Best Practice & Research Clinical Obstetrics and Gynaecology 63 (2020) 24e36

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Obstetrics and Gynaecology
journal homepage: www.elsevier.com/locate/bpobgyn

Current and potential methods for second

trimester abortion
Klaira Lerma, MPH *, Paul D. Blumenthal, MD, MPH
Stanford University, Department of Obstetrics & Gynecology, Division of Family Planning Services &
Research, Stanford, CA 94503, USA

a b s t r a c t
Keywords:
Second trimester abortion Medical and surgical methods can both be recommended for
Medical abortion second trimester abortion (after 12-weeks of gestational age).
Dilation and evacuation Induced abortion with a mifepristone and misoprostol regimen is
Mifepristone the preferred approach; where mifepristone is not available,
Misoprostol misoprostol alone for medical abortion is also effective. Dilation
Osmotic dilators
and evacuation (D&E) is the procedure of choice for surgical
abortions, and adequate cervical preparation contributes signifi-
cantly to safety. Availability of drugs and instruments, ability to
provide pain control, provider skill and comfort, client preference,
cultural considerations, and local legislation all influence the
method of abortion likely to be performed in a given setting. Both
surgical and modern medical methods are safe and effective when
provided by a trained, experienced provider.
© 2019 Elsevier Ltd. All rights reserved.

Introduction

Abortion is a core service in reproductive health care globally and one of the most common pro-
cedures not only in gynecology but also in all of medicine. An estimated 56.3 million abortions occur
annually, which is 25% of all pregnancies [1]. The majority of abortions occur in the first trimester of
pregnancy before 12 weeks of gestational age. Abortion in the second trimester, after 12 weeks of
gestational age, is less prevalent but still occurs in both developed and developing countries. In some
settings, largely due to poor training or preparation, the majority of abortion complications occur in

* Corresponding author. 300 Pasteur Drive, HG332, Stanford, CA 94503, USA.

E-mail address: klerma@stanford.edu (K. Lerma).

https://doi.org/10.1016/j.bpobgyn.2019.05.006
1521-6934/© 2019 Elsevier Ltd. All rights reserved.
 K. Lerma, P.D. Blumenthal / Best Practice & Research Clinical Obstetrics and Gynaecology 63 (2020) 24e36 25

second trimester procedures, even though it is a small proportion of the total abortion cases. In the United
States, 7.6% of all abortions were performed at 14e20 weeks of gestational age and 1.3% after 20 weeks of
gestational age (2014 data) [2]. Similarly, 10% of abortions are after 12 weeks of gestational age in the
United Kingdom (2017 data) [3]. Pregnant individuals need abortion services in the second trimester for a
variety of reasonsdsocial motivations, lack of access to services, and maternal or fetal indications [4].
Both medical and surgical methods are available for second trimester abortion. Dilation and
evacuation procedures (D&E) is the more prevalent method in the United States [2]. Medical methods,
also known as induction abortion, are more common in the United Kingdom [3], in Europe, and in
developing countries. Availability of drugs and instruments, ability to provide pain control, provider
skill and comfort, client preference, cultural considerations, and local legislation all influence the
method of abortion likely to be performed in a given setting. Both surgical and modern medical
methods are safe and effective when provided by a trained, experienced provider. The rate of com-
plications in these procedures increases with gestational age, with an estimated complication rate of
0.4e0.6% [4e11]. Complications commonly include uterine perforation, cervical laceration, hemor-
rhage requiring transfusion, uterine rupture, and infection.
This article covers current and potential practice of surgical and medical abortion in the second
trimester with a focus on cervical preparation for surgical abortion, regimens for medical abortion, and
inducing fetal demise.

Current practicedmedical abortion in the second trimester

Advancements in medication abortion in the second trimester of pregnancy have transformed

