Human Reproduction, Vol.28, No.8 pp.

2118 2125, 2013

Advanced Access publication on June 5, 2013 doi:10.1093/humrep/det240

ORIGINAL ARTICLE Fertility control

Misoprostol prior to inserting an

intrauterine device in nulligravidas:
a randomized clinical trial
Adriana Scavuzzi1,*, Alex S.R. Souza 1, Aurelio A.R. Costa1,2,
and Melania M.R. Amorim 1,3
Postgraduate Program on Maternal and Child Health, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Pernambuco, Brazil
Obstetrics and Gynecology at the Faculdade Pernambucana de Saude (FPS), Recife, Pernambuco, Brazil 3Obstetrics and Gynecology, Federal
University of Campina Grande, Campina Grande, Paraba, Brazil
2

*Correspondence address. Rua Edson Alvares, 317/1702, Casa Forte, 52061-450 Recife, PE, Brazil. E-mail: adrianascavuzzi@hotmail.com

Submitted on September 10, 2012; resubmitted on April 22, 2013; accepted on April 29, 2013

study question: How effective is the vaginal administration of misoprostol in dilating the cervix prior to inserting an intrauterine device
(IUD) in nulligravidas?

summary answer: The use of misoprostol at a dose of 400 mg administered vaginally 4 h prior to IUD insertion increased the ease of
insertion and reduced the incidence of pain during the procedure, although the frequency of cramps increased following misoprostol use.
what is known and what this paper adds: Misoprostol has been widely used in Obstetrics and Gynecology; however, its
usefulness and efcacy in facilitating IUD insertion in nulligravidas have yet to be established. The present study shows that the benets of misoprostol use prior to IUD insertion include facilitating insertion and reducing pain during the procedure; therefore, weighing up the benets
encountered against the only negative side effect (cramps prior to insertion), these results suggest that misoprostol use should become standard
practice to facilitate IUD insertion in nulligravidas.
study design, size duration: A randomized, double-blind clinical trial was conducted.
participants/materials, setting methods: Nulligravid women of reproductive age were submitted to IUD insertion
between July 2009 and November 2011 at the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, Brazil. A total of 179
women were randomly allocated to two groups: 86 to receive 400 mg of misoprostol vaginally 4 h prior to IUD insertion and 93 to receive
placebo. Risk ratios (RRs) were calculated as measures of relative risk, together with their 95% condence intervals (95% CI). The number
needed to treat (NNT) and the number needed to harm (NNH) were also calculated.

main results and the role of chance: Signicant differences were found between the groups for all the immediate end points
studied, with less difculty in inserting the IUD [RR 0.49 (23/86 versus 51/93); 95% CI: 0.33 0.72; P 0.00005], a lower risk of dilatation
,4 mm [RR 0.48 (24/86 versus 54/93); 95% CI: 0.33 0.70; P 0.0001], a reduction in moderate-to-severe pain at IUD insertion [RR
0.56 (32/86 versus 62/93]; 95% CI: 0.41 0.76; P 0.00008), as well as a lesser likelihood of experiencing a disagreeable or very disagreeable
sensation [RR 0.49(29/86 versus 64/93); 95% CI: 0.35 0.68; P 0.000004] in the group that was given misoprostol compared with the group
that received placebo. There was no signicant difference between the groups in relation to complications during IUD insertion. There were no
cases of uterine perforation in either group. The frequency of cramps was 40% higher in the misoprostol group.

limitations, reasons for caution: The present study showed a positive balance between the benets and risks of the use of
misoprostol; however, it is not feasible to conclude that its use is imperative prior to IUD insertion in nulligravidas and IUD insertion should
not be canceled when the medication is unavailable.

winder implications of the findings: In view of its effect in promoting cervical dilatation, misoprostol may be used prior to IUD
insertion both in nulligravidas and in any women with cervical stenosis irrespective of parity.
study funding: This study was funded by the Instituto de Medicina Integral Prof Fernando Figueira.
competing interests: None.
Key words: intrauterine devices / misoprostol / nulligravidas / contraception
& The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
For Permissions, please email: journals.permissions@oup.com

