EDITORIAL
Update on the intrauterine contraceptive device _______~
Acia Ohmet Gynecol Scand 1992; 71: 163-165
Intrauterine contraceptive devices (IUDs) are presently estimated to be used by 84 million women world-wide. Approximately 86% of the users are in the People’s Republic of China. In other countries, the frequency of users among fertile couples varies greatly, with no consistent trend along socioeconomic lines. For example, only 2 to 4% of fertile women in the USA, Canada, Australia and New Zealand use IUDs, while use in the Scandinavian countries is much more common. The most recent population-based figure from Norway, derived from the fertility survey carried out by the Central Bureau of Statistics in 1988, is 31%. Curiously, in Norway and Sweden and most likely in some other countries the device is still popularly called ‘the spiral’ although few realise that the word refers to Margulie’s short-lived spiral-shaped device from the early 1960s. Neither loops nor bows nor shields nor sevens became catchwords. Although IUDs were never very popular in the USA, the unfortunate case of the Dalkon Shield undoubtedly caused a set-back. Women fitted with that device developed pelvic inflammatory disease (PID) disturbingly often. Like most other IUDs the Dalkon Shield had a thread which, according to instructions, should protrude through the external cervical 0s into the vagina. As it later turned out, the thread of this particular device was multifilamentous while all the other IUDs had a single-filament thread. It was shown that the multi-filament thread ‘sucked’ or transported bacteria into the uterine cavity by capillary attraction. This is the most plausible explanation for the preponderance of infectious complications caused by the Dalkon Shield. The ensuing claims for economic compensation frightened most of the I U D manufacturers into withdrawing their devices from the US market. Only two are now left. One of these is the progesterone-releasing Progestasert, which fell into disrepute long ago because of unacceptable failure rates and ectopic pregnancies. Besides, it has to be replaced yearly. Between I?’
1982 and 1988, the number of women using IUDs in the USA declined by two-thirds. Religious and ethnic beliefs pose other constraints on I U D use. In Catholic countries, concern that the I U D acts as an abortifacient makes it widely suspect. However, in Mexico the user-prevalence is about 10%, and in some other Latin American countries, notably Brazil, it is at least beginning to be tolerated, according to personal information from an informed source in the World Health Organization. On research, past and present Except for sterilization and Norplant, the I U D i s the only modern contraceptive modality which is largely user-independent. Its effect is reversible, although removal of the device requires medical assistance which, in any but the most exceptional case, is an easy matter. High continuation rates attest to its popularity. Over the years, much research has been carried out on the mode of action, contraceptive efficacy, expulsion rates and side-effects of the IUDs, such as uterine perforation, abdominal cramps, increased blood loss, ectopic pregnancy and PID. For a brief overall review, I recommend the WHO Technical Report Series 753, from 1987, ‘Mechanism of action, safety and efficacy of intrauterine devices’, which also has an extensive bibliography. The copper-containing IUDs were smaller than the inert models, a clear advantage with regard to side-effects. On the other hand, they had to be changed from time to time because of gradual loss of copper, and n o one in the beginning knew how long they retained their contraceptive effect. To b e o n the safe side, the manufacturers initially advised a change of device every one or two years. This increased sales, added to the workload of physicians and caused user-anxiety. With careful long-term follow-up studies the recommended interval before change has gradually increased. This is in large part Acta Obstet Gynecol Scand 71 (1992)
164
Per Bergsje
due to research initiated by the World Health Organization's (WHO'S) Special Programme of Research, Development and Research Training in Human Reproduction (the Human Reproduction Programme. o r HRP). HRP, which I described in the Acta Editorial in No. 4-5, 1991, has a Research Group on Intrauterine Devices. This group has now released data with important news on the long-term efficacy of the most widely used copper IUDs and on the IUD-associated risk of PID. There was an article in Contruception in August 1990, No. 2 (1990; 42: 141-58) which gave the results of HRP-conducted long-term randomized comparative trials with u p to 7 years' observation time, on the devices TCu220C, Multiload 250, Nova T and TCu380A. In one of these, the Nova T was discontinued because it had significantly higher cumulative pregnancy rates after 