abortion care globally in recent decades. The use of sublingual, buccal, or vaginal pharmacologic agents
is currently standard of care, and intrauterine instillation methods and oxytocin approaches are both
less common [12] and not recommended. Instillation methods are associated with more complications,
are invasive, and generally less expeditious. Sublingual, buccal, or vaginal pharmacologic agents for
medical abortion in the second trimester have become the recommended practice by numerous
professional societies [13e17].
Misoprostol is the prostaglandin analog (PGE1) of choice for second trimester medical abortion.
Gemeprost is another analog commonly reported in the literature. Several studies have compared the
use of these two analogs for second trimester medical abortion, and both have been found to be
effective. However, misoprostol has several advantages compared to gemeprost.
Misoprostol1 is inexpensive, can be stored at room temperature for long periods, and is often
available where medical abortions occur, as it is used to treat postpartum hemorrhage and used for first
trimester medical abortion or post abortion care (PAC). Gemeprost must be stored below
10
Celsiusda barrier to many providers in developing countries. Therefore, misoprostol is the most
widely used analog.
The use of misoprostol alone for second trimester medical abortion is effective and widely used
globally. The use of mifepristone,2 an antiprogesterone, and misoprostol together has been shown to
make the medical abortion procedure significantly more effective and efficient, as it reduces the
induction-to-abortion interval by almost 50% [13]. The addition of mifepristone has increased the
safety of second trimester medical abortion by decreasing procedure times significantly and reducing
the total dose of misoprostol required, thereby lessening associated side effects and morbidity. Mife-
pristone has been added to the World Health Organization's list of essential medications because of the
documented evidence on its safety and efficacy in these settings. However, where mifepristone is not
available or is not cost-feasible, misoprostol-alone regimens are effective.
The medication abortion practice for the second trimester supported by the evidence, and rec-
ommended by professional societies, is mifepristone (200 mg orally)3 followed by misoprostol (400 mg
every 3e4 h) 24 h later until expulsion of the fetus [13,14,17].

1
In many countries, the use of misoprostol for second trimester medical abortion is considered an off-label use.
2
The use of mifepristone for second trimester medical abortion is an off-label use of the drug.
3
Unless otherwise documented, all references of mifepristone are dosed at 200 mg orally.
26 K. Lerma, P.D. Blumenthal / Best Practice & Research Clinical Obstetrics and Gynaecology 63 (2020) 24e36

Second trimester medical abortion with mifepristone and misoprostol

A placebo-controlled, double-blind, randomized controlled trial compared misoprostol-alone to

the mifepristone-misoprostol regimen (n ¼ 260) [18]. Twenty-four hours before the hospital-based
procedure, mifepristone or placebo was self-administered by clients' at gestational ages 14e21
weeks. Upon hospital admission, 400 mg of misoprostol were dosed every 3 h by buccal adminis-
tration. Investigators set an arbitrary limit of five doses or 15 h. No feticide was used. Complete
uterine evacuation by 15 h occurred in 79.8% versus 36.9% of cases in the mifepristone-misoprostol
and misoprostol regimen groups, respectively (risk ratio 2.16; 95% CI 1.7e2.75). The mifepristone-
misoprostol regimen resulted in a faster induction to abortion interval, with a median time of
7.5 h than 10.8 h in the misoprostol-alone group (p < 0.01). Side effects and acceptability were
similar between regimen groups. This trial documented that as gestational age increased
misoprostol-alone was less effective; among clients at 20e21 weeks of gestational age, 13% had fetal
expulsion by 15 h compared to 80% in the mifepristone-misoprostol regimen (risk ratio 6.13; 95% CI
2.07e18.15).
This trial demonstrated the efficacy of a mifepristone-misoprostol regimen for second trimester
medical abortion without feticide, with very strict cut-off times for procedure success. Before this trial,
previous data on the addition of mifepristone were largely observational, with few large prospective,
powered-randomized trials [19e22]. The literature included studies conducted with 200e600 mg of
mifepristone administered most commonly from 36 to 48 h before misoprostol or gemeprost, and
route and dose of prostaglandin analog were variable [23]. The previous recommendations were to
dose the mifepristone 36e48 h before starting the misoprostol dosing, as this was estimated to be the
time for maximum effect [24].
A more recent placebo-controlled, double-blind randomized controlled trial conducted by Dabash
et al. (2015) [25] replicated the Ngoc et al. (2011) study with a few important differences. The cutoff
time was extended from 15 h to 48 hdstill keeping the limit of five consecutive doses but allowing for
24 h of rest and up to five repeat doses. Median time to complete abortion was significantly shorter in
the mifepristone-misoprostol group than in the misoprostol-alone group (8.6 versus 18.2 h; p < 0.001).
In the mifepristone-misoprostol group, 91.7% of clients had complete expulsion by 48 h compared to
71.7% in the misoprostol-alone group (relative risk 1.28 (95% CI 1.07e1.53). There were no differences in
side effects. Those who had been randomized to the mifepristone-misoprostol regimen were more
likely to find the length of hospital stay very acceptable or acceptable compared to those in the
misoprostol-alone group (91.7% and 78.3%; p ¼ 0.04). Documented experiences of the introduction of
mifepristone into routine service delivery have been positive [26].

