Copper in the menstrual and physiological cycle cervical mucus of copper IUD users (author's transl)

The article studies the concentration of copper in the cervical mucus of users and nonusers of copper IUDs. Of the 170 samples taken 90 were basal, i.e. taken from nonusers, and 80 were taken from users of No-Gravid, Dalkon Shield, Gravigard, Copper T, and Progestasert. Concentration of copper was much higher in IUD wearers than in nonwearers, even after 2 years from insertion, except in wearers of Dalkon Shield and of Progestasert. Copper concentration in wearers of Gravigard and Copper T were lower than concentrations found in wearers of No-Gravid.     

Selecting patients and inserting the Progestasert

In this article, the author discusses what is presently known about the Progestasert IUD, a progesterone delivery system. Progestasert delivers progesterone on a daily basis and in continuous fashion into the endometric cavity. It has no systemic effects, although there is increasing evidence of its effects on hypermenorrhea na dysmenorrhea. Evidence suggests that Progestasert may avoid one of the major problems associated with former IUDs (particularly the Dalkon Shield): salpingitis. More than 10 years ago, physicians observed during sterilization procedures that a large number of women wearing inert or copper IUDs had salpingitis. