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Correspondence: Vasileios Pergialiotis, MD, 80, Vasilisis Sofias Avenue, Athens 115 28, Greece. E-mail: [email protected]
I N T R O D U C T I O N
Fear of pain during and after insertion of an intrauterine
contraceptive may prevent many women from selecting
this method either for fertility regulation or as an
alternative to treat certain gynaecological conditions.
The efficacy of various substances in reducing pain
during this procedure has been studied. Allen et al .
evaluated, in a meta-analysis, interventions that seem
to offer analgesia during IUD insertion1 . Since then,
several additional studies have been published addressing
the efficacy of different analgesics during insertion
of an intrauterine device (IUD) or a levonorgestrel
The European Journal of Contraception and Reproductive Health Care, 2014; 19: 149–160
Analgesic options for placement
of an intrauterine contraceptive:
A meta-analysis
Vasileios Pergialiotis, Dimitrios G. Vlachos, Athanasios Protopappas and Georgios D. Vlachos
1st Department of Obstetrics and Gynaecology, Athens University, Medical School, Alexandra Hospital, Athens, Greece
A B S T R A C T Objective Several randomised controlled trials have been published in the last few years
which evaluated the efficacy of various analgesics in reducing visual analogue (VAS) pain
scores during intrauterine device (IUD) placement. Their results seem to be conflicting andinconclusive.
Methods We searched Medline (1966 –2013), Scopus (2004 –2013), Clinicaltrials.org
(1997 –2013), Popline (1973 –2013), Cochrane CENTRAL (1999 –2013) and Google Scholar
(2004 –2013) engines for published randomised controlled trials, as well as the reference lists
from all electronically retrieved studies.
Results Thirteen studies, involving 1353 women, were finally included in the present
meta-analysis. Among the products used, and with respect to their mode of delivery, only
paracervical lidocaine was effective in producing lower VAS pain scores related to tenaculum
placement (mean difference [MD]: 20.54; 95% confidence interval [CI]: 39.92, 1.15)
and IUD insertion (MD: 28.99; 95% CI: 53.14, 4.84). Misoprostol produced higher
VAS pain scores for the immediate post-insertion period (MD: 2.83; 95% CI: 0.79, 6.45)
and it caused various side effects.Conclusion Paracervical administration of lidocaine prior to IUD insertion reduces VAS
pain scores. In view of the small number of studies assessing its efficacy further studies should
confirm our findings.
K E Y W O R D S Analgesia; Intrauterine device; Lidocaine; Misoprostol; Pain; Visual analogue scale (VAS)
© 2014 The European Society of Contracept ion and Reproductive Health
DOI: 10.3109/13625187.2014.903238
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Analgesia for IUD/IUS insertion Pergialiotis et al.
150 The European Journal of Contraception and Reproductive Health Care
releasing-intrauterine system (LNG-IUS)2 –11 . The
administration of lidocaine for analgesia was not assessed
in the aforementioned meta-analysis1 because there
were no randomised trials on record. Furthermore, a
sub-group analysis was needed to investigate whetherthe action of the local anaesthetic depended on its route
of administration. Pharmaceutically-induced cervical
dilatation with a prostaglandin E1 analogue (misopros-
tol) has been claimed to contribute to better visual
analogue scale (VAS) pain scores12 –15 . For this reason
we also included studies addressing VAS among patients
receiving misoprostol.
Aim of the study
We assessed published data pertaining to the efficacy
of various substances (analgesics or not) in prevent-ing pain related to the insertion of an intrauterine
contraceptive.
M E T H O D S
Study design
The present review was designed according to the
PRISMA guidelines16 .
Literature search
We identified relevant papers via Medline (1966 –2013),
Scopus (2004 –2013), Clinicaltrials.org (1997 –2013),
Popline (1973 –2013), Cochrane CENTRAL (1999 –
2013) and Google Scholar (2004 –2013) search engines,
and by screening reference lists of selected studies.
Medline was searched via Pubmed using the
Mesh Terms (‘intrauterine devices’[MeSH Terms]
OR (‘intrauterine’[All Fields] AND ‘devices’[All
Fields]) OR ‘intrauterine devices’[All Fields] OR
(‘intrauterine’[All Fields] AND ‘device’[All Fields]) OR
‘intrauterine device’[All Fields]) AND (‘pain’[MeSH
Terms] OR ‘pain’[All Fields]).
Scopus was also searched using the words (intrauterine
device AND pain). We also searched Clinicaltrials.org for
(intrauterine device pain). Cochrane’s CENTRAL wassearched with two different strategies (intrauterine
device and pain) and (IUD and pain).
An extended search through Google Scholar was
carried out using the terms (intrauterine device, iud,
intrauterine system, pain, tenaculum) in order to ren-
der feasible a manual search. All investigators agreed to
restrict the search to ‘humans’. No language or date
restrictions were applied. Search results are shown in
Figure 1.
Figure 1 Flow diagram representing the method used for article retrieval.
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Analgesia for IUD/IUS insertion Pergialiotis et al.
The European Journal of Contraception and Reproductive Health Care 151
Type of studies
Only randomised controlled trials (RCTs) or quasi-
randomised controlled trials were eligible for inclusion
in the study. We assessed the quality of randomisation
by means of the JADAD scale17 . No studies other than
those comparing single medication treatments with
placebo treatment or no treatment were included. Sim-
ilarly, only studies with copper-IUDs and LNG-IUSs
were taken into consideration. Studies that assessed
other intrauterine contraceptives, which are not com-
mercially distributed, or which were withdrawn from
the market, were not included.
Outcome definitions
Primary and secondary outcomes were agreed
upon and predetermined by all authors. Pain outcomes
during tenaculum placement, at IUD insertion and
following insertion were defined as primary outcomes.
Secondary outcomes included physician-perceived
ease of placement, and adverse effects.
Data extraction
Two authors (PV and VD) transferred data abstracted
from each selected article to two structured forms
(Tables 1 and 2) and the other authors reviewed the
data independently in order to increase reliability.
Statistical analysis
For the statistical meta-analysis we resorted to the
RevMan 5.1 software (Copenhagen: The Nordic
Cochrane Centre, The Cochrane Collaboration, 2011).
Meta-analysis was performed for indices presented
among at least four studies. Confidence intervals (CIs)
were set at 95%. With the chi-squared test and the
I-squared test we screened for inconsistency in the results
of the studies. A p value smaller than 0.05 was defined
as indicating statistical significance in the analysis of
heterogeneity. Odds ratios (ORs), mean differences
(MDs) and 95% CIs for all primary and secondary out-
comes were calculated, using the DerSimonian-Laird
random effects model (REM). The random effects
model assumes that heterogeneity exists regarding the
underlying effect among included studies18,19 . In our
analysis we seldom used the REM to estimate out-
comes due to heterogeneity of included studies because
data presented below were originated by independent
researchers, and it would be unlikely that all these
studies would be functionally equivalent. Publication
bias was not assessed due to the small number of
studies retained for the present review, which rendered
its interpretation ambiguous
20
.Indices expressed in median values and range were
transformed into mean and variance (standard devia-
tion) using the formula proposed by Hozo et al .21 .
Ten-scale VAS scores were converted to 100-scale
VAS in order to submit the observed outcomes to
meta-analysis.
R E S U L T S
Included studies
Thirteen studies, involving 1353 women, were finallyretained for the meta-analysis2 –4,6,8 –13,15,22,23 . Study
characteristics and demographic data are presented
in Table 1.
Excluded studies
Seven RCTs we had retrieved were excluded from
the present meta-analysis. One study was not taken
into consideration due to insufficient data5 and two
more due to differences in interpreting findings that
rendered tabulation impossible (data were presented as
discrete variables)24,25 . Two RCTs were not retained
because both the treated- and the control groups addi-
tionally received 100 mg diclofenac14,26 . Guney et al .
investigated the efficacy of lidocaine for removal, not
insertion, of IUDs24 . Massey et al . studied the anal-
gesic effect of naproxen during insertion of Dalkon
Shields, IUDs which for several decennia have not
been available7 .
Characteristics of included studies
and potential bias
Alizadeh et al . enrolled both parous and nulliparous
women and used both copper-IUDs and LNG-IUSs.