Misoprostol route and dose

Route of administration has an effect on the bioavailability of misoprostol. Sublingual administra-

tion is associated with the highest levels of bioavailability, followed by vaginal administration, which is
documented to be three times higher than that of oral administration [27,28]. Buccal administration of
misoprostol is associated with a uterine response and side effects similar to those of vaginal admin-
istration and has a lower peak plasma concentration [29,30].
Sublingual versus vaginal route of misoprostol (400 mg) administration was compared in a ran-
domized controlled trial in a sample of clients at 13e24 weeks of gestational age (n ¼ 134) presenting
for misoprostol-alone medical abortion [31]. Dosing of misoprostol occurred every 6 h. The routes were
found to be equivalent in terms of number of doses, abortion time, side effects, and rate of surgical
intervention.
In another study, vaginal and buccal routes of administration were compared for efficacy in
misoprostol-alone medical abortion in a sample of clients 13e24 weeks of gestational age (n ¼ 130)
[32]. Up to six doses of misoprostol were dosed at 400 mg every 3 h, with protocols in place for a second
round of misoprostol-dosing if abortion had not occurred after 24 h. Those in the vaginal adminis-
tration group had a shorter induction to abortion intervals than those in the buccal administration
group (25 ± 17 h versus 40 ± 29 h, respectively, p ¼ 0.001). Despite this, overall complete abortion rates
were found to be similar between vaginal and buccal administration groups, 78% and 83% (p ¼ 0.5),
 K. Lerma, P.D. Blumenthal / Best Practice & Research Clinical Obstetrics and Gynaecology 63 (2020) 24e36 27

respectively. The median number of misoprostol doses was different between the vaginal (3, 1e14) and
buccal (5, 1e18) groups (p < 0.001).
The effect of unlimited misoprostol dosing was evaluated in a randomized trial among clients at
13e22 weeks of gestational age receiving mifepristone-misoprostol medical abortion (n ¼ 120) [33].
Twenty-four to 48 h following mifepristone, 400 mg of misoprostol was dosed every 3 h until complete
abortion. Complete abortion was achieved in 99.2% (n ¼ 119) of cases; median induction to abortion
interval was 10.3 h (range 4e17.4 h).
Some researchers have considered the use of an initial vaginal loading dose of 600e800 mg of
misoprostol, followed by repeat doses of 400 mg [34,35]. The use of a loading dose is not supported by
the evidence and not recommended by the World Health Organization [36].
Even when considering the bioavailability and clinical trial data, buccal administration may be the
best programmatic choice, as it is the most common administration of misoprostol in first trimester
medical abortion, meaning providers may already be comfortable with administration [33]. There are
further circumstances where buccal administration of misoprostol may have advantages over vaginal
administration and clients may prefer buccal administration. Clients may not be comfortable self-
administering a vaginal drug (or having it administered), and a vaginal exam is not needed every
3e6 h with buccal administration, hence decreasing the burden on medical staff.

Mifepristone-misoprostol dosing interval

The interval between mifepristone-misoprostol has been well studied and is multifactorial. A long
interval between mifepristone and misoprostol (24e48 h) is associated with a shorter induction time
(time from first misoprostol dose to fetal expulsion). The induction time is the most resource-intensive
portion of the procedure, and clients are experiencing the most symptoms. However, the longer the
mifepristone-misoprostol interval, the longer is the total procedure time (time from mifepristone
administration to fetal expulsion).
A systematic review evaluated the effect of the mifepristone-misoprostol dosing interval on in-
duction time, total abortion time, and safety and efficacy in medical abortion at 13e24 weeks of
gestational age [37]. One-day interval abortions had a median induction time of 7.3 h (range 7e8.5 h),
while two-day interval abortions had a median induction time of 6.8 h (range 6.3e7.2 h). There was no
difference in fetal expulsion by 12 h or 24 h. The reduction in induction time of less than 1 h is not
clinically significant, and there was no difference in reported complications by interval. The
mifepristone-misoprostol dosing interval should be dependent on logistical considerations of the
provider and client, rather than the previously purported advantage of a longer mifepristone-
misoprostol interval. This systematic review provides evidence that the total procedure time can be
decreased by at least 24 h. However, even when using a 24-h mifepristone-misoprostol interval, the
total procedure will still require two visits to the health care facility.
To investigate the possibility of a same-day outpatient medical abortion regimen for the second
trimester, Abbas et al. (2016) investigated simultaneous administration of mifepristone and miso-
prostol in a placebo-controlled, double-blind, randomized controlled trial (n ¼ 509) [38]. Clients at
13e22 weeks of gestational age were randomized to receive mifepristone 24 h before (control arm)
or at the time of (simultaneous arm) the first misoprostol dose. The protocol was 400 mg of buccal
misoprostol every 3 h for up to 48 h or until fetal expulsion. At 24 h after the first misoprostol dose,
94.4% of those in the control arm had expelled compared to 85.0% in the simultaneous arm (relative
risk 1.11 (95% CI 1.05e1.18)). At 48 h, the rate was similar between groups (96.8% and 95.7% in the
control arm and simultaneous arm, respectively (relative risk 1.01 (95% CI 0.97e1.04)). The simul-
taneous arm had longer median induction times (control arm: 7.7 h (2.1e40.3 h) and simultaneous
arm: 13 h (4.9e47.8 h), p¼<0.001) and more total misoprostol doses (24 h interval arm: three (1e14)
and simultaneous arm: five (2e16), p < 0.001). Simultaneous dosing may allow for a same-day
outpatient medical abortion with shorter total procedure time than that for misoprostol alone,
when accounting for the 24-h waiting period after mifepristone, median total procedure times were
32.3 h (26.9e64.8 h) versus 13.0-h (4.9e47.8 h) in the control and simultaneous arms, respectively
(p < 0.001).
28 K. Lerma, P.D. Blumenthal / Best Practice & Research Clinical Obstetrics and Gynaecology 63 (2020) 24e36

