CONTRACEPTION

EFFECTIVENESS OF IUDs: A REVIEW

Irving Sivin and Frederick Schmidt

The Population Council

1230 York Avenue
New York, New York 10021

ABSTRACT

Large, multicenter, randomized trials of IUDs conducted between 1970

and 1986 encompass more than 50,000 woman-years of experience in the two-
year interval following device insertion. Taken singly and collec-
tively, these trials demonstrate that IUD failure rates are strongly
affected by the age of participants , notably by the proportion of women
under age 25 admitted to the studies. Individual trials and overall
comparisons indicate further that:

1. Non-medicated devices such as the Mahua steel ring and Lippes

loop D have pregnancy rates above 2 per 100 woman-years.

2. The first approved copper IUD% the Copper 7 and the TCu 200, do
not markedly differ in pregnancy rates from standard plastic devices
with rates significantly above 2 per 100 woman-years.

3. Five more recent, widely used copper IUDs have had faflure rates
significantly below 2 per 100 woman-years in mult1center trials. The
point estimate of the failure rate was less than 1 pregnancy per 100
woman-years for three of these IUDs. One copperbearing device had a
failure rate significantly below 1 per 100 woman-years.

4. Devices releasing either 25 mcg/day of progesterone or 2 mcg/day

of levonorgestrel have had significantly higher failure rates than the
more effective copperreleasing IUDs; however, devices releasing 20
mcg/day of levonorgestrel appear at least as effective as the most
effective copper IUDs.

Long-term IUD failure rates derived from straight assignment as well

as randomized trials indicate 4-year gross cumulative failure rates do
not exceed 10 per 100 for any of the standard copper devices or the
Lippes loop D. Point estimates of the four-year gross cumulative preg-
nancy rates have been below 5 per 100 users in studies of the TCu 22OC,
the Nova T, the TCu 380A1 and the MLCu 375.

JULY 1987 VOL. 36 NO. I 55

CONTRACEPTION

INTRODUCTION

Overwhelming evidence has accrued to establish the proposition that

failure rates of intrauterine contraceptive devices'average below or
well below 5 per 100 WOrnen per year (12). Repeated studies have also
shown that among groups of women who adopt reversible methods of contra-
ception, users of intrauterine contraceptive devices tend to have the
highest continuation rates (3-7). These factors, effectiveness, pro-
longed use and acceptability, together with the moderate cost of devices
have permitted the IUD to play a major role in family planning
throughout the world.

MATERIALS AND METHODS

We review here and more closely define the performance of classes

and of specific types of IUDs with respect to effectiveness. The two
broad classes of devices, medicated and non-medicated, may each be
divided into two groups. Ring devices, usually made of stainless steel,
and plastic devices constitute the non-medicated devices. Copper-
releasing and steroid-releasing IUDs are the medicated devices. The
review focuses on the small number of devices which are in widespread
use, both those in production today and a few models whose production
has ceased recently. Studies of steroid devices include some which do
not have regulatory approval. The analysis centers on the performance
of IUDs in large, multicenter, randomized trials but utilizes supporting
data from other randomized trials or from cohort studies. By multi-
center we mean the involvement of at least three clinics, with essen-
tially equal numbers of women. By large we mean that the trial measured
or enrolled at least 300 women per device. (A 3 per 100 failure rate
with 300 in the trial would have a standard error of 1 per 100.1 There
are relatively few such studies in the literature, most undertaken by
organizations involved in developing and testing new contraceptives: the
World Health Organization (WHO), the Population Council, or Family
Health International (FHI).

The protocols for these multicenter studies, as indicated by state-

ments of methods and materials, have been similar in that the subjects
had no physical contraindication to IUD user most accepted an IUD for
the first time within the pregnancy interval, and have been followed for
one segment. No studies of immediate or very early postpartum inser-
tions have been included in the general summary because the practice is
uncommon, because few devices have been studied in randomized trials,
and because one-year failure rates may be lowered by prolonged lacta-
tional amenorrhea.

The studies reviewed have published failure rates for one or two
years of use and sometimes for both. Not all large studies have been
carried to two years, however, and not all two-year studies have pub-
lished one-year data. A preferred statistic for summary of these data
by device and for comparison of devices is the single decrement life
table rate computed at one and at two years. Single decrement rates are
"net probabilitiesw or "net rates" in the WHO nomenclature and are

56 JULY 1987 VOL. 36 NO. I

 CONTRACEPTION

"gross rates" in the Tietze-Potter system. Publications, some of multi-

ple decrement rates only, however lack the detail for accurate and pre-
cise computation of summary single decrement rates for each device.

On the other hand, the number of pregnancies have been published for
each comparative study or may be derived with precision by using the
published rates. standard errors and other data. Together with data on
woman-years (or months) of exposure, the pregnancy numbers permit calcu-
lation of a Pearl index for each device in a comparative study. When
confined to summaries and comparisons over short and equal time periods
for all studies, the Pearl index minimizes or avoids altogether the bias
traditionally ascribed to it. This bias, a function of heterogeneity of
risk and exposure in the study group s derives from the inordinate con-
tribution subfecund groups make to the denominator (woman-years) of the
Pearl index; a bias manifest when an index including long-term users is
compared with an index in which method use for all is short. Contrary
to our expectations however and despite the fact that we excluded
immediate and very early postpartum insertion studies, Pearl indices in
the second year were higher than in the first year in 17 (68%) of the 25
multicentered copper IUD trials which had both one-and two-year data.
In only seven (28%) of these studies did second year Pearl pregnancy
rates decline. (The two-sided binomial probability of these observa-
tions is P = .06.) It thus becomes incumbent to show both one- and two-
year Pearl indices for uniform summary and comparison. The index allows
for Chi-square tests of the homogeneity of the studies of each device.
The index may be viewed as a whazardn rate computed on an annual rather
than on a smaller time unit. Given the low risks of failure of contem-
porary IUDs, this index mirrors the gross rate. Controlled by uniform
and short maximum durations of user one or two years, the index is an
excellent summary statistic (7-9).

Tables II and V-XII show the Pearl index for the first year of each
large multicenter randomized trial, and a separate index computed for
two-year studies. Standard errors of the summary ongand two-year Pearl
indices for each device are shown in Table XIII for the large multicen-
tered trials, and in Tables XIV-XVI for the smaller or single center
randomized trials.

Bge Fffects

It is evident, but worth repeating. that comparative trials of IUDs

produce comparative evidence on failure rates, but not necessarily on
the effectiveness of the methods. To measure effectiveness requires a
referent group of fecund, cohabiting wcmen using no contraception. No
such groups are included in contraceptive trials. An unknown proportion
of women who are (secondarily) sterile are included in IUD trials. This
proportion increases with age more rapidly after age 30, than under that
age (10). Increased sterility with age and decreased frequency of
intercourse may account for sharply declining age-specific failure rates
in United States studies of IUDs (Fig. 11.

JULY 1987 VOL. 36 NO. 1 57

CONTRACEPTION

16

14
- STEEL RING

15-19 20-24 25-29 30-34 35+

AGE

Figure 1

TWO-YEAR GROSS CUMULATIVE PREGNANCY RATES

UNITED STATES DATA
BY DEVICE AND AGE

58 JULY 1987 VOL. 36 NO. 1

 CONTRACEPTION

Age effects on failure rates have in some cases prevented us from

seeing clearly differences that exist among devices. Allonen and his
colleagues (11) in a Scandinavian trial found that, device apart, age
and clinic or country were the factors significantly affecting the
observed failure rates. They found in examining pregnancy rates that
"the risk ratio was 0.9 per year of age. ItThis coefficient implies that
a woman aged 30 would have a risk of pregnancy during IUD use of only 59
percent of a woman aged 25; while a wcman aged 35 would have a risk of
only 35 percent of that of the 25-year-old woman. Neither U.S. data nor
Taiwanese data show such marked reductions in risk among younger women
as indicated by the Scandinavian analysis (Table I), but the point
remains valid. Different studies produce different results when the
ages of the population studied differ markedly, but individual American
and other studies of copper IUDs show similar pregnancy rates in year 1
and year 2 (Fig. 2). but the studies differ in the level of failure
rates. The failure rates were significantly higher in studies where the
median age was less than 25 years as compared with studies in which the
median age at admission was 25 years or older (Fig. 2).