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Misoprostol and IUD insertion in nulligravidas

Introduction

Materials and Methods

A randomized, double-blind clinical trial was conducted involving nulligravid
women of reproductive age submitted to insertion of an IUD (TCu 380 A,
Optima, Injeex, Sao Paulo, Brazil) with prior use of vaginal misoprostol
(400 mg) or placebo at the Instituto de Medicina Integral Prof. Fernando Figueira
(IMIP), Recife, Pernambuco, Brazil between January 2009 and November
2011. The study protocol was approved by the institutions review board
and all women signed an informed consent prior entering the study. The
study protocol was registered at ClinicalTrials.gov under reference number
NCT01383889. The study protocol and Consort checklist are available as
Supplementary data.
Sample size was calculated using the OpenEpi software program, version
2.3.1, considering a frequency of subjective difculty in inserting the IUD of
45% in the placebo group and a 50% reduction in this rate with the use of misoprostol (Saav et al., 2007). According to the calculation, 152 women would
be necessary (76 women in each group). Predicting losses or cases of protocol violation of up to 20%, this number was increased and, as a safety
measure, 190 boxes of the study medication containing misoprostol or
placebo were prepared.
Nulligravidas of reproductive age who had never been submitted to
surgery of the uterine cervix and who had requested to use an IUD as a
contraceptive method were included in the study. Women with a contraindication to the use of an IUD as dened in categories 3 and 4 of the

World Health Organizations (2004) medical eligibility criteria (2004) for

contraceptive use were excluded from the study.
The women were initially identied at the family planning clinic of IMIPs
Womens Healthcare Center (CAM). During the IUD insertion, all women
were menstruating. The day of the menstrual cycle for IUD insertion
ranged from rst to ninth. At that time, the women were randomized to
the vaginal misoprostol (400 mg) group or placebo group. The tablet was
introduced by the principal investigator into the posterior vaginal fornix of
the woman 4 h prior to IUD insertion. All insertions were performed by
the principal investigator using the standard technique (Edelman et al., 2011).
The IUD used was the copper T380A (Optimaw) and all insertions were
performed by the principal investigator, using the standard technique for IUD
insertion (Edelman et al., 2011).
Each woman was identied by a sequential ordinal number corresponding
to a sealed box containing either two tablets of placebo or two tablets each
containing 200 mg of misoprostol. In addition to the sequential number, each
box was identied with the womans name and registration number, and was
only opened when the tablets had to be inserted into the vagina. Neither the
investigator nor the woman was aware if misoprostol or placebo was to be
administered. Randomization was carried out (1:1) in accordance with a
list created using the block randomization method and containing sequential
numbers from 1 to 190 (the number of women to be randomized). This list
was prepared by a statistician not directly involved in the study, using the
Random Allocation Software program, version 1.0 (Isfahan, Iran) and using
only the letters A and B, without being aware of their meaning. This list
was sent to the pharmaceutical company, where the coding (misiprostol or
placebo) of each letter, A and B, was randomly selected. The boxes were prepared by the pharmacist in accordance with the randomization established by
the statistician. The investigators were aware of the contents of boxes A and
B, only after the statistical analysis was complete when the randomization
code was broken and the coding of each letter was revealed.
The vaginal misoprostol tablets at the dose of 200 mg each, a total dose per
woman of 400 mg, were commercialized and developed specically for
vaginal use by Hebron Industria Farmaceutica (Caruaru, Pernambuco, Brazil)
according to good manufacturing practice, who also prepared the placebo
tablets, which were identical to the active drug in shape, size, color and
weight, and were made specically for this study.
The primary end point was the subjective difculty (as reported by the investigator) in inserting the IUD. Secondary end points were the frequency of
women with cervical dilation 4 mm (measured by inserting a #4 Hegar
dilator through the internal orice of the cervix uteri immediately prior to
IUD insertion) and pain at insertion, as judged subjectively by the woman
and evaluated by the investigator using a visual analog scale (Saav et al.,
2007). The scale ranged from 0 to 10, in which 0 is the absence of pain and
10 the worst pain imaginable. The scores were later dichotomized into
absent/mild (0 5) and moderate/severe (6 10). A further secondary
end point was the womans subjective evaluation of the procedure (IUD insertion), classied as not disagreeable, slightly disagreeable, disagreeable or
very disagreeable.
The frequency of immediate side effects (those occurring prior to IUD insertion) and late side effects (those occurring 24 h after IUD insertion)
(cramps, nausea, vomiting, diarrhea and hyperthermia) was also evaluated,
as well as the side effects that occurred during IUD insertion such as
cramps, nausea, vomiting, vasovagal reaction, uterine perforation and
failure to insert the device. We requested information about the 24 h
events by phone calls. We explained how they should measure the temperature and we provided a thermometer if they did not have one.
Thirty days after IUD insertion, the women were contacted by telephone
and requested to attend the gynecology clinic to evaluate complications such
as heavy menstrual bleeding, intermenstrual bleeding, spotting, the intensity
of cramps, candidiasis, bacterial vaginosis and IUD expulsion. Whenever any
complication was identied, the appropriate treatment was provided.

