Cervical preparation for dilation and evacuation at 12 to 24 weeks gestation

Tesfaye H Tufa; Fiona Stewart; Karen Meckstroth; Justin T Diedrich; Sara J Newmann

doi:10.1002/14651858.CD007310.pub3

. 2025 Mar 3;2025(3):CD007310. doi: 10.1002/14651858.CD007310.pub3

Cervical preparation for dilation and evacuation at 12 to 24 weeks gestation

Tesfaye H Tufa ¹, Fiona Stewart ², Karen Meckstroth ³, Justin T Diedrich ⁴, Sara J Newmann ^5,^✉

Editor: Cochrane Fertility Regulation Group

PMCID: PMC11873992 PMID: 40028776

Abstract

Background

Abortion is a common procedure. Complications associated with abortion increase as gestational age increases. Cervical preparation is recommended prior to second trimester surgical abortion. Evidence is lacking as to the most effective methods of cervical preparation.

Objectives

To assess the effectiveness of cervical preparation methods for people undergoing second trimester surgical abortion at gestational age between 12 and 24 0/7 weeks.

Search methods

We searched CENTRAL, MEDLINE ALL, Embase.com, Global Index Medicus, Scopus, and Google Scholar on 20 December 2021. We also searched reference lists, review articles, books, and conference proceedings. We contacted experts for information on other published or unpublished research. The COVID‐19 pandemic greatly disrupted the writing and publication of this review; the search is outdated, but an updated search will be performed prior to the next update.

Selection criteria

We included randomized controlled trials (RCTs) investigating any cervical preparation method for second trimester surgical abortion from 12 to 24 weeks gestation.

Data collection and analysis

We used standard Cochrane methods.

Main results

We identified 21 RCTs (3029 participants). Some trials were at high risk of detection and reporting bias.

Prostaglandin versus osmotic dilators (4 studies, 373 participants; 12 6/7 to 20 weeks)

Prostaglandin may result in little to no difference in ability to complete procedure (risk ratio [RR] 0.99, 95% confidence interval [CI] 0.95 to 1.03; low‐certainty evidence), but probably leads to less dilation achieved (mean difference [MD] −3.58 mm, 95% CI −4.58 to −2.58; moderate‐certainty evidence) when compared to osmotic dilators.

Mifepristone plus 400 μg buccal misoprostol versus osmotic dilators (1 study, 49 participants; 15 0/7 to 18 0/7 weeks)

Mifepristone plus misoprostol may have little to no effect on ability to complete procedure (RR 1.00, 95% CI 0.92 to 1.08; low‐certainty evidence) and procedure time (MD −0.30, 95% CI −3.46 to 2.86) when compared to osmotic dilators. The combination may lead to less dilation achieved (MD −1.67 mm, 95% CI −3.19 to −0.15; low‐certainty evidence) and increased need for additional dilation (RR 1.92, 95% CI 1.16 to 3.18; low‐certainty evidence) compared to osmotic dilators.

400 μg buccal misoprostol plus osmotic dilators versus placebo plus osmotic dilators (4 studies, 545 participants; 13 to 23 6/7 weeks)

Misoprostol plus osmotic dilators probably has no effect on ability to complete procedure (RR 0.99, 95% CI 0.96 to 1.02; moderate‐certainty evidence), but probably increases dilation achieved (MD 1.83 mm, 95% CI 0.27 to 3.39; moderate‐certainty evidence) and reduces need for additional dilation (RR 0.65, 95% CI 0.50 to 0.84; moderate‐certainty evidence) and procedure time (MD −0.99 min, 95% CI −2.05 to 0.06; moderate‐certainty evidence) compared to placebo plus osmotic dilators.

Mifepristone plus osmotic dilators versus placebo plus osmotic dilators (1 study, 198 participants; 16 0/7 to 23 6/7 weeks)

Mifepristone plus osmotic dilators probably has little to no effect on ability to complete procedure when compared to placebo plus osmotic dilators (RR 1.00, 95% CI 0.97 to 1.03; moderate‐certainty evidence). Mifepristone plus osmotic dilators may reduce procedure time (2.46 min shorter: median, interquartile range, 9.12 min, 7.7 to 10.6; compared to 11.58 minutes, 10.0 to 13.1; low‐certainty evidence) and probably increases dilation achieved (MD 2.00 mm, 95% CI 0.60 to 3.40; moderate‐certainty evidence). There appears to be no effect on need for additional dilation.

400 μg buccal misoprostol plus osmotic dilators versus mifepristone plus osmotic dilators (1 study, 199 participants; 16 0/7 to 23 6/7 weeks)

There is likely no difference in ability to complete procedure between groups (RR 0.99, 95% CI 0.96 to 1.02; moderate‐certainty evidence). Misoprostol plus osmotic dilators does not appear to affect procedure time, dilation achieved, and need for additional dilation compared with mifepristone plus osmotic dilators.

Mifepristone plus 400 μg buccal misoprostol plus osmotic dilators compared to 400 μg buccal misoprostol plus osmotic dilators (1 study, 96 participants; 19 to 23 6/7 weeks)

Mifepristone plus misoprostol plus osmotic dilators may have little to no effect on procedure time, dilation achieved, or need for additional dilation compared with misoprostol plus osmotic dilators.

400 μg buccal or vaginal misoprostol plus osmotic dilators versus 400 μg buccal or vaginal misoprostol (1 study, 163 participants; 14 to 19 6/7 weeks)

There is probably no difference between groups in ability to complete procedure (RR 1.00, 95% CI 0.98 to 1.02; moderate‐certainty evidence). Misoprostol plus osmotic dilators likely increases dilation (MD 3.9 mm, 95% CI 3.1 to 4.7; moderate‐certainty evidence) and reduces need for additional dilation (RR 0.77, 95% CI 0.63 to 0.93; moderate‐certainty evidence).

Laminaria versus synthetic osmotic dilators (1 study, 219 participants; 13 6/7 to 24 0/7 weeks)

Laminaria japonica may reduce ability to complete procedure at first attempt compared with synthetic osmotic dilators (RR 0.85, 95% CI 0.75 to 0.96; low‐certainty evidence). It is uncertain if there is a difference in procedure time between groups. Laminaria likely does not effect dilation achieved (RR 1.0, 95% CI 0.8 to 1.3; moderate‐certainty evidence).

Same‐day Dilapan‐S versus overnight laminaria (1 study, 69 participants; 13 6/7 to 17 6/7 weeks)

Same‐day Dilapan‐S may increase procedure time (MD 2.20 min, 95% CI 0.10 to 4.30; low‐certainty evidence); reduce dilation achieved (MD −11.70 mm, 95% CI −16.74 to −6.66; low‐certainty evidence); and increase need for additional dilation (RR 2.83, 95% CI 1.47 to 5.46; low‐certainty evidence) compared with laminaria. There appears to be no difference in ability to complete procedure.

Authors' conclusions

We identified a heterogeneous body of evidence comparing different cervical priming approaches. Compared with osmotic dilators plus placebo, misoprostol plus osmotic dilators probably reduces procedure time, increases pre‐procedure cervical dilation, and reduces the number of people who need additional dilation. Compared with osmotic dilators plus placebo, mifepristone plus osmotic dilators may reduce procedure time and probably increases pre‐procedure cervical dilation. Overnight laminaria may reduce procedure time, increase pre‐procedure dilation, and reduce need for additional dilation compared to same‐day Dilapan‐S.

Further studies are needed that focus on both provider and patient acceptability and satisfaction.

Plain language summary

What are the benefits and risks of different cervical preparation methods for surgical abortion in the second trimester of pregnancy?

Key messages

• Prostaglandin and osmotic dilators are likely safe and effective methods of cervical priming agents before second trimester surgical abortion.

• Misoprostol plus osmotic dilators probably increases pre‐procedure cervical dilation and reduces procedure time and need for additional dilation compared to placebo (dummy treatment) plus osmotic dilators.

• Overnight laminaria may improve procedure time, pre‐procedure dilation, and need for additional dilation compared to same‐day Dilapan‐S.

• Future studies should be larger and look at Foley catheters as a method of cervical priming for second‐trimester surgical abortion.

Why is this question important?

Pregnant people prefer to have options to choose for their pregnancy termination, that is medical abortion versus surgical abortion using dilation and evacuation (D&E, a procedure that opens the cervix so tissue in the uterus can be removed using an instrument). Most providers use cervical priming agents prior to second trimester uterine surgical evacuation. Commonly used medical methods for cervical preparation are prostaglandins (misoprostol) and an antiprogesterone (mifepristone). Mechanical methods of cervical priming include osmotic dilators (laminaria and Dilapan‐S). Providers may use medicine or mechanical methods, or both, based on different factors, including gestational age. There is no agreement on the best method of cervical priming agent used before D&E.

What did we do?

We searched for studies comparing the effects of different forms of cervical priming agents used before second trimester surgical abortion. We compared and summarized the results and rated our confidence in the evidence based on factors such as study methods and sizes.

What did we find?

We found 21 studies involving 3029 participants. Few studies compared the same two cervical priming agents. Mifepristone was taken 24 to 48 hours prior to misoprostol or osmotic dilators, except in one study where it was used at the same time as laminaria. Mifepristone was used at a dose of 200 mg and misoprostol at a dose of 400 to 600 μg.

Prostaglandin versus osmotic dilators

Prostaglandin may have little to no effect on procedure time, but probably leads to less dilation achieved compared with osmotic dilators.

Mifepristone plus misoprostol versus osmotic dilators

Mifepristone plus misoprostol may have little to no effect on procedure time, but it may lead to less dilation achieved and an increased need for additional dilation and have little to no effect on ability to complete procedure compared with osmotic dilators.

Misoprostol plus osmotic dilators versus placebo plus osmotic dilators

Misoprostol plus osmotic dilators probably reduces procedure time; increases dilation achieved; reduces need for additional dilation; and has little to no effect on ability to complete procedure compared with placebo plus osmotic dilators.

Mifepristone plus osmotic dilators versus placebo plus osmotic dilators

Mifepristone plus osmotic dilators may reduce procedure time, and probably increases dilation achieved compared with placebo plus osmotic dilators. Mifepristone plus osmotic dilators may have little to no effect on need for additional dilation, but there is probably little to no effect on ability to complete procedure.

Misoprostol plus osmotic dilators versus mifepristone plus osmotic dilators

Misoprostol plus osmotic dilators may have little to no effect on procedure time, dilation achieved, and need for additional dilation compared with mifepristone plus osmotic dilators. There is probably little to no difference in ability to complete procedure.

Mifepristone plus misoprostol plus dilators compared to misoprostol plus osmotic dilators

Mifepristone plus misoprostol plus osmotic dilators may have little to no effect on procedure time, dilation achieved, and need for additional dilation compared with misoprostol plus osmotic dilators. Ability to complete procedure was not reported.

Misoprostol plus osmotic dilators versus misoprostol

Misoprostol plus osmotic dilators probably increases procedure time (if procedure time includes the time elapsed for insertion of osmotic dilators); increases dilation achieved; reduces the need for additional dilation; and has little to no effect on ability to complete procedure compared with misoprostol alone.

Laminaria versus synthetic osmotic dilators

It is uncertain if laminaria has any effect on procedure time, but probably makes little to no difference in dilation achieved, and may reduce ability to complete procedure compared with synthetic osmotic dilators.

Same‐day Dilapan‐S versus overnight laminaria

Same‐day Dilapan‐S may increase procedure time; reduce dilation achieved; and increase need for additional dilation compared with overnight laminaria. There may be little to no difference in ability to complete procedure between groups.

What are the limitations of the evidence?

We have only moderate to little confidence in the evidence because of differences in the size or direction of effect and few people contributing data to the analyses. More studies are needed to increase our confidence in the evidence.

How up‐to‐date is this review?

The evidence is current to 20 December 2021.

Summary of findings

Summary of findings 1. Prostaglandin compared to osmotic dilators for second trimester dilation and evacuation (12 6/7 weeks to 20 weeks).

Prostaglandin compared to osmotic dilators for second trimester dilation and evacuation
Patient or population: second trimester dilation and evacuation Setting: abortion clinics Intervention: prostaglandin Comparison: osmotic dilators
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with osmotic dilators	Risk with prostaglandin
Procedure time (minutes)	In 1 study (83 participants) misoprostol took 3.8 minutes longer than laminaria (P = 0.01). In 1 study (84 participants) misoprostol took 1.0 minute less than laminaria (P = 0.03). In 1 study (156 participants) misoprostol took 0.3 minutes longer than laminaria (P = 0.693).		‐	323 (3 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}	Prostaglandin may have little to no effect on procedure time compared with osmotic dilators. Gestational ages: 12 weeks 6 days to 15 weeks 6 days, 13 weeks to 19 weeks, 13 weeks to 20 weeks
Dilation achieved (millimeters)	The mean dilation achieved without prostaglandin ranged from 8.7 to 12.4 mm.	MD 3.58 mm lower (4.58 lower to 2.58 lower)	‐	217 (3 RCTs)	⊕⊕⊕⊝ MODERATE ³	Prostaglandin probably results in a reduction in dilation achieved compared with osmotic dilators. Gestational ages: 12 weeks 6 days to 15 weeks 6 days, 13 to 20 weeks, 15 to 20 weeks
Need for additional dilation	Study population		RR 1.85 (0.45 to 7.52)	167 (2 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 4}	It is uncertain if prostaglandin has any effect on the need for additional dilation compared with dilators. Gestational ages: 12 weeks 6 days to 15 weeks 6 days, 13 weeks to 20 weeks
	271 per 1000	501 per 1000 (122 to 1000)
Ability to complete procedure	Study population		RR 0.99 (0.95 to 1.03)	167 (2 RCTs)	⊕⊕⊝⊝ LOW ⁴	Prostaglandin may result in little to no difference in ability to perform procedure compared with osmotic dilators. Gestational ages: 12 weeks 6 days to 15 weeks 6 days, 13 weeks to 20 weeks
	1000 per 1000	990 per 1000 (950 to 1000)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

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¹Downgraded one level for inconsistency: large difference in direction of effect. ²Downgraded one level for imprecision: low numbers of participants, data not pooled. ³Downgraded one level for imprecision: low numbers of participants. ⁴Downgraded two levels for imprecision: low numbers of participants and 95% CI spanning possible harm and possible benefit.

Summary of findings 2. Mifepristone plus misoprostol compared to osmotic dilators for second trimester dilation and evacuation (15 0/7 weeks to 18 0/7 weeks).

Mifepristone + misoprostol compared to osmotic dilators for second trimester dilation and evacuation
Patient or population: second trimester dilation and evacuation Setting: abortion clinics Intervention: mifepristone + misoprostol Comparison: osmotic dilators
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with osmotic dilators	Risk with mifepristone + misoprostol
Procedure time (minutes)	The mean procedure time in the osmotic dilators group was 14.3 minutes.	MD 0.3 lower (3.46 lower to 2.86 higher)	‐	49 (1 RCT)	⊕⊕⊝⊝ LOW ¹	Mifepristone + misoprostol may have little to no effect on procedure time compared with osmotic dilators. Gestational age range: 15 weeks 0 days to 18 weeks 0 days
Dilation achieved (millimeters)	The mean dilation achieved in the osmotic dilators group was 15.67 mm.	MD 1.67 lower (3.19 lower to 0.15 lower)	‐	49 (1 RCT)	⊕⊕⊝⊝ LOW ²	Mifepristone + misoprostol may lead to less dilation achieved compared with osmotic dilators. Gestational age range: 15 weeks 0 days to 18 weeks 0 days
Need for additional dilation	Study population		RR 1.92 (1.16 to 3.18)	49 (1 RCT)	⊕⊕⊝⊝ LOW ²	Mifepristone + misoprostol may increase the need for additional dilation compared with osmotic dilators. Gestational age range: 15 weeks 0 days to 18 weeks 0 days
	450 per 1000	864 per 1000 (522 to 1000)
Ability to complete procedure	Study population		RR 1.00 (0.92 to 1.08)	49 (1 RCT)	⊕⊕⊝⊝ LOW ²	Mifepristone + misoprostol may have little to no effect on ability to perform procedure compared with osmotic dilators. Gestational age range: 15 weeks 0 days to 18 weeks 0 days
	1000 per 1000	1000 per 1000 (920 to 1000)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

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¹Downgraded two levels for imprecision: few participants and 95% CIs spanning possible benefit and possible harm. ²Downgraded two levels for imprecision: very few participants.

Summary of findings 3. Misoprostol plus osmotic dilators compared to placebo plus osmotic dilators for second trimester dilation and evacuation (13 0/7 weeks to 23 6/7 weeks).

Misoprostol + osmotic dilators compared to placebo + osmotic dilators for second trimester dilation and evacuation
Patient or population: second trimester dilation and evacuation Setting: abortion clinics Intervention: misoprostol + osmotic dilators Comparison: placebo + osmotic dilators
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo + osmotic dilators	Risk with misoprostol + osmotic dilators
Procedure time (minutes)	The mean procedure time in the control group ranged from 6.4 to 11.1minutes.	MD 0.99 lower (2.05 lower to 0.06 higher)	‐	545 (4 RCTs)	⊕⊕⊕⊝ MODERATE ¹	Misoprostol + osmotic dilators probably reduces procedure time slightly compared with placebo + osmotic dilators. Gestational ages: 13 weeks 0 days to 20 weeks 6 days, 16 weeks to 20 weeks 6 days, 16 weeks 0 days to 23 weeks 6 days, 21 weeks to 23 weeks 1 day
Dilation achieved (millimeters)	The mean dilation achieved achieved in the control group ranged from 16.97 to 75mm.	MD 1.83 mm more (0.27 more to 3.39 more)	‐	484 (4 RCTs)	⊕⊕⊕⊝ MODERATE ¹	Misoprostol + osmotic dilators probably results in a slight increase in dilation achieved compared with placebo + osmotic dilators. Gestational ages: 13 weeks 0 days to 20 weeks 6 days, 16 weeks 0 days to 20 weeks 6 days, 21 weeks 0 days to 23 weeks 1 day
Need for additional dilation	Study population		RR 0.65 (0.50 to 0.84)	546 (4 RCTs)	⊕⊕⊕⊝ MODERATE ²	Misoprostol + osmotic dilators probably reduces the number of people who need additional dilation compared with placebo + osmotic dilators. Gestational ages: 13 weeks 0 days to 20 weeks 6 days, 16 weeks 0 days to 20 weeks 6 days, 21 weeks 0 days to 23 weeks 1 day, 16 weeks 0 days to 23 weeks 6 days
	313 per 1000	203 per 1000 (156 to 263)
Ability to complete procedure (number completed on first attempt)	Study population		RR 0.99 (0.96 to 1.02)	199 (1 RCT)	⊕⊕⊕⊝ MODERATE ³	Misoprostol + osmotic dilators probably has little to no effect on ability to complete procedure compared with placebo + osmotic dilators. Gestational age: 16 weeks to 23 weeks 6 days
	990 per 1000	980 per 1000 (950 to 1000)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

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¹Downgraded one level for inconsistency: differences in size of effect probably due to one trial with lower gestational age range. ²Downgraded one level for imprecision: low event rate. ³Downgraded one level for imprecision: few participants.

Summary of findings 4. Mifepristone plus osmotic dilators compared to placebo plus osmotic dilators for second trimester dilation and evacuation (16 0/7 weeks to 23 6/7 weeks).

Mifepristone + dilators compared to placebo + dilators for second trimester dilation and evacuation
Patient or population: second trimester dilation and evacuation Setting: abortion clinics Intervention: mifepristone + osmotic dilators Comparison: placebo + osmotic dilators
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo + osmotic dilators	Risk with mifepristone + osmotic dilators
Procedure time (minutes)	In 1 study mifepristone plus osmotic dilator took 2.46 minutes less than placebo plus osmotic dilator: median (IQR) mifepristone plus osmotic dilators group: 9.12 minutes (7.7 to 10.6); placebo plus osmotic dilators group: 11.58 minutes (10.0 to 13.1).		‐	196 (1 RCT)	⊕⊕⊝⊝ LOW ¹	Mifepristone + osmotic dilators may lead to a reduction in procedure time compared with placebo + osmotic dilators. Gestational age: 16 weeks to 23 weeks 6 days
Dilation achieved (millimeters)	The mean dilation achieved in the placebo + osmotic dilator group was 22 mm.	MD 2 higher (0.6 higher to 3.4 higher)	‐	197 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	Mifepristone + osmotic dilators probably increases dilation achieved compared with placebo + osmotic dilators. Gestational age: 12 weeks 6 days to 15 weeks 6 days
Need for additional dilation	Study population		RR 0.61 (0.35 to 1.06)	197 (1 RCT)	⊕⊕⊝⊝ LOW ²	Mifepristone + osmotic dilators may have little to no effect on need for additional dilation compared with placebo + osmotic dilators. Gestational age: 16 weeks to 23 weeks 6 days
	265 per 1000	162 per 1000 (93 to 281)
Ability to complete procedure (number completed on first attempt)	Study population		RR 1.00 (0.97 to 1.03)	198 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	Mifepristone + osmotic dilators probably has little to no effect on ability to complete procedure compared with placebo + osmotic dilators. Gestational age: 16 weeks to 23 weeks 6 days
	990 per 1000	990 per 1000 (960 to 1000)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; IQR: interquartile range; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

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¹Downgraded one level for imprecision: few participants. ²Downgraded two levels for imprecision: few participants, few events, and 95% CI consistent with possible benefit and possible harm.

Summary of findings 5. Misoprostol plus osmotic dilators compared to mifepristone plus osmotic dilators for second trimester dilation and evacuation (16 0/7 weeks to 23 6/7 weeks).

Misoprostol + osmotic dilators compared to mifepristone + osmotic dilators for second trimester dilation and evacuation
Patient or population: second trimester dilation and evacuation Setting: abortion clinics Intervention: misoprostol + osmotic dilators Comparison: mifepristone + osmotic dilators
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with mifepristone + osmotic dilators	Risk with misoprostol + osmotic dilators
Procedure time (minutes)	Misoprostol + osmotic dilator (median 10.13 minutes, IQR 8.6 to 11.6; 98 participants) took 1.01 minutes longer than mifepristone + osmotic dilators (median 9.12 minutes, IQR 7.7 to 10.6; 98 participants).		‐	196 (1 RCT)	⊕⊕⊝⊝ LOW ¹	Misoprostol + osmotic dilators may have little to no effect on procedure time compared to mifepristone + osmotic dilators. Gestational age: 16 weeks 0 days to 23 weeks 6 days
Dilation achieved (millimeters)	The mean dilation achieved in the mifepristone + osmotic dilators group was 24 mm.	MD 1 higher (1.05 lower to 3.05 higher)	‐	195 (1 RCT)	⊕⊕⊝⊝ LOW ²	Misoprostol + osmotic dilators may have little to no effect on dilation achieved compared with mifepristone + osmotic dilators. Gestational age: 16 weeks 0 days to 23 weeks 6 days
Need for additional dilation	Study population		RR 0.56 (0.26 to 1.21)	198 (1 RCT)	⊕⊕⊝⊝ LOW ²	Misoprostol + osmotic dilators may have little to no effect on need for additional dilation compared with mifepristone + osmotic dilators. Gestational age: 16 weeks 0 days to 23 weeks 6 days
	162 per 1000	91 per 1000 (42 to 196)
Ability to complete procedure (number completed on first attempt)	Study population		RR 0.99 (0.96 to 1.02)	199 (1 RCT)	⊕⊕⊕⊝ MODERATE ³	Misoprostol + osmotic dilators probably results in little to no difference in ability to complete procedure compared with mifepristone + osmotic dilators. Gestational age: 16 weeks 0 days to 23 weeks 6 days
	990 per 1000	980 per 1000 (950 to 1000)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; IQR: interquartile range; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

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¹Downgraded two levels for imprecision: few participants, and no P value reported. ²Downgraded two levels for imprecision: few participants, and 95% CI spans possible benefit and possible harm. ³Downgraded one level for imprecision: few participants.

Summary of findings 6. Mifepristone plus misoprostol plus osmotic dilators compared to misoprostol plus osmotic dilators for second trimester dilation and evacuation (19 0/7 weeks to 23 6/7 weeks).

Mifepristone + misoprostol + osmotic dilators compared to misoprostol + osmotic dilators for second trimester dilation and evacuation
Patient or population: second trimester dilation and evacuation Setting: abortion clinics Intervention: mifepristone + misoprostol + osmotic dilators Comparison: misoprostol + osmotic dilators
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with misoprostol + osmotic dilator	Risk with mifepristone + misoprostol + osmotic dilators
Procedure time (minutes)	In 1 study (49 participants) the mean procedure time in the mife + miso + osmotic dilators group was 0.96 minutes longer (1.94 shorter to 3.86 longer) than the miso + osmotic dilators group. In another study (47 participants) the median time was 1 minute shorter (P = 0.76).		‐	96 (2 RCTs)	⊕⊕⊝⊝ LOW ¹	Mifepristone + misoprostol + osmotic dilators may have little to no effect on procedure time compared with misoprostol + osmotic dilators. Gestational age: 19 weeks 0 days to 23 weeks 6 days
Dilation achieved (millimeters)	1 study (48 participants) reported median (range) dilation achieved: mife + miso + osmotic dilators: 30 mm (0.5 to 5); miso + osmotic dilators: 30 mm (0.5 to 5).		‐	48 (1 RCT)	⊕⊕⊝⊝ LOW ¹	Mifepristone + misoprostol + osmotic dilators may have little to no effect on dilation achieved compared with misoprostol + osmotic dilators. Gestational age: 19 weeks 0 days to 23 weeks 6 days
Need for additional dilation	Study population		RR 1.17 (0.38 to 3.61)	48 (1 RCT)	⊕⊕⊝⊝ LOW ²	Mifepristone + misoprostol + osmotic dilators may have little to no effect on need for additional dilation compared with misoprostol + osmotic dilators. Gestational age: 19 weeks 0 days to 23 weeks 6 days
	190 per 1000	223 per 1000 (72 to 688)
Ability to complete procedure—not reported	‐	‐	‐	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

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¹Downgraded two levels for imprecision: pooling of data not possible, few participants. ²Downgraded two levels for imprecision: few participants and wide 95% CI consistent with possible benefit and possible harm.

Summary of findings 7. Misoprostol plus osmotic dilators compared to misoprostol for second trimester dilation and evacuation (14 0/7 weeks to 19 6/7 weeks).

Misoprostol + osmotic dilators compared to misoprostol for second trimester dilation and evacuation
Patient or population: second trimester dilation and evacuation Setting: abortion clinics Intervention: misoprostol + osmotic dilators Comparison: misoprostol
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with misoprostol	Risk with misoprostol + osmotic dilators
Procedure time (minutes)	The mean procedure time in the misoprostol group was 10.8 minutes.	MD 3.2 more (1.77 more to 4.63 more)	‐	161 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	Misoprostol + osmotic dilators probably leads to longer procedure time compared with misoprostol alone. Gestational age: 14 weeks 0 days to 19 weeks 6 days
Dilation achieved (millimeters)	The mean dilation achieved in the misoprostol group was 11.7 mm.	MD 3.9 more (3.1 more to 4.7 more)	‐	161 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	Misoprostol + osmotic dilators probably leads to greater dilation achieved compared with misoprostol alone. Gestational age: 14 weeks 0 days to 19 weeks 6 days
Need for additional dilation	Study population		RR 0.77 (0.63 to 0.93)	161 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	Misoprostol + osmotic dilators probably reduces need for additional dilation compared with misoprostol alone. Gestational age: 14 weeks 0 days to 19 weeks 6 days
	829 per 1000	638 per 1000 (522 to 771)
Ability to complete procedure	Study population		RR 1.00 (0.98 to 1.02)	161 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	Misoprostol + osmotic dilators probably results in little to no difference in ability to complete procedure compared with misoprostol alone. Gestational age: 14 weeks 0 days to 19 weeks 6 days
	1000 per 1000	1000 per 1000 (980 to 1000)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

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¹Downgraded one level for imprecision: few participants.

Summary of findings 8. Laminaria compared to synthetic osmotic dilators for second trimester dilation and evacuation (13 6/7 weeks to 24 0/7 weeks).

Laminaria compared to synthetic osmotic dilators for second trimester dilation and evacuation
Patient or population: second trimester dilation and evacuation Setting: abortion clinics Intervention: laminaria Comparison: synthetic osmotic dilators
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with synthetic osmotic dilator	Risk with laminaria
Procedure time (minutes)	Mean (SD) reported in 1 study (180 participants, numbers of participants per group not reported). Early cohort (18 weeks 0 days to 0 weeks 6 days): laminaria was shorter: 5.9 minutes (3.06) compared with 6.31 minutes (4.45). Late cohort (21 weeks 0 days to 23 weeks 6 days): laminaria was longer: 9.03 minutes (3.61) compared with 8.86 minutes (4.47).		‐	(1 RCT)	⊕⊝⊝⊝ VERY LOW ^{1 2}	The evidence is very uncertain about the effect of laminaria on procedure time compared with synthetic osmotic dilators. Gestational age: 18 weeks 0 days to 23 weeks 6 days
Dilation achieved (rate per 100 abortions of initial dilation ≥ 37 French units)	Study population		RR 1.0 (0.8 to 1.3)	219 (1 RCT)	⊕⊕⊕⊝ MODERATE ³	Laminaria probably results in little to no difference in dilation achieved compared with synthetic osmotic dilators. Gestational age: 13 weeks 6 days to 16 weeks 0 days
	438 per 1000	438 per 1000 (350 to 569)
Need for additional dilation—not reported	‐	‐	‐	‐	‐
Ability to complete procedure	Study population		RR 0.85 (0.75 to 0.96)	173 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 4}	Laminaria may result in a slight reduction in ability to complete procedure compared with synthetic osmotic dilators. Gestational age: 18 weeks 0 days to 23 weeks 6 days
	931 per 1000	791 per 1000 (698 to 894)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SD: standard deviation
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

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¹Downgraded one level for risk of bias: unclear randomization and high risk of selective reporting. ²Downgraded two levels for imprecision: pooling of data not possible, denominators not reported. ³Downgraded one level for indirectness: indirect measurement of outcome. ⁴Downgraded one level for imprecision: few participants.

Summary of findings 9. Same‐day Dilapan‐S compared to overnight laminaria for second trimester dilation and evacuation (13 6/7 weeks and 17 6/7 weeks).

Same‐day Dilapan‐S compared to overnight laminaria for second trimester dilation and evacuation
Patient or population: second trimester dilation and evacuation Setting: abortion clinics Intervention: same‐day Dilapan‐S Comparison: overnight laminaria
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with overnight laminaria	Risk with same day
Procedure time (minutes)	The mean procedure time in the overnight group was 5.9 minutes.	MD 2.2 higher (0.1 higher to 4.3 higher)	‐	67 (1 RCT)	⊕⊕⊝⊝ LOW ¹	Same‐day Dilapan‐S may result in a slight increase in procedure time compared with overnight laminaria. Gestational age: 13 weeks 6 days to 17 weeks 6 days
Dilation achieved (millimeters)	The mean dilation achieved in the overnight group was 59.7 mm.	MD 11.7 lower (16.74 lower to 6.66 lower)	‐	69 (1 RCT)	⊕⊕⊝⊝ LOW ¹	Same‐day Dilapan‐S may result in less dilation achieved compared with overnight laminaria. Gestational age: 13 weeks 6 days to 17 weeks 6 days
Need for additional dilation	Study population		RR 2.83 (1.47 to 5.46)	69 (1 RCT)	⊕⊕⊝⊝ LOW ¹	Same‐day Dilapan‐S may result in more people needing additional dilation compared with overnight laminaria. Gestational age: 13 weeks 6 days to 17 weeks 6 days
	229 per 1000	647 per 1000 (336 to 1000)
Ability to complete procedure	1000 per 1000	950 per 1000	RR 1.00 (0.95 to 1.06)	69 (1 RCT)	⊕⊕⊝⊝ LOW ¹	Same‐day Dilapan‐S may have little or no effect on ability to complete procedure compared with overnight laminaria. Gestational age: 13 weeks 6 days to 17 weeks 6 days
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

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¹Downgraded two levels for imprecision: few participants.

Summary of findings 10. Vaginal misoprostol compared to buccal misoprostol for second trimester dilation and evacuation (14 weeks to 19 6/7 weeks).

