Contraception xxx (xxxx) xxx

Contents lists available at ScienceDirect

Contraception
journal homepage: www.elsevier.com/locate/con

Misoprostol as an adjunct to overnight osmotic dilators prior

to second trimester dilation and evacuation: A systematic review
and meta-analysis q,qq
Erica P. Cahill a,⇑, Andrea Henkel a, Jonathan G. Shaw a,b, Kate A. Shaw a
a
Department of Obstetrics and Gynecology, Division of Family Planning Services and Research, Stanford University School of Medicine, United States
b
Department of Medicine, Division of Primary Care and Population Health, Stanford University School of Medicine, United States

a r t i c l e i n f o a b s t r a c t

Article history: Objective: To understand effect of adjunct misoprostol on cervical preparation with overnight osmotic
Received 6 March 2019 dilators for dilation and evacuation after 16 weeks gestation.
Received in revised form 26 August 2019 Methods: We searched on-line reference databases using search terms for second trimester, abortion,
Accepted 15 September 2019
misoprostol, and dilators. Randomized controlled trials of cervical preparation for second trimester
Available online xxxx
D&E using overnight osmotic dilators comparing adjunct misoprostol to placebo were included.
Weighted mean with standard deviation (SD) and pooled binary outcomes were compared.
MeSH Terms:
Results: Among 84 articles identified, three met inclusion criteria (n = 457 subjects) adjunct misoprostol
Abortion, Induced
Abortion, Therapeutic
did not significantly decrease mean procedure times (8.5 ± 4.6 vs 9.6 ± 5.8 min, p = 0.78) or manual dila-
Abortifacient Agents, Nonsteroidal tion (18% vs 28%, p = 0.23) when compared to placebo. There was no difference in total complications
Misoprostol (p = 0.61), major complications (p = 0.44), or cervical lacerations (p = 0.87).
Conclusion: Current limited evidence suggests adjunct misoprostol with osmotic dilators after 16 weeks
does not affect procedure time or need for manual dilation.
Implications: Further research is needed to determine the effect of adjunct misoprostol on major compli-
cations and blood loss.
Ó 2019 Elsevier Inc. All rights reserved.

1. Introduction abortion complications occur during second trimester abortions

[2]. Adequate cervical preparation reduces the risk of these compli-
In the United States, nearly 700,000 legal abortions are per- cations and has been the focus of recent research. At this time,
formed every year, making abortion one of the most common sur- there is insufficient evidence to define a strict cervical preparation
gical procedures [1]. The Center for Disease Control (CDC) reports protocol for patients desiring abortion in the mid to late second tri-
that the vast majority (>90%) occur prior to 13 weeks; safe abortion mester. Current clinical practice and expert opinion for cervical
in the second trimester remains an important option for women dilation in the mid to late second trimester include osmotic dila-
with barriers to accessing earlier abortion or with fetal anomalies tors overnight, often two sets of dilators for later gestations.
not discovered until the second trimester ultrasound. Dilation Several studies have investigated adding adjunctive medica-
and evacuation (D&E) is a safe procedure and complications are tions to osmotic dilators to improve cervical dilation without
rare. However, the risk of complication from D&E increases dispro- extending the days required for cervical preparation [3–5]. The
portionately with gestational age; approximately two-thirds of all medications most commonly used are mifepristone, a proges-
terone receptor modulator, and misoprostol, a synthetic prosta-
q
glandin. While mifepristone is a valuable tool in cervical
Declaration of Competing Interest: The authors declare that they have no known
competing financial interests or personal relationships that could have appeared to
preparation, it is both expensive and has limited access [4]. Miso-
influence the work reported in this paper. prostol has several important advantages for clinical use: it is
qq
Funding: Some of this research was reported as a poster abstract at the National widely available, stable at room temperature, and inexpensive.
Abortion Federation (NAF) Conference (April 2018) and the International Federation Buccal misoprostol has similar efficacy as a vaginal route [6]. Cur-
of Obstetrics and Gynecology (FIGO) Conference in Sao Paolo, Brazil (October 2018).
⇑ Corresponding author. rent Society of Family Planning Guidelines suggest adjunct miso-
E-mail address: [email protected] (E.P. Cahill).
prostol may be helpful in improving cervical dilation though it is

https://doi.org/10.1016/j.contraception.2019.09.005
0010-7824/Ó 2019 Elsevier Inc. All rights reserved.

