Medical treatment for early fetal death (less than 24 weeks): Cochrane systematic review
Assessed as up to date: 2006/04/24
In most pregnancies that miscarry, arrest of embryonic or fetal development occurs some time (often weeks) before the miscarriage occurs. Ultrasound examination can reveal abnormal findings during this phase by demonstrating anembryonic pregnancies or embryonic or fetal death. Treatment before 14 weeks has traditionally been surgical but medical treatments may be effective, safe, and acceptable, as may be waiting for spontaneous miscarriage.Objectives
To assess the effectiveness, safety and acceptability of any medical treatment for early pregnancy failure (anembryonic pregnancies or embryonic and fetal deaths before 24 weeks).Search methods
We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 November 2005). We updated this search on 6 August 2012 and added the results to the awaiting classification section of the review.Selection criteria
Randomised trials comparing medical treatment with another treatment (e.g. surgical evacuation), or placebo, or no treatment for early pregnancy failure. Quasi-random studies were excluded.Data collection and analysis
Data were extracted unblinded.Main results
Twenty four studies (1888 women) were included.
Vaginal misoprostol hastens miscarriage (complete or incomplete) when compared with placebo: e.g. miscarriage less than 24 hours (two trials, 138 women, relative risk (RR) 4.73, 95% confidence interval (CI) 2.70 to 8.28), with less need for uterine curettage (two trials, 104 women, RR 0.40, 95% CI 0.26 to 0.60) and no significant increase in nausea or diarrhoea. Lower-dose regimens of vaginal misoprostol tend to be less effective in producing miscarriage (three trials, 247 women, RR 0.85, 95% CI 0.72 to 1.00) with similar incidence of nausea. There seems no clear advantage to administering a 'wet' preparation of vaginal misoprostol or of adding methotrexate, or of using laminaria tents after 14 weeks. Vaginal misoprostol is more effective than vaginal prostaglandin E in avoiding surgical evacuation. Oral misoprostol was less effective than vaginal misoprostol in producing complete miscarriage (two trials, 218 women, RR 0.90, 95% CI 0.82 to 0.99). Sublingual misoprostol had equivalent efficacy to vaginal misoprostol in inducing complete miscarriage but was associated with more frequent diarrhoea. The two trials of mifepristone treatment generated conflicting results. There was no statistically significant difference between vaginal misoprostol and gemeprost in the induction of miscarriage for fetal death after 13 weeks.Authors' conclusions
Available evidence from randomised trials supports the use of vaginal misoprostol as a medical treatment to terminate non-viable pregnancies before 24 weeks. Further research is required to assess effectiveness and safety, optimal route of administration and dose. Conflicting findings about the value of mifepristone need to be resolved by additional study.
[Note: the 108 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
Neilson James P, Hickey Martha, Vazquez Juan C
Medical treatment for early fetal death (less than 24 weeks)
Medical treatments for inevitable miscarriage.
Pregnancies that miscarry can sometimes be identified earlier at an ultrasound scan if the loss is due to the baby having died or no baby having developed. In the past, treatment before 14 weeks has usually been by surgery (D&C) but drugs have now been developed which may be helpful, or waiting for the miscarriage to happen may be a better alternative. The review of trials assessed various potential drug treatments using different routes and different doses, compared with waiting for the miscarriage. This review identified 24 studies involving 1888 women of less than 24 weeks gestation, where the baby had died in the uterus or the baby had not formed in the uterus. Most studies were of good quality. Vaginal misoprostol brought forward the time of the miscarriage, but the studies were too small to adequately assess potential adverse effects, including future fertility. Oral misoprostol seemed less effective than the vaginal route, and women took more sick-leave with the oral drugs. Some women may wish to hasten an inevitable miscarriage, and others may not. It appears that both forms of care can be available to women. Women who are breastfeeding an older baby may prefer to wait rather than have drug treatment. Further research is needed on drug doses, routes of administration and potential adverse effects, including future fertility, and also on women's views of drug treatment, surgery and waiting for spontaneous miscarriage.
Implications for practice
Available evidence from randomised trials supports the use of vaginal misoprostol as one possible option for the treatment of non-viable pregnancies before 24 weeks.
Implications for research
Ultrasound demonstration of early pregnancy failure before 14 weeks is a common problem that merits greater research effort than has occurred to date. Further research is required to assess the effectiveness, safety and side-effects of misoprostol, including optimal route of administration and dose. Conflicting findings about the value of mifepristone need to be resolved by additional study. Women's views about the acceptability of medical treatment, surgical treatment and expectant management should be integral to future research protocols, as should economic assessments. Long-term outcome, notably subsequent fertility, deserves further study in appropriately powered randomised controlled studies.
[Note: the 108 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]Get full text at The Cochrane Library
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