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. 2019 Jun 17;6(6):CD002253.
doi: 10.1002/14651858.CD002253.pub4.

Medical treatment for early fetal death (less than 24 weeks)

Marike Lemmers  1 , Marianne Ac Verschoor, Bobae Veronica Kim, Martha Hickey, Juan C Vazquez, Ben Willem J Mol, James P Neilson
Affiliations

Medical treatment for early fetal death (less than 24 weeks)

Marike Lemmers et al. Cochrane Database Syst Rev. .

Abstract

Background: 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 has traditionally been surgical but medical treatments may be effective, safe, and acceptable, as may be waiting for spontaneous miscarriage. This is an update of a review first published in 2006.

Objectives: To assess, from clinical trials, the effectiveness and safety of different medical treatments for the termination of non-viable pregnancies.

Search methods: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (24 October 2018) and reference lists of retrieved studies.

Selection criteria: Randomised trials comparing medical treatment with another treatment (e.g. surgical evacuation), or placebo, or no treatment for early pregnancy failure. Quasi-randomised studies were excluded. Cluster-randomised trials were eligible for inclusion, as were studies reported in abstract form, if sufficient information was available to assess eligibility.

Data collection and analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach.

Main results: Forty-three studies (4966 women) were included. The main interventions examined were vaginal, sublingual, oral and buccal misoprostol, mifepristone and vaginal gemeprost. These were compared with surgical management, expectant management, placebo, or different types of medical interventions were compared with each other. The review includes a wide variety of different interventions which have been analysed across 23 different comparisons. Many of the comparisons consist of single studies. We limited the grading of the quality of evidence to two main comparisons: vaginal misoprostol versus placebo and vaginal misoprostol versus surgical evacuation of the uterus. Risk of bias varied widely among the included trials. The quality of the evidence varied between the different comparisons, but was mainly found to be very-low or low quality.Vaginal misoprostol versus placeboVaginal misoprostol may hasten miscarriage when compared with placebo: e.g. complete miscarriage (5 trials, 305 women, risk ratio (RR) 4.23, 95% confidence interval (CI) 3.01 to 5.94; low-quality evidence). No trial reported on pelvic infection rate for this comparison. Vaginal misoprostol made little difference to rates of nausea (2 trials, 88 women, RR 1.38, 95% CI 0.43 to 4.40; low-quality evidence), diarrhoea (2 trials, 88 women, RR 2.21, 95% CI 0.35 to 14.06; low-quality evidence) or to whether women were satisfied with the acceptability of the method (1 trial, 32 women, RR 1.17, 95% CI 0.83 to 1.64; low-quality evidence). It is uncertain whether vaginal misoprostol reduces blood loss (haemoglobin difference > 10 g/L) (1 trial, 50 women, RR 1.25, 95% CI 0.38 to 4.12; very-low quality) or pain (opiate use) (1 trial, 84 women, RR 5.00, 95% CI 0.25 to 101.11; very-low quality), because the quality of the evidence for these outcomes was found to be very low.Vaginal misoprostol versus surgical evacuation Vaginal misoprostol may be less effective in accomplishing a complete miscarriage compared to surgical management (6 trials, 943 women, average RR 0.40, 95% CI 0.32 to 0.50; Heterogeneity: Tau² = 0.03, I² = 46%; low-quality evidence) and may be associated with more nausea (1 trial, 154 women, RR 21.85, 95% CI 1.31 to 364.37; low-quality evidence) and diarrhoea (1 trial, 154 women, RR 40.85, 95% CI 2.52 to 662.57; low-quality evidence). There may be little or no difference between vaginal misoprostol and surgical evacuation for pelvic infection (1 trial, 618 women, RR 0.73, 95% CI 0.39 to 1.37; low-quality evidence), blood loss (post-treatment haematocrit (%) (1 trial, 50 women, mean difference (MD) 1.40%, 95% CI -3.51 to 0.71; low-quality evidence), pain relief (1 trial, 154 women, RR 1.42, 95% CI 0.82 to 2.46; low-quality evidence) or women's satisfaction/acceptability of method (1 trial, 45 women, RR 0.67, 95% CI 0.40 to 1.11; low-quality evidence).Other comparisonsBased on findings from a single trial, vaginal misoprostol was more effective at accomplishing complete miscarriage than expectant management (614 women, RR 1.25, 95% CI 1.09 to 1.45). There was little difference between vaginal misoprostol and sublingual misoprostol (5 trials, 513 women, average RR 0.84, 95% CI 0.61 to 1.16; Heterogeneity: Tau² = 0.10, I² = 871%; or between oral and vaginal misoprostol in terms of complete miscarriage at less than 13 weeks (4 trials, 418 women), average RR 0.68, 95% CI 0.45 to 1.03; Heterogeneity: Tau² = 0.13, I² = 90%). However, there was less abdominal pain with vaginal misoprostol in comparison to sublingual (3 trials, 392 women, RR 0.58, 95% CI 0.46 to 0.74). A single study (46 women) found mifepristone to be more effective than placebo: miscarriage complete by day five after treatment (46 women, RR 9.50, 95% CI 2.49 to 36.19). However the quality of this evidence is very low: there is a very serious risk of bias with signs of incomplete data and no proper intention-to-treat analysis in the included study; and serious imprecision with wide confidence intervals. Mifepristone did not appear to further hasten miscarriage when added to a misoprostol regimen (3 trials, 447 women, RR 1.18, 95% CI 0.95 to 1.47).

Authors' conclusions: Available evidence from randomised trials suggests that medical treatment with vaginal misoprostol may be an acceptable alternative to surgical evacuation or expectant management. In general, side effects of medical treatment were minor, consisting mainly of nausea and diarrhoea. There were no major differences in effectiveness between different routes of administration. Treatment satisfaction was addressed in only a few studies, in which the majority of women were satisfied with the received intervention. Since the quality of evidence is low or very low for several comparisons, mainly because they included only one or two (small) trials; further research is necessary to assess the effectiveness, safety and side effects, optimal route of administration and dose of different medical treatments for early fetal death.

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Conflict of interest statement

Marike Lemmers: for previous work (the MisoREST trial), which focuses on miscarriage treatment, my institution (AMC) received a ZonMW grant. ZonMW is a Dutch governmental organization for Health Research and Development.

Marianne AC Verschoor: my institution linked received a ZonMW grant for the MisoREST study.

Bobae Veronica Kim: none known.

Martha Hickey: none known.

Juan C Vazquez: none known.

Ben Willem J Mol: my institution and I have received payment for consultancy from ObsEva Geneva. I have received payment for review preparation from Eur J Obste Gynaecol and I have received travel/accommodation/meeting expenses for various non‐commercial scientific meetings.