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The intrauterine device (IUD) is a safe, extremely effective and longacting reversible contraceptive (LARC). Nevertheless, only 15% of
women of reproductive age in developing countries and 8% in developed
countries use it as a contraceptive method (dArcangues, 2007). It is possible that difculty in inserting the device limits its use in nulligravidas
(Grimes and Schulz, 2001).
Until a short time ago, it was assumed that the IUD should not be used
in nulligravidas, since this contraceptive method was believed to be associated with an increased risk of pelvic inammatory disease (PID) that
could result in infertility (Hubacher et al., 2001). Although recent
studies have conducted more thorough evaluations of this association,
and have concluded that the risk of infection is small so that nulliparity
is no longer a contraindication to the use of the method, many healthcare
professionals (HCPs) still limit its use in this group of women, claiming
that insertion of the device is difcult (Grimes and Schulz, 2001).
In an attempt to improve the ease of IUD insertion in nulligravidas,
some investigators tested the use of misoprostol prior to the procedure
(Schaefer et al., 2010; Dijkhuizen et al., 2011). A recent clinical trial evaluated the use of 400 mg of misoprostol sublingually 90 min prior to IUD
insertion in 40 nulligravidas. No signicant difference in the pain reported
by the woman was found when compared with controls (Edelman et al.,
2011). Another two studies also failed to show any reduction in pain or in
the degree of difculty in inserting the IUD (Scavuzzi et al., 2009; Heikinheimo et al., 2010). Nevertheless, the protocol design in these three
studies may have affected the results.
No consensus has yet been reached in the literature with respect to
the efcacy, dose, timing and route of administration of misoprostol
prior to IUD insertion. The objective of the present study was to determine whether the use of vaginal misoprostol prior to IUD insertion
facilitates the procedure and reduces the women perception of pain,
as well as the immediate and late side effects.

2119

2120
The analysis was conducted under the intention-to-treat principle. Initially,
the distribution tables of frequency were constructed for the categorical variables, and measures of central tendency and dispersion were calculated for
the numerical variables. The x 2 test of association and Fishers exact test
were used, as appropriate, to determine the association between the variables and the use of misoprostol or placebo. Two-tailed values were used
for all the tests. Risk ratios (RR) were calculated as a measure of relative
risk, together with their relevant 95% condence intervals. The number
needed to treat (NNT) and the number needed to harm (NNH) were
also calculated, together with their respective 95% condence intervals.

Results

between the two groups when the frequency of heavy menstrual bleeding, intermenstrual bleeding, spotting, cramps, PID or expulsion rates
were compared (Table V).

