Het is echter wel schadelijk om overmatig te alcohol te drinken, zeker als u een infectie heeft. Dit komt de infectie eerder verergerd door het gebruik van alcohol antibiotica en ibuprofen samen Doorgaans worden ze voorgeschreven bij bacteriële infecties die om de één of andere reden niet uit zichzelf over gaan; ze doden dan de bacteriën.
Untitled
Hum. Reprod. Advance Access published May 8, 2012
Human Reproduction, Vol.0, No.0 pp. 1 – 7, 2012
The efficacy of intrauterine devices foremergency contraception: a systematicreview of 35 years of experience
Kelly Cleland1,*, Haoping Zhu2, Norman Goldstuck3, Linan Cheng4,and James Trussell1,5
1Office of Population Research, Princeton University, 218 Wallace Hall, Princeton, NJ 08544, USA 2Minhang Central Hospital, ShanghaiJiaotong University, Shanghai 201100, People’s Republic of China 3Reproduction Research South Africa, St John’s Rd, Sea Point, Cape Town
8005, South Africa 4Shanghai Institute of Planned Parenthood Research, Xie Tu Rd, Shanghai 200032, People’s Republic of China 5The HullYork Medical School, University of Hull, Hull HU6 7RX, UK
*Correspondence address: Tel: +1-609-258-1395; Fax: +1-609-258-1039; E-mail: [email protected]
Submitted on February 1, 2012; resubmitted on March 19, 2012; accepted on March 23, 2012
background: Intrauterine devices (IUDs) have been studied for use for emergency contraception for at least 35 years. IUDs are safeand highly effective for emergency contraception and regular contraception, and are extremely cost-effective as an ongoing method. Theobjective of this study was to evaluate the existing data to estimate the efficacy of IUDs for emergency contraception.
methods: The reference list for this study was generated from hand searching the reference lists of relevant articles and our own articlearchives, and electronic searches of several databases: Medline, Global Health, Clinicaltrials.gov, Popline, Wanfang Data (Chinese) andWeipu Data (Chinese). We included studies published in English or Chinese, with a defined population of women who presented for emer-gency contraception and were provided with an IUD, and in which the number of pregnancies was ascertained and loss to follow-up was
clearly defined. Data from each article were abstracted independently by two reviewers.
results: The 42 studies (of 274 retrieved) that met our inclusion criteria were conducted in six countries between 1979 and 2011 andincluded eight different types of IUD and 7034 women. The maximum timeframe from intercourse to insertion of the IUD ranged from 2days to 10 or more days; the majority of insertions (74% of studies) occurred within 5 days of intercourse. The pregnancy rate (excluding oneoutlier study) was 0.09%.
conclusions: IUDs are a highly effective method of contraception after unprotected intercourse. Because they are safe for the ma-jority of women, highly effective and cost-effective when left in place as ongoing contraception, whenever clinically feasible IUDs should beincluded in the range of emergency contraception options offered to patients presenting after unprotected intercourse. This review is limitedby the fact that the original studies did not provide sufficient data on the delay between intercourse and insertion of the IUD, parity, cycle dayof intercourse or IUD type to allow analysis by any of these variables.
Key words: emergency contraception / intrauterine device / unintended pregnancy / unprotected intercourse / contraception
common medication option is 1.5 mg levonorgestrel, sold in one-pillor two-pill formulations. A newer formulation is 30 mg ulipristal
Unintended pregnancy is a significant problem worldwide. It is esti-
acetate, marketed in the USA as ellaw and in much of Europe as
mated that globally at least 36% of pregnancies are unintended
ellaOnew. In a few places, such as China, Vietnam and Russia,
(and in the USA nearly half of pregnancies are un-
mifepristone in small doses is available for emergency contraception.
