The New England Journal of Medicine

Original Article
Volume 345:561-567

August 23, 2001

Number 8
Use of Copper Intrauterine Devices and the Risk of Tubal Infertility among
Nulligravid Women
David Hubacher, Ph.D., Roger Lara-Ricalde, M.D., Douglas J. Taylor, Ph.D.,
Fernando Guerra-Infante, Ph.D., and Raymundo Guzman-Rodriguez, M.D.

ABSTRACT
Background Previous studies of intrauterine devices (IUDs), many of which
are no longer in use, suggested that they might cause tubal infertility. The
concern that IUDs that contain copper — currently the most commonly used
type — may increase the risk of infertility in nulligravid women has limited
the use of this highly effective method of birth control.
Methods We conducted a case–control study of 1895 women recruited between
1997 and 1999. We enrolled 358 women with primary infertility who had tubal
occlusion documented by hysterosalpingography, as well as 953 women with
primary infertility who did not have tubal occlusion (infertile controls)
and 584 primigravid women (pregnant controls). We collected information on
the women's past use of contraceptives, including copper IUDs, previous
sexual relationships, and history of genital tract infections. Each woman's
blood was tested for antibodies to Chlamydia trachomatis. We used stratified
analyses and logistic regression to assess the association between the
previous use of a copper IUD and tubal occlusion.
Results In analyses involving the women with tubal occlusion and the
infertile controls, the odds ratio for tubal occlusion associated with the
previous use of a copper IUD was 1.0 (95 percent confidence interval, 0.6 to
1.7). When the primigravid women served as the controls, the corresponding
odds ratio was 0.9 (95 percent confidence interval, 0.5 to 1.6). Tubal
infertility was not associated with the duration of IUD use, the reason for
the removal of the IUD, or the presence or absence of gynecologic problems
related to its use. The presence of antibodies to chlamydia was associated
with infertility.
Conclusions The previous use of a copper IUD is not associated with an
increased risk of tubal occlusion among nulligravid women, whereas infection
with C. trachomatis is.
  _____