Vaginal misoprostol compared to buccal misoprostol for second trimester dilation and evacuation
Patient or population: second trimester dilation and evacuation Setting: abortion clinics Intervention: vaginal misoprostol Comparison: buccal misoprostol
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with buccal misoprostol	Risk with vaginal misoprostol
Procedure time (minutes)	The mean procedure time in the buccal misoprostol group was 9.9 minutes.	MD 0.4 lower (2.55 lower to 1.75 higher)	‐	68 (1 RCT)	⊕⊕⊝⊝ LOW ¹	Vaginal misoprostol may have little to no effect on procedure time compared with buccal misoprostol. Gestational age: 16 weeks 0 days to 20 weeks 6 days
Dilation achieved (French units)	Median (IQR): vaginal miso + mife: 47 French (45 to 44), 35 participants; buccal miso + mife: 47 French (37 to 53), 33 participants		‐	68 (1 RCT)	⊕⊕⊝⊝ LOW ²	Vaginal misoprostol may have little to no effect on dilation achieved compared with buccal misoprostol. Gestational age: 16 weeks 0 days to 20 weeks 6 days
Need for additional dilation	Study population		RR 0.94 (0.84 to 1.06)	68 (1 RCT)	⊕⊕⊝⊝ LOW ³	There may be little to no difference in need for additional dilation between vaginal misoprostol and buccal misoprostol. Gestational age: 16 weeks 0 days to 20 weeks 6 days
	970 per 1000	912 per 1000 (815 to 1000)
Ability to complete procedure	Study population		RR 1.00 (0.95 to 1.06)	68 (1 RCT)	⊕⊕⊝⊝ LOW ¹	There may be little to no difference in ability to complete procedure between vaginal misoprostol and buccal misoprostol. Gestational age: 16 weeks 0 days to 20 weeks 6 days
	1000 per 1000	1000 per 1000 (950 to 1000)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; IQR: interquartile range; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

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¹Downgraded two levels for imprecision: few participants, and 95% CI spans possible benefit and possible harm. ²Downgraded two levels for imprecision: few participants, and no P value reported. ³Downgraded two levels for imprecision: few participants.

Background

Description of the condition

Abortion remains one of the most common procedures among reproductive‐aged women (Jones 2017). Between 2010 and 2014, around 55.9 million abortions occurred annually among women aged 15 to 49 years (Guttmacher 2018). While the majority of abortions worldwide take place in the first trimester, for a variety of reasons pregnancy terminations also occur in the second trimester (Ashok 2004; Lohr 2008; Zane 2015). Reasons leading to second trimester abortions include second trimester diagnoses of pregnancy or fetal anomalies, logistic and financial barriers to abortion services, abortion restrictions, ambivalence, and fear of disclosure or of the procedure (Drey 2006; George 1996; Grimes 1998; Ingham 2008). Procedure‐related complications slightly increase as gestational age increases (Zane 2015).

Description of the intervention

Both medical and procedural (or 'surgical') methods of abortion have continued to be developed over the last five decades. Dilation and evacuation (D&E), introduced in the 1970s, has become the preferred surgical technique over dilation and curettage, hysterotomy, and hysterectomy because of its relative safety (Cates 1982; Grimes 1985). Dilation and evacuation involves preparing the cervix using mechanical or pharmacologic means, or both, followed by evacuation of the uterine content through the introduction of instruments into the uterine cavity through the cervix (Lohr 2008; Poon 2007).

How the intervention might work

Osmotic dilators are the common mechanical methods of cervical priming agents used. There are two types of osmotic dilators: Laminaria japonica and Dilapan‐S (Drunecký 2015; Eaton 1972). Laminaria japonica expands slowly by absorbing interstitial fluid from the cervix. The maximum effect on the cervix is usually achieved after 24 hours of laminaria application. Dilapan‐S is a synthetic dilator that acts rapidly to open the cervix and reaches its maximum dilation effect on the cervix after six hours (Drunecký 2015). Prostaglandins and antiprogesterones are the common pharmacologic methods used for cervical preparation. Misoprostol, a prostaglandin E1 analogue used for cervical priming, is stable at room temperature and can be administered orally, buccally, sublingually, or vaginally (Goldberg 2001; Meckstroth 2006). Mifepristone is a synthetic steroid that acts as an antiprogesterone, competitively binding to progesterone receptors and softening the cervix. It is provided 24 to 48 hours prior to the surgical abortion (Baulieu 1997; Cadepond 1997).

Why it is important to do this review

Many agents are used for cervical priming, and little is known about the optimal method of cervical priming agent for second trimester D&E. There is also a knowledge gap in determining the effectiveness and safety of combining priming agents prior to D&E. Since the publication of the first systematic review on this topic, multiple studies have been conducted comparing the use of various cervical priming agents, thus the importance of updating the previous systematic review.

Objectives

To assess the effectiveness of cervical preparation methods for people undergoing second trimester surgical abortion at the gestational age of between 12 and 24 0/7 weeks.

Methods

Criteria for considering studies for this review

Types of studies

We included randomized controlled trials (RCTs) that compared different cervical priming agents before D&E between 12 and 24 weeks of gestational age. Trials using quasi‐random methods of allocation and cluster‐randomized trials were also eligible. Cross‐over studies were not eligible because we considered this to be an unsuitable study design for our clinical question.

Types of participants

We included trials of reproductive‐age participants having a second trimester surgical abortion with cervical preparation using medical or mechanical methods, or both. We included studies where the gestational duration was between 12 weeks 0 days and 23 weeks 6 days.

Types of interventions

We included trials of any mechanical or pharmacological methods of cervical priming. We also included studies that evaluated same‐day and overnight cervical priming as well as one day and two days of cervical preparation before the procedure (D&E).

Types of outcome measures

Primary outcomes

Procedure time
Dilation achieved
Need for additional dilation
Ability to complete procedure

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)
Side effects (gastrointestinal [nausea, vomiting, diarrhea] and fever/chills)
Complications (including but not limited to hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)
Patient acceptability and/or satisfaction
Pain experienced between initiation of cervical preparation method and abortion procedure
Provider acceptability and/or satisfaction
Provider assessment of difficulty of procedure

Search methods for identification of studies

The Cochrane Fertility Regulation Group Information Specialist conducted a search for all published, unpublished, and ongoing studies, with no restrictions on language or publication status, on 20 December 2021. We applied a date limit of 2008 to capture literature published since the previous review. The previous systematic review search included the POPLINE database; however, due to its cessation in 2019 it was not included in this update. The search strategies were heavily edited to adhere to current Methodological Expectations of Cochrane Intervention Reviews (MECIR) standards. We have provided updated search strategies in Appendix 1 and previous search strategies in Appendix 2. We considered adverse effects described in the included studies only.

Electronic searches

We searched the following databases.

Cochrane Central Register of Controlled Trials (CENTRAL) (Ovid EBM Reviews) (searched 20 December 2021)
MEDLINE ALL (Ovid) (1946 to 20 December 2021)
Embase.com (1947 to 20 December 2021)
Global Index Medicus (pesquisa.bvsalud.org/gim/?lang=en) (1948 to 20 December 2021)
Global Health (Ovid) (1973 to 2021 Week 12)
Scopus (conference abstracts only) (2004 to 20 December 2021)
Google Scholar (2004 to 23 December 2021)

Searching other resources

We searched the reference lists of identified studies, relevant review articles, book chapters, and conference proceedings for additional, previously unidentified trials. We contacted experts in the field for information on other published or unpublished trials.

Data collection and analysis

Selection of studies

Two review authors (SN and TT) independently screened the titles and abstracts of studies identified by the search for potential relevance. We obtained the full text of studies deemed potentially relevant, and the same two review authors assessed the full‐text reports for inclusion in the review. Any conflicts between review authors were resolved through discussion. We also reviewed six studies included in the previous version of the review for eligibility in the current review.

Data extraction and management

At least two review authors (SN, TT, FS) independently extracted data from the included studies. Discrepancies between review authors were resolved through discussion. We attempted to contact the authors of the original studies for further information as needed.

Assessment of risk of bias in included studies

Two review authors independently performed risk of bias assessment using the Cochrane RoB 1 tool (Higgins 2011). We assessed each included study for risk of bias in the following domains: random sequence generation; allocation concealment; blinding of participants and personnel; blinding of outcome assessment; incomplete outcome data; selective reporting; and other bias. Any differences of opinion were resolved through consensus or by consulting a third review author.

Measures of treatment effect

Dichotomous data

For dichotomous data, we presented results as risk ratios (RR) with 95% confidence intervals (CI).

Continuous data

For combining continuous data in meta‐analysis, we presented mean difference (MD) and 95% CI. If we identify studies that use different scales to measure the same outcome in future updates, we will analyze the data using standardized mean difference (SMD) and 95% CI with the following interpretation:

SMD 0.8 or greater = large effect;
SMD greater than 0.49 and less than 0.8 = medium effect;
SMD greater than 0.19 and less than 0.5 = small effect;
SMD less than 0.2 = trivial or no effect.

Where studies reported medians and interquartile ranges (IQRs), we converted the data to means and standard deviations (SDs) using the methods described in Wan 2014. If the median and mean were similar, we included the converted data (mean, SD) in meta‐analysis.

Where dilation achieved was reported differently by trials in the same meta‐analysis, we converted French units to millimeters by dividing by three.

Unit of analysis issues

The unit of analysis was per person randomized. In studies with more than two arms, we combined study arms where there was sufficient clinical homogeneity, such as in a three‐ or four‐arm trial where two groups received the same drug, but in one group it was administered sublingually and the other vaginally.

Dealing with missing data

To the greatest degree possible, we undertook analysis on an intention‐to‐treat basis for all studies, that is all participants were analyzed in the group to which they had initially been allocated regardless of whether or not they received the intended treatment.

We contacted study authors to obtain missing data for the outcomes included in our summary of findings tables.

Assessment of heterogeneity

We explored heterogeneity in meta‐analysis through examining the I² statistic and visual inspection of the forest plot, in addition to study characteristics and effects across studies.

We interpreted I² based on the following guidance (Higgins 2020):

0% to 40%: heterogeneity might not be important;
30% to 60%: may represent moderate heterogeneity;
50% to 90%: represent substantial heterogeneity;
75% to 100%: represent considerable heterogeneity.

The variance components of a random‐effects model cannot be adequately estimated, and the I² is less valid for assessing heterogeneity when very few studies are available for meta‐analysis (fewer than five). Consequently, variations in study characteristics and in effects across studies were additionally noted to evaluate consistency, rather than only statistical heterogeneity.

Assessment of reporting biases

If in future updates we identify 10 or more studies with data suitable for pooling in a meta‐analysis, we will construct funnel plots and use Egger’s statistical test to assess funnel plot symmetry. Where we identify substantial funnel plot symmetry, we will explore the possible underlying reasons, which may be related to small‐study effects, lack of publication of non‐statistically significant results, or chance (Higgins 2020).

Data synthesis

We used Review Manager 5 and RevMan for statistical analysis (Review Manager 2020; RevMan 2024). In cases where the randomized trials were sufficiently similar, we undertook a pooled analysis with meta‐analysis statistical techniques to estimate effect. We used fixed‐effect meta‐analysis except where there was substantial statistical heterogeneity, in which case we used random‐effects meta‐analysis.

Subgroup analysis and investigation of heterogeneity

We intended to investigate possible sources of heterogeneity through subgroup analysis by using gestational age classification of up to 19 + 6 weeks and beyond, but this was not possible due to the low number of trials in each comparison. In subsequent updates as more data become available, we will perform subgroup analysis for the primary outcomes by stratifying the data into two or more gestational age groups.

Sensitivity analysis

Given that five or fewer studies were available for meta‐analysis, we reported the random‐effects estimate for the pooled effect, but also conducted sensitivity analyses using the fixed‐effect model, considering whether the included studies were similar in size, quality, and direction of the effect, since the fixed‐effect model weights larger studies more heavily and generally results in a more precise effect estimate. If we found results to differ substantially on the basis of the model choice, we reported the more conservative estimate (generally the random‐effects estimate). Inconsistent results depending on the model choice were noted, and increased uncertainty with regard to the finding. In future updates where there are sufficient data, we will perform sensitivity analysis for the primary outcomes by removing from the analysis studies with high risk of bias in any one of the random sequence generation, allocation concealment, or incomplete outcome data domains.

Summary of findings and assessment of the certainty of the evidence

We assessed the certainty of evidence using the GRADE approach and created summary of findings tables for the following comparisons.

Prostaglandin versus osmotic dilators
Mifepristone plus misoprostol versus osmotic dilators
Misoprostol plus osmotic dilators versus placebo plus osmotic dilators
Mifepristone plus osmotic dilators versus placebo plus osmotic dilators
Misoprostol plus osmotic dilators versus mifepristone plus osmotic dilators
Mifepristone plus misoprostol plus osmotic dilators versus misoprostol plus osmotic dilators
Misoprostol plus osmotic dilators versus misoprostol
Laminaria versus synthetic osmotic dilator
Same‐day Dilapan‐S versus overnight laminaria
Vaginal misoprostol versus buccal misoprostol

We included the following outcomes in the summary of findings tables.

Procedure time
Dilation achieved
Need for additional dilation
Ability to complete procedure

Two review authors independently assessed the certainty of the evidence as high, moderate, low, or very low based on the five GRADE considerations (risk of bias, consistency of effect, imprecision, indirectness, and publication bias) (Guyatt 2008). We used the methods and recommendations described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2020), employing GRADEpro GDT software (GRADEpro GDT). Any disagreements on certainty ratings were resolved by discussion. We provided justification for our decisions using footnotes and made comments to aid the reader's understanding of the review where necessary.

Results

Description of studies

Results of the search

A total of 4313 abstracts were identified in the literature search for title and abstract screening, of which 33 articles were eligible for full‐text screening. Twenty‐one articles fulfilled the eligibility criteria and were included in the review. Six studies were included in the previous systematic review, and 15 were identified by the updated search (Figure 1).

Included studies

Study design

All studies included in the review were RCTs. Two trials had four arms (Carbonell 2007; Shakir 2019), and two other trials had three arms (Dayananda 2016; Shaw 2017). The remaining 17 RCTs had two arms.

Participants

All participants in the studies were of reproductive age undergoing surgical abortion in second trimester. The included studies involved a wide range of gestational ages, from 12 weeks to 24 weeks (see Table 11). Fourteen studies only included participants aged 18 years or older (Boraas 2016; Borgatta 2012; Casey 2016; Casey 2018; Dayananda 2016; Drey 2014; Goldberg 2005; Goldberg 2015; Grossman 2014; Newmann 2014; Paris 2020; Shakir 2019; Shaw 2015; Shaw 2017). In one trial the lower age limit was 15 (Sagiv 2015). Two trials imposed an upper age limit of 45 (Borgatta 2012; Paris 2020). The remaining studies did not specify age limit criteria to be included in the study. Thirteen studies made subgroup analysis with parity (nulliparous versus parous) (Boraas 2016; Borgatta 2012; Casey 2016; Casey 2018; Drey 2014; Edelman 2006; Goldberg 2005; Goldberg 2015; Grossman 2014; Newmann 2014; Paris 2020; Shakir 2019; Stubblefield 1982).

1. Gestational ages.

Study	Minimum gestational age	Maximum gestational age
Boraas 2016	16 0/7	20 6/7
Borgatta 2012	14	16
Carbonell 2007	12	20
Casey 2016	14	19 6/7
Casey 2018	16	20 6/7
Dayananda 2016	18	23 6/7
Dean 2017	18	24 0/7
Drey 2014	21	23 1/7
Edelman 2006	13	20 6/7
Goldberg 2005	13	16
Goldberg 2015	16	23 6/7
Grimes 1987	Approximately 13 6/7 (biparietal diameter of the fetus 25 to 33 mm)	Approximately 16 0/7
Grossman 2014	13	19
Newmann 2014	13 6/7	17 6/7
Paris 2020	15	18
Sagiv 2015	13	20
Shakir 2019	14	19 6/7
Shaw 2015	19	23 6/7
Shaw 2017	19	23 6/7
Stubblefield 1982	17	19
Zamblera 1994	15	20

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Except for one study that used menstrual dating for gestational age determination (Stubblefield 1982), all of the included studies used ultrasound to ascertain gestational age prior to abortion. Seven studies excluded people with pregnancy complicated by intrauterine fetal death (Borgatta 2012; Casey 2016; Casey 2018; Dayananda 2016; Goldberg 2015; Paris 2020; Shakir 2019). Three studies excluded pregnancies with multiple gestations (Boraas 2016; Grossman 2014; Sagiv 2015). Two studies excluded people with more than one previous cesarean scar (Goldberg 2015; Grossman 2014). One study excluded people with any uterine scar and did not specify the type or number of uterine scars (Drey 2014).

Setting

Seventeen studies were conducted in the USA (Boraas 2016; Borgatta 2012; Casey 2016; Casey 2018; Dayananda 2016; Dean 2017; Drey 2014; Edelman 2006; Goldberg 2005; Goldberg 2015; Grimes 1987; Newmann 2014; Paris 2020; Shakir 2019; Shaw 2015; Shaw 2017; Stubblefield 1982). One study each took place in South Africa (Grossman 2014), Israel (Sagiv 2015), the UK (Zamblera 1994), and Spain (Carbonell 2007).

Sample size

Study sample sizes ranged from 29, Boraas 2016, to 900, Carbonell 2007 (median sample size = 84). One study did not state how many participants were randomized or analyzed (Dean 2017).

Interventions

We identified studies investigating the following comparisons.

A. Medication versus osmotic dilators

Mifepristone versus osmotic dilators (Borgatta 2012)
Prostaglandin versus osmotic dilators (Goldberg 2005; Grossman 2014; Sagiv 2015; Zamblera 1994)
Mifepristone plus misoprostol versus osmotic dilators (Paris 2020)
Mifepristone plus misoprostol versus osmotic dilators plus placebo and misoprostol (Shaw 2017)

B. Medication plus osmotic dilators versus osmotic dilators

Misoprostol plus osmotic dilators versus placebo plus osmotic dilators (Boraas 2016; Drey 2014; Edelman 2006; Goldberg 2015)
Mifepristone plus osmotic dilators versus placebo plus osmotic dilators (Goldberg 2015)

C. Medication plus osmotic dilators versus medication

Misoprostol plus osmotic dilators versus misoprostol (Shakir 2019)
Misoprostol plus mifepristone plus osmotic dilators versus misoprostol plus mifepristone (Shaw 2017)

D. Medication versus medication

Mifepristone plus misoprostol versus misoprostol (Carbonell 2007; Casey 2016)
Mifepristone plus misoprostol (plus osmotic dilators) versus misoprostol (plus osmotic dilators) (Shaw 2015; Shaw 2017)
Misoprostol (plus osmotic dilators) versus mifepristone (plus osmotic dilators) (Goldberg 2015)

E. Osmotic dilators versus osmotic dilators

Laminaria versus synthetic osmotic dilator (Dayananda 2016; Grimes 1987)
Same‐day Dilapan‐S versus overnight laminaria (Newmann 2014)
One day laminaria versus two days laminaria (Stubblefield 1982)

F. Different routes of medication administration

Vaginal misoprostol versus buccal misoprostol (Shakir 2019)
Vaginal misoprostol plus osmotic dilators versus buccal misoprostol plus osmotic dilators (Shakir 2019)
Vaginal misoprostol (plus mifepristone) versus buccal misoprostol (plus mifepristone) (Casey 2018)

G. Different doses and intervals of medication

Misoprostol 400 μg three hours prior to procedure versus misoprostol 600 μg 90 minutes prior to procedure (Dean 2017)

Outcomes

All included studies reported at least one of our primary outcomes.

Procedure time

Eighteen trials reported procedure time (Boraas 2016; Borgatta 2012; Carbonell 2007; Casey 2016; Casey 2018; Dayananda 2016; Dean 2017; Drey 2014; Goldberg 2005; Goldberg 2015; Grossman 2014; Newmann 2014; Paris 2020; Sagiv 2015; Shakir 2019; Shaw 2015; Shaw 2017; Stubblefield 1982).

There was heterogeneity in the way that the included studies defined procedure time. Seven studies defined procedure time as time elapsed from speculum in to speculum out following the end of the procedure (Borgatta 2012; Goldberg 2015; Grossman 2014; Paris 2020; Shakir 2019; Shaw 2015; Shaw 2017). Four studies described procedure time as initial insertion of either forceps or dilators until the last instrument was removed from the cervix (Boraas 2016; Drey 2014; Newmann 2014; Sagiv 2015). One study defined procedure time as time taken from induction of anesthesia to removal of speculum (Carbonell 2007). Two studies defined it as time from completion of cervical dilation to removal of the speculum (Casey 2016; Casey 2018). Five studies did not describe the method used to define procedure time (Dayananda 2016; Dean 2017; Edelman 2006; Goldberg 2005; Stubblefield 1982).

Dilation achieved

Twenty trials assessed pre‐procedure cervical dilation (Boraas 2016; Borgatta 2012; Carbonell 2007; Casey 2016; Casey 2018; Dayananda 2016; Dean 2017; Drey 2014; Edelman 2006; Goldberg 2005; Goldberg 2015; Grimes 1987; Newmann 2014; Paris 2020; Sagiv 2015; Shakir 2019; Shaw 2015; Shaw 2017; Stubblefield 1982; Zamblera 1994). Fifteen trials measured cervical dilation by determining the dilator circumference where no resistance was felt, after starting dilation with the largest dilator and decreasing in circumference until one would easily pass through the internal cervical os (Boraas 2016; Borgatta 2012; Casey 2016; Casey 2018; Drey 2014; Edelman 2006; Goldberg 2005; Goldberg 2015; Grimes 1987; Newmann 2014; Paris 2020; Sagiv 2015; Shakir 2019; Stubblefield 1982; Zamblera 1994).

One study used a reverse method for cervical dilation assessment by recording the diameter of the Hegar dilator inserted into the cervix just before cervical resistance was first noticed (Carbonell 2007). Two studies assessed cervical dilation using bimanual exam (Shaw 2015; Shaw 2017). Three studies did not describe the method used for cervical dilation (Dayananda 2016; Dean 2017; Grossman 2014).

The dates of two trials straddled the first and second decades of the 21st century (Borgatta 2012; Sagiv 2015). Two trials did not report the dates when the study took place (Stubblefield 1982; Zamblera 1994).

Funding sources

Fourteen trials reported funding from educational institutions, charitable sources, or family planning research funds (Boraas 2016; Borgatta 2012; Casey 2016; Casey 2018; Drey 2014; Edelman 2006; Goldberg 2005; Goldberg 2015; Grossman 2014; Newmann 2014; Paris 2020; Shakir 2019; Shaw 2015; Shaw 2017).

One trial reported funding from commercial sources (Carbonell 2007), and six trials did report their sources of funding (Dayananda 2016; Dean 2017; Grimes 1987; Sagiv 2015; Stubblefield 1982; Zamblera 1994)

Declarations of interest

Twelve trials explicitly stated that the authors had no declarations of interest to make (Boraas 2016; Borgatta 2012; Casey 2016; Casey 2018; Drey 2014; Goldberg 2015; Grossman 2014; Newmann 2014; Paris 2020; Sagiv 2015; Shaw 2015; Shaw 2017).

One trial reported potential conflicts of interest for two authors who declared involvement with commercial companies producing healthcare products (Shakir 2019).

Eight trials did not report any details of declarations of interest (Carbonell 2007; Dayananda 2016; Dean 2017; Edelman 2006; Goldberg 2005; Grimes 1987; Stubblefield 1982; Zamblera 1994).

Excluded studies

We excluded 12 studies (see Characteristics of excluded studies) for the following reasons:

wrong study design (Cahill 2018; Chambers 2011a; Chambers 2011b; Lyus 2013; Shaw 2016b);
wrong patient population (Bartz 2013);
study was withdrawn due to funding changes before any participants were recruited (NCT02679092);
study results not available (NCT01678703; NCT02013960; NCT02279914; NCT02363556; NCT03714880).

Risk of bias in included studies

Risk of bias summaries are presented in Figure 2 and Figure 3.

Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgments about each risk of bias item for each included study.

Allocation

Random sequence generation

We judged three studies as at unclear risk of bias because the method of random number generation is not clearly stated. We judged the remaining studies as at low risk of bias because they used computer‐generated random numbers (Dayananda 2016; Dean 2017; Zamblera 1994).

Allocation concealment

We assessed five studies as at unclear risk of bias because they did not clearly describe the allocation process. We assessed the remaining studies as low risk for allocation concealment because they used opaque, sealed envelopes to conceal the allocation (Dayananda 2016; Dean 2017; Drey 2014; Stubblefield 1982; Zamblera 1994).

Blinding

Blinding of participants and personnel

We assessed one study as at unclear risk of performance bias because it did not clearly describe blinding of participants and personnel (Zamblera 1994). The remaining studies clearly described the blinding of participants and personnel and so were assessed as at low risk of performance bias.

Blinding of outcome assessment

We assessed four studies as at unclear risk of detection bias because they did not clearly describe blinding of outcome assessors (Carbonell 2007; Dean 2017; Stubblefield 1982; Zamblera 1994). We assessed one study as high risk because the outcome assessor was not blinded (Borgatta 2012). We assessed the remaining studies as at low risk of detection bias because they described blinding of outcome assessment.

Incomplete outcome data

We assessed all studies but one as at low risk of attrition bias because there was no evidence of high or differential attrition. We assessed Dean 2017 as at unclear risk of bias because they did not report any denominators, thereby preventing a determination of whether outcome data were complete.

Selective reporting

We assessed eight studies as at unclear risk of reporting bias because we could not find any trial registry records or published protocols to judge whether the outcomes reported in the published papers were the same as those prespecified when the trials began (Carbonell 2007; Drey 2014; Edelman 2006; Goldberg 2005; Grimes 1987; Shaw 2017; Stubblefield 1982; Zamblera 1994).

We assessed three studies as at high risk of reporting bias: two because they did not report outcomes according to randomization group (Dayananda 2016; Shakir 2019), and one because the primary outcome was not reported with full data (Dean 2017).

We assessed the remaining studies as at low risk of reporting bias because the trial registration records were available, and we judged that all the outcomes were reported in full, per randomization groups.

Other potential sources of bias

We identified no other obvious source of bias in the included studies and therefore assessed all of the included studies as at low risk of bias.

Effects of interventions

See: Table 1; Table 2; Table 3; Table 4; Table 5; Table 6; Table 7; Table 8; Table 9; Table 10

Comparison 1: prostaglandin versus osmotic dilators (12 6/7 to 20 weeks)

Four trials investigated prostaglandin compared with osmotic dilators (Goldberg 2005; Grossman 2014; Sagiv 2015; Zamblera 1994).

Primary outcomes

Procedure time

Prostaglandin may have little to no effect on procedure time compared with osmotic dilators (low‐certainty evidence; Table 1). Three studies reported procedure time in a way that could not be pooled in a meta‐analysis; we have presented the medians and mean (no SD reported) in Analysis 1.1.

1.1. Analysis.

Comparison 1: Prostaglandin versus osmotic dilators, Outcome 1: Procedure time

Procedure time
Study	Misoprostol	Laminaria	Measure	Result
Goldberg 2005	7.2 minutes (1.1‐18.3) 41 women	3.4 minutes (1.1–20.9) 42 women	Median (range)	Effect of misoprostol compared with laminaria 3.8 minutes longer P = 0.01
Grossman 2014	12.8 minutes 78 women	12.5 minutes 78 women	Mean (no SD reported)	P = 0.693
Sagiv 2015	10 minutes (3–20) 41 women	11 minutes (5–30) 43 women	Median (range)	Effect of misoprostol compared with laminaria 1 minute shorter P = 0.03

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Two studies reported median procedure time after prostaglandin compared with osmotic dilators and found conflicting results (Goldberg 2005; Sagiv 2015). In one study (Goldberg 2005), prostaglandin led to an increase in procedure time significantly (P = 0.01), while the other study found that prostaglandin led to a reduction in procedure time by one minute (P = 0.03) (Analysis 1.1) (Sagiv 2015).

Dilation achieved

Compared with osmotic dilators, prostaglandin probably leads to a reduction in dilation achieved (mean difference (MD) −3.58 mm, 95% confidence interval (CI) −4.58 to −2.58; I² = 39%; 3 studies; 217 participants; moderate‐certainty evidence; Table 1; Analysis 1.2).

1.2 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 2: Dilation achieved (mm)

Need for additional dilation

It is uncertain if prostaglandin has any effect on the need for additional dilation compared to osmotic dilators (risk ratio (RR) 1.85, 95% CI 0.45 to 7.52; I² = 90%; 2 studies; 167 participants; very low‐certainty evidence; Analysis 1.3; Table 1) because the certainty of evidence is low, and the 95% CI is consistent with possible benefit and possible harm.

1.3 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 3: Need for additional dilation

Ability to complete procedure

Prostaglandin may result in little to no difference in ability to complete procedure compared to osmotic dilators (RR 0.99, 95% CI 0.95 to 1.03; I² = 0%; 2 studies; 167 participants; low‐certainty evidence; Analysis 1.4; Table 1).

1.4 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 4: Ability to complete procedure (number completed on first attempt)

Secondary outcomes

Adverse events related to cervical preparation agents

It is uncertain if prostaglandin has any effect on the risk of pre‐procedure expulsion (RR 5.00, 95% CI 0.24 to 102.49; I² = 0%; 1 study; 156 participants; Analysis 1.5). Other adverse events were not reported.

1.5 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 5: Adverse events (pre‐procedure expulsion)

Side effects

Nausea

It is uncertain if prostaglandin has any effect on nausea compared with osmotic dilators (RR 1.38, 95% CI 0.41 to 4.71; 3 studies; 319 participants; I² = 59%; Analysis 1.6.1). The effect estimate was similar in one study that also reported nausea at three to four hours after taking prostaglandin or placebo (RR 1.37, 95% CI 0.33 to 5.73; 1 study; 83 participants; Analysis 1.6.2).

1.6 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 6: Side effects: nausea

Vomiting

It is uncertain if prostaglandin has any effect on vomiting compared with osmotic dilators (RR 0.84, 95% CI 0.11 to 3.19; 3 studies; 319 participants; I² = 65%; Analysis 1.7.1). The effect estimate was similar in one study that also reported nausea at three to four hours after taking prostaglandin or placebo (RR 0.34, 95% CI 0.04 to 3.15; 1 study; 83 participants; Analysis 1.7.2).

1.7 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 7: Side effects: vomiting

Diarrhea

Prostaglandin may increase the risk of diarrhea (RR 2.95, 95% CI 1.33 to 6.54; 3 studies; 319 participants; I² = 0%; Analysis 1.8).

1.8 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 8: Side effects: diarrhea

Chills/fever

Prostaglandin may increase the risk of chills (RR 3.17, 95% CI 1.72 to 5.83; 3 studies; 319 participants; I² = 0%; Analysis 1.9.1). Another study reported that 2/41 participants in the prostaglandin group had fever, compared with 0/43 in the dilator group (RR 5.24, 95% CI 2.26 to 105.93; 1 study; 83 participants; Analysis 1.9.2).

1.9 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 9: Side effects: fever/chills

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

Compared with osmotic dilators, it is uncertain if prostaglandin has any effect on the risk of hemorrhage requiring transfusion (RR 0.35, 95% CI 0.01 to 8.34; 1 study; 84 participants; Analysis 1.10.1); uterine perforation (RR 3.04, 95% CI 0.32 to 28.73; 2 studies; 239 participants; I² = 0%; Analysis 1.10.2); or endometritis (RR 0.34, 95% CI 0.04 to 3.19; 2 studies; 239 participants; I² = 0%; Analysis 1.10.3).

1.10 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 10: Complications

Patient acceptability and/or satisfaction

One study measured the number of participants who would choose the same cervical preparation method again (Goldberg 2005). Prostaglandin may increase the number of participants who would choose the same method again compared with osmotic dilators (RR 1.50, 95% CI 1.16 to 1.93; 1 study; 83 participants; Analysis 1.11).

1.11 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 11: Patient acceptability and/or satisfaction

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

It is uncertain if prostaglandin has any effect on pain compared with osmotic dilators (RR 2.59, 95% CI 0.23 to 28.94; 2 studies; 206 participants; I² = 83%; Analysis 1.12). The high statistical heterogeneity appears to be due to differences between studies in direction and size of effect.

1.12 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 12: Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Two studies reported median pain scores (Goldberg 2015; Sagiv 2015). In one study, prostaglandin led to less pain compared with osmotic dilators (P < 0.01), while in the other study there was no significant difference between prostaglandin and misoprostol (P = 0.8) (Analysis 1.13).

