Original research article
A multicenter randomized clinical trial of one-rod etonogestrel and
two-rod levonorgestrel contraceptive implants with nonrandomized
copper-IUD controls: methodology and insertion data☆,☆☆,★,★★
Olav Meirika,b,⁎, Vivian Brachec, Kiriwat Orawand, Ndema Abu Habiba, Johannes Schmidta,e,
Nuriye Ortaylia,f, Kelly Culwella,g, Emily Jacksona,h, Moazzam Alia
The WHO study group on contraceptive implants for women
aUNDP, UNFPA, WHO, World Bank Special Programme of Research Development and Reaserch Training in Human Reproduction, Geneva, Switzerland
bInstituto Chileno de Medicina Reproductiva (ICMER), Santiago, Chile
cPROFAMILIA, Santo Domingo, Dominican Republic
dSiriraj Hospital, Mahidol University, Bangkok, Thailand
eGlaxosmithkline Biologicals, Wavre, Belgium
fUNFPA, New York, NY, USA
gDepartment of Obstet/Gynecol, University of California, Davis, Sacramento, CA, USA
hDepartment of Family Medicine, University of Southern California, Los Angeles, CA, USA
Received 29 March 2012; revised 30 August 2012; accepted 30 August 2012
Background: Comparative data on etonogestrel and two-rod levonorgestrel contraceptive implants are lacking.
Study Design: A multicenter, open, parallel-group trial with random allocation of implants was performed. For every second implant user,
an age-matched woman choosing an intrauterine device (IUD) (TCu380A) was admitted. Methods and data on implant/IUD insertion and
6-week follow-up are reported.
Results: A total of 2008 women were randomized to an implant, and 974 women were enrolled in the IUD group. Results from 997
etonogestrel implant users, 997 levonorgestrel implant users and 971 IUD users were analyzed. In the etonogestrel and levonorgestrel groups,
respectively, mean insertion durations were 51 (SD 50.2) s and 88 (SD 60.8) s; complication rates at insertion were 0.8% and 0.2%; and at
follow-up, 27.2% and 26.7% of women, respectively, had signs or symptoms at the insertion site. At follow-up within 6 weeks after insertion,
all implants were in situ, while 2.1% of IUDs were expelled.
Conclusion: Performance of etonogestrel and levonorgestrel implants at insertion and within the first 6 weeks is similar. Short-term
(6 weeks) continuation rates appear higher for implants than TCu380A.
© 2013 Elsevier Inc. All rights reserved.
Keywords: Etonogestrel; Levonorgestrel; Implant; TCu380A; Contraceptive; Implanon; Jadelle
Contraception 87 (2013) 113–120
☆Funding: United Nations Development Programme/United Nations Population Fund/WHO/World Bank Special Programme of Research, Development
and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization, and Family Health International.
☆☆Conflict of interest: We declare no conflicts of interest.
★Role of funding source: The organizations funding the study had no part in study design, data collection, data analysis, data interpretation or writing of
★★Disclaimer: The authors alone are responsible for the views expressed in this publication, and these views do not necessarily represent the decisions,
policy or views of the World Health Organization.
⁎Corresponding author. Instituto Chileno de Medicina Reproductiva (ICMER), Santiago, Chile. Tel.: +56 2 233 1590; fax: +56 18 541 922.
E-mail address: firstname.lastname@example.org (O. Meirik).
0010-7824/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
The 3-year one-rod etonogestrel (Implanon®) and the 5-
year two-rod levonorgestrel (Jadelle®) contraceptive im-
plants for women had first regulatory approvals in 1998 in
Indonesia and 1996 in Finland, respectively. These two long-
term reversible contraceptive methods are highly effective,
with annual pregnancy rates in the order of 0.0–0.5 per 100
women . A World Health Organization (WHO) technical
consultation in 2001 on implantable contraceptives for
women observed that no comparative trial of the two
implants had been done . Hence, the UNDP/UNFPA/
WHO/World Bank Special Programme of Research, Devel-
opment and Research Training in Human Reproduction in
WHO (HRP/WHO) developed a multicenter randomized
comparative trial of the etonogestrel and the levonorgestrel
implants. A control group of women using a long-term
reversible nonhormonal method, an intrauterine device
(IUD), was added to address lack of reliable data on
common nonserious side effects typically attributed to the
use of progestogen-only contraceptives . Additionally, it
was noted that very few pregnancies caused by method
failure had been reported for the etonogestrel implant during
3 years of use , and pharmacokinetic data indicated the
etonogestrel implant is likely to be effective for contracep-
tion beyond 3 years of use . Consideration was therefore
given to lengthen the trial up to 5 years if review of data
would justify extended use of the etonogestrel implant. We
present here the objectives and methodology of the trial, and
data on insertion and 6 weeks postinsertion follow-up of the
two implants and the TCu380A IUD. Other findings from
the trial such as contraceptive effectiveness, continuation of
use and side effects will be described in subsequent articles.
