management of first-trimester spontaneous miscarriage. Further comparative studies on the dosage and drug treatment interval are needed.
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Acknowledgements |
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Notes |
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References |
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Chung, T.K.H., Cheung, L.P., Leung, T.Y. et al. (1995) Misoprostol in the management of spontaneous abortion. Br. J. Obstet. Gynaecol., 102, 832835.[ISI][Medline]
Chung, T.K.H., Lee, T.S., Cheung, L.P. et al. (1999) Spontaneous abortion: a randomized controlled trial comparing surgical evacuation with conservative management using misoprostol. Fertil. Steril., 71, 10541059.[ISI][Medline]
Farell, R.G., Stonington, D.T. and Ridgeway, R.A. (1982) Incomplete and inevitable abortion: treatment by suction curettage in the emergency department. Ann. Emerg. Med., 11, 652658.[ISI][Medline]
Hammerslough, C.R. (1992) Estimating the probability of spontaneous abortion in the presence of induced abortion and vice versa. Pub. Health. Rep., 107, 269277.[ISI][Medline]
Henshaw, R.C., Cooper, K., El-Refaey, H. et al. (1993) Medical management of miscarriage: non-surgical uterine evacuation of incomplete and inevitable spontaneous abortion. Brit. Med. J., 306, 894895.[ISI][Medline]
Heisterberg, L., Hebjorn, S., Andersen, L.F. and Pertersen, H. (1986) Sequelae of induced first-trimester abortion. A prospective study assessing the role of postabortal pelvic inflammatory disease and prophylactic antibiotics. Am. J. Obstet. Gynecol., 155, 7680.[ISI][Medline]
Herabutya, Y. and Prasertwawat, P.O. (1997) Misoprostol in the management of missed abortion. Int. J. Gynecol. Obstet., 56, 263266.[ISI][Medline]
Ho, P.C., Ngai, S.W., Liu, K.L. et al. (1997) Vaginal misoprostol compared with oral misoprostol in termination of second-trimester pregnancy. Obstet. Gynecol., 90, 735738.
Huges, J., Ryan, M., Henshaw, R. et al. (1996) The costs of treating miscarriage: a comparison of medical and surgical management. Br. J. Obstet. Gynaecol., 103, 12171221.[ISI][Medline]
Laferia, J.J. (1986) Spontaneous abortion. Clin. Obstet. Gynecol., 13, 105114.
Letterie, G.S., Hibbert, M.L. and Ramirez, E.J. (1991) Expectant management of abnormal concentration of human chorionic gonadotropin during the first trimester of pregnancy. Gynecol. Obstet. Invest., 31, 176178.[ISI][Medline]
Meinert, C.L. (1986) In Randomization and the mechanics of treatment masking. Clinical trial design, conduct and analysis. Oxford University Press, Oxford, pp. 90112.
Ngai, S.W., Chan, Y.M., Tang, O.S. and Ho, P.C. (1999) The use of misoprostol for pre-operative cervical dilatation prior to vacuum aspiration: a randomized trial. Hum. Reprod., 14, 21392142.
Nielsen, S. and Hahlin, M. (1995) Expectant management of first trimester spontaneous abortion. Lancet, 345, 8486.[ISI][Medline]
Nielsen, S., Hahlin, M. and Jens, P-C. (1999) Randomised trial comparing expectant with medical management for first trimester miscarriages. Br. J. Obstet. Gynecol., 106, 804807.[ISI][Medline]
Winikoff, B., Ellertson, C. and Clark, S. (1996) Analysis of failure in medical abortion. Contraception, 54, 323327.[ISI][Medline]
Submitted on August 25, 2000; accepted on March 14, 2001.