Unlimited misoprostol dosing

As research translates into clinical practice, the regimented protocols necessary for gold standard
clinical investigation become burdensome clinical guidelines that do not always transfer well into real-
world practice. An example of this is the limit set on misoprostol doses during second trimester medical
abortion. Limiting providers to five total doses of misoprostol can be logistically limiting if the women
have not yet had complete abortion after five doses; this often results in a prolonged procedure because
of the rest guidelines. The Louie et al. (2017) and Abbas et al. (2016) experience with unlimited miso-
prostol dosing until expulsion provides important efficacy and safety data for clinical practice [33,38].
Providers should consider their local guidelines, facility capabilities, and client preference in their
clinical judgement in cases where clients have not yet had fetal expulsion after five misoprostol doses. In
some low-resource settings, where mid-level providers are managing second trimester medical abor-
tion many miles away from a facility that can manage complications, it may be appropriate to adopt a
more conservative protocol. Best practice is to consider resources before setting a clinical guideline that
may be a result of previous research. The International Federation of Gynecology and Obstetrics (FIGO)
issued guidelines that no longer recommend a maximum dose of misoprostol for second trimester
abortions and the World Health Organization no longer recommends a maximum dose [36].

Future practicedmedical abortion in the second trimester

Flexible mifepristone-misoprostol interval

To optimize medical abortion in the second trimester and make it more patient-centered, flexible
mifepristone-misoprostol intervals must be considered. The regimen is clinically safe, effective, and
acceptable to clients in all reported intervals. Setting up a service delivery model that allows for
flexibility is well warranted.
Recent reports of a flexible interval have revealed median induction times (time of misoprostol to
fetal expulsion) of 12.9, 11.7, and 9.3 h in cohorts of clients with mifepristone-misoprostol intervals of
12 h, 12e24 h, and >24 h, respectively (p ¼ 0.18) [39], whereas total abortion times in these groups
were 20.7, 30.6, and 42.8 h, respectively (p < 0.001). Shortened mifepristone-misoprostol intervals
significantly decrease the total abortion time while maintaining a clinically similar induction abortion
time. Strict adherence to guidelines may unnecessarily prolong the abortion procedure. It is reasonable
for providers to consider flexible mifepristone-misoprostol intervals if it is preferential to the client or
the facility.

One-day service delivery model

Further, evidence supports a one-day service delivery model for second trimester medical abortion
among those 18 weeks of gestational age, where women take mifepristone at home 24e48 h before
initial dose of misoprostol [40]. In a pooled analysis of 868 cases, 8 h after the first misoprostol dose,
59.3% and 28.3% of clients of gestational ages 13e18 weeks and 19e22 weeks, respectively, had a
successful, complete abortion (p < 0.001). A consideration to increase the number of clients with fetal
expulsion by 8 h post-misoprostol dosing is to instruct clients to take mifepristone and the first dose of
misoprostol at home before going to the facility. This is reasonable, given the extensive evidence of
clients' capability to take mifepristone at home before coming to a facility. Implementing this strategy
could be in interest of clients, providers, and health care systems that seek to expand limited access to
second trimester abortion. Preliminary data examining this strategy in clients of gestational ages 13e18
weeks are promising (personal communication with Gynuity Health Projects).

Self-managed abortion

The use of pharmacologic agents (mifepristone and/or misoprostol) outside of the formal health
care system for self-managed abortion is increasing in incidence globally. Under a harm-reduction
model, several initiatives have supported pregnant individuals seeking to self-manage their
 K. Lerma, P.D. Blumenthal / Best Practice & Research Clinical Obstetrics and Gynaecology 63 (2020) 24e36 29