Please cite this article as: E. P. Cahill, A. Henkel, J. G. Shaw et al., Misoprostol as an adjunct to overnight osmotic dilators prior to second trimester dilation
and evacuation: A systematic review and meta-analysis, Contraception, https://doi.org/10.1016/j.contraception.2019.09.005
2 E.P. Cahill et al. / Contraception xxx (xxxx) xxx

unclear if it decreases patient risks [7]. Since the publication of

these guidelines over ten years ago, several studies have evaluated
adjunct misoprostol for cervical preparation for mid to late second
trimester dilation and curettage. However, they are all relatively
small studies and not powered for more than their primary
outcomes.
Our aim was to systematically review currently available data
to determine the potential benefits and risks of use of misoprostol
as an adjunct to osmotic dilators for mid to late second trimester
D&E procedures.

2. Materials and methods

2.1. Data sources and searches

We searched PubMed database, MEDLINE, ClinicalTrials.gov,

Cochrane Register for Controlled Trials, and POPLINE from incep-
tion through 2019 with search terms including abortion, cervical
preparation, misoprostol, and second trimester. For example, our
PubMed Search strategy was: ((((((((‘‘Abortion, Induced” [Mesh])
OR ‘‘Abortion, Therapeutic” [Mesh])) AND ((‘‘Abortifacient Agents,
Nonsteroidal” [Mesh]) AND ‘‘Misoprostol” [Mesh])) AND cervical)
NOT labor, labor, induced, induction)) NOT first). The search was
limited to English-language trials. From all sources, a total of 84
articles were identified.

2.2. Study selection criteria

We reviewed titles as well as abstracts to identify studies exam-

ining adjunctive misoprostol with osmotic dilators. Criteria for
inclusion in the analysis were 1) data including D&E procedures
performed at 16 weeks or later, 2) use of overnight osmotic dila-
tors, 3) randomized, blinded trial comparing adjunctive misopros-
tol to placebo.

2.3. Data extraction and quality assessment

Fig. 1. Forest plots of meta-analysis outcomes for overnight dilators with adjunc-
tive misoprostol compared to placebo for second trimester abortion.
Two authors independently reviewed each study to determine
if it met inclusion criteria and assessed its quality. Of the 84 articles
initially identified, three met inclusion criteria. The meta-analysis profiles, as these were described differently in the three studies.
therefore includes a total of 457 patients who had osmotic dilators As each paper discussed estimated blood loss differently, this data
placed overnight. Of these, 228 patients received adjunctive miso- was unable to be pooled for analysis.
prostol and 229 patients received placebo. All data included were
from randomized placebo-controlled trials and were judged to be
of high quality by Cochrane Review risk of bias tools for RCT based 3. Results
on appropriate randomization, blinding of providers and subjects,
and consideration of confounders. Our search strategy identified 84 abstracts that were screened,
with three full-text manuscripts meeting all inclusion criteria:
2.4. Data synthesis and analysis Edelman (2006) [9], Drey (2014) [10], and Goldberg (2015) [11]
for a total of 457 patients.
We were interested in three major effects of adjunctive miso- All included studies were randomized controlled trials using
prostol: 1) effect on procedure time and ease of procedure, 2) effect osmotic dilators combined with either placebo or misoprostol for
on complication rates, specifically complications caused by lack of cervical preparation for D&E after 16 weeks gestation (Table 1).
cervical dilation, 3) side effect profile including timing and The study protocols in our analysis varied in several significant
duration. ways including by gestational age of patients, type of osmotic dila-
Individual data were not available, therefore the summary data tor used, and procedure location [9–11]. All studies used buccal
from each study were used for meta-analysis. The results from the misoprostol 400 mcg for dosing and route, but with variation in
three trials were pooled and weighted by the number of partici- timing from 90 minutes to three hours prior to procedure [9–11].
pants to calculate crude summary statistics (Table 3). We used The protocols also varied in the type of osmotic dilator used; two
RevMan Software [8] to perform meta-analysis (Table 4, Fig. 1). used laminaria whereas in the final, largest study, providers used
For the meta-analysis we used a random effects model weighted both laminaria and DilapanÒ.
by inverse variance to account for variance in our pooled measures. Each study reported procedure times and initial dilation
We used the I2 statistic to evaluate for heterogeneity (0–100%) and (Table 2). Procedure times in minutes were shorter with adjunctive
considered I2 values of <60% to be evidence of mild to moderate misoprostol than placebo by approximately one and a half min-
heterogeneity. We also used descriptive analysis for side-effect utes. Additional manual dilation was high in both groups, with

Please cite this article as: E. P. Cahill, A. Henkel, J. G. Shaw et al., Misoprostol as an adjunct to overnight osmotic dilators prior to second trimester dilation
and evacuation: A systematic review and meta-analysis, Contraception, https://doi.org/10.1016/j.contraception.2019.09.005
 E.P. Cahill et al. / Contraception xxx (xxxx) xxx 3

Table 1
Individual study characteristics and misoprostol timing for overnight dilators with adjunctive misoprostol compared to placebo for second trimester abortion.