Intrauterine devices (IUDs) have long been believed to cause pelvic
inflammatory disease and subsequent tubal infertility. Many IUDs were
withdrawn from the market in the United States and other countries because
of concern about safety, and the use of one — the Dalkon Shield — was
eventually shown to be strongly associated with pelvic inflammatory disease.
Copper-containing IUDs were first approved for use in the United States in
1976 and are still being marketed. Lingering concern about the potential
risks of IUDs has discouraged women — particularly those who have never been
pregnant — from using even copper devices.
Research on IUDs in the 1970s and 1980s was marked by confusion and
controversy. Two early reports from the Women's Health Study in the United
States showed that the use of an IUD increased the risk of pelvic
inflammatory disease by at least 60 percent, 1
<http://content.nejm.org/cgi/content/full/345/8/#R1> , 2
<http://content.nejm.org/cgi/content/full/345/8/#R2>  although subsequent
reanalyses suggested a less marked increase in risk. 3
<http://content.nejm.org/cgi/content/full/345/8/#R3> , 4
<http://content.nejm.org/cgi/content/full/345/8/#R4> , 5
<http://content.nejm.org/cgi/content/full/345/8/#R5>  The Oxford Family
Planning Association contraceptive study 6
<http://content.nejm.org/cgi/content/full/345/8/#R6> , 7
<http://content.nejm.org/cgi/content/full/345/8/#R7>  initially reported
that IUD use increased the risk of pelvic inflammatory disease by a factor
of 10 ; however, a refined analysis using better comparison groups and
separating results according to the type of device found no significant
increase in the risk of pelvic inflammatory disease with medicated devices
such as copper IUDs. 8 <http://content.nejm.org/cgi/content/full/345/8/#R8>
More recent studies by the World Health Organization 9
<http://content.nejm.org/cgi/content/full/345/8/#R9>  and by a team of
researchers in the United States 10
<http://content.nejm.org/cgi/content/full/345/8/#R10>  found that the
incidence of pelvic inflammatory disease among IUD users is less than 2
episodes per 1000 years of use, consistent with conservative estimates of
the incidence of pelvic inflammatory disease in the general population. 11
<http://content.nejm.org/cgi/content/full/345/8/#R11>  A recent
meta-analysis of 36 studies concluded that the use of any IUD is positively
associated with pelvic inflammatory disease. 12
<http://content.nejm.org/cgi/content/full/345/8/#R12>  Good evidence
suggests that the increase in the risk of pelvic inflammatory disease
associated with IUD use is related only to the process of inserting the
device and that after the first month of use, the risk of infection is not
significantly higher than that in women without IUDs. 13
<http://content.nejm.org/cgi/content/full/345/8/#R13>
The recognized association between pelvic inflammatory disease and tubal
infertility 14 <http://content.nejm.org/cgi/content/full/345/8/#R14>  has
aroused some concern that the use of an IUD may lead to this complication.
Two case–control studies in the United States published more than 15 years
ago 15 <http://content.nejm.org/cgi/content/full/345/8/#R15> , 16
<http://content.nejm.org/cgi/content/full/345/8/#R16>  reported positive
associations between IUD use and tubal infertility. In subanalyses
evaluating the risk according to the type of IUD used, copper devices were
reported to increase the risk of tubal infertility in one study 16
<http://content.nejm.org/cgi/content/full/345/8/#R16>  (though only among
women with more than one sexual partner) but not in the other 15
<http://content.nejm.org/cgi/content/full/345/8/#R15> ; however, later
reanalysis of the data in the second study suggested an increased risk of
infertility associated with the copper IUD. 17
<http://content.nejm.org/cgi/content/full/345/8/#R17>  Since then, numerous
case–control studies 18
<http://content.nejm.org/cgi/content/full/345/8/#R18> , 19
<http://content.nejm.org/cgi/content/full/345/8/#R19> , 20
<http://content.nejm.org/cgi/content/full/345/8/#R20> , 21
<http://content.nejm.org/cgi/content/full/345/8/#R21>  and cohort studies 22
<http://content.nejm.org/cgi/content/full/345/8/#R22> , 23
<http://content.nejm.org/cgi/content/full/345/8/#R23> , 24
<http://content.nejm.org/cgi/content/full/345/8/#R24> , 25
<http://content.nejm.org/cgi/content/full/345/8/#R25>  have attempted to
clarify the relation, but controversy has persisted.
Methods
We conducted an unmatched case–control study in three public hospitals in
Mexico City, Mexico (the National Perinatology Institute, Gynecology and
Obstetrics Hospital Number 4 of the Mexican Social Security Institute, and
the Women's Hospital). All consecutive nulligravid, infertile women 18 years
of age or older who were scheduled for diagnostic hysterosalpingography were
invited to participate. Infertility was defined by the failure to conceive
after one year or more of unprotected intercourse. Criteria for exclusion
included previous pregnancy, tubal sterilization, and previous diagnostic
laparoscopy. After undergoing hysterosalpingography, the infertile women
were classified on the basis of the radiologic evidence as women with tubal
occlusion (case subjects) or as infertile controls. From the same hospitals,
we recruited a second control group consisting of primigravid women in their
first or second trimester. In face-to-face interviews lasting an average of