1.13. Analysis.

Comparison 1: Prostaglandin versus osmotic dilators, Outcome 13: Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Pain experienced by participants between initiation of cervical preparation method and abortion procedure
Study	Misoprostol	Laminaria	Measure	Result
Goldberg 2005	41 women Overnight: 0 (0–3) 3‐4 hours after misoprostol (i.e., pain immediately before procedure): 2 (0–5)	42 women Overnight: 1 (0–5) 3‐4 hours after placebo (i.e., pain immediately before procedure): 0 (0–4)	Median (range) 0‐5 scale Higher score = greater pain	Overnight: misoprostol reduced pain compared with placebo plus laminaria (P < 0.01) 3‐4 hours after misoprostol/placebo: misoprostol increased pain compared with placebo plus laminaria (P < 0.01)
Sagiv 2015	41 women Overnight: 5.5 (1–10)	43 women Overnight: 3 (1–10)	0‐10 VAS (median, range) (higher score = greater pain)	Effect of misoprostol compared with laminaria: 1.5 VAS points more painful (P = 0.8)

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Provider acceptability and/or satisfaction

Prostaglandin may lead to lower provider satisfaction with cervical preparation compared with osmotic dilators (RR 0.38, 95% CI 0.26 to 0.58; 1 study; 83 participants; Analysis 1.14).

1.14 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 14: Provider acceptability and/or satisfaction

Provider assessment of difficulty of procedure

Providers may be much more likely to assess procedures as difficult when using prostaglandin compared with osmotic dilators (RR 6.31, 95% CI 1.74 to 22.94; 2 studies; 133 participants; I² = 0%; Analysis 1.15).

1.15 — Comparison 1: Prostaglandin versus osmotic dilators, Outcome 15: Provider assessment of difficulty of procedure

A further study reported that 16/27 of the prostaglandin arm procedures and 1/6 of the osmotic dilator arm procedures that required mechanical dilation were rated as difficult by the providers (Grossman 2014), but we did not include these data in the meta‐analysis because difficulty of procedure was only rated in participants who required mechanical dilation. Since requiring mechanical dilation or not could be affected by the original randomized allocation to either prostaglandin or osmotic dilators, the subset of the trial population that provided data for the outcome 'provider assessment of difficulty of procedure' is no longer a valid comparison between the randomized groups.

Comparison 2: mifepristone plus 400 μg buccal misoprostol versus osmotic dilators (15 to 18 weeks)

One study investigated mifepristone plus misoprostol compared with osmotic dilators (Paris 2020).

Primary outcomes

Procedure time

Mifepristone plus misoprostol may have little to no effect on procedure time compared with osmotic dilators (MD −0.30, 95% CI −3.46 to 2.86; 1 study; 49 participants; low‐certainty evidence; Analysis 2.1; Table 2).

2.1 — Comparison 2: Mifepristone + misoprostol versus osmotic dilators, Outcome 1: Procedure time (minutes)

Dilation achieved

Mifepristone plus misoprostol may lead to less dilation achieved compared with osmotic dilators (MD −1.67, 95% CI −3.19 to −0.15; 1 study; 49 participants; low‐certainty evidence; Analysis 2.2; Table 2).

2.2 — Comparison 2: Mifepristone + misoprostol versus osmotic dilators, Outcome 2: Dilation achieved (mm)

Need for additional dilation

Mifepristone plus misoprostol may increase the need for additional dilation compared with osmotic dilators (RR 1.92, 95% CI 1.16 to 3.18; 1 study; 49 participants; low‐certainty evidence; Analysis 2.3; Table 2).

2.3 — Comparison 2: Mifepristone + misoprostol versus osmotic dilators, Outcome 3: Need for additional dilation

Ability to complete procedure

Mifepristone plus misoprostol may have little to no effect on ability to complete procedure compared with osmotic dilators (RR 1.00, 95% CI 0.92 to 1.08; 1 study; 49 participants; low‐certainty evidence; Analysis 2.4; Table 2).

2.4 — Comparison 2: Mifepristone + misoprostol versus osmotic dilators, Outcome 4: Ability to complete procedure

Secondary outcomes

Adverse events related to cervical preparation agents

Not reported.

Side effects

It is uncertain if mifepristone plus misoprostol has any effect on the risk of nausea or vomiting, or both, the night before the procedure, compared with osmotic dilators (RR 0.57, 95% CI 0.20 to 1.63; 1 study; 49 participants; Analysis 2.5).

2.5 — Comparison 2: Mifepristone + misoprostol versus osmotic dilators, Outcome 5: Side effects: nausea/vomiting

The same study also reported 0/29 participants in the mifepristone plus misoprostol group and 0/20 participants in the osmotic dilators group experienced nausea or vomiting, or both, on the morning of the procedure.

No other side effects were reported for this comparison.

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

One study reported: “There were no immediate complications, including incomplete abortion, cervical laceration, repeat procedure, infection or excessive blood loss” (0/29 and 0/20) (Paris 2020).

Patient acceptability and/or satisfaction

Mifepristone plus misoprostol may lead to greater patient satisfaction compared with osmotic dilators (RR 2.87, 95% CI 1.45 to 5.70; 1 study; 49 participants; Analysis 2.6).

2.6 — Comparison 2: Mifepristone + misoprostol versus osmotic dilators, Outcome 6: Patient acceptability

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

It is uncertain if mifepristone plus misoprostol has any effect on pain compared with osmotic dilators (RR 0.46, 95% CI 0.08 to 2.51; 1 study; 49 participants; Analysis 2.7).

2.7 — Comparison 2: Mifepristone + misoprostol versus osmotic dilators, Outcome 7: Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Provider acceptability and/or satisfaction

Not reported.

Provider assessment of difficulty of procedure

It is uncertain if mifepristone plus misoprostol has any effect on provider assessment of difficulty compared with osmotic dilators (RR 0.92, 95% CI 0.23 to 3.67; 1 study; 49 participants; Analysis 2.8).

2.8 — Comparison 2: Mifepristone + misoprostol versus osmotic dilators, Outcome 8: Provider assessment of difficulty of procedure

Comparison 3: 400 μg buccal misoprostol plus osmotic dilators versus placebo plus osmotic dilators (13 0/7 and 23 6/7 weeks)

Four studies investigated misoprostol plus osmotic dilators compared with placebo plus osmotic dilators (Boraas 2016; Drey 2014; Edelman 2006; Goldberg 2015).

Primary outcomes

Procedure time

Misoprostol plus osmotic dilators probably reduces procedure time slightly compared with placebo plus osmotic dilators (MD −0.99, 95% CI −2.05 to 0.06; 4 studies; 545 participants; I² = 65%; moderate‐certainty evidence; Analysis 3.1; Table 3).

3.1 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 1: Procedure time

For transparency, we have also presented the original data, which we converted from median (IQR) to mean (SD) (Analysis 3.2).

3.2. Analysis.

Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 2: Procedure time

Procedure time
Study	Misoprostol + dilators	Placebo + dilators	Measure	Result
Goldberg 2015	10.13 minutes (8.6–11.6) 98 women	11.58 minutes (10.0–13.1) 98 women	Median (IQR)	Effect of adding misoprostol to dilator ‐1.45 minutes

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Dilation achieved

Misoprostol plus osmotic dilators probably results in a slight increase in dilation achieved compared with placebo plus osmotic dilators (MD 1.83, 95% CI 0.27 to 3.39; 4 studies; 484 participants; I² = 65%; moderate‐certainty evidence; Analysis 3.3; Table 3).

3.3 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 3: Dilation achieved (mm)

For transparency, we have also presented the original data, which we converted from median (IQR) to mean (SD) (Analysis 3.4).

3.4. Analysis.

Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 4: Dilation achieved

Dilation achieved
Study	Misoprostol + dilators	Placebo + dilators	Measure	Result
Drey 2014	75 mm (71–79) 98 women	73 mm (67–77) 98 women	Median, IQR	Greater dilation with misoprostol plus dilator compared to placebo plus dilator P = 0.04

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Need for additional dilation

Misoprostol plus osmotic dilators probably reduces the number of participants who need additional dilation compared with placebo plus osmotic dilators (RR 0.65, 95% CI 0.50 to 0.84; 4 studies; 546 participants; I² = 55%; moderate‐certainty evidence; Analysis 3.5; Table 3).

3.5 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 5: Need for additional dilation

Ability to complete procedure

Adding misoprostol to osmotic dilators probably has little to no effect on ability to complete procedure compared to placebo plus osmotic dilators (RR 0.99, 95% CI 0.96 to 1.02; 1 study; 199 participants; moderate‐certainty evidence; Analysis 3.6; Table 3).

3.6 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 6: Ability to complete procedure (number completed on first attempt)

Secondary outcomes

Adverse events related to cervical preparation agents

It is uncertain if there is any difference between misoprostol plus osmotic dilators versus placebo plus osmotic dilators in risk of adverse events (cervical tear requiring suturing: RR 1.62, 95% CI 0.76 to 3.46; 3 studies; 423 participants; I² = 45%; Analysis 3.7). No other adverse events were reported.

3.7 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 7: Adverse events: cervical tear requiring suturing

Side effects

Nausea/vomiting

It is uncertain if there is any difference between misoprostol plus osmotic dilators versus placebo plus osmotic dilators in risk of nausea or vomiting (RR 0.86, 95% CI 0.61 to 1.23; 2 studies; 224 participants; I² = 0%; Analysis 3.8). One study also reported nausea or vomiting in the overnight period (34/97 in the misoprostol plus osmotic dilators group; 52/98 in the placebo plus osmotic dilators group) and nausea or vomiting after the procedure (25/97 in the misoprostol plus osmotic dilators group; 32/98 in the placebo plus osmotic dilators group) (Drey 2014).

3.8 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 8: Side effects: nausea/vomiting

Diarrhea

It is uncertain if there is any difference between misoprostol plus osmotic dilators versus placebo plus osmotic dilators in risk of diarrhea (RR 0.98, 95% CI 0.18 to 5.45; 2 studies; 224 participants; I² = 0%; Analysis 3.9). One study also reported diarrhea in the overnight period (8/97 in the misoprostol plus osmotic dilators group; 14/98 in the placebo plus osmotic dilators group) and diarrhea after the procedure (0/97 in the misoprostol plus osmotic dilators group; 2/98 in the placebo plus osmotic dilators group) (Drey 2014).

3.9 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 9: Side effects: diarrhea

Chills/fever

Misoprostol plus osmotic dilators may substantially increase the risk of chills compared with placebo plus osmotic dilators (RR 3.90, 95% CI 2.61 to 5.81; 3 studies; 423 participants; I² = 0%; Analysis 3.10). One study also reported chills in the overnight period (17/97 in the misoprostol plus osmotic dilators group; 11/98 in the placebo plus osmotic dilators group) and chills after the procedure (40/97 and 30/97) (Drey 2014).

3.10 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 10: Side effects: chills

Additionally, one study reported that 8 of 100 participants in the misoprostol plus osmotic dilators group and 0 of 99 participants in the placebo plus osmotic dilators group experienced fever (Goldberg 2015).

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

It is uncertain if there is any difference between misoprostol plus osmotic dilators versus placebo plus osmotic dilators in risk of the following complications: hemorrhage requiring transfusion (RR 2.34, 95% CI 0.35 to 15.69; 2 studies; 394 participants; I² = 0%; Analysis 3.11.1); uterine perforation (RR 1.01, 95% CI 0.06 to 15.92; 1 study; 195 participants; Analysis 3.11.2); hospitalization (RR 1.26, 95% CI 0.34 to 4.59; 2 studies; 394 participants; I² = 0%; Analysis 3.11.3); re‐aspiration (RR 1.00, 95% CI 0.14 to 7.03; 2 studies; 394 participants; I² = 0%; Analysis 3.11.4).

3.11 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 11: Complications

Patient acceptability and/or satisfaction

It is uncertain if there is any difference between misoprostol plus osmotic dilators versus placebo plus osmotic dilators in numbers of participants satisfied (RR 1.13, 95% CI 0.98 to 1.30; 1 study; 228 participants; Analysis 3.12).

3.12 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 12: Patient acceptability/satisfaction

Another study reported median (IQR) satisfaction with cervical preparation: 4 (3 to 5) in both groups (P = 0.67; Analysis 3.13) (Drey 2014).

3.13. Analysis.

Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 13: Patient acceptability/satisfaction

Patient acceptability/satisfaction
Study	Misoprostol plus dilators	Placebo plus dilators	Measure	Result
Drey 2014	4 (3–5) 97 women	4 (3–5) 98 women	Satisfaction with cervical preparation Median (IQR) 1‐5 scale (higher score = greater satisfaction)	P = 0.67

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Pain experienced by participants between initiation of cervical preparation method and abortion procedure

It is uncertain if there is any difference between misoprostol plus osmotic dilators versus placebo plus osmotic dilators in pain experienced after medication on day one (RR 0.89, 95% CI 0.49 to 1.60; 1 study; 199 participants; Analysis 3.14.1).

3.14 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 14: Pain experienced by participants between initiation of cervical preparation method and abortion procedure

After medication on day two, misoprostol plus osmotic dilators may lead to greater pain compared with placebo plus osmotic dilators (RR 4.07, 95% CI 2.08 to 7.98; 1 study; 199 participants; Analysis 3.14.2).

At any time between initiation of cervical preparation method and the abortion procedure, misoprostol plus osmotic dilators may lead to greater pain compared with placebo plus osmotic dilators (RR 4.66, 95% CI 2.64 to 8.24; 2 studies; 224 participants; I² = 8%; Analysis 3.14.3).

Provider acceptability and/or satisfaction

It is uncertain if there is any difference between misoprostol plus osmotic dilators versus placebo plus osmotic dilators in provider satisfaction (RR 1.10, 95% CI 0.94 to 1.29; 1 study; 198 participants; Analysis 3.15).

3.15 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 15: Provider acceptability/satisfaction

Provider assessment of difficulty of procedure

Providers may assess procedures with misoprostol plus osmotic dilators as less difficult than those with placebo plus osmotic dilators (RR 0.69, 95% CI 0.50 to 0.97; 3 studies; 547 participants; I² = 0%; Analysis 3.16).

3.16 — Comparison 3: Misoprostol + osmotic dilators versus placebo + osmotic dilators, Outcome 16: Provider assessment of the procedure as very difficult

Comparison 4: mifepristone plus osmotic dilators versus placebo plus osmotic dilators (16 0/7 to 23 6/7 weeks)

One study investigated mifepristone plus osmotic dilators compared with placebo plus osmotic dilators (Goldberg 2015).

Primary outcomes

Procedure time

Mifepristone plus osmotic dilators may reduce procedure time compared with placebo plus osmotic dilators (2.46 minutes shorter: median, IQR 9.12 minutes, 7.7 to 10.6; compared with 11.58 minutes, 10.0 to 13.1; low‐certainty evidence; Analysis 4.1; Table 4).

4.1. Analysis.

Comparison 4: Mifepristone + osmotic dilators versus placebo + osmotic dilators, Outcome 1: Procedure time

Procedure time
Study	Mifepristone + dilators	Placebo + dilators	Measure	Result
Goldberg 2015	9.12 minutes (7.7–10.6) 98 women	11.58 minutes (10.0–13.1) 98 women	Median (IQR)	Effect of adding mifepristone to dilator ‐2.46 minutes

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Dilation achieved

Mifepristone plus osmotic dilators probably increases cervical dilation compared with placebo plus osmotic dilators (MD 2.00 mm, 95% CI 0.60 to 3.40; 1 study; 197 participants; moderate‐certainty evidence; Analysis 4.2; Table 4).

4.2 — Comparison 4: Mifepristone + osmotic dilators versus placebo + osmotic dilators, Outcome 2: Dilation achieved (mm)

Need for additional dilation

Mifepristone plus osmotic dilators may have little to no effect on need for additional dilation compared with placebo plus osmotic dilators (RR 0.61, 95% CI 0.35 to 1.06; 1 study; 197 participants; low‐certainty evidence; Analysis 4.3; Table 4).

4.3 — Comparison 4: Mifepristone + osmotic dilators versus placebo + osmotic dilators, Outcome 3: Need for additional dilation

Ability to complete procedure

Mifepristone plus osmotic dilators probably has little to no effect on ability to complete procedure compared with placebo plus osmotic dilators (RR 1.00, 95% CI 0.97 to 1.03; 1 study; 198 participants; moderate‐certainty evidence; Analysis 4.4; Table 4).

4.4 — Comparison 4: Mifepristone + osmotic dilators versus placebo + osmotic dilators, Outcome 4: Ability to complete procedure (number completed on first attempt)

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

It is uncertain if there is any difference between mifepristone plus osmotic dilators and placebo plus osmotic dilators in risk of cervical laceration (RR 0.14, 95% CI 0.01 to 2.70; 1 study; 199 participants; Analysis 4.5). No other adverse events were reported.

4.5 — Comparison 4: Mifepristone + osmotic dilators versus placebo + osmotic dilators, Outcome 5: Adverse events: cervical laceration

Side effects

Nausea/vomiting

Not reported.

Diarrhea

Not reported.

Chills/fever

It is uncertain if there is any difference between mifepristone plus osmotic dilators and placebo plus osmotic dilators in risk of fever (RR 1.50, 95% CI 0.76 to 2.95; 1 study; 198 participants; Analysis 4.6). One study also reported that 0 of 99 participants in the mifepristone plus osmotic dilators group and 0 of 99 participants in the placebo plus osmotic dilators group experienced chills (Goldberg 2015).

4.6 — Comparison 4: Mifepristone + osmotic dilators versus placebo + osmotic dilators, Outcome 6: Side effects: fever

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

It is uncertain if there is any difference between mifepristone plus osmotic dilators compared with osmotic dilators alone in complications (bleeding requiring intervention beyond uterine massage or uterotonics) (RR 0.14, 95% CI 0.01 to 2.70; 1 study; 199 participants; I² = 0%).

Patient acceptability and/or satisfaction

It is uncertain if mifepristone plus osmotic dilators has any effect on patient satisfaction compared with placebo plus osmotic dilators (RR 1.11, 95% CI 0.95 to 1.30; 1 study; 198 participants; Analysis 4.7).

4.7 — Comparison 4: Mifepristone + osmotic dilators versus placebo + osmotic dilators, Outcome 7: Patient satisfaction

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

It is uncertain if mifepristone plus osmotic dilators has any effect on pain compared with placebo plus osmotic dilators (after day one medication: RR 0.89, 95% CI 0.49 to 1.62; 1 study; 198 participants; after day two medication: RR 0.89, 95% CI 0.36 to 2.21; 1 study; 198 participants; Analysis 4.8).

4.8 — Comparison 4: Mifepristone + osmotic dilators versus placebo + osmotic dilators, Outcome 8: Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Provider acceptability and/or satisfaction

Mifepristone plus osmotic dilators may lead to greater satisfaction than placebo plus osmotic dilators (RR 1.21, 95% CI 1.05 to 1.40; 1 study; 197 participants; Analysis 4.9).

4.9 — Comparison 4: Mifepristone + osmotic dilators versus placebo + osmotic dilators, Outcome 9: Provider acceptability/satisfaction

Provider assessment of difficulty of procedure

Providers may assess procedures with mifepristone plus osmotic dilators as less difficult than those with placebo plus osmotic dilators (RR 0.20, 95% CI 0.06 to 0.68; 1 study; 197 participants; Analysis 4.10).

4.10 — Comparison 4: Mifepristone + osmotic dilators versus placebo + osmotic dilators, Outcome 10: Provider assessment of the procedure as very difficult

Comparison 5: 400 μg buccal misoprostol plus osmotic dilators versus mifepristone plus osmotic dilators (16 0/7 and 23 6/7 weeks)

One study investigated misoprostol plus osmotic dilators compared with mifepristone plus osmotic dilators (Goldberg 2015).

Primary outcomes

Procedure time

Misoprostol plus osmotic dilators may have little to no effect on procedure time compared with mifepristone plus osmotic dilators (median (IQR) 10.13 (8.6 to 11.6) minutes compared with 9.12 minutes (7.7 to 10.6); low‐certainty evidence; Analysis 5.1; Table 5).

5.1. Analysis.

Comparison 5: Misoprostol + osmotic dilators versus mifepristone + osmotic dilators, Outcome 1: Procedure time

Procedure time
Study	Misoprostol + dilators	Mifepristone + dilators	Measure	Result
Goldberg 2015	10.13 minutes (8.6–11.6) 98 women	9.12 minutes (7.7–10.6) 98 women	Median (IQR)	Misoprostol: 1.01 minutes longer than mifepristone

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Dilation achieved

Misoprostol plus osmotic dilators may have little to no effect on dilation achieved compared with mifepristone plus osmotic dilators (MD 1.00 mm, 95% CI −1.05 to 3.05; 1 study; 195 participants; low‐certainty evidence; Analysis 5.2; Table 5).

5.2 — Comparison 5: Misoprostol + osmotic dilators versus mifepristone + osmotic dilators, Outcome 2: Dilation achieved (mm)

Need for additional dilation

Misoprostol plus osmotic dilators may have little to no effect on need for additional dilation compared with mifepristone plus osmotic dilators (RR 0.56, 95% CI 0.26 to 1.21; 1 study; 198 participants; low‐certainty evidence; Analysis 5.3; Table 5).

5.3 — Comparison 5: Misoprostol + osmotic dilators versus mifepristone + osmotic dilators, Outcome 3: Need for additional dilation

Ability to complete procedure

There is probably little to no difference between misoprostol plus osmotic dilators and mifepristone plus osmotic dilators in ability to complete procedure (RR 0.99, 95% CI 0.96 to 1.02; 1 study; 199 participants; moderate‐certainty evidence; Analysis 5.4; Table 5).

5.4 — Comparison 5: Misoprostol + osmotic dilators versus mifepristone + osmotic dilators, Outcome 4: Ability to complete procedure (number completed on first attempt)

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

Not reported.

Side effects

Nausea/vomiting

Not reported.

Diarrhea

Not reported.

Fever/chills

It is uncertain if misoprostol plus osmotic dilators has any effect on the risk of fever compared with mifepristone plus osmotic dilators (RR 16.83, 95% CI 0.98 to 287.72; 1 study; 199 participants; Analysis 5.6).

5.6 — Comparison 5: Misoprostol + osmotic dilators versus mifepristone + osmotic dilators, Outcome 6: Side effects: fever

Misoprostol plus osmotic dilators may increase the risk of chills compared with mifepristone plus osmotic dilators (RR 2.15, 95% CI 1.32 to 3.48; 1 study; 199 participants; Analysis 5.7).

5.7 — Comparison 5: Misoprostol + osmotic dilators versus mifepristone + osmotic dilators, Outcome 7: Side effects: chills

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

It is uncertain if there is any difference between misoprostol plus osmotic dilators and mifepristone plus osmotic dilators in risk of the following complications: uterine perforation (RR 3.00, 95% CI 0.12 to 72.77; 1 study; 200 participants; Analysis 5.5.1); hospitalization (RR 1.00, 95% CI 0.06 to 15.77; 1 study; 200 participants; Analysis 5.5.2); re‐aspiration (RR 1.00, 95% CI 0.06 to 15.77; 1 study; 200 participants; Analysis 5.5.3).

5.5 — Comparison 5: Misoprostol + osmotic dilators versus mifepristone + osmotic dilators, Outcome 5: Complications

Patient acceptability and/or satisfaction

It is uncertain if there is any difference between misoprostol plus osmotic dilators and mifepristone plus osmotic dilators in number of participants satisfied or very satisfied (RR 0.99, 95% CI 0.86 to 1.14; 1 study; 199 participants; Analysis 5.8).

5.8 — Comparison 5: Misoprostol + osmotic dilators versus mifepristone + osmotic dilators, Outcome 8: Patient satisfaction

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

It is uncertain if misoprostol plus osmotic dilators has any effect on pain experienced after day one medication compared with mifepristone plus osmotic dilators (RR 0.99, 95% CI 0.54 to 1.83; 1 study; 199 participants), but after day two medication there may be a higher risk of pain with misoprostol plus osmotic dilators (RR 4.58, 95% CI 2.25 to 9.33; 1 study; 199 participants; Analysis 5.9).

5.9 — Comparison 5: Misoprostol + osmotic dilators versus mifepristone + osmotic dilators, Outcome 9: Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Provider acceptability and/or satisfaction

It is uncertain if there is any difference between misoprostol plus osmotic dilators and mifepristone plus osmotic dilators in number of providers satisfied or very satisfied (RR 0.91, 95% CI 0.80 to 1.03; 1 study; 197 participants; Analysis 5.10).

5.10 — Comparison 5: Misoprostol + osmotic dilators versus mifepristone + osmotic dilators, Outcome 10: Provider acceptability/satisfaction

Provider assessment of difficulty of procedure

Misoprostol plus osmotic dilators may increase the number of providers who assess the procedure as very difficult (RR 3.63, 95% CI 1.04 to 12.61; 1 study; 197 participants; Analysis 5.11).

5.11 — Comparison 5: Misoprostol + osmotic dilators versus mifepristone + osmotic dilators, Outcome 11: Provider assessment of the procedure as very difficult

Comparison 6: mifepristone plus 400 μg buccal misoprostol plus osmotic dilators versus 400 μg buccal misoprostol plus osmotic dilators (19 to 23 6/7 weeks)

Two studies investigated mifepristone plus misoprostol plus osmotic dilators compared with misoprostol plus osmotic dilators (Shaw 2015; Shaw 2017).

Primary outcomes

Procedure time

Mifepristone plus misoprostol plus osmotic dilators may have little to no effect on procedure time compared with misoprostol plus osmotic dilators (MD 0.96, 95% CI −1.94 to 3.86; 1 study; 49 participants; Analysis 6.1); one other study reported a median procedure time that was shorter by one minute in the mifepristone plus misoprostol plus osmotic dilator compared to misoprostol plus osmotic dilator plus placebo group (47 participants; P = 0.76; low‐certainty evidence; Analysis 6.2; Table 6).

6.1 — Comparison 6: Mifepristone + misoprostol + osmotic dilators versus misoprostol + osmotic dilators, Outcome 1: Procedure time (minutes)

6.2. Analysis.

Comparison 6: Mifepristone + misoprostol + osmotic dilators versus misoprostol + osmotic dilators, Outcome 2: Procedure time

Procedure time
Study	Mifepristone + misoprostol + dilators	Misoprostol + dilators (+ placebo)	Measure	Result
Shaw 2017	12 minutes (7–25) 26 women	13 minutes (6–26) 21 women	Median, range	median ‐1 minute shorter with mifepristone + misoprostol + dilators compared with misoprostol + dilators, P = 0.76

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Dilation achieved

Mifepristone plus misoprostol plus osmotic dilator may have little to no effect on dilation achieved compared with misoprostol plus osmotic dilator plus placebo. One study (48 participants) reported the same median (range) dilation in each group: 30 mm (0.5 to 5) (low‐certainty evidence; Analysis 6.3; Table 6).

6.3. Analysis.

Comparison 6: Mifepristone + misoprostol + osmotic dilators versus misoprostol + osmotic dilators, Outcome 3: Dilation achieved

Dilation achieved
Study	Mifepristone + misoprostol + dilators	Misoprostol + dilators (+ placebo)	Measure	Result
Shaw 2017	3 cm (0.5–5) 27 women	3 cm (0.5–5) 21 women	Median (range)	No difference between groups

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Need for additional dilation

Mifepristone plus misoprostol plus osmotic dilator may have little to no effect on need for additional dilation compared with misoprostol plus osmotic dilator plus placebo (RR 1.17, 95% CI 0.38 to 3.61; 1 study; 48 participants; low‐certainty evidence; Analysis 6.4; Table 6).

6.4 — Comparison 6: Mifepristone + misoprostol + osmotic dilators versus misoprostol + osmotic dilators, Outcome 4: Need for additional dilation

Ability to complete procedure

Not reported.

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

It is uncertain if there is any difference between mifepristone plus misoprostol plus osmotic dilators and misoprostol plus osmotic dilators in risk of adverse events (RR 0.38, 95% CI 0.06 to 2.45; 2 studies; 97 participants; I² = 0%; Analysis 6.5).

6.5 — Comparison 6: Mifepristone + misoprostol + osmotic dilators versus misoprostol + osmotic dilators, Outcome 5: Adverse events

Side effects

Not reported.

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy).

It is uncertain if there is any difference between mifepristone plus misoprostol plus osmotic dilators and misoprostol plus osmotic dilators plus placebo in risk of uterine perforation (RR 0.26, 95% CI 0.03 to 2.32; 1 study; 48 participants; Analysis 6.6). No other complications were reported.

6.6 — Comparison 6: Mifepristone + misoprostol + osmotic dilators versus misoprostol + osmotic dilators, Outcome 6: Complications: uterine perforations

Patient acceptability and/or satisfaction

One study measured participants’ overall experience on a visual analogue scale (VAS), where higher score equals greater satisfaction, and reported lower median scores in the mifepristone plus misoprostol plus osmotic dilators group (90.5, range 4 to 99) compared with the misoprostol plus osmotic dilators plus placebo group (93, range 47 to 99) (Shaw 2017). The same study measured on a VAS how likely participants were to recommend the procedure, where higher score equals more likely to recommend, and reported higher median scores in the mifepristone plus misoprostol plus osmotic dilators group (94, range 5 to 99) compared with the misoprostol plus osmotic dilators plus placebo group (89, range 4 to 97) (Analysis 6.7).

6.7. Analysis.

Comparison 6: Mifepristone + misoprostol + osmotic dilators versus misoprostol + osmotic dilators, Outcome 7: Patient acceptability/satisfaction

Patient acceptability/satisfaction
Study	Mifepristone + misoprostol + dilators	Misoprostol + dilators (+ placebo)	Measure	Result
Overall experience
Shaw 2017	90.5 (4–99) 27 women	93 (47–99) 21 women	0‐100 VAS (median, range) (higher score = greater satisfaction)	Effect of adding mifepristone to misoprostol plus dilator ‐2.5 VAS points (less satisfaction)
Likely to recommend to a friend
Shaw 2017	94 (5–99) 27 women	89 (4–97) 21 women	0‐100 VAS (median, range) (higher score = more likely to recommend)	Effect of adding mifepristone to misoprostol plus dilator 6 VAS points (more likely to recommend)

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Pain experienced by participants between initiation of cervical preparation method and abortion procedure

One study reported greater median pain scores in the mifepristone plus misoprostol plus osmotic dilators group (49, range 4 to 97) compared with the misoprostol plus osmotic dilators plus placebo group (31, range 1 to 87) (higher score = greater pain) (Analysis 6.8) (Shaw 2017).

6.8. Analysis.

Comparison 6: Mifepristone + misoprostol + osmotic dilators versus misoprostol + osmotic dilators, Outcome 8: Pain (preoperative, post‐misoprostol)

Pain (preoperative, post‐misoprostol)
Study	Mifepristone + misoprostol + dilators	Misoprostol + dilators (+ placebo)	Measure	Result
Shaw 2017	49 (4–97) 27 women	31 (1–87) 21 women	0‐100 VAS (median, range) (higher score = greater pain)	Effect of adding mifepristone to misoprostol plus dilator: 18 VAS points more painful (P value not reported)

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Provider acceptability and/or satisfaction

Not reported.

Provider assessment of difficulty of procedure

One study measured providers’ assessment of difficulty on a 0‐to‐100 VAS, where higher score equals greater difficulty, and reported median 30 (IQR 18 to 49) in the mifepristone plus misoprostol plus osmotic dilators group compared with median 29 (range 23 to 52) in the misoprostol plus osmotic dilators plus placebo group (Analysis 6.9) (Shaw 2017).

6.9. Analysis.

Comparison 6: Mifepristone + misoprostol + osmotic dilators versus misoprostol + osmotic dilators, Outcome 9: Provider assessment of difficulty of procedure

Provider assessment of difficulty of procedure
Study	Mifepristone + misoprostol + dilators	Misoprostol + dilators	Measure	Result
Shaw 2015	30 (18‐49) 24 procedures	29 (23‐52) 21 procedures	0‐100 VAS scale (higher score = greater difficulty) (median, IQR)	P = 0.76

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In one study (Shaw 2015), two days of osmotic dilator was used prior to the day of the D&E procedure.

Comparison 7: 400 μg buccal or vaginal misoprostol plus osmotic dilators versus 400 μg buccal or vaginal misoprostol (14 to 19 6/7 weeks)

One study investigated misoprostol plus osmotic dilators compared with misoprostol alone (Shakir 2019).

Primary outcomes

Procedure time

Misoprostol plus osmotic dilators probably increases procedure time compared with misoprostol alone (MD 3.2 minutes, 95% CI 1.77 to 4.63; 1 study; 161 participants; moderate‐certainty evidence; Analysis 7.1; Table 7). The procedure time in the osmotic dilator arm includes the time elapsed for insertion of the osmotic dilator in addition to the actual procedure time, which has probably increased the total procedure time.