abortions in an effort to reduce morbidity and mortality. These efforts are largely for first trimester
abortion (<12 weeks of gestational age) and have been successful [41]; individuals have effectively and
safely terminated their pregnancies with the support of counseling services or resources.
For those seeking abortion beyond 12 weeks of gestational age, on a global scale, there are fewer
safe service providers available, especially in restrictive settings. A strategy to improve access and
reduce morbidity and mortality associated with unsafe abortion in the second trimester is to provide
support services to individuals self-managing second trimester medical abortions. Gerdts et al. (2018)
published the experience of a safe abortion hotline that supported individuals self-managing abortion
beyond 12 weeks of gestational age [42]. Ninety-six callers were given initial information; five did not
call back and 91 received further support. Gestational ages of callers ranged from 13 to 22 weeks (mean
15.6± 2.5 weeks). The majority (82.4%, n ¼ 75) used a combination of mifepristone and misoprostol.
Successful abortion was confirmed in 91.2% of cases (n ¼ 83). This demonstrates that this model of care
is feasible. Callers who had signs of complications sought care in this sample, consistent with self-
managed abortion data in the first trimester. Future research is needed to optimize this practice. As
it is well documented that individuals who cannot access safe abortion care often seek alternatives that
are associated with increased maternal mortality, innovative strategies are needed to ensure access to
second trimester services under a harm-reduction model.

Current practicedsurgical abortion in the second trimester

D&E is the most common technique for surgical abortion in the second trimesterdreplacing the
seldom-used hysterotomy and hysterectomy. In D&E, the uterus is instrumented trans-cervically with
specialized forceps for fetal extraction, following cervical preparation and aspiration of amniotic fluid.
Cervical preparation, compared to manual dilation alone, reduces the risk of cervical laceration and
uterine perforation, the most common complications of D&E [11,43].
As previously described, D&E is a safe procedure, and complications are rare. When translating the
research evidence into practice, consider the infrequency of these complications and the unfeasible,
large sample size that would be needed to compare complication rates between interventions. As a
proxy for complications, researchers use pre-procedure cervical dilation and procedure time, as
inadequate cervical dilation and longer procedure times are associated with a more challenging pro-
cedure that is more likely to have complications. These measures are not perfect, as preprocedure
cervical dilation determined by an individual provider is subjective and procedure times can be
confounded by a number of factors that are not indicative of safety. Therefore, other important out-
comes include client-reported pain and procedure acceptability, pre-procedure fetal expulsion, and
inability to complete the procedure at the scheduled time.

Cervical preparation

Osmotic dilators alone

Cervical preparation with osmotic dilators alone is a safe and effective method. Two main types of
osmotic dilators are used independently or in conjunction: laminaria and Dilapan-S. Laminaria,
composed of seaweed, exerts minimum effect in 6 h and maximum effect in 12e24 h and dilate two to
three times their initial size. Dilapan-S, composed of synthetic material, exert minimum effect in 3 h
and maximum effect in 4e6 h. Both come in a variety of sizes. Dilapan-S is commonly used for same-
day cervical preparation owing to its faster maximum effect, hence decreasing the time and number of
osmotic dilators needed to adequately prepare the cervix [44].
Overnight osmotic dilators alone in the second trimester are commonly used as the control inter-
vention in studies investigating new strategies for cervical preparation and are effective for all
gestational ages in the second trimester. Overnight laminaria and same-day Dilapan-S result in similar
procedure times among clients of gestational ages 14e18 weeks; a comparative randomized controlled
trial reports procedure time of 5.9 versus 8.1 min, respectively). Clients with same-day Dilapan-S
placed 4e6 h before the procedure required more mechanical dilation. Overall, clients preferred the
same-day procedure with Dilapan-S [45]. Utilizing Dilapan-S for same-day procedures has the
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potential to decrease barriers at the client and facility levels. Experience with same-day Dilapan-S
alone for gestational ages more than 18 weeks is not well documented; however, this practice may
be feasible.

Pharmacologic agents as adjuncts

To improve client experience and decrease the provider- and facility-level effort, the use of phar-
macologic agents as adjunctive medications to aid in cervical preparation in second trimester surgical
abortion has been successful.

Misoprostol

Current evidence supports the use of preprocedure misoprostol (3 h preoperatively, 400 mg) in
conjunction with same-day Dilapan-S cervical prep. The study did not reach their sample size for
statistical power and documented a decrease in complications with the use of misoprostol and no
difference in operative times among clients at 16e20 weeks of gestational age [46].
At gestational ages less than 16 weeks, overnight osmotic dilators with adjunctive misoprostol
(400 mg) 90 min before the procedure are not associated with improved dilation [47]. Over 16 weeks of
gestational age, benefits of preprocedure misoprostol as an adjunct to overnight osmotic dilators
include improved preprocedure cervical dilation and shorter procedure times. The use of misoprostol is
associated with more cramping and, in some cases, increased side effects (nausea, diarrhea, and chills)
[46e52]. Despite this, the benefits of improved cervical dilation and shorter procedure times with
adjunct misoprostol support its use to decrease risk of complications intraoperatively.