Allocation to either intrauterine contraceptive was
based on random sequences formed with computer-
generated programmes and concealed in opaque
envelopes. Lidocaine and lubricant were transferred
to identical sterile containers by a member of the
research team who was not involved in the allocation of
participants or data collection. Administration of either
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T a b l e
1
D e s c r i p t i v e c h a r a c t e r i s t i c s o f s t u d i e s a n d p a t i e n t s ( p a t i e n t s
r e c e i v i n g a n a l g e s i a v s . c o n t r o l s )
F i r s t a u t h o r ; y e a r
S t u d y
J a d a d
s c o r e §
S u b s t a n c e
D o s
a g e
M o d e o f d e l i v e r y
N u m b e r o f p a t i e n t s
T r e a t e d v s . c o n t r o l s
A g e , y e a r s *
T y p e o f I U C
( C u - I U D s p e r
t o t a l ) *
A l i z a d e h , 2 0 1 0 1 0
D B - R C T
3
L i d o c a i n e
2 % u n
k n o w n
q u a n t i t y
I n t h e c e r v i c a l c a n a l
6 5
3 1 v s 3 4
2 9 . 1 6 . 7 v s
2 6 . 7 6 . 0
N o t s p e c i fi e d
M a g u i r e , 2 0 1 2 6
D B - R C T
5
L i d o c a i n e
2 % u n
k n o w n
q u a n t i t y
I n t h e c e r v i c a l c a n a l
2 0 0
1
0 0 v s 1 0 0
2 7 . 1 6 v s
2 7 . 6 6
6 8 / 1 0 0 v s
7 0 / 1 0 0
M c N i c h o l a s , 2 0 1 2 8
D B - R C T
5
L i d o c a i n e
2 % , 2 - 3 m l
I n t h e c e r v i c a l c a n a l
1 9 9
9 9 v s 1 0 0
N / A
2 4 / 9 9 v s
2 3 / 1 0 0
M o d y , 2 0 1 2 9
R C T
2
L i d o c a i n e
1 % , 1 0 m l
P a r a c e r v i c a l b l o c k
5 0
2 6 v s 2 4
3 1 . 9 5 . 9 v s
3 3 . 2 6 . 2
5 / 2 6 v s
7 / 2 4
N e l s o n , 2 0 1 3 1 1
D B - R C T
4
L i d o c a i n e
2 % , 1 . 2 m l
I n s i d e t h e u t e r i n e
c a v i t y
4 0
2 0 v s 2 0
3 2 . 0 6 ( 1 9 – 4 6 ) v s
3 2 . 0 5 ( 2 0 – 4 3 )
N o t s p e c i fi e d
C i r i k , 2 0 1 3 2
S B - R C T
2
L i d o c a i n e
1 % , 1 0 m l
P a r a c e r v i c a l b l o c k
6 4
3 4 v s 3 0
2 8 . 5 5 . 7 5 v s
2 7 . 0 5 . 7 5
N o t s p e c i fi e d
A l l e n , 2 0 1 3 3
D B - R C T
5
L i d o c a i n e
2 % , 6
m l
I n t h e c e r v i c a l c a n a l
1 4 5
7 2 v s 7 3
2 5 . 2 5 . 0 v s
2 6 . 2 5 . 3
1 0 / 7 2 v s
1 0 / 7 3
K a r a b a y i r l i , 2 0 1 2 2 2
D B - R C T
2
T r a m a d o l
1 h b e f o r e
5 0 m g
P e r o s
6 9
3 5 v s 3 4
3 6 4 v s
3 7 6
3 5 / 3 5 v s
3 4 / 3 4
K a r a b a y i r l i , 2 0 1 2 2 2
D B - R C T
2
N a p r o x e n
1 h b e f o r e
5 5 0 m
g
P e r o s
6 8
3 4 v s 3 4
3 5 4 v s
3 7 6
3 4 / 3 4 v s
3 4 / 3 4
C h o r , 2 0 1 2 4
D B - R C T
5
I b u p r o f e n
4 5 m i n b e f o r e
8 0 0 m
g
P e r o s
8 7
4 4 v s 3 7
2 4 . 7 5 . 4 v s
2 7 . 9 6 . 5
0 / 4 4 v s
0 / 3 7
B e d n a r e k , 2 0 1 3 2 3
D B - R C T
5
N i t r o p r u s s i d e g e l
1 0 m g
( 1 m l )
I n t h e c e r v i c a l c a n a l
2 4
1 3 v s 1 1
2 4 . 2 4 . 4 v s
2 4 . 4 4 . 4
0 / 1 3 v s
0 / 1 1
D i j k h u i z e n , 2 0 1 1 1 2
D B - R C T
5
M i s o p r o s t o l
3 h b e f o r e
4 0 0 µ g
V a g i n a l
1 9 9
1 0 2 v s 9 7
3 1 . 6 8 . 6 v s
3 0 . 7 8 . 4
1 1 / 1 0 2 v s
9 / 9 7
E d e l m a n 2 0 1 1 1 3
D B - R C T
5
M i s o p r o s t o l
9 0 m i n b e f o r e
4 0 0 µ g
P e r o s
3 5
1 7 v s 1 8
N / A
2 / 1 7 v s
2 / 1 8
S w e n s o n ; 2 0 1 2 1 5
D B - R C T
5
M i s o p r o s t o l
3 – 4 h b e f o r e
4 0 0 µ g
P e r o s o r v a g i n a l
1 0 8
5 4 v s 5 1
2 4 . 6 3 . 8 v s
2 4 . 8 4 . 2
1 1 / 5 4 v s
1 6 / 5 1
I U C , i n t r a u t e r i n e c o n t r a c e p t i v
e ; C u - I U D , c o p p e r r e l e a s i n g - i n t r a u t e r i n e d e v i c e ; D B , d o u b l e b l i n d ; S B , s i n g l e b l i n d ; R C T , r a n d o m i s e d c o n t r o l l e d t r
i a l § T
h e J a d a d
s c o r e a s s e s s e s t h e q u a l i t y o f
c l i n i c a l t r i a l s w i t h r e g a r d t o r a n d o m a s
s i g n m e n t , d o u b l e b l i n d i n g , a n d t h e fl o
w o f p a t i e n t s ; t h e r a n g e o f p o s s i b l e s c o r e s i s 0 ( b a d )
t o 5 ( g o o d ) . * S
t u d y g r o u p v s . c o n t r o l s
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Analgesia for IUD/IUS insertion Pergialiotis et al.
