Medical methods for first trimester abortion.
BACKGROUND
Surgical abortion up to 63 days by vacuum aspiration or dilatation and curettage has been the method of choice since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins.


OBJECTIVE
To compare different medical methods for first trimester abortion.


METHODS
The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted.


METHODS
Types of studies. Randomised controlled trials comparing different medical methods (e.g. single drug, combination), ways of application, or different dose regimens, single or combined, for medical abortion, were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant in the first trimester, undergoing medical abortion were the participants. Different medical methods used for first trimester abortion, compared with each other or placebo were included. The outcomes sought include mortality, failure to achieve complete abortion, surgical evacuation (as emergency procedure, non-emergency procedure, or undefined), ongoing pregnancy at follow-up, time until passing of conceptus (> 3-6 hours), blood transfusion, blood loss (measured or clinically relevant drop in haemoglobin), days of bleeding, pain resulting from the procedure (reported by the women or measured by use of analgesics), additional uterotonics used, women's dissatisfaction with the procedure, nausea, vomiting, diarrhoea.


METHODS
Two reviewers independently selected trials for inclusion from the results of the search strategy described previously. The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. A form was designed to facilitate the data extraction. Data were processed using Revman software.


RESULTS
Thirty-nine trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. 2) Mifepristone alone is less effective compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Similarly, the 5 trials included in the comparison of prostaglandin compared to the combined regimen reported in all but one higher effectiveness with the combined regime compared to prostaglandin. The results of these studies were not pooled but the RR of failure with prostaglandin alone is between 1.4 to 3.75 and the 95% confidence intervals indicate statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference when using split dose compared to single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin: there was no statistically significant difference in failure to achieve complete abortion comparing methotrexate administered intramuscular to oral (RR 2.04, 95% CI 0.51 to 8.07). Similarly, early (day 3) vs late (day 5) administration of prostaglandin showed no significant of prostaglandin showed no significant difference (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs methotrexate and no statistically significant differences were observed in effectiveness between the groups.


CONCLUSIONS
Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Misoprostol vaginally is more effective than orally. Some of the results are based on small studies only and therefore carry some uncertainty. Almost all trials were conducted in hospital settings with good access to support and emergency services. It is therefore not clear if the results are readily applicable to under-resourced settings where such services are lacking even if the agents used are available.
Kulier
R
R
Geneva Foundation for Medical Education and Research, Route de Florissant 3, Geneva, Switzerland, CH-1208.
Gülmezoglu
A M
AM
Hofmeyr
G J
GJ
Cheng
L N
LN
Campana
A
A
D000019:Abortifacient Agents / Q000008:administration & dosage*; D000027:Abortion, Incomplete / Q000139:chemically induced; D000028:Abortion, Induced / Q000009:adverse effects / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D015735:Mifepristone / Q000008:administration & dosage; D016595:Misoprostol / Q000008:administration & dosage; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011453:Prostaglandins / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000008:administration & dosage
D000019:Abortifacient Agents; D011453:Prostaglandins; D013629:Tamoxifen; D016595:Misoprostol; D015735:Mifepristone; D008727:Methotrexate