TABLE I
Failure Risk by Age Group Relative to That
of Next Younger Age Group

One-Year
Relative- J.&X! XL-34 352

TCu 200 (27)X 1 .83 .76 .81 .lO

TCu 220C (27) 1 1.38 1.00 0
TCu 380A (27) 1 .67 .75 0
Taiwan-Loop (54) NA 1 1.02 .85 .65

Two-Year
RelativeI%&

Loop c (17) NA 1 .79 .71 .42

Loop D (17) NA 1 .78 .58 .52
Steel Ring (17) NA 1 .62 .74 .74
Taiwan-Loop (54) NA 1 1.01 .82 .50

1 = Youngest or referent group.

*Source

Allonen's (11) finding that clinical or country factors affect

observed failure rates -- age-specific failures in Finland were 1.9
times as high as in Sweden or Denmark -- is another instance of what
Mishell (12) called the clinic factor. Variation in failure rates and

JULY 1987 VOL. 36 NO. 1 59

CONTRACEPTION

2.5 -

0” 2.0 -
7

ii?
a 1.5 -

If

Fz l.O-

0.5 -

0 L
YEAR 1 2 1+2
MEDIAN AGE
AT ADMISSION <25 225 ALL AGES
(Yrs.1

Figure 2

COPPER IUDs
FIRST AND SECOND YEAR PREGNANCY RATES
PER 100 WOMAN-YEARS, BY MEDIAN AGE OF
WOMEN IN MULTICENTER RANDOMIZED STUDIES

60 JULY 1987 VOL. 36 NO. I

 CONTRACEPTION

in other aspects of IUD performance at different clinics derives from

the different training and experience of the personnel who do the inser-
tions and is affected by characteristics of the clinic population other
than age or parity, as well as by the conscious and unconscious selec-
tion criteria used. The virtue of multicenter trials is that sampling
variance ascribable to the "between clinicw factor can be controlled by
the inclusion of relatively large numbers of disparate clinics. This
variance decreases inversely -as the number of clinics in study. Our
review then begins with results from the multicenter studies. The
results are supplemented by data from cohort studies and from those of
smaller randomized trials.

RESULTS

Non-Medicated Devices

Rina Stainless steel rings are today among the most commonly
used IUDs. They are the principal type of IUD used in the People's
Republic of China (1). There has been one major multicenter, randomized
trial of rings and other IUDs. The Mahua double steel ring was compared
at five clinics in Tianjin (where these rings are made) with the TCu
220C and the TCu 380Ag (13,141. The size of the ring inserted depended
on the uterine measurement, but distribution of ring size was not
reported. The Pearl Index for the Mahua was 3.3 per 100 woman-years
(W.Y.1 in the first year and 2.7 over two years (Table II). At both one
and at two years this ring had significantly higher failure rates than
did either of the two copper devices. First segment continuation rates
were also higher for the copper devices. The median age of the women,
31.8, is the highest of any of the multicenter studies under review.
The failure rates for each of the copper devices in this study were the
lowest observed in any study of these devices. We may infer that among
younger women the failure rate of the Mahua device would likely be some-
what higher than the overall rate observed in this trial.

From Beijing, China, a second randomized trial of rings in one

clinic has been recently published (15). Here, too, rings of different
size were inserted, depending on the uterine size. The median age of
the women was high, 29.1 (Table XIV). At one year the Pearl index for
the ring device wa; 6.0 and at two years it was 4.2. In the second year
the Pearl index fell to 2.0 oer 100 W.Y. In this trial, as in the Tian-
jin study, the ring device had significantly higher failure rates than
did the Copper TCu 22OC, with which it was compared.

Tailless ring devices were used in both these Chinese studies.

Muramatsu (16) reported pregnancy rates with Ota rings in 4 prefec-

tures in Japan. These data do not derive from a randomized trial. The
results are summarized in Table III. The Japanese data may be viewed as
consistent with the Chinese in regard to pregnancy rates for ring dev-
ices, a Pearl index above 2 per 100 W.Y.

JULY 1987 VOL. 36 NO. 1 61

CONTRACEPTION

TABLE II

Pearl Pregnancy Rates in Large, Multicenter, Randomized Studies

Mahua Ring and Lippes loop D

Pearl Index
Sponsor or Median Per 100 W.Y. Woman-Years
EiiXtAuthor &Q yaarl 2XQaJXyaprl2~

-BFng
Sung, Qian 31.8 3.3 2.7 a74 1345
(13,141

Pop. Council (19) <25 3.8 480 -

WHO-vs 71220 (20) 28.2 1.9 1.9 049 1418
WHeMTP (21) 28.7 3.4 3.1 583 933
WHO-SPAB (22) 28.5 2.3 2.3 266 436

Summary 2.8 2.4 2178 2787

TABLE III

Multiple Decrement Cumulative Pregnancy Rates per 100 Women

Japanese Experience With the Ota Ring (Source 16)

District Xc1 Xc2

A 4.7 7.7
B 2.2 2.7
C 3.0 4.8
D 5.8 8.4

Prospective cohort studies in the United States showed that ring

devices had higher failure rates at each age than did the Lippes C or
Lippes D loops (Table IV) (17). The overall comparisons, whether or not
age standardized, show the Lippes C and D to have significantly lower
failure rates than did the steel ring (P<.O5).

D C. D. and Saf _-
T Coil L In the studies of Tietze and Lewit
(17) the plastic devices widely used in the U.S., Loop C, Loop D and the
Saf-T-Coil, all had two year Pearl indices of 2.0-3.0 per hundred (Table
IV). Oxford data for women 25-34 years of age for the first two years
show these devices with slightly lower failure rates (18)~ 2.3-2.4 per
hundred, than the studies in the U.S., but the data of the Oxford group

62 JULY 1987 VOL. 36 NO. 1

 CONTRACEPTION

excluded experience during the first 5 months of use. Data from Oxford
indicate, as did the U.S. data, failure rates were between 1 or 2 per
100 woman-years for wcnnen aged 35 and over (Table IV).

TABLE IV

Non-Medicated Devices: Pregnancy Data

Gross Rate or Pearl Index in Cohort Studies
Rates Per 100 in First Two Years of Use

Gross Pearl Median

&
Fata (17)

Loop A 11.7 6.3 0.8 26.9

B 7.1 3.7 0.6 26.0
C 5.1 2.8 0.3 27.0
D 4.9 2.6 0.2 27.2
Saf-T-Coil 3.8 3.0 0.4 25.7
Steel Ring 8.3 5.0 0.5 26.2

Age 25-34
Loop c 2.4 0.5
Loop D 2.3 0.6
Saf-T-Coil 2.3 0.5

Age 35+
Loop c 1.1 0.4
Loop D 1.8 0.7
Saf-T-Coil 1.6 0.5

Results of the 4 multicenter trials with the Loop D (Table II) are
quite similar to those of the cohort studies (H-22). Women in their
late twenties (median age) at initiation of Loop use experienced failure
rates over a two-year period that yielded Pearl indices of 1.9-3.1. The
overall summary index was 2.4 per 100. The one-year summary Pearl index
of 2.8 includes the Population Council's comparative study among younger
women (19). In neither the one-year studies nor in the two-year studie3
was the variation between trial results statistically significant by X
tests. Within the individual trials, the TCu 220C device was found to
have significantly lower failure rates than the loop D in the two larger
WHO trials (20,211. Studies of various sizes of specific plastic dev-
ices indicated -- whatever the exact mechanism of action of these dev-
ices -- that "pregnancy rates were inversely associated with size --
lower for the larger loops than for the smaller -- and for the large
spiral and bow compared with the smaller sizes of the same models.w (17)
The introduction of medicated copper devices by Zipper and Tatum (23)
permitted some disassociation between size of device and effectiveness.

JULY 1987 VOL. 36 NO. 1 63

CONTRACEPTION

However, neither in the Population Council's early randomized comparison

of the Copper T 200 and the Loop D (19) nor in the three WHO studies of
the Loop D and the Copper 7 (20-221 was there a significant difference
in failure rates between the copper devices and the plastic devices.
Whatever advantage one or another of these plastic or copper devices had
with regard to expulsion rates , acceptability, duration of use or price,
none was found with regard to failure rates.