Discussion
In the present study, prior use of misoprostol at a dose of 400 mg was
found to be associated with less subjective difculty in inserting the
IUD in nulligravidas, less risk of cervical dilatation 4 mm and less
pain, as reported by the women; however, there was a greater incidence
of cramps.
The effect of misoprostol on the cellular matrix of the uterine cervix
causes dissolution of collagen bers, increasing the amount of uid in
the stroma and consequently causing cervical effacement. This effect
makes use of this drug a feasible proposition for certain gynecological
and obstetrical conditions (Fiala et al., 2007; Tang et al., 2002; Tang
et al., 2007).
Some studies have already been conducted to seek scientic evidence
in support of using misoprostol prior to IUD insertion in nulligravidas;
however, the variation in the doses, timing of administration and
routes of administration render comparison of these results difcult
(Li et al., 2005; Saav et al., 2007; Dijkhuizen et al., 2011). Furthermore,
small sample sizes may have been responsible for the lack of any signicant effects found in some studies. Despite the different timing and
routes of administration, the present ndings are in agreement with
the results published by other authors with respect to the degree of difculty at insertion (Li et al., 2005; Saav et al., 2007). However, some
studies failed to nd any reduction in pain during the procedure and
found no increase in the likelihood of insertion being successful (Schaefer
et al., 2010; Dijkhuizen et al., 2011).
Two of the principal ndings of the present study were the easier insertion of the IUD and the greater likelihood of cervical dilatation
.4 mm with the prior use of misoprostol. Other investigators have
reported similar results (Li et al., 2005; Saav et al., 2007). In one clinical
trial, the authors reported that sublingual administration of 400 mg of
misoprostol 1 h prior to IUD insertion in 47 nulligravidas women
made insertion signicantly easier and reduced the rates of insertion
failure (Saav et al., 2007). In another study involving a small series of
cases in which insertion failed due to cervical stenosis, the use of
400 mg of misoprostol vaginally resulted in successful insertion in all
the women involved, suggesting greater ease of insertion of the IUD
with the prior use of misoprostol (Li et al., 2005).
A recently published clinical trial in which 400 mg of misoprostol was
used orally 90 min prior to IUD insertion in 35 nulligravidas found no signicant difference in the pain reported by the women (Edelman et al.,
2011). In that study, a greater frequency of side effects, particularly
cramps and nausea, was found in the misoprostol group. The nding of
a greater frequency of cramps is not surprising, since this side effect is
caused by the increase in uterine contractility provoked by misoprostol,
which is a potent prostaglandin (Arias, 2000; Tang et al., 2007). In the
present study, a greater frequency of cramps was also found in the
group of women who received misoprostol, although no signicant difference was found in relation to the other side effects (nausea, vomiting,
diarrhea and hyperthermia). A question asked by several authors is could
this increase in uterine contractions lead to an increased risk of expulsion
of the device and this remains to be claried (Edelman et al., 2011). No
evidence of this was found in the present study; however, the sample was

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Initially, the IUD was offered as a contraceptive method to 220 nulligravid