The European Journal of Contraception and Reproductive Health Care 153
substance was performed with cotton swabs. Products
to be given were numbered by allocation sequence.
There were no drop-outs. Results were given in
10-scale VAS scores and their means standard devia-
tions (SDs) were analysed
10
.Also Dijkhuisen et al . included parous- as well as
nulliparous women and used both copper-IUDs and
LNG-IUSs. Randomisation was generated by a com-
puter and was concealed from the investigators. The
200 µ g-misoprostol and placebo tablets had an identi-
cal appearance. Participants were instructed to place
two tablets high up in the vagina three hours prior to
insertion of the intrauterine contraceptive. There were
34 drop-outs in the misoprostol group, and 37 in the
placebo group, before insertion of the intrauterine
contraceptives. Results were presented as 100-scale
VAS scores and analysed as mean SD12 .Edelman et al . enrolled only primiparous women
without a history of prior IUD insertion or of prior
procedure on the cervix. Either a copper-IUD or a
LNG-IUS was fitted. Randomisation was done by
phone. Identical tablets containing either 400 µ g of
misoprostol or placebo were removed from sealed
opaque envelopes and administered to patients via the
buccal route 90 min before the procedure. Three with-
drawals before intervention in the misoprostol- and
two in the control group were recorded. Results were
presented in 100-scale VAS scores and analysed as
mean SD13 .Karabayirli et al . enlisted exclusively parous women
in their study and used only copper-IUDs. Randomi-
sation was computer-generated. The study was
described as having been double-blinded, but the
products administered had a different appearance.
Tramadol 50 mg capsules, naproxen sodium 550 mg
tablets and placebo empty capsules were administered
orally by a physician who was blinded to the study,
one hour prior to insertion of the IUD. No withdraw-
als were recorded. Results were presented in 10-scale
VAS scores and analysed as mean SD22 .
Maguire et al . recruited both parous and nulliparous
women and used both copper-IUDs and LNG-
IUSs. Randomisation was computer-generated and
concealed in opaque envelopes. Lidocaine gel or a
placebo identical in appearance was instilled into a
sterile tube by a research assistant. The product was
transferred with a cotton swab into the cervical canal.
One failed insertion of the intrauterine contraceptive
was described in the lidocaine group, and two in the
control group. All women were included in the final
analysis. Results were presented as 100-scale VAS
scores and analysed as mean SD6 .
McNicholas et al . included parous as well as nullipa-
rous women and used both copper-IUDs and LNG-IUSs. Randomisation was achieved by computer-
generated blocks and was concealed in opaque
envelopes. A physician blinded to the nature of the
product applied 0.5 mL of lidocaine or placebo to
the ectocervix and then instilled 2 –3 mL of the gel
(lidocaine or placebo) into the endocervical canal.
Results were presented as 10-scale VAS scores and
analysed as median range8 .
Mody et al . did not accurately describe exclusion
criteria. They enrolled both nulliparous and parous
women. Both copper-IUDs and LNG-IUSs were
offered as options. Block randomisation with strati-fication by parity was performed. The study was
not blinded, as controls received no treatment. Ten
millilitres of a 1% solution of lidocaine were admin-
istered paracervically. One unsuccessful insertion was
observed in the group treated with lidocaine. Results
were presented as 100-scale VAS-scores and analysed
as mean SD9 .
