- Email: [email protected]
The intrauterine device, pelvic inflammatory disease, and infertility: the confusion between hypothesis and knowledge
Perspectives FERTILITY AND STERILITY Copyright
©
1992 The American Fertility Society
Vol. 58, No.4, October 1992
Printed on acid-free paper in U.S.A.
The intrauterine device, pelvic inflammatory disease, and infertility: the confusion between hypothesis and knowledge
David A. Grimes, M.D. Departments of Obstetrics and Gynecology and Preventive Medicine, University of Southern California School of Medicine, Los Angeles, California
As suggested by a recent editorial (1) in this journal, the intrauterine device (IUD) is intimately related to the health and well being of women in an overcrowded world. Contrary to the conclusions of the editorial, however, that relationship is strongly beneficial (2). The editorial accompanied a review article about the Dalkon Shield (3), which has not been marketed in over 15 years; extrapolation from experience with the Dalkon Shield to today's medicated IUDs is neither timely nor justified. In medicine, the intensity of opinions about a controversial issue tends to be related inversely to the amount of information available. The IUD is a paradigm. For many years, limited information based on flawed studies spawned passionately held views on IUD safety. Larger more sophisticated epidemiologic studies in recent years have allowed passions to cool, yet much misinformation persists (1). "Modern efficacious contraception has not very effectively reduced human reproduction (1)." This nihilistic claim (without any reference) is refuted by experience around the world. The introduction of family-planning programs has lowered dramatically fertility rates in countries as diverse as Hong Kong, Indonesia, Singapore, Thailand, Mexico, Tunisia, and Mauritius. Although improved socioeconomic conditions play an important role in fertility declines, modern contraception clearly works. Much of the failure of fertility control is because "The most compelling female drive is to become a
Received July 13, 1992. Reprint requests: David A. Grimes, M.D., Department of Obstetrics and Gynecology, Women's Hospital, 1240 North Mission Road, Los Angeles, California 90033. 670
Grimes
The intrauterine device
mother (1)." For physicians (especially those of us who are men) to publish broad generalizations about "female drives" seems insensitive at best. For some women, the most compelling drive may be to become a concert violinist, pilot, or nun. Attributing high fertility rates in developing countries to maternal longings may be blaming the victims. In some cultures, the social value of women derives from their bearing children. Women in these societies may have little control over the frequency or timing of coitus, and their access to contraception may be limited. Moreover, their sexual partners may oppose or prohibit their use of contraception. One hundred thousand to 200,000 deaths from illegal abortions worldwide each year testify to the determination-indeed, desperation-of many women to limit their childbearing. The IUD is a "potential threat to future fertility (1)." Ironically, coitus is the real threat to future fertility. The risk may increase with frequent intercourse, multiple partners, or exposure to sexually transmitted diseases. Although many factors have been linked to impaired fertility, ranging from cocaine use to cigarette smoking, coitus is the presumed mechanism for acquisition of nearly all upper genital tract infections leading to tubal infertility. Based on two case-control studies, prior IUD use increases the risk of tubal infertility from two- to sixfold (1). What do these studies (4-6) say about contemporary IUDs? The initial Seattle-based study (4) found no statistically significant increase in the risk of primary tubal infertility for women who had ever used (or only used) a copper IUD. The same held true for women who had only used a copper IUD and who had the IUD removed because of medical problems. In the companion paper from the East Fertility and Sterility
coast (5), the role of number of sexual partners dominated. Women with only one sexual partner had no significant increase in the risk of primary tubal infertility associated with IUD use. The third reference (6) cited in the editorial (1) was a letter to the editor reanalyzing the initial study (4). With a different mix of cases and controls, the relative risk of primary tubal infertility associated with copper IUDs became statistically significant. If one assumes that the conclusion about the safety of copper IUDs (consistent with the literature) in the initial study (4) was incorrect, it is unclear why nearly 7 years were required to recognize and correct this error. Consistency of findings is an important criterion for judging whether associations may