2. Materials and methods
This was a randomized, open, parallel-group trial of the
one-rod etonogestrel and the two-rod levonorgestrel contra-
ceptive implants with a 1:1 allocation ratio and a
nonrandomized control group of women using the
TCu380A IUD. The study took place in family planning
clinics (centers) in Campinas, Brazil; Santiago, Chile; Santo
Domingo, Dominican Republic; Szeged, Hungary; Bang-
kok, Thailand; Ankara (three sites), Turkey; and Harare,
2.1. The contraceptives
The etonogestrel implant (Implanon®, Merck & Co., Inc.,
Whitehouse Station, NJ, USA) contains 68 mg etonogestrel
embedded in one ethylene-vinyl-acetate rod . Etonoges-
trel is also known as 3-keto-desogestrel, the biologically
active metabolite of desogestrel used in combined and
progestogen-only contraceptive pills.
The levonorgestrel implants (Jadelle®, Bayer Healthcare,
Berlin, Germany) contain 75 mg levonorgestrel embedded
in two silicone copolymer rods . Levonorgestrel is
commonly used in combined and progestogen-only contra-
The TCu380A IUD is well known and has been
extensively studied in clinical trials [6,7]. The implants and
IUDs were provided by HRP/WHO.
2.2. Study objectives, outcomes and duration
The main objectives of the trial are to compare the annual
and the 3-year cumulative rates of contraceptive effective-
ness and method continuation, the incidence of side effects
between the two implants and incidence of common
complaints associated with use of progestogen-only contra-
ception and that of the nonhormonal TCu380A IUD.
Subsidiary objectives were to compare, between the three
contraceptives, reasons for method discontinuation and time
to conception after stopping method use because of desire of
pregnancy. Additionally, for the two implants, contraceptive
effectiveness by body weight of users, bleeding patterns, and
duration of and complications at implant insertion and
removal will be examined.
Based on review of data on pharmacokineticsand efficacy
of the etonogestrel implant beyond 3 years [4,8–11], it was
4- and 5-year annual and cumulative rates of effectiveness,
continuation and side effects to the study objectives. All
centers, except the center in Hungary, agreed to take part in
the extended follow-up.
Outcomes included in this paper are duration of implant
insertion (measured as time from when the scalpel or the
applicator needle first touch the skin until placement of
sterile dressing), complications at insertion, ease of insertion
(easy, slightly difficult or difficult), perception of pain by the
woman receiving the implant (none, mild, moderate or
severe), and signs and symptoms of the site of the insertion at
postinsertion follow-up. For the TCu380A IUD, complica-
tions at insertion and follow-up are reported.
The randomization sequence for implant users was
computer-generated by HRP/WHO with variable block
size of six or eight and stratified by center. Each center
received a list of subject identification numbers for implant
users which were assigned sequentially at admission,
together with a set of opaque sealed envelopes on which
only the center and the subject number of implant users were
printed. The envelope with the corresponding subject
number was opened immediately before implant insertion
by clinic staff, and the type of implant to be inserted was read
from a slip of paper inside. Women in the IUD group were
frequency-matched by age (in 5-year bands) with every
second woman admitted to the implant group. The study was
114O. Meirik et al. / Contraception 87 (2013) 113–120
2.4. Admission and exclusion criteria
Admission criteria were as follows: healthy women aged
≥18 and b45 years; not pregnant; regularly menstruating or,
if in lactational amenorrhea, ≥6 weeks postpartum; able to
keep a menstrual diary; willing to return to the clinic for
follow-up visits over 3 years; and able to understand
information about the study and to give informed consent
to participate. Exclusion criteria were as follows: breastfeed-
ing an infant b6 weeks old; systolic blood pressure N159 mm
Hg or diastolic N99 mm Hg; current venous thromboembo-
lism; current ischemic heart disease; unexplained vaginal
bleeding with suspicion of serious underlying condition;
history of breast or cervical cancer; active viral hepatitis;
severe (decompensated) cirrhosis of liver; benign or
malignant tumor of the liver; and current use of rifampicin,
griseofulvin or anticonvulsants .