Cnpper 7 (Cu 7lr The Copper 7 was studied in 5 multicenter

trials (20-22,24-26,551. The Pearl index was 2.9 per 100 in one-year
studies and 2.7 per 100 W.Y. in two-year studies (Table V). There was
great variability between studies , and the Chi-square value was signifi-
cant (X2 = 12.70, 4d.f.). One must look somewhat askance at the overall
Pearl index for this device. The performance of the device may be sen-
sitive to the insertion technique which underwent considerable evolution
in the hands of clinicians. The summary or overall pregnancy rates
closely matched the summary rates of the Loop D (Table II). In two of
the WHO studies pregnancy rates of the Cu 7 were significantly above
those of the TCu 220C (20,211. This was the case also in the Southeast
Asian study (25,26,55).

Copper T 700 (TCu 200): Five multicenter randomized studies of the

TCu 200 principally in younger women (Table VI) produced a first year
Pearl rate of 2.5 per 100 W.Y. and a two-year Pearl rate of 3.0 per hun-
dred (19,24,27,28). In the four two-year studies, the Pearl index for
this IUD was higher at two years than it had been at one year. The
first Copper T model has been shown to have significantly higher failure
rates than the TCu 220C1 TCu 380A and the Nova T. The randomized stu-
dies taken together show little if any difference at one or at two years
among the Loop D, the Cu 7 and the Copper T 200.

Both th2 Cu 7 and the TCu 200 have copper wire with a surface area
of 200 mm * Although Zipper 8 Tatum (23) had demonstrated a marked
reduction in failure rates by adding copper wire to the plastic T-shaped
device, the experimental proof that it was copper rather than the
increased surface area had to be repeated after Kamalls study (29).
Andolsek and colleagues (30) wound nylon thread on a plastic T and in a
randomized study demonstrated that the Copper T 200 had a significantly
lower accidental pregnancy rate at one.year than did its counterpart
wound with 200 mm2 of nylon thread. Copper does make a difference.

Nova T:The extent of copper surface area alone does not permit one
to predict copper IUD performance. The Nova T has 200 mm of copper
wire'with a core'of silver; but in the Scandinavian randomized ccm-
parison with the silver core Copper T 200Ag, a significantly lower
failure rate was observed at two years among users of the Nova T dev-
ice (28). Three large multicenter trials of the Nova T device have been
undertaken (Table VII) (28,31-33). In none of these has the one- or
two-year Pearl index exceeded 2.0 per hundred. Over the three studies,
the Pearl index has been 1.2 at one year and 1.3 per 100 W.Y. at two

64 JULY 1987 VOL. 36 NO. I

 CONTRACEPTION

TABLE V

Pearl Pregnancy Rates in Large, Multicenter, Randomized Studies

Cu 7 Device

Pearl Index
Sponsor or Median Per 100 W.Y. Woman-Years
Eic&Authar Baa ysracl ZbMJz yaps1 zb&cs

Pop. Council (24) c25 3.4 3.4 1024 1306

WHO-vs220rD (20) 27.6 1.8 1.9 880 1494
WHO-MTP (21) 28.6 3.4 3.1 562 912
WHO-SPA6 (221 28.2 1.1 1.5 283 465
Gob, Huptapea 27.4 4.9 3.1 328 866
(25,26,55)

Summary 2.9 2.7 3077 5043

TABLE VI

Pearl Pregnancy Rates in Large, Multicenter, Randomized Studies

TCu 200 Device

Pearl Index
Sponsor or Median Per 100 W.Y. Woman-Years
E_iJztAuthor Aw YA3JzlZr_eaJ.X yaarl.2

Pop. Council-Loop D (191 (25 2.5 - 645 -

Pop. Council-Cu 7 (24) (25 1.7 2.3 1144 1502
Pop. Council-380 (27) 22.6 3.6 3.7 1311 2056
Pop. Council-220 (271 23.0 2.5 3.2 681 1067
Luukkainen (281 27.7 2.1 2.4 811 1420

Summary 2.5 3.0 4592 6045

TABLE VII

Pearl Pregnancy Rates in Large, Multicenter, Randomized Studies

Nova T Device

Pearl Index
Sponsor or Median Per 100 W.Y. Woman-Years
E.iJdAuthor Bae ha.cl zx!zmx yaarl zY_Q&E

Luukkainen (28) 27.5 0.8 0.9 763 1344

WHOvsLNg 2 (31) 29.6 1.8 1609
Saure, (33) 31.0 1.9 1.1 361 718
Hirvonen (32)

Summary 1.2 1.3 1124 3671

JULY 1987 VOL. 36 NO. 1 65

CONTRACEPTION

years. Both values are significantly below 2 per 100.

With a somewhat larger copper surface area

t the Multiload MLCu 250 has, like the Nova Tt exhibited one-
and two-year failure rates that are below 2.0 per 100 W.Y. (Table
VIII) (25,26,34,55). The Pearl index for a two-year period is signifi-
cantly below 2 per 100 W.Y. In the S.E. Asian study the MLCu 250 had
significantly lower pregnancy rates than did the Copper 7 dev-
3ce (25r76).
TABLE VIII

Pearl Pregnancy Rates in Large, Multicenter, Randomized Trials

MLCu 250 Device

Pearl Index
Sponsor or Median Per 100 W.Y. Woman-Years
UJz&Author Bae yaprl ZYJUJzi yaacl zY&aJzi

WHO (34) NA 1.0 1634

Gob, Huptapea 27.7 1.7 1.5 356 934
(25,26,55)

Summary 1.7 1.2 356 2568

Short versfon2 of the MLCu 250 devices with the same copper surface
area of 250 mm s howeverr appear to be associated with higher failure
rates than observed for the parent MLCu 250 device (35). It is not
clear whether design or physical size factors are associated with the
higher failure rate of the short MLCu model.

Multiload 375 (MICu 375)~ The increase of copper surface to 375 mm2
in the MLCu 375 device appears to be associated with a further decrease
in IUD failure rates (Table IX). In two multicenter studies the fallure
rate of this device did not exceed 1 per 100 woman-years (32,33,36~37).
The summary statistic of the first year's performance is 0.6 per 100.
The upper confidence limit exceeds 1.1 per 100. In a 3-way comparative
study in Ftnland the lowest failure rate was observed among users of the
MLCu 375, which had the greatest copper surface area, while the highest
failure rate was observed among2wcmen using the device with smallest
copper surface area* 200 mm (32,331. The intermediate failure rate
belonged to the device with intermediate surface area. In the com-
parison with the Copper T 38OAg, both the MLCu 375 and the 380 had
failure rates below 1 per hundred at one year (36,371.

66 JULY 1987 VOL. 36 NO. 1

 CONTRACEPTION

TABLE IX

Pearl Pregnancy Rates in Large, Multicenter, Randomized Trials

MLCu 375 Device

Pearl Index
Sponsor or Median Per 100 W.Y. Woman-Years
Eiccif.Author A!B yaarl zY&acs -1 zY_%lJz

FHI (36,371 27.5 0.8 646

Saute, Hirvonen 30.6 0.3 0.5 343 653
(33) (32)

Summary 0.6 0.5 989 653

OC (TCu 27Oc)1 In the last decade the two most widely

studied copper IUDs have been the collared T devices, model TCu 220C and
TCu 380A or TCu 380Ag. Ten multicenter trials of the TCu 220C device
have been conducted, seven by WHO (Table XI (13,14,20-22,25-
27,31,34,38,39,55, Rowe, personal communication). More than 14,000
woman-years of experience have been observed during the first two years
of use. Over the two-year period the highest Pearl pregnancy rate
recorded for the TCu 22OC, 1.2 per 100 W.Y., was found in the U.S.
study (27) of young women and in WHO's study (21) following medical ter-
mination of pregnancy. The summary Pearl index for this device over the
ten studies falls below 1 per 100 woman-years both for the one-year stu-
dies and for the two-year studies. In the various multicenter trials
the device has proved significantly more effective than the TCu 200
(once), Cu 7 (3 times), the Lippes loop D (2 times), the IPCS (once),
the levonorgestrel device releasing 2 micrograms per day (once), the
Nova T (once), and the Tianjin steel ring (once). In neither of the two
multicenter comparisons with the MLCu 250 was the difference in preg-
nancy rates significant, though in both trials the TCu 220C was observed
to have the lower pregnancy rate (34,391. This device has not been
explicitly compared with the MLCu 375 in a randomized trial.