Mifepristone

Mifepristone is associated with fewer side effects than misoprostol. Goldberg et al. (2015) inves-
tigated the use of adjunctive mifepristone for D&E between 16 and 24 weeks of gestational age. The
three arms of the RCT (n ¼ 300) were as follows: 1) overnight osmotic dilators alone, 2) overnight
osmotic dilators and 400 mg buccal misoprostol 3 h preprocedure, 3) overnight osmotic dilators and
mifepristone at the time of osmotic dilator insertion. There were no differences in complications. The
use of adjunctive mifepristone did not result in shorter procedure times: 16e18 weeks of gestational
age: 1) 5.11 min, 2) 4.99 min, 3) 4.33 min (p ¼ 0.34); 19e23 weeks of gestational age: 1) 7.5 min, 2)
7.62 min, 3) 6.74 min (p ¼ 0.53). However, D&E procedures in clients who received mifepristone were
reported as less difficult by providers and were well tolerated [51].
Historically, some providers required clients with later gestational ages to complete two separate
osmotic dilation insertions before the D&E, as in two sets of osmotic dilators placed 18e24 h apart in
the two days before the procedure. The use of mifepristone as an adjunct to osmotic dilators has
eliminated the need for two days of cervical preparation. A study compared one set of osmotic dilators
and adjunct mifepristone the day before D&E to two sets of osmotic dilators placed 18e24 h apart in
the two days before D&E for clients at 19e24 weeks of gestational age. All participants received pre-
procedure misoprostol (400 mg by buccal administration 90 min before procedure). Preprocedure
cervical dilation did not differ between groups, and similar procedure times and provider-reported
ease of procedure were observed [53]. This study demonstrated that cervical preparation for two
days is not necessary to achieve adequate cervical preparation before D&E and the utility of mife-
pristone as an adjunct to overnight osmotic dilators for gestational ages of 19e24 weeks.

Pain control for laminaria insertion

Another motivation to use one set of osmotic dilators is discomfort with insertion. In the Shaw et al.
(2015) study, client-reported pain with the second set of dilators was significantly greater than the pain
experienced with the first set [53]. Pain scores following insertion of osmotic dilators range from 13 to
70 mm on a 100-mm visual analog scale (VAS) [54e56] and have included interventions such as
paracervical block, intrauterine lidocaine and paracervical block, and vaginal lidocaine gel for pain
 K. Lerma, P.D. Blumenthal / Best Practice & Research Clinical Obstetrics and Gynaecology 63 (2020) 24e36 31

control. Paracervical block (18 ml 1% lidocaine and 2 ml sodium bicarbonate) [56] and vaginal lidocaine
gel (2% 20 ml intravaginally) [55] were found to be effective in controlling pain with osmotic dilator
insertion. Continued research and practice change to improve client experience with osmotic dilator
placement is needed.

Pharmacologic agents versus osmotic dilators

One strategy to improve client experience and omit uncomfortable osmotic dilator insertion is to
omit the procedure altogether. The use of pharmacologic agents alone for cervical preparation before
D&E is highly preferential to clients [50,52,57].

Same-day cervical preparation with pharmacologic agents alone

For 12e19 weeks of gestational age, misoprostol alone (400 mg, 3e4 h preprocedure) is associated
with similar procedure times, client-reported pain and satisfaction, and complication rates to over-
night osmotic dilators alone. The misoprostol-alone regimen for cervical preparation in this gestational
age range often requires more mechanical dilation and is associated with the most common miso-
prostol side effects [58e60]. Reportedly, a second dose of misoprostol was needed in many cases (42%
of cases at gestational ages 13e15 weeks; 79% of cases at gestational ages over 16 weeks) [59]. Clients
report similar satisfaction with both methods of cervical preparation [58,59].
A case series (n ¼ 1177) that describes the clinical experience of same-day cervical preparation with
misoprostol alone before D&E procedures between 17 and 23 weeks of gestational age, only two cases
(0.2%) were not able to be completed in the same day. The majority of the cases were between 17 and
20 weeks of gestational age (98%). Misoprostol doses varied by gestational age group; the average
across all groups was 3 (range 1e5). The mean procedure time for all gestational ages was 13 min, and
procedure times were not statistically different between gestational age groups. Alike, mean total
abortion time (misoprostol administration to procedure complete) was 4.9 h (SD±1.7 h) and was not
different between gestational age groups. The complication rate in this case series was 2% (n ¼ 21),
which is higher than the total complication rate reported in the literature (0.4e0.6% [10,11]);
complications included cervical laceration, endometritis, and hemorrhage [61]. With this in mind,
this strategy should be reserved for experienced surgeons who are prepared for these potential
complications.
A study of mifepristone and misoprostol (400 mg) in combination 4e6 h before D&E for clients at
14e19 weeks of gestational age did not improve cervical preparation compared to misoprostol alone
[62]. For same-day cervical preparation, mifepristone in conjunction with misoprostol 4e6 h before
procedure does not appear to be a cost-effective intervention, as this interval may not be optimal to see
the effects of mifepristone.
Same-day cervical preparation with misoprostol-alone is effective in the second trimester. There are
many clinical scenarios where same-day cervical preparation is needed. In the United States, several
state-level laws require waiting periods of 24e72 h between consent and abortion procedures. Where
clients must travel long distances for care, the time and inconvenience of overnight cervical prepa-
ration with two clinic visits may not be optimal or feasible. Additionally, osmotic dilators are not
available globallydwhereas misoprostol is generally available. Of note, the providers in the reported
case series were experienced surgeons, and this should be considered in interpreting the data [61].