Author, year Gest Age n Groups N per Timing: Timing: Primary Procedure Setting(s)
(weeks) group miso to dilators to Outcome
procedure procedure
Edelman, 2006 16–20 6/7 63 L+M 31 60–90 min 1 day prior Initial Urban surgical center
L+P 32 Dilation

19–20 6/7 29 L+M 12

L+P 17
Drey, 2014 21–23 1/7 196 L+M 98 3–4 h 1 day prior Procedure Urban hospital-based abortion clinic
Time
L+P 98
Goldberg, 2015 16–18 6/7 102 D+P+M 51 3 h ± 30 min 1 day prior Procedure Multiple urban stand-alone abortion clinics,
D+P+P 51 Time hospital-based abortion clinics and hospital
operating rooms
19–23 6/7 96 D+P+M 48
D+P+P 48

Legend: L = Laminaria, D = osmotic Dilators of any type, P = Placebo, M = Misoprostol.

Table 2
Individual study procedure characteristics for overnight dilators with adjunctive misoprostol compared to placebo for second trimester abortion.

Author, year Gest Age, N Groups Mean Procedure Time, p Pre-Op Cervical Dilation, mm p Additional p
weeks minutes mean ± SD mean ± SD Median (IQR) Dilation n (%)
Edelman, 2006 16–20 6/7 63 L+M 7.5 ± 3.2 0.65 17 ± 1.9 0.16 19 (61%) 0.79

L+P 7.8 ± 2.6 16.3 ± 1.7 21 (65%)

19–20 6/7 29 L+M 8.5 ± 3.3 0.85 18 ± 1.8 0.01 6 (50%) 0.44

L+P 8.3 ± 2.5 16 ± 1.7 11 (64%)

Drey, 2014 21–23 1/7 196 L+M 10.6 ± 4.9 0.02 25 (23.7–26.3) 0.04 9 (8%) 1

L+P 13.1 ± 8.1 24.3 (22.3–25.7) 10 (8%)

Goldberg, 2015 16–18 6/7 102 D+P+M 8.26 ± 5.9 0.33 24 ± 10 0.02 5 (10%) 0.03

D+P+P 8.19 ± 5.9 20 ± 4.0 18 (35%)

19–23 6/7 98 D+P+M 10.35 ± 7.9 0.01 25 ± 8.0 0.19 4 (8%) 0.34

D+P+P 13.39 ± 8.5 24 ± 5.0 8 (17%)

Legend: L = Laminaria, D = osmotic Dilators of any type, P = Placebo, M = Misoprostol.

more subjects who received placebo requiring manual dilation For the meta-analysis, data from each study were pooled and
(16.2% vs 24.9%). We pooled results and reported overall crude weighted by the inverse variance from each study (Table 4,
summary statistics, weighted by number of participants (Table 3). Fig. 1). None of our outcomes of interest were statistically signifi-
When we weighted by inverse variance, no outcome was statisti- cant (Fig. 1). Most studies reported the most commonly known
cally significant in the meta-analysis (Table 4). complications of D&E including cervical laceration, uterine perfora-
tion, hemorrhage, delivery prior to procedure as well as a total
complication score. In all studies, complications were rare. Com-
Table 3 paring adjunctive misoprostol to placebo, there was no statistical
Pooled analysis of procedure characteristics and complications for overnight dilators
with adjunctive misoprostol compared to placebo for second trimester abortion.
difference in total complications (p = 0.61), major complications
(p = 0.44), or cervical lacerations specifically (p = 0.87).
Misoprostol Placebo The highest total complication rate (23% in misoprostol group,
Total Participants, N 228 229 16% in placebo group) was reported in the study of women 21–
Procedure Time (min) 8.3 ± 4.6 9.6 ± 5.9 23 weeks and was mainly cervical lacerations (13% in misoprostol
Mean ± SD
group, 6% in placebo group). The authors attribute much of this to
Additional Dilation Required 37 (16.2%) 57 (24.9%)
N (%) lower uterine segment pressure, defined as a subjective sensation
All complications* 25 (11%) 26 (12%) by the surgeon of the fetal parts compressing against the lower
N (%) uterine segment and making it difficult to pass instruments. They
Major Complications** 10 (4.4%) 16 (7.0%)
suggest that the contractions caused by the misoprostol may make
N (%)
Cervical Lacerations 13 (5.7%) 9 (3.9%)
this sensation more likely. Lower uterine segment pressure was
N (%) not reported in any of the other studies, making comparison
difficult.
*All complications: uterine perforation, hospitalization, hemorrhage requiring more
intervention than uterotonics alone, cervical laceration, re-aspiration.
We also compared side effects in the misoprostol versus
**Major complications: uterine perforation, hospitalization, hemorrhage requiring placebo groups, specifically cramping. Each study had different
more intervention than uterotonics. metrics for evaluating and reporting side effects making a