7.1 — Comparison 7: Misoprostol + osmotic dilators versus misoprostol, Outcome 1: Procedure time (minutes)

Dilation achieved

Misoprostol plus osmotic dilators probably increases dilation achieved compared with misoprostol alone (MD 3.9 mm, 95% CI 3.1 to 4.7; 1 study; 161 participants; moderate‐certainty evidence; Analysis 7.2; Table 7).

7.2 — Comparison 7: Misoprostol + osmotic dilators versus misoprostol, Outcome 2: Dilation achieved (mm)

Need for additional dilation

Misoprostol plus osmotic dilators probably reduces the need for additional dilation compared with misoprostol alone (RR 0.77, 95% CI 0.63 to 0.93; 1 study; 161 participants; moderate‐certainty evidence; Analysis 7.3; Table 7).

7.3 — Comparison 7: Misoprostol + osmotic dilators versus misoprostol, Outcome 3: Need for additional dilation

Ability to complete procedure

There is probably little to no difference between misoprostol plus osmotic dilator and misoprostol alone in ability to complete procedure (RR 1.00, 95% CI 0.98 to 1.02; 1 study; 161 participants; moderate‐certainty evidence; Analysis 7.4; Table 7).

7.4 — Comparison 7: Misoprostol + osmotic dilators versus misoprostol, Outcome 4: Ability to complete procedure

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

Not reported.

Side effects

Nausea/vomiting

Not reported.

Diarrhea

Not reported.

Fever/chills

It is uncertain if misoprostol plus osmotic dilator has any effect on the risk of chills compared with misoprostol alone (RR 0.70, 95% CI 0.47 to 1.04; 1 study; 79 participants; Analysis 7.5). Fever was not reported.

7.5 — Comparison 7: Misoprostol + osmotic dilators versus misoprostol, Outcome 5: Side effects: chills

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

It is uncertain if there is any difference between misoprostol plus osmotic dilators and misoprostol alone in risk of complications (uterine perforation: RR 2.69, 95% CI 0.11 to 64.97; 1 study; 161 participants; Analysis 7.6).

7.6 — Comparison 7: Misoprostol + osmotic dilators versus misoprostol, Outcome 6: Complications: uterine perforation

Patient acceptability and/or satisfaction

One study reported that 60/85 participants in the misoprostol plus osmotic dilator group and 62/76 participants in the misoprostol alone group would have the same procedure again (RR 0.87, 95% CI 0.73 to 1.03) (Shakir 2019). The same study reported that more participants in the misoprostol plus osmotic dilator group would recommend their procedure to a friend (RR 0.85, 95% CI 0.74 to 0.99; 161 participants; Analysis 7.7).

7.7 — Comparison 7: Misoprostol + osmotic dilators versus misoprostol, Outcome 7: Patient acceptability

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Not reported.

Provider acceptability and/or satisfaction

Not reported.

Provider assessment of difficulty of procedure

It is uncertain if there is any difference between misoprostol plus osmotic dilator and misoprostol alone in provider assessment of difficulty (RR 1.09, 95% CI 0.48 to 2.46; 1 study; 161 participants; Analysis 7.8).

7.8 — Comparison 7: Misoprostol + osmotic dilators versus misoprostol, Outcome 8: Provider assessment of difficulty

Comparison 8: laminaria versus synthetic osmotic dilators (13 6/7 to 24 0/7 weeks)

Two studies investigated laminaria compared with synthetic osmotic dilators (Dayananda 2016; Grimes 1987).

Primary outcomes

Procedure time

It is uncertain if laminaria has any effect on procedure time compared with synthetic osmotic dilators. One study reported procedure time but did not provide data according to randomized group allocation (very low‐certainty evidence; Analysis 8.1; Table 8) (Dayananda 2016).

8.1. Analysis.

Comparison 8: Laminaria versus synthetic dilator, Outcome 1: Procedure time

Procedure time
Study	Laminaria	Synthetic dilator	Measure	Comment
Dayananda 2016	Early cohort 5.9 minutes (3.06) Late cohort 9.03 minutes (3.61)	Early cohort 6.31 minutes (4.45) Late cohort 8.86 minutes (4.47)	Mean (SD)	Numbers of women per group are not reported

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Dilation achieved

There is probably little to no difference between laminaria and synthetic osmotic dilators in dilation achieved, defined as rate per 100 abortions of initial dilation ≥ 37 French units (RR 1.0, 95% CI 0.8 to 1.3; 1 study; 219 participants; moderate‐certainty evidence; Analysis 8.2; Table 8) (Dayananda 2016).

8.2. Analysis.

Comparison 8: Laminaria versus synthetic dilator, Outcome 2: Dilation achieved

Dilation achieved
Study	Laminaria	Synthetic dilator (Lamicel)	Measure	Result
Grimes 1987	47.3 (110 women)	47.7 (109 women)	Rate per 100 abortions of initial dilation ≥ 37 French units	Relative risk 1.0, 95% CI 0.8 to 1.3

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Need for additional dilation

Not reported.

Ability to complete procedure

Laminaria may result in a slight reduction in ability to complete procedure at first attempt compared with synthetic dilators (RR 0.85, 95% CI 0.75 to 0.96; 1 study; 173 participants; low‐certainty evidence; Analysis 8.3; Table 8).

8.3 — Comparison 8: Laminaria versus synthetic dilator, Outcome 3: Ability to complete procedure

Secondary outcomes

Adverse events related to cervical preparation agents (infection, cervical laceration, pre‐procedure expulsion)

It is uncertain if laminaria has any effect on the risk of cervical injury compared with synthetic dilators (RR 0.14, 95% CI 0.01 to 2.71; 1 study; 219 participants; Analysis 8.4). No other adverse events were reported.

8.4 — Comparison 8: Laminaria versus synthetic dilator, Outcome 4: Adverse events: cervical injury

Side effects

Not reported.

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

One study reported data for "acute complications" but provided no further details (Dayananda 2016). It is uncertain if there is any difference between laminaria and synthetic dilators in risk of acute complications (RR 0.34, 95% CI 0.04 to 3.18; 1 study; 173 participants; Analysis 8.5).

8.5 — Comparison 8: Laminaria versus synthetic dilator, Outcome 5: Complications

Patient acceptability and/or satisfaction

Not reported.

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Data for pain were not reported, but one study stated: “There was no difference in either gestational cohort with regard to initial dilation, procedure difficulty and pain” (Dayananda 2016).

Provider acceptability and/or satisfaction

Not reported.

Provider assessment of difficulty of procedure

No data were reported, but one study stated: “There was no difference in either gestational cohort with regard to initial dilation, procedure difficulty, and pain” (Dayananda 2016).

Comparison 9: same‐day Dilapan‐S versus overnight laminaria (13 6/7 and 17 6/7 weeks)

One study investigated same‐day Dilapan‐S compared with overnight laminaria (Newmann 2014).

Primary outcomes

Procedure time

Same‐day Dilapan‐S may result in a slight increase in procedure time compared with overnight laminaria (MD 2.20, 95% CI 0.10 to 4.30; 1 study; 67 participants; low‐certainty evidence; Analysis 9.1; Table 9).

9.1 — Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 1: Procedure time (minutes)

Dilation achieved

Same‐day Dilapan‐S may result in less dilation achieved compared with overnight laminaria (MD −11.70, 95% CI −16.74 to −6.66; 1 study; 69 participants; low‐certainty evidence; Analysis 9.2; Table 9).

9.2 — Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 2: Dilation achieved (mm)

Need for additional dilation

Same‐day Dilapan‐S may result in more participants needing additional dilation compared with overnight laminaria (RR 2.83, 95% CI 1.47 to 5.46; 1 study; 69 participants; low‐certainty evidence; Analysis 9.3; Table 9).

9.3 — Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 3: Need for additional dilation

Ability to complete procedure

There may be little to no difference between same‐day Dilapan‐S and overnight laminaria in ability to complete procedure (RR 1.00, 95% CI 0.95 to 1.06; 1 study; 69 participants; low‐certainty evidence; Analysis 9.4; Table 9).

9.4 — Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 4: Ability to complete procedure

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

It is uncertain if same‐day Dilapan‐S has any effect on the risk of cervical tear compared with overnight laminaria (RR 0.34, 95% CI 0.01 to 8.13; 1 study; 69 participants; Analysis 9.5). No other adverse events were reported.

9.5 — Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 5: Adverse events: cervical tear

Side effects

Nausea

Same‐day Dilapan‐S may reduce the risk of overnight nausea compared with overnight laminaria (RR 0.16, 95% CI 0.04 to 0.67; 1 study; 67 participants; Analysis 9.6.1). It is uncertain if same‐day Dilapan‐S has any effect on the risk of nausea immediately before abortion (RR 0.97, 95% CI 0.35 to 2.71; 1 study; 67 participants; Analysis 9.6.2) or after the procedure (RR 0.65, 95% CI 0.12 to 3.63; 1 study; 67 participants; Analysis 9.6.3) compared with overnight laminaria.

9.6 — Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 6: Nausea

Vomiting

Same‐day Dilapan‐S may reduce the risk of overnight vomiting compared with overnight laminaria (RR 0.22, 95% CI 0.07 to 0.71; 1 study; 67 participants; Analysis 9.7.1). It is uncertain if same‐day Dilapan‐S has any effect on the risk of vomiting immediately before abortion (RR 0.97, 95% CI 0.31 to3.04; 1 study; 67 participants; Analysis 9.7.2) or after the procedure (RR 0.97, 95% CI 0.21 to 4.47; 1 study; 67 participants; Analysis 9.7.3) compared with overnight laminaria.

9.7 — Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 7: Vomiting

Diarrhea

It is uncertain if same‐day Dilapan‐S has any effect on the risk of diarrhea compared with overnight laminaria (RR 0.97, 95% CI 0.06 to 14.88; 1 study; 67 participants; Analysis 9.8).

9.8 — Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 8: Diarrhea

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

It is uncertain if there is any difference between same‐day Dilapan‐S and overnight laminaria in risk of complications (bleeding requiring uterotonics: RR 0.72, 95% CI 0.31 to 1.67; 1 study; 69 participants; Analysis 9.9.1; re‐aspiration: RR 1.54, 95% CI 0.27 to 8.67; 1 study; 69 participants; Analysis 9.9.2; cervical laceration: RR 0.34, 95% CI 0.01 to 8.13; 1 study; 69 participants; Analysis 9.9.3).

9.9 — Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 9: Complications

Patient acceptability and/or satisfaction

Compared with overnight laminaria, it is uncertain if same‐day Dilapan‐S has any effect on patient satisfaction with the procedure (RR 1.05, 95% CI 0.79 to 1.39; 1 study; 67 participants) or satisfaction with the overall clinic experience (RR 1.10, 95% CI 0.81 to 1.51; 1 study; 67 participants) (Analysis 9.10).

9.10 — Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 10: Patient satisfaction

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Same‐day Dilapan‐S may reduce overnight pain compared with overnight laminaria (RR 0.08, 95% CI 0.02 to 0.33; 1 study; 67 participants), but may increase pain experienced immediately before the procedure (RR 3.47, 95% CI 1.74 to 6.90; 1 study; 67 participants) (Analysis 9.12).

9.12 — Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 12: Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Provider acceptability and/or satisfaction

Not reported.

Provider assessment of difficulty of procedure

There may be little to no difference between same‐day Dilapan‐S and overnight laminaria in provider assessment of difficulty of procedure as measured on a 0‐to‐4 scale, where higher score = greater difficulty (median (IQR) same‐day Dilapan‐S group: 0 (0 to 1), 32 participants; 0 (0 to 1), 30 participants) (Analysis 9.11).

9.11. Analysis.

Comparison 9: Same‐day Dilapan‐S versus overnight osmotic dilators, Outcome 11: Provider assessment of difficulty of procedure

Provider assessment of difficulty of procedure
Study	Same day dilators	Overnight dilators	Measure	Result
Newmann 2014	0 (0–1) 32 procedures	0 (0–1) 30 procedures	Median (IQR) 0‐4 scale Higher score = greater difficulty	P = 0.17

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Comparison 10: vaginal misoprostol versus buccal misoprostol (14 to 19 6/7 weeks)

One study investigated vaginal misoprostol with or without osmotic dilators compared with buccal misoprostol with or without osmotic dilators (Shakir 2019), but data were not reported according to the groups allocated to different administration of misoprostol.

One study investigated vaginal misoprostol (plus mifepristone) compared with buccal misoprostol (plus mifepristone) (Casey 2018).

Primary outcomes

Procedure time

Vaginal misoprostol may have little to no effect on procedure time compared with buccal misoprostol (MD −0.40, 95% CI −2.55 to 1.75; 1 study; 68 participants; low‐certainty evidence; Analysis 10.1; Table 10) because the certainty of evidence is low, and the 95% CI spans possible benefit and possible harm.

10.1 — Comparison 10: Vaginal misoprostol versus buccal misoprostol, Outcome 1: Procedure time (minutes)

Dilation achieved

Vaginal misoprostol may have little to no effect on dilation achieved compared with buccal misoprostol (low‐certainty evidence; Analysis 10.2; Table 10).

10.2. Analysis.

Comparison 10: Vaginal misoprostol versus buccal misoprostol, Outcome 2: Dilation achieved (French)

Dilation achieved (French)
Study	Vaginal misoprostol (+ mifepristone)	Buccal misoprostol (+ mifepristone)	Measure	Result
Casey 2018	47 French (45‐44) 35 women	47 French (37‐53) 33 women	Median (IQR)	Little difference between groups

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Need for additional dilation

There may be little to no difference in need for additional dilation between vaginal misoprostol and buccal misoprostol (RR 0.94, 95% CI 0.84 to 1.06; 1 study; 68 participants; low‐certainty evidence; Table 10).

Ability to complete procedure

There may be little to no difference in ability to complete procedure between vaginal misoprostol and buccal misoprostol (RR 1.00, 95% CI 0.95 to 1.06; 1 study; 68 participants; low‐certainty evidence; Table 10)

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

Not reported.

Side effects

Nausea

It is uncertain if vaginal misoprostol has any effect on the risk of nausea compared with buccal misoprostol (first medication: RR 1.51, 95% CI 0.55 to 4.15; 1 study; 68 participants; second medication: RR 0.67, 95% CI 0.24 to 1.91; 1 study; 68 participants; Analysis 10.5).

10.5 — Comparison 10: Vaginal misoprostol versus buccal misoprostol, Outcome 5: Side effects: nausea

Vomiting

It is uncertain if vaginal misoprostol has any effect on the risk of vomiting compared with buccal misoprostol (RR 0.10, 95% CI 0.01 to 1.88; 1 study; 68 participants; Analysis 10.6).

10.6 — Comparison 10: Vaginal misoprostol versus buccal misoprostol, Outcome 6: Side effects: vomiting

Diarrhea

It is uncertain if vaginal misoprostol has any effect on the risk of diarrhea compared with buccal misoprostol (RR 1.89, 95% CI 0.18 to 19.83; 1 study; 68 participants; Analysis 10.7).

10.7 — Comparison 10: Vaginal misoprostol versus buccal misoprostol, Outcome 7: Side effects: diarrhea

Fever/chills

It is uncertain if vaginal misoprostol has any effect on the risk of fever or chills, or both, compared with buccal misoprostol (RR 0.60, 95% CI 0.26 to 1.36; 1 study; 68 participants; Analysis 10.8).

10.8 — Comparison 10: Vaginal misoprostol versus buccal misoprostol, Outcome 8: Side effects: fever and/or chills

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

One study stated: “All 68 procedures were completed without hemorrhage, cervical laceration, or other observed complications” (Casey 2018).

Patient acceptability and/or satisfaction

One study reported various measures of patient satisfaction, finding no clear differences between vaginal misoprostol and buccal misoprostol (Analysis 10.9).

10.9 — Comparison 10: Vaginal misoprostol versus buccal misoprostol, Outcome 9: Patient acceptability and/or satisfaction

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Not reported.

Provider acceptability and/or satisfaction

It is uncertain if there is any difference between vaginal misoprostol and buccal misoprostol in the number of providers who would use the same method again for the same patient (RR 1.03, 95% CI 0.95 to 1.12; 1 study; 68 participants) or who would recommend this method to other patients (RR 1.06, 95% CI 0.96 to 1.18; 1 study; 68 participants) (Analysis 10.10).

10.10 — Comparison 10: Vaginal misoprostol versus buccal misoprostol, Outcome 10: Provider acceptability and/or satisfaction

Provider assessment of difficulty of procedure

It is uncertain if there is any difference between vaginal misoprostol and buccal misoprostol in the number of providers who found the procedure difficult (RR 0.19, 95% CI 0.01 to 3.79; 1 study; 68 participants; Analysis 10.11).

10.11 — Comparison 10: Vaginal misoprostol versus buccal misoprostol, Outcome 11: Provider assessment of difficulty of procedure

Comparison 11: mifepristone versus osmotic dilators (14 to 16 weeks)

One study compared mifepristone versus osmotic dilators (Borgatta 2012).

Primary outcomes

Procedure time

It is uncertain if there is any difference in mean procedure time between mifepristone and osmotic dilators (RR 1.74, 95% CI 0.71 to 2.77; 1 study; 49 participants; Analysis 11.1).

11.1 — Comparison 11: Mifepristone versus osmotic dilators, Outcome 1: Procedure time

Dilation achieved

One study reported lower median dilation achieved in the mifepristone group (35 French units) compared with the osmotic dilator group (“over 39 French units”) (Analysis 11.2) (Borgatta 2012).

11.2. Analysis.

Comparison 11: Mifepristone versus osmotic dilators, Outcome 2: Dilation achieved (French)

Dilation achieved (French)
Study	Mifepristone	Osmotic dilator	Measure	Result
Borgatta 2012	35 French units 25 women	"over 39" French units 25 women	Median (IQR not reported)	P < 0001

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Need for additional dilation

Not reported.

Ability to complete procedure

Not reported.

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

It is uncertain if there is any difference between mifepristone and osmotic dilators in risk of pre‐procedure expulsion (RR 0.33, 95% CI 0.01 to 7.81; 1 study; 50 participants; Analysis 11.3). No other adverse events were reported.

11.3 — Comparison 11: Mifepristone versus osmotic dilators, Outcome 3: Adverse events: pre‐procedure expulsion

Side effects

Nausea/vomiting

It is uncertain if mifepristone has any effect on the risk of nausea or vomiting, or both, during the night before the procedure compared with osmotic dilators (RR 0.75, 95% CI 0.31 to 1.83; 48 participants; Analysis 11.4). The same study also reported that 0 of 23 participants in the mifepristone group and 0 of 25 participants in the osmotic dilators group experienced nausea or vomiting, or both, on the morning of the procedure (Borgatta 2012).

11.4 — Comparison 11: Mifepristone versus osmotic dilators, Outcome 4: Side effects: nausea and/or vomiting

The denominators differ between the two time points because the trial reported that data were missing from one participant in each group at the first time point and from two participants in the mifepristone group at the second time point.

Diarrhea

It is uncertain if mifepristone has any effect on the risk of diarrhea compared with osmotic dilators (RR 0.11, 95% CI 0.01 to 1.96; 1 study; 50 participants; Analysis 11.5).

11.5 — Comparison 11: Mifepristone versus osmotic dilators, Outcome 5: Side effects: diarrhea

Fever/chills

Not reported.

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

Not reported.

Patient acceptability and/or satisfaction

Not reported.

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Mifepristone may reduce the risk of pain at two time points: the night before the abortion procedure (RR 0.15, 95% CI 0.04 to 0.61; 1 study; 50 participants) and the morning of the abortion procedure (RR 0.27, 95% CI 0.09 to 0.86; 1 study; 50 participants) (Analysis 11.6).

11.6 — Comparison 11: Mifepristone versus osmotic dilators, Outcome 6: Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Provider acceptability and/or satisfaction

Not reported.

Provider assessment of difficulty of procedure

It is uncertain if there is any difference between mifepristone and osmotic dilators in provider assessment of difficulty (RR 2.88, 95% CI 0.64 to 12.90; 1 study; 49 participants; Analysis 11.7).

11.7 — Comparison 11: Mifepristone versus osmotic dilators, Outcome 7: Provider assessment of difficulty of procedure

Comparison 12: mifepristone plus 400 μg buccal misoprostol versus osmotic dilators plus placebo plus misoprostol (19 and 23 6/7 weeks)

One study investigated mifepristone plus misoprostol compared with osmotic dilators plus placebo plus misoprostol (Shaw 2017).

Primary outcomes

Procedure time

In one study median procedure time was 5.5 minutes longer in the mifepristone plus misoprostol group compared with the osmotic dilators plus placebo plus misoprostol group (P = 0.01; Analysis 12.1) (Shaw 2017).

12.1. Analysis.

Comparison 12: Mifepristone + misoprostol versus osmotic dilators + placebo + misoprostol, Outcome 1: Procedure time

Procedure time
Study	Mifepristone + misoprostol	Placebo + miso + dilator	Measure	Result
Shaw 2017	18.5 minutes (8–52) 25 women	13 minutes (6–26 21 women	Median (range)	Effect of mifepristone plus misoprostol compared with misoprostol plus dilator 5.5 minutes longer, P = 0.01

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Dilation achieved

In one study median dilation achieved was 0.5 cm (range 0 to 4) in the mifepristone plus misoprostol group compared with 3 cm (range 0.5 to 5) in the osmotic dilators plus placebo plus misoprostol group (Analysis 12.2) (Shaw 2017).

12.2. Analysis.

Comparison 12: Mifepristone + misoprostol versus osmotic dilators + placebo + misoprostol, Outcome 2: Dilation achieved (cm)

Dilation achieved (cm)
Study	Mifepristone + misoprostol	Placebo + miso + dilator	Measure	Result
Shaw 2017	0.5 cm (0–4) 27 women	3 cm (0.5–5) 21 women	Median (range)	Effect of mifepristone compared with dilator ‐2.5 cm

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Need for additional dilation

Mifepristone plus misoprostol may increase the need for additional dilation compared with osmotic dilators plus placebo plus misoprostol (RR 4.67, 95% CI 1.91 to 11.38; 1 study; 48 participants; Analysis 12.3).

12.3 — Comparison 12: Mifepristone + misoprostol versus osmotic dilators + placebo + misoprostol, Outcome 3: Need for additional dilation

Ability to complete procedure

Not reported.

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

It is uncertain if there is any difference between mifepristone plus misoprostol and osmotic dilators plus placebo plus misoprostol in risk of cervical laceration (RR 3.89, 95% CI 0.49 to 30.82; 1 study; 48 participants; Analysis 12.4). No other adverse events were reported.

12.4 — Comparison 12: Mifepristone + misoprostol versus osmotic dilators + placebo + misoprostol, Outcome 4: Adverse events: cervical laceration

Side effects

Not reported.

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

It is uncertain if there is any difference between mifepristone plus misoprostol and osmotic dilators plus placebo plus misoprostol in risk of uterine perforation (RR 3.93, 95% CI 0.20 to 77.70; 1 study; 48 participants; Analysis 12.5). No other complications were reported.

12.5 — Comparison 12: Mifepristone + misoprostol versus osmotic dilators + placebo + misoprostol, Outcome 5: Complications: uterine perforation

Patient acceptability and/or satisfaction

One study used 0‐to‐100 VAS to measure patient satisfaction with the overall experience and likelihood to recommend the procedure to a friend (higher score = greater satisfaction) (Shaw 2017). The data were reported as median and range. The median score for overall experience in the mifepristone plus misoprostol group was 10 points lower than in the misoprostol plus osmotic dilator group. The median score for ‘likely to recommend to a friend’ was one point lower in the mifepristone plus misoprostol group than in the osmotic dilators plus placebo plus misoprostol group (Analysis 12.6).

12.6. Analysis.

Comparison 12: Mifepristone + misoprostol versus osmotic dilators + placebo + misoprostol, Outcome 6: Patient acceptability/satisfaction

Patient acceptability/satisfaction
Study	Mifepristone + misoprostol	Placebo + miso + dilator	Measure	Result
Overall experience
Shaw 2017	83 (15–100) 27 women	93 (47–99) 21 women	0‐100 VAS (median, range) (higher score = greater satisfaction)	Effect of mifepristone compared with dilator ‐10 VAS points (less satisfaction)
Likely to recommend to a friend
Shaw 2017	90 (44–99) 27 women	89 (4–97) 21 women	0‐100 VAS (median, range) (higher score = more likely to recommend)	Effect of mifepristone compared with dilator 1 VAS point

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Pain experienced by participants between initiation of cervical preparation method and abortion procedure

One study used 0‐to‐100 VAS to measure pain (higher score = more pain) (Shaw 2017). The data were reported as median and range. The median score in the mifepristone plus misoprostol group was 20 points greater than in the osmotic dilators plus placebo plus misoprostol group (Analysis 12.7).

12.7. Analysis.

Comparison 12: Mifepristone + misoprostol versus osmotic dilators + placebo + misoprostol, Outcome 7: Pain (preoperative, post‐misoprostol)

Pain (preoperative, post‐misoprostol)
Study	Mifepristone + misoprostol	Placebo + miso + dilator	Measure	Result
Shaw 2017	51 (10–96) 27 women	31 (1–87) 21 women	0‐100 VAS (median, range) (higher score = greater pain)	Effect of mifepristone compared with dilator 20 VAS points (more painful)

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Provider acceptability and/or satisfaction

Not reported.

Provider assessment of difficulty of procedure

Not reported.

Comparison 13: misoprostol plus mifepristone plus osmotic dilators versus misoprostol plus mifepristone (19 and 23 6/7 weeks)

One study investigated misoprostol plus mifepristone plus osmotic dilators compared with misoprostol plus mifepristone (Shaw 2017).

Primary outcomes

Procedure time

One study reported shorter median procedure time with mifepristone plus misoprostol plus osmotic dilator compared with mifepristone plus misoprostol (6.5 minutes shorter; Analysis 13.1).

13.1. Analysis.

Comparison 13: Misoprostol + mifepristone + osmotic dilators versus misoprostol + mifepristone, Outcome 1: Procedure time

Procedure time
Study	Misoprostol + mifepristone + dilators	Misoprostol + mifepristone	Measure	Result
Shaw 2017	12 minutes (7–25) 26 women	18.5 minutes (8–52) 25 women	Median (range)	Adding dilator to mifepristone plus misoprostol: 6.5 minutes shorter

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Dilation achieved

One study reported greater median dilation with mifepristone plus misoprostol plus osmotic dilator compared with mifepristone plus misoprostol (2.5 cm greater; Analysis 13.2).

13.2. Analysis.

Comparison 13: Misoprostol + mifepristone + osmotic dilators versus misoprostol + mifepristone, Outcome 2: Dilation achieved

Dilation achieved
Study	Misoprostol + mifepristone + dilators	Misoprostol + mifepristone	Measure	Result
Shaw 2017	3 cm (0.5–5) 27 women	0.5 cm (0–4) 27 women	Median (range)	Adding dilator to mifepristone plus misoprostol: 2.5 cm greater dilation

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Need for additional dilation

Mifepristone plus misoprostol plus osmotic dilator may reduce the need for additional dilation compared with mifepristone plus misoprostol (RR 0.25, 95% CI 0.12 to 0.51; 1 study; 54 participants; Analysis 13.3).

13.3 — Comparison 13: Misoprostol + mifepristone + osmotic dilators versus misoprostol + mifepristone, Outcome 3: Need for additional dilation

Ability to complete procedure

Not reported.

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

It is uncertain if there is any difference between mifepristone plus misoprostol plus osmotic dilator and mifepristone plus misoprostol in risk of cervical laceration (RR 0.26, 95% CI 0.01 to 6.12; 1 study; 48 participants; Analysis 13.4). No other adverse events were reported.

13.4 — Comparison 13: Misoprostol + mifepristone + osmotic dilators versus misoprostol + mifepristone, Outcome 4: Adverse events: cervical laceration

Side effects

Not reported.

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

It is uncertain if there is any difference between mifepristone plus misoprostol plus osmotic dilator and mifepristone plus misoprostol in risk of uterine perforation (RR 0.50, 95% CI 0.05 to 5.19; 1 study; 54 participants; Analysis 13.5).

13.5 — Comparison 13: Misoprostol + mifepristone + osmotic dilators versus misoprostol + mifepristone, Outcome 5: Complications: uterine perforation

Patient acceptability and/or satisfaction

One study reported that the mifepristone plus misoprostol plus osmotic dilators group had greater median overall satisfaction and were more likely to recommend to a friend compared with the mifepristone plus misoprostol group (both medians measured on 0‐to‐100 VAS; Analysis 13.6) (Shaw 2017).

13.6. Analysis.

Comparison 13: Misoprostol + mifepristone + osmotic dilators versus misoprostol + mifepristone, Outcome 6: Patient acceptability/satisfaction

Patient acceptability/satisfaction
Study	Misoprostol + mifepristone + dilators	Misoprostol + mifepristone	Measure	Result
Overall experience
Shaw 2017	90.5 (4–99) 27 women	83 (15–100) 27 women	0‐100 VAS (median, range) (higher score = greater satisfaction)	Adding dilator to mifepristone plus misoprostol: 7 VAS points (more satisfaction)
Likely to recommend to a friend
Shaw 2017	94 (5–99) 27 women	90 (44–99) 27 women	0‐100 VAS (median, range) (higher score = more likely to recommend)	Adding dilator to mifepristone plus misoprostol: 4 VAS points (more likely to recommend)

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Pain experienced by participants between initiation of cervical preparation method and abortion procedure

One study reported less severe pain in the mifepristone plus misoprostol plus osmotic dilators group compared with the mifepristone plus misoprostol group (median measured on 0‐to‐100 VAS; Analysis 13.7) (Shaw 2017).

13.7. Analysis.

Comparison 13: Misoprostol + mifepristone + osmotic dilators versus misoprostol + mifepristone, Outcome 7: Pain (preoperative, post‐misoprostol)

Pain (preoperative, post‐misoprostol)
Study	Misoprostol + mifepristone + dilators	Misoprostol + mifepristone	Measure	Result
Shaw 2017	49 (4–97) 27 women	51 (10–96) 27 women	0‐100 VAS (median, range) (higher score = greater pain)	Adding dilator to mifepristone plus misoprostol: ‐2 VAS points (less pain)

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Provider acceptability and/or satisfaction

Not reported.

Provider assessment of difficulty of procedure

Not reported.

Comparison 14: mifepristone plus misoprostol versus misoprostol (12 to 19 6/7 weeks)

Two studies investigated mifepristone plus misoprostol versus misoprostol (Carbonell 2007; Casey 2016).

Primary outcomes

Procedure time

In one study mifepristone plus misoprostol reduced mean procedure time compared with misoprostol alone (MD −0.93 minutes, 95% CI −1.62 to −0.24; 1 study; 877 participants; Analysis 14.1). In the second study there was little to no difference in median procedure time (P = 0.54; Analysis 14.2).

14.1 — Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 1: Procedure time (minutes)

14.2. Analysis.

Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 2: Procedure time (minutes)

Procedure time (minutes)
Study	Mifepristone + misoprostol	Misoprostol (+ placebo)	Measure	Result
Casey 2016	9.0 mm (7–12.5) 48 women	10.5 (7–16) 48 women	Median (IQR)	P = 0.54

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Dilation achieved

Mifepristone plus misoprostol may lead to greater dilation achieved compared with misoprostol alone (MD 4.00 mm, 95% CI 3.60 to 4.40; 1 study; 877 participants; Analysis 14.3). The second study reported mean dilation achieved without reporting SDs (11.7 mm, 48 participants compared with 10.9 mm, 48 participants) and median (IQR) dilation achieved (11.0 mm, 9 to 13 in both groups) (Casey 2016).

14.3 — Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 3: Dilation achieved (mm)

Need for additional dilation

Mifepristone plus misoprostol may reduce the need for additional dilation compared with misoprostol alone (RR 0.57, 95% CI 0.48 to 0.67; 1 study; 877 participants; Analysis 14.5).

14.5 — Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 5: Need for additional dilation

Ability to complete procedure

There may be little to no difference between mifepristone plus misoprostol and misoprostol alone in ability to complete procedure (RR 1.00, 95% CI 1.00 to 1.00; 1 study; 982 participants; Analysis 14.6).

14.6 — Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 6: Ability to complete procedure

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

It is uncertain if there is any difference between mifepristone plus misoprostol and misoprostol alone in risk of cervical laceration (RR 0.33, 95% CI 0.03 to 3.16; 1 study; 877 participants; Analysis 14.7.1). Mifepristone plus misoprostol may increase the risk of pre‐procedure expulsion compared with misoprostol alone (RR 4.95, 95% CI 1.58 to 15.49; 2 studies; 977 participants; I² = 0%; Analysis 14.7.2).