5 years of use than TCu220C, the rates being 12.3% and 6.6% respectively. The randomized study comparing the copper devices TCu220C and TCu3XOA has now passed 9 ycars o f observation for 534 of the enrolled women (267 on each device). At the end of 9 years, the cumulative pregnancy rates were 5.4 per 100 woman-years for TCu220C and 2.1 for TCu380A. Broken down into annual failure rates, the figure is less than 1 pregnancy per 100 woman-years from the second year of use for TCu220C and considerably less for TCu380A. with no indication of a change with time. The difference in failure rates between the two devices in this trial is highly significant 0, < 0.001 at 9 years). An important consequence of this study was that the United States Food and Drug Administration last year (1991) approved the use of TCu380A for up to 8 years without change. In a newer, randomized study which started in 1989, TCu3XOA is compared with Multiload 375. Interim data at 18 completed months show low failure rates, low expulsion rates and continuation rates of about 90% for both devices. It is too early to publish this information, as data keep coming in, but the figures I have seen for Multiload 375 coincide nicely with thosc in LGvset's 4-year observational study, published in Actu Ohstetricia et Cynecologica Scandinavica in 1990 (1990: 69: 521-6). Another H R P study on IUDs and PID was publishcd in The Lancet 28. March 1992 (Vol. 339: 7XSf). The researchers (Farley et al.) utilized collective information from 12 randomized studies, in which every case of suspected PID was reviewed by a gynecologist who was unaware o f which I U D type the women had used. The analysis included almost 23.000 I U D insertions, with up to 10 years' ohservation time for some of the subjects. Briefly stated, the overall PID rate was 1.6 cases per 1,000 woman-
years of use, which is reassuringly low. Furthermore. it was found that PID risk was more than six times higher during the 20 days following insertion than later, when it was low and constant over time. The risk was higher for IUDs inserted before than after 1980, higher for insertions in Africa than in other regions, lowest in China, and higher in women below 25 years of age.
What is rhe lesson? What, then, is the lesson learned and how can we utilize the new knowledge in our daily practice? As already mentioned, the news is reassuring. The use of large databases derived from carefully planned and supervised studies attests to the quality and robustness of the results. When certain precautions are taken, the best copper-containing IUDs rank among the safest and most efficient contraceptive modalities. When one type of I U D has been shown to be significantly more efficacious than one o r two others, should women be advised to have old devices of the latter types replaced by the better o n e ? The answer will depend on the degree o f demonstrated difference in efficacy and on a comparison of other qualities of the devices in question. In the present case, TCu380A performed better than TCu2XOC. However, the latter device is still highly protective against pregnancy, and it may be argued that changing devices represents a risk in itself which more than outweighs the possible advantage. On the other hand, for new insertions TCu38OA may be advised, if comparison of side-effects and price does not disqualify it. Such information must be sought elsewhere. Given the present knowledge about long-term efficacy of the two types of Copper-T, it does not seem irresponsible to advise that these devices can be retained without changing them for as long as the individual wearer needs contraception. As most o f the long-term users will be in their thirties, they have the added security of gradual, age-dependent decreasing fertility plus, in most cases, a decline in sexual activity. The fact that the first 20 days after insertion is a period of substantially increased PID risk should give rise to a discussion about pre-insertion tcsting for gonococci and chlamydiac, and antibiotics as prophylaxis at insertion. The best advice at present would be to employ these measures on an individual basis. If every woman fitted with an I U D were t o have an antibiotic, about 2,000 would have to take the medicine unnecessarily for each case in need. However, it may be wise to arrange for a control consultation as early as 2 weeks after insertion, at a
Editoriul time when an imminent infectious complication may be detected and treated. Truly, not every question concerning IUD use was ;Iddressed in the new studies, continued vigilance is required, and more data will certainly be analyzed, but we need hardly fear any untoward surprises.
165
Addendum: During the preparation of this Editorial. I had fruitful discussions with, and received valuable comments from, Timothy M. M. Farley, Olav Mcirik and Patrick J. Rowe at in Geneva. I thank them all. P. B .