Please cite this article as: E. P. Cahill, A. Henkel, J. G. Shaw et al., Misoprostol as an adjunct to overnight osmotic dilators prior to second trimester dilation
and evacuation: A systematic review and meta-analysis, Contraception, https://doi.org/10.1016/j.contraception.2019.09.005
4 E.P. Cahill et al. / Contraception xxx (xxxx) xxx

Table 4
Summary of weighted meta-analysis outcomes for overnight dilators with adjunctive misoprostol compared to placebo for second trimester abortion.

Outcome Total Participants, n % (CI) I2 p

IV, random effect
Procedure Time 457 0.32 ( 2.53, 1.89) 88% 0.78
Only > 19 weeks 321 1.66 ( 3.64, 0.32) 52% 0.10
Additional Dilation Required 457 0.68 (0.36, 1.28) 67% 0.23
Only > 19 weeks 321 0.75 (0.47, 1.21) 0% 0.24
Pre-Operative Cervical Dilation# 165 2.04 ( 1.14, 5.21) 77% 0.21
All Complications*,^ 457 0.61 (0.09, 4.13) 83% 0.61
Major Complications**,^ 457 0.47 (0.07, 3.20) 67% 0.44
Cervical Lacerations^ 457 0.81 (0.06, 10.49) 66% 0.87

*All complications: uterine perforation, hospitalization, hemorrhage requiring more intervention than uterotonics alone, cervical laceration, re-aspiration.
**Major complications: uterine perforation, hospitalization, hemorrhage requiring more intervention than uterotonics.
#Does not include Drey et al. as no mean (SD) of dilation was reported.
^Does not include Edelman et al. as no RR could be calculated due to 0 complications reported in either group.