14.7 — Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 7: Adverse events

Side effects

Nausea

It is uncertain if mifepristone plus misoprostol has any effect on the risk of nausea compared with misoprostol alone (RR 1.04, 95% CI 0.29 to 3.72; 2 studies; 987 participants; I² = 81%; Analysis 14.8).

14.8 — Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 8: Side effects: nausea

Vomiting

It is uncertain if mifepristone plus misoprostol has any effect on the risk of vomiting compared with misoprostol alone (RR 1.60, 95% CI 0.94 to 2.72; 2 studies; 987 participants; I² = 18%; Analysis 14.9).

14.9 — Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 9: Side effects: vomiting

Diarrhea

Mifepristone plus misoprostol may increase the risk of diarrhea compared with misoprostol alone (RR 2.88, 95% CI 1.15 to 7.25; 2 studies; 987 participants; I² = 0%; Analysis 14.10).

14.10 — Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 10: Side effects: diarrhea

Fever/chills

Mifepristone plus misoprostol may increase the risk of fever or chills, or both, compared with misoprostol alone (RR 0.95, 95% CI 0.83 to 1.08; 987 participants; I² = 0%; Analysis 14.11).

14.11 — Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 11: Side effects: fever/chills

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

Carbonell 2007 reports: “There were no infections, perforations, incomplete abortions with retained products of conception or anesthetic problems”. They also report: “Two patients required transfusions.” “Five patients were hospitalized: three because of hemorrhage cases, one subject due to significant thrombocytopenia (19 000 platelets and HIV) and another patient because of fibrinogen drop from 418 to 125 mg/dL who was preventively hospitalized”. The paper does not report which intervention groups these participants were in.

Patient acceptability and/or satisfaction

One study reported that more participants would recommend mifepristone plus misoprostol to a friend compared with misoprostol alone (RR 1.67, 1.09 to 2.55; 96 participants; Analysis 14.12) (Casey 2016).

14.12 — Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 12: Patient acceptability and/or satisfaction

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Not reported.

Provider acceptability and/or satisfaction

It is uncertain if there is any difference between mifepristone plus misoprostol and misoprostol alone in provider acceptability (RR 1.31, 95% CI 0.79 to 2.19; 1 study; 96 participants; Analysis 14.13).

14.13 — Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 13: Provider acceptability and/or satisfaction

Provider assessment of difficulty of procedure

Not reported.

Comparison 15: different doses and intervals of medication (13 to 16 weeks)

One study investigated 600 mg misoprostol compared with 400 μg misoprostol (Dean 2017).

Primary outcomes

Procedure time

One study measured procedure time but only reported the difference between groups: 7.59 s (95% CI 3.25 to 4.09 minutes, P = 0.77) (Dean 2017).

Dilation achieved

Dilation achieved in the group receiving misoprostol 400 μg three hours prior to procedure was lower than in the group receiving misoprostol 600 μg 90 minutes prior to procedure (9.78 mm and 10.95 mm, respectively; P = 0.01). Numbers of participants per group were not reported, and it is unclear whether the provided data are means or medians (Dean 2017).

Need for additional dilation

The proportion of participants needing additional dilation was greater in the group receiving misoprostol 400 μg three hours prior to procedure than in the group receiving misoprostol 600 μg 90 minutes prior to procedure (97% and 85%, respectively; P = 0.05). Numbers of participants per group were not reported (Dean 2017).

Ability to complete procedure

Not reported.

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

Not reported.

Side effects

Side effects between the two groups were reported as similar with no further data provided.

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

One study reported “No complications occurred”, but with no further information or any data provided (Dean 2017).

Patient acceptability and/or satisfaction

The proportion of participants who found cervical preparation time unacceptable was lower in the group receiving misoprostol 400 μg three hours prior to procedure than in the group receiving misoprostol 600 μg 90 minutes prior to procedure (2% and 15%, respectively; P = 0.02). Numbers of participants per group were not reported (Dean 2017). This study also reported that “satisfaction with the abortion experience did not differ between groups”.

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Not reported.

Provider acceptability and/or satisfaction

The proportion of physicians who rated cervical preparation as adequate was 97% in the group receiving misoprostol 400 μg three hours prior to procedure and 90% in the group receiving misoprostol 600 μg 90 minutes prior to procedure (P = 0.27). No further data were reported (Dean 2017).

Provider assessment of difficulty of procedure

Not reported.

Comparison 16: one‐day laminaria versus two‐day laminaria (17 to 19 weeks)

One study investigated one‐day laminaria compared with two‐day laminaria (Stubblefield 1982).

Primary outcomes

Procedure time

It is uncertain if one‐day laminaria has any effect on procedure time compared with two‐day laminaria (MD −0.30 minutes, 95% CI −1.93 to 1.33; 1 study; 60 participants; Analysis 15.1).

15.1 — Comparison 15: One‐day versus two‐day osmotic dilators, Outcome 1: Procedure time (minutes)

Dilation achieved

One‐day laminaria may lead to less dilation achieved compared with two‐day laminaria (MD −4.20 mm, 95% CI −5.59 to −2.81; 1 study; 60 participants; Analysis 15.2).

15.2 — Comparison 15: One‐day versus two‐day osmotic dilators, Outcome 2: Dilation achieved (mm)

Need for additional dilation

Not reported.

Ability to complete procedure

Not reported.

Secondary outcomes

Adverse events related to cervical preparation agents (e.g. infection, cervical laceration, pre‐procedure expulsion)

Not reported.

Side effects

Not reported.

Complications (including, but not limited to: hemorrhage requiring transfusion, infection requiring hospitalization or antibiotics, uterine perforation, laparotomy, hysterectomy)

Not reported.

Patient acceptability and/or satisfaction

Not reported.

Pain experienced by participants between initiation of cervical preparation method and abortion procedure

Participants receiving two‐day laminaria were more likely to report pain during laminaria treatment than those receiving one‐day laminaria (x = 5.7, P = 0.017).

Provider acceptability and/or satisfaction

Not reported.

Provider assessment of difficulty of procedure

It is uncertain if one‐day laminaria has any effect on provider assessment of difficulty of the procedure compared with two‐day laminaria (RR 0.38, 95% CI 0.08 to 1.74; 1 study; 60 participants; Analysis 15.3).

15.3 — Comparison 15: One‐day versus two‐day osmotic dilators, Outcome 3: Provider assessment of difficulty of procedure

Discussion

Summary of main results

We identified 21 trials involving 3029 participants in this updated review. The interventions varied, and there were few comparisons with sufficient data to permit meaningful meta‐analysis. The results were similar in sensitivity analyses conducted using the fixed‐effect model for the pooled effect.

Prostaglandin versus osmotic dilators

See Table 1.

Prostaglandin may have little to no effect on procedure time compared with osmotic dilators because the data were not suitable for combining in a meta‐analysis, therefore our conclusions are only based on a narrative synthesis of heterogeneous measures of procedure time (low‐certainty evidence). Prostaglandin probably leads to less dilation achieved compared with osmotic dilators (moderate‐certainty evidence). It is uncertain if prostaglandin has any effect on need for additional dilation compared with osmotic dilators because the certainty of evidence is very low, and the 95% CI is consistent with possible benefit and possible harm. Prostaglandin may make little to no difference in ability to complete procedure (low‐certainty evidence) compared with osmotic dilators.

Mifepristone plus misoprostol versus osmotic dilators

See Table 2.

Mifepristone plus misoprostol may have little to no effect on procedure time compared with osmotic dilators because the certainty of evidence is low, and the 95% CI is consistent with possible benefit and possible harm. Mifepristone plus misoprostol may lead to less dilation achieved (low‐certainty evidence); increase the need for additional dilation (low‐certainty evidence); and have little to no effect on ability to complete procedure compared with osmotic dilators (low‐certainty evidence).

Misoprostol plus osmotic dilators versus placebo plus osmotic dilators

See Table 3.

Adding misoprostol to osmotic dilators probably reduces procedure time (moderate‐certainty evidence); increases dilation achieved (moderate‐certainty evidence); reduces the need for additional dilation (moderate‐certainty evidence); and has little to no effect on ability to complete procedure (moderate‐certainty evidence) compared with placebo plus osmotic dilators.

Mifepristone plus osmotic dilators versus placebo plus osmotic dilators

See Table 4.

Adding mifepristone to osmotic dilators may reduce procedure time (low‐certainty evidence), and probably increases dilation achieved (moderate‐certainty evidence) compared with placebo plus osmotic dilators.

Mifepristone plus osmotic dilators may have little to no effect on need for additional dilation, but there is probably little to no difference in ability to complete procedure (moderate‐certainty evidence) compared with placebo plus osmotic dilator.

Misoprostol plus dilators versus mifepristone plus osmotic dilators

See Table 5.

Misoprostol plus osmotic dilators may have little to no effect on procedure time compared with mifepristone plus osmotic dilators because the data were reported as medians per group and were not suitable for further analysis (low‐certainty evidence).

Misoprostol plus osmotic dilators may have little to no effect on dilation achieved and need for additional dilation compared with mifepristone plus osmotic dilators because the certainty of evidence is low, and the 95% CI spans possible benefit and possible harm. There is probably little to no difference in ability to complete procedure (moderate‐certainty evidence).

Mifepristone plus misoprostol plus osmotic dilators versus misoprostol plus osmotic dilators

See Table 6.

Mifepristone plus misoprostol plus osmotic dilators may have little to no effect on procedure time and dilation achieved because there were few data, and they were unsuitable for meta‐analysis (low‐certainty evidence). Mifepristone plus misoprostol plus osmotic dilators may also have little to no effect on need for further dilation because there were too few participants contributing data, and the 95% CI was consistent with possible benefit and possible harm (low‐certainty evidence).

Misoprostol plus osmotic dilators versus misoprostol

See Table 7.

Compared with misoprostol alone, misoprostol plus osmotic dilators probably increases procedure time (moderate‐certainty evidence); leads to greater dilation (moderate‐certainty evidence); and reduces the number of participants who need additional dilation (moderate‐certainty evidence). There is probably little to no difference between misoprostol plus osmotic dilators and misoprostol alone in ability to complete procedure (moderate‐certainty evidence).

Laminaria versus synthetic osmotic dilator

See Table 8.

It is uncertain if laminaria has any effect on procedure time compared with synthetic osmotic dilator because the reported data were insufficient to perform analysis (very low‐certainty evidence). There is probably little to no difference between laminaria and synthetic osmotic dilator in dilation achieved (moderate‐certainty evidence), but laminaria may result in a slight reduction in ability to complete procedure (low‐certainty evidence). Need for additional dilation was not reported.

Same‐day Dilapan‐S versus overnight laminaria

See Table 9.

Same‐day Dilapan‐S may result in an increase in procedure time (low‐certainty evidence); a reduction in dilation achieved (low‐certainty evidence); and an increase in the number of participants who need additional dilation (low‐certainty evidence) compared with overnight laminaria. Same‐day Dilapan‐S may have little or no effect on ability to complete procedure compared with overnight laminaria.

Vaginal misoprostol versus buccal misoprostol

See Table 10.

Vaginal misoprostol may have little to no effect on procedure time compared with buccal misoprostol because few participants contributed data, and the 95% CI of the effect estimate is consistent with appreciable harm and appreciable benefit (low‐certainty evidence). Vaginal misoprostol may have little to no effect on dilation achieved compared with buccal misoprostol because the reported data were not suitable for analysis (low‐certainty evidence). There may be little to no difference between vaginal misoprostol and buccal misoprostol in the number of participants who need additional dilation (low‐certainty evidence) and in ability to complete procedure (low‐certainty evidence).

Secondary outcomes

It is uncertain if there is a difference in gastrointestinal side effects (nausea, vomiting, and diarrhea) between different types of cervical priming agents for most of the comparisons. Similarly, it is uncertain if there is a difference in adverse events between different forms of cervical priming agents for the majority of comparisons.

Overall completeness and applicability of evidence

The RCTs included in this review incorporated a variety of cervical priming agents. Most trials reported our most important outcomes. Trials that performed subgroup analyses on the effect of parity (nulliparous versus parous) on procedure time or dilation achieved found either benefit (reduced procedure time) and/or increased cervical dilation, Borgatta 2012; Goldberg 2005; Goldberg 2015; Stubblefield 1982, or no effect (Boraas 2016; Casey 2016; Casey 2018; Drey 2014; Edelman 2006; Grossman 2014; Newmann 2014; Paris 2020). Heterogeneity in the way the studies defined procedure time needs to be considered when interpreting this outcome. While the majority of studies measured the time elapsed between speculum insertion and speculum removal, few studies measured the time lapsed between the initial insertion of either forceps or dilators until the last instrument was removed from the cervix or the time from completion of cervical dilation to removal of the speculum.

We have included evidence from both middle‐ and high‐income countries, covering a wide range of gestational ages (12 to 24 weeks), in our review. A broad range of available cervical priming agents were also covered, making the review generalizable in similar settings. We could not find a study that utilized Foley catheter as a priming agent, which is used in clinical settings that have limitations in accessing laminaria and Dilapan‐S.

Quality of the evidence

The included studies were generally at low risk of bias for random sequence generation, allocation concealment, blinding of participants and personnel, and incomplete outcome data. We judged some trials as high risk of bias for blinding of outcome assessment and selective reporting. Furthermore, there was insufficient information to assess risk of bias for blinding of outcome assessment and selective reporting for a substantial proportion of studies.

The certainty of the evidence ranged from moderate to very low, downgraded for the following reasons: imprecision, due to few participants contributing data, 95% CI spanning appreciable benefit and appreciable harm, and/or data that were unsuitable for meta‐analysis; and inconsistency, due to large differences in size or direction of effect. Except for procedure time and ability to complete procedure for the comparison laminaria versus synthetic dilator, we did not downgrade any other findings for risk of bias.

Potential biases in the review process

We made every effort to reduce bias in the review process. We conducted a comprehensive literature search without limitations on language or publication status. At least two members of the author team independently selected studies from the search results, extracted data, assessed risk of bias, and conducted the GRADE assessment of the certainty of evidence.

For the 2021 update, we selected outcomes for inclusion in summary of findings tables. Since several members of the author team were already aware of the data included in the previous version of the review, there was a small risk of bias in the selection of outcomes. However, we minimized this risk by discussing the choice of outcomes with a review author who was new to the team for this version of the review.

The COVID‐19 pandemic greatly disrupted the writing and publication of this review; the search is outdated, but an updated search will be performed prior to the next update.

Agreements and disagreements with other studies or reviews

Multiple Cochrane reviews have addressed cervical priming agents prior to first trimester surgical abortion, but this is the only Cochrane review to investigate the safety and effectiveness of cervical priming agents in the second trimester other than the previously published review by Newmann and colleagues (Newmann 2010). Unlike Newmann 2010, which included only participants at gestational age of between 14 and 21 weeks, the current review included participants at gestational age of between 12 and 24 weeks. Another recent review by O’Shea and colleagues also included participants at gestational age of between 14 and 24 weeks (O'Shea 2021).

Our review is in agreement with the Newmann 2010 and O'Shea 2021 reviews on the effectiveness of osmotic dilators over prostaglandins. Both reviews concluded with moderate certainty that osmotic dilators likely achieve more pre‐procedure cervical dilation than prostaglandins.

Our findings are consistent with Newmann 2010 in terms of maternal safety. Fever and chills may be higher in the prostaglandin group compared to the osmotic dilator group. Same‐day procedure cervical priming using misoprostol is a safe and reasonable option. We are not certain if there is a difference in procedure‐related adverse events or complications between the available cervical priming agents.

Similar to Newmann 2010 and O'Shea 2021, we could not identify a gold‐standard cervical priming agent supported by evidence that is superior for use prior to dilation and evacuation.

Authors' conclusions

Implications for practice.

Our review identified a heterogeneous body of evidence for comparing different cervical priming approaches.

We found the following moderate‐certainty evidence.

Misoprostol plus osmotic dilators, compared with placebo plus osmotic dilators, probably reduces procedure time, increases pre‐procedure cervical dilation, and reduces the number of participants who need additional dilation.
Misoprostol plus osmotic dilators, compared with misoprostol alone, probably increases procedure time due to the time elapsed with osmotic dilator insertion, but also probably increases pre‐procedure cervical dilation and reduces the number of participants who need additional dilation.
Prostaglandin probably leads to a reduction in dilation achieved compared with osmotic dilators.
Mifepristone plus osmotic dilators probably results in an increase in cervical dilation compared with placebo plus osmotic dilators.

Our findings show that using osmotic dilators alone compared to misoprostol alone or adding misoprostol or mifepristone to osmotic dilators probably results in more pre‐procedure cervical dilation and shorter procedure times. However, providers should always make decisions based on patient preference with respect to side effects and time needed for the cervical preparation agent to have maximum effect. In addition, there is no definitive evidence that mechanically dilating the cervix after some type of cervical preparation has been administered results in a significant risk of complications.

Serious adverse events and complications were rare in our review, and no significant difference was detected between different cervical priming agents when they were reported. Although evidence on safety was limited by the relatively small studies reporting these outcomes, it is reassuring that side effects and adverse events were uncommon and the existing cervical priming agents can be safely administered; choice should be dictated by patient preferences, provider experience, and clinic flow.

Implications for research.

We believe that we have evidence from methodologically well‐designed and executed studies about the safety and effectiveness of the currently used cervical priming agents: prostaglandin and osmotic dilators.

Our review did not find a study comparing Foley catheter with prostaglandins or osmotic dilators. As the Foley catheter is one of the priming agents in resource‐limited settings, it is important to conduct studies comparing the safety and effectiveness of Foley catheter for cervical preparation.

More adequately powered studies are also needed to compare and make strong conclusions on the rate of serious maternal complications among different priming agents. Our review found only limited studies that assessed patient and provider satisfaction and acceptability. Further studies are encouraged that focus on both provider and patient acceptability and satisfaction.

What's new

Date	Event	Description
3 March 2025	New citation required and conclusions have changed	15 new studies added; summary of findings tables added.
3 March 2025	New search has been performed	New search

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History

Protocol first published: Issue 3, 2008 Review first published: Issue 8, 2010

Notes

The COVID‐19 pandemic greatly disrupted the writing and publication of this review. We know the literature search is outdated, but the team had to move forward to publication. An updated search will be performed prior to the next update.

Acknowledgements

We acknowledge the help and support of Cochrane Fertility Regulation. We would like to thank the authors of the original review: Andrea Dalve‐Endres, Justin T Diedrich, Jody E Steinauer, Karen Meckstroth, and Eleanor A Drey. We thank Fracen Casey, a trial author who provided unpublished data. We would also like to thank the editors, peer reviewers, and copy‐editors who provided comments to improve this review.

Appendices

Appendix 1. Update search strategies

Cochrane Central Register of Controlled Trials (Ovid EBM Reviews) Date searched: 20 December 2021 1 (abortion* or D&E or "D & E" or D&X or "D & X" or feticid* or foeticid* or ((interrupt* or terminat*) adj2 pregnan*) or ((dilation or dilatation or electric or gestation or manual or pregnan* or sharp or suction or surgical or uterine or uterus or vacuum) adj3 (aspiration* or curettage or evacuation* or extraction or terminat*))).ti,ab. (29785) 2 ("2nd trimester" or "second trimester" or mid‐trimester or midtrimester or (("14" or "15" or "16" or "17" or "18" or "19" or "20" or "21" or "22" or "23" or "24") adj3 weeks) or days).ti,ab. (314686) 3 (balloon* or cervical or cervix or dilat* or hygroscopic or intracervical* or intra‐cervical* or matur* or osmotic or matur* or prepar* or prime* or priming or ripen* or hydrophilic polymer* or hypan or laminaria or antiprogesterone or anti‐progesterone or carboprost or dinoprostone or gemeprost or "isosorbide mononitrate" or "magnesium sulfate" or meteneprost or mifepristone or misoprostol or nitroglycerin or "nitric oxide" or "NO Donor*" or PGE* or prostaglandin* or sulprostone or tent or tents or Cervagem or Dilapan* or Foley* or Lamicel or Mifegyne or Nalador or RU‐486 or RU486).ti,ab. (131884) 4 1 and 2 and 3 (2023) 5 4 and (2008* or 2009* or 2010* or 2011* or 2012* or 2013* or 2014* or 2015* or 2016* or 2017* or 2018* or 2019* or 2020* or 2021* or 2022*).yr. (1376)

MEDLINE ALL (Ovid) Date searched: 20 December 2021 1 Abortion, Induced/ or Abortion, Eugenic/ or Abortion, Legal/ or Abortion, Therapeutic/ or Abortion, Incomplete/ or Abortion, Septic/ or Abortion, Criminal/ or "Dilatation and Curettage"/ or Vacuum Curettage/ (44856) 2 (abortion* or D&E or "D & E" or D&X or "D & X" or feticid* or foeticid* or ((interrupt* or terminat*) adj2 pregnan*) or ((dilation or dilatation or electric or gestation or manual or pregnan* or sharp or suction or surgical or uterine or uterus or vacuum) adj3 (aspiration* or curettage or evacuation* or extraction or terminat*))).ti,ab,kf. (372840) 3 or/1‐2 (385510) 4 Pregnancy Trimester, Second/ (15627) 5 ("2nd trimester" or "second trimester" or mid‐trimester or midtrimester or (("14" or "15" or "16" or "17" or "18" or "19" or "20" or "21" or "22" or "23" or "24") adj3 weeks) or days).ti,ab,kf. (1545244) 6 or/4‐5 (1550863) 7 exp Abortifacient Agents, Nonsteroidal/ or Cervical Ripening/ or Cervix Uteri/ or Dilatation/ or Labor Stage, First/ or Laminaria/ or Prostaglandins/ (123439) 8 (balloon* or cervical or cervix or dilat* or hygroscopic or intracervical* or intra‐cervical* or matur* or osmotic or matur* or prepar* or prime* or priming or ripen* or hydrophilic polymer* or hypan or laminaria or antiprogesterone or anti‐progesterone or carboprost or dinoprostone or gemeprost or "isosorbide mononitrate" or "magnesium sulfate" or meteneprost or mifepristone or misoprostol or nitroglycerin or "nitric oxide" or "NO Donor*" or PGE* or prostaglandin* or sulprostone or tent or tents or Cervagem or Dilapan* or Foley* or Lamicel or Mifegyne or Nalador or RU‐486 or RU486).tw,kf. (2323298) 9 or/7‐8 (2380772) 10 and/3,6,9 (7563) 11 (randomized controlled trial or controlled clinical trial).pt. (643532) 12 (groups or placebo or random* or trial).ab. or drug therapy.fs. (5355186) 13 or/11‐12 (5447399) 14 and/10,13 (2391) 15 (2008* or 2009* or 2010* or 2011* or 2012* or 2013* or 2014* or 2015* or 2016* or 2017* or 2018* or 2019* or 2020* or 2021* or 2022*).dp. (15065636) 16 and/14‐15 (1244) 17 (((medical or medically or medicinal or medication or medicine or drug) adj3 abortion*) not (surgical or aspiration or evacuation or suction or curettage or manual or electric or sharp)).ti,ab,kf. (2272) 18 16 not 17 (1157)

Embase.com Date searched: 20 December 2021 #1 'pregnancy termination'/de OR 'labor induction'/de OR 'induced abortion'/de OR 'dilation and evacuation'/de OR 'illegal abortion'/de OR 'legal abortion'/de OR 'surgical abortion'/de OR 'therapeutic abortion'/de OR 'vacuum aspiration'/de (62,465) #2 abortion*:ti,ab,kw OR 'd&e':ti,ab,kw OR 'd & e':ti,ab,kw OR 'd/e':ti,ab,kw OR feticid*:ti,ab,kw OR foeticid*:ti,ab,kw OR (((interrupt* OR terminat*) NEAR/2 pregnan*):ti,ab,kw) OR (((dilation OR dilatation OR electric OR gestation OR manual OR pregnan* OR sharp OR suction OR surgical OR uterine OR uterus OR vacuum) NEAR/3 (aspiration* OR curettage OR evacuation* OR extraction* OR terminat*)):ti,ab,kw) (117,744) #3 #1 OR #2 (148,158) #4 'second trimester pregnancy'/exp (25,976) #5 '2nd trimester':ti,ab,kw OR 'second trimester':ti,ab,kw OR 'mid‐trimester':ti,ab,kw OR midtrimester:ti,ab,kw OR (((14 OR 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21 OR 22 OR 23 OR 24) NEAR/3 weeks):ti,ab,kw) OR days:ti (272,502) #6 #4 OR #5 (281,156) #7 'abortive agent'/exp OR 'carboprost'/exp OR 'dilapan'/exp OR 'gemeprost'/exp OR 'lamicel'/exp OR 'meteneprost'/exp OR 'mifepristone'/exp OR 'misoprostol'/exp OR 'prostaglandin f2 alpha'/de OR 'sulprostone'/exp OR 'uterine cervix ripening'/exp OR 'uterine cervix'/exp OR 'uterine cervix dilatation'/exp OR 'laminaria'/exp OR 'labor stage 1'/exp OR 'prostaglandin'/exp (301,137) #8 balloon*:ti,ab,kw OR cervical:ti,ab,kw OR cervix:ti,ab,kw OR dilat*:ti,ab,kw OR hygroscopic:ti,ab,kw OR intracervical*:ti,ab,kw OR 'intra cervical*':ti,ab,kw OR matur*:ti,ab,kw OR osmotic:ti,ab,kw OR prepar*:ti,ab,kw OR prime*:ti,ab,kw OR priming:ti,ab,kw OR ripen*:ti,ab,kw OR acupuncture:ti,ab,kw OR antiprogesterone:ti,ab,kw OR 'anti progesterone':ti,ab,kw OR carboprost:ti,ab,kw OR dinoprostone:ti,ab,kw OR gemeprost:ti,ab,kw OR 'isosorbide mononitrate':ti,ab,kw OR laminaria:ti,ab,kw OR 'magnesium sulfate':ti,ab,kw OR meteneprost:ti,ab,kw OR mifepristone:ti,ab,kw OR misoprostol:ti,ab,kw OR nitroglycerin:ti,ab,kw OR 'nitric oxide':ti,ab,kw OR 'no donor*':ti,ab,kw OR pge*:ti,ab,kw OR prostaglandin:ti,ab,kw OR prostaglandins:ti,ab,kw OR sulprostone:ti,ab,kw OR tent:ti,ab,kw OR tents:ti,ab,kw OR cervagem:ti,ab,kw OR dilapan*:ti,ab,kw OR foley*:ti,ab,kw OR lamicel:ti,ab,kw OR mifegyne:ti,ab,kw OR nalador:ti,ab,kw OR 'ru 486':ti,ab,kw OR ru486:ti,ab,kw (2,967,862) #9 #7 OR #8 (3,112,027) #10 #3 AND #6 AND #9 (4,345) #11 #10 AND (2008:py OR 2009:py OR 2010:py OR 2011:py OR 2012:py OR 2013:py OR 2014:py OR 2015:py OR 2016:py OR 2017:py OR 2018:py OR 2019:py OR 2020:py OR 2021:py OR 2022:py) AND ('controlled clinical trial'/de OR 'randomized controlled trial'/de OR trial:ti,ab OR random*:ti,ab OR groups:ab OR placebo:ab) (655) #12 #11 AND [embase]/lim NOT ([embase]/lim AND [medline]/lim) (325)

Global Health (Ovid) Date searched: 20 December 2021 1 (abortion* or D&E or "D & E" or D&X or "D & X" or feticid* or foeticid* or ((interrupt* or terminat*) adj2 pregnan*) or ((dilation or dilatation or electric or gestation or manual or pregnan* or sharp or suction or surgical or uterine or uterus or vacuum) adj3 (aspiration* or curettage or evacuation* or extraction or terminat*))).ti,ab. (53371) 2 ("2nd trimester" or "second trimester" or mid‐trimester or midtrimester or (("14" or "15" or "16" or "17" or "18" or "19" or "20" or "21" or "22" or "23" or "24") adj3 weeks) or days).ti,ab. (339200) 3 (balloon* or cervical or cervix or dilat* or hygroscopic or intracervical* or intra‐cervical* or matur* or osmotic or matur* or prepar* or prime* or priming or ripen* or hydrophilic polymer* or hypan or laminaria or antiprogesterone or anti‐progesterone or carboprost or dinoprostone or gemeprost or "isosorbide mononitrate" or "magnesium sulfate" or meteneprost or mifepristone or misoprostol or nitroglycerin or "nitric oxide" or "NO Donor*" or PGE* or prostaglandin* or sulprostone or tent or tents or Cervagem or Dilapan* or Foley* or Lamicel or Mifegyne or Nalador or RU‐486 or RU486).ti,ab. (310583) 4 1 and 2 and 3 (601) 5 4 and (2008* or 2009* or 2010* or 2011* or 2012* or 2013* or 2014* or 2015* or 2016* or 2017* or 2018* or 2019* or 2020* or 2021* or 2022*).yr. (416)

Global Index Medicus Date searched: 23 December 2021 tw:((ti:(abort* OR feticid* OR interrup* OR "termination of pregnancy" OR "pregnancy termination" OR "pregnancy terminations" OR ((dilation OR dilatation OR electric OR gestation OR manual OR sharp OR suction OR surgical OR uterine OR uterus OR vacuum) AND (aspiration* OR curettage OR evacuation* OR extraction OR terminat*)) OR foeticid*))) AND ( type_of_study:("clinical_trials")) AND (year_cluster:[2008 TO 2022]) (75)

Scopus Date searched: 23 December 2021 ( TITLE‐ABS‐KEY ( ( abortion* OR d&e OR "D & E" OR d&x OR "D & X" OR feticid* OR foeticid* OR ( ( interrupt* OR terminat* ) W/2 AND pregnan* ) OR ( ( dilation OR dilatation OR electric OR gestation OR manual OR pregnan* OR sharp OR suction OR surgical OR uterine OR uterus OR vacuum ) W/3 ( aspiration* OR curettage OR evacuation* OR extraction OR terminat* ) ) ) ) AND TITLE‐ABS‐KEY ( ( "2nd trimester" OR "second trimester" OR mid‐trimester OR midtrimester OR ( ( "14" OR "15" OR "16" OR "17" OR "18" OR "19" OR "20" OR "21" OR "22" OR "23" OR "24" ) W/3 weeks ) OR days ) ) AND TITLE‐ABS‐KEY ( ( balloon* OR cervical OR cervix OR dilat* OR hygroscopic OR intracervical* OR intra‐cervical* OR matur* OR osmotic OR matur* OR prepar* OR prime* OR priming OR ripen* OR hydrophilic AND polymer* OR hypan OR laminaria OR antiprogesterone OR anti‐progesterone OR carboprost OR dinoprostone OR gemeprost OR "isosorbide mononitrate" OR "magnesium sulfate" OR meteneprost OR mifepristone OR misoprostol OR nitroglycerin OR "nitric oxide" OR "NO Donor*" OR pge* OR prostaglandin* OR sulprostone OR tent OR tents OR cervagem OR dilapan* OR foley* OR lamicel OR mifegyne OR nalador OR ru‐486 OR ru486 ) ) ) AND ( LIMIT‐TO ( PUBYEAR , 2022 ) OR LIMIT‐TO ( PUBYEAR , 2021 ) OR LIMIT‐TO ( PUBYEAR , 2020 ) OR LIMIT‐TO ( PUBYEAR , 2019 ) OR LIMIT‐TO ( PUBYEAR , 2018 ) OR LIMIT‐TO ( PUBYEAR , 2017 ) OR LIMIT‐TO ( PUBYEAR , 2016 ) OR LIMIT‐TO ( PUBYEAR , 2015 ) OR LIMIT‐TO ( PUBYEAR , 2014 ) OR LIMIT‐TO ( PUBYEAR , 2013 ) OR LIMIT‐TO ( PUBYEAR , 2012 ) OR LIMIT‐TO ( PUBYEAR , 2011 ) OR LIMIT‐TO ( PUBYEAR , 2010 ) OR LIMIT‐TO ( PUBYEAR , 2009 ) OR LIMIT‐TO ( PUBYEAR , 2008 ) ) AND ( LIMIT‐TO ( DOCTYPE, "cp" ) (16) )

Google Scholar Date searched: 23 December 2021 Various combinations of the following terms were used, with 101 results. The first ten pages of results were reviewed for results.