-per T 380A or 380&g (TCu SOA or 38Ou In two of the ten multi-
center randomized trials the TCu 220C was tested against a second col-
lared T device, the TCu 380A or Ag (13,14,39r Rowe, personal communica-
tion). The TCu 380Ag has a silver core wire. In both cases the TCu 380
had the lesser failure rate. In the large WHO study the TCu 380A had a
significantly lower pregnancy rate than did the TCu 220C (39, Rowe, per-
sonal communication). The TCu 380A or Ag has also been shown to be sig-
nificantly more effective than the TCu 200 (27) and the Mahua
ring (13,141. A 5-center study conducted by FHI showed no significant
difference between the TCu 380Ag, and the MLCu 375, although the point
estimate of the Pearl index was lower for the 380Ag device (36,371. In
the single trial to date in which the point estimate of the failure rate
did not favor the TCu 380, it had a Pearl index of 0.3 per 100 in year 1
and 0.4 per 100 in the first two years (40,411. The device with the
lower index releases 20 mcg/day of levonorgestrel.

JULY 1987 VOL. 36 NO. 1 67

CONTRACEPTION

TABLE X

Pearl Pregnancy Rates in Large , Multicenter, Randomized Studies

TCu 220C Device

Pearl Index
Sponsor or Median Per 100 W.Y. Woman-Years
UJz&Author aae yaacl 2baJzi yaarl ilwLlz%

Pop. Council (27) 22.1 1.1 1.2 747 1155

WHO-vs.7tD (20) 27.8 0.4 0.8 903 1562
WHO-MTP (21) 28.1 1.6 1.2 633 1042
WHQ-SPA6 (22) 28.9 0.7 0.9 286 463
WHO vs IPCS (38) 28.2 1.0 0.8 1172 2064
WHO vs IP, ML (34) 28.4 NA 0.7 NA 1683
WHO vs 380 (39,') 0.9 1.1 1350 2429
WHO vs LNg2 (31) 29.3 NA 0.6 NA 1575
Sung, Qian 31.9 0.4 0.7 799 1297
(13,141
Goht Huptapea 27.5 0.8 1.0 357 914
(25,26,55)

Summary 0.9 0.9 6247 14184

*P. Rowe, personal communication.

TABLE XI

Pearl Pregnancy Rates in Large t Multicenter, Randomized Studies

TCu380A or TCu380Ag Devices

Pearl Index
Sponsor or Median Per 100 W.Y. Woman-Years
UJz&Author aoa yaarl zyaars yaacl ZbaJz

Pop. Council (27) 22.6 1.3 0.8 1194 1870

Pop. Council (40,41). 27.1 0.3 0.4 1007 1703
FHI (36,371 26.7 0.3 654
WHO (39,") 0.3 0.3 1373 2492
Sung,Qian 32.0 0.1 0.2 810 1281
(13.14)

Summary 0.5 0.4 5038 7346

*P. Rowe, personal communication.

68 JULY 1987 VOL. 36 NO. 1

 CONTRACEPTION

The 5 trials of the TCu 380 involve experience of 8,000 woman-years.

The Pearl indices computed at 1 or 2 years are well below 1 per 100 and
for women over age 25 at inception of use, the failure rate is signifi-
cantly below 1 per 100 for this device (Table XI).

Medicated Devices: Steroid-Releasing__Il&

v (IpCS+Z& The second class of medicated

devices includes those which release natural or synthetic hormones, pro-
gesterone or levonorgestrel, each at two different dosage levels. Use
of these steroids in IUDs is associated with diminished blood loss in
comparison with either copper or with non-medicated devices. The
ProgestasertR, releasing 65 mcg/day of progesterone, has not been stu-
died in any large multicentered randomized comparative trial. Its rela-
tively short effective life. 12-18 months, and the indicated high
fncidence of ectopic pregnancy, 4-6 per 1000 woman-years associated with
its use, may have dampened interest in the device. (Single clinic ran-
domized studies of this device are shown in Table XVI.) A second device
releasing progesterone at the rate of 25 mcg/day, IPCS-52, has been stu-
died by WHO (38,39). Failure rates observed in the first two years
ranged between 1.2 and 2.2 per 100 W.Y. in two trials (Table XII).
Failure rates, however, increased markedly toward the end of the third
year of use, and ectopic pregnancy rates were also high.

TABLE XII

Pearl Pregnancy Rates in Large, Multicenter, Randomized Studies

Steroid-Releasing Devices

Pearl Index
Sponsor or Median Per 100 W.Y. Woman-Years
~A!JzhQc Bge yaarl z&JAlz yaarl 2YBJ.z

IPCS - 25 KG/Day

WHO-Int (38) 21.9 2.2 2.2 1145 1802

WHO-MTP (38) 28.1 0.8 1.2 885 1498

Summary 1.6 1.7 2030 3300

LNg2 ZMCG/Day

WHO (31) 29.1 2.3 2.1 1030 1422

LNg20 20MCG/Day

Pop. Council 26.9 0.2 0.1 991 1637

(40,41)

JULY 1987 VOL. 36 NO. 1 69

CONTRACEPTION

. mca/dav The WHO-developed-IUD releasing 2

mcg/day of levonorgestrel has been studied in a single large multicenter
trial (31). Its performance in this interval trial was similar to that
of the IPCS-52 interval trial, a Pearl index of 2.1 per 100 W.Y. at 2
years (Table XII). Like the ProgestasertR and the IPCS-52r this device
has been troubled by a high incidence of ectopic pregnancy. The total
pregnancy rate was significantly higher than that of the TCu 220C.

. w The Population Council developed

a levonorgestrel-releasing device on a Nova T frame with a daily
delivery of 20 mcg. It has been observed in one large published and one
small randomized trial (40-44). The large multicenter study recorded
two failures in 1637 woman-years of user a Pearl index of only 0.12 per
100 (Table XII) (41). Neither of the pregnancies in the large study was
ectopic. In Nilsson's small multicenter study only a single pregnancy
occurred (42-44). It was ectopic. The total experience with this dev-
ice shows an ectopic pregnancy rate below 1 per 1000 woman-years. Fil-
ing for regulatory approval in the country of manufacture has been com-
pleted.

v of Multicenter Studies

Results from all the large multicenter randomized studies are sum-
marized by device in Table XIII and Figure 3. Table XIII exhibits
separately device summaries of the first year of trials, device sum-
maries of two-year duration and, in the right hand columns, results
obtained by adding pregnancies and woman-years from studies that pro-
ceeded only one year to those which proceeded two years. These trials
demonstrate substantial progress in reducing failure rates associated
with IUDs following the introduction of second generation medicated
IUDs. Plastic and ring devices had first year failure rates signffi-
cantly above 2 per 100 as did the Copper 7 and the Copper T 200. One
should note, however, that in 4 of the 5 multicentered randomized trials
of the TCu 200, median age at entrance was below 25 years. No other
device was studied even twice in groups so young. Thus, the overall
Pearl index here attributed to the TCu 200 is likely to be higher than
were this confounding element removed. Nonetheless, in the randomized
studies among young women the TCu 200 had significantly higher failure
rates than did either the TCu 220C or the TCu 380A. The latter devices
and the Multiload Cu375 have overall Pearl indices below 1 per 100 W.Y.
for women over age 25. In the case of the TCu 380, the failure rates
are significantly below 1 per 100 W.Y. The clear demonstration that
these three devices have failure rates at or below 1 per 100 W.Y. has
required a decade of trials.