Swenson et al . enlisted parous as well as nulliparous
women and used both copper-IUDs and LNG-IUSs.
Computer-generated randomisation was performed
with regard to allocation to either misoprostol (400µ g)
or placebo tablets, which were identical in appearance,taste and smell. Participants were instructed to ingest
the tablets or to insert these into the vagina. Allocation
concealment was not described. There were two failed
insertions in the misoprostol group, and three in the
control group. These women were not accounted for
in the final analysis. Results were presented as 100-
scale VAS scores and analysed as mean SD15 .
Chor et al . offered only LNG-IUSs. Computer-
generated randomisation and identical tablets
(containing either 800 mg ibuprofen or placebo) were
given orally and the nature of the product adminis-
tered was concealed from providers and patients.
Three insertions failed in each group. The 10-scale
VAS scores were analysed as mean SD4 .
Nelson et al . recruited both parous and nulliparous
women and used copper-IUDs as well as LNG-IUSs.
Randomisation was done in a 1:1 ratio using random-
generated numbers. The group to which each of the
participants would be allocated was mentioned on slips
of paper which were separately inserted in sequentially
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Analgesia for IUD/IUS insertion Pergialiotis et al.
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numbered opaque envelopes. A research nurse opened
each patient’s randomisation envelope and placed a
small, but not clearly defined, amount of a 2% lido-
caine solution of lidocaine or saline in a semi-opaque
endometrial aspirator. Both the active compound andthe placebo were instilled into the lower-, the middle-
and the upper third of the endometrial cavity. There
were no withdrawals. Results were presented as
10-scale VAS scores and analysed as mean SD11 .
Bednarek et al . enlisted only nulliparous women
in their study and inserted exclusively LNG-IUSs.
Randomisation was computer-generated. Nitroprusside
gel (1 mL containing 10 mg of the active compound)
or placebo were identical in appearance and allocation
concealment was performed by the hospital’s pharmacy.
Either product was administered into the cervical canal
by means of an angiocatheter. One patient allocated tothe nitroprusside group withdrew from the trial and
was not taken into account in the final analysis. Results
were presented as 100-scale VAS scores and analysed
as mean SD23 .
Cirik et al . provided no information regarding the
type of intrauterine contraceptive they used. Neither
did they describe the methods of randomisation and
of blinding of the procedure. Patients were divided
into three groups according to the product which was
administered paracervically prior to insertion of the
IUD: 10 ml of a 1% solution of lidocaine, 10 ml of a0.9% NaCl solution, or nothing at all. Withdrawals
were not reported. Results were presented as 10-scale
VAS scores and analysed as median range2 .
Allen et al . included both nulliparous and parous
women and used LNG-IUSs as well as copper-
IUDs. Randomisation was done in a 1:1 ratio using
computer-generated numbers3 . The lidocaine gel
(6 ml, 2% concentration) and the placebo (K-Y® jelly)
were identical in appearance. Women and providers
were blinded to the nature of the product that was
instilled into the cervical canal by means of an
angiocatheter, as the latter had been prepared by thehospital’s pharmacy. Two withdrawals were reported
in the placebo arm due to non-insertion of the
intrauterine contraceptive (IUC) and three among
women allocated to the lidocaine group, one due
to non-insertion of the IUC and two because of
protocol violation3 .
Figure 2 Forest plot of the effect of lidocaine on tenaculum placement VAS pain scores. Differences between treated
women and controls were statistically significant only in the case of paracervical block (p 0.04). ‘Intracervical’ in
the cervical canal.
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The European Journal of Contraception and Reproductive Health Care 155
Primary outcomes
The difference in VAS scores dur ing tenaculum place-
ment was not statistically significant for women treated
with lidocaine, regardless of the route of administra-
tion, when compared with controls (722 women,
DerSimonian-Laird random effects model [REM],
mean difference [MD]: 8.33, 95% CI: 18.80, 2.13;
data from seven studies 2,3,6,8,9,11,23 ; Figure 2). How-
ever, when we stratified the studies according to the
mode of delivery of lidocaine we found significantly
decreased pain VAS scores among women treated with
paracervical lidocaine (REM, MD: 20.54, 95% CI:
39.92, 1.15).
Similar results were also observed for IUD inser-
tion following administration of lidocaine: the local
anaesthetic did not significantly diminish VAS painscores when analysed irrespective of the mode of
administration (787 women, REM, MD: 10.93, 95%
CI: 23.68, 1.82; data from eight studies2,3,6,8 –11,23 ;
Figure 3). However, once more, when we stratified
studies per mode of administration a significant effect
was observed among women treated with
paracervical lidocaine (REM, MD: 28.99, 95% CI:
53.14, 4.84).