1st group of terms: "second trimester" "2nd trimester" midtrimester 2nd group of terms: abortion "interruption of pregnancy" "termination of pregnancy""pregnancy termination" 3rd group: cervical

Appendix 2. Previous search strategies

Medline (PubMed)  second trimester OR midtrimester OR mid‐trimester OR pregnancy trimesters[mh:noexp] OR abortion OR (uterine OR uterus OR vacuum AND aspiration[tiab]) OR (pregnancy OR abortion AND (termination* OR evacuat* OR (dilat* AND (curettage OR extraction*)))) AND (hygroscopic OR dilapan OR lamicel OR (magnesium sulfate AND polyvinyl alcohol) OR hypan OR gemeprost OR prostaglandin OR laminaria OR polyvinyls OR misoprostol OR meteneprost OR dinoprostone OR dinoprost OR hydrophilic polymer* OR sulprostone OR mifepristone OR (osmotic OR cervical OR cervix OR intracervical OR intra‐cervical AND (dilat* OR preparation* OR priming OR maturation OR ripening)) OR abortifacient agents[majr] OR abortifacient*[ti] OR foley* OR balloon catheter* OR nitric oxide) OR (pregnancy trimester, second OR pregnancy trimesters[mh:noexp] AND (abortion, induced/methods)) AND (randomized controlled trial OR randomized controlled trials OR radnomized OR clinical trial OR clinical trials OR "controlled study" OR "controlled studies" OR controlled clinical trial* OR random allocation[mh] OR double‐blind method[mh] OR single‐blind method[mh] OR research design[mh:noexp]) NOT (labor[ti] OR labour[ti])

EMBASE.com 'second trimester' OR 'pregnancy termination' OR abortionOR (uterine OR uterus AND aspiration) OR 'vacuum aspiration' OR (pregnancy AND (termination* OR evacuation* OR (dilat* AND (curettage OR extract*)))) AND (hygroscopic OR 'dilapan'/exp OR dilapan OR 'lamicel'/exp OR lamicel OR ('magnesium sulfate'/exp OR 'magnesium sulfate' AND ('polyvinyl alcohol'/exp OR 'polyvinyl alcohol')) OR hypan OR 'gemeprost'/exp OR gemeprost OR 'prostaglandin'/exp OR prostaglandin OR 'prostaglandins'/exp OR prostaglandins OR 'laminaria'/exp OR laminaria OR 'polyvinyl alcohol sponge'/exp OR 'polyvinyl alcohol sponge' OR 'polyvinyl alcohol sponges' OR 'misoprostol'/exp OR misoprostol OR 'meteneprost'/exp OR meteneprost OR 'dinoprostone'/exp OR dinoprostone OR 'dinoprost'/exp OR dinoprost OR 'hydrophilic polymer'/exp OR 'hydrophilic polymer' OR 'hydrophilic polymers' OR 'sulprostone'/exp OR sulprostone OR 'mifepristone'/exp OR mifepristone OR (osmotic OR cervical OR 'cervix'/exp OR cervix OR intracervical OR 'intra‐cervical' AND (dilat* OR preparation* OR priming OR 'maturation'/exp OR maturation OR ripening)) OR 'foley near/5 catheter'OR 'foley near/5 catheters' OR 'foley near/5 balloon' OR 'foley near/5 balloons' OR 'foley near/5 bulb' OR 'foley near/5 bulbs'OR 'balloon catheter'/exp OR 'balloon catheter' OR 'nitric oxide'/exp OR 'nitric oxide' OR 'abortive agent'/exp OR 'uterine cervix ripening' OR 'uterine cervix dilatation') OR ('second trimester' OR midtrimester OR 'mid‐trimester' AND ('induced abortion' OR (abortion AND induction) OR 'surgical abortion')) AND ('randomized controlled trial' OR 'randomized controlled trials' OR radnomized OR 'clinical trial' OR 'clinical trials'OR 'controlled study' OR 'controlled studies' OR 'controlled clinical trial' OR 'controlled clinical trials' OR 'double blind procedure' OR 'single blind procedure') NOT (labor:ti OR labour:ti)

POPLINE Strategy 1:  (hygroscopic / dilapan / lamicel / (magnesium sulfate & polyvinyl alcohol) / hypan / gemeprost / prostaglandin* / laminaria / polyvinyl / polyvinyls / misoprostol / meteneprost / dinoprostone / dinoprost / hydrophilic polymer* / sulprostone / mifepristone / ((osmotic / cervical / cervix / intracervical / intra‐cervical) & (dilat* / preparation* / priming / maturation / ripening)) / abortifacient* / foley / balloon catheter* / nitric oxide) & (trimester / midtrimester / mid‐trimester / abortion / pregnancy / fertility control postconception / ((uterine / uterus / vacuum) & aspiration) / (pregnancy & (termination* / evacuat* / (dilat* & curettage) / (dilat* & extract*)))) & (randomized / radnomized / clinical trial* / controlled study / controlled studies / =”studies”)

Strategy 2:  (second trimester / midtrimester / mid‐trimester) & (induced abortion / (induction & abortion) / surgical abortion) & (randomized / radnomized / clinical trial* / controlled study / controlled studies / ="studies")

Cochrane Database (((midtrimester OR mid‐trimester OR trimester OR abortion OR pregnancy):ti,ab,kw OR (uterine OR uterus OR vacuum) AND aspiration:ti,ab,kw) AND (hygroscopic OR dilapan OR lamicel OR (magnesium sulfate AND polyvinyl alcohol) OR hypan OR gemeprost OR prostaglandin* OR laminaria OR polyvinyls OR misoprostol OR meteneprost OR dinoprostone OR dinoprost OR hydrophilic polymer* OR sulprostone OR mifepristone OR ((osmotic OR cervical OR cervix OR intracervical OR intra‐cervical) AND (dilat* OR preparation* OR priming OR maturation OR ripening)) OR abortifacient* OR foley* OR balloon catheter* OR nitric oxide):ti,ab,kw OR ((midtrimester OR mid‐trimester OR second trimester):ti,ab,kw AND (induced abortion OR (abortion AND induction) OR surgical abortion):ti,ab,kw)) NOT (labor OR labour):ti

Data and analyses

Comparison 1. Prostaglandin versus osmotic dilators.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Procedure time	0		Other data	No numeric data
1.2 Dilation achieved (mm)	3	217	Mean Difference (IV, Fixed, 95% CI)	‐3.58 [‐4.58, ‐2.58]
1.3 Need for additional dilation	2	167	Risk Ratio (M‐H, Random, 95% CI)	1.85 [0.45, 7.52]
1.4 Ability to complete procedure (number completed on first attempt)	2	167	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.95, 1.03]
1.5 Adverse events (pre‐procedure expulsion)	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.6 Side effects: nausea	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.6.1 Any nausea	3	319	Risk Ratio (M‐H, Random, 95% CI)	1.38 [0.41, 4.71]
1.6.2 Nausea 3‐4 hours after miso or placebo	1	83	Risk Ratio (M‐H, Random, 95% CI)	1.37 [0.33, 5.73]
1.7 Side effects: vomiting	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.7.1 Vomiting	3	319	Risk Ratio (M‐H, Random, 95% CI)	0.84 [0.22, 3.19]
1.7.2 Vomiting 3‐4 hours after miso or placebo	1	83	Risk Ratio (M‐H, Random, 95% CI)	0.34 [0.04, 3.15]
1.8 Side effects: diarrhea	3	319	Risk Ratio (M‐H, Fixed, 95% CI)	2.95 [1.33, 6.54]
1.9 Side effects: fever/chills	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
1.9.1 Chills	3	319	Risk Ratio (M‐H, Fixed, 95% CI)	3.17 [1.72, 5.83]
1.9.2 Fever	1	84	Risk Ratio (M‐H, Fixed, 95% CI)	5.24 [0.26, 105.93]
1.10 Complications	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
1.10.1 Haemorrhage requiring transfusion	1	84	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.01, 8.34]
1.10.2 Uterine perforation	2	239	Risk Ratio (M‐H, Fixed, 95% CI)	3.04 [0.32, 28.73]
1.10.3 Endometritis requiring antibiotics	2	239	Risk Ratio (M‐H, Fixed, 95% CI)	0.34 [0.04, 3.19]
1.11 Patient acceptability and/or satisfaction	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.12 Pain experienced by participants between initiation of cervical preparation method and abortion procedure	2	206	Risk Ratio (M‐H, Random, 95% CI)	2.59 [0.23, 28.94]
1.13 Pain experienced by participants between initiation of cervical preparation method and abortion procedure	0		Other data	No numeric data
1.14 Provider acceptability and/or satisfaction	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.15 Provider assessment of difficulty of procedure	2	133	Risk Ratio (M‐H, Fixed, 95% CI)	6.31 [1.74, 22.94]
1.16 Provider assessment of difficulty of procedure	0		Other data	No numeric data

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1.16. Analysis.

Comparison 1: Prostaglandin versus osmotic dilators, Outcome 16: Provider assessment of difficulty of procedure

Provider assessment of difficulty of procedure
Study	Misoprostol	Laminaria	Measure	Result
Sagiv 2015	1 (0–4) 41 procedures	1 (0–4) 43 procedures	Median (range) on 0‐5 scale Higher score = greater difficulty	P = 0.4

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Comparison 2. Mifepristone + misoprostol versus osmotic dilators.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
2.1 Procedure time (minutes)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.2 Dilation achieved (mm)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.3 Need for additional dilation	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
2.4 Ability to complete procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
2.5 Side effects: nausea/vomiting	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
2.6 Patient acceptability	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
2.7 Pain experienced by participants between initiation of cervical preparation method and abortion procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
2.8 Provider assessment of difficulty of procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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Comparison 3. Misoprostol + osmotic dilators versus placebo + osmotic dilators.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Procedure time	4	545	Mean Difference (IV, Random, 95% CI)	‐0.99 [‐2.05, 0.06]
3.2 Procedure time	0		Other data	No numeric data
3.3 Dilation achieved (mm)	4	484	Mean Difference (IV, Random, 95% CI)	1.83 [0.27, 3.39]
3.4 Dilation achieved	0		Other data	No numeric data
3.5 Need for additional dilation	4	546	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.50, 0.84]
3.6 Ability to complete procedure (number completed on first attempt)	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3.7 Adverse events: cervical tear requiring suturing	3	423	Risk Ratio (M‐H, Fixed, 95% CI)	1.62 [0.76, 3.46]
3.8 Side effects: nausea/vomiting	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.8.1 After pills	2	224	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.61, 1.23]
3.8.2 Overnight	1	195	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.48, 0.92]
3.8.3 After procedure	1	195	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.51, 1.23]
3.9 Side effects: diarrhea	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.9.1 After pills	2	224	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.18, 5.45]
3.9.2 Overnight	1	195	Risk Ratio (M‐H, Fixed, 95% CI)	0.58 [0.25, 1.31]
3.9.3 After procedure	1	195	Risk Ratio (M‐H, Fixed, 95% CI)	0.20 [0.01, 4.15]
3.10 Side effects: chills	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.10.1 After pills	3	423	Risk Ratio (M‐H, Fixed, 95% CI)	3.90 [2.61, 5.81]
3.10.2 Overnight	1	195	Risk Ratio (M‐H, Fixed, 95% CI)	1.56 [0.77, 3.16]
3.10.3 After procedure	1	195	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.92, 1.97]
3.10.4 Fever only	1	199	Risk Ratio (M‐H, Fixed, 95% CI)	16.83 [0.98, 287.72]
3.11 Complications	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.11.1 Hemorrhage requiring transfusion	2	394	Risk Ratio (M‐H, Fixed, 95% CI)	2.34 [0.35, 15.69]
3.11.2 Uterine perforation	1	195	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.06, 15.92]
3.11.3 Hospitalization	2	394	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.34, 4.59]
3.11.4 Reaspiration	2	394	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.14, 7.03]
3.12 Patient acceptability/satisfaction	2	228	Risk Ratio (M‐H, Fixed, 95% CI)	1.13 [0.98, 1.30]
3.13 Patient acceptability/satisfaction	0		Other data	No numeric data
3.14 Pain experienced by participants between initiation of cervical preparation method and abortion procedure	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.14.1 After day 1 medication	1	199	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.49, 1.60]
3.14.2 After day 2 medication	1	199	Risk Ratio (M‐H, Fixed, 95% CI)	4.07 [2.08, 7.98]
3.14.3 Any time between initiation of preparation method and abortion procedure	2	224	Risk Ratio (M‐H, Fixed, 95% CI)	4.66 [2.64, 8.24]
3.15 Provider acceptability/satisfaction	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3.16 Provider assessment of the procedure as very difficult	3	547	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.50, 0.97]

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Comparison 4. Mifepristone + osmotic dilators versus placebo + osmotic dilators.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Procedure time	0		Other data	No numeric data
4.2 Dilation achieved (mm)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
4.3 Need for additional dilation	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
4.4 Ability to complete procedure (number completed on first attempt)	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
4.5 Adverse events: cervical laceration	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
4.6 Side effects: fever	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
4.7 Patient satisfaction	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
4.8 Pain experienced by participants between initiation of cervical preparation method and abortion procedure	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
4.8.1 After day 1 medication	1	198	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.49, 1.62]
4.8.2 After day 2 medication	1	198	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.36, 2.21]
4.9 Provider acceptability/satisfaction	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
4.10 Provider assessment of the procedure as very difficult	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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Comparison 5. Misoprostol + osmotic dilators versus mifepristone + osmotic dilators.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
5.1 Procedure time	0	Other data	No numeric data
5.2 Dilation achieved (mm)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
5.3 Need for additional dilation	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.4 Ability to complete procedure (number completed on first attempt)	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.5 Complications	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.5.1 Uterine perforation	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.5.2 Hospitalization	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.5.3 Reaspiration	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.6 Side effects: fever	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.7 Side effects: chills	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.8 Patient satisfaction	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.9 Pain experienced by participants between initiation of cervical preparation method and abortion procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.9.1 After day 1 medication	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.9.2 After day 2 medication	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.10 Provider acceptability/satisfaction	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.11 Provider assessment of the procedure as very difficult	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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Comparison 6. Mifepristone + misoprostol + osmotic dilators versus misoprostol + osmotic dilators.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Procedure time (minutes)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
6.2 Procedure time	0		Other data	No numeric data
6.3 Dilation achieved	0		Other data	No numeric data
6.4 Need for additional dilation	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
6.5 Adverse events	2	97	Risk Ratio (M‐H, Fixed, 95% CI)	0.38 [0.06, 2.45]
6.6 Complications: uterine perforations	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
6.7 Patient acceptability/satisfaction	1		Other data	No numeric data
6.7.1 Overall experience	1		Other data	No numeric data
6.7.2 Likely to recommend to a friend	1		Other data	No numeric data
6.8 Pain (preoperative, post‐misoprostol)	0		Other data	No numeric data
6.9 Provider assessment of difficulty of procedure	0		Other data	No numeric data

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Comparison 7. Misoprostol + osmotic dilators versus misoprostol.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
7.1 Procedure time (minutes)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
7.2 Dilation achieved (mm)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
7.3 Need for additional dilation	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
7.4 Ability to complete procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
7.5 Side effects: chills	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
7.6 Complications: uterine perforation	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
7.7 Patient acceptability	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
7.7.1 Would have the same procedure again	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
7.7.2 Would recommend to a friend	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
7.8 Provider assessment of difficulty	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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Comparison 8. Laminaria versus synthetic dilator.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
8.1 Procedure time	0	Other data	No numeric data
8.2 Dilation achieved	0	Other data	No numeric data
8.3 Ability to complete procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
8.4 Adverse events: cervical injury	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
8.5 Complications	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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Comparison 9. Same‐day Dilapan‐S versus overnight osmotic dilators.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
9.1 Procedure time (minutes)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
9.2 Dilation achieved (mm)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
9.3 Need for additional dilation	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.4 Ability to complete procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.5 Adverse events: cervical tear	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.6 Nausea	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.6.1 Overnight	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.6.2 Immediately before abortion	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.6.3 After procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.7 Vomiting	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.7.1 Overnight	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.7.2 Immediately before abortion	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.7.3 After procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.8 Diarrhea	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.9 Complications	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.9.1 Bleeding requiring uterotonics	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.9.2 Reaspiration	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.9.3 Cervical laceration	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.10 Patient satisfaction	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.10.1 Satisfied with the procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.10.2 Satisfied with overall clinic experience	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.11 Provider assessment of difficulty of procedure	0	Other data	No numeric data
9.12 Pain experienced by participants between initiation of cervical preparation method and abortion procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.12.1 Overnight pain	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.12.2 Pain immediately before procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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Comparison 10. Vaginal misoprostol versus buccal misoprostol.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
10.1 Procedure time (minutes)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
10.2 Dilation achieved (French)	0	Other data	No numeric data
10.3 Need for additional dilation	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.4 Ability to complete procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.5 Side effects: nausea	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.5.1 Nausea first medication	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.5.2 Nausea second medication	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.6 Side effects: vomiting	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.6.1 Vomiting	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.7 Side effects: diarrhea	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.8 Side effects: fever and/or chills	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.9 Patient acceptability and/or satisfaction	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.9.1 “I did not mind taking the medication in my cheeks”	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.9.2 “I did not mind taking the medication in my vagina”	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.9.3 Medications were easy to take	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.9.4 Would choose the same method again	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.9.5 Would recommend this method	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.10 Provider acceptability and/or satisfaction	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.10.4 Would use the same method again for this patient	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.10.5 Would recommend this method for other patients	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.11 Provider assessment of difficulty of procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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10.3 — Comparison 10: Vaginal misoprostol versus buccal misoprostol, Outcome 3: Need for additional dilation

10.4 — Comparison 10: Vaginal misoprostol versus buccal misoprostol, Outcome 4: Ability to complete procedure

Comparison 11. Mifepristone versus osmotic dilators.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
11.1 Procedure time	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
11.2 Dilation achieved (French)	0	Other data	No numeric data
11.3 Adverse events: pre‐procedure expulsion	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.4 Side effects: nausea and/or vomiting	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.4.1 Night before procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.4.2 Morning of procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.5 Side effects: diarrhea	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.5.1 Diarrhea	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.6 Pain experienced by participants between initiation of cervical preparation method and abortion procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.6.1 Moderate/severe pain in the night prior to the procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.6.2 Moderate/severe pain in the morning of the procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.7 Provider assessment of difficulty of procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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Comparison 12. Mifepristone + misoprostol versus osmotic dilators + placebo + misoprostol.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
12.1 Procedure time	0	Other data	No numeric data
12.2 Dilation achieved (cm)	0	Other data	No numeric data
12.3 Need for additional dilation	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
12.4 Adverse events: cervical laceration	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
12.5 Complications: uterine perforation	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
12.6 Patient acceptability/satisfaction	1	Other data	No numeric data
12.6.1 Overall experience	1	Other data	No numeric data
12.6.2 Likely to recommend to a friend	1	Other data	No numeric data
12.7 Pain (preoperative, post‐misoprostol)	0	Other data	No numeric data

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Comparison 13. Misoprostol + mifepristone + osmotic dilators versus misoprostol + mifepristone.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
13.1 Procedure time	0	Other data	No numeric data
13.2 Dilation achieved	0	Other data	No numeric data
13.3 Need for additional dilation	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
13.4 Adverse events: cervical laceration	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
13.5 Complications: uterine perforation	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
13.6 Patient acceptability/satisfaction	1	Other data	No numeric data
13.6.1 Overall experience	1	Other data	No numeric data
13.6.2 Likely to recommend to a friend	1	Other data	No numeric data
13.7 Pain (preoperative, post‐misoprostol)	0	Other data	No numeric data

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Comparison 14. Mifepristone + misoprostol versus misoprostol.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
14.1 Procedure time (minutes)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
14.1.1 Mife + sublingual miso v sublingual miso	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
14.1.3 Mife + vaginal miso v vaginal miso	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
14.2 Procedure time (minutes)	0		Other data	No numeric data
14.3 Dilation achieved (mm)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
14.4 Dilation achieved	0		Other data	No numeric data
14.5 Need for additional dilation	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
14.6 Ability to complete procedure	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
14.7 Adverse events	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
14.7.1 Cervical laceration	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
14.7.2 Pre‐procedure expulsion	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
14.8 Side effects: nausea	2	987	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.29, 3.72]
14.9 Side effects: vomiting	2	987	Risk Ratio (M‐H, Fixed, 95% CI)	1.60 [0.94, 2.72]
14.10 Side effects: diarrhea	2	987	Risk Ratio (M‐H, Fixed, 95% CI)	2.88 [1.15, 7.25]
14.11 Side effects: fever/chills	2	987	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.83, 1.08]
14.12 Patient acceptability and/or satisfaction	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
14.13 Provider acceptability and/or satisfaction	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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14.4. Analysis.

Comparison 14: Mifepristone + misoprostol versus misoprostol, Outcome 4: Dilation achieved

Dilation achieved
Study	Mifepristone + misoprostol	Misoprostol (+ placebo)	Measure	Result
Casey 2016	11.7 mm 48 women	10.9 mm 48 women	Mean (no SD reported)	Little or no difference between groups
Casey 2016
Casey 2016
Casey 2016	11.0 mm (9–13) 48 women	11.0 mm (9–13) 48 women	Median (IQR)	No difference between groups

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Comparison 15. One‐day versus two‐day osmotic dilators.

Outcome or subgroup title	No. of studies	Statistical method	Effect size
15.1 Procedure time (minutes)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
15.2 Dilation achieved (mm)	1	Mean Difference (IV, Fixed, 95% CI)	Totals not selected
15.3 Provider assessment of difficulty of procedure	1	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Boraas 2016.

*Study characteristics*
Methods	Study design: Randomized controlled trial Study grouping: Parallel group
Participants	Included criteria: People who desired D&E for induced abortion or intrauterine fetal death (IUFD) treatment, at least 18 years old, spoke English, had a pregnancy between 16 0/7 and 20 6/7 weeks' gestation on the day of D&E confirmed by ultrasound Excluded criteria: People with multiple‐gestation pregnancy, known allergy to misoprostol, active bleeding disorder or anticoagulation, or any signs of infection or cervical insufficiency at enrollment Pretreatment: None
Interventions	Intervention characteristics Group A (n = 14): 400 μg buccal misoprostol + laminaria. Time (hours) prior to the abortion procedure: 3 h Group B (n = 15): placebo (4 mg folic acid) + laminaria. Time (hours) prior to the abortion procedure: 3 h
Outcomes	Pre‐procedure cervical dilation: fully reported, French Time to complete the procedure: fully reported, minutes Need for additional dilation Side effects: diarrhea, severe nausea or vomiting, cervical tear requiring intervention Provider satisfied or very satisfied by the procedure
Notes	Sponsorship source: Society of Family Planning Research Fund Country: USA Setting: 2 centers: Magee‐Women's Hospital of the University of Pittsburgh Medical Center (MWH) and Planned Parenthood of Western Pennsylvania (PPWP) in Pittsburgh, Pennsylvania Dates of study: October 2013 to March 2014 Declarations of interest: "None of the authors has any related conflicts of interest"
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Research staff randomized participants 1:1 to receive misoprostol or placebo using computer‐generated block randomization with random block sizes of 2, 4 and 6 prepared by a statistician not responsible"
Allocation concealment (selection bias)	Low risk	Quote: "Research staff not performing the D&E opened the next sequentially numbered, opaque, sealed envelope containing the participant's allocated study medication, tablets of similar size and shape within identical"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Judgement Comment: The patient, the physician and outcomes assessors are blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "or oral (PPWP) doxycycline (200 mg). The participant, research staff and physician performing the D&E were all blinded to the assigned allocation. Research staff administered a questionnaire to participants immediately preoperatively"
Incomplete outcome data (attrition bias) All outcomes	Low risk	There was no loss to follow up
Selective reporting (reporting bias)	Low risk	There is a prospective trial registration that specified the outcomes and these outcomes are described in the study
Other bias	Low risk	Nothing to indicate any other source of bias

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Borgatta 2012.

*Study characteristics*
Methods	Study design: Randomized controlled trial Study grouping: Parallel group
Participants	Baseline characteristics Mifepristone Age (SD): 24.5 +/− 5 Parity (> 0): 13 (52%) Reproductive history (previous 1 or more abortion): 15 (60%) Gestational age (mean days and SD): 105 +/− 4 Osmotic dilator Age (SD): 25 +/− 6 Parity (> 0): 19 (76%) Reproductive history (previous 1 or more abortion): 16 (64%) Gestational age (mean days and SD): 104 +/− 4 Included criteria: Participants aged 18 to 45 years requesting an induced abortion between 14 and 16 menstrual weeks Excluded criteria: Fetal demise, ruptured membranes, spontaneous abortion, active substance abuse, or did not speak English or Spanish Pretreatment: Similar baseline
Interventions	Group A (n = 25): oral mifepristone 200 mg 20 to 24 hours before the procedure Group B (n = 25): osmotic dilator 3 to 6 vaginal laminarias 20 to 24 hours before the procedure
Outcomes	Pre‐procedure cervical dilation: French Time to complete the procedure: minutes Side effects: severe nausea or vomiting, overnight bleeding Pre‐procedure expulsion Severe pain in the morning of the abortion procedure Severe pain in the night prior to the procedure Provider assessment of the procedure as difficult
Notes	Source of funding: "This study was supported by a grant from the Society of Family Planning Research Fund." Country: USA Setting: Boston Medical Center Study period: October 2009 to March 2011 Declarations of interest: "The authors have no conflicts of interest."
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated sequence generation
Allocation concealment (selection bias)	Low risk	Opaque sealed envelope is used
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The surgeon is not blinded to the treatment. The subject is also aware of which method was provided but the outcomes of the study are not likely to be affected by lack of blinding.
Blinding of outcome assessment (detection bias) All outcomes	High risk	outcome assessor not blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	There was no loss to follow up. One patient in the laminaria group expelled before D and E and her data were included in the outcomes related to symptoms and opinions
Selective reporting (reporting bias)	Low risk	There is a prospective trial registration that specified the outcomes and these outcomes are described in the study
Other bias	Low risk	Nothing to indicate any other sources of bias

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Carbonell 2007.

*Study characteristics*
Methods	Study design: Randomized clinical trial Computer‐generated random list Single center (Clinica Mediterrania Medica, Valencia, Spain) Power calculation/sample size: Average cervical dilation expected to be 1.5 mm more in the mifepristone and misoprostol group, power of 90%, one‐tail test with significance level of 0.05, minimum sample size 190 participants per group and increased 15% for losses. Adjusted significance level to 0.10 when ANOVA performed Study approved by the Scientific and Ethics Committee of the Clinic.
Participants	Inclusion criteria: People presenting for termination between 12 and 20 weeks via D&E, gestational age by ultrasound with BPD 20 to 46 mm, willing to abstain from intercourse for 14 days after procedure Exclusion criteria: Hemoglobin < 9.0, blood pressure > 160/90, uterine bleeding, active genital infection, intolerance/allergy to misoprostol or mifepristone Number of participants randomized: 900
Interventions	Group A (n = 225): mifepristone 200 mg + misoprostol 600 µg sublingually 48 h later Group B (n = 225): mifepristone 200 mg + misoprostol 600 µg vaginally 48 h later Group C (n = 225): 600 µg misoprostol sublingually 48 h later Group D (n = 225): 600 µg misoprostol vaginally 48 h later 4 groups: 200 mg mifepristone administered or not administered 48 hours before administration of 600 μg sublingual or vaginal misoprostol. Participants then waited 1.5 to 2.5 hours. When examined at misoprostol placement, if felt “not adequate cervical conditions”, 1 or 2 Dilapan tents were inserted intracervically.
Outcomes	Primary outcome: Degree of cervical dilation reached prior to procedure measured by diameter of Hegar dilator before cervical resistance first noticed Secondary outcomes: Surgical time from anesthesia administration to speculum removal Other outcomes: Side effects (nausea, vomiting, diarrhea, fever/chills), amount of external cervical orifice dilation at inspection, presence of blood/products of conception in external os and/or vagina, immediate complications
Notes	Warned participants of fetal risks once mifepristone administered Study dates: July 2004 to February 2006 Declarations of interest: Not reported Funding source: "All the materials, medicines and funding were covered by ClÍnica Mediterrania Médica, Valencia, Spain."
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated sequence
Allocation concealment (selection bias)	Low risk	Assignment by sequentially numbered, sealed opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Physician and patient aware of treatment group but degree of dilation and procedure time not likely to be affected by lack of blinding
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not reported whether the outcome assesor is blinded or not
Incomplete outcome data (attrition bias) All outcomes	Low risk	There was loss to follow up, but in a small number. 9 post randomization dropouts (9/450) after taking Mifepristone before administration of misoprostol. 2 of these were gestational expulsions due to only the effect of mifepristone and 7 of them did not return after misoprostol and outcome is not known. In the misoprostol‐only group, there were 14 dropouts (14/450) after randomization and the outcome is not known.
Selective reporting (reporting bias)	Unclear risk	No protocol or prospective trial registration
Other bias	Low risk	Nothing to indicate any other source of bias

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Casey 2016.

*Study characteristics*
Methods	Study design: Randomized controlled trial Study grouping: Parallel group
Participants	Included criteria: Healthy people, over 18 years of age, eligible for non‐urgent D&E at 14 weeks plus 0 days to 19 weeks plus 6 days gestation, confirmed by sonogram Excluded criteria: Emergent need for D&E, fetal demise, allergy or contraindication to mifepristone or misoprostol
Interventions	Group A (n = 50): mifepristone 200 mg oral + 400 μg misoprostol vaginally 15 minutes later. Time (hours) prior to the abortion procedure: 4 to 6 h Group B (n = 50): placebo oral + 400 μg misoprostol vaginally 15 minutes later. Time (hours) prior to the abortion procedure: 4 to 6 h
Outcomes	Pre‐procedure cervical dilation: millimeters Time to complete the procedure: minutes Pre‐procedure expulsion Provider satisfied and highly recommend for other patients Patient acceptability described as "would recommend to my friends"
Notes	Country: USA Setting: 2 centers, MedStar Washington Hospital Center and Planned Parenthood of Metropolitan Washington Year of study: February 2013 to January 2014 Declarations of interest: "The authors do not have any conflicts of interest." Source of funding: "The Society of Family Planning Research Fund"
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "computer‐generated randomization sequences, one for each site."
Allocation concealment (selection bias)	Low risk	Quote: "Research pharmacy staff encapsulated mifepris‐ tone 200 mg or placebo in a dark gelatin capsules. The pharmacy staff then prepared two sets of sequentially numbered opaque sealed envelopes containing one capsule of mifepristone or placebo, according to the randomization sequence for each site."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "As the medications looked, smelled, and tasted alike, the participants were blinded to allocation, as were the research staff and clinical providers."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "coordinators were involved in randomization generation or creation of the envelopes. As the medications looked, smelled, and tasted alike, the participants were blinded to allocation, as were the research"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "We conducted an intent‐to‐treat analysis and included one subject with a protocol violation in the mifepristone arm. After enrollment,"
Selective reporting (reporting bias)	Low risk	There is a prospective trial registration that specified the outcomes and these outcomes are described in the study
Other bias	Low risk	Nothing to indicate any other source of bias

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Casey 2018.

*Study characteristics*
Methods	Study design: Randomized controlled trial Setting: Virginia, USA
Participants	70 participants randomized. Inclusion criteria: Healthy English‐ or Spanish‐speaking participants, over 18 years of age, eligible for non‐urgent D&E at 16 0/7 weeks to 20 6/7 weeks gestation, confirmed by sonogram, and willing/able to undergo informed consent Exclusion criteria: Emergent need for D&E, intrauterine infection, fetal demise, molar pregnancy, intolerance, allergy or contraindication to mifepristone or misoprostol
Interventions	Group A (n = 36): vaginal misoprostol (plus mifepristone); 20 to 24 hours following administration of 200 mg mifepristone, the participant went to the bathroom to insert the vaginal suppository Group B (n = 34): buccal misoprostol (plus mifepristone) 20 to 24 hours following administration of 200 mg mifepristone, a research staff member observed the participant taking the buccal powder, allowing absorption for 30 minutes as with buccal administration of misoprostol.
Outcomes	Procedure time Blood loss Final dilation required Acceptability with respect to ease of dilation on a 10‐point scale Assessment of procedure difficulty Recommendation for future use on a 5‐point Likert scale
Notes	Dates of study: September 2016 to June 2017 Funding sources: “The Society of Family Planning Research Fund SFPRF9‐14, CTSA/CCTR 16 grant number: UL1TR002649” Declarations of interest: “The authors do not have any conflicts of interest.” Correspondence with trial author (August 2020): attempts to publish the full paper have so far been unsuccessful, but the trialist has provided a copy of the manuscript
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“A pharmacy research staff member at the VCU Medical Center not involved in study recruitment or analysis created a 1:1 computer‐generated randomization sequence in block sizes of 2, 4, and 6”
Allocation concealment (selection bias)	Low risk	“A pharmacy research staff member at the VCU Medical Center not involved in study recruitment… prepared two sets of sequentially numbered opaque sealed pouches or envelopes containing the buccal and vaginal medications”
Blinding of participants and personnel (performance bias) All outcomes	Low risk	“Participants and providers were blinded as the medications 107 and placebos looked, felt and for buccal, tasted, identical”
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Correspondence with trialist Oct 2020: "the investigators and outcome assessors were blinded"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low attrition and not differential A 1/36 and B 1/34 not included in analysis (one products expelled prior to D&E, one assignment package opened)
Selective reporting (reporting bias)	Low risk	Pre‐specified outcomes are reported in full (in unpublished manuscript provided by trialist)
Other bias	Low risk	Nothing to indicate any other source of bias

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Dayananda 2016.