women, 30 of whom were excluded from the study. Of these, 16 did not
fulll the inclusion criteria (never having been pregnant and never having
undergone any surgical procedure of the uterine cervix) and 14 were
excluded for other reasons (the presence of purulent cervicitis, vaginal
bleeding of undened cause and submucous myomas deforming the
uterine cavity). Ten women refused to participate in the study. Therefore, 190 women were randomized, 95 to the placebo group and 95
to the vaginal misoprostol group. Following randomization, eight boxes
containing misoprostol and two containing placebo were accidentally
damaged and could no longer be used. Of the 87 women remaining in
the misoprostol group, 1 woman discontinued the study after having
been given the medication; therefore, 179 nulligravid women remained
in the study, 86 in the vaginal misoprostol group and 93 in the placebo
group (Fig. 1).
There were no signicant differences between the two groups with
respect to the characteristics of the women in the sample (Table I). Signicant differences were found between the groups for all the immediate
end points evaluated, with less difculty in inserting the IUD (RR 0.49;
95% CI: 0.33 0.72; NNT 3; P 0.00001) and less risk of cervical dilatation 4 mm (RR 0.49; 95% CI: 0.33 0.70; NNT 4; P
0.00005) when misoprostol was used prior to insertion. The group of
women submitted to prior use of misoprostol also had a 44% reduction
in moderate-to-severe pain during IUD insertion compared with the
placebo group (RR 0.56; 95% CI: 0.41 0.76; NNT 3; P
0.00004). Likewise, fewer women reported a subjective sensation of a
disagreeable or very disagreeable experience with the use of misoprostol
(RR 0.49; 95% CI: 0.35 0.68; NNT 3; P 0.000004) (Table II).
There were no signicant differences between the groups in relation to
complications during IUD insertion. The frequency of bleeding, vasovagal
reaction, cramps, nausea, vomiting and insertion failures was similar in
both groups. No cases of uterine perforation occurred in either group
(Table III).
There were no signicant differences in the frequency of the majority
of the immediate side effects such as nausea, vomiting, hyperthermia and
diarrhea, evaluated prior to IUD insertion. Nevertheless, there was a signicant increase in cramps with the prior use of misoprostol compared
with placebo (RR 1.40; 95% CI: 1.05 1.86; NNH 6; P 0.002).
In relation to the side effects evaluated 24 h after IUD insertion, no signicant differences were found between the misoprostol and placebo
groups (Table IV).
Because insertion of the device failed in some cases, the evaluation
conducted 30 days later included 82 women in the misoprostol group
and 90 in the placebo group. No signicant differences were found

Scavuzzi et al.

2121

Misoprostol and IUD insertion in nulligravidas

Table I Characteristics of the nulligravidas according to

whether vaginal misoprostol or placebo was
administered prior to the insertion of an IUD.
Characteristics

Misoprostol
(n 5 86)

Placebo
(n 5 93)

........................................................................................
Age (years)
Range

16 44

18 45

Mean + SD

25.4 + 5.5

25.2 + 5.5

4 18

4 16

12

12

1st to 9th

1st to 9th

Education level (years of schooling)

Range
Median
Day of the menstrual cycle for
IUD insertion (range)

Position of the body of the uterus (n; %)

Anteverted/anteexed

71; 82.6%

73; 78.5%

Midposition

6; 7%

12; 12.9%

Retroverted/retroexed

9; 10.5%

8; 8.6%

inadequately powered to reveal any differences in expulsion rates

between the groups.
IUD is a safe, effective, LARC method and it is currently considered an
ideal contraceptive for young, nulligravid women, from the moment at
which they initiate their sexual life until they decide to have their rst
child (American College of Obstetricians and Gynecologists, 2007). In
the past, the IUD was indicated only for multiparas, this recommendation
probably originating from misgivings regarding a possible increase in the
incidence of acute PID and the association between this condition and
infertility. Although all subsequent studies have conrmed that this risk
is low, many HCPs still discourage women who have never been pregnant from using this contraceptive method (Hubacher et al., 2001;
Morgan, 2006; Stanback and Shelton, 2008).
Another factor that limits use of the IUD in nulligravidas is that insertion could be technically more difcult and more painful in this group.
Despite the lack of scientic evidence, misoprostol has been used and
is recommended by many HCPs to facilitate this procedure. One study
recently published in the USA evaluated the opinion of 2211 physicians
working in the eld of reproductive medicine. Overall, 1905 (86%) of
the individuals interviewed reported inserting IUDs in nulligravidas and,

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Figure 1 Flowchart showing the enrollment of the participants to the study (Consort, 2011).

2122

Scavuzzi et al.

Table II Principal measurements during insertion of the IUD in nulligravidas according to whether vaginal misoprostol or
placebo was administered prior to the procedure.
End points

Misoprostol (n 5 86)

Placebo (n 5 93)

n (%)

n (%)

RR

95% CI

P-value

.............................................................................................................................................................................................
Cervical dilatationa
4 mm

24 (27.9)

54 (58.1)

0.48

.4 mm

62 (72.1)

39 (41.9)

1.00

Difcult/very difcult

23 (26.7)

51 (54.8)

0.49

Easy

63 (73.3)

42 (45.2)

1.00

Moderate/severe

32 (37.2)