70 JULY 1987 VOL. 36 NO. 1

 CONTRACEPTION

3.3 MA HUA

2.8 LOOP D

2.9 cu 7

2.5 TCu 200

1.7 I ML 250

1.2 NOVA T

0.9 TCu 220C

0.6 ML 375

0.5 TCu 380A

LNg 2
2.3 t ’
1.6 IPCS 25

LNg 20

I I I I I I
0 0.5 1.0 1.5 2.0 2.5 3.0

RATE PER 100

Figure 3

PEARL PREGNANCY RATE PER 100 BY IUD TYPE

MULTICENTER, RANDOMIZED TRIALS: YEAR 1

JULY 1987 VOL. 36 NO. 1 71

CONTRACEPTION

TABLE XIII
Pearl Pregnancy Rates in Large, Multicenter, Randomized Trials
by Type and Specific Device

Type No. of Pearl Index f. S.E. Woman-Years

&Device yrl. 2.Y& H_t&zY_rz .E_iJz&zY_cs

NoJiZMQd_&&d

=Bina
Mahua 1 3.3TO.6 2.7t0.4 2.7M.4 1345
Plastic
Loop D 4 2.8t0.4 2.4iO.3 2.610.3 3267

Medicated

5 2.920.3 2.7kO.2 2.7LO.2 5043

TCu 200 5 2.5LO.2 3.OkO.2 2.920.2 6690
Nova T 3 1.2iO.3 1.3t0.2 1.3kO.2 3671
MLCu 250 2 1.7kO.7 1.2kO.2 1.220.2 2568
TCu 220C 10 0.9~0.1 0.9iO.l 0.9~0.1 14184
MLCu 375 2 0.6kO.2 0.5&0.3 0.6LO.2 1299
TCu 380 5 0.5to.1 0.4*0.1 0.420.1 8000

25 mcg/day 2 1.6kO.3 1.7kO.2 1.7kO.2 3300

p 1 2.3kO.5 2.150.4 2.1kO.4 1422

20 mcg/day 1 0.2LO.l 0.1*0.1 0.1~0.1 1637

Single center and small multicenter randomized studies (Tables XIV-

XVI) contributed fewer than 600 woman-years of experience to our
knowledge of first year failure rates of ring devicesR the Lippes loop
D, the Copper 7, the Copper T 380, the Progestasert , and of the levo-
norgestrel 20 rrcg/day devices. Consequently. data from these trials do
not generally alter the understanding derived from the large, multicen-
tered studies. Steel rings and the Lippes loop D had point failure
rates in these studies above 2 per 100 as did the Copper 7. There were
seven studies of the TCu 200 among wcmen somewhat older on average than
participants in the multicenter trials. Results had, in sum, a first
year Pearl index of 1.9 per 100. First year failure rates for the MLCu
375, the TCu 220C1 and the TCu 380 were, as in the multicenter trials.
at or below 1 per 100. Again among copper IUDs, the TCu 380 had the
lowest estimated Pearl index, 0.5 per 100 in year one.

72 JULY 1987 VOL. 36 NO. 1

 CONTRACEPTION

One year experience in seven published small or single center trials of

the Nova T (Table XV) exceeds the number of woman-years in the large multicen-
tered trials (Table VII). In the more numerous smaller studies9 the one year
Pearl index ranged from 1.1 to 2.8 per 100, 1.7 per 100 W.Y. overall as com-
pared to 1.2 per 100 in the larger trials (P > 0.05). Data for 2 years were
quite similar for the large and small studies (1.3 and 1.5, respectively).

TABLE XIV
Small Multicenter or Single Clinic Randomized Trials
Pearl Indices
Non-Medicated Devices

Sponsor or Median Pearl Index Woman-Years

-Author aoe yrl z&Z yrl 2YJZs

s.taalRjJQ
Gao (15) 29.1 6.0 4.2 182 334
Standard Error 1.8 1.1

LQQBn
FHI (56), Europe NA 3.1 359
FHI (561, Latin Am. NA 2.6 151
Summary 2.9 510
Standard Error 0.7

The greatest disparity between point estimates in single center and in

multicenter studies was for the MLCu 250 device. In the single published 1
year multicenter study, the Pearl jndex was 1.7 (Table VIII). In contrast,
none of the 5 single center studies produced a Pearl pregnancy rate above 1.0
per 100 W.Y. (Table XV). However, this difference is not statistically signi-
ficant.

TABLE XV
Small Multicenter or Single Center Randomized Trials
Pearl Indices
Medicated Devices - Copper IUDs

Sponsor or Median Pearl Index Woman-Years

-Author Baa yrl zyrs yrl 2yrs

Pizarro (57) 1.5 130

FHI (56) NA 2.6 384
Summary 2.3 514
Standard Error 0.7
(Cont.)

JULY 1987 VOL. 36 NO. 1 73

CONTRACEPTION

TABLE XV (Cont.)
Sponsor or Median Pearl Index Woman-Years
E&z&Author 2xc.s Y_cl

Ladehoff (58) -8I 2M 1.0 98

Larsen (59) -2317 2.5 162
Batar (60) NA 2.2 312
Thiery (61) 30.3 1.0 0.8 622 882
Kozuh (62) 29.8 3.2 3.2 379 627
Andolsek (30) -28.3 0
FHI (56) NA 2.6 1::
Summary 1.9 1.8 1816 1509
Standard Error 0.3 0.3

Roy (63)
Gao (15)
Yi-2918 1.1 1.2 742 1230
0.5 0.5 203 371
Summary 1.0 1.1 945 1601
Standard Error 0.3 0.3

Roy (63) YE?=- 0.6 0.6 324 528

Diaz (64) 26:5 0.0 118
Summary 0.5 0.6 442 528
Standard Error 0.3 0.3
MLGllz5Qo
Lim (65) 26.7 0.8 0.9 247 429
Thiery (61) 30.2 0.5 0.6 567 787
Ladehoff (58) -23.6 0.9 107
McCarthy (66) NA 0.6 0.4 177 280
Klvijarvi (35) NA 0.6 168
Summary 0.6 0.7 1266 1496
Standard Error 0.2 0.2
I!lLcuw
Lim (65) 26.2, 2.1 1.3 236 395
De Castro (67) -36.8 0.3 595
Summary 0.8 1.3 834 395
Standard Error 0.3 0.6

NQ!LaI
Nilsson (42,441 30.4 2.8 2.0 142 249
Kozuh (62) 29.8 1.1 0.9 378 635
Batar (60) NA 1.6 309
Fylling (68) 25.4 2.4 124
McCarthy (66) NA ** 1.8 2.3 168 261
De Castro (67) -35.7 1.7 597
Summary 1.7 1.5 1718 1145
Standard Error 0.3 0.2

I$ignificantly higher than mean age of randomized control.

Significantly lower than mean age of randomized control.

74 JULY 1987 VOL. 36 NO. 1

 CONTRACEPTION

In the case of the ProgestasertRt the four small randomized studies have
no multicenter counterpart. Three of the 4 randomized trials of this device
had failures above 2 per 100 W.Y. (Table XVI).

TABLE XVI
Small Multicenter or Single Center Randomized Trials
Pearl Indices
Medicated Devices - Steroid-Releasing IUDs

Sponsor or Median Pearl Index Woman-Years

-Author &.e yr 1 2.u yrl 2m

mR
Fylling (68) 26.1 4.9 144
Pizarro (57) 27.0 1.5 131
Larsen (59) -23.7 2.4 166
Brenner (69) NA 2.7 73
Summary 2.9 514
Standard Error 0.7

Nilsson (42,44) 31.4 0.7 0.4 138 257

Standard Error

Duration of Action

One price that has been paid for the achievements of the past decade or so
is that the costs of the medicated devices exceed those of the non-medicated
devices by a substantial multiple. But as steel rings and plastic devices may
remain undisturbed _in w for 1 or 2 decades, the relatively short life of
the initial medicated devices , whether copper or steroid, not only increases
the cost of protection because of the need for renewal, but increases the
chances of infection because of the need for a second insertion. Removal at
the end of a period of effective use also tends to decrease long-term device-
specific continuation rates. The low daily release rate steroid devices and
the collars on the TCu 220C and TCu 380A and silver core wire in the Nova T,
TCu 200Ag, and TCu 38OAg, however, appear to provide means by which the life-
time of medicated devices can be prolonged. We briefly examine long-term IUD
failure rates.

Apart from two studies by Luukkainen and colleagues (28,431 in Scandina-

via, there have been no randomized trials carrying performance through five or
more years. Several straight assignment studies of four or more years'
experience have been published, however, which permit exact or approximate
computation of annual Pearl or gross pregnancy rates (Table XVII)." In the
Tietze and Lewit study of 1970 (171, failure rates of the Loop D declined siq-
nificantly after the end of the second year of use to a level'of 1.0 per 150
W.Y. in years 3 and 4 and to 0.3 in year 5. Significantly lower continuation
rates among younger women may account for a large part of this decline. The

JULY 1987 VOL. 36 NO. 1 7.5

CONTRACEPTION

group of wcmen at risk in later years was relatively enriched in the age
groups over 30 at insertion.