be causal. Corroboration of the alleged increased risk of tubal infertility (1) associated with modern IUD use is lacking (2). As recommended by the World Health Organization (WHO) Scientific Group (2), two studies (7, 8) have specifically addressed the important issue of fertility among women who had their IUDs removed because of complications. In a followup study of~opper IUD users from New Zealand (7), women who discontinued use because of complications had compa~able fertility rates at 36 months, as did women who had the device removed for a planned pregnancy (92% versus 94%). This finding was corroborated by a similar study (8) of copper IUD users in Norway. " . . . the IUD causes PID (1)." As the author noted, there is wide agreement concerning a transient increase in the risk after IUD insertion in some women; this risk is presumably related to passive introduction of bacteria into the uterus during the insertion process. There is now both microbiologic and epidemiologic evidence (9) to support the hypothesis that instrumentation of the uterus may cause pelvic inflammatory disease (PID). But what of the IUD itself? Here again, evidence is lacking. As pointed out by the WHO Scientific Group (2) and others, three persistent methodologic flaws in early studies of this question led to a spurious estimate of the relative risk. First, many studies used the wrong comparison group, i.e., women using birth control pills, barrier contraceptives, or spermicides, all of which lower the risk of PID. If these methods reduce the risk by one half and if the IUD has no effect on the risk, then the apparent relative risk of PID associated with IUD use compared with other methods is 2.0, or a 100% "increase." Second, because the diagnosis of PID is rarely made by objective means, there is a strong possibility of selective Vol. 58, No.4, October 1992
overdiagnosis of PID in women with pelvic complaints and a telltale string protruding from the cervix. Third, many studies inadequately controlled for the potentially confounding influence of factors such as number of sexual partners and cigarette smoking. A telling example of the impact of these biases is the recent reanalysis of the Oxford/Family Planning Association study. In 1981, Vessey and his associates (see Buchan et al. [10]) reported a highly significant relative risk of PID of 10.5 associated with IUD use. After taking into account the biases identified by the WHO Scientific Group (2), Vessey's team reanalyzed their data and found no statistically significant increase in the risk of PID associated with medicated IUDs. The largest and most sophisticated study of this question in the United States has been the Women's Health Study, a multicenter case-control study analyzed by the Centers for Disease Control. In 1983, Lee and her associates (9) demonstrated that the risk of PID associated with IUD use was inversely related to time from insertion: by 5 or more months after insertion, the risk was not significantly elevated. In a further analysis of the Women's Health Study, Lee and her colleagues showed that for women who were married or cohabiting and with only one sexual partner in the past 6 months, there was no significant increase in the risk of PID even in the first critical months after insertion. Is there a problem with the IUD? The Achilles heel of the IUD is that, unlike other modern contraceptives' it does not protect a woman from the consequences of her partner's sexual behavior or her own sexual behavior. Unlike other contraceptives, the IUD does not reduce the risk of PID. The IUD "facilitates the development of PID in patients with Neisseria gonorrhoeae and Chlamydia trachomatis (1)." To support this hypothesis, the author cited a Swedish study (11) of women with gonorrhea. Interestingly, the study (11) did not reach this conclusion; instead, the Swedish authors noted that "No significant difference [in the risk of PID] was found between IUD-users and patients using neither hormonal contraceptives nor IUDs (p. 153)." The other study (12) cited in defense of this hypothesis had objective assessment of outcomes but used the wrong comparison group and failed to control for potential confounding factors, such as numbers of sexual partners. These methodologic shortcomings (2) preclude any inferences about the potential role of the IUD. "It is important to realize that most PID occurs 6 months or more after insertion . . . (1)." This Grimes
The intrauterine device
671