20 minutes, all participants were asked about their past use of
contraceptives, previous sexual relationships, and history of genital tract
infections; the interviews with the infertile women were conducted before
they knew whether they had tubal occlusion. The instruments for recording
the results of hysterosalpingography were adapted from the recommendations
of the American Fertility Society (now the American Society for Reproductive
Medicine). 26 <http://content.nejm.org/cgi/content/full/345/8/#R26>
Participants also donated a sample of blood to be tested for antibodies to
Chlamydia trachomatis. The institutional review boards of Family Health
International and the participating hospitals approved the study; written
informed consent was obtained from all enrolled women. Recruitment began in
September 1997 and was completed in October 1999; data analysis was
completed in December 2000.
We recruited 1311 infertile women (358 women with tubal occlusion and 953
controls) and 584 pregnant controls; fewer than 5 percent of the women who
met the eligibility criteria declined to participate. We designed the study
to have 90 percent power to detect a doubling of the risk of tubal occlusion
with IUD use in analyses involving the infertile controls; the study had 87
percent power to detect a doubling of the risk in analyses involving the
pregnant controls (two-sided test, 0.05 alpha level). 27
<http://content.nejm.org/cgi/content/full/345/8/#R27>  If we set the power
at the standard 80 percent level, we had enough study subjects to detect
odds ratios of 1.8 and 1.9 in analyses involving the infertile controls and
the pregnant controls, respectively.
Before recruitment began, the radiologists met to standardize their approach
to classifying tubal pathology. Tubal occlusion was diagnosed if a
water-based contrast medium failed to spill from either tube into the
peritoneal cavity. Fluoroscopy was used, and the last films were taken 15
minutes after the contrast medium had been injected. The radiologists were
unaware of the information collected in the women's interviews.
Serologic tests for detecting antibodies to chlamydia are accepted measures
of past infection. 28 <http://content.nejm.org/cgi/content/full/345/8/#R28>
, 29 <http://content.nejm.org/cgi/content/full/345/8/#R29> , 30
<http://content.nejm.org/cgi/content/full/345/8/#R30>  An indirect
fluorescent IgG antibody–staining kit (Hemagen Diagnostics, Columbia, Md.)
was used to process the serum samples. As in previous studies using these
kits, samples that tested positive at dilutions of 1:256 were considered
diagnostic of past exposure to C. trachomatis. 31
<http://content.nejm.org/cgi/content/full/345/8/#R31>  All serum samples
were processed as recommended by the manufacturer.
Our primary exposure variable was the previous use or nonuse of an IUD
containing copper. Other variables that were considered as possibly
predictive of tubal infertility included the presence or absence of
antibodies to C. trachomatis, the number of lifetime sexual partners, the
presence or absence of a history of genital tract infections, the presence
or absence of a history of gynecologic symptoms suggestive of infection, the
past use or nonuse of other methods of contraception, family income,
education, employment status, and the presence or absence of a history of
coitus during the teenage years. Regarding their most recent sexual partners
(up to six), the women were asked about the length of the relationship and
whether they believed their partners had engaged in concurrent sexual
relations with other women. To adjust for age, we used the age when the
infertile women first suspected they were unable to conceive and the age
when the pregnant women first began attempting to conceive. We excluded from
the analyses exposure that occurred after the onset of infertility.
We classified women into one of six mutually exclusive groups on the basis
of use of contraceptive methods: no previous method (or rhythm or
withdrawal), condoms only, vaginal spermicides only, hormonal methods only
(oral or injectable contraceptives), condoms and hormonal methods, and IUDs
(none of the women reported a history of diaphragm use). If a previous user
of vaginal spermicides had also used one of the other methods, she was
assigned to the group that used that other method. All women who had used an
IUD reported having used a device containing copper. The vast majority of
the copper IUDs used by the women in the study were T-shaped (containing
either 220 mm2 or 380 mm2 of copper surface). Data were collected on the
duration of use of a given method, any gynecologic problems that occurred
during its use, and the reasons for the discontinuation of its use.
We calculated crude and adjusted odds ratios (with 95 percent confidence
intervals) as measures of the association between IUD use and tubal
occlusion. Logistic regression was used to control for other factors
simultaneously.
Results
The infertile women with tubal occlusion (case subjects) and the infertile
controls were similar in terms of level of education, employment status,
family income, and number of months spent attempting to conceive ( Table 1
<http://content.nejm.org/cgi/content/full/345/8/#T1> ). As compared with the
women with tubal occlusion, the pregnant controls were younger, better
educated, and less likely to work outside the home and had lower family
incomes.