meta-analysis of this data impossible. For example, Edelman et al. gest no force be applied to ring forceps on cervical lip as pregnancy
asked women about cramping and found a higher frequency in tissue is removed. Instead, counter traction with pressure on
women who received misoprostol compared with placebo (81% speculum during removal and using only gentle traction can
vs 50%, p = 0.02). Drey et al. used a four-point scale (0–4) for decrease risk of cervical lacerations.
assessing pain before, during, and after procedure. Women who Misoprostol is a prostaglandin analog that acts on receptors to
received adjunctive misoprostol were more likely to report severe soften the cervix. This may expedite the procedure and reduce
or unbearable pain before the procedure (52% vs 11% p < 0.001) but complications as additional dilation is not as likely to be needed.
there was no difference in pain after procedure. Goldberg et al. It also causes uterine contractions, which may serve to expedite
report the percentage of women experiencing ‘‘unacceptable or the procedure, as pregnancy may be in the process of expulsion.
very unacceptable” pain levels prior to procedure was higher in It also may explain the potential for a reduction in blood loss as
misoprostol group (37% vs 9%, p < 0.001), but the authors do not bleeding is reduced when the uterus contracts down more quickly.
report on pain during or after procedure. Regardless of metric used, We were unable to explore adjunctive misoprostol’s effect on
all studies found that women who received misoprostol reported blood loss in this analysis due to differences in reporting of this
more pain after administration of medication and before procedure outcome between the studies. Recent work demonstrates that esti-
than women who received placebo. mated blood loss may severely underestimate actual blood loss in
D&E, particularly at later gestational ages [13]. Further research to
evaluate the impact of misoprostol on blood loss is needed.
4. Discussion Misoprostol has many advantages for use for cervical prepara-
tion, including it is inexpensive, stable at room temperature, and
We found that adjunctive misoprostol did not significantly widely available. While mifepristone has been shown to have a
decrease procedure time or the need for additional dilation when similar efficacy to an additional day of osmotic dilators and to be
compared with placebo in a weighted meta-analysis. There was better tolerated than misoprostol, it is not widely available; there-
insufficient data, even with three pooled studies, to definitively fore alternative options are clinically important [4]. Misoprostol is
demonstrate differences in complication rates or blood loss. Both already widely used for cervical preparation in early second trime-
of these outcomes are important and further studies should be ster abortion alone or with osmotic dilators. A recent retrospective
done with the aim of investigating these outcomes. study of 274 women evaluated cervical preparation with same-day
One concern some have with use of misoprostol is greater osmotic dilators plus misoprostol for D&E by highly skilled sur-
potential for cervical lacerations due to a more softened cervix. geons from 18 to 21 + 6 weeks gestation [14]. All procedures were
Indeed, in one study there were significantly more cervical lacera- completed the same day with a mean procedure time of 10 min
tions in the adjunctive misoprostol group [10]. The authors of this (SD 4.2), which is within the range of the procedure times found
study suggest that increased lower uterine segment pressure was a in this meta-analysis. The authors found only two immediate com-
potential cause for this increase in lacerations. This increase in cer- plications (one cervical laceration, one extramural delivery)
vical lacerations in the misoprostol group was not demonstrated in occurred. While this was retrospective and not compared with pla-
the two other studies. In a different study evaluating adjunctive cebo, this study does demonstrate feasibility of one-day cervical
misoprostol with same-day osmotic dilators (excluded from our preparation with adjunctive misoprostol for mid-second trimester
meta-analysis), a decrease in cervical lacerations was noted in procedures. Particularly for women living in states where they
the misoprostol group compared with placebo [12]. In all studies have to travel far distances to obtain a safe abortion in the mid
included in this analysis, overall complication rates including cer- to late second trimester, who may have to miss work, pay for child-
vical lacerations were very low and we did not have adequate sta- care, as well as lodging in the area while undergoing an abortion
tistical power to evaluate in this analysis, or to evaluate differences procedure, any regimen that improves ability to obtain a safe abor-
in techniques that may confound this risk. However, given the tion in the fewest days possible will increase access and ease.
large difference in complication rates between sites, it is possible Our study includes all available data on a randomized compar-
that different techniques of D&E may lend themselves to different ison of adjunctive misoprostol compared with placebo for cervical
risks of cervical laceration and perforation. For example, given the preparation for mid to late second trimester abortion to date. It
mechanism of misoprostol, the uterus is more likely to contract provides an important foundation for conducting further research
down and push pregnancy tissue into lower uterine segment. This on adjunctive misoprostol and provides a framework for future
may reduce the risk of perforation as pregnancy tissue is farther studies.
from fundus. However, it can be more difficult to compress in this The biggest limitation is the heterogeneity of the studies in
part of the uterus. To reduce the risk of cervical laceration, we sug- terms of gestational ages included, administration of misoprostol,

Please cite this article as: E. P. Cahill, A. Henkel, J. G. Shaw et al., Misoprostol as an adjunct to overnight osmotic dilators prior to second trimester dilation
and evacuation: A systematic review and meta-analysis, Contraception, https://doi.org/10.1016/j.contraception.2019.09.005
 E.P. Cahill et al. / Contraception xxx (xxxx) xxx 5