claim relates only to numerators, not to incidence rates or relative risks of PID, the more relevant issues. Because the IUD does not protect women from community-acquired PID, women using IUDs can be expected to continue to experience the usual rates of PID, estimated to be 1 to 2% per year. Thus, over many years of use, "most" cases of PID may occur more than 6 months after insertion. However, this provides no information about a potential causal relation to the IUD. On the other hand, large case-series reports, cohort studies, case-control studies (9), and randomized controlled trials (13) all indicate that any increased risk of PID related solely to the IUD closely follows insertion. In the recent analysis of WHO trials (13) encompassing over 22,000 women, the incidence of PID in IUD users beyond the first 20 days after insertion was low and stable. "Because of this increased risk with insertion, IUDs should be left in place up to their maximum lifespan and should not routinely be replaced earlier . . . (13)." Bacteria colonize in a biofilm on the string and body of IUDs, posing risks of abscesses (1). If this hypothetical mechanism were of etiologic importance, then rates of infection should increase with duration of use. As demonstrated above, the opposite is true (9, 13). In addition, IUDs with tailstrings should be associated with higher rates of infection than those without strings. Both cohort studies and a randomized controlled trial (14) refute this notion. One report found a significant difference in this regard, but it focused on removals rather than on diagnoses of infection. This finding was the result of a self-fulfilling prophecy: devices with strings are more likely to be removed for a given complaint than are devices without strings, which require an intrauterine operation to remove. The claim that prolonged IUD use leads to abscess formation probably stems from six patients in a single study (15). This finding appears to result from heavy representation of the Dalkon Shield in the long-term data (more than 5 years of use); however, there was no representation of copper IUDs in the long-term data. Unlike other analyses of the Women's Health Study (9), this analysis (15) used the wrong comparison group (2). The "weight of evidence from controlled studies of PID and infertility. . . demonstrates a clear cause and effect relationship between the IUD and PID (1)." Four references were offered in support ofthis hypothesis. What is the "weight of evidence" provided? The first study (4) showed no significant increase in the risk of primary tubal infertility among 672
Grimes
The intrauterine device
former users of copper IUDs; the second (5) showed no significant increase in risk for IUD users withonly one sexual partner. The third (9) showed no significant increase in the risk of PID beyond 4 months after insertion. Further analysis of this study showed no significant increase in the risk of PID even in the first 4 months of IUD use among lowrisk women. The fourth (16) argued that the third (9) had exaggerated the relative risk estimate; after reanalysis ofthe Women's Health Study, the authors determined that "The conclusion ofthe WHS should have been that IUDs do not increase the risk of PID (p. 110)." These four citations hardly support the hypothesis that IUDs cause PID; indeed, they argue against it. Uncritical thinking affords hypotheses the credibility and respect that should be reserved for knowledge. This does a disservice to the IUD and, ultimately, to the women whom we serve. A dispassionate examination of the evidence, now encompassing hundreds of millions of woman-years of worldwide experience, supports the conclusion of experts around the world: "the currently available copper and hormone-releasing IUDs, when properly used, are probably the most effective and reliable reversible method of fertility regulation (2)." Key Words: Intrauterine device, pelvic inflammatory disease, salpingitis, tubal infertility, epidemiology, Neisseria gonorrhoeae, Chlamydia trachomatis, tail strings. REFERENCES 1. Eschenbach DA. Earth, motherhood, and the intrauterine device. Fertil Steril 1992;57:1177-9. 2. World Health Organization Scientific Group. Mechanism of action, safety and efficacy of intrauterine devices. Geneva: World Health Organization Technical Report Series 753, 1987. 3. Mumford SD, Kessel E. Was the Dalkon Shield a safe and effective intrauterine device? The conflict between case-control and clinical trial study findings. Fertil Steril 1992;57: 1151-76. 4. Daling JR, Weiss NS, Metch BJ, Chow WH, Soderstrom RM, Moore DE, et al. Primary tubal infertility in relation to the use of an intrauterine device. N Engl J Med 1985;312: 937-4l. 5. Cramer DW, Schiff I, Schoenbaum SC, Gibson M, Belisle S, Albrecht B, et aI. Tubal infertility and the intrauterine device. N Engl J Med 1985;312:941-7. 6. Daling JR, Weiss NS, Voigt LF, McKnight B, Moore DE. The intrauterine device and primary infertility. N Engl J Med 1992;326:203-4. 7. Wilson JC. A prospective New Zealand study of fertility after removal of copper intrauterine contraceptive devices for conception and because of complications: a four-year study. Am J Obstet GynecoI1989;160:391-6.