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Table 1. Selected Characteristics of the Infertile and Pregnant Women.

The prevalence of the possible risk factors for tubal occlusion was similar
among the women with tubal occlusion and the infertile controls ( Table 2
<http://content.nejm.org/cgi/content/full/345/8/#T2> ). However, as compared
with the women with tubal occlusion, the pregnant controls had had more
sexual partners, were more likely to report suspected infidelity by
partners, and had lower rates of previous upper genital tract infection,
symptoms of pelvic inflammatory disease, and positive tests for antibodies
to chlamydia.


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[in this window] <http://content.nejm.org/cgi/content/full/345/8/561/T2>
[in a new window] <http://content.nejm.org/cgi/content-nw/full/345/8/561/T2>

Table 2. Possible Risk Factors for Tubal Occlusion.

When no previous contraceptive use was defined as the reference category,
previous use of a copper IUD was not associated with an increased risk of
tubal occlusion either in the analysis including the infertile controls
(odds ratio, 1.0; 95 percent confidence interval, 0.6 to 1.6) or in the
analysis including the pregnant controls (odds ratio, 0.7; 95 percent
confidence interval, 0.4 to 1.2) ( Table 3
<http://content.nejm.org/cgi/content/full/345/8/#T3> ). In the latter
analysis, women whose sexual partners used condoms had a 50 percent lower
risk of tubal occlusion than those who used no contraception.


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[in this window] <http://content.nejm.org/cgi/content/full/345/8/561/T3>
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Table 3. Previous Use of Contraceptives and the Risk of Tubal Occlusion.

Similarly, when no previous IUD use was defined as the reference category,
previous use of a copper IUD was not associated with tubal occlusion in the
analyses including either the infertile controls (odds ratio, 1.0; 95
percent confidence interval, 0.6 to 1.7) or the pregnant controls (odds
ratio, 0.9; 95 percent confidence interval, 0.5 to 1.6) ( Table 4
<http://content.nejm.org/cgi/content/full/345/8/#T4> ). A longer duration of
use of a copper IUD, the removal of the IUD because of side effects, and a
history of gynecologic symptoms during the use of a copper IUD were not
associated with increased odds of tubal occlusion.


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[in this window] <http://content.nejm.org/cgi/content/full/345/8/561/T4>
[in a new window] <http://content.nejm.org/cgi/content-nw/full/345/8/561/T4>

Table 4. History of Use of a Copper IUD and the Risk of Tubal Occlusion.

The presence of antibodies to C. trachomatis among women who had not used a
copper IUD was associated with tubal occlusion (odds ratio, 2.4; 95 percent
confidence interval, 1.7 to 3.2) in the analysis including the pregnant
controls ( Table 5 <http://content.nejm.org/cgi/content/full/345/8/#T5> ).
Among women who had used an IUD, there was no significant association
between antibodies to C. trachomatis and tubal infertility, but there were
relatively few women in this group.


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[in this window] <http://content.nejm.org/cgi/content/full/345/8/561/T5>
[in a new window] <http://content.nejm.org/cgi/content-nw/full/345/8/561/T5>

Table 5. Use of a Copper IUD, the Presence of Antibodies to Chlamydia
trachomatis, and the Risk of Tubal Occlusion.