osmotic dilator type, and outcomes investigated. In the outcomes References

analyzed, the I2 statistic, a measure of heterogeneity ranged from
0% to 88%, with all outcomes >60%, signifying greater than moder- [1] Jatlaoui TC, Boutot ME, Mandel MG, Whiteman MK, Ti A, Petersen E, et al.
Abortion surveillance - United States, 2015. MMWR Surveill Summ. 2018;67
ate heterogeneity. Despite being the only studies that met our (13):1–45.
inclusion criteria, they differed in very significant ways, including [2] Lohr PA, Hayes JL, Gemzell-Danielsson K. Surgical versus medical methods for
gestational age, procedure setting, osmotic dilators used, timing second trimester induced abortion. Cochrane Database Syst. Rev. 2008;1:
CD006714.
of misoprostol, and outcome measurements. However, this is the [3] Patel A, Talmont E, Morfesis J, Pelta M, Gatter M, Momtaz MR, et al. Adequacy
only data we have available at this time. Meta-analyses remind and safety of buccal misoprostol for cervical preparation prior to termination
us of the importance of standardizing outcome measurements, of second-trimester pregnancy. Contraception 2006;73(4):420–30.
[4] Shaw KA, Shaw JG, Hugin M, Velasquez G, Hopkins FW, Blumenthal PD.
particularly reports of pain and blood loss, in order to draw conclu-
Adjunct mifepristone for cervical preparation prior to dilation and evacuation:
sions about optimal cervical preparation. All studies had high rates a randomized trial. Contraception 2015;91(4):313–9.
of manual dilation ranging from 8% to over 60%, with over 50% of [5] Wilson LC, Meyn LA, Creinin MD. Cervical preparation for surgical abortion
patients in the Edelman study requiring additional dilation in all between 12 and 18 weeks of gestation using vaginal misoprostol and Dilapan-
S. Contraception 2011;83(6):511–6.
groups (Table 2). In that study, the mean number of laminaria [6] Al R, Yapca O. Vaginal misoprostol compared with buccal misoprostol for
placed was just over two in the over 19-week gestation group, termination of second-trimester pregnancy: a randomized controlled trial.
whereas all participants in the Drey et al. study had at least eight Obstet. Gynecol. 2015;126(3):593–8.
[7] Newmann S, Dalve-Endres A, Drey EA, Society of Family P. Clinical guidelines.
laminaria placed and the participants in the Goldberg study had Cervical preparation for surgical abortion from 20 to 24 weeks’ gestation.
over seven dilators placed, on average. Contraception 2008;77(4):308–14.
The primary outcome in two of these studies is procedure time, [8] Review Manager (RevMan) Version 5.3. ed. Copenhagen: The Nordic Cochrane
Centre: The Cochrane Collaboration; 2014.
which is perhaps not the most clinically relevant outcome, despite [9] Edelman AB, Buckmaster JG, Goetsch MF, Nichols MD, Jensen JT. Cervical
being considered a surrogate for time spent managing complica- preparation using laminaria with adjunctive buccal misoprostol before
tions. More clinically relevant outcomes have been suggested second-trimester dilation and evacuation procedures: a randomized clinical
trial. Am. J. Obstet. Gynecol. 2006;194(2):425–30.
including ability to complete the procedure the same day (com- [10] Drey EA, Benson LS, Sokoloff A, Steinauer JE, Roy G, Jackson RA. Buccal
pared to two-day dilators) and complication rates, including blood misoprostol plus laminaria for cervical preparation before dilation and
loss or cervical lacerations. Additionally, even pooling this data did evacuation at 21–23 weeks of gestation: a randomized controlled trial.
Contraception 2014;89(4):307–13.
not provide adequate power to detect differences in such small
[11] Goldberg AB, Fortin JA, Drey EA, Dean G, Lichtenberg ES, Bednarek PH, et al.
rates of complications. Cervical preparation before dilation and evacuation using adjunctive
While second trimester abortion remains uncommon, it is misoprostol or mifepristone compared with overnight osmotic dilators
increasingly more common for women to have to travel distances alone: a randomized controlled trial. Obstet. Gynecol. 2015;126(3):599–609.
[12] Boraas CM, Achilles SL, Cremer ML, Chappell CA, Lim SE, Chen BA. Synthetic
to access care. This has increased the importance of finding meth- osmotic dilators with adjunctive misoprostol for same-day dilation and
ods that decrease cervical preparation time without increasing evacuation: a randomized controlled trial. Contraception 2016;94(5):467–72.
procedure time or complication rates. [13] Serapio ET, Pearlson GA, Drey EA, Kerns JL. Estimated versus measured blood
loss during dilation and evacuation: an observational study. Contraception
The findings of this meta-analysis do not demonstrate a clear 2018;97(5):451–5.
benefit of adjunctive misoprostol with overnight osmotic dilators. [14] Lyus R, Lohr PA, Taylor J, Morroni C. Outcomes with same-day cervical
Further research is needed to definitively determine if adjunctive preparation with Dilapan-S osmotic dilators and vaginal misoprostol before
dilatation and evacuation at 18 to 21+6 weeks’ gestation. Contraception
misoprostol has an effect on blood loss and rate of complications. 2013;87(1):71–5.

Please cite this article as: E. P. Cahill, A. Henkel, J. G. Shaw et al., Misoprostol as an adjunct to overnight osmotic dilators prior to second trimester dilation
and evacuation: A systematic review and meta-analysis, Contraception, https://doi.org/10.1016/j.contraception.2019.09.005