With regard to misoprostol, VAS pain scores during
IUD insertion among treated women did not signifi-
cantly differ from those of controls (339 women,REM, MD: 2.83, 95% CI: 0.79, 6.45; data from
three studies12,13,15 ; Figure 4).
VAS pain scores related to the pain felt after the
IUD insertion significantly differed only in the case of
misoprostol (140 women, REM, MD: 7.15, 95% CI:
3.61, 10.68; data from two studies13,15 ; Figure 5).
Secondary outcomes
Physician-perceived insertion of the IUD seemed to
be significantly easier among treated women (363
women, REM, MD:
2.29, 95% CI:
3.60,
0.98;data from four studies12,13,15,23 ; Figure 6). However, in
subgroup analysis this effect seemed to remain signifi-
cant only in the case of misoprostol (Figure 6).
Adverse effects were underreported in the included
studies and were assessed using different definitions,
hence they were excluded from analysis.
Figure 3 Forest plot of the effect of lidocaine on VAS pain scores related to insertion of the intrauterine contraceptives.
Differences between treated women and controls were statistically significant only in the case of paracervical block
(p 0.02). ‘Intracervical’ in the cervical canal.
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D I S C U S S I O N
Fear of pain prevents many women from selecting
intrauterine contraceptives for birth control. Pain is
usually experienced during insertion of the speculum
into the vagina, cervical tenaculum placement, andinsertion of the device. Of these procedures, tenacu-
lum placement and insertion of the IUD seem to hurt
most: they are associated with higher VAS scores than
speculum insertion.
Findings and interpretation
In the present meta-analysis we evaluated the impact of
lidocaine in reducing pain VAS scores during placement
of the tenaculum on the cervix and found that it seems
to be effective only when it is injected paracervically;
this also applied to IUD insertion. On the contrary,
instillation of lidocaine, whether into the cervical canal
or in the endometrial cavity, failed to significantly lower
VAS scores of experienced pain.
Misoprostol is not an analgesic. However, its poten-
tial to reduce pain and facilitate IUD insertion could
be achieved by softening and ripening the cervix. Our
results, however, clearly indicate that it is inefficacious
in that respect.
With regard to lidocaine and nitroprusside, VAS
pain scores related to the pain felt after IUD insertion
of treated women did not significantly differ from
Figure 4 Forest plot of the effect of misoprostol and placebo on VAS pain scores related to insertion of the intrauterine
contraceptives. VAS scores of women treated with misoprostol were significantly higher than those of controls
(p 0.001).
Figure 5 Forest plot of VAS pain scores related to the period immediately following insertion of the intrauterine
contraceptive. The mean VAS score was significantly higher among misoprostol-treated women (p 0.001).
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The European Journal of Contraception and Reproductive Health Care 157
those of controls (Figure 4). However, in the case of
misoprostol, pain scores were significantly higher
among treated women. This could be explained by the
uterine contractions that misoprostol elicits, thus aug-
menting the pain experienced in the post-insertion
period.
We would have liked to perform a meta-analysis
of the actual cervical dilatation that misoprostol pro-
duces, in order to clarify whether misoprostol failed
to reduce the pain scores due to insufficient ripeningof the cervix. However, the studies included in the
present review did not evaluate this parameter, but
rather the actual number of patients who required
additional mechanical dilatation4,9,13,15 (Table 2). Pre-
viously, however, cervical dilatation after treatment
with misoprostol was assessed with 4 mm Hegar dila-
tors by Saav et al . in a RCT comparing patients
(n 39) given misoprostol (400 µ g) and diclofenac
(100 mg) orally and control patients (n 40) who
had received only diclofenac26 . No significant differ-
ences were found between the two groups. Similar
results were also reported recently by Ibrahim et al .
among women who were randomly allocated to
receive either 400 µ g misoprostol and 100 mg
diclofenac sublingually (n 130) or only 100 mg
diclofenac (n 125)14 . The findings of these two
studies are intriguing14,26 ; they are not in line with
the results of a previous meta-analysis comparing
cervical dilatation among women undergoing hyst-
eroscopy who received either misoprostol (via the
oral-, the sublingual- or the vaginal route) (n 264)
or were left untreated (n 272)27 . In this latter meta-
analysis researchers concluded that cervical dilatation
was significantly greater among treated women
(mean difference of 2.47 mm, 95% CI: 1.81 –3.13;
p 0.001)27 .