62 (66.7)

0.56

Mild/absent

54 (62.8)

31 (33.3)

1.00

Disagreeable/very disagreeable

29 (33.7)

64 (68.8)

0.49

Slightly disagreeable/not disagreeable

57 (66.3)

29 (31.2)

1.00

0.33 0.70

0.00005

0.33 0.72

0.0001

0.41 0.76

0.00008

0.35 0.68

0.000004

Difculty in inserting IUDb

Pain at insertionc

RR, relative risk.

a
Number needed to treat and obtain a benet (NNT) 3; 95% condence interval 26.
b
NNT 4; 95% CI 2 7.
c
NNT 3; 95% CI 2 7.
d
NNT 3; 95% CI 2 5.

Table III Side effects during insertion of an IUD in nulligravidas according to whether vaginal misoprostol or placebo was
administered prior to the procedure.
Variable

Misoprostol (n 5 86)

Placebo (n 5 93)

n (%)

n (%)

RR

95% CI

P-value

.............................................................................................................................................................................................
.0.99b

Bleeding

0 (0)

1 (1.1)

NC

NC

Vasovagal reaction

6 (7.0)

7 (7.5)

0.93

0.32 2.65

0.89a

Cramps

82 (95.3)

87 (93.5)

1.02

0.95 1.09

0.85b

Nausea

18 (20.9)

28 (30.1)

0.69

0.42 1.16

0.16a

Vomiting

0 (0)

4 (4.3)

NC

NC

0.14b

Failed insertion

4 (4.7)

3 (3.2)

1.44

0.33 6.26

0.91b

NC, not calculated; RR, relative risk.

a 2
x test.
b
Fishers exact test.

of these, 947 (42.7%) use misoprostol prior to the procedure, with the
majority (n 515; 54%) believing that the use of this medication greatly
facilitates insertion of the device (Ward et al., 2011).
To the best of our knowledge no other study has been published in
which 400 mg of misoprostol was used vaginally 4 h prior to IUD insertion. In other studies, doses have ranged from 100 to 800 mg, while
the drug has been administered sublingually, orally, vaginally and rectally,
and the timing of administration has ranged from 1 to 12 h prior to the
procedure (Scavuzzi et al., 2009; Schaefer et al., 2010; Dijkhuizen et al.,
2011; Edelman et al., 2011). When selecting the vaginal route of administration and the moment of administration prior to IUD insertion, the
pharmacokinetics of the drug were taken into consideration as a function

of the different routes of administration, with an interval of 4 h being considered the most appropriate.
A peak misoprostol concentration occurs in ,30 min when the drug
is used orally or sublingually and decreases rapidly from this moment on.
On the other hand, when the vaginal route is used, the peak plasma concentration occurs after 1 h and its decrease is gradual, with levels remaining high for at least 6 h, at substantially higher levels than when
administered by the oral or sublingual routes (el-Refaey et al., 1995;
Aronsson et al., 2004). When administered by the vaginal route, the
side effects of misoprostol are milder and more self-limiting compared
with the oral route, with less nausea, cramps and hyperthermia
(Hamoda et al., 2004; Fiala et al., 2007).

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Subjective sensation as reported by the womand

2123

Misoprostol and IUD insertion in nulligravidas

Table IV Immediate side effects prior to insertion of an IUD and late side effects 24 h after IUD insertion in nulligravidas
according to whether vaginal misoprostol or placebo was administered prior to the procedure.
Side effects

Misoprostol (n 5 86)

Placebo (n 5 93)

n (%)

n (%)

RR

95% CI

P-value

.............................................................................................................................................................................................
Immediate
Nausea

6 (7)

2 (2.2)

3.24

0.6715.64

0.23b

Crampsc

53 (61.6)

41 (44.1)

1.40

1.051.86

0.002a

Vomiting

5 (5.8)

2 (2.2)

2.70

0.5413.57

0.38b

Diarrhea

4 (4.7)

6 (6.5)

0.72

0.212.47

0.85b

Nausea

1 (1.2)