Non-hormonal IUDs (primarily copper-bearing) have been used for
women an important strategy to prevent pregnancy after intercourse
emergency contraception for at least 35 years (
in cases of contraceptive accidents or non-use, or in situations of
(The levonorgestrel intrauterine system, sold in the USA and Europe
sexual violence. There are two forms of emergency contraception
under the brand name Mirenaw, has not been studied for use for
available today: pills and intrauterine devices (IUDs). The most
emergency contraception.) Negative experiences with the Dalkon
& The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: [email protected]
Shield, an IUD available in the 1970s in the USA, led to years of
available published data. The reference list for this study was generated
concern about the safety of IUDs and very low levels of IUD use.
from searching our own archives, references lists of relevant articles and
However, the design of modern IUDs available today is vastly
queries of several databases using the following search terms:
improved, and guidelines from major medical organizations, such as
MEDLINE: ‘Contraception, Postcoital’ [Mesh] AND ‘Intrauterine
the Centers for Disease Control and Prevention, the World Health
Organization, the UK Faculty of Sexual and Reproductive Healthcare
Clinicaltrials.gov: ‘intrauterine device’ AND ‘emergency contraception’,
and American College of Obstetricians and Gynecologists, note that
Popline: ‘IUD’ & ‘Emergency Contraception’,
IUDs are a safe choice for the majority of patients, including young
Global Health: ‘intrauterine device’ AND ‘emergency contracept*’ OR
Wanfang Data (Chinese): (emergency contraception, intrauterine
Weipu Data (Chinese): (emergency contraception, intrauterine device).
One of the major advantages of copper IUDs is that following use
This review includes any peer-reviewed study published by August 2011
for emergency contraception, they can then be left in place to provide
in English or Chinese, with a defined population of women who presented
at least 10 years of highly effective ongoing contraception. [In the USA
for emergency contraception and were provided with an IUD, and in
ParaGardw is labeled for 10 years of use but there is evidence of ef-
which the number of pregnancies was ascertained and loss to follow-up
was clearly defined. Chinese data were included because of the tremen-
shown to be among the most cost-effective methods of contraception
dous amount of contraceptive research taking place in that country.
the fact that this is a ‘forgettable’ method that
Once relevant articles were identified, data from each study were
does not require action on the part of the user means that there is
abstracted independently by two reviewers using a common data entry
form that captured the language of publication, country in which data
were collected, type(s) of IUD used, maximum time from intercourse to
IUDs are experiencing a moderate comeback after years of very
IUD insertion, initial study enrollment, efficacy-evaluable population, loss
low uptake in the USA ). In 2008 (the last
to follow-up and number of treatment failures (pregnancies).
year for which data are available), 4.9% of American women at risk
We computed Blyth – Still – Casella exact 95% binomial confidence
intervals (CI) for proportions and used either Fisher’s Exact Test (for
is a marked increase from the 0.7% of women at risk of pregnancy
2 × 2) or Fisher–Freeman –Halton (for R × 2) to test for homogeneity.
All calculations were performed in StatXact in Cytel Studio 8 (Cytel
than the use in Europe, where 10% of British women (data from
2009) () and 24% of French women (data from 2005)) at risk of pregnancy use IUDs. No comparable
statistic is available for IUD use among all women at risk of pregnancy
in China, but the Chinese National Population and Family PlanningCommission reported that 53% of married women using contracep-
Our search found 274 articles, and we assessed 48 of these in depth
to determine their eligibility for inclusion. Five studies were excluded
from our analysis because they did not provide sufficient detail
IUD use is higher in China than in the world overall; a
2005 report noted that 43% of Chinese women using contraception
used IUDs, compared with 13% in the rest of the world (
Guidelines for the use of IUDs for emergency contraception
both in English and Chinese, and we included the English version in this
typically recommend inserting the IUD within 5 days of unprotected
included a subject who presented 95 h after unprotected intercourse
for Disease Control, the World Health Organization and the UK
and was believed to be pregnant as a result of an act of intercourse 16
Faculty of Sexual and Reproductive Healthcare specify that an IUD
days prior to insertion of the IUD; this individual was excluded from
can be used beyond 5 days, as long as the time of ovulation can be
the analysis. One study was designed to compare the insertion toler-
reasonably determined and the insertion occurs no more than 5
ability of the GyneFix IUD versus the Gyne-T380S IUD for emergency
contraception but it did report that no pregnancies occurred in the
trial, and so we included it in our final dataset (
Forty-two studies were included in the final review.