TABLE XVII

Annual Pearl or Gross Pregnancy Rates Through 4 or 5 Years

Selected Studies, First Segment of Use

Sponsor or Annual Pearl Index/Year

-Author Device 12 14 5

Pop. Council (17) Loop D 2.9 2.1 1.0 1.0 0.3

Pop. Council (271 TCu 200 3.1 3.7 2.4 1.1 NA
Zhang (45) TCu 200 1.7 1.7 1.1 1.3 1.3
Luukkainen (28) TCu 200Ag 2.1 2.8 1.8 0.6 1.8
Zipper (46) TCu 200 2.5 2.1 1.9 2.0 3.7
Zipper (47) Copper 7 2.6 1.9 2.4 1.0 NA
Gobeaux-Castadot** (481 Copper 7 1.8 3.2 0.7 0 6.9
Luukkainen (281 Nova T 0.8 1.0 0.9 0.3 0.5
Luukkainen (43) Nova T 3.2 1.0 1.2 1.4 0.0
Pop. Councii (701 TCu 380A 1.1 0.4 0.5
Van De& Pas (711 TCu 220C 1.3 1.5 ::: 0.8 iA9
Thiery (72) MLCu 375 0.4 1.1 0.4 0.6 0.4

Luukkainen (43) LNG-20 0.8 0 0 0 0

LNG-30 0 0 0 0 0
*
** Estimated annual gross pregnancy rates.
Year 5 based on ( 20 women.

Annual failure rates observed among wearers of the Copper T 200 (27,28,45)
after two years were also below the values observed in the first two years
except for the fifth year of Zipper's (461 study of the TCu 200.
Zipper's (471 long-term Copper 7 data extend to 4 years but do not indicate
any marked change in failure rates during years 3 and 4 in comparison with
years 1 or 2. The New York data of Gobeaux-Castadot aj; al. (481 provide
strong evidence only through three years. In most studies, the numbers at
risk in years 4 and 5 are small.

Long-term failure rates of the more effective copper devices have not been
quantitatively different from device-specific rates in the first two years.
The highest annual failure rate reported for the Nova T, the TCu 220CI the TCu
380A, or the MLCu 375 beyond 3 years was 1.4 per 100. All these devices but
the MLCu 375 have features predictive of sustained release of copper for
extended periods either in the form of copper collars and/or silver core

76 JULY 1987 VOL. 36 NO. 1

 CONTRACEPTION

copper wire. Thiery e% &I_. (49) has observed the TCu 22OC for ten years.
Average annual pregnancy rates remained at about 1 per 100 or below in years 4
through 10.

In a small pilot randomized study of two levonorgestrel-releasing ILIDs,

Luukkainen and colleagues (43) observed no pregnancies in years 2 through 5 of
use. Larger studies of the device releasing 20 mcg/day are under way and are
now reaching 5 years.

The distinction in performance between Loop D and the first copper IUDs on
the one hand, and 4 of the more widely used contemporary copper IUDs on the
other, may be summarized finally by cumulative gross pregnancy rates at 4 or
at 5 years (Table XVIII). Cumulative failure rates of the Loop D, the TCu
200. and the Copper 7 ranged between 5 per 100 to almost 10 per 100 at 4
years, but were below 5 per 100 for the MLCu 375, TCu 380A, and TCu 220C. The
five-year pregnancy rate reported for the MLCu 375 is markedly below the rates
for the majority of the other IUDs with 5-year data except for the larger
study of the Nova T conducted in Scandinavia. The Nova T had a 5-year gross
cumulative pregnancy rate of 3.4 per 100 (28). The smaller trial of the Nova
T in Finland had gross cumulative pregnancy rates of 6.6t1.6 per 100 women at
years 4 and 5 (43). If the preliminary data on the levonorgestrel IUD releas-
ing 20 mcg is sustained, it, too, will show cumulatfve failure rates well
below 5 per 100 at 5 years.
TABLE XVIII

Four- and Five-Year Gross Cumulative Pregnancy Rates Per 100 Women
Selected Studies, First Segment of Use

Gross Cumulative
Pregnancy Rates
Sponsor or
EQs.tAuthor Device k!l. Lfi

Thiery (72) MLCu 375 2.5 2.9

Pop. Council (70) TCu 380A 2.8 NA
Luukkainen,(PB) Nova T 2.9 3.4
Luukkainen (43) Nova T 6.6 6.6
WHO (39) TCu 220C 3.9 NA
Van Der Pas (711, TCu 220C 4.7 5.6
Gobeaux-Castadot (48) Copper 7 5.7 12.1
WHO (30) Copper 7 6.2 NA
ZippeE (471 Copper 7 7.7 NA
Zhang (45) TCu 200 5.7 6.9
Luukkainen (28) TCu 200Ag 7.1 8.7
Zipper (46) TCu 200 8.2 11.7
Pop: Council (27) TCu 200 9.7 NA
Pop. Council (17) Loop D 6.7 7.1
*
Estimated gross cumulative pregnancy rates.

JULY 1987 VOL. 36 NO. 1 77

CONTRACEPTION

PERSPECTIVE

We have dwelt on the Qse effectivenessw of intrauterine contraceptives.

It is appropriate to consider briefly what Tietze and Lewit (50) called
wextended use effectiveness,w examining the joint effects of failure and con-
tinuation rates. The widely used Lfppes loops C and D repeatedly and con-
sistently demonstrated high continuation rates in national family planning
programs in developing countries and in national samples of married women in
developed countries. These continuation rates have been above those of oral
contraceptives (3-6). Improved copper IUDs such as the TCu 220C have exhi-
bited higher continuation rates than Loop D or the Copper 7 as a result of
reduced failure and expulsion rates. The combination of low failure and high
continuation rates has meant marked reductions in fertility per user. Indeed
age-specific or age-standardized basis reduction in fertility has been
iFea:tr for IUD users than for users of oral contraceptives (5,6). In several
developing countries failure rates during pill use have been higher than dur-
ing IUD use (4-6). WHO clinical trials of various oral contraceptives in
developing countries have shown failure rates higher than those observed in
the WHO trials of IUDs discussed above (51,521. Based on national continua-
tion and failure rates reported in Thailand for injectable!% it appears that
the higher continuation rates of the IUD would lead to its having greater
extended use effectiveness (53). Among reversible methods only implant con-
traceptian with capsules has rivaled IUD continuation rates. After 5 years of
Norplant use, however, the failure rate of capsules rises above 3 per 100 per
year and implants must be replaced. Hence today, twenty-five years or so
after its reintroduction, the IUD remains among the most effective reversible
means of contraception. When program costs are considered, the IUD appears to
be the most cost-effective reversible method in the contraceptive armamen-
tarium.

REFERENCES

1. Population Reports IUDs: An appropriate choice for many women. Series B

B4:BlOl-8135 (1982)

2. Taturn, H.J. and Connell, E.B. A decade of intrauterine contraception:

1976 to 1986. Fertil. Steril. 46:173-192 (1986)

3. Grady, W.R., Hirsch, M.B., Keen, N., and Vaughan, B. Contraceptive

failure and continuation among married women in the Unfted States,
1970-75. Stud. Fam. Plann. 14:9-19 (1983)

4. Kreager, P. Family Planning Drop-outs Reconsidered. International

Planned Parenthood Federation (London) (1977)

5. Laing, J.E. Estfmating the effects of contraceptive use on fertility:

Techniques and findings from the 1974 Philippine National Acceptor Sur-
vey. Stud. Fam. Plann. 9:150-162 (1978)

6. Sivin, I. Contraception and Fertility Change in the International Post-

partum Program. The Population Council , New York(1974)

78 JULY 1987 VOL. 36 NO. 1

 CONTRACEPTION

7. Sivin, I. Measuring contraceptive efficacy and side effects. Int. J.

Gynaecol. Obstet. 16:460-465 (1979)