Fertility and Sterility
8. Skjeldestad F, Bratt H. Fertility after complicated and noncomplicated use of IUDs. A controlled prospective study. Adv Contracept 1988;4:179-84. 9. Lee NC, Rubin GL, Ory HW, Burkman RT. Type of intrauterine device and the risk of pelvic inflammatory disease. Obstet Gynecol1983;62:1-6. 10. Buchan H, Villard-Mackintosh L, Vessey M, Yeates D, McPherson K. Epidemiology of pelvic inflammatory disease in parous women with special reference to intrauterine device use. Br J Obstet Gynaecol 1990;97:780-8. 11. Ryden G, Fahraeus L, Molin L, Ahman K. Do contraceptives influence the incidence of acute pelvic inflammatory disease in women with gonorrhea? Contraception 1979;20:149-57. 12. Gump DW, Gibson M, Ashikaga T. Evidence of prior pelvic inflammatory disease and its relationship to Chlamydia trachomatis antibody and intrauterine contraceptive device use in infertile women. Am J Obstet Gynecol1983;146:153-9. 13. Farley TMM, Rosenberg MJ, Rowe PJ, Chen J-H, Meirik O. Intrauterine devices and pelvic inflammatory disease: an international perspective. Lancet 1992;339:785-8. 14. Chi I, Champion CB, Farr G, Potts M. Two clinical trials designed to evaluate the prevention of pelvic inflammatory disease in IUD users. Infect Med Dis Letters Obstet Gynecol 1990;12:3-6. 15. Stadel BV, Schlesselman S. Extent of surgery for pelvic inflammatory disease in relation to duration of intrauterine device use. Obstet Gynecol1984;63:171-8.
Vol. 58, No.4, October 1992
16. Kronmal RA, Whitney CW, Mumford SD. The intrauterine device and pelvic inflammatory disease: the Women's Health Study reanalyzed. J Clin Epidemiol 1991;44:109-22.
Note. Additional references are available from author upon request.
Comment
Nothing in recent memory has ignited such an intense desire to express counter-opinion as the Editor's Corner (1) that accompanied the Modern Trends article on the Dalkon Shield published in the June 1992 issue of Fertility and Sterility (3). There are many of our colleagues in this country and with the World Health Organization abroad who see another part of the elephant and strongly support modern IUD usage. Therefore, we are pleased to publish Dr. Grimes' counter-opinion in this new Perspectives section. As others before me have observed, if an editor can stimulate thoughtful congenial debate, perhaps he or she is doing something right. The Editor
Grimes
The intrauterine device
673
©
1992 The American Fertility Society
Vol. 58, No.4, October 1992
Printed on acid-free paper in U.S.A.
The intrauterine device, pelvic inflammatory disease, and infertility: the confusion between hypothesis and knowledge
David A. Grimes, M.D. Departments of Obstetrics and Gynecology and Preventive Medicine, University of Southern California School of Medicine, Los Angeles, California
As suggested by a recent editorial (1) in this journal, the intrauterine device (IUD) is intimately related to the health and well being of women in an overcrowded world. Contrary to the conclusions of the editorial, however, that relationship is strongly beneficial (2). The editorial accompanied a review article about the Dalkon Shield (3), which has not been marketed in over 15 years; extrapolation from experience with the Dalkon Shield to today's medicated IUDs is neither timely nor justified. In medicine, the intensity of opinions about a controversial issue tends to be related inversely to the amount of information available. The IUD is a paradigm. For many years, limited information based on flawed studies spawned passionately held views on IUD safety. Larger more sophisticated epidemiologic studies in recent years have allowed passions to cool, yet much misinformation persists (1). "Modern efficacious contraception has not very effectively reduced human reproduction (1)." This nihilistic claim (without any reference) is refuted by experience around the world. The introduction of family-planning programs has lowered dramatically fertility rates in countries as diverse as Hong Kong, Indonesia, Singapore, Thailand, Mexico, Tunisia, and Mauritius. Although improved socioeconomic conditions play an important role in fertility declines, modern contraception clearly works. Much of the failure of fertility control is because "The most compelling female drive is to become a
Received July 13, 1992. Reprint requests: David A. Grimes, M.D., Department of Obstetrics and Gynecology, Women's Hospital, 1240 North Mission Road, Los Angeles, California 90033. 670
Grimes
The intrauterine device