1 (1.1)

1.08

0.0717.02

Cramps

32 (37.2)

30 (32.3)

1.15

0.771.73

Vomiting

1 (1.2)

1 (1.1)

1.08

0.0717.02

.0.99b

Hyperthermia

1 (1.2)

5 (5.4)

0.22

0.003 1.81

0.25b

Diarrhea

2 (2.3)

0 (0)

NC

NC

0.46b

24 h later
.0.99b
0.49a

Table V Side effects 30 days after insertion of an IUD in nulligravidas according to whether vaginal misoprostol or placebo
was administered prior to the procedure.
Complaints

Misoprostol (n 5 82)a

Placebo (n 5 90)a

n (%)

n (%)

RR

95% CI

P-value

.............................................................................................................................................................................................
Heavy menstrual bleeding

34 (41.5)

43 (47.8)

0.87

0.621.21

0.41b

Intermenstrual bleeding

20 (24.4)

25 (27.8)

0.88

0.531.46

0.61b

Spotting

29 (35.4)

37 (41.1)

0.86

0.591.26

0.44b

Cramps

62 (75.6)

72 (80)

0.95

0.811.11

0.49b

Acute PID

1 (1.2)

1 (1.1)

1.10

0.0717.27

.0.99c

Expulsion

3 (3.7)

1 (1.1)

3.29

0.3531.03

0.55c

RR, relative risk.

a
Four cases in the misoprostol group and three cases in the placebo group were excluded because insertion failed.
b 2
x test.
c
Fishers exact test.

A pilot study conducted in this institute using the same dose of 400 mg
1 h prior to IUD insertion in 30 nulligravidas women found no signicant
differences between the misoprostol and placebo groups, and that
nding was also taken into consideration in designing the protocol of
the present study. Therefore, regarding timing of administration, it was
decided to increase the interval to 4 h in an attempt to reach a balance
between achieving the maximum effect of misoprostol with as few side
effects as possible (Scavuzzi et al., 2009). In addition, there was no signicant difference between the groups with regard to complications during
IUD insertion.
The major question to be discussed appears to be whether the benets of the use of this drug outweigh the side effects presented, since IUD
insertion, as evaluated by the professionals, is generally a simple

procedure, with few women requiring cervical dilatation, paracervical

block or to be submitted to an ultrasound-guided procedure (Allen
et al., 2009).
On the other hand, it should be taken into consideration that although
IUD insertion is a simple, inexpensive, fast procedure performed on an
outpatient setting and with low complication rates, even in nulligravidas
(Bahamondes et al., 2011), many women report pain during insertion and
for this reason often opt for other methods that are less effective or irreversible (Forthofer, 2009).
In an attempt to evaluate the actual benets of the use of misoprostol
in clinical practice, the NNT was calculated for the benecial end points in
the present study. It was found that for every three IUD insertions, with
the prior use of misoprostol one woman would have an easier procedure

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NC, not calculated; RR, relative risk.

a 2
x test.
b
Fishers exact test.
c
Number needed to harm (NNH) 6; 95% condence interval (95% CI) 333.

2124

Ethics approval
This study was approved by the internal review board of the Instituto
Materno Infantil Prof Fernando Figueira, Recife, Pernambuco, Brazil.

Supplementary data
Supplementary data are available at http://humrep.oxfordjournals.org/.

Authors roles
All authors actively participated in drafting the paper in all its stages. Each
author listed in the manuscript has seen and approved the submission of
this version of the manuscript and takes full responsibility for its content.
A.S.C.C., main author, participated in the project design, data collection and analysis, preparation of the manuscript, critical discussion and
general coordination of the study.
A.S.R.S. was involved in the conception and design of the project, critical discussion and data analysis.
A.A.R.C. was involved in the conception and design of the project.
M.M.R.A. was involved in the conception, design of the project and
data analysis, as well as in preparing and reviewing the paper.

Funding
This study was funded by the Instituto de Medicina Integral Prof Fernando
Figueira.

Conict of interest
None declared.

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Scavuzzi et al.

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