We considered using a broader definition of a case to include either tubal
occlusion or adhesions, but hysterosalpingography has a limited ability to
identify adhesions. 32 <http://content.nejm.org/cgi/content/full/345/8/#R32>
, 33 <http://content.nejm.org/cgi/content/full/345/8/#R33>  To address the
concern that our case group was defined too narrowly because we excluded
women who had adhesions only, we performed an additional analysis. This
analysis involved reclassifying as case subjects the infertile controls who
had no occlusion but had adhesions identified on hysterosalpingography and
positive serologic tests for C. trachomatis. Previous research suggests that
serologic testing for chlamydia may improve the accuracy of the diagnosis of
tubal disease when used in conjunction with, or even in place of,
hysterosalpingography. 34
<http://content.nejm.org/cgi/content/full/345/8/#R34> , 35
<http://content.nejm.org/cgi/content/full/345/8/#R35>  After this
reclassification, the adjusted odds ratios for tubal infertility associated
with IUD use were 1.2 (95 percent confidence interval, 0.7 to 1.9) for the
analysis including the infertile controls and 1.0 (95 percent confidence
interval, 0.6 to 1.5) for that including the pregnant controls.
Although hysterosalpingography is the standard method for evaluating tubal
patency, 36 <http://content.nejm.org/cgi/content/full/345/8/#R36>  it has
some diagnostic limitations that laparoscopy does not have. Of the 1311
infertile women in our study, only 321 (24 percent) underwent laparoscopy.
Those with abnormal results on hysterosalpingography were twice as likely as
women with negative results to undergo laparoscopy. Using the laparoscopy
reports, we divided this subgroup into 185 women with any evidence of tubal
disease, including adhesions, and 136 infertile controls with no evidence of
tubal disease. The adjusted odds ratio for tubal infertility associated with
previous IUD use was 1.5 (95 percent confidence interval, 0.7 to 3.5) in
analyses including the infertile controls and 1.9 (95 percent confidence
interval, 1.0 to 3.5) in analyses using the pregnant controls.
Discussion
Our finding that the use of a copper IUD was not a risk factor for tubal
occlusion among nulligravid women contradicts some previous reports that
aroused concern about future fertility in women who use copper IUDs. 15
<http://content.nejm.org/cgi/content/full/345/8/#R15> , 16
<http://content.nejm.org/cgi/content/full/345/8/#R16>  Given the media
attention to the problems with the Dalkon Shield and the associated
litigation in U.S. courts during the 1970s and 1980s, women who were
infertile and had previously used an IUD may have been more inclined to
investigate the cause of their condition than infertile women who had never
used an IUD. Consequently, women with a history of IUD use may have been
disproportionately represented in previous studies in the United States of
women with tubal infertility. In contrast, our study was conducted in
Mexico, where IUD use is well accepted and where such bias is unlikely to
occur.
Past research on this topic used only primigravid women as controls. We
included an infertile control group for several reasons. First, we wanted to
ensure that the women with tubal occlusion came from the same population as
the controls. Second, this approach minimizes bias due to the differential
recall of IUD use according to diagnosis. We also included a control group
of pregnant women to address the association between IUD use and the
inability to conceive.
Exposure to C. trachomatis has been cited as an important cause of tubal
infertility. 21 <http://content.nejm.org/cgi/content/full/345/8/#R21> , 37
<http://content.nejm.org/cgi/content/full/345/8/#R37>  We found higher rates
of positive tests for antibodies to chlamydia, a validated marker of past
exposure, 28 <http://content.nejm.org/cgi/content/full/345/8/#R28> , 29
<http://content.nejm.org/cgi/content/full/345/8/#R29> , 30
<http://content.nejm.org/cgi/content/full/345/8/#R30>  among women with
tubal occlusion and among infertile controls than among pregnant women. A
weakness of the antibody test is that it does not indicate whether exposure
to C. trachomatis preceded the onset of tubal disease, although it is likely