For the IUD group, additional exclusion criteria were
distorted uterine cavity; current or recent history (3 months)
of pelvic inflammatory disease; current sexually transmitted
infection or purulent cervicitis; being at increased risk of
sexually transmitted infection; and endometrial cancer .
2.5. Admission procedures
Women admitted to the study attended the participating
family planning clinics and requested reversible long-term
contraception. Women opting for implant or IUD were
informed in writing and verbally about the study and what
participation involved. Women choosing implants were
informed that they would be randomized to either the 3-
year etonogestrel or the 5-year levonorgestrel implant and
that, if they were randomized to the 3-year implant, they
would have the option to have another implant of their
choice, inserted without cost if they wanted to continue
implant contraception beyond 3 years. All women accepting
participation signed an informed consent.
At admission, women were interviewed and had a
physical examination according to the routines of the clinic
including cervical cytology, blood pressure, hemoglobin and
measurement of weight and height. The women were
scheduled for implant or IUD insertion on days 1 through
5 after the start of menstrual bleeding, following insertion
procedures recommended by the manufacturers. The in-
sertions were done by nurses, midwifes or physicians trained
in insertion of the two types of implants and the IUD.
Follow-up visits were scheduled 2 weeks after implant/
IUD insertion, at 3 and 6 months after insertion, and
semiannually thereafter. In the results presented here,
postinsertion visits within 6 weeks are included. At follow-
up visits, women were interviewed about their health,
medication, visits to health care facilities or hospitalization.
If a health care contact had occurred, reasons for seeking
care, treatment and diagnoses were elicited. In instances of
hospitalization, the case record was reviewed for dates of
admission, treatments and discharge diagnoses. Women
were questioned about vaginal bleeding patterns and
pregnancy. Any suspicion of pregnancy led to urine
pregnancy testing. Blood pressure, hemoglobin and weight
were measured, and cervical cytology was taken if indicated
according to routines of the centers. At each visit, literate
women completed the Edinburgh Depression Scale .
Women were encouraged to attend or telephone the clinic for
any question, advice or symptoms needing medical consul-
tation. Follow-up stopped when the implant or IUD was
removed or expelled, at end of study or if the woman no
longer wished to participate. Women requesting removal of
their device in order to attempt to conceive were followed up
for up to 1 year after method discontinuation, until they
became pregnant or until they restarted use of an effective
At the end of 3 years of use, all study participants were
invited to participate in the study extension for an additional
2years. Women with the etonogestrel implant were informed
that the use of the implant after 3 years was experimental,
and informed consent was obtained from those accepting
extended use. Women with levonorgestrel implant or IUD
accepting the extended follow-up also provided informed
consent for extended participation. Women not accepting
extended use of etonogestrel implant were offered, free of
charge, an implant of their own choice. All women
participating in the extended follow-up continued with
follow-up visits every 6 months.
2.7. Sample size
With assumptions that 40% of implant or IUD users
would discontinue use of the method, that 5% of women
would be lost to follow-up by 3 years, and that discontin-
uations and losses were evenly distributed over the 3 years, a
sample of 1000 women in each implant group would allow
detection, with 80% statistical power and 95% significance
level in two-sided tests, of the following: a 1.6 per 100
difference in the cumulative 3-year pregnancy rate, assuming
a cumulative rate of 0.5 per 100 woman-years; a 7%
difference in the 3-year cumulative discontinuation rate,
assuming that the rate in the two groups is 40%; a 6%–8%
difference in the 3-year cumulative rate of perceived side
effects, assuming that the rate is between 25% and 35%; and
a 3%–4.5% difference in the rate of insertion complications,
assuming that these occur at a rate of 2%–3%. Based on
these calculations, a sample size of 2000 women randomized
to the etonogestrel or levonorgestrel implants (1000 in each
arm) was chosen, with 1000 women in the TCu380A IUD
group. It was assumed that 10 centers would participate in
the trial, each enrolling 300 women.