8. Shelton. J.D. and Taylor, R.N., Jr. The Pearl pregnancy index reexam-
ined: Still useful for clinical trials of contraceptives. Am. J.
Obstet. Gynecol. 139:592-596 (1981)

9. Higgins, J.E. and Wilkens. L.R. Statistical comparison of Pearl rates.

Am. J. Obstet. Gynecol. 151:656-659 (1985)

10. Menken, J., Trussel, J., and Larsen, U. Age and infertility. Science
233:1389-1394 (1986)

11. Allonen, H., Luukkainen, T., Nielsen, N.C., Nygren, K.-G., and Pybrllll,
T. Factors affecting the clinical performance of Nova T and Copper T
zoo. Obstet. Gynecol. 64:524-529 (1984)

12. Mishell, D.R.,Jr. The clinic factor in evaluating IUDs. In: Analysis of
Intrauterine Contraception (Hefnawi, F. and Segal, S.J.,eds).North
Holland/American Elsevier , Amsterdam/New York, pp 27-36 (1975)

13. Sung. S., Qian, L.-J., and Liu, X. Comparative clinical experience with
3 IUDs, TCu 380 Ag. TCu 220C1 and Mahua ring, in Tianjin, People's
Republic of China. Contraception 29:229-239 (1984)

14. Sung, S., Qian, L.-J., and Liu, X. Two-year comparative clinical
experience with three IUDs in China. In: Intrauterine Contraception:
Advances and Future Prospects (Zatuchni, G.I., Goldsmith, A., Sciarra,
J.J., eds).Harper B Row , Philadelphia. pp 109-114 (1985)

15. Gao, J., Shen. H., Zheng, S., Fan, H-M., Wu, M-H., Han, L-h., and Yao,
G.2. A randomized comparative clinical evaluation of the steel ring,
the VCu 200 and the TCu22Oc IUDs. Contraception 33:443-454 (19861

16. Muramatsu, M. Statistical Analysis of Long Term Wearers of Ota Ring,

Department of Public Health Demography. The Institute of Public Health,
Tokyo, (September 1973)

17. Tietze, C. and Lewit, S. Evaluation of intrauterine devices: Ninth pro-

gress report of the Cooperative Statistical Program. Stud. Fam. Plann.
1 (55):1-40 (1970)

18. Vessey, M., Lawless. M., and Yeates, D. Efficacy of different contra-
ceptive methods. Lancet 1:841-842 (1982)

19. Tietze, C. and Lewit, S. Comparison of the Copper-T and Loop D: A

research report. Stud. Fam. Plann. 3:277-278 (1972)

20. World Health Organization Task Force on Intrauterine Devices for Fertil-
ity Regulation. Interval IUD insertion in parous women: A randomized
multicentre comparative trial of the Lippes Loop D, TCu22OC and the
Copper 7. Contraception 26:1-22 (1982)

JULY 1987 VOL. 36 NO. 1 79

CONTRACEPTION

21. World Health Organization Task Force on Intrauterine Devices for Fertil-
ity Regulation; IUD insertion following termination of pregnancy: A
clinical trial of the TCu 22OC, Lippes
.. LOOD D, and Coooer
.. 7. Stud. Fam.
Plann. 14:99-108 (1983)

22. World Health Organization Task Force on Intrauterine Devices for Fertil-
ity Regulation. IUD insertion following spontaneous abortion: A clini-
cal trial of the TCu 22OC, Lippes Loop D, and Copper 7. Stud. Fam.
Plann. 14:109-114 (1983)

23. Zipper, J., Taturn, H.J., Pastene, L.9 Medel, M., and Rivera, M. Metal-
lic copper as an intrauterine contraceptive adjunct to the wT1' device.
Am. J. Obstet. Gynecol. 105:1274-1278 (1969)

24. Jainr A.K. Comparative performance of three types of IUDs in the United
States. In: Analysis of Intrauterine Contraception (Hefnawi, F. and
Segal, S.J.,eds).North-Holland/American Elsevier, Amsterdam/New York,
pp 3-16 (1975)

25. Hutapea, H., McCarthy, T., Gob, T.H., Hanafiah, M.J., Simadjuntak, P.,
Lim, L.S., Karim, S.M.M., Ratnam, S.S., Yang, Y.M., Sinnathuray, T.A.,
Sivanesaratnam, V., and Sen, D.K. The acceptability of the Copper 7,
Multiload 250 and Copper T 220C intrauterine devices. Contracept.
Deliv. Syst. 5:11-16 (i&34)

26. Goht T.H., Hutapea, H., McCarthy, T., Sinnathuray, T.A., Sivanesaratnam,
V ., Sen, D.K., Nanafiah, M.J., Simadjuntak, P., Lim, L.S., Ratnam, S.S.,
and Karim, S.M. A multicenter randomized comparative investigation of
ML Cu250, TCu-220C and Cu 7 IUDs. Adv. Contracept. Deliv. Svst. Mono-
graph 1:126-129 (1985)

27. Sivin, I. and Stern, J. Long-acting, more effective Copper T IUDs: A

summary of U.S. experience, 1970-75. Stud. Fam. Plann. 10:263-281
(1979)

28. Luukkainen, T., Allonen, H., Nielsen, N.-C.. Nygren, K.-G., and PyBrtlll,
T. Five years' experience of intrauterine contraception with the Nova-T
and the Copper-T-200. Am. J. Obstet. Gynecol. 147:885-892 (1983)

29. Kamal, I., Shaaban, H., Ezzat, R., and Zaki, S. The "Nylon Tn intrau-
terine device: Surface area versus copper adjunct. Int. J. Gynaecol.
Obstet. 19:119-124 (1981)

30. Andolsek, L., Kozuh-Novak, M., and Waszak, C. A comparative study of

the Nylon T and Copper T 200. Contracept. Deliv. Syst. 4:297-300
(1983)

31. World Health Organization Task Force on Intrauterine Devices for Fertil-
ity Regulation. Microdose intrauterine levonorgestrel for contracep-
tion. Contraception 35:363-379 (1987)

32. Hirvonen, E. and Kaivola, S. Fincoid-350 IUD. In: Intrauterine

80 JULY 1987 VOL. 36 NO. 1

 CONTRACEPTION

Contraception: Advances and Future Prospects (Zatuchni, G.I.,

Goldsmith, A., Sciarra, J.J.,eds).Harper 8 Row, Philadelphia, pp 251-
262 (1985)

33. Saure, A., Hirvonen, E., Kivijlrvir A., and Timonen. H. Comparative
performance of Fincoid, Nova-T and ML 375 IUDs. In: Intrauterine Contra-
ception: Advances and Future Prospects (Zatuchni, G.I., Goldsmith, A.,
Sciarra, J.J.,eds).Harper & Row, Philadelphia, pp 104-108 (1985)

34. World Health Organization, Special Proaramme of Research, Development

and Research Training in Human Reproduction. Intrauterine devices.
12th Annual Report,40-45 (1983)

35. Kivij\lrvir A. Randomtzed comparison of multiload standard and short

devices. Contracept. Deliv. Syst. 4:289-292 (1983)

36. Cole, L.P., Potts, D.M., Aranda, C., Behlilovict B.1 Etman, E-S.,
Moreno, J., Randic, L., Apelo, R., and Thomas, M. Comparative copper
IUD trials. In: Intrauterine Contraception: Advances and Future Pros-
pects (Zatuchni, G.I., Goldsmith, A., Sciarra, J.J.,eds).Harper A Row,
Philadelphia, pp 95-100 (1985)

37. Cole, L.P., Potts, D.M., Aranda, C., Behlilovic, B.1 Etman, E-S.1
Moreno, J., and Randic. L. An evaluation of the TCu 380Ag and the Mul-
tiload Cu375. Fertil. Steril. 43:214-217 (1985)

38. World Health Organization Task Force on Intrauterine Devices for Fertil-
ity Regulation. The Alza T IPCS 52, a longer acting progesterone IUD:
Safety and efficacy compared to the TCu 22OC and Multiload 250 in two
randomized multicentre trials. Clinical Reproduction Fertility 2:113-
128 (1983)

39. World Health Organization, Special Programme of Research, Development

and Research Training in Human Reproduction. Intrauterine devices.
13th Annual Report,52-57 (1984)