Per Bergsjg
Acto Obstei
Cynrcol Scand 71 (1YY2)
Update on the intrauterine contraceptive device _______~
Acia Ohmet Gynecol Scand 1992; 71: 163-165
Intrauterine contraceptive devices (IUDs) are presently estimated to be used by 84 million women world-wide. Approximately 86% of the users are in the People’s Republic of China. In other countries, the frequency of users among fertile couples varies greatly, with no consistent trend along socioeconomic lines. For example, only 2 to 4% of fertile women in the USA, Canada, Australia and New Zealand use IUDs, while use in the Scandinavian countries is much more common. The most recent population-based figure from Norway, derived from the fertility survey carried out by the Central Bureau of Statistics in 1988, is 31%. Curiously, in Norway and Sweden and most likely in some other countries the device is still popularly called ‘the spiral’ although few realise that the word refers to Margulie’s short-lived spiral-shaped device from the early 1960s. Neither loops nor bows nor shields nor sevens became catchwords. Although IUDs were never very popular in the USA, the unfortunate case of the Dalkon Shield undoubtedly caused a set-back. Women fitted with that device developed pelvic inflammatory disease (PID) disturbingly often. Like most other IUDs the Dalkon Shield had a thread which, according to instructions, should protrude through the external cervical 0s into the vagina. As it later turned out, the thread of this particular device was multifilamentous while all the other IUDs had a single-filament thread. It was shown that the multi-filament thread ‘sucked’ or transported bacteria into the uterine cavity by capillary attraction. This is the most plausible explanation for the preponderance of infectious complications caused by the Dalkon Shield. The ensuing claims for economic compensation frightened most of the I U D manufacturers into withdrawing their devices from the US market. Only two are now left. One of these is the progesterone-releasing Progestasert, which fell into disrepute long ago because of unacceptable failure rates and ectopic pregnancies. Besides, it has to be replaced yearly. Between I?’
1982 and 1988, the number of women using IUDs in the USA declined by two-thirds. Religious and ethnic beliefs pose other constraints on I U D use. In Catholic countries, concern that the I U D acts as an abortifacient makes it widely suspect. However, in Mexico the user-prevalence is about 10%, and in some other Latin American countries, notably Brazil, it is at least beginning to be tolerated, according to personal information from an informed source in the World Health Organization. On research, past and present Except for sterilization and Norplant, the I U D i s the only modern contraceptive modality which is largely user-independent. Its effect is reversible, although removal of the device requires medical assistance which, in any but the most exceptional case, is an easy matter. High continuation rates attest to its popularity. Over the years, much research has been carried out on the mode of action, contraceptive efficacy, expulsion rates and side-effects of the IUDs, such as uterine perforation, abdominal cramps, increased blood loss, ectopic pregnancy and PID. For a brief overall review, I recommend the WHO Technical Report Series 753, from 1987, ‘Mechanism of action, safety and efficacy of intrauterine devices’, which also has an extensive bibliography. The copper-containing IUDs were smaller than the inert models, a clear advantage with regard to side-effects. On the other hand, they had to be changed from time to time because of gradual loss of copper, and n o one in the beginning knew how long they retained their contraceptive effect. To b e o n the safe side, the manufacturers initially advised a change of device every one or two years. This increased sales, added to the workload of physicians and caused user-anxiety. With careful long-term follow-up studies the recommended interval before change has gradually increased. This is in large part Acta Obstet Gynecol Scand 71 (1992)
164
Per Bergsje
due to research initiated by the World Health Organization's (WHO'S) Special Programme of Research, Development and Research Training in Human Reproduction (the Human Reproduction Programme. o r HRP). HRP, which I described in the Acta Editorial in No. 4-5, 1991, has a Research Group on Intrauterine Devices. This group has now released data with important news on the long-term efficacy of the most widely used copper IUDs and on the IUD-associated risk of PID. There was an article in Contruception in August 1990, No. 2 (1990; 42: 141-58) which gave the results of HRP-conducted long-term randomized comparative trials with u p to 7 years' observation time, on the devices TCu220C, Multiload 250, Nova T and TCu380A. In one of these, the Nova T was discontinued because it had significantly higher cumulative pregnancy rates after 5 