2.8. Data management and statistical analysis
Data were recorded on study-specific case report self-
copying forms at all visits during the study. Data quality was
115 O. Meirik et al. / Contraception 87 (2013) 113–120
assured by computer-generated and manual queries sent to
the investigators in the centers, with subsequent correction to
the database. The Coordinating Investigator and expert
committees in HRP/WHO monitored and reviewed the
conduct and the progress of the study from regular reports
from the data management center. Regular on-site monitor-
ing of the participating centers started in 2006 when Family
Health International, Research Triangle Park, North Caroli-
na, USA, joined the study and took on the responsibility for
monitoring according to Good Clinical Practice Guidelines.
Until August 2006, the centers sent originals of completed
forms to the data management center of the study at HRP/
WHO, Geneva, Switzerland, at regular intervals. In Septem-
ber 2006, the data management was transferred to Centro
Rosarino de Estudios Perinatales (CREP), Rosario, Argen-
tina. However, because of difficulties implementing quality
monitoring of data at CREP, HRP/WHO again took over
data management in September 2010.
The data were analyzed at HRP/WHO using SAS/STAT
version 9.2. Comparisons between groups were made using
the Pearson χ2test (two-sided) for categorical outcome
variables. Relative risks with 95% confidence interval (95%
CI) were computed for binary outcomes using the log-
binomial model adjusted for center. For continuous out-
comes, linear regression was used for mean difference and
95% CI adjusted for center. No adjustments for baseline
prognostic variables except center were done. Only women
without any protocol violations as detected at the time of
analysis were included in the data analyzed here.
The study was approved by the Scientific and Ethical
Review Group at HRP/WHO and the WHO Secretariat
Committee on Research Involving Human Subjects. Each
center obtained approval for the study from local or national
Ethics Committees, or both. The study extension was
approved by the WHO Ethics committee and at each center
by local or national Ethics Committees, or both. The trial is
registered as ISRCTN33378571.
Enrolmentof women took place in family planning clinics
in centers in Campinas, Brazil; Santiago, Chile; Santo
Thailand; Turkey (three sites); and Harare, Zimbabwe, from
12 May 2003 to 31 January 2008. Since fewer centers than
anticipated participated, centers in Brazil, Chile, the Domin-
of women they admitted (Table 1). Four centers had
concurrent experience of implant contraception. Three
centers had provided implants in the past except, among the
latter three, there was one site with no implant experience.
As seen from Fig. 1, of the 2992 women assessed eligible
for use of implant or IUD, 997 women with etonogestrel
implant, 997 with levonorgestrel implant and 971 with IUD
were included in the current analysis. The losses to follow-up
within 6 weeks of the implant/IUD insertions were 11 (1.1%)
women in each of the two implant groups and 8 (0.8%)
women in the IUD group.
Table 2 shows selected demographic and reproductive
characteristics of women having levonorgestrel implant,
etonogestrel implant or IUD inserted. Women in the two
implant groups have similar characteristics, while IUD
users were more likely to have had higher education, to
have been pregnant and to not have used hormonal
Data on insertion time was available for 992 insertions of
etonogestrel and 995 of levonorgestrel implants. The mean
duration of insertion was 51 s (SD 50.2) for etonogestrel
implants and 88 s (SD 60.8) for the levonorgestrel device,
with a mean difference of 37 s (95% CI 33–41 s) adjusted for
center (Wald p value b.0001). The median insertion times
(with lower and upper quartiles) were 40 s (22, 60) and 70 s
(50, 110), respectively.
Fig. 2 shows the distribution of duration of insertion in
20-s intervals for the two implants. There is considerable
overlap of the two distributions, with a clear tendency to
longer insertion times for the levonorgestrel implant.
Twenty-four (2.4%) of etonogestrel and 47 (4.7%) of
levonorgestrel implant insertions had a duration of 180 s (3
min) or more; of these, 21(88%) and 44 (94%) insertions,
respectively, took place in the three study centers with the
least recent experience inserting implants.