James P Neilson: none known.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Vaginal misoprostol versus placebo, Outcome 1 Complete miscarriage.
1.2
1.2. Analysis
Comparison 1 Vaginal misoprostol versus placebo, Outcome 2 Death or serious complications: uterine perforation.
1.3
1.3. Analysis
Comparison 1 Vaginal misoprostol versus placebo, Outcome 3 Blood transfusion.
1.4
1.4. Analysis
Comparison 1 Vaginal misoprostol versus placebo, Outcome 4 Blood loss: haemoglobin difference > 10 g/L.
1.5
1.5. Analysis
Comparison 1 Vaginal misoprostol versus placebo, Outcome 5 Days of bleeding: vaginal bleeding 2 weeks after treatment.
1.6
1.6. Analysis
Comparison 1 Vaginal misoprostol versus placebo, Outcome 6 Nausea.
1.7
1.7. Analysis
Comparison 1 Vaginal misoprostol versus placebo, Outcome 7 Diarrhoea.
1.8
1.8. Analysis
Comparison 1 Vaginal misoprostol versus placebo, Outcome 8 Pain (opiate use).
1.9
1.9. Analysis
Comparison 1 Vaginal misoprostol versus placebo, Outcome 9 Woman's satisfaction with treatment.
2.1
2.1. Analysis
Comparison 2 Vaginal misoprostol versus expectant management, Outcome 1 Complete miscarriage.
2.2
2.2. Analysis
Comparison 2 Vaginal misoprostol versus expectant management, Outcome 2 Pelvic infection.
3.1
3.1. Analysis
Comparison 3 Vaginal misoprostol versus surgical evacuation of uterus, Outcome 1 Complete miscarriage.
3.2
3.2. Analysis
Comparison 3 Vaginal misoprostol versus surgical evacuation of uterus, Outcome 2 Uterine perforation.
3.3
3.3. Analysis
Comparison 3 Vaginal misoprostol versus surgical evacuation of uterus, Outcome 3 Blood loss: post‐treatment haematocrit (%).
3.4
3.4. Analysis
Comparison 3 Vaginal misoprostol versus surgical evacuation of uterus, Outcome 4 Pain relief.
3.5
3.5. Analysis
Comparison 3 Vaginal misoprostol versus surgical evacuation of uterus, Outcome 5 Pelvic infection.
3.6
3.6. Analysis
Comparison 3 Vaginal misoprostol versus surgical evacuation of uterus, Outcome 6 Nausea.
3.7
3.7. Analysis
Comparison 3 Vaginal misoprostol versus surgical evacuation of uterus, Outcome 7 Diarrhoea.
3.8
3.8. Analysis
Comparison 3 Vaginal misoprostol versus surgical evacuation of uterus, Outcome 8 Woman's satisfaction.
4.1
4.1. Analysis
Comparison 4 Vaginal misoprostol versus vaginal dinoprostone, Outcome 1 Complete miscarriage.
4.2
4.2. Analysis
Comparison 4 Vaginal misoprostol versus vaginal dinoprostone, Outcome 2 Blood transfusion.
4.3
4.3. Analysis
Comparison 4 Vaginal misoprostol versus vaginal dinoprostone, Outcome 3 Nausea.
4.4
4.4. Analysis
Comparison 4 Vaginal misoprostol versus vaginal dinoprostone, Outcome 4 Duration of hospital stay (days).
5.1
5.1. Analysis
Comparison 5 Vaginal misoprostol lower versus higher‐dose regimens, Outcome 1 Complete miscarriage < 13 weeks.
5.2
5.2. Analysis
Comparison 5 Vaginal misoprostol lower versus higher‐dose regimens, Outcome 2 Complete miscarriage 13‐23 weeks.
5.3
5.3. Analysis
Comparison 5 Vaginal misoprostol lower versus higher‐dose regimens, Outcome 3 Nausea.
5.4
5.4. Analysis
Comparison 5 Vaginal misoprostol lower versus higher‐dose regimens, Outcome 4 Diarrhoea.
6.1
6.1. Analysis
Comparison 6 Vaginal misoprostol wet versus dry vaginal preparations, Outcome 1 Complete miscarriage.
6.2
6.2. Analysis
Comparison 6 Vaginal misoprostol wet versus dry vaginal preparations, Outcome 2 Diarrhoea.
6.3
6.3. Analysis
Comparison 6 Vaginal misoprostol wet versus dry vaginal preparations, Outcome 3 Vomiting.
6.4
6.4. Analysis
Comparison 6 Vaginal misoprostol wet versus dry vaginal preparations, Outcome 4 Acceptability of method: would wish/probably wish same treatment in future nonviable pregnancy.
7.1
7.1. Analysis
Comparison 7 Vaginal misoprostol + methotrexate versus vaginal misoprostol alone, Outcome 1 Complete miscarriage.
7.2
7.2. Analysis
Comparison 7 Vaginal misoprostol + methotrexate versus vaginal misoprostol alone, Outcome 2 Haemorrhage.
7.3
7.3. Analysis
Comparison 7 Vaginal misoprostol + methotrexate versus vaginal misoprostol alone, Outcome 3 Pain relief.
8.1
8.1. Analysis
Comparison 8 Vaginal misoprostol plus laminaria tents versus vaginal misoprostol alone, Outcome 1 Complete miscarriage.
9.1
9.1. Analysis
Comparison 9 Vaginal misoprostol versus sublingual misoprostol, Outcome 1 Complete miscarriage < 13 weeks.
9.2
9.2. Analysis
Comparison 9 Vaginal misoprostol versus sublingual misoprostol, Outcome 2 Complete miscarriage 13‐23 weeks.
9.3
9.3. Analysis
Comparison 9 Vaginal misoprostol versus sublingual misoprostol, Outcome 3 Blood loss: excessive (> menstruation).
9.4
9.4. Analysis
Comparison 9 Vaginal misoprostol versus sublingual misoprostol, Outcome 4 Pain.
9.5
9.5. Analysis
Comparison 9 Vaginal misoprostol versus sublingual misoprostol, Outcome 5 Nausea.
9.6
9.6. Analysis
Comparison 9 Vaginal misoprostol versus sublingual misoprostol, Outcome 6 Vomiting.
9.7
9.7. Analysis
Comparison 9 Vaginal misoprostol versus sublingual misoprostol, Outcome 7 Diarrhoea.
10.1
10.1. Analysis
Comparison 10 Vaginal misoprostol versus intravenous oxytocin, Outcome 1 Complete miscarriage 13‐23 weeks.
10.2
10.2. Analysis
Comparison 10 Vaginal misoprostol versus intravenous oxytocin, Outcome 2 Blood loss: excessive.
11.1
11.1. Analysis
Comparison 11 Vaginal misoprostol versus vaginal gemeprost, Outcome 1 Complete miscarriage 13‐23 weeks.
11.2
11.2. Analysis
Comparison 11 Vaginal misoprostol versus vaginal gemeprost, Outcome 2 Opiates for pain relief.
11.3
11.3. Analysis
Comparison 11 Vaginal misoprostol versus vaginal gemeprost, Outcome 3 Vomiting.
11.4
11.4. Analysis
Comparison 11 Vaginal misoprostol versus vaginal gemeprost, Outcome 4 Diarrhoea.
12.1
12.1. Analysis
Comparison 12 Sublingual misoprostol versus oral misoprostol, Outcome 1 Complete miscarriage.
12.2
12.2. Analysis
Comparison 12 Sublingual misoprostol versus oral misoprostol, Outcome 2 Pain.
12.3
12.3. Analysis
Comparison 12 Sublingual misoprostol versus oral misoprostol, Outcome 3 Nausea and/or vomiting.
12.4
12.4. Analysis
Comparison 12 Sublingual misoprostol versus oral misoprostol, Outcome 4 Diarrhoea.
12.5
12.5. Analysis
Comparison 12 Sublingual misoprostol versus oral misoprostol, Outcome 5 Woman's satisfaction with treatment.
13.1
13.1. Analysis
Comparison 13 Sublingual powdery versus sublingual compact misoprostol, Outcome 1 Complete miscarriage.
13.2
13.2. Analysis
Comparison 13 Sublingual powdery versus sublingual compact misoprostol, Outcome 2 Nausea/vomiting.
13.3
13.3. Analysis
Comparison 13 Sublingual powdery versus sublingual compact misoprostol, Outcome 3 Diarrhoea.
14.1
14.1. Analysis
Comparison 14 Sublingual misoprostol with versus without extended course, Outcome 1 Complete miscarriage.
14.2
14.2. Analysis
Comparison 14 Sublingual misoprostol with versus without extended course, Outcome 2 Nausea.