*Study characteristics*
Methods	Study design: Randomized controlled trial Setting: Planned Parenthood of New York City, New York, NY, USA
Participants	Number of participants: 180 Number of withdrawals (per group if available): 4/90 and 3/90 not included in the analysis "due to missing data" Inclusion criteria: 18 years of age and older, seeking pregnancy termination from 18 0/7 to 24 0/7 weeks of gestation, eligible for pregnancy termination at Planned Parenthood of New York City, able to give informed consent, English speaking Exclusion criteria: Active bleeding or hemodynamically unstable at enrollment, signs of chorioamnionitis or clinical infection at enrollment, signs of spontaneous labor or cervical insufficiency at enrollment, spontaneous intrauterine fetal demise, allergy to laminaria or Dilapan‐S
Interventions	Group A (n = 90): laminaria. Participants in this arm will receive laminaria cervical dilators 1 day before D&E procedure. Group B (n = 90): Dilapan‐S. Participants in this arm will receive Dilapan‐S cervical dilators 1 day before D&E procedure.
Outcomes	Primary outcome: Procedure time Secondary outcomes: Cervical dilation Pain Ability to complete procedure on first attempt Complications
Notes	Dates of study: Not reported (first registered on ClinicalTrials.gov January 2014, results posted September 2018) Funding sources: Not reported Declarations of interest: Not reported Contacted trialist August 2020 to ask for clarification about data; awaiting reply
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	“We randomized 180 women evenly across treatment arms”
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	From trial registration entry: "Triple blind: Participant, Care Provider, Investigator"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	From trial registration entry: "Triple blind: Participant, Care Provider, Investigator"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low attrition and not differential. A 4/90 and B 3/90 not included in the analysis ‘due to missing data’
Selective reporting (reporting bias)	High risk	Primary outcome of procedure time not reported per randomised group as per trial registration. It is reported by gestational cohort within randomised group. Other outcomes not reported in full.
Other bias	Low risk	Nothing to indicate any other source of bias

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Dean 2017.

*Study characteristics*
Methods	Study design: Randomized controlled trial Setting: New York, USA
Participants	Number of participants: Unclear. States that 118 was the recruitment target but does not report how many were randomized Number of withdrawals (per group if available): Not reported Inclusion criteria: 18 years of age and older, eligible for pregnancy, termination at Planned Parenthood of NYC, able to give informed consent, English speaking Exclusion criteria: Reports active bleeding, severe pain, or symptoms of spontaneous labor at enrollment, intrauterine fetal demise identified on preoperative ultrasound, allergy to misoprostol
Interventions	Group A (n = ?): misoprostol 400 μg 3 hours prior to procedure Group B (n = ?): misoprostol 600 μg 90 minutes prior to procedure
Outcomes	Primary outcome: Procedure time Secondary outcomes: To compare the doses and intervals of misoprostol for differences in: initial cervical dilation; need for mechanical dilation and ease of dilation if required; ability to complete the abortion procedure without further cervical preparation; complications; provider variables including ease of procedure and satisfaction with cervical preparation; patient variables including preoperative side effects, postoperative pain, and acceptability.
Notes	Dates of study: Trial registration states started November 2014 and finished August 2016. Funding sources: Not reported Declarations of interest: Not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	“Allocation: randomized” Randomisation process not described in detail
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Care provider blinded. Lack of blinding of subjects is unlikely to affect procedure time outcome
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No denominators reported so we do not know if there was any attrition
Selective reporting (reporting bias)	High risk	Data not reported in full for primary outcome, only reported as difference between groups.
Other bias	Low risk	Nothing to indicate any other source of bias

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Drey 2014.

*Study characteristics*
Methods	Study design: Randomized controlled trial Study grouping: Parallel group
Participants	Baseline characteristics Laminaria + misoprostol Age (mean): 25.2 Gestational age: 22.2 BMI >/= 30: 26% Laminaria + placebo Age (mean): 25.3 Gestational age: 22.3 BMI >/= 30: 23% Included criteria: English and Spanish speakers who were at least 18 years old, certain of their decision to have a termination by D&E, and 21 weeks 0 days to 23 weeks 1 day pregnant by ultrasound BPD on the day of dilator placement Excluded criteria: Contraindications to misoprostol; previous uterine surgery; people who were able to describe the appearance of misoprostol, which would interfere with study blinding
Interventions	Group A (n = 98): medium laminaria tents + buccal misoprostol 200 μg on day 2. Time (hours) prior to the abortion procedure: 3 to 4 h prior to the procedure Group B (n = 98): laminaria + buccal placebo, medium laminaria tents + 2 x 50‐milligram vitamin B₆ tablets. Time (hours) prior to the abortion procedure: 3 to 4 h prior to the procedure
Outcomes	Pre‐procedure cervical dilation: millimeters Time to complete the procedure: minutes Need for additional dilation Diarrhea following the procedure Nausea or vomiting following the procedure Cervical tear requiring intervention Bleeding requiring transfusion Pre‐procedure expulsion Uterine perforation Hospitalization Re‐aspiration Severe pain following the procedure Provider assessment of the procedure as difficult Median satisfaction score with the abortion procedure
Notes	GA of study participants, beyond 21 weeks Funding source: "Supported by the Fellowship in Family Planning, Hellman Family Awards for Early‐Career Faculty Development and an anonymous foundation." Country: USA Year of study: October 2003 to May 2005 Declarations of interest: "No potential conflicts of interest for any of the authors"
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was accomplished using a computer‐generated, random‐number‐producing algorithm."
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "staff filled sequentially labeled but otherwise identical, opaque pill containers with either two 200 mcg misoprostol tablets or two 50‐mg vitamin B6 tablets (placebo). Because no identical‐appearing placebo exists for misoprostol, to ensure blinding of research and clinical staff, subjects self‐administered study tablets in private."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "A research assistant who was uninvolved with collection of data was available to assist patients with correct buccal placement. All other clinic and research staff were blinded to the study group assignments until data analysis was complete."
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants except one were available for intention‐to‐treat analysis
Selective reporting (reporting bias)	Unclear risk	No protocol or prospective trial registration
Other bias	Low risk	Nothing to indicate any other source of bias

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Edelman 2006.

*Study characteristics*
Methods	Study design: Randomized, double‐blind, placebo‐controlled trial Computer‐generated block randomization by gestational age group (early/mid) Single center (Lovejoy Surgicenter in Portland, Oregon, USA) Power calculation/sample size: Expected difference in cervical circumference of 4 mm, 80% power, alpha level of 0.05, 72 participants needed Study protocols approved by the Institutional Review Board at Oregon Health and Sciences University. Published as full study
Participants	Inclusion criteria: People seeking D&E termination between 13 and 20 weeks 6 days confirmed by ultrasound, age > 18 years old, good general health, English speaking Exclusion criteria: Inability to receive deep conscious sedation, contraindication to misoprostol, pregnancies beyond 20 weeks 6 days excluded because they undergo a 2‐day cervical preparation procedure Number of participants randomized: 138 (closed prior to planned 144 participants due to longer‐than‐expected enrollment period)
Interventions	Group A (n = 69): laminaria plus misoprostol. 1 to 2 (size LL Nippon) laminaria overnight plus 400 μg buccal misoprostol 60 to 90 minutes prior to D&E Group B (n = 69): laminaria plus placebo. 1 to 2 (size LL Nippon) laminaria overnight plus 500 mg buccal magnesium oxide (placebo) 60 to 90 minutes prior to D&E Laminaria placement based on gestational age: Early (13 to 15 weeks 6 days) 1‐laminaria, mid (16 to 20 weeks 6 days) 2‐laminaria, an additional laminaria was placed when needed to assist with successful retention of laminaria
Outcomes	Primary outcome: Degree of cervical dilation reached prior to procedure measured by diameter of dilator where loss of resistance first noted Secondary outcomes: Difficulty of dilation on a 100‐millimeter VAS (0 = very easy to 100 mm = very hard), need for additional dilation and if difficult (yes/no), procedure time (from speculum insertion to removal), estimated blood loss Other outcomes: Side effects (cramping, nausea, diarrhea, bleeding), immediate complications
Notes	2 experienced abortion providers performed procedures. Study dates: September 2002 to October 2004 Declarations of interest: Not reported Funding support by Lovejoy Surgicenter
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	computer‐generated sequence
Allocation concealment (selection bias)	Low risk	Assignment by sealed opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Both the surgeons performing the procedures and staff counseling and enrolling subjects were blinded to treatment allocation
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The assessor, the patient and the surgeon are blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	A total of 4 patients in the 13 to 15 6/7 weeks group (Incomplete data and 1 ineligible subject) and 9 patients in the 16 to 20 6/7 weeks group were not included in the final analysis for reasons unlikely to be related to the intervention (decided not to proceed with the procedure [laminaria = 2, laminaria and misoprostol = 2], did not take study medication [laminaria = 2, laminaria and misoprostol=1], study packet opened but patient declined study [laminaria and misoprostol = 1], patient given clinic misoprostol instead of study medication [laminaria and misoprostol=1])
Selective reporting (reporting bias)	Unclear risk	No protocol or prospective trial registration
Other bias	Low risk	Nothing to indicate any other sources of bias

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Goldberg 2005.

*Study characteristics*
Methods	Study design: Randomized, double‐blind, placebo‐controlled trial Block randomization from a computer‐generated random numbers table Single center (San Francisco General Hospital, San Francisco, California, USA) Power calculation/sample size: To detect a 4.5‐minute difference between groups, two‐tailed hypothesis with alpha error 0.05 and 95% power, 78 participants needed Study approved by Committee on Human Research of the University of California, San Francisco Published as full study
Participants	Inclusion criteria: People seeking abortion procedures between 12 weeks 6 days and 15 weeks 6 days verified by ultrasound, English/Spanish speaking, good health, > 18 years old Exclusion criteria: More than 1 prior cesarean delivery, multiple gestation, fetal demise, documented cervical or lower uterine segment myoma (> 3 cm), history of prior cone biopsy or loop electrosurgical excision procedure, bleeding disorder or anticoagulation therapy, IUD in place, allergy to tomisoprostol, breastfeeding and unwilling to temporarily discard milk Number of participants randomized: 84 (1 participant in misoprostol group failed to appear on second day for procedure)
Interventions	Group A (n = 42): misoprostol. Day 1: placebo (speculum exam with sham placement). Day 2 (procedure day): 400 µg misoprostol placed in the posterior fornix of the vagina 3 to 4 hours prior to the procedure Group B (n = 42): laminaria. Day 1: overnight laminaria. Day 2 (procedure day): 2 placebo tablets (vitamin B₆) placed in the posterior fornix of the vagina 3 to 4 hours prior to the procedure
Outcomes	Primary outcome: Procedure time Secondary outcomes: Degree of cervical dilation reached prior to procedure measured by diameter of Pratt dilator where loss of resistance first noticed, difficulty of additional dilation (if required), overall procedural difficulty, ability to complete the procedure on first attempt, patient acceptability (pain scores, adverse effects, preferences) Other outcomes: Side effects (pain, nausea, vomiting, diarrhea, chills), immediate complications
Notes	Funding sources: "Financial support for this study was received from the University of California San Francisco Center for Reproductive Health Research and Policy." Study dates: February 2002 to September 2003 Declarations of interest: Not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	computer‐generated sequence
Allocation concealment (selection bias)	Low risk	Opaque sealed envelope
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The nurse practitioner and the surgeon doing the procedure are blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Researcher is separate than the one who recruit the patients.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Only one patient in the misoprostol group was lost to follow up (did not return for abortion on day 2)
Selective reporting (reporting bias)	Unclear risk	No protocol or prospective trial registration
Other bias	Low risk	Nothing to indicate any other sources of bias

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Goldberg 2015.

*Study characteristics*
Methods	Study design: Randomized controlled trial
Participants	Baseline characteristics Misoprostol with osmotic dilator Age: 25.9 +/− 5.9 Gestational age: 17 wk 7 d +/− 7.32 d Parity: 1 (0, 2) Mifepristone with osmotic dilator Age: 25.3 +/− 5.8 Gestational age: 17 wk 6 d +/− 6.53 d Parity: 1 (0, 2) Placebo plus osmotic dilator Age: 24.6 +/− 5.7 Gestational age: 17 wk 6 d +/− 6.12 d Parity: 1 (0, 2) Inclusion criteria: 16 weeks 0 days to 23 weeks 6 days of gestation, English/ Spanish‐speaking people who were in good health, at least 18 years old, and sure of their decision to have an outpatient pregnancy termination Exclusion criteria: More than 1 prior cesarean delivery, multiple gestation, fetal demise confirmed by ultrasound examination, documented cervical or lower uterine segment myoma measuring > 3 cm in diameter, history of prior cone biopsy or loop electrosurgical excision procedure, bleeding disorder or current anticoagulation therapy, IUD in place, allergy to misoprostol, or if breastfeeding and unwilling to temporarily discard milk
Interventions	Group A (n = 100): misoprostol plus placebo plus osmotic dilator. Day 1: placebo (for mifepristone) + medium‐sized laminaria. Day 2: 400 mg buccal misoprostol received 3 h prior to the procedure Group B (n = 100): mifepristone plus placebo plus osmotic dilator. Day 1: 200 mg oral mifepristone + medium‐sized laminaria. Day 2: placebo (for misoprostol) received 3 h prior to the procedure Group C (n = 100): placebo plus osmotic dilator alone. Day 1: dilators and placebo (for mifepristone). Day 2: placebo (for misoprostol) received 3 h prior to the procedure
Outcomes	Pre‐procedure cervical dilation Time to complete the procedure Need for additional dilation Hospitalization for acute management of hemorrhage Cervical tear requiring intervention Provider satisfied or very satisfied by the procedure Pain after day 2 medication (misoprostol or placebo) on pain scale Hemorrhage requiring intervention
Notes	Funding source: "Supported by the Society of Family Planning Research Fund (SFPRF)" Country: USA Setting: Family Planning Associates Medical Group, Chicago, Illinois; Planned Parenthood of New York City, New York; Women’s Options Center, San Francisco General Hospital, San Francisco, California; Lovejoy Surgicenter, Portland, Oregon; Magee‐Women’s Hospital of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and Brigham and Women’s Hospital and Boston Medical Center, Boston, Massachusetts Year of study: February 2013 to February 2014 Declarations of interest: "The authors did not report any potential conflicts of interest."
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Using computer‐generated blocked ran‐ domization with a block size of six, women were as signed in a one‐to‐one‐to‐one ratio to receive:"
Allocation concealment (selection bias)	Low risk	Quote: "staff not involved in trial conduct prepared the sequentially numbered, opaque randomization envelopes containing the study medications."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Patients, operating physicians, and research staff collecting data were blinded to treatment arm."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "study medications. Patients, operating physicians, and research staff collecting data were blinded to treatment arm. Abortions were started 3 hours (630 minutes) after day 2 medication administration."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low attrition and not differential. A 2/100 not included in procedure time analysis (1 expelled pregnancy on initial examination; 1 dilation and evacuation not completed on first attempt, primary outcome not collected on day 3); B 2/100 not included in procedure time analysis (1 woman found to be ineligible; 1 dilation and evacuation not completed on first attempt, primary outcome not collected on day 3) C 1/100 not included in analysis (woman withdrew).
Selective reporting (reporting bias)	Low risk	There is a prospective trial registration that specified the outcomes and these outcomes are described in the study
Other bias	Low risk	Nothing to indicate any other sources of bias

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Grimes 1987.

*Study characteristics*
Methods	Study design: Randomized, double‐blind trial Table of random numbers to select random permuted blocks of 6 Single center (Midtown Hospital, Atlanta, Georgia, USA)
Participants	Inclusion criteria: People seeking abortion procedures between 14 and 16 weeks gestational age, confirmed by ultrasound (BPD 25 to 33 mm) Exclusion criteria: None stated Number of participants randomized: 219 Study dates: 4 February 1984 to 21 December 1985
Interventions	Group A (n = 109): Lamicel group had a 5‐millimeter Lamicel inserted; if 5‐millimeter would not fit, a 3‐millimeter diameter Lamicel was used Group B (n = 110): laminaria group had multiple laminaria placed, medium‐sized dilators until snug, then small until cervix tightly packed or participant could no longer tolerate Both groups had dilators in place for a minimum of 2 hours.
Outcomes	Primary outcome: Cervical dilation measured by if larger than 37 French units prior to procedure, ability to dilate to 43 French units Secondary outcomes: Vasovagal reaction, bleeding upon removal of dilators, cervical injury Other outcomes: Immediate complications
Notes	Cost of the devices also mentioned by authors: Lamicel costs USD 4.50/each, laminaria USD 2.00/each; mean cost of treatment for participants with laminaria is then USD 10.80. Using initial cervical dilation of 37 French units as a dichotomous variable, to demonstrate a 2x increase over the 16% rate with laminaria, power of 80% and alpha of 0.05 (two‐tailed), 111 participants per group Funding support: Not reported Declarations of interest: Not reported Study dates: February 1984 to December 1985 No statement of ethics committee approval Published as full study
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Sequence generated using table of random number
Allocation concealment (selection bias)	Low risk	Assignment by sequentially numbered opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The physician was unaware of which treatment the patient had received. The surgeon guessed the allocation of the subjects in 30 % of the cases while removing the cervical priming agents but lack of blinding is unlikely to affect the dilation outcome.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Researcher is unaware of patient’s allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	There was no loss to follow up
Selective reporting (reporting bias)	Unclear risk	No protocol of prospective trial registration
Other bias	Low risk	Nothing to indicate any other sources of bias

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Grossman 2014.

*Study characteristics*
Methods	Study design: Randomized controlled trial Study grouping: Parallel group
Participants	Included criteria: Between 13.0 and 19.0 weeks on the day of D&E confirmed by ultrasound, at least 18 years old, ability to speak English, Afrikaans, or Xhosa, staying within 1‐hour travel time to the hospital the night prior to the D&E, and ability to be contacted by telephone Excluded criteria: Active cervicitis, had a multiple gestation or fetal demise by ultrasound, had a history of bleeding disorder or current anticoagulation therapy, allergic to misoprostol, currently breastfeeding and unable to temporarily discard milk, or had more than 1 prior cesarean
Interventions	Group A (n = 79): laminaria: 3 to 5 sets of laminaria, 1 day prior to procedure Group B (n = 80): 200 μg buccal misoprostol, at least 1 hour prior to procedure
Outcomes	Time to complete the procedure Need for additional dilation Diarrhea Nausea Vomiting Extreme pain related with abortion procedure Moderate pain related with abortion procedure Uterine perforation and hospital admission Pre‐procedure expulsion Hemorrhage requiring intervention
Notes	Funding source: "This study was funded by grants from the Society of Family Planning, the World Health Organization and the South African Medical Research Council." Country: Cape Town, South Africa Setting: Secondary‐level public hospital near Cape Town, South Africa Year of study: May 2012 to June 2013 Declarations of interest: "The authors did not report any potential conflicts of interest"
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A researcher not involved with the study prepared the randomization sequence using random permuted blocks between four and eight."
Allocation concealment (selection bias)	Low risk	Quote: "Treatment allocation was concealed using sequentially numbered opaque envelopes."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The participants were not blinded and the surgeon was not fully blinded but the outcomes of procedure time and need for additional dilation are unlikely to be affected by lack of blinding
Blinding of outcome assessment (detection bias) All outcomes	High risk	Judgement Comment: The study nurse who is collecting all the study related information is not blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Judgement Comment: The study was stopped early before due to slow enrollment and low incidence of primary outcome but attrition was low and not differential (1/79 and 2/80 subjects not included in the analysis)
Selective reporting (reporting bias)	Low risk	There is a prospective trial registration that specified the outcomes and these outcomes are described in the study
Other bias	Low risk	Nothing to indicate any other source of bias

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Newmann 2014.

*Study characteristics*
Methods	Study design: Randomized controlled trial Study grouping: Parallel group
Participants	Baseline characteristics Same‐day synthetic dilator Age (mean and SD): 26.5 (22.0 to 32.0) Gestational age: 16.6 +/− 1.1 Reproductive history (prior induced abortion): 22 (64.7%) BMI: 27.1 (23.4 to 31.4) Overnight laminaria Age (mean and SD): 21.0 (19.0 to 26.0) Gestational age: 16.2 +/− 1.1 Reproductive history (prior induced abortion): 22 (62.9%) BMI: 27.5 (23.6 to 32.6) Included criteria: English‐ and Spanish‐speaking people who were at least 18 years old and between 13 6/7 and 17 6/7 weeks of gestation by ultrasound dating the day before their abortions Excluded criteria: incarcerated, did not understand Spanish or English, or had a known allergy to synthetic osmotic dilators or laminaria
Interventions	Group A (n = 36): same‐day synthetic dilator: 2 to 3 synthetic dilators, the same day as procedure Group B (n = 36): overnight laminaria: medium‐sized laminaria, night before procedure
Outcomes	Pre‐procedure cervical dilation Time to complete the procedure Need for additional dilation Diarrhea Nausea Vomiting Pain in the recovery room following the procedure Bleeding requiring uterotonics Cervical tear requiring intervention Re‐aspiration Patient satisfied with the procedure Provider assessment of difficulty of the procedure (median) Patient preference of 2‐day procedure
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was completed using a computer‐ generated, random number‐producing algorithm with permuted block randomization in blocks of four and six."
Allocation concealment (selection bias)	Low risk	Quote: "Study allocation was concealed in sequentially numbered, opaque, sealed envelopes prepared by a research assistant not involved in the study."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and surgeons are blinded. "To maintain subject blinding, all study participants underwent a speculum examination on the day before the abortion. Women randomized to same‐day dilators underwent a sham examination, including placement of a sterile gauze, and women randomized to overnight Laminaria received a paracervical block and insertion of medium Laminaria (mean diameter 4 mm) followed by placement of a sterile gauze. The health care provider performing the examination was a resident physician, attending physician, or certified nurse midwife, all of whom had experience with dilator insertion and were not going to do the dilation and evacuation. All women heard the same script from health care providers performing the “sham” or actual dilator placement."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "A research assistant, blinded to group assignment, used a stopwatch to time the abortion, which either began with mechanical dilation of the cervix"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Judgement Comment: only 3 patients withdraw from the study. 1 patient from each group decided to continue the pregnancy after randomization. 1 patient from synthetic osmotic dilator group rescheduled due to transportation difficulty. Intention to treat is used for one another patient who changed a group
Selective reporting (reporting bias)	Low risk	There is a prospective trial registration that specified the outcomes and these outcomes are described in the study
Other bias	Low risk	Nothing to indicate any other source of bias

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Paris 2020.

*Study characteristics*
Methods	Study design: Randomized controlled trial Setting: Boston Medical Center, USA
Participants	Number of participants: 50 randomized participants Number of withdrawals (per group if available): “One woman was enrolled in error after a failed attempt to insert dilators and was removed from the study” Inclusion criteria: Participants aged 18 to 45 years requesting an induced abortion between 15 weeks 0 days and 18 weeks 0 days, confirmed by ultrasound dating (consistent with BPD 30 to 40 mm) Exclusion criteria: Fetal demise, ruptured membranes, spontaneous abortion, active substance abuse or intoxication, did not speak English or Spanish, serious underlying medical illnesses, BMI > 45 kg/m², or contraindications to any of the study medications or procedures
Interventions	Group A (n = 29): medical group: participants received mifepristone 200 mg orally with ingestion observed, on the day prior to the abortion. They were given 400 μg misoprostol buccally 2 hours before the expected time of procedure. No antibiotics or other medications were used at this time. All participants were instructed to take ibuprofen if they had pain overnight. Group B (n = 20): laminaria group: participants in the dilator group had osmotic dilators placed on the day before abortion. Prior to insertion they received ibuprofen 800 mg orally. The cervix was cleansed with povidone‐iodine solution and infiltrated with 10 mL 1% lidocaine. Laminaria (2 mm and 4 mm) (Medgyn, Addison, IL, USA) and 4‐millimeter Dilapan‐S (Medicem s.r.o., Prague, Czech Republic) dilators were used. Mechanical pre‐dilation was not used. Doxycycline 200 mg orally was given after the dilators were inserted. Participants in both groups were scheduled to return 20 to 24 hours after treatment for their abortion procedure.
Outcomes	Primary outcome: Length of procedure Secondary outcomes: Subject discomfort before the abortion Pain medication (fentanyl and/or midazolam) during the abortion Cervical dilation at start of procedure Acceptability to patient: asked whether they would choose to be in the same group again if they had a similar procedure again Difficulty of procedure. Provider assessment of difficulty of procedure categories were: "very easy", "easy", "moderate", "difficult", or "very difficult".
Notes	Dates of study: October 2011 to August 2013 Funding sources: “This study was supported by a grant from the Society of Family Planning Research Fund.” Declarations of interest: “None declared.” Note: The trial registration number provided in the trial report is incorrect. The correct one is NCT01436279.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Women were allocated 3:2 to one of two groups, the medication group or the dilator group, respectively. The randomisation scheme was computer‐generated, using a block size of 10."
Allocation concealment (selection bias)	Low risk	"Allocation was carried out using sequentially numbered sealed opaque vials which contained either the mifepristone tablet or the assignment to dilators; the vials concealed the group assignment until they were opened. The vials were prepared by the research pharmacy"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Once allocation had occurred, treatment was not blinded but lack of blinding is not likely to influence the outcomes
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	One woman was enrolled in error after a failed attempt to insert dilators and was removed from the study. Forty‐nine participants were analysed. All subjects received their assigned treatment.
Selective reporting (reporting bias)	Low risk	The outcomes specified in the prospective trial registration are reported in full in the published paper
Other bias	Low risk	Nothing to indicate any other source of bias

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Sagiv 2015.

*Study characteristics*
Methods	Study design: Randomized controlled trial
Participants	Baseline characteristics Misoprostol Age median and range: 30 (15 to 47) Gestational age: 17 (14 to 20) Reproductive history (has history of previous vaginal deliveries): 15 (36.5%) Laminaria Age median and range: 29 (17 to 45) Gestational age: 16 (14 to 20) Reproductive history (has history of previous vaginal deliveries): 18 (41.8%) Included criteria: At least 15 years old, in good general health. Gestational age confirmed by first trimester ultrasound examination between 13 and 20 weeks. Excluded criteria: Allergy to misoprostol, fetal demise, bleeding disorder, current anticoagulation therapy, previous loop electrosurgical excision procedure or conization procedure, multiple gestation, and breastfeeding
Interventions	Group A (n = 41): 600 μg vaginal misoprostol, at midnight Group B (n = 43): 1 to 6 laminaria at midnight
Outcomes	Pre‐procedure cervical dilation Time to complete the procedure Need for additional dilation Diarrhea Vomiting Nausea Bleeding requiring uterotonics Bleeding requiring transfusion Pre‐procedure expulsion Pain in the recovery room following the procedure: 1 to 10 on VAS (higher score = greater pain)
Notes	Funding source: Not reported Country: Israel Setting: Edith Wolfson Hospital in Holon, Israel Year of study: January 2008 to January 2011 Declarations of interest: "No potential conflicts of interest for any of the authors."
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization was performed using a computer‐generated list of random numbers
Allocation concealment (selection bias)	Low risk	Treatment allocation was concealed by placing assignments in sequentially numbered opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	Low risk	There was no blinding but the procedure time and dilation outcomes are unlikely to be affected.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Outcome assessors not blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Judgement Comment: There was no loss to follow up
Selective reporting (reporting bias)	Low risk	There is a prospective trial registration that specified the outcomes and these outcomes are described in the study.
Other bias	Low risk	Nothing to indicate any other source of bias

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Shakir 2019.

*Study characteristics*
Methods	Study design: 4‐arm randomized controlled trial Setting: Washington, DC, USA
Participants	Number of participants: 163 Number of withdrawals (per group if available): Group A: 2/38 (1 had procedure outside the 4 to 6 hours for cervical preparation, 1 decided after randomization not to have D&E procedure); Group B: 0/40; Group C: 0/43; Group D: 0/42 Inclusion criteria: Healthy English‐speaking people 18 years of age or older presenting for a same‐day abortion between 14 and 19 6/7 weeks of gestation by ultrasound Exclusion criteria: Non‐English speaking people, those with emergent need for D&E or fetal demise, and women with an intolerance, allergy, or contraindication to misoprostol or hygroscopic dilators
Interventions	Group A (n = 38): misoprostol administered vaginally. Participants self‐administered 2 misoprostol 200 μg tablets. “We instructed women assigned vaginal misoprostol to insert the tablets 'as high as possible' in the bathroom.” Group B (n = 40): misoprostol administered buccally. Participants self‐administered 2 misoprostol 200 μg tablets. “We instructed women assigned buccal misoprostol to place two tablets buccally (one tablet in each cheek or both tablets in one cheek) and swallow the remaining misoprostol after 30 min with water.” Group C (n = 43): misoprostol administered vaginally with Dilapan‐S. “We inserted a standardized number of dilators based on gestational age, after a lidocaine 1% 20 mL paracervical block: (a) 14–15 6/7 weeks: 1–2 Dilapan and 1 laminaria; (b) 16–17 6/7 weeks: 2–3 Dilapan and 1 laminaria; (c) 18–19 6/7 weeks: 3–4 Dilapan and 1 laminaria. After insertion of the osmotic dilators, women randomized to vaginal misoprostol had one misoprostol 200 mcg tablet placed in each lateral vaginal fornix.” Group D (n = 42): misoprostol administered buccally with Dilapan‐S. “We inserted a standardized number of dilators based on gestational age, after a lidocaine 1% 20 mL paracervical block: (a) 14–15 6/7 weeks: 1–2 Dilapan and 1 laminaria; (b) 16–17 6/7 weeks: 2–3 Dilapan and 1 laminaria; (c) 18–19 6/7 weeks: 3–4 Dilapan and 1 laminaria. Women randomized to buccal misoprostol initiated use (with the same instructions as the misoprostol‐only group) after sitting up upon completion of dilator placement.” All groups: “We administered an oral non‐steroidal anti‐inflammatory drug, an opioid analgesic such as tramadol, an anxiolytic such as alprazolam, an antiemetic (most commonly promethazine), as well as an antibiotic at the time of cervical preparation. We brought participants back to the procedure room 4–6 h later to complete a side effect survey, initiate intravenous sedation, and perform the D&E procedure.”
Outcomes	Primary outcome: Total procedure time (time for both hygroscopic dilator insertion plus D&E time) Secondary outcomes: Pre‐procedure cervical dilation Participants and provider acceptability
Notes	Dates of study: January 2015 to June 2016 Funding sources: “This work was supported by the Society of Family Planning Research Fund, grant number: SFPR14‐22.” Declarations of interest: “Matthew F. Reeves, MD MPH is a consultant for ContraMed LLC and Cooper Surgical. Pamela S. Lotke, MD MPH is on an international advisory board for Bayer Healthcare. The other authors have no conflicts of interest to disclose.”
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“A research staff member at the MedStar Health Research Institute uninvolved in study recruitment or analysis created two computer‐generated randomization sequences with 1:1 allocation: one for cervical preparation (misoprostol vs. misoprostol‐dilators) and one for misoprostol administration route (buccal vs. vagina)”
Allocation concealment (selection bias)	Low risk	“Sequentially numbered opaque envelopes with the assigned groups were prepared and opened after eligibility was confirmed. Neither the investigators nor research coordinators were involved in the randomization generation or creation of the envelopes.”
Blinding of participants and personnel (performance bias) All outcomes	Low risk	“Neither providers nor participants were blinded to the treatment” but we judge that lack of blinding is unlikely to affect outcomes
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	No differential attrition. A 2/38 (one had procedure outside the 4‐6 hours for cervical preparation, one decided after randomisation not to have D&E procedure). B 0/40. C 0/43. D 0/42
Selective reporting (reporting bias)	High risk	Not all pre‐specified outcomes are reported per randomised group
Other bias	Low risk	Nothing to indicate any other source of bias

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Shaw 2015.