For both types of implants, more than 98% of the
providers inserting the implants reported that they found the
insertion to be easy (Table 3). There were few complications
at insertion. In five instances, insertion of the etonogestrel
implant failed in the first attempt (the implant was
withdrawn together with the trocar and the plunger),
however, the same implant was successfully inserted in a
second attempt in all five instances. Fifty (5.0%) of the 997
women in the etonogestrel and 78 (7.8%) of the 997 in the
levonorgestrel group, respectively, reported mild or moder-
ate pain at insertion.
Number of women randomly allocated to etonogestrel or levonorgestrel
implant, and women eligible for TCu380A IUD, by center
Center Contraceptive method
116O. Meirik et al. / Contraception 87 (2013) 113–120
Twelve (1.2%) of the 971 IUD insertions had compli-
cations: in five women, the first insertion attempt failed,
another four women were treated with misoprostol
vaginally, and one received ibuprofen before insertion
because of narrow cervical canal; two women reported
strong pain after insertion.
Analysis of data collected at the postinsertion visit
included women attending within 6 weeks of insertion
(Table 4). Pain and itching at the insertion site were the two
most frequently reported symptoms among women with
implants, the latter more frequent in users of etonogestrel
than levonorgestrel implant. Overall, the signs and
symptoms observed within 6 weeks of insertion did not
differ between the two implants. No method discontinua-
tions were reported in the first 6 weeks for women in either
Among the 963 women with IUD attending a follow-up
visit within 6 weeks of the insertion, the IUD had been
expelled in 20 women (2.1%); in three women, the threads of
the IUD were not visible (all three IUDs were confirmed by
ultrasound to be in uteri), one woman complained of
spotting, and one was diagnosed with bacterial vaginosis.
Seven serious adverse events were reported within 6
weeks of follow-up: in users of etonogestrel implants, one
diagnosis each of influenza and pyelonephritis; in
levonorgestrel users, one each of cervical dysplasia and
ductal carcinoma of the breast; in IUD users, two
diagnoses of appendicitis and one trauma of the ankle.
None of these were assessed as being associated with
In our study, the mean duration of insertion of the one-rod
etonogestrel contraceptive implant was 37 s shorter than that
of the two-rod levonorgestrel implant, 51 vs. 88 s,
respectively. Mascarenhas (1998), in a study of 1466
2992 women screened and assessed eligible for implant or IUD
3 women changed their mind, 2 proved
pregnant, 1 post-menopausal.
2012 women eligible, consenting, scheduled
for randomization and insertion of implant
974 women eligible, consenting,
scheduled for insertion of IUD
4 women had implants
2008 women were randomized
1003 women randomised to
1005 women randomised to
4 women changed mind
about implant use1
2 women randomized to
5 women got expired
2 women randomized to
1 woman pregnant at
971 IUD insertion
11 women missed
11 women missed
8 women missed
963 women followed-up
within 6 weeks
986 women followed-
up within 6 weeks
986 women followed-
up within 6 weeks
Fig. 1. Flowchart of women screened for eligibility and admitted for use of implant or IUD, women randomized to type of contraceptive implant and reasons for
noninclusion in analysis.1Four women changed their mind about implant use after randomization and before implant insertion.2By mistake, the types of
implants were swapped.
117 O. Meirik et al. / Contraception 87 (2013) 113–120
etonogestrel implant insertions, reported a mean insertion
time of 1.5 min (SD 1.6), although without clearly defining
“insertion time” . The same author reported that 2% of
etonogestrel implant insertions had durations of N3 min; we
found 2.4% of these insertions were ≥3 min. In a US study,
the time from when the tip of the etonogestrel implant
applicator touched the skin until its removal was 0.5 min,
with a range of 0.05–15 min . Unsurprisingly, we found
that clinics with little recent experience with implant
insertion had more insertions with long duration than clinics
with more experience. The rates of complications at insertion
were 0.8% and 0.2% for etonogestrel and levonorgestrel
Selected characteristics of women having an implant or IUD inserted, by
type of implant/device, and included in the analyses
Age in years,
Marital status, n (%)
No regular partner
27.7 (6.2)28.1 (6.4)28.7 (6.6)
848 (85.1)862 (86.6) 845 (87.0)
106 (10.6) 92 (9.3) 97 (10.0)
Time in seconds
600580560540520500480460440 420400380360 340320300280260240220200180160140120100 806040200
Relative Frequency (%)
Duration of insertion, by type of implant
Fig. 2. Distribution of duration of insertion of etonogestrel and levonorgestrel implants in intervals of 20 s.