14.3
14.3. Analysis
Comparison 14 Sublingual misoprostol with versus without extended course, Outcome 3 Pain.
14.4
14.4. Analysis
Comparison 14 Sublingual misoprostol with versus without extended course, Outcome 4 Vomiting.
14.5
14.5. Analysis
Comparison 14 Sublingual misoprostol with versus without extended course, Outcome 5 Diarrhoea.
15.1
15.1. Analysis
Comparison 15 Sublingual + vaginal misoprostol versus only vaginal misoprostol, Outcome 1 Complete miscarriage.
15.2
15.2. Analysis
Comparison 15 Sublingual + vaginal misoprostol versus only vaginal misoprostol, Outcome 2 Blood loss: haemoglobin level.
15.3
15.3. Analysis
Comparison 15 Sublingual + vaginal misoprostol versus only vaginal misoprostol, Outcome 3 Nausea.
15.4
15.4. Analysis
Comparison 15 Sublingual + vaginal misoprostol versus only vaginal misoprostol, Outcome 4 Vomiting.
15.5
15.5. Analysis
Comparison 15 Sublingual + vaginal misoprostol versus only vaginal misoprostol, Outcome 5 Diarrhoea.
15.6
15.6. Analysis
Comparison 15 Sublingual + vaginal misoprostol versus only vaginal misoprostol, Outcome 6 Pain.
15.7
15.7. Analysis
Comparison 15 Sublingual + vaginal misoprostol versus only vaginal misoprostol, Outcome 7 Woman's satisfaction with treatment.
16.1
16.1. Analysis
Comparison 16 Oral misoprostol versus vaginal misoprostol, Outcome 1 Complete miscarriage < 13 weeks.
16.2
16.2. Analysis
Comparison 16 Oral misoprostol versus vaginal misoprostol, Outcome 2 Complete miscarriage > 13‐23 weeks.
16.3
16.3. Analysis
Comparison 16 Oral misoprostol versus vaginal misoprostol, Outcome 3 Blood loss: excessive.
16.4
16.4. Analysis
Comparison 16 Oral misoprostol versus vaginal misoprostol, Outcome 4 Pain (visual analogue scale).
16.5
16.5. Analysis
Comparison 16 Oral misoprostol versus vaginal misoprostol, Outcome 5 Pain.
16.6
16.6. Analysis
Comparison 16 Oral misoprostol versus vaginal misoprostol, Outcome 6 Vomiting.
16.7
16.7. Analysis
Comparison 16 Oral misoprostol versus vaginal misoprostol, Outcome 7 Nausea.
16.8
16.8. Analysis
Comparison 16 Oral misoprostol versus vaginal misoprostol, Outcome 8 Diarrhoea.
16.9
16.9. Analysis
Comparison 16 Oral misoprostol versus vaginal misoprostol, Outcome 9 Woman's satisfaction with treatment.
17.1
17.1. Analysis
Comparison 17 Oral misoprostol + mifepristone versus expectant management, Outcome 1 Complete miscarriage.
17.2
17.2. Analysis
Comparison 17 Oral misoprostol + mifepristone versus expectant management, Outcome 2 Blood loss (severe).
17.3
17.3. Analysis
Comparison 17 Oral misoprostol + mifepristone versus expectant management, Outcome 3 Days of bleeding.
17.4
17.4. Analysis
Comparison 17 Oral misoprostol + mifepristone versus expectant management, Outcome 4 Pain.
17.5
17.5. Analysis
Comparison 17 Oral misoprostol + mifepristone versus expectant management, Outcome 5 Pelvic infection.
17.6
17.6. Analysis
Comparison 17 Oral misoprostol + mifepristone versus expectant management, Outcome 6 Woman's satisfaction with treatment (visual analogue scale day 14).
18.1
18.1. Analysis
Comparison 18 Buccal misoprostol lower versus higher‐dose regimen, Outcome 1 Complete miscarriage 13‐23 weeks.
18.2
18.2. Analysis
Comparison 18 Buccal misoprostol lower versus higher‐dose regimen, Outcome 2 Nausea.
18.3
18.3. Analysis
Comparison 18 Buccal misoprostol lower versus higher‐dose regimen, Outcome 3 Vomiting.
18.4
18.4. Analysis
Comparison 18 Buccal misoprostol lower versus higher‐dose regimen, Outcome 4 Diarrhoea.
18.5
18.5. Analysis
Comparison 18 Buccal misoprostol lower versus higher‐dose regimen, Outcome 5 Pain.
18.6
18.6. Analysis
Comparison 18 Buccal misoprostol lower versus higher‐dose regimen, Outcome 6 Woman's satisfaction with treatment (satisfied or very satisfied).
19.1
19.1. Analysis
Comparison 19 Mifepristone versus placebo, Outcome 1 Complete miscarriage.
19.2
19.2. Analysis
Comparison 19 Mifepristone versus placebo, Outcome 2 Days of bleeding.
19.3
19.3. Analysis
Comparison 19 Mifepristone versus placebo, Outcome 3 Pain.
20.1
20.1. Analysis
Comparison 20 Mifepristone + vaginal misoprostol versus vaginal misoprostol alone, Outcome 1 Complete miscarriage.
20.2
20.2. Analysis
Comparison 20 Mifepristone + vaginal misoprostol versus vaginal misoprostol alone, Outcome 2 Blood transfusion.
20.3
20.3. Analysis
Comparison 20 Mifepristone + vaginal misoprostol versus vaginal misoprostol alone, Outcome 3 Pelvic infection.
20.4
20.4. Analysis
Comparison 20 Mifepristone + vaginal misoprostol versus vaginal misoprostol alone, Outcome 4 nausea.
20.5
20.5. Analysis
Comparison 20 Mifepristone + vaginal misoprostol versus vaginal misoprostol alone, Outcome 5 Diarrhoea.
20.6
20.6. Analysis
Comparison 20 Mifepristone + vaginal misoprostol versus vaginal misoprostol alone, Outcome 6 Woman's satisfaction.
21.1
21.1. Analysis
Comparison 21 Vaginal gemeprost versus surgical evacuation of uterus, Outcome 1 Complete miscarriage.
21.2
21.2. Analysis
Comparison 21 Vaginal gemeprost versus surgical evacuation of uterus, Outcome 2 Death or serious complications (uterine perforation).
21.3
21.3. Analysis
Comparison 21 Vaginal gemeprost versus surgical evacuation of uterus, Outcome 3 Nausea.
22.1
22.1. Analysis
Comparison 22 Misoprostol intravaginal extraamniotic versus vaginal misoprostol, Outcome 1 Complete miscarriage.
22.2
22.2. Analysis
Comparison 22 Misoprostol intravaginal extraamniotic versus vaginal misoprostol, Outcome 2 Nausea.
22.3
22.3. Analysis
Comparison 22 Misoprostol intravaginal extraamniotic versus vaginal misoprostol, Outcome 3 Vomiting.
22.4
22.4. Analysis
Comparison 22 Misoprostol intravaginal extraamniotic versus vaginal misoprostol, Outcome 4 Diarrhoea.
22.5
22.5. Analysis
Comparison 22 Misoprostol intravaginal extraamniotic versus vaginal misoprostol, Outcome 5 Pain (use of analgesics).
22.6
22.6. Analysis
Comparison 22 Misoprostol intravaginal extraamniotic versus vaginal misoprostol, Outcome 6 Time to expulsion.
23.1
23.1. Analysis
Comparison 23 Vaginal misoprostol with versus without extended course, Outcome 1 Complete miscarriage.
23.2
23.2. Analysis
Comparison 23 Vaginal misoprostol with versus without extended course, Outcome 2 Nausea.
23.3
23.3. Analysis
Comparison 23 Vaginal misoprostol with versus without extended course, Outcome 3 Vomiting.
23.4
23.4. Analysis
Comparison 23 Vaginal misoprostol with versus without extended course, Outcome 4 Diarrhoea.
23.5
23.5. Analysis
Comparison 23 Vaginal misoprostol with versus without extended course, Outcome 5 Pain (use of analgesics).
23.6
23.6. Analysis
Comparison 23 Vaginal misoprostol with versus without extended course, Outcome 6 Woman's satisfaction with treatment.
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References

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    1. Gilles JM, Creinin MD, Barnhart K, Westhoff C, Frederick MM, Zhang J. A randomized trial of saline solution‐moistened misoprostol versus dry misoprostol for the first‐trimester pregnancy failure. American Journal of Obstetrics and Gynecology 2004;190:389‐94. - PMC - PubMed
Graziosi 2004 {published data only}
    1. Graziosi GC, Bruinse HW, Reuwer PJ, Teteringen O, Mol BW. Fertility outcome after a randomized trial comparing curettage with misoprostol for treatment of early pregnancy failure. Human Reproduction 2005;20:1749‐50. - PubMed
    1. Graziosi GC, Bruinse HW, Reuwer PJ, Kessel PH, Westerweel PE, Mol BW. Misoprostol versus curettage in women with early pregnancy failure: impact on women's health‐related quality of life. A randomized controlled trial. Human Reproduction 2005;20:2340‐7. - PubMed
    1. Graziosi GC, Mol BW, Reuwer PJ, Drogtrop A, Bruinse HW. Misoprostol versus curettage in women with early pregnancy failure after initial expectant management: a randomized trial. Human Reproduction 2004;19:1894‐9. - PubMed
    1. Graziosi GC, Steeg JW, Reuwer PH, Drogtrop AP, Bruinse HW, Mol BW. Economic evaluation of misoprostol in the treatment of early pregnancy failure compared to curettage after an expectant management. Human Reproduction 2005;20:1067‐71. - PubMed
Herabutya 1997 {published data only}
    1. Herabutya Y, O‐Prasertsawat P. Misoprostol in the management of missed abortion. International Journal of Gynecology & Obstetrics 1997;56:263‐6. - PubMed
Jain 1996* {published data only}
    1. Jain JK, Mishell DR. A comparison of misoprostol with and without laminaria tents for induction of second‐trimester abortion. American Journal of Obstetrics and Gynecology 1996;175:173‐7. - PubMed
Kara 1999* {published data only}
    1. Kara M, Ozden S, Eroglu M, Cetin A, Arioglu P. Comparison of misoprostol and dinoproston administration for the induction of labour in second trimester pregnancies in cases of intrauterine fetal loss. Italian Journal of Gynecology and Obstetrics 1999;1:13‐6.
Kovavisarach 2002 {published data only}
    1. Kovavisarach E, Sathapanachai U. Intravaginal 400 micrograms misoprostol for pregnancy termination in cases of blighted ovum: a randomised controlled trial. Australian and New Zealand Journal of Obstetrics and Gynaecology 2002;42:161‐3. - PubMed
    1. Sathapanachai U. Intravaginal 400 micrograms misoprostol for pregnancy termination in cases of blighted ovum. Thai Journal of Obstetrics and Gynaecology 2000;12(4):363. - PubMed
Kovavisarach 2005 {published data only}
    1. Kovavisarach E, Jamnansiri C. Intravaginal misoprostol 600mcg and 800mcg for the treatment of early pregnancy failure. International Journal of Gynecology & Obstetrics 2005;90:208‐12. - PubMed
Kushwah 2009 {published data only}
    1. Kushwah B, Singh A. Sublingual versus oral misoprostol for uterine evacuation following early pregnancy failure. International Journal of Gynecology & Obstetrics 2009;106(1):43‐5. - PubMed
    1. Kushwah DS, Kushwah B, Salman MT, Verma VK. Acceptability and safety profile of oral and sublingual misoprostol for uterine evacuation following early fetal demise. Indian Journal of Pharmacology 2011;43(3):306‐10. [DOI: 10.4103/0253-7613.81513; CRSREF: 3293000] - DOI - PMC - PubMed
Lelaidier 1993 {published data only}
    1. Lelaidier C, Baton‐Saint‐Mleux C, Fernandez H, Bourget P, Frydman R. Mifepristone (RU 486) induces embryo expulsion in first trimester non‐developing pregnancies: a prospective randomized trial. Human Reproduction 1993;8:492‐5. - PubMed
Lister 2005 {published data only}
    1. Lister MS, Shaffer LE, Bell JG, Lutter KQ, Moorma KH. Randomized, double‐blind, placebo‐controlled trial of vaginal misoprostol for management of early pregnancy failures. American Journal of Obstetrics and Gynecology 2005;193:1338‐43. - PubMed
Marwah 2016 {published data only}
    1. Marwah S, Gupta S, Batra NP, Bhasin V, Sarna V, Kaur N. A comparative study to evaluate the efficacy of vaginal vs oral prostaglandin E1 analogue (misoprostol) in management of first trimester missed abortion. Journal of Clinical and Diagnostic Research 2016;10(5):QC14‐8. - PMC - PubMed
Mitwaly 2016* {published data only}
    1. Mitwally AB. Intra uterine extra amniotic (200 µg) versus vaginal (200 µg) misoprostol for second trimester pregnancy termination: randomized controlled trial. clinicaltrials.gov/ct2/show/NCT02669420 (first received 1 February 2016).
    1. Mitwaly AB, Abbas AM, Abdellah MS. Intra uterine extra‐amniotic versus vaginal misoprostol for termination of second trimester miscarriage: a randomized controlled trial. International Journal of Reproductive Biomedicine 2016;14(10):643‐8. - PMC - PubMed
Mizrachi 2017 {published data only}
    1. Mizrachi Y, Dekalo A, Gluck O, Miremberg H, Dafna L, Feldstein O, et al. Single versus repeat doses of misoprostol for treatment of early pregnancy loss‐a randomized clinical trial. Human Reproduction 2017;32(6):1202‐7. - PubMed
Muffley 2002 {published data only}
    1. Muffley PE, Stitely ML, Gherman RB. Early intrauterine pregnancy failure: a randomized trial of medical versus surgical treatment. American Journal of Obstetrics and Gynecology 2002;187:321‐6. - PubMed
Ngoc 2004 {published data only}
    1. Ngoc NT, Blum J, Westheimer E, Quan TTV, Winikoff B. Medical treatment of missed abortion using misoprostol. International Journal of Gynecology & Obstetrics 2004;87:138‐42. - PubMed
Nielsen 1999 {published data only}
    1. Nielsen S, Hahlin M, Platz‐Christensen J. Expectant management or pharmacological treatment for first trimester spontaneous abortion: a randomised trial. Acta Obstetricia et Gynecologica Scandinavica 1997;76(167:2):77.
    1. Nielsen S, Hahlin M, Platz‐Christensen J. Randomised trial comparing expectant with medical management for first trimester miscarriages. British Journal of Obstetrics and Gynaecology 1999;106:804‐7. - PubMed
Niromanesh 2005* {published data only}
    1. Niromanesh S, Hashemi‐Feasharaki M, Mosavi‐Jarrahi A. Second trimester abortion using intravaginal misoprostol. International Journal of Gynecology & Obstetrics 2005;89:276‐7. - PubMed
Petersen 2013 {published data only}
    1. Petersen SG, Perkins A, Gibbons K, Bertolone J, Devenish‐Meares P, Cave D, et al. Can we use a lower intravaginal dose of misoprostol in the medical management of miscarriage? A randomised controlled study. Australian & New Zealand Journal of Obstetrics & Gynaecology 2013;53(1):64‐73. - PubMed
Rita 2006 {published data only}
    1. Rita, Gupta S, Kumar S. A randomised comparison of oral and vaginal misoprostol for medical management of first trimester missed abortion. JK Science 2006;8(1):35‐8.
Saichua 2009 {published data only}
    1. Saichua C, Phupong V. A randomized controlled trial comparing powdery sublingual misoprostol and sublingual misoprostol tablet for management of embryonic death or anembryonic pregnancy. Archives of Gynecology and Obstetrics 2009;280(3):431‐5. - PubMed
Schreiber 2018 {published data only}
    1. Schreiber CA, Sonalkar S, Barnhart KT, Ratcliffe SJ, Creinin MD, Atrio J. Mifepristone pretreatment for the medical management of early pregnancy loss. New England Journal of Medicine 2018;378(23):2161‐70. - PMC - PubMed
Shah 2010* {published data only}
    1. Shah N, Azam SI, Khan NH. Sublingual versus vaginal misoprostol in the management of missed miscarriage. JPMA ‐ Journal of the Pakistan Medical Association 2010;60(2):113‐6. - PubMed
Sinha 2018 {published data only}
    1. Sinha P, Suneja A, Guleria K, Aggarwal R, Vaid NB. Comparison of mifepristone followed by misoprostol with misoprostol alone for treatment of early pregnancy failure: a randomized double‐blind placebo‐controlled trial. Journal of Obstetrics and Gynecology of India 2018;68(1):39‐44. - PMC - PubMed
Sonsanoh 2014 {published data only}
    1. Sonsanoh A, Chullapram T. Comparison of sublingual and vaginal misoprostol for termination of early pregnancy failure: a randomized controlled trial. Thai Journal of Obstetrics and Gynaecology 2014;22(3):128‐36.
Tang 2003 {published data only}
    1. Tang OS, Lau WN, Ng EHY, Lee SW, Ho PC. A prospective randomized study to compare the use of repeated doses of vaginal with sublingual misoprostol in the management of first trimester silent miscarriage. Human Reproduction 2003;18:176‐81. - PubMed
Tang 2006 {published data only}
    1. Tang OS, Ong CY, Tse KY, Ng EH, Lee SW, Ho PC. A randomized trial to compare the use of sublingual misoprostol with or without an additional 1 week course for the management of first trimester silent miscarriage. Human Reproduction 2006;21(1):189‐92. - PubMed
Tanha 2010a {published data only}
    1. Tanha FD, Feizi M, Shariat M. Sublingual versus vaginal misoprostol for the management of missed abortion. Journal of Obstetrics and Gynaecology Research 2010;36(3):525‐32. - PubMed
Trinder 2006 {published data only}
    1. Petrou S, Trinder J, Brocklehurst P, Smith L. Economic evaluation of alternative management methods of first‐trimester miscarriage based on results from the MIST trial. BJOG: An International Journal of Obstetrics & Gynaecology 2006;113(8):879‐89. [DOI: 10.1111/j.1471-0528.2006.00998.x; CRSREF: 3293040] - DOI - PubMed
    1. Smith L. Extension to: randomised controlled trial of expectant, medical and surgical management of early miscarriage. Research Findings Register (www.refer.nhs.uk) (accessed 7 March 2006) 2006.
    1. Trinder J, Brocklehurst P, Porter R, Read M, Vyas S, Smith L. Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial). BMJ 2006;332(7552):1235‐40. - PMC - PubMed
Wood 2002 {published data only}
    1. Wood SL, Brain PH. Medical management of missed abortion: a randomized clinical trial. Obstetrics & Gynecology 2002;99:563‐6. - PubMed

References to studies excluded from this review

Abbas 2018 {published data only}
    1. Abbas AM, NCT03584698. The effect of adding vaginal evening primrose oil to misoprostol during induction of second‐trimester missed miscarriage; a randomized controlled trial. https://clinicaltrials.gov/ct2/show/NCT03584698 (12 July 2018).
Abdel Fattah 1997 {published data only}
    1. Abdel Fattah IH. PGE1 analogue for the induction of midtrimester abortion in cases of intrauterine fetal death. Acta Obstetricia et Gynecologica Scandinavica Supplement 1997;76(167:2):26.
Abd‐El‐Maeboud 2012 {published data only}
    1. Abd‐El‐Maeboud KH, Ghazy A, Ibrahim A, Hassan N, El‐Bohoty A, Gamal‐El‐Din I. Vaginal acidity enhancement with a 3% acetic acid gel prior to misoprostol treatment for pregnancy termination in the midtrimester. International Journal of Gynecology and Obstetrics 2012;119(3):248‐52. - PubMed
Al‐Bdour 2007 {published data only}
    1. Al‐Bdour AN, Akasheh H, Al‐Jayousi T. Missed abortion: termination using single‐dose versus two doses of vaginal misoprostol tablets. Pakistan Journal of Medical Sciences 2007;23(6):920‐3.
Ali 2018 {published data only}
    1. Ali MK, Botros HA, Mostafa SA. Foley's catheter balloon for induction of mid‐trimester missed abortion with or without traction applied: a randomized controlled trial. Journal of Maternal‐Fetal & Neonatal Medicine 2018 [Epub ahead of print]. - PubMed
Almog 2005 {published data only}
    1. Almog B, Levin I, Winkler N, Fainaru O, Pauzner D, Lessing JB, et al. The contribution of laminaria placement for cervical ripening in second trimester termination of pregnancy induced by intra‐amniotic injection of prostaglandin F2alpha followed by concentrated oxytocin infusion. European Journal of Obstetrics & Gynecology and Reproductive Biology 2005;118:32‐5. - PubMed
Altaf 2006 {published data only}
    1. Altaf F, Sultana N, Iqbal N. Therapeutic abortions; efficacy of intra‐vaginal misoprostol in comparison to extra amniotically administered prostaglandin f2a. Professional Medical Journal 2006;13(3):417‐22.
Amjad 1999 {published data only}
    1. Amjad T, Akhtar S. Termination of pregnancy with foetal death in second trimester: Foley's catheter versus extra amniotic prostaglandins. Journal of College of Physicians & Surgeons Pakistan 1999;9(9):403‐5.
Anderman 2000 {published data only}
    1. Anderman S, Jaschevatzky OE, Ballas S. Comparison between a double balloon device and the foley catheter in extraamniotic prostaglandin F2a infusion for termination of midtrimester missed abortion. XVI FIGO World Congress of Obstetrics & Gynecology; 2000 Sept 3‐8; Washington DC, USA. 2000:162.
Anderson 2009 {published data only}
    1. Anderson J, Gouk E, Young L, Turnbull L, Sayeed G, Elattar A, et al. A randomised controlled trial of oral versus vaginal misoprostol for medical management of early fetal demise. International Journal of Gynecology & Obstetrics 2009;107(Suppl 2):S533.
Ara 2009 {published data only}
    1. Ara G, Nargis S, Khatun R, Saha A. Vaginal misoprostol as a medical management in early pregnancy loss. International Journal of Gynecology & Obstetrics 2009;107(Suppl 2):S533‐S534.
Arellano 2009 {published data only}
    1. Arellano M, Durocher J, Leon W, Montesinos R, Pena M, Winikoff B. Introduction of misoprostol for incomplete abortion care in Latin America: evidence from Ecuador. International Journal of Gynecology & Obstetrics 2009;107(Suppl 2):S49.
Avila‐Vergara 1997 {published data only}
    1. Avila‐Vergara MA, Morgan‐Ortiz F, Fragoza‐Sosa O, Haro‐Garcia L. Cervical labor induction with prostaglandin E2 in patients with fetal death [Maduracion cervical con prostaglandina E2 en pacientes con feto muerto]. Ginecologia y Obstetricia de Mexico 1997;65:155‐8. - PubMed
Aye 2017 {published data only}
    1. Aye TT, Aung KL, Myint SS. A comparative study on effect of sublingual versus vaginal misoprostol in management of first trimester miscarriage in Magway Teaching Hospital. Journal of Obstetrics and Gynaecology Research 2017;43:185‐6, Abstract no: 9020.
Azra 2007 {published data only}
    1. Azra B, Shakeel S, Nilofer M. A comparison of two protocols of intra vaginal misoprostol for second trimester medical termination of pregnancy. Pakistan Armed Forces Medical Journal 2007;57(1):61‐5.
Bagratee 2009 {published data only}
    1. Bagratee J, Regan L, Khullar V, Moodley J, Connolly C. Does the volume of retained products of conception and hormonal parameters influence the success of conservative methods of management of first trimester miscarriage?. International Journal of Gynecology & Obstetrics 2009;107(Suppl 2):S116.
Bani‐Irshaid 2006 {published data only}
    1. Bani‐Irshaid I, Athamneh TZ, Bani‐Khaled D, Al‐Momani M, Dahamsheh H. Termination of second and early third trimester pregnancy: comparison of 3 methods. Eastern Mediterranean Health Journal 2006;12(5):605‐9. - PubMed
Bartz 2013 {published data only}
    1. Bartz D, Maurer R, Allen RH, Fortin J, Kuang B, Goldberg AB. Buccal misoprostol compared with synthetic osmotic cervical dilator before surgical abortion: a randomized controlled trial. Obstetrics and Gynecology 2013;122(1):57‐63. - PubMed
Bebbington 2002 {published data only}
    1. Bebbington MW, Kent N, Lim K, Gagnon A, Delisle MF, Tessier F, et al. A randomized controlled trial comparing two protocols for the use of misoprostol in midtrimester pregnancy termination. American Journal of Obstetrics and Gynecology 2002;187:853‐7. - PubMed
Behrashi 2008 {published data only}
    1. Behrashi M, Mahdian M. Vaginal versus oral misoprostol for second‐trimester pregnancy termination: a randomized trial. Pakistan Journal of Biological Sciences 2008;11(21):2505‐8. - PubMed
Behrashi 2010 {published data only}
    1. Behrashi M. Comparison between the oral and vaginal misoprostol effects on pregnancy termination in second trimester. irct.ir/trial/129 (first received 29 August, 2008).
Ben‐Meir 2009 {published data only}
    1. Ben‐Meir A, Erez Y, Feigenberg T, Hamani Y, Laufer N, Rojansky N. Mifepristone followed by high‐dose oxytocin drip for second‐trimester abortion: a randomized, double‐blind, placebo‐controlled, pilot study. Journal of Reproductive Medicine 2009;54(8):511‐6. - PubMed
Betstadt 2007 {published data only}
    1. Betstadt SJ. MiMi: a randomized trial of mifepristone and misoprostol for treatment of early pregnancy failure. clinicaltrials.gov/ct2/show/NCT00468299 (first received 1 May, 2007).
Bique 2007 {published data only}
    1. Bique C, Usta M, Debora B, Chong E, Westheimer E, Winikoff B. Comparison of misoprostol and manual vacuum aspiration for the treatment of incomplete abortion. International Journal of Gynecology & Obstetrics 2007;98(3):222‐6. - PubMed
Biswas 2007 {published data only}
    1. Biswas SC, Dey R, Jana R, Chattopadhyay N. Comparative study of intravaginal misoprostol and extra amniotic ethacridine lactate instillation for mid trimester pregnancy termination. Journal of Obstetrics and Gynaecology of India 2007;57(3):211‐3.
Blohm 2005 {published data only}
    1. Blohm F, Friden BE, Milsom I, Platz‐Christensen JJ, Nielsen S. A randomised double blind trial comparing misoprostol or placebo in the management of early miscarriage. BJOG: an international journal of obstetrics and gynaecology 2005;112(8):1090‐5. - PubMed
Brouns 2010 {published data only}
    1. Brouns JF, Wely M, Burger MP, Wijngaarden WJ. Comparison of two dose regimens of misoprostol for second‐trimester pregnancy termination. Contraception 2010;82(3):266‐75. - PubMed
Cabrol 1990 {published data only}
    1. Cabrol D, Dubois C, Cronje H, Gonnet JM, Guillot M, Maria B, et al. Induction of labour with mifepristone (RU 486) in intrauterine fetal death. American Journal of Obstetrics and Gynecology 1990;163:540‐2. - PubMed
Caliskan 2005 {published data only}
    1. Caliskan E, Dilbaz S, Doger E, Ozeren S, Dilbaz B. Randomized comparison of 3 misoprostol protocols for abortion induction at 13‐20 weeks of gestation. Journal of Reproductive Medicine 2005;50(3):173‐80. - PubMed
Caliskan 2009 {published data only}
    1. Caliskan E, Doger E, Cakiroglu Y, Corakci A, Yucesoy I. Sublingual misoprostol 100 microgram versus 200 microgram for second trimester abortion: a randomised trial. European Journal of Contraception & Reproductive Health Care 2009;14(1):55‐60. - PubMed
Chaudhuri 2015 {published data only}
    1. Chaudhuri P, Datta S. Mifepristone and misoprostol compared with misoprostol alone for induction of labor in intrauterine fetal death: a randomized trial. Journal Obstetrics and Gynaecology Research 2015;41(12):1884‐90. - PubMed
    1. Datta S. A randomized double‐blind study to compare efficacy of mifepristone and misoprostol versus misoprostol alone for induction of labour in intrauterine foetal death. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=7823 (first received 21 March 2014).
Chowdhury 2012 {published data only}
    1. Chowdhury S, Uddin AW. Misoprostol in the management of second trimester missed abortion: a randomized controlled trial. International Journal of Gynaecology and Obstetrics 2012;119(Suppl 3):S310.
Clevin 2001 {published data only}
    1. Clevin L, Munk T, Hansen TR. Spontaneous abortion. Drug treatment versus surgery [Spontan abort. Medicinsk versus kirurgisk behandling]. Ugeskrift for Laeger 2001;163(15):2136‐9. - PubMed
Dabash 2009 {published data only}
    1. Dabash R, Cherine M, Darwish E, Blum J, Hassanein N, Abdel Daiem T, et al. Bleeding following surgical (MVA) and medical (400 ug sublingual misoprostol) treatment of incomplete abortion. International Journal of Gynecology & Obstetrics 2009;107(Suppl 2):S150‐S151.
Dao 2007 {published data only}
    1. Dao B, Blum J, Thieba B, Raghavan S, Ouedraego M, Lankoande J, et al. Is misoprostol a safe, effective and acceptable alternative to manual vacuum aspiration for postabortion care? Results from a randomised trial in Burkina Faso, West Africa. BJOG: an international journal of obstetrics and gynaecology 2007;114(11):1368‐75. - PubMed
Das 2014 {published data only}
    1. Das CM, Sharma M, Pardeep K, Khurshid F. To compare the safety and efficacy of manual vacuum aspiration with misoprostol (st mom) 600mg in incomplete miscarriage. Journal of the Liaquat University of Medical and Health Sciences 2014; Vol. 13, issue 3:93‐6.
David 2003 {published data only}
    1. David M, Chen FC, Lichtenegger W. NO‐donor nitroglycerin versus the prostaglandin gemeprost for cervical ripening in first trimester missed abortion. International Journal of Gynecology & Obstetrics 2003;83:71‐2. - PubMed
David 2005 {published data only}
    1. David M, Chen FC. Comparison of isosorbide mononitrate (Mono Mack) and misoprostol (Cytotec) for cervical ripening in the first trimester missed abortion. Archives of Gynecology and Obstetrics 2005;273(3):144‐5. - PubMed
Demirezen 2018 {published data only}
    1. Demirezen G, Aslan Cetin B, Aydogan Mathyk B, Koroglu N, Yildirim G. Efficiency of the Foley catheter versus the double balloon catheter during the induction of second trimester pregnancy terminations: a randomized controlled trial. Archives of Gynecology and Obstetrics 2018;298(5):881–7. - PubMed
Dickinson 1998 {published data only}
    1. Dickinson JE, Godfrey M, Evans SF. Efficacy of intravaginal misoprostol in second‐trimester pregnancy termination: a randomized controlled trial. Journal of Maternal‐Fetal Medicine 1998;7:115‐9. - PubMed
Dickinson 2002 {published data only}
    1. Dickinson JE, Evans SF. The optimization of intravaginal misoprostol dosing schedules in second‐trimester pregnancy termination. American Journal of Obstetrics and Gynecology 2002;186:470‐4. - PubMed
Dickinson 2003 {published data only}
    1. Dickinson JE, Evans SF. A comparison of oral misoprostol with vaginal misoprostol administration in second‐trimester pregnancy termination for fetal abnormality. Obstetrics & Gynecology 2003;101:1294‐9. - PubMed
Diop 2009 {published data only}
    1. Diop A, Raghavan S, Rakotovao JP, Comendant R, Blumenthal PD, Winikoff B. Two routes of administration for misoprostol in the treatment of incomplete abortion: a randomized clinical trial. Contraception 2009;79(6):456‐62. - PubMed
Elami‐Suzin 2013 {published data only}
    1. Elami‐Suzin M, Freeman MD, Porat N, Rojansky N, Laufer N, Ben‐Meir A. Mifepristone followed by misoprostol or oxytocin for second‐trimester abortion: a randomized controlled trial. Obstetrics and Gynecology 2013;122(4):815‐20. - PubMed
    1. Freeman MD, Porat N, Rojansky N, Elami‐Suzin M, Winograd O, Ben‐Meir A. Physical symptoms and emotional responses among women undergoing induced abortion protocols during the second trimester. International Journal of Gynaecology and Obstetrics 2016;135(2):154‐7. [DOI: 10.1016/j.ijgo.2016.05.008] - DOI - PubMed
Elhassan 2008 {published data only}
    1. Elhassan EM, Abubaker MS, Adam I. Sublingual compared with oral and vaginal misoprostol for termination of pregnancy with second‐trimester fetal demise. International Journal of Gynecology & Obstetrics 2008;100(1):82‐3. - PubMed
El Sokkary 2016 {published data only}
    1. Sokkary HH. Comparison between sublingual and vaginal administration of misoprostol in management of missed abortion. Journal of Obstetrics and Gynaecology of India 2016;66(S1):S24‐S29. - PMC - PubMed
Eppel 2005 {published data only}
    1. Eppel W, Facchinetti F, Schleussner E, Piccinini F, Pizzi C, Gruber DM, et al. Second trimester abortion using isosorbide mononitrate in addition to gemeprost compared with gemeprost alone: a double blind randomized, placebo‐controlled multicenter trial. American Journal of Obstetrics and Gynecology 2005;192:856‐61. - PubMed
Eslamian 2007 {published data only}
    1. Eslamian L, Gosili R, Jamal A, Alyassin A. A prospective randomized controlled trial of two regimens of vaginal misoprostol in second trimester termination of pregnancy. Acta Medica Iranica 2007;45(6):497‐500.
Fadalla 2004* {published data only}
    1. Fadalla FA, Mirghani OA, Adam I. Oral misoprostol vs vaginal misoprostol for termination of pregnancy with intrauterine fetal demise in the second‐trimester. International Journal of Gynecology & Obstetrics 2004;86:52‐3. - PubMed
Feldman 2003 {published data only}
    1. Feldman DM, Borgida AF, Rodis JF, Leo MV, Campbell WA. A randomized comparison of two regimens of misoprostol for second‐trimester pregnancy termination. American Journal of Obstetrics and Gynecology 2003;189:710‐3. - PubMed
Fernlund 2018 {published data only}
    1. Fernlund A, Jokubkiene L, Sladkevicius P, Valentin L. A randomised controlled trial comparing misoprostol to expectant care in early pregnancy failure. Ultrasound in Obstetrics & Gynecology 2017;50(Suppl 1):15, Abstract no: OC08.03.
    1. Fernlund A, Jokubkiene L, Sladkevicius P, Valentin L. Misoprostol treatment vs expectant management in women with early non‐viable pregnancy and vaginal bleeding: a pragmatic randomized controlled trial. Ultrasound in Obstetrics & Gynecology 2018;51(1):24‐32. - PubMed
Fiala 2005 {published data only}
    1. Fiala C, Swahn ML, Stephansson O, Gemzell‐Danielsson K. The effect of non‐steroidal anti‐inflammatory drugs on medical abortion with mifepristone and misoprostol at 13‐22 weeks gestation. Human Reproduction 2005;20(11):3072‐7. - PubMed
Ghorab 1998 {published data only}
    1. Ghorab MN, Helw BA. Second‐trimester termination of pregnancy by extra‐amniotic prostaglandin F2alpha or endocervical misoprostol. Acta Obstetricia et Gynecologica Scandinavica 1998;77:429‐32. - PubMed
Gonzalez 2001 {published data only}
    1. Gonzalez JA, Carlan SJ, Alverson MW. Outpatient second trimester pregnancy termination. Contraception 2001;63:89‐93. - PubMed
Grimes 2004 {published data only}
    1. Grimes DA, Smith MS, Witham AD. Mifepristone and misoprostol versus dilatation and evacuation for midtrimester abortion: a pilot randomised controlled trial. BJOG: an international journal of obstetrics and gynaecology 2004;111:148‐53. - PubMed
Gronland 2002 {published data only}
    1. Gronland A, Gronland L, Clevin L, Andersen B, Palmegren N, Lidegaard O. Management of missed abortion: comparison of medical treatment with either mifepristone + misoprostol or misoprostol alone with surgical evacuation. A multi‐center trial in Copenhagen county, Denmark. Acta Obstetricia et Gynecologica Scandinavica 2002;81:1060‐5. - PubMed
Guix 2005 {published data only}
    1. Guix C, Palacio M, Figueras F, Bennasar M, Zamora L, Coll O, et al. Efficacy of two regimens of misoprostol for early second‐trimester pregnancy termination. Fetal Diagnosis and Therapy 2005;20(6):544‐8. - PubMed
Halimi 2004 {published data only}
    1. Halimi M. Therapeutic termination of second trimester pregnancy: a comparison of extra‐amniotic foley`s catheter balloon alone with the combined use of foley`s catheter balloon and extra‐amniotic instillation of prostaglandin f2‐alpha. Journal of Postgraduate Medical Institute 2004;18(3):408‐18.
Hassan 2007 {published data only}
    1. Hassan FI, Mostapha MK, Sattar MA, Marouf E, Azim SA. Oral versus rectal route of misoprostol administration: a randomized controlled trial. Middle East Fertility Society Journal 2007;12(1):53‐6.
Hausler 1997 {published data only}
    1. Häusler MC, Koroschetz F, Tamussino K, Walcher W. Is a curettage after spontaneous abortion still relevant. A prospective randomised study [Ist eine Curettage nach Abortus completus noch zeitgemäb?. Eine prospektiv randomisierte Studie]. Geburtshilfe und Frauenheilkunde 1997;57:396‐9.
Heard 2002 {published data only}
    1. Heard MJ, Stewart GM, Buster JE, Carson SA, Miller HJ. Outpatient management of missed abortion with vaginal misoprostol [abstract]. Obstetrics & Gynecology 2002;99(4 Suppl):20S.
Herabutya 1997a {published data only}
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Zhang 2005 {published data only}
    1. Chen BA, Reeves MF, Creinin MD, Gilles JM, Barnhart K, Westhoff C, et al. Misoprostol for treatment of early pregnancy failure in women with previous uterine surgery. American Journal of Obstetrics & Gynecology 2008;198(6):626.e1‐626.e5. [DOI: ] - PMC - PubMed
    1. Creinin MD, Huang X, Westhoff C, Barnhart K, Gilles JM, Zhang J, et al. Factors related to successful misoprostol treatment for early pregnancy failure. Obstetrics & Gynecology 2006;107(4):901‐7. - PMC - PubMed
    1. Davis AR, Hendlish SK, Westhoff C, Frederick MM, Zhang J, Gilles JM, et al. Bleeding patterns after misoprostol vs surgical treatment of early pregnancy failure: results from a randomized trial. American Journal of Obstetrics and Gynecology 2007;196(1):31. [10.1016/j.ajog.2006.07.053] - PubMed
    1. Harwood B, Nansel T, National Institute of Child Health and Human Development Management of Early Pregnancy Failure Trial. Quality of life and acceptability of medical versus surgical management of early pregnancy failure. BJOG: an international journal of obstetrics and gynaecology 2008;115(4):501‐8. [DOI: 10.1111/j.1471-0528.2007.01632.x] - DOI - PMC - PubMed
    1. Rausch M, Lorch S, Chung K, Frederick M, Zhang J, Barnhart K. A cost‐effectiveness analysis of surgical versus medical management of early pregnancy loss. Fertility and Sterility 2012;97(2):355‐60.e1. [DOI: 10.1016/j.fertnstert.2011.11.044] - DOI - PMC - PubMed