that it did. The fact that the prevalence of antibodies was similar among
women with tubal occlusion and infertile controls is not surprising, since
the infertile controls may have had other evidence of disease attributable
to chlamydia, such as adhesions, which are not readily detectable by
hysterosalpingography. 32
<http://content.nejm.org/cgi/content/full/345/8/#R32> , 33
<http://content.nejm.org/cgi/content/full/345/8/#R33>  Thus, it is possible
that previous studies found an increased risk of tubal infertility
associated with the use of a copper IUD because of the unmeasured
confounding effect of exposure to sexually transmitted disease —
specifically, C. trachomatis.
Laparoscopy is another diagnostic procedure for women with infertility. The
decision about whether to undergo laparoscopy is an individual one that
depends on clinical findings (including those from hysterosalpingography)
and other factors, such as the presence or absence of a history of pelvic
pain. In our study, only one quarter of the women underwent laparoscopy,
including a disproportionate number of those with abnormal results on
hysterosalpingography. The adjusted odds ratios for tubal infertility
according to the analysis of the women who underwent laparoscopy, although
higher than those calculated on the basis of all the women who underwent
hysterosalpingography, were not inconsistent with the results of the primary
analysis, and the differences between these ratios may reflect selection
bias. An unbiased study in which laparoscopy was required for the
identification of cases would not be feasible because of its cost, the time
it would consume, and the ethical problems it would raise. Our analysis,
based on hysterosalpingographic results, focused on damage to the lumen of
the fallopian tubes; it is unlikely that we found no increased risk
associated with IUD use simply because copper IUDs affect only structures
exterior to the fallopian tubes.
More than 100 million women worldwide use IUDs. Asia accounts for the
majority of use, but IUD use is also common among married women of
reproductive age in Scandinavian countries (prevalence, 18 percent) and in
other European countries (7 percent). 38
<http://content.nejm.org/cgi/content/full/345/8/#R38>  In contrast, only 1
percent of women in the United States use the IUD. 39
<http://content.nejm.org/cgi/content/full/345/8/#R39>  This low rate is
thought to reflect the widespread concern about health risks associated with
the method. In lieu of using an IUD, women may prematurely request
sterilization (and may regret it later 40
<http://content.nejm.org/cgi/content/full/345/8/#R40> , 41
<http://content.nejm.org/cgi/content/full/345/8/#R41> ), choose less
effective or less convenient methods, or risk an unwanted pregnancy.
This study suggests that the use of copper IUDs is much safer than was
previously thought. Nulligravid women who are not at risk for a sexually
transmitted disease are appropriate candidates for the copper IUD.
Contemporary copper IUDs may be among the safest, most effective, and least
expensive reversible contraceptives available. 42
<http://content.nejm.org/cgi/content/full/345/8/#R42> , 43
<http://content.nejm.org/cgi/content/full/345/8/#R43>
<http://weeklybriefings.org/feature.asp?strXmlDoc=3450802>
Supported by the U.S. Agency for International Development (USAID) through a
contract with Family Health International (contract CCP-A-00-95-00022-02)
and by the National Institute for Child Health and Human Development,
National Institutes of Health, through an Interagency Agreement
(Y1-HD-7230-01) with USAID. This article does not necessarily reflect the
views or policies of the Department of Health and Human Services or of
USAID, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. government.
We are indebted to the participants for making this research possible and to
Rocío Dávila-Mendoza, Dr. Zigor Campos-Goenaga, Dr. Maria del Carmen
Tavera-Hernández, Maria Elena Guevara-Reyes, Enimia Zárate-Aragón, Bersabe
Bautista-García, Deborah Cousins, Dr. Jaroslav Hulka, Cathy Dudnanski,
Carmen Cardenas-Lopez, Dr. David Grimes, Dr. Ken Schulz, Dr. Julio de la
Jara, Dr. Esteben Garcia, Dr. Alonso Garcia-Luna, Marie McLeod, and Research
Triangle Institute.