years of use than TCu220C, the rates being 12.3% and 6.6% respectively. The randomized study comparing the copper devices TCu220C and TCu3XOA has now passed 9 ycars o f observation for 534 of the enrolled women (267 on each device). At the end of 9 years, the cumulative pregnancy rates were 5.4 per 100 woman-years for TCu220C and 2.1 for TCu380A. Broken down into annual failure rates, the figure is less than 1 pregnancy per 100 woman-years from the second year of use for TCu220C and considerably less for TCu380A. with no indication of a change with time. The difference in failure rates between the two devices in this trial is highly significant 0, < 0.001 at 9 years). An important consequence of this study was that the United States Food and Drug Administration last year (1991) approved the use of TCu380A for up to 8 years without change. In a newer, randomized study which started in 1989, TCu3XOA is compared with Multiload 375. Interim data at 18 completed months show low failure rates, low expulsion rates and continuation rates of about 90% for both devices. It is too early to publish this information, as data keep coming in, but the figures I have seen for Multiload 375 coincide nicely with thosc in LGvset's 4-year observational study, published in Actu Ohstetricia et Cynecologica Scandinavica in 1990 (1990: 69: 521-6). Another H R P study on IUDs and PID was publishcd in The Lancet 28. March 1992 (Vol. 339: 7XSf). The researchers (Farley et al.) utilized collective information from 12 randomized studies, in which every case of suspected PID was reviewed by a gynecologist who was unaware o f which I U D type the women had used. The analysis included almost 23.000 I U D insertions, with up to 10 years' ohservation time for some of the subjects. Briefly stated, the overall PID rate was 1.6 cases per 1,000 woman-
years of use, which is reassuringly low. Furthermore. it was found that PID risk was more than six times higher during the 20 days following insertion than later, when it was low and constant over time. The risk was higher for IUDs inserted before than after 1980, higher for insertions in Africa than in other regions, lowest in China, and higher in women below 25 years of age.
What is rhe lesson? What, then, is the lesson learned and how can we utilize the new knowledge in our daily practice? As already mentioned, the news is reassuring. The use of large databases derived from carefully planned and supervised studies attests to the quality and robustness of the results. When certain precautions are taken, the best copper-containing IUDs rank among the safest and most efficient contraceptive modalities. When one type of I U D has been shown to be significantly more efficacious than one o r two others, should women be advised to have old devices of the latter types replaced by the better o n e ? The answer will depend on the degree o f demonstrated difference in efficacy and on a comparison of other qualities of the devices in question. In the present case, TCu380A performed better than TCu2XOC. However, the latter device is still highly protective against pregnancy, and it may be argued that changing devices represents a risk in itself which more than outweighs the possible advantage. On the other hand, for new insertions TCu38OA may be advised, if comparison of side-effects and price does not disqualify it. Such information must be sought elsewhere. Given the present knowledge about long-term efficacy of the two types of Copper-T, it does not seem irresponsible to advise that these devices can be retained without changing them for as long as the individual wearer needs contraception. As most o f the long-term users will be in their thirties, they have the added security of gradual, age-dependent decreasing fertility plus, in most cases, a decline in sexual activity. The fact that the first 20 days after insertion is a period of substantially increased PID risk should give rise to a discussion about pre-insertion tcsting for gonococci and chlamydiac, and antibiotics as prophylaxis at insertion. The best advice at present would be to employ these measures on an individual basis. If every woman fitted with an I U D were t o have an antibiotic, about 2,000 would have to take the medicine unnecessarily for each case in need. However, it may be wise to arrange for a control consultation as early as 2 weeks after insertion, at a
Editoriul time when an imminent infectious complication may be detected and treated. Truly, not every question concerning IUD use was ;Iddressed in the new studies, continued vigilance is required, and more data will certainly be analyzed, but we need hardly fear any untoward surprises.
165
Addendum: During the preparation of this Editorial. I had fruitful discussions with, and received valuable comments from, Timothy M. M. Farley, Olav Mcirik and Patrick J. Rowe at in Geneva. I thank them all. P. B .
Per Bergsjg
Acto Obstei
Cynrcol Scand 71 (1YY2)