References to ongoing studies

ACTRN12615000483550 {published data only}
    1. Abdellah AS. Clinical randomized trial to compare efficacy and safety of vaginal and buccal misoprostol in second trimester abortion due to intrauterine fetal death. anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367522 (first received 15 May 2015).
Ali 2017 {published data only}
    1. Ali MK, NCT03148314. Home‐based extended low dose buccal misoprostol versus hospital‐based standard vaginal dose in management of first trimester missed abortion. https://clinicaltrials.gov/ct2/show/NCT03148314 (first received 11 May 2017).
El Shahawy 2016 {published data only}
    1. Shahawy A, NCT02686840. Sublingual versus vaginal misoprostol in medical treatment of first trimestric missed miscarriage: a randomized controlled trial. https://clinicaltrials.gov/ct2/show/NCT02686840 (first received 22 February 2016).
NCT02620904 {published data only}
    1. Atrio J. Mifepristone induction for fetal demise, a randomized control trial. clinicaltrials.gov/ct2/show/NCT02620904 (first received 1 December 2015).
NCT02633761 {published data only}
    1. Bracken H. Mifepristone and misoprostol versus misoprostol alone for treatment of fetal death at 14‐28 weeks of pregnancy: a randomized, placebo‐controlled double‐blinded trial. clinicaltrials.gov/ct2/show/NCT02633761 (first received 17 December 2015).
NCT03212352 2017 {published data only}
    1. NCT03212352. Comparing two medical treatments for early pregnancy failure. https://clinicaltrials.gov/show/nct03212352 (first received 11 July 2017).

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