According to our findings, physician-perceived ease
of placement of IUDs was significantly greater in
women pre-treated with misoprostol. Two more trials,
excluded from the present review, provided controver-sial results regarding the effect of misoprostol in this
respect14,26 .
Strengths and weaknesses of the study
Our study’s main strength was the comparison of
groups that received treatment as monotherapy, thus
avoiding potential bias arising from co-administered
medications. In all included studies subjects allocated
to the control groups received either placebo or no
therapy at all. Furthermore, we were able to stratify
studies assessing the effect of lidocaine according to
the route of its administration. This way we observed
that its analgesic activity did not always achieve the
expected decrease in VAS pain scores.
On the other hand, discrepancies in scaling of
visual analogue scores among included studies
required the conversion of 10-scale VAS to 100-scale,
in order to analyse and interpret results. For the same
reason values of median and range were converted to
Figure 6 Forest plot of physician-perceived ease of placement. Differences between groups were not statistically
significant (p 0.78).
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158 The European Journal of Contraception and Reproductive Health Care
T a b l e
2
V A S s c o r e s a n d c e r v
i c a l d i l a t a t i o n , s t u d y g r o u p v s . c o n t r o l s .
F i r s t a u t h o r ; y e a r
P a i n a
t I U D / I U S i n s e r t i o n
S p e c u l u m p l a c e m e n t
T e n a c u l u m p l a c e m e n t
C e r v i c a l
d i l a t a t i o n
E a s e o f
p l a c e m e n t
P a i n a f t e r i n s e r t i o n
A l i z a d e h , 2 0 1 0 1 0
3 . 4 1 . 9 v s
3 . 4 1 . 7
N / A
N / A
N / A
N / A
N / A
M a g u i r e , 2 0 1 2 6
5 1 . 0 3
1 v s
5 0 . 9 3
2
N / A
3 5 . 4 2
6 v s
3 4 . 3 2
5
N / A
N / A
N / A
M c N i c h o l a s , 2 0 1 2 8
5 ( 0 – 1 0 ) v s
6 ( 0 – 1 0 )
N / A
4 ( 0 – 1 0 ) v s
4 ( 0 – 1 0 )
N / A
N / A
N / A
M o d y , 2 0 1 2 9
3 7 . 3 3
5 v s
5 2 . 5 2
7 . 5
1 3 . 8 1 3 .
1 v s
1 2 . 9 1 2 .
9
1 8 . 8 2
1 . 8 v s
2 9 . 0 1
6 . 2
2 / 2 6 v s
2 / 2 4
N / A
2 0
. 5 2
5 . 7 v s
1 9
. 4 1
8 . 4
N e l s o n , 2 0 1 3 1 1
2 . 9 5 2 . 6 1 v s
3 . 6 8 2 . 7 1
N / A
2 . 2 0 2 . 4 2 v s
2 . 7 0 2 . 0 3
N / A
N / A
2 . 2 v s
1 . 6 3
C i r i k , 2 0 1 3 2
2 0 1
2 . 5 v s
6 0 1
2 . 5
N / A
4 0 1
5 v s
7 0 1
2 . 5
N / A
N / A
1 0 1
0 v s
4 0 1
2 . 5
A l l e n , 2 0 1 3 3
3 5 . 2 2
7 . 7 v s
3 6 . 7 3
0
2 3 . 5 2 3 .
8 v s
2 1 . 5 2 3 .
7
3 7 . 5 2
6 . 2 v s
4 1 . 6 3
1 . 5
N / A
N / A
2 0
. 6 2
4 v s
2 1 . 4 2
5 . 2
K a r a b a y i r l i , 2 0 1 2 2 2
2 . 3 1 0 . 6 0 v s
4 . 8 8 1 . 0
N / A
N / A
N / A
N / A
N / A
K a r a b a y i r l i l , 2 0 1 2 2 2
2 . 9 4 0 . 7 1 v s
4 . 8 8 1 . 0
N / A
N / A
N / A
N / A
N / A
C h o r , 2 0 1 2 4
3 6 . 9 3
4 v s
3 3 . 4 2
7
N / A
3 8 . 6 2
9 v s
3 8 . 1 3
0
2 / 4 4 v s
1 / 3 7
N / A
N / A
B e d n a r e k , 2 0 1 3 2 3
6 1 2
5 v s
7 4 1
8
2 3 2 2
v s
2 6 1 3
3 0 2
7 v s
4 0 2
7
N / A
3 2 . 4 2
2 . 7 v s
2 6 . 5 2
7 . 2
3 7 3
3 v s
5 0 2
1
D i j k h u i z e n , 2 0 1 1 1 2
4 6 2
8 v s
4 0 2
7
N / A
N / A
N / A
2 . 9 2 . 8 v s
2 . 8 2 . 6
N / A
E d e l m a n , 2 0 1 1 1 3
6 5 2
1 v s
5 5 2
1
1 7 2 2
v s
9 8
3 5 2
5 v s
3 6 2
0
0 / 1 7 v s
3 / 1 8
2 4 1
9 v s
2 9 2
1
2 0 2
3 v s
2 0 1
9
S w e n s o n , 2 0 1 2 1 5
5 8 . 4 3 . 3 v s
5 6 . 9 3 . 0
N / A
N / A
5 / 9 v s
5 / 1 0
2 5 3 . 5 v s
2 7 . 4 3 . 5
3 5
. 1 3 . 4 v s
2 7 . 5 2 . 4
I U D , i n t r a u t e r i n e d e v i c e ; I U S ,
i n t r a u t e r i n e s y s t e m ; N / A , n o t a p p l i c a b l e .