40. Sivin, I., Alvarez, F., Diaz, J., Diaz, S., El Mahgoub. S., Coutinho,
E . . Brache, V.. Diaz, M.M., Faundes, A., Pavez, M., Mattes, C.E.R., and
Stern, J. Intrauterine contraception with copper and with levonorges-
trel: A randomized study of the TCu 380Ag and levonorgestrel 20 mcg/day
devices. Contraception 30:443-456 (1984)

41. Sivin, I., Stern, J., Diaz, J., Diazr M.M., Faundes, A., El Mahgoub, S.,
Diaz, S., Pavez, M., Coutinho, E., Mattes, C.E.R., McCarthy, T.,
Mishell, D.R.,Jr., Shoupe, D., Alvarez, F., Brache, V.* and Jimenez, E.
Two years of intrauterine contraception with levonorgestrel and with
Copper: A randomized comparison of the TCu 380Ag and levonorgestrel 20
mcg/day devices. Contraception 35:245-255 (1987)

42. Nilsson, C.G., Luukkainen. T., Diaz, J., and Allonen. H. Intrauterine
contraception with levonorgestrel: A comparative randomised clinical
performance study. Lancet 1:577-580 (1981)

JULY 1987 VOL. 36 NO. 1 81

CONTRACEPTION

43. Luukkainen, T., Allonen, H., Haukkamaa, M., Llhteenmlki. P., Nilsson,
C.G., and Toivonen. J. Five years' experience with levonorgestrel-
releasing IUDs. Contraception 33:139-148 (19861

44. Nilsson, C.G., Allonen. H., Dial, J., and Luukkainen, T. Two years'
experience with two levonorgestrel-releasing intrauterine devices and
one copper-releasing intrauterine device: A randomized comparative per-
formance study. Fertil. Steril. 39:187-192 (1983)

45. Zhang, P-Z. Five years experience with the Copper T 200 in Shanghai -
856 cases. Contraception 22:561-571 (1980)

46. Zipper, J., Medel, M., Goldsmith, A., and Edelman, D.A. Six-year con-
tinuatlon rates for Cu-T-200 users. J. Reprod. Med. 18:95-97 (1977)

47. Zipper, J., Medel, M., Pastene, L., Rivera, M., Torres, L.. Osorio, A.,
and Toscanini, C. Four years experience with the Cu7 200 device -
endouterine copper in fertility control. Contraception 13:7-15 (1976)

48. Gobeaux-Castadot, M.-J., Boris, M.C., Chervenak, F.A., and Aubert, J.M.
Five year clinical experience with the Copper 7 intrauterine devfce.
Int. J. Gynaecol. Obstet. 19:181-192 (1981)

49. Thiery, M., Van Der Pas, H., and Van Kets, H. A decade of experience
with the TCu22OC. Adv. Contracept. 1:313-318 11985)

50. Tietze, C. and Lewit. S. Statistical evaluation of contraceptive

methods: Use-effectiveness and extended use effectiveness. Demography
5:931-940 (1968)

51. World Health Organization Task Force on Oral Contraceptives. A random-

ized. double-blind study of six combined oral contraceptives. Contra-
ception 25:231-241 (1982)

52. World Health Organization Task Force on Oral Contraceptives. A random-

ized, double-blind study of two combined and two progestogen-only oral
contraceptives. Contraception 25:243-252 (1982)

53. Narkavonnakit, T., Bennett, T.t and Balakrishnan, T.R. Continuation of

injectable contraceptives in Thailand. Stud. Fam. Plann. 13:99-105
(1982)

54. Potter, R.G.,Jr., Chow, L.P., Jain, A.K.. and Lees C.H. Effectiveness
of Intrauterine Contraception: Termination Levels and Correlates in Fam-
ily Planning in Taiwan (Freedman, R. and Takeshita, J.Y.,eds). Prince-
ton University Press, Princeton, pp 241-279 (Tables X-6 8 X-71 (19691

55. Goh, T.H., Sinnathuray, T.A., Sivanesaratnam, V., Sen, D.K.1 Lim, L.S.,
Ratnam, S.S.. Karim, S.M.M., McCarthy, T., Hutapea# H.r Hanafiah, M.J.,
and Simandjuntak, P. A randomfsed comparative evaluation of the Copper
7, Multiload Copper 250 and T Copper-220C IUDs. Contraception 27:75-84
(1983)

82 JULY 1987 VOL. 36 NO. 1

 CONTRACEPTION

56. Cole, L.P. and Edelman, D.A. A comparison of the Lippes Loop and two
coppel-bearing intrauterine devices. Int. J. Gynaecol. Obstet. 18:35-
39 (1980)

57. Pizarro, E., Gomez-Rogers, C., Rowe, P.J., and Lucero, S. Comparative
study of the progesterone T (65 ug daily) and Copper 7 IUD. Contracep-
tion 16:313-323 (1977)

58. Ladehoff, P., Hansen, M.K., Larsen, S., Sorensen. T., and Westergaard,
J.G. A comparison of two IUDs: Multiload Cu 250 and Copper T 200. Con-
tracept. Deliv. Syst. 4:9-13 (1983)

59. Larsen, S., Hansen, M.K., Jacobsen, J.C., Ladehoff, P., Sorensen, T.,
and Westergaard, J.G. Comparison between two IUDs: Progestasert and Cu
T ZOO. Contracept. Deliv. Syst. 2:281-286 (1981)

60. Batar, I., Lampe, L., and Allonen, H. Randomized use-effectiveness com-
parison of Nova T and Copper T 200 - Preliminary report. Contracept.
Deliv. Syst. 4:Abstract 49 (1983)

61. Thiery, M., Van Der Pas, H., Delbeke, L., and Van Kets, H. Comparative
performance of two coppepwired IUDs (ML Cu 250 and T Cu 200). Immedi-
ate postpartum and interval insertion. Contracept. Deliv. Syst. 1:27-
35 (1980)

62. Kozuh, M., Andolsek, L., and Allonen. H. A randomized comparative trial
of Nova-T and TCu200Ag in Yugoslavia. Adv. Contracept. 2:31-36 (1986)

63. Roy, S., Casagrande, J., Cooper, D.L., and Mishell, D.R.,Jr. Comparison
of three different models of the Copper T intrauterine contraceptive
device. Am. J. Obstet. Gynecol. 134:568-574 (1979)

64. Diaz, J., Diaz, M.M., Pastene, L., Araki, R., and Faundes, A. Random-
ized clinical study of the T-Cu 380A and the Lippes Loop C, in Campinas,
Brazil. Contraception 26:221-228 (1982)

65. Lim, L.S., McCarthy, T.G., Yang, Y.M., and Ratnam, S.S. Post-abortion
insertion of MLCu 250 and MLCu 375 - A comparative trial. Contraception
31:471-477 (1985)

66. McCarthy, T., Ramachandran, L., Huang, H.S.. and Ratnam, S. Postabor-
tion insertion of the Nova T and MLCu250: Preliminary results of a com-
parative study. Adv. Contracept. 1:161-165 (1985)

67. De Castro, A. and Anguiano, J.M. Comparative performance of two copper

IUDs: Nova-T and MLCu375. Adv. Contracept. 2:155-159 (1986)

68. Fylling, P. and Fagerhol, M. Experience with two different medicated

intrauterine devices: A comparative study of the Progestasert and Nova-
T. Fertil. Steril. 31:138-141 (1979)

69. Brenner, P.F., Cooper. D.L., and Mishell, D.R.,Jr. Clinical study of a

JULY 1987 VOL. 36 NO. I 83

CONTRACEPTION

progesterone-releasing intrauterine contraceptive device. Am. J.

Obstet. Gynecol. 121:704-706 (1975)

70. Sivin, I. and Taturn, H.J. Four years of experience with the TCu 380A
intrauterine contraceptive device. Fertil. Steril. 36:159-163 (1981)

71. Van Der Pas, H., Thiery, M., Delbeke, L., Van Kets, H., and Haspels, A.
Six years' experience with the T Cu 220C intrauterine contraceptive dev-
ice. Contracept. Deliv. Syst. l:l-10 (1980)

72. Thiery, M., Van Der Pas, H., and Van Kets, H. The MLCu375 intrauterine
contraceptive device. Adv. Contracept. 1:37-44 (19851

84 JULY 1987 VOL. 36 NO. 1