Overnight cervical preparation with pharmacologic agents alone

The use of mifepristone-alone for overnight cervical preparation is a promising development. For
clients at gestational ages 14e16 weeks, mifepristone-alone 24 h before cervical preparation for D&E
results in similar procedure times to overnight osmotic dilators alone (9.9 versus 8.0 min, respectively).
Clients who have mifepristone-alone cervical preparation avoid the overnight and preprocedure pain
associated with osmotic dilators and prefer cervical preparation with mifepristone-alone [57].
Adding preoperative misoprostol (400 mg 90 min to 2 h before procedure) to the mifepristone-
alone 24 h before D&E cervical preparation strategy for gestations between 15 and 18 weeks of
32 K. Lerma, P.D. Blumenthal / Best Practice & Research Clinical Obstetrics and Gynaecology 63 (2020) 24e36

gestational age is associated with less initial cervical dilation and similar procedure times than os-
motic dilators alone [52].
Shaw et al. (2017) compared three strategies of cervical preparation: 1) mifepristone and miso-
prostol; 2) osmotic dilators with mifepristone plus misoprostol; 3) osmotic dilators and misoprostol
in a double-blind, randomized controlled trial (n ¼ 75). Mifepristone and osmotic dilators were
provided the day before the procedure. Misoprostol was given preoperatively, 90 min before the
procedure if the client received osmotic dilators and 2e3 h before the procedure if the client did not
receive osmotic dilators. Total procedure time was different between groups (1) 18.5; 2) 12; and 3)
13 min, respectively (p < 0.005). When excluding the time needed for mechanical dilation, procedure
times were similar (1) 10.5; 2) 8.5; and 3) 10 min, respectively (p ¼ 0.10). There were complications
in seven cases, in six of which the primary surgeon was a trainee. There was no difference in client
satisfaction between groups [63].
Utilizing overnight mifepristone and preprocedure misoprostol alone for cervical preparation in the
second trimester is effective in adequately preparing the cervix. The use of pharmacologic agents alone
for cervical preparation before D&E is associated with less initial apparent dilation and the need for
more mechanical dilation, which is usually performed very easily in these patients, during the pro-
cedure. Up to 18 weeks of gestational age, the use of mifepristone and misoprostol for cervical prep-
aration before D&E is recommended. After 18 weeks of gestational age, providers should take a more
cautious approach, considering the documented experience of Shaw et al. (2017) [63]. After 18 weeks of
gestational age, only highly experienced surgeons should attempt D&E cervical preparation with
pharmacologic agents alone.

Potential practicedsurgical abortion in the second trimester

Alternatives to mifepristone

Despite significant public health efforts to register mifepristone and make it widely available
globally, it is only available in 46 countries, the majority of which are high-income or upper-middle-
income countries [64]. The utility of mifepristone in the second trimester abortion is significant
enough to warrant the exploration of alternative antiprogestin pharmacologic agents as an alternative.
An ideal medication would be available over the counter, have multiple uses (e.g., first trimester
abortion, second trimester abortion, and contraception) to encourage stocking and universal con-
sumption, and be safe and effective.
In the United States, the Food and Drug Administration (FDA) restricts mifepristone with a Risk
Evaluation and Mitigation Strategies (REMS). The purported purpose of this is to ensure the benefits
outweigh the risks. However, the REMS is not clinically relevant for first trimester abortion, as the well-
published experience of medical abortion since the inception of the REMS has documented that
medical abortion in the first trimester is highly safe and effective [65]. The use of mifepristone for
pregnancy termination in the second trimester is an off-label use. The REMS prevent providers in the
United States from using tele-medicine in cervical preparation strategies that serve to reduce burden
on clients, providers, and health systems. An alternative antiprogesterone medication could be a work-
around to allow providers and patients more flexibility and abortion access in the second trimester.