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Analgesia for IUD/IUS insertion Pergialiotis et al.
The European Journal of Contraception and Reproductive Health Care 159
mean and variance according to the formula pro-
posed by Hozo et al .21 . Publication bias was precluded
due to the low number of included studies20 . Sam-
pling bias and in particular exclusion bias was observed
among certain studies, affecting the external validityof comparisons, thus precluding the analysis based on
the fixed-effects model. Several factors related to
lidocaine treatment, such as route of administration
(into the cervical canal, intrauterine, paracervical),
mode of administration (cotton swab, angiocatheter)
and quantity of applied lidocaine could also have
contributed to the observed discrepancies between
studies (Table 1). As already mentioned, in the case
of misoprostol, the route of administration (per os or
vaginal) and interval of administration prior to IUD
placement differed (Table 1).
Differences in results in relation
to previous studies
Allen et al . concluded in their previous meta-analysis
that NSAIDS failed to reduce pain experienced dur-
ing IUD insertion1 . Their study, however, had limita-
tions with regard to the interpretation of the data due
to the small number of included studies. In one of
the latter, the IUD that was fitted, the Dalkon Shield,
is no longer available on the market and its size and
cumbersome insertion technique do not allow the
comparison of the pain or discomfort it caused whenplaced, to those observed with the currently utilised
LNG-IUSs or copper IUDs7 . In the study assessing
misoprostol, which Allen et al . took into consider-
ation, both the study and the control groups received
100 mg diclofenac26 whose analgesic action in all
likelihood blurred the interpretation of the facilitat-
ing effect the PGE1 analogue might have had1 . All
things considered, lidocaine seems to be the only
compound eliciting analgesia when administered
before IUD insertion.
Implications for clinicians
We evaluated VAS pain scores among women being
fitted with an intrauterine contraceptive in accordance
with a standardised procedure that included insertion
of a speculum, use of an antiseptic applied on the
cervix, placement of the tenaculum, and insertion of
the device. The closing of the tenaculum – unless slowly
and smoothly done over some four to five seconds
- is painful. Therefore, in many institutions, tenacula
are seldom used when insertion can be accomplishedwithout their assistance. The present meta-analysis
could not determine whether analgesia significantly
reduces VAS pain scores among women in whom
the device can be fitted without grasping the cervix
with an instrument. But our study does show that,
in cases where use was made of a tenaculum, only
paracervically-injected lidocaine effectively reduces
pain during placement of that instrument and
IUD/IUS insertion. However, firm conclusions are pre-
cluded as only two studies in the present meta-analysis
assessed the effect of paracervically-administered
lidocaine on VAS pain scores.
Future research
Later studies might examine the effect of lidocaine
(or other local anaesthetics) administered paracervically
to clarify whether it should become a standard prac-
tice prior to insertion of an intrauterine contraceptive.
One may contemplate assessing whether analgesia is
necessary when an IUD can be placed without the
use of a tenaculum.
C O N C L U S I O N
Of the various substances assessed, only lidocaine,
when injected paracervically, reduces VAS pain
scores related to tenaculum placement and IUD
insertion. However, firm conclusions are precluded
due to the small number of the included studies.
Misoprostol administration is associated with signifi-
cantly higher VAS pain scores after the completion of
the procedure.
Funding: None.
Declaration of interest: The authors report no con-
flicts of interest. The authors alone are responsible for
the content and the writing of the text.
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160 The European Journal of Contraception and Reproductive Health Care
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