mother (1)." For physicians (especially those of us who are men) to publish broad generalizations about "female drives" seems insensitive at best. For some women, the most compelling drive may be to become a concert violinist, pilot, or nun. Attributing high fertility rates in developing countries to maternal longings may be blaming the victims. In some cultures, the social value of women derives from their bearing children. Women in these societies may have little control over the frequency or timing of coitus, and their access to contraception may be limited. Moreover, their sexual partners may oppose or prohibit their use of contraception. One hundred thousand to 200,000 deaths from illegal abortions worldwide each year testify to the determination-indeed, desperation-of many women to limit their childbearing. The IUD is a "potential threat to future fertility (1)." Ironically, coitus is the real threat to future fertility. The risk may increase with frequent intercourse, multiple partners, or exposure to sexually transmitted diseases. Although many factors have been linked to impaired fertility, ranging from cocaine use to cigarette smoking, coitus is the presumed mechanism for acquisition of nearly all upper genital tract infections leading to tubal infertility. Based on two case-control studies, prior IUD use increases the risk of tubal infertility from two- to sixfold (1). What do these studies (4-6) say about contemporary IUDs? The initial Seattle-based study (4) found no statistically significant increase in the risk of primary tubal infertility for women who had ever used (or only used) a copper IUD. The same held true for women who had only used a copper IUD and who had the IUD removed because of medical problems. In the companion paper from the East Fertility and Sterility
coast (5), the role of number of sexual partners dominated. Women with only one sexual partner had no significant increase in the risk of primary tubal infertility associated with IUD use. The third reference (6) cited in the editorial (1) was a letter to the editor reanalyzing the initial study (4). With a different mix of cases and controls, the relative risk of primary tubal infertility associated with copper IUDs became statistically significant. If one assumes that the conclusion about the safety of copper IUDs (consistent with the literature) in the initial study (4) was incorrect, it is unclear why nearly 7 years were required to recognize and correct this error. Consistency of findings is an important criterion for judging whether associations may be causal. Corroboration of the alleged increased risk of tubal infertility (1) associated with modern IUD use is lacking (2). As recommended by the World Health Organization (WHO) Scientific Group (2), two studies (7, 8) have specifically addressed the important issue of fertility among women who had their IUDs removed because of complications. In a followup study of~opper IUD users from New Zealand (7), women who discontinued use because of complications had compa~able fertility rates at 36 months, as did women who had the device removed for a planned pregnancy (92% versus 94%). This finding was corroborated by a similar study (8) of copper IUD users in Norway. " . . . the IUD causes PID (1)." As the author noted, there is wide agreement concerning a transient increase in the risk after IUD insertion in some women; this risk is presumably related to passive introduction of bacteria into the uterus during the insertion process. There is now both microbiologic and epidemiologic evidence (9) to support the hypothesis that instrumentation of the uterus may cause pelvic inflammatory disease (PID). But what of the IUD itself? Here again, evidence is lacking. As pointed out by the WHO Scientific Group (2) and others, three persistent methodologic flaws in early studies of this question led to a spurious estimate of the relative risk. First, many studies used the wrong comparison group, i.e., women using birth control pills, barrier contraceptives, or spermicides, all of which lower the risk of PID. If these methods reduce the risk by one half and if the IUD has no effect on the risk, then the apparent relative risk of PID associated with IUD use compared with other methods is 2.0, or a 100% "increase." Second, because the diagnosis of PID is rarely made by objective means, there is a strong possibility of selective Vol. 58, No.4, October 1992