Feticide

After 20 weeks of gestational age, some providers induce fetal demise before both medical and
surgical abortion. This practice is largely to avoid transient fetal survival and can be motivated by legal,
ethical, and psychological factors. Intra-amniotic injection of digoxin is most commonly used, although
intrafetal digoxin has been reported to be more effective in a shorter time course [66]; digoxin has high
efficacy and a low complication rate and can be performed with or without ultrasound guidance. In
many abortion-focused settings, digoxin is preferred to intracardiac potassium chloride owing to
simplicity of administration and less need for advanced ultrasound skills. The use of digoxin is asso-
ciated with greater cervical priming, but this has never been demonstrated in a powered study as the
primary outcome [67]. Where feticide is not possible, clients should still be provided abortion services.
 K. Lerma, P.D. Blumenthal / Best Practice & Research Clinical Obstetrics and Gynaecology 63 (2020) 24e36 33

Preliminary research has examined the use of 1% lidocaine, a widely available medication, for feticide
and has seen promising results [68]. With further research, lidocaine could be established as an
acceptable alternative to digoxin.

Summary

Abortion in the second trimester of pregnancy remains a common procedure in reproductive health
care. Medical and surgical methods have continued to evolve, and research has focused on client-
centered outcomes. With regard to medical methods, the use of mifepristone has significantly
decreased the induction-to-abortion interval and has provided the opportunity to examine a one-day
model for second trimester medical abortion services. Future research should focus on the feasibility,
cost-effectiveness, and client satisfaction with same-day services. With regard to surgical methods,
D&E remains the recommended and most common procedure, with the technical aspects not changing
in recent decades. Cervical preparation remains the most important aspect of surgical abortion in the
second trimester. Mifepristone, alike in medical abortion, for cervical preparation has provided an
opportunity to decrease burden on clients, providers, and facilities. Despite its utility, mifepristone
remains unavailable in many settings; an alternative antiprogestin would be of considerable value to
reproductive health care. Where osmotic dilators cannot be avoided, clients should be provided
adequate pain control, as the insertion procedure is painful. Finally, no one-size-fits-all strategy exists
for second trimester services. Client, cervix, and circumstances should all be evaluated by providers
before choosing a strategy for medical or surgical abortion. Research has provided several safe and
effective strategies for second trimester abortion, and all the strategies should be considered in
providing client-centered care.

Multiple Choice Questions (MCQs)

Question 1: During second trimester medical abortion:

a) Mifepristone should be administered before misoprostol dosing, where available.

b) An initial vaginal loading dose of misoprostol (600e800 mg) is recommended.
c) No more than five doses of misoprostol can be administered.
d) Inducing fetal demise is not mandatory.

Answers to Question 1: a) True; b) False; c) False; d) True.

Explanation to Question 1:

a) See professional society guidelines and World Health Organization guidelines.

b) Evidence does not support this practice. See updated World Health Organization guidance.
c) Evidence does not support this practice. The International Federation of Gynecology and Ob-
stetrics (FIGO) issued guidelines that no longer recommend a maximum dose of misoprostol for
second trimester abortions. Additionally, see updated World Health Organization guidance.
d) Where feticide is not possible, clients should still be provided abortion services.

Question 2: During second trimester surgical abortion, dilation and evacuation (D&E):

a) Adequate cervical preparation significantly reduces complications.

b) Same-day cervical preparation is not possible.
c) Preprocedure misoprostol decreases risk of complications and improves cervical dilation but is
associated with more client-reported cramping and side effects.
d) Cervical preparation can be done with osmotic dilators alone, osmotic dilators with adjunct
pharmacologic agents, and with pharmacologic agents alone
34 K. Lerma, P.D. Blumenthal / Best Practice & Research Clinical Obstetrics and Gynaecology 63 (2020) 24e36

Answers to Question 2: a) True; b) False; c) True; d) True.

Explanation to Question 2:

a) Cervical preparation, compared to manual dilation alone, reduces the risk of cervical laceration and
uterine perforation, the most common complications of D&E.
b) False. This is possible. Same-day cervical preparation is dependent on gestational age and avail-
ability of mifepristone, misoprostol, and osmotic dilators.
c) All of these strategies are possible. Client, cervix, and circumstances should all be evaluated by
providers before choosing a strategy.

Practice points

 A one-size-fits-all-strategy is not ideal or client-centered in second trimester services.

 Consider the client, circumstances, and provider-experience when choosing.
 Cervical preparation method for surgical abortion.
 Mifepristone-misoprostol interval for medical abortion.

Research agenda

 Alternatives to mifepristone for cervical preparation in the second trimester.

 Continued research and practice change to improve client experience with osmotic dilator
placement for cervical preparation before D&E is needed.
 Same-day second trimester medical abortion services.

Conflicts of interest

The authors have no conflicts of interest.

Acknowledgments

None.

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