Difficulties and complications at implant insertion, and pain as perceived by
women at insertion, by type of implant: numbers and percentages in
Observations at insertion;
difficulty, complications, pain
Difficulty of insertion (%)
Perception of pain at
Complication at insertion (%)
bComplicationsat etonogestrelinsertion: first insertionattempt failed in
five women, notable bleeding two, hematoma in one.
cComplications at levonorgestrel insertion: blunt insertion trocar in one
woman, notable bleeding in one.
118O. Meirik et al. / Contraception 87 (2013) 113–120
implants, respectively, and in the same order of magnitude as
that reported previously for the etonogestrel and the two-rod
levonorgestrel implants [14,16].
Overall, more than 90% of women reported no pain at
insertion. Mild to moderate pain during insertion was
reported by slightly more women having levonorgestrel
implants inserted than those who had the etonogestrel
implant placed: 7.8% vs. 5.0%, respectively. At follow-up
after implant insertion, women with etonogestrel implants
more often reported itching at the site of the implant than
women with levonorgestrel implants. Otherwise, no
clinically important differences were observed at the time
of insertion or within 6 weeks of follow-up.
While the study was randomized, it was not blinded.
From the outset, we had no indications that one implant
should have been preferred over the other in any of the
participating centers, which should have minimized any
reporting bias. The problems of data quality monitoring
during a period of 4 years in the middle of the study meant
that the consolidation of the data has been delayed. The
strengths of this trial are the randomized allocation of type
of implant and the different levels of experience with
contraceptive implants among participating centers, fea-
tures that enhance the generalizability of our findings.
Data from this study on insertion of these two
contraceptive implants have not revealed any clinically
important differences between them up to 6 weeks
following insertion. The differences of duration of
insertion do not appear to be important in the context
of the up to 3- to 5-year duration of use of these implants
and should not alone determine choice of implant. Future
publications from this study will provide comparative data
on safety, contraceptive effectiveness and rates of
continuation of each of the two implants and the
TCu380 IUD. Such information will be useful to decision
makers when choosing type of implant for family
WHO study group on contraceptive implants for
women: Investigators: Luis Bahamondes, Maria Valeria
Bahamondes, Universidade Estadual de Campinas (UNI-
CAMP), Campinas, Brazil; Rebeca Massai, Juan Carlos
Montero, Dr. Claudio Villarroel, Instituto Chileno de
Medicina Reproductiva (ICMER), Santiago, Chile; Vivian
Brache, PROFAMILIA, Santo Domingo, Dominican
Republic; Laszlo Kovacs, Attila Pal, Sandor Koloszar,
Albert Szent-Gyorgi Medical University, Szeged, Hungary;
Kiriwat Orawan, Siriraj Hospital, Mahidol University,
Bangkok, Thailand; Ayse Akin, Nüket Paksoy Erbaydar,
Türküler Erdost, Güldali Aybaş, Sinan Beksac, Hacettepe
University Medical School, Ankara; Berna Dilbaz, Ali
Haberal, Cuma Kurttekin, Emine Giray, Etlik Maternity
and Gynecological Training Hospital, Ankara; Hale Aktün,
Leyla Mollamahmutoglu, Erdoğan Tümay, Ayşe Evran,
Zekai Tahir Burak Maternity Hospital, Ankara, Turkey;
Jonathan Kasule, Tsungai Chipato, University Hospital of
Zimbabwe, Harare, Zimbabwe.
Research protocol development: Olav Meirik, Instituto
Chileno de Medicina Reproductiva (ICMER), Johannes
Schmidt, Tim Farley, Nuriye Ortayli, UNDP/UNFPA/
WHO/World Bank Special Programme of Research,
Development and Research Training in Human Repro-
duction (HRP), World Health Organization (WHO),
Study coordination and data management: Johannes
Schmidt, Nuriye Ortayli, Kelly Culwell, Emily Jackson,
Moazzam Ali, Tim Farley, Gilda Piaggio, Sihem Landoulsi,
Catherine Hazelden, Ndema Habib Abu, HRP/WHO;
Markus Steiner, David Hubacher, Ninky Acevedo, Joy
Coker, Orawan Kijkuarn, Family Health International (FHI),
Research Triangle Park, NC, USA; Daniel Wojdyla, Liana
Campodonico, Fernando Burgueno Centro Rosarino de
Estudios Perinatales (CREP), Rosario, Argentina.