Source Information
From Family Health International, Research Triangle Park, N.C. (D.H.,
D.J.T.); and the National Perinatology Institute, Mexico City, Mexico
(R.L.-R., F.G.-I., R.G.-R.).
Address reprint requests to Dr. Hubacher at Family Health International,
P.O. Box 13950, Research Triangle Park, NC 27709, or at [log in to unmask]
<mailto:[log in to unmask]> .
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BEditorial
Volume 345:608-610

August 23, 2001

Number 8
Time to Pardon the IUD?

The report in this issue of the Journal on the effect of copper intrauterine
contraceptive devices on the risk of infertility in nulliparous women
deserves the attention of American women and their clinicians. 1
<http://content.nejm.org/cgi/content/full/345/8/#R1>  Despite the efficacy
of the intrauterine device (IUD) in preventing pregnancy, concern that the
use of an IUD may cause pelvic infection and infertility has made it a
contraceptive option that is rarely used in the United States.
Hubacher et al. report the results of a case–control study involving nearly
2000 women in Mexico City, Mexico. 1
<http://content.nejm.org/cgi/content/full/345/8/#R1>  The study compared
nulligravid infertile women who had tubal occlusion with infertile women who
did not have tubal occlusion, as well as with pregnant women, in terms of
the previous use of IUDs and other potential risk factors for infertility.
They also tested the women for the presence of antibodies to Chlamydia
trachomatis, the most important contributor to infertility. The authors
found no increase in the risk of tubal occlusion associated with the
previous use of copper IUDs; in analyses involving the infertile controls,
the odds ratio associated with the use of a copper IUD was 1.0 (95 percent
confidence interval, 0.6 to 1.7), and similar results were found in analyses
involving the pregnant controls. By contrast, there was a strong association
between previous chlamydial infection and infertility in these women. This
important study could not have been conducted in the United States, because
nulliparous women rarely use intrauterine contraception here, and even women
in this country who have already borne a child have tended to shun these
devices, but the results should change current opinion about copper IUDs.
The use of intrauterine contraception has declined in the United States even
as it has increased in the rest of the world. Thirty years ago, nearly 10
percent of women in the United States who used contraception chose IUDs, but
now less than 1 percent do so. In contrast, more than one in five women in
Denmark and Germany use IUDs. Reluctance to use IUDs and other highly
effective methods of contraception is one reason why, by the end of their
childbearing years, nearly half of the women in the United States (46
percent) have had at least one elective abortion, and 27 percent have
undergone surgery for sterilization. These rates are about three times as
high as those in western Europe.
It is ironic that the modern IUD, now largely rejected here, was developed
by gynecologists in the United States, and its use was a routine part of
gynecologic practice in this country 30 years ago. What changed? Research to
create IUDs that caused less menstrual pain and bleeding, the principal
reasons why women had the devices removed, led to the development of the
infamous Dalkon Shield, a poorly designed and poorly tested device designed
to accommodate nulliparous women. Introduced just at the time the danger of
venous thrombosis associated with oral contraceptives was becoming widely
publicized, the Dalkon Shield appealed to sexually active young women.
I and many other gynecologists inserted the new Dalkon Shield, with its
spiny margins and braided tail, in our young patients because we thought it
would be better tolerated than earlier IUDs by a uterus that had never
sustained a pregnancy and because we had been deceived about its efficacy. 2
<http://content.nejm.org/cgi/content/full/345/8/#R2>  We did not worry about
health risks because IUDs were considered safe on the basis of early
research. 3 <http://content.nejm.org/cgi/content/full/345/8/#R3> , 4
<http://content.nejm.org/cgi/content/full/345/8/#R4>  The Food and Drug
Administration (FDA) was not yet responsible for evaluating the safety of
such devices in clinical trials.
Our complacency was disturbed in 1973 when the Family Planning Evaluation
Division at the Centers for Disease Control reported several deaths due to
pelvic infection related to the use of IUDs. 5
<http://content.nejm.org/cgi/content/full/345/8/#R5> , 6
<http://content.nejm.org/cgi/content/full/345/8/#R6>  Subsequent
retrospective case–control studies linked IUDs with sexually transmitted
infections, which had become a major cause of infertility. 7