overdiagnosis of PID in women with pelvic complaints and a telltale string protruding from the cervix. Third, many studies inadequately controlled for the potentially confounding influence of factors such as number of sexual partners and cigarette smoking. A telling example of the impact of these biases is the recent reanalysis of the Oxford/Family Planning Association study. In 1981, Vessey and his associates (see Buchan et al. [10]) reported a highly significant relative risk of PID of 10.5 associated with IUD use. After taking into account the biases identified by the WHO Scientific Group (2), Vessey's team reanalyzed their data and found no statistically significant increase in the risk of PID associated with medicated IUDs. The largest and most sophisticated study of this question in the United States has been the Women's Health Study, a multicenter case-control study analyzed by the Centers for Disease Control. In 1983, Lee and her associates (9) demonstrated that the risk of PID associated with IUD use was inversely related to time from insertion: by 5 or more months after insertion, the risk was not significantly elevated. In a further analysis of the Women's Health Study, Lee and her colleagues showed that for women who were married or cohabiting and with only one sexual partner in the past 6 months, there was no significant increase in the risk of PID even in the first critical months after insertion. Is there a problem with the IUD? The Achilles heel of the IUD is that, unlike other modern contraceptives' it does not protect a woman from the consequences of her partner's sexual behavior or her own sexual behavior. Unlike other contraceptives, the IUD does not reduce the risk of PID. The IUD "facilitates the development of PID in patients with Neisseria gonorrhoeae and Chlamydia trachomatis (1)." To support this hypothesis, the author cited a Swedish study (11) of women with gonorrhea. Interestingly, the study (11) did not reach this conclusion; instead, the Swedish authors noted that "No significant difference [in the risk of PID] was found between IUD-users and patients using neither hormonal contraceptives nor IUDs (p. 153)." The other study (12) cited in defense of this hypothesis had objective assessment of outcomes but used the wrong comparison group and failed to control for potential confounding factors, such as numbers of sexual partners. These methodologic shortcomings (2) preclude any inferences about the potential role of the IUD. "It is important to realize that most PID occurs 6 months or more after insertion . . . (1)." This Grimes
The intrauterine device
671
claim relates only to numerators, not to incidence rates or relative risks of PID, the more relevant issues. Because the IUD does not protect women from community-acquired PID, women using IUDs can be expected to continue to experience the usual rates of PID, estimated to be 1 to 2% per year. Thus, over many years of use, "most" cases of PID may occur more than 6 months after insertion. However, this provides no information about a potential causal relation to the IUD. On the other hand, large case-series reports, cohort studies, case-control studies (9), and randomized controlled trials (13) all indicate that any increased risk of PID related solely to the IUD closely follows insertion. In the recent analysis of WHO trials (13) encompassing over 22,000 women, the incidence of PID in IUD users beyond the first 20 days after insertion was low and stable. "Because of this increased risk with insertion, IUDs should be left in place up to their maximum lifespan and should not routinely be replaced earlier . . . (13)." Bacteria colonize in a biofilm on the string and body of IUDs, posing risks of abscesses (1). If this hypothetical mechanism were of etiologic importance, then rates of infection should increase with duration of use. As demonstrated above, the opposite is true (9, 13). In addition, IUDs with tailstrings should be associated with higher rates of infection than those without strings. Both cohort studies and a randomized controlled trial (14) refute this notion. One report found a significant difference in this regard, but it focused on removals rather than on diagnoses of infection. This finding was the result of a self-fulfilling prophecy: devices with strings are more likely to be removed for a given complaint than are devices without strings, which require an intrauterine operation to remove. The claim that prolonged IUD use leads to abscess formation probably stems from six patients in a single study (15). This finding appears to result from heavy representation of the Dalkon Shield in the long-term data (more than 5 years of use); however, there was no representation of copper IUDs in the long-term data. Unlike other analyses of the Women's Health Study (9), this analysis (15) used the wrong comparison group (2). The "weight of evidence from controlled studies of PID and infertility. . . demonstrates a clear cause and effect relationship between the IUD and PID (1)." Four references were offered in support ofthis hypothesis. What is the "weight of evidence" provided? The first study (4) showed no significant increase in the risk of primary tubal infertility among 672
Grimes
The intrauterine device