that the guidelines around the time of insertion are not related to ef-
The 42 studies that fit our eligibility criteria and were included in the
ficacy or safety but to ensure that the IUD is inserted before the im-
review ranged in the year of publication from 1979 to 2011 (Table
plantation of an embryo (thus ensuring its function as a contraceptive,
Of these, 28 were published in Chinese and 14 in English. The English
rather than an early abortifacient).
literature included data collected in China, Egypt, Italy, the Nether-lands, USA and the UK. Nearly all of the IUDs were copper-bearing,
although a small number of plastic IUDs (the Lippes Loop series) wereused in two of the earlier studies (;
This study is a systematic review designed to provide a current estimate of
The majority of studies in our review (31 studies, 74%) fol-
the efficacy of IUDs used for emergency contraception, based on all of the
lowed the current standard protocol of inserting the IUD within 5
Intrauterine device efficacy in emergency contraception
Table I Studies included in review of the efficacy of IUDs for emergency contraception over 35 years, in order ofpublication.
aWhere the pregnancy rate is zero, a one-sided 97.5% CI is calculated. Otherwise, a 95% exact binomial CI is calculated. bIndicates publication in English; otherwise, studies were published in Chinese.
days of unprotected intercourse, although one study included 18 (out
in the expectant management group. The failure rate in the treatment
of 998) insertions beyond 5 days (three studies
arm of this study is surprisingly high, and significantly higher than the
provided insertions up to 7 days after intercourse
rate in all other countries combined (P ¼ 0.0001); in contrast, the
results among the five countries excluding Egypt are homogeneous
up to 10 days ) and one included 24 insertions
(P ¼ 1). If the true failure rate in Egypt were the same as in the
(out of 64) at 10 or more days post-coitus (). One
other five countries (0.000878), then the chance of observing four
study did not specify the time to insertion at all
or more pregnancies is vanishingly small,
The studies did not include sufficient information on the
0.00004). This high failure rate can possibly be explained by the fact
delay between intercourse and insertion of the IUD to enable us to
that women were specifically selected if they had had intercourse
around the time of ovulation; in any event Egypt is a clear outlier. If
Among 7034 post-coital IUD insertions, there were 10 pregnancies,
the unusual results from the Egypt study were excluded, the overall
for an overall failure rate of 0.14% (95% CI ¼ 0.08 – 0.25%) (Table
failure rate would be 0.09% (95% CI ¼ 0.04 – 0.19%); this is our pre-
Six pregnancies occurred among 5629 subjects in the studies con-
ducted in China (failure rate ¼ 0.11%; 95% CI ¼ 0.05 – 0.23%) andthe remaining four pregnancies occurred among 200 subjects in one
study conducted in Egypt Strikingly, this studyis the only RCT with a non-treatment arm for a contraceptive
Our data suggest that IUDs are a highly effective method of emer-
product that we are aware of. Three hundred women who had
gency contraception, with a failure rate of less than one per thousand.
engaged in unprotected intercourse around the time of ovulation
The copper IUD is by far the most effective emergency contraceptive
(and so had a relatively high probability of pregnancy) were rando-
option, followed by mid-dose mifepristone (25 – 50 mg) or ulipristal
mized to either post-coital insertion of a Cu T-200 or no treatment.
1.4%) and then levonorgestrel (failure rate
The pregnancy rates were 2% among the treatment group and 22%
Intrauterine device efficacy in emergency contraception
Table II Failure rates for IUD use as emergency contraception, by country.