<http://content.nejm.org/cgi/content/full/345/8/#R7> , 8
<http://content.nejm.org/cgi/content/full/345/8/#R8>  Further research found
a direct relation between IUD use and infertility due to tubal occlusion. 9
<http://content.nejm.org/cgi/content/full/345/8/#R9> , 10
<http://content.nejm.org/cgi/content/full/345/8/#R10>  These reports formed
the foundation for litigation, first against the sellers of the Dalkon
Shield and then against other companies that manufactured IUDs. Although the
FDA forced only the Dalkon Shield from the market, the other U.S.
manufacturers abandoned sales in order to avoid legal costs. As a result, no
IUDs were sold in the United States between 1983 and 1988, and many women,
frightened by reports of infection and infertility, had their IUDs removed.
Soon, teaching about contraception condemned IUDs, and the few physicians
who still trusted intrauterine contraception had neither devices to insert
nor patients who wanted them.
In the rest of the world, however, intrauterine contraceptive devices
continued to be used, and ongoing research resulted in better devices. One,
the copper T 380 (with 380 mm2 of copper surface), was introduced to an
empty U.S. market in 1988 by a company too small to attract litigation or,
initially, many customers. This device (which goes under the trade name
ParaGard) is the only copper IUD available in the United States but is one
of several used in Mexico and other countries. Although few IUDs were
provided to women in the United States during the past 20 years, reanalyses
of previously collected data and new retrospective case–control studies have
helped to identify the characteristics of IUDs and their users that were
associated with pelvic infection and infertility. 11
<http://content.nejm.org/cgi/content/full/345/8/#R11>  The use of the Dalkon
Shield was associated with a much higher relative risk of pelvic infection
than any of the others (eight times as high), indicating that its inclusion
in previous studies had inflated the risk associated with IUDs in general.
12 <http://content.nejm.org/cgi/content/full/345/8/#R12>  Other results
demonstrated that women in relationships that were more likely to be
exclusive (marriage or cohabitation) were not at increased risk, 13
<http://content.nejm.org/cgi/content/full/345/8/#R13>  supporting the
contention that "men, not IUDs," cause pelvic infection.
Because pelvic infection can occlude the oviducts and cause infertility,
epidemiologists in Seattle and Boston examined the relation between previous
IUD use and subsequent tubal infertility. 9
<http://content.nejm.org/cgi/content/full/345/8/#R9> , 10
<http://content.nejm.org/cgi/content/full/345/8/#R10>  It is with these two
case–control studies, published in the Journal 16 years ago, that the report
in this week's issue of the Journal should be compared. Neither found a
significantly increased risk of tubal infertility associated with the use of
a copper IUD (relative risk, 1.5 [95 percent confidence interval, 0.8 to
3.0] and 1.3 [95 percent confidence interval, 0.6 to 3.0], respectively),
and both determined that IUDs made of plastic did increase the risk.
Although the 95 percent confidence intervals span 1.0 (indicating no
increased risk), the point estimates were used to indict copper IUDs along
with all other types.
The finding of the present study that exposure to chlamydia is associated
with infertility provides an explanation for previous reports of an
increased risk of pelvic infection among women who were not involved in
exclusive relationships and an increased risk associated with the insertion,
but not the prolonged use, of IUDs. 14
<http://content.nejm.org/cgi/content/full/345/8/#R14>  At the time of these
earlier studies, 9 <http://content.nejm.org/cgi/content/full/345/8/#R9> , 10
<http://content.nejm.org/cgi/content/full/345/8/#R10>  C. trachomatis was
not recognized as an important cause of tubal infertility.
No matter what form of contraception a woman chooses, the increasing
prevalence of chlamydia and other sexually transmitted pathogens, including
the human immunodeficiency virus, means that condoms should be used with
high-risk partners. But the findings reported by Hubacher et al. should
reassure clinicians and women alike that copper IUDs, which are by far the
most common type of IUD used in the United States and around the world, are
not a threat to the health or future fertility of the women who use them,
including those without children.

Philip D. Darney, M.D.
University of California, San Francisco
San Francisco, CA 94110
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Edward E. Rylander, M.D.
Diplomat American Board of Family Practice.
Diplomat American Board of Palliative Medicine.