Observations at first follow-up visit within 6 weeks of implant insertion, number of women with percentages in parenthesis, and relative risk for etonogestrel vs.
Symptoms/signs at insertion sitea
Relative risk 95% CI, etonogestrel vs.
One or more sign/symptom
0.75 ( 0.53–1.07)
0.69 ( 0.37–1.28)
aA women could have more than one symptom or sign.
cEtonogestrel implant: movable implant in two, tenderness and swelling in three, pigmentation in one.
dLevonorgestrel implant : bended implant in one, tenderness and swelling in three, infection in one, bleeding in one.
eNot adjusted for center.
119O. Meirik et al. / Contraception 87 (2013) 113–120
Analysis group: Ndema Abu Habib, Sihem Landoulsi, Download full-text
Olav Meirik, Gilda Piaggio, Alain Pinol, Moazzam Ali.
Writing group: Olav Meirik, Vivian Brache, Kiriwat
Orawan, Ndema Abu Habib, Johannes Schmidt, Nuriye
Ortayli, Kelly Culwell, Emily Jackson, Moazzam Ali.
 Glasier A. Implantable contraceptives for women: effectiveness,
discontinuation rates, return of fertility, and outcome of pregnancies.
 Meirik O, Fraser I, d'Arcangues C, for the WHO Consultation on
Implantable Contraceptives for Women. Implantable contraceptives
for women. Hum Reprod Update 2003;9:49–59.
 Brache V, Faundes A, Alvarez F, Cochon L. Nonmenstrual adverse
events during use of implantable contraceptives for women: data from
clinical trials. Contraception 2002;65:63–74.
 Huber J. Pharmacokinetics of Implanon. Contraception 1998;58:
 Croxatto HB. Mechanisms that explain the contraceptive action of
progestin implants for women. Contraception 2002;65:21–7.
 United Nations Development Programme, United Nations Population
Fund, World Health Organization, World Bank, Special Programme of
Research, Development and Research Training in Human Reproduc-
tion. Long-term reversible contraception: twelve years experience with
TCu380A and TCu220C. Contraception 1997;56:341–52.
 Sivin I, Tatum HJ. Four years of experience with the TCu 380A
intrauterine contraceptive device. Fertil Steril 1981;36:159–63.
 KiriwatO,PatanayindeeA,KoetsawangS, KorverT, CoelingBennink
HJT. A 4-year pilot study on the efficacy and safety of Implanon®, a
single rod hormonal contraceptive implant, in healthy women in
Thailand. Eur J Contracept Reprod Health Care 1998;3:85–91.
 Croxatto HB, Makarainen L. The pharmacodynamics and efficacy of
Implanon. Contraception 1998;58:91S–7S.
 Makarainen L, Tuomivaara L, Asplund B, Bennink HC. Ovarian
function during the use of a single contraceptive implant: Implanon
compared with Norplant. Fertil Steril 1998;69:714–21.
 DaviesGC, Feng LX, Newton JR, Van Beek A, Coeling-Bennink HJT.
Release characteristics, ovarian activity and menstrual bleeding pattern
with a single implant releasing 3-ketodesogestrel. Contraception 1993;
 World Health Organization Reproductive Health and Research.
Medical eligibility criteria for contraceptive use. 2nd ed. Geneva:
World Health Organization; 2000.
 Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression
development of the 10-item Edinburgh postnatal depression scale. Br J
 Mascarenhas L. Insertion and removal of Implanon®. Contraception
 Funk S, Miller MM, Mishell Jr DR, et al. Safety and efficacy of
Implanon, a single-rod implantable contraceptive containing desoges-
trel. Contraception 2005;71:319–26.
 Sivin I, Alvarez F, Mishell Jr DR, et al. Contraception with two
levonorgestrel rod implants; a 5-year study in the United States and
Dominican Republic. Contraception 1998;58:275–82.
120 O. Meirik et al. / Contraception 87 (2013) 113–120