Data from two randomized trials of the ulipristal acetate and levo-
is a limitation that relevant studies in other languages were omitted,
norgestrel regimens suggest that the efficacy of levonorgestrel declines
as these might have added strength to these results. However, we
sharply as BMI increases. Statistical models indicate that, among
believe that English and Chinese journals include the majority of pub-
women with a BMI of 26 kg/m2 or higher presenting after unprotected
intercourse, levonorgestrel is no more effective than no treatment.
Ulipristal acetate appears to retain its efficacy at higher BMI levelsbut is no more effective than no treatment at a BMI of 35 or higher
(There is no clinical concern about the loss of ef-
Despite the limitations of the original data, this study contributes to
fectiveness of the IUD with an increase in BMI; therefore, an IUD
the literature and to clinical practice by providing the most compre-
would be a particularly good choice for obese women presenting
hensive review to date of the efficacy of IUDs used for emergency
contraception. These results provide clear evidence that IUDs are
Several recent studies exploring the awareness of and the interest in
a highly effective method of emergency contraception, as 99.86%
IUDs among women seeking emergency contraception identified bar-
of users overall did not become pregnant after unprotected inter-
riers to a greater use of IUDs including cost, waiting time (patients are
course when an IUD was inserted post-coitally. When we exclude
not always able to get an IUD the day that they present for emergency
the data from the Egyptian study (which does not represent the
contraception), low levels of awareness and understanding among
typical clinical scenario because the investigators intentionally
patients and lack of participation among providers (
selected women who were at a greater risk of pregnancy), the
). Two of these studies found that around 12% of women pre-
The cost, clinical protocols and lack of awareness among both
senting for emergency contraception or walk-in pregnancy testing
patients and providers are barriers to a greater uptake of IUDs for
would consider an IUD as an alternative to emergency contraceptive
emergency contraception. Increasing the use of IUDs for emergency
contraception is an important strategy for reducing an individual
considerable potential to increase IUD uptake among women who
woman’s chance of becoming pregnant after unprotected intercourse.
have recently had unprotected sex. A study of contraceptive providers
In addition, if left in place for ongoing contraception, copper IUDs
in CA, USA, showed that 85% of clinicians never recommended the
provide highly effective contraception for at least 10 years, and can
IUD for emergency contraception, and 93% require at least two
contribute to decreasing unintended pregnancy rates over the long
term. Therefore, we conclude that IUDs should be routinely included
Our review has several limitations. The initial intention of this study
as an emergency contraceptive option whenever clinically feasible and
was to assess the efficacy of IUDs for emergency contraception by the
day of insertion (how many days had elapsed between unprotectedintercourse and insertion of the IUD), but the studies generally didnot include sufficient detail about the day of insertion among the
efficacy-evaluable population. Therefore, our analysis groups allcases together, regardless of the length of delay between intercourse
K.C. conducted the English literature search, abstracted data from the
and insertion of the IUD. Similarly, we are unable to provide estimates
English literature and drafted the article. H.Z. conducted the Chinese
of the efficacy by parity, individual pregnancy risk (the cycle day on
literature search, abstracted data from the Chinese literature and pro-
which intercourse occurred) and IUD type, as most studies did not
vided comments on the manuscript. N.G. abstracted data from the
provide detailed information on these variables. Finally, as in any
English literature and provided comments on the manuscript. L.C.
review, it is possible that studies may have been unintentionally
abstracted data from the Chinese literature and provided comments
excluded owing to incomplete search results. We were not able to
on the manuscript. J.T. oversaw the quantitative analysis and provided
include publications in languages other than English and Chinese; it
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Principal Investigator/Program Director (Last, First, Middle) : CURRICULUM VITAE Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. Michel DRANCOURT Professeur des Universités - Praticien Hospitalier EDUCATION/TRAINING (Begin with baccalaureate o
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