former users of copper IUDs; the second (5) showed no significant increase in risk for IUD users withonly one sexual partner. The third (9) showed no significant increase in the risk of PID beyond 4 months after insertion. Further analysis of this study showed no significant increase in the risk of PID even in the first 4 months of IUD use among lowrisk women. The fourth (16) argued that the third (9) had exaggerated the relative risk estimate; after reanalysis ofthe Women's Health Study, the authors determined that "The conclusion ofthe WHS should have been that IUDs do not increase the risk of PID (p. 110)." These four citations hardly support the hypothesis that IUDs cause PID; indeed, they argue against it. Uncritical thinking affords hypotheses the credibility and respect that should be reserved for knowledge. This does a disservice to the IUD and, ultimately, to the women whom we serve. A dispassionate examination of the evidence, now encompassing hundreds of millions of woman-years of worldwide experience, supports the conclusion of experts around the world: "the currently available copper and hormone-releasing IUDs, when properly used, are probably the most effective and reliable reversible method of fertility regulation (2)." Key Words: Intrauterine device, pelvic inflammatory disease, salpingitis, tubal infertility, epidemiology, Neisseria gonorrhoeae, Chlamydia trachomatis, tail strings. REFERENCES 1. Eschenbach DA. Earth, motherhood, and the intrauterine device. Fertil Steril 1992;57:1177-9. 2. World Health Organization Scientific Group. Mechanism of action, safety and efficacy of intrauterine devices. Geneva: World Health Organization Technical Report Series 753, 1987. 3. Mumford SD, Kessel E. Was the Dalkon Shield a safe and effective intrauterine device? The conflict between case-control and clinical trial study findings. Fertil Steril 1992;57: 1151-76. 4. Daling JR, Weiss NS, Metch BJ, Chow WH, Soderstrom RM, Moore DE, et al. Primary tubal infertility in relation to the use of an intrauterine device. N Engl J Med 1985;312: 937-4l. 5. Cramer DW, Schiff I, Schoenbaum SC, Gibson M, Belisle S, Albrecht B, et aI. Tubal infertility and the intrauterine device. N Engl J Med 1985;312:941-7. 6. Daling JR, Weiss NS, Voigt LF, McKnight B, Moore DE. The intrauterine device and primary infertility. N Engl J Med 1992;326:203-4. 7. Wilson JC. A prospective New Zealand study of fertility after removal of copper intrauterine contraceptive devices for conception and because of complications: a four-year study. Am J Obstet GynecoI1989;160:391-6.
Fertility and Sterility
8. Skjeldestad F, Bratt H. Fertility after complicated and noncomplicated use of IUDs. A controlled prospective study. Adv Contracept 1988;4:179-84. 9. Lee NC, Rubin GL, Ory HW, Burkman RT. Type of intrauterine device and the risk of pelvic inflammatory disease. Obstet Gynecol1983;62:1-6. 10. Buchan H, Villard-Mackintosh L, Vessey M, Yeates D, McPherson K. Epidemiology of pelvic inflammatory disease in parous women with special reference to intrauterine device use. Br J Obstet Gynaecol 1990;97:780-8. 11. Ryden G, Fahraeus L, Molin L, Ahman K. Do contraceptives influence the incidence of acute pelvic inflammatory disease in women with gonorrhea? Contraception 1979;20:149-57. 12. Gump DW, Gibson M, Ashikaga T. Evidence of prior pelvic inflammatory disease and its relationship to Chlamydia trachomatis antibody and intrauterine contraceptive device use in infertile women. Am J Obstet Gynecol1983;146:153-9. 13. Farley TMM, Rosenberg MJ, Rowe PJ, Chen J-H, Meirik O. Intrauterine devices and pelvic inflammatory disease: an international perspective. Lancet 1992;339:785-8. 14. Chi I, Champion CB, Farr G, Potts M. Two clinical trials designed to evaluate the prevention of pelvic inflammatory disease in IUD users. Infect Med Dis Letters Obstet Gynecol 1990;12:3-6. 15. Stadel BV, Schlesselman S. Extent of surgery for pelvic inflammatory disease in relation to duration of intrauterine device use. Obstet Gynecol1984;63:171-8.
Vol. 58, No.4, October 1992
16. Kronmal RA, Whitney CW, Mumford SD. The intrauterine device and pelvic inflammatory disease: the Women's Health Study reanalyzed. J Clin Epidemiol 1991;44:109-22.
Note. Additional references are available from author upon request.
Comment
Nothing in recent memory has ignited such an intense desire to express counter-opinion as the Editor's Corner (1) that accompanied the Modern Trends article on the Dalkon Shield published in the June 1992 issue of Fertility and Sterility (3). There are many of our colleagues in this country and with the World Health Organization abroad who see another part of the elephant and strongly support modern IUD usage. Therefore, we are pleased to publish Dr. Grimes' counter-opinion in this new Perspectives section. As others before me have observed, if an editor can stimulate thoughtful congenial debate, perhaps he or she is doing something right. The Editor
Grimes
The intrauterine device
673