*Study characteristics*
Methods	Study design: Randomized controlled trial Setting: Stanford Hospital and Clinics or Santa Clara Valley Medical Center, USA Institution: Stanford Hospital and Clinics or Santa Clara Valley Medical Center
Participants	Baseline characteristics Mifepristone + 1 set of osmotic dilator Age, mean (SD): 27.7 (6.7) Gestational age: 20.9 (1.2) BMI, mean (SD): 27.7 (6.7) Misoprostol + 2 sets of osmotic dilator Age, mean (SD): 27.6 (6.5) Gestational age: 20.8 (1.1) BMI, mean (SD): 27.6 (6.5) Included criteria: Singleton, viable intrauterine pregnancy between 19 and 23 6/7 weeks of gestation by ultrasound, fluent in English or Spanish, more than 18 years of age, able to give informed consent and comply with study protocol Excluded criteria: Allergy to any study medication
Interventions	Group A (n = 26): mifepristone + misoprostol + 1 set of osmotic dilator. 200 mg mifepristone orally plus 1 set of 4 to 5 osmotic dilators a day prior to the procedure plus 400 μg buccal misoprostol 90 minutes preoperatively. Route: mifepristone: oral, misoprostol: buccal, laminaria: vaginal Time (hours) prior to the abortion procedure: mifepristone and laminaria 1 day prior to the procedure, misoprostol on the day of the procedure Group B (n = 24): misoprostol + 2 sets of osmotic dilator. 2 sets of laminaria (2 to 4 osmotic dilators placed 2 days prior to the procedure, and another 4 to 5 osmotic dilators added the day prior to the scheduled abortion [total 6 to 9]) plus 400 μg buccal misoprostol 90 minutes preoperatively. Time (hours) prior to the abortion procedure: laminaria 1 day prior to the procedure, misoprostol on the day of the procedure
Outcomes	Pre‐procedure cervical dilation of 4 cm: reported as dichotomous outcome Time to complete the procedure: minutes Cervical tear requiring intervention Hospitalization for IV antibiotics Pre‐procedure expulsion Postprocedure pain score: VAS 0 to 100 Procedure difficulty on a scale of 50 Provider assessment of the procedure as difficult on a scale of 100 Pre‐procedure cervical dilation of 5 cm
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "We randomized subjects, using a computer‐generated, site‐stratified, variable block size randomization sequence to receive either (a) two sets of osmotic dilators placed 18–24 h apart starting 2 days"
Allocation concealment (selection bias)	Low risk	Quote: "mifepristone the day prior to their procedure [18] (mifepristone group). Using opaque, numbered envelopes, allocation was revealed to research participants and coordinators at the time of randomization."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "All procedures were performed by a provider blinded to the treatment arm, in an operating room, under deep sedation or general anesthesia using standard extraction techniques." Trial registration entry states participants would not be blinded but this is unlikely to affect the dilation and procedure time outcomes.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Trial registration entry states outcome assessors would be blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Judgement Comment: A total of five subjects were not included in the final analysis after randomization. 3 patients (2 in the control and 1 in the intervention group) have expelled before D and E.1 patient in the intervention group did not receive the allocated medication and one subject in the Control group underwent unscheduled D and E. LOTFU intervention group, 2/26,7.7% and 3/24, 12.5% in the comparator group.
Selective reporting (reporting bias)	Low risk	There is a prospective trial registration that specified the outcomes and these outcomes are described in the study
Other bias	Low risk	Nothing to indicate any other sources of bias

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Shaw 2017.

*Study characteristics*
Methods	Study design: Randomized controlled trial
Participants	Baseline characteristics Mifepristone + misoprostol Age mean +/− SD: 28.2 (7) Gestational age mean +/− SD: 21.2 (1.3) Reproductive history (prior vaginal delivery): 14 (52%) BMI mean +/− SD: 26.5 (7.8) Mifepristone + laminaria + misoprostol Age mean +/− SD: 27.5 (6.4) Gestational age mean +/− SD: 20.9 (1.2) Reproductive history (prior vaginal delivery): 12 (44%) BMI mean +/− SD: 27.9 (5.6) Laminaria + misoprostol Age mean +/− SD: 27.3 (6.1) Gestational age mean +/− SD: 20.9 (1.5) Reproductive history (prior vaginal delivery): 10 (48%) BMI mean +/− SD: 27.2 (5.1) Inclusion criteria: 18 years of age and older, have alive singleton pregnancy between 19 and 23 6/7 weeks of gestation by LMP confirmed by ultrasound, able to provide informed consent and comply with study protocol, and fluent in English or Spanish Exclusion criteria: Allergy to misoprostol or mifepristone and being eligible for an outpatient procedure
Interventions	Group A (n = 28): mifepristone + laminaria + misoprostol. Day 1: oral mifepristone + laminaria, day 2: 400 μg buccal misoprostol 2 to 3 hours preoperatively Group B (n = 28): mifepristone + misoprostol. 200 mg oral mifepristone on day 1 and 400 μg buccal misoprostol 2 to 3 hours preoperatively on day 2 Group C (n = 24): laminaria + misoprostol. Day 1: placebo with laminaria, day 2 400 μg buccal misoprostol 90 minutes preoperatively
Outcomes	Pre‐procedure cervical dilation: centimeters Time to complete the procedure Need for additional dilation Cervical tear requiring intervention Uterine perforation Postprocedure pain score: 0‐to‐100 VAS score (higher score = more pain) Patient satisfaction with the procedure on a scale of 0 to 100 (higher score = more satisfaction
Notes	Funding source: "The David and Lucile Packard Foundation provided the funding for this research" Country: USA Setting: Stanford Hospital and Clinics and Santa Clara Valley Medical Center Year of study: November 2013 to November 2015 Declarations of interest: "None declared. Completed disclosure of interests forms available to view online as supporting information."
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "were randomised to one of three treatment groups by block randomisation, using a computer‐generated, site‐stratified, gestational age‐ stratified, variable block size randomisation sequence to ensure balance of treatment"
Allocation concealment (selection bias)	Low risk	Quote: "employee not on the study team prepared sealed and labelled opaque envelopes containing a card indicating the treatment group to which the participant was assigned along with a smaller envelope containing study medication"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	There was no blinding in the arm not receiving osmotic dilators but the procedure time and dilation outcomes are unlikely to be affect by lack of blinding
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessor is blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	No differential attrition. 1/28 participants in the Mifepristone + Misoprostol group did not return to clinic to undergo the procedure. 1/28 participants in the Dilators + Mifepristone + Misoprostol group did not receive allocated intervention was not included in the analysis. 2/24 participants in the Dilators + Placebo + Misoprostol group were not included in the analysis (one did not return to clinic, one underwent induction abortion).
Selective reporting (reporting bias)	Unclear risk	No protocol or prospective trial registration
Other bias	Low risk	Nothing to indicate any other sources of bias

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Stubblefield 1982.

*Study characteristics*
Methods	Study design: Randomized controlled trial Setting: Brigham and Women's Hospital, Boston, Massachusetts, USA
Participants	Inclusion criteria: People presenting for termination between 17 and 19 menstrual weeks, confirmed by ultrasound Exclusion criteria: None noted Number of participants randomized: 60
Interventions	Group A (n = 32): received 1 set of 3 to 7 small or medium laminaria tents, and abortion performed the next morning Group B (n = 28): returned on the second day for removal of the first set of laminaria and insertion of a second set of 7 to 19 tents, with the abortion performed on the third day (44 to 48 hours after first insertion of laminaria)
Outcomes	Primary outcome: Cervical dilation (1) prior to laminaria placement, (2) immediately prior to abortion, (3) follow‐up visit 2 weeks postabortion based on largest Hegar dilator that passed without resistance Secondary outcomes: Procedure time (start of uterine evacuation to removal of instruments) Pain Estimated blood loss Other outcomes: Immediate complications, 24‐hour phone number for emergency use and questionnaire administered to return by mail, 3‐month questionnaire mailed
Notes	Study dates: Not reported Funding source: Not reported Declarations of interest: Not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Table of random number is used
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The surgeon doing the procedure removed the laminaria but the dilation and procedure outcomes are unlikely to be affected by lack of blinding
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No blinding described
Incomplete outcome data (attrition bias) All outcomes	Low risk	there was no loss to follow up.
Selective reporting (reporting bias)	Unclear risk	No protocol or prospective trial registration
Other bias	Low risk	Nothing to indicate any other sources of bias

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Zamblera 1994.

*Study characteristics*
Methods	Study design: Randomized Setting: Termination of pregnancy (TOP) clinic, King's College Hospital, London
Participants	Inclusion criteria: People presenting for termination between 15 and 20 weeks, confirmed by ultrasound Exclusion criteria: None noted Number of participants randomized: 50 Study dates: Not specified
Interventions	Group A (n = 25): Dilapan‐S: participants had a 3 x 55‐millimeter hypan dilator (15 to 17 weeks of gestation) or a 4 x 65‐millimeter hypan dilator (18 to 20 weeks of gestation) inserted into the cervix 24 h preoperatively as an outpatient procedure Group B (n = 25): prostaglandin: 1 mg gemeprost vaginal pessary inserted 4 to 6 hours preoperatively (nulliparous participants received additional 1 mg gemeprost 2 to 4 hours preoperatively)
Outcomes	Ease of dilation (easy, moderate, difficult) Preoperative bleeding Pain (pre and post) Side effects (abortion, vomiting, diarrhea, flushes) Immediate complications 6‐week postprocedure follow‐up for delayed complications
Notes	Funding sources: Not reported Study dates: Not reported Declarations of interest: Not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Fifty women consecutively undergoing midtrimester dilatation and evacuation who consented to the study were randomised into two groups" ‐ no further details about randomisation process
Allocation concealment (selection bias)	Unclear risk	Unspecified
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not specified
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not specified
Incomplete outcome data (attrition bias) All outcomes	Low risk	there was no loss to follow up.
Selective reporting (reporting bias)	Unclear risk	No protocol or prospective trial registration
Other bias	Low risk	Nothing to indicate any other sources of bias

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ANOVA: analysis of variance BMI: body mass index BPD: biparietal diameter D&E: dilation and evacuation GA: gestational age IUD: intrauterine device IV: intravenous LMP: last menstrual period SD: standard deviation VAS: visual analogue scale wk: weeks

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Bartz 2013	Wrong patient population
Cahill 2018	Wrong study design
Chambers 2011a	Wrong study design: retrospective analysis
Chambers 2011b	Wrong study design: retrospective analysis
Lyus 2013	Wrong study design: retrospective chart review
NCT02679092	Study withdrawn (funding changes, no participants recruited)
Shaw 2016b	Wrong study design

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Characteristics of ongoing studies [ordered by study ID]

NCT01678703.

Study name	Comparison of laminaria and misoprostol for cervical preparation before second trimester surgical abortion
Methods	This is a prospective randomized study.
Participants	Inclusion criteria: Pregnant patients with a viable singleton Pregnancy 14 to 20 weeks of gestation Admitted for termination of pregnancy Exclusion criteria: Contraindication for administration of misoprostol Patients with more than one previous cesarean section scar Patients with impaired coagulation Significant pulmonary or cardiac disease Non‐viable pregnancy Placenta accreta or previa by ultrasound
Interventions	Device: laminaria (MedGyn Products Inc, USA) Drug: misoprostol
Outcomes	Primary outcome measures : Initial cervical opening and the need for further dilatation at the start of the procedure [ Time Frame: 8 to 12 hours after insertion of laminaria or misoprostol ] The surgical abortion will be performed 8 to 12 hours after the insertion of laminaria, or after vaginal application of misoprostol. Secondary outcome measures: Pain score during cervical preparation and after the procedure [ Time Frame: at the time of the insertion, immediately before the abortion, and immediately upon recovery from anesthesia ] The pain score will be accessed immediately after insertion of laminaria or vaginal misoprostol. Pain score will be recorded again right before performing the abortion and will address the 8 to 12 hours elapsed from the insertion. Another assessment of pain will be recorded immediately after the abortion following recovery from general anesthesia. Other outcome measures: The degree of difficulty to accomplish the abortion [ Time Frame: at the time of performing the surgical abortion ] The difficulty score will be recorded by the surgeon at the operating room immediately upon completion of the procedure.
Starting date	November 2007
Contact information	Study Director: Ron Sagiv, MD Tel Aviv University, Sackler Medical School, Israel
Notes

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NCT02013960.

Study name	Comparison between sublingual misoprostol vs. sublingual misoprostol and laminaria for second trimester termination of pregnancy
Methods	Randomized controlled trial Parallel assignment
Participants	Target recruitment: 100 participants Inclusion criteria: Age 18 to 50 years, second trimester pregnancy, no evidence of chorioamnionitis Exclusion criteria: Allergy to misoprostol, evidence for infection, asthma
Interventions	Group A: sublingual misoprostol Group B: combination of sublingual misoprostol with laminaria
Outcomes	Duration of time until pregnancy termination
Starting date	Start date: January 2014 Estimated study completion date: December 2014
Contact information	Dr Nibal Awad, Rambam Health Care Campus
Notes	Last updated December 2013. "Enrolling by invitation"

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NCT02279914.

Study name	Misoprostol dose and timing before surgical abortion at 13 to 16 weeks' gestation: a randomized trial
Methods	This study is a blinded randomized trial to compare 2 different doses and intervals of buccal misoprostol for cervical preparation before surgical abortion at 13 to 16 weeks' gestation: 400 μg administered 3 hours before D&E, and 600 μg administered 1.5 hours before D&E.
Participants	Inclusion criteria: 18 years of age and older Eligible for pregnancy termination at Planned Parenthood of NYC Able to give informed consent English speaking Exclusion criteria: Reports active bleeding, severe pain, or symptoms of spontaneous labor at enrollment Intrauterine fetal demise identified on preoperative ultrasound Allergy to misoprostol
Interventions	Drug: misoprostol 400 μg 3 hours prior to procedure Drug: misoprostol 600 μg 90 minutes prior to procedure
Outcomes	Procedure time [ Time Frame: day of abortion procedure ] Operative time defined as time from speculum in vagina to speculum out of vagina
Starting date	November 2014
Contact information	Principal Investigator: Gillian Dean, MD, MPH Planned Parenthood of NYC
Notes

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NCT02363556.

Study name	Comparing misoprostol alone to dilapan with misoprostol and comparing buccal to vaginal misoprostol
Methods	This randomized controlled trial will use a 2 x 2 factorial design to assess methods of cervical preparation prior to D&Es at 14 0/7 to 19 6/7 weeks gestational age. In total, 160 women will be randomized to misoprostol alone or Dilapan with misoprostol and separately randomized to buccal or vaginal administration of 400 μg misoprostol. A total of 80 women will receive 400 μg misoprostol only (40 vaginal and 40 buccal). Another 80 women will have Dilapan inserted and then use misoprostol (40 vaginal and 40 buccal). 4 to 6 hours later, the D&E procedure will be performed.
Participants	Inclusion criteria: Healthy pregnant women 18 years of age or older Eligible for non‐urgent D&E at 14 0/7 to 19 6/7 weeks gestation confirmed by sonogram Exclusion criteria: Women who do not speak English Fetal demise Intolerance, allergy, or contraindication to misoprostol or Dilapan
Interventions	Procedure: misoprostol administered vaginally Procedure: misoprostol administered buccally Procedure: misoprostol administered vaginally with Dilapan Procedure: misoprostol administered buccally with Dilapan
Outcomes	Primary outcome measures: Total procedure time [ Time Frame: 4 to 6 hours ] Total procedure time is defined as the time required for dilator insertion plus the D&E time. Secondary outcome measures: D&E procedure time [ Time Frame: 0 to 60 minutes ] Initial cervical dilation [ Time Frame: 0 to 10 minutes ]. Measured by the largest Hegar dilator accepted without resistance prior to the start of the procedure
Starting date	January 2015
Contact information	Principal Investigator: Dr Matthew Reeves, MD, MPH MedStar Washington Hospital Center & Planned Parenthood of Metropolitan Washington
Notes

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NCT03714880.

Study name	Cervical preparation with mifepristone prior to osmotic dilators: a randomized, double‐blind, placebo‐controlled pilot study
Methods	Randomized controlled trial, parallel assignment
Participants	Estimated enrollment: 68 participants Inclusion criteria: Age 18 to 45 years. Gestational age to be 20 weeks 0 days through 23 weeks 6 days on procedure date. Signed informed procedure consent for D&E. Willing to sign informed consent and follow study protocol Exclusion criteria: Allergy or known intolerance to mifepristone Known contraindication to mifepristone for cervical preparation prior to D&E: Chronic adrenal failure or insufficiency Concurrent use of long‐term corticosteroid therapy Inherited porphyrias Any condition that in the opinion of the investigator could impede study participation or collection of study data
Interventions	Group A: mifepristone 200 mg oral medication once 18 to 24 hours prior to dilator placement Group B: placebo oral medication once 18 to 24 hours prior to dilator placement
Outcomes	Primary outcome: Number of osmotic dilators placed prior to D&E procedure Secondary outcomes: Placement of appropriate number of dilators: the number of participants having placement of the appropriate number of dilators the day prior to the procedure based on this university's standard protocol Cervical dilation at time of procedure Requirement of mechanical dilation at time of procedure Pain dilator placement using visual analogue scale: participants will mark level of pain or discomfort on a 10‐centimeter line marked at left side with "no pain" and right side with "worst pain" Pain medications 18 to 24 hours between dilator placement (visit 2) and procedure (visit 3): number of tablets utilized for ibuprofen and codeine/paracetamol (Tylenol #3) after dilator placement Provider survey to ease of procedure and difficulty in dilation, if necessary Number of complications: composite of complications including cervical lacerations requiring repair, perforations, blood transfusions, emergency department visits, hospitalizations, infections, additional surgical procedures, or extramural deliveries
Starting date	Start date: April 2019 Estimated completion: July 2021
Contact information	Dr Mitchell D Creinin; mdcreinin@ucdavis.edu Dr Suji Uhm; sujiuhm@gmail.com
Notes

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D&E: dilation and evacuation

Differences between protocol and review

We amended our secondary outcome 'adverse events' to clarify the types of adverse events.

We amended our secondary outcome 'patient pain score' to clarify the time point for measuring pain.

We created a summary of findings table and assessed the certainty of evidence for our four most important outcomes using the GRADE approach.

We included participants at gestational age between 12 and 24 weeks, which differed from the previous review, which included participants at gestational age between 14 and 21 weeks.

We expanded the following parts of the Methods section to be in line with current Cochrane methods.

Measures of treatment effect
Unit of analysis issues
Dealing with missing data
Assessment of heterogeneity
Assessment of reporting biases
Data synthesis
Subgroup analysis and investigation of heterogeneity
Sensitivity analysis

Contributions of authors

Tesfaye H Tufa: screening of articles, data extraction, risk of bias assessment, GRADE assessment, manuscript preparation

Fiona Stewart: data extraction, risk of bias assessment, GRADE assessment, writing of results

Eleanor A Drey: review of results and manuscript

Karen Meckstroth: review of results and manuscript

Justin T Diedrich: review of results and manuscript

Sara Newmann: oversaw manuscript team and assisted with the literature review, data extraction, risk of bias, and GRADE assessment processes, and manuscript preparation

Sources of support

Internal sources

New Source of support, Other

External sources

No sources of support provided

Declarations of interest

Tesfaye H Tufa: none known

Fiona Stewart: none known

Eleanor A Drey: none known

Karen Meckstroth: none known

Justin T Diedrich: none known

Sara Newmann: none known

New search for studies and content updated (conclusions changed)

References

References to studies included in this review

Boraas 2016 {published data only}

Boraas C, Achilles S, Cremer M, Chappell C, Chen B. Dilapan-S with adjunctive misoprostol for same day dilation and evacuation: a randomized controlled trial. Contraception 2014;90(3):302. [DOI: 10.1016/j.contraception.2014.05.035] [DOI] [PubMed] [Google Scholar]
Boraas CM, Achilles SL, Cremer ML, Chappell CA, Lim SE, Chen BA. Synthetic osmotic dilators with adjunctive misoprostol for same-day dilation and evacuation: a randomized controlled trial. Contraception 2016;94(5):467-72. [DOI: 10.1016/j.contraception.2016.05.008] [DOI] [PubMed] [Google Scholar]
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Borgatta 2012 {published data only}

Borgatta L, Roncari D, Sonalkar S, Mark A, Hou MY, Finneseth M, et al. Mifepristone vs. osmotic dilator insertion for cervical preparation prior to surgical abortion at 14-16 weeks: a randomized trial. Contraception 2012;86(5):567-71. [DOI: 10.1016/j.contraception.2012.05.002] [DOI] [PubMed] [Google Scholar]
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Carbonell 2007 {published data only}

Carbonell JL, Gallego FG, Llorente MP, Bermudez SB, Sala ES, Gonzalez LV, et al. Vaginal vs sublingual misoprostol with mifepristone for cervical priming in second-trimester abortion by dilation and evacuation: A randomized clinical trial. Contraception 2007;75(3):230-7. [DOI] [PubMed] [Google Scholar]

Casey 2016 {published data only}

Casey F, Moreno-Ruiz N, Dinneen J, Perritt J, Hathaway M, Reeves M. A randomized double-blinded comparison of same-day mifepristone and misoprostol with misoprostol only for cervical preparation in second-trimester surgical abortion. Contraception 2014;90(3):293. [DOI: 10.1016/j.contraception.2014.05.207] [DOI] [Google Scholar]
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Casey 2018 {published and unpublished data}

Casey FE, Wegelin J, Reeves M. Twenty-four hour mifepristone combined with vaginal versus buccal misoprostol prior to D&E. Obstetrics and Gynecology 2018;131:76S. [Google Scholar]
NCT03134183. 24-hour mifepristone and buccal versus mifepristone and vaginal misoprostol for cervical preparation for D&E [A randomized double-blinded comparison of 24-hour interval-mifepristone and buccal misoprostol versus mifepristone and vaginal misoprostol for cervical preparation in second-trimester surgical abortion]. clinicaltrials.gov/ct2/show/NCT03134183.

Dayananda 2016 {published data only}

Dayananda I, Colarossi L, Porsch L, Balakumar K, Dean G. Laminaria compared with Dilapan-S™ for cervical preparation before dilation and evacuation at 18-24 weeks of gestation: A randomized controlled trial. Contraception 2016;94(4):388. [DOI: 10.1016/j.contraception.2016.07.026] [DOI] [Google Scholar]
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Dean 2017 {published data only}

Dean G, Colarossi L, Porsch L, Balakumar K, Dayananda I. Misoprostol dose and timing before surgical abortion at 13 to 16 weeks' gestation: A randomized trial. Contraception 2017;96(4):264. [DOI: 10.1016/j.contraception.2017.07.015] [DOI] [Google Scholar]
NCT02279914. Misoprostol dose and timing before surgical abortion at 13 to 16 weeks' gestation: a randomized trial. clinicaltrials.gov/ct2/show/NCT02279914.

Drey 2014 {published data only}

Drey EA, Benson LS, Sokoloff A, Steinauer JE, Roy G, Jackson RA. Buccal misoprostol plus laminaria for cervical preparation before dilation and evacuation at 21-23 weeks of gestation: a randomized controlled trial. Contraception 2014;89(4):307-13. [DOI: ] [DOI] [PubMed] [Google Scholar]

Edelman 2006 {published data only}

Edelman AB, Buckmaster JG, Goetsch MF, Nichols MD, Jensen JT. Cervical preparation using laminaria with adjunctive buccal misoprostol before second-trimester dilation and evacuation procedures: a randomized clinical trial. American Journal of Obstetrics and Gynecology 2006;194(2):425-30. [DOI] [PubMed] [Google Scholar]

Goldberg 2005 {published data only}

Goldberg AB, Drey EA, Whitaker AK, Kang MS, Meckstroth KR, Darney PD. Misoprostol compared with laminaria before early second-trimester surgical abortion: a randomized trial. Obstetrics Gynecology 2005;106(2):234-41. [DOI] [PubMed] [Google Scholar]

Goldberg 2015 {published data only}

Goldberg A, Fitzmaurice G, Fortin J, McKetta S, Dean G, Drey E, et al. Cervical preparation before second-trimester dilation and evacuation: A multicenter randomized trial comparing osmotic dilators alone to dilators plus adjunctive misoprostol or mifepristone. Contraception 2014;90(3):292. [DOI: 10.1016/j.contraception.2014.05.202] [DOI] [Google Scholar]
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Grimes 1987 {published data only}

Grimes DA, Ray IG, Middleton CJ. Lamicel versus laminaria for cervical dilation before early second-trimester abortion: a randomized clinical trial. Obstetrics and Gynecology 1987;69(6):887-90. [PubMed] [Google Scholar]

Grossman 2014 {published data only}

Grossman D, Constant D, Lince-Deroche N, Harries J, Kluge J. A randomized trial of misoprostol versus laminaria before dilation and evacuation in South Africa. Contraception 2014;90(3):234-41. [DOI: ] [DOI] [PubMed] [Google Scholar]
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Newmann 2014 {published and unpublished data}

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Paris 2020 {published data only}

Borgatta L, Sonalkar S, McClusky J, Kattan D, Paris A, Petricone R, et al. Mifepristone and misoprostol versus osmotic dilator use prior to surgical abortion at 15-18 weeks: A noninferiority study. Contraception 2014;90(3):307. [DOI: 10.1016/j.contraception.2014.05.052] [DOI] [Google Scholar]
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Sagiv 2015 {published data only}

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Sagiv R, Mizrachi Y, Glickman H, Kerner R, Keidar R. Laminaria vs. vaginal misoprostol for cervical preparation before second-trimester surgical abortion: a randomized clinical trial. Contraception 2015;91(5):406-11. [DOI: ] [DOI] [PubMed] [Google Scholar]

Shakir 2019 {published data only}

NCT02363556. Comparing misoprostol alone to dilapan with misoprostol and comparing buccal to vaginal misoprostol [A factorial-design randomized controlled trial comparing misoprostol alone to dilapan with misoprostol and comparing buccal to vaginal misoprostol for same-day cervical preparation prior to dilation & evacuation]. clinicaltrials.gov/ct2/show/NCT02363556. [DOI] [PubMed]
Shakir JM, Ye PP, Perritt J, Lotke P, Reeves M. A factorial-design randomized controlled trial comparing misoprostol alone with dilapan with misoprostol and comparing buccal with vaginal misoprostol for same-day cervical preparation prior to dilation & evacuation (MIDI Study). Contraception 2017;96(4):271. [DOI: 10.1016/j.contraception.2017.07.039] [DOI] [PubMed] [Google Scholar]
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NCT01615731. Value of mifepristone in cervical preparation prior to dilation and evacuation 19-24 weeks [Value of mifepristone in eliminating the need for a second set of osmotic dilators prior to dilation and evacuation between 19-24 weeks: a randomized trial]. clinicaltrials.gov/ct2/show/NCT01615731.
Shaw KA, Shaw JG, Hugin M, Velasquez G, Hopkins FW. Adjunct mifepristone for cervical preparation prior to dilation and evacuation: a randomized trial. Contraception 2015;91(4):313-9. [DOI: ] [DOI] [PubMed] [Google Scholar]

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References to studies excluded from this review

Bartz 2013 {published data only}

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 & Gynecology 2013;122(1):57-63. [DOI: ] [DOI] [PubMed] [Google Scholar]
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Cahill 2018 {published data only}

Cahill E, Henkel A, Shaw J, Blumenthal PD, Shaw KA. Adjunctive misoprostol for late second trimester D&E: A systematic review and meta-analysis. International Journal of Gynecology and Obstetrics 2018;143:818. [DOI: 10.1002/ijgo.12583] [DOI] [Google Scholar]

Chambers 2011a {published data only}

Chambers DG, Willcourt RJ, Laver AR, Baird JK, Herbert WY. Comparison of two misoprostol regimens for cervical priming before surgical pregnancy termination at 13 to 16 weeks gestations. Open Journal of Obstetrics and Gynecology 2011;1(04):187. [Google Scholar]

Chambers 2011b {published data only}

Chambers DG, Willcourt RJ, Laver AR, Baird JK, Herbert WY. Comparison of dilapan-s and laminaria for cervical priming before surgical pregnancy termination at 17–22 weeks’ gestation. International Journal of Women's Health 2011;3:347. [DOI] [PMC free article] [PubMed] [Google Scholar]

Lyus 2013 {published data only}

Lyus R, Lohr PA, Taylor J, Morroni C. Outcomes with same-day cervical preparation with dilapan-S osmotic dilators and vaginal misoprostol before dilatation and evacuation at 18 to 21+ 6 weeks’ gestation. Contraception 2013;87(1):71-5. [DOI] [PubMed] [Google Scholar]

NCT02679092 {published data only}

NCT02679092. Mifepristone versus osmotic dilators in conjunction with misoprostol for cervical preparation prior to D&E at 14-19 weeks. clinicaltrials.gov/ct2/show/NCT02679092.

Shaw 2016b {published data only}

Shaw KA, Lerma K. Update on second-trimester surgical abortion. Current Opinion in Obstetrics & Gynecology 2016;28(6):510-6. [DOI] [PubMed] [Google Scholar]

References to ongoing studies

NCT01678703 {published data only}

NCT01678703. Comparison of laminaria and misoprostol for cervical preparation before second trimester surgical abortion. clinicaltrials.gov/study/NCT01678703.

NCT02013960 {published data only}

NCT02013960. Misoprostol vs. sublingual misoprostol and laminaria for second trimester termination of pregnancy. clinicaltrials.gov/ct2/show/NCT02013960.

NCT02279914 {published data only}

NCT02279914. Misoprostol dose and timing before surgical abortion at 13 to 16 weeks' gestation: a randomized trial. https://clinicaltrials.gov/ct2/show/NCT02279914.

NCT02363556 {published data only}

NCT02363556. A factorial-design randomized controlled trial comparing misoprostol alone to dilapan with misoprostol and comparing buccal to vaginal misoprostol for same-day cervical preparation prior to dilation & evacuation. clinicaltrials.gov/study/NCT02363556. [DOI] [PubMed]

NCT03714880 {published data only}

NCT03714880. Cervical preparation with mifepristone prior to osmotic dilators: a randomized, double-blind, placebo-controlled pilot study. clinicaltrials.gov/ct2/show/NCT03714880. [DOI] [PubMed]

Additional references

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PERMALINK

Cervical preparation for dilation and evacuation at 12 to 24 weeks gestation

Tesfaye H Tufa

Fiona Stewart

Karen Meckstroth

Justin T Diedrich

Sara J Newmann

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Summary of findings 1. Prostaglandin compared to osmotic dilators for second trimester dilation and evacuation (12 6/7 weeks to 20 weeks).

Summary of findings 2. Mifepristone plus misoprostol compared to osmotic dilators for second trimester dilation and evacuation (15 0/7 weeks to 18 0/7 weeks).

Summary of findings 3. Misoprostol plus osmotic dilators compared to placebo plus osmotic dilators for second trimester dilation and evacuation (13 0/7 weeks to 23 6/7 weeks).

Summary of findings 4. Mifepristone plus osmotic dilators compared to placebo plus osmotic dilators for second trimester dilation and evacuation (16 0/7 weeks to 23 6/7 weeks).

Summary of findings 5. Misoprostol plus osmotic dilators compared to mifepristone plus osmotic dilators for second trimester dilation and evacuation (16 0/7 weeks to 23 6/7 weeks).

Summary of findings 6. Mifepristone plus misoprostol plus osmotic dilators compared to misoprostol plus osmotic dilators for second trimester dilation and evacuation (19 0/7 weeks to 23 6/7 weeks).

Summary of findings 7. Misoprostol plus osmotic dilators compared to misoprostol for second trimester dilation and evacuation (14 0/7 weeks to 19 6/7 weeks).

Summary of findings 8. Laminaria compared to synthetic osmotic dilators for second trimester dilation and evacuation (13 6/7 weeks to 24 0/7 weeks).

Summary of findings 9. Same‐day Dilapan‐S compared to overnight laminaria for second trimester dilation and evacuation (13 6/7 weeks and 17 6/7 weeks).

Summary of findings 10. Vaginal misoprostol compared to buccal misoprostol for second trimester dilation and evacuation (14 weeks to 19 6/7 weeks).

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Dichotomous data

Continuous data

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

1.

Included studies

Study design

Participants

1. Gestational ages.

Setting

Sample size

Interventions

A. Medication versus osmotic dilators

B. Medication plus osmotic dilators versus osmotic dilators

C. Medication plus osmotic dilators versus medication

D. Medication versus medication

E. Osmotic dilators versus osmotic dilators

F. Different routes of medication administration

G. Different doses and intervals of medication

Outcomes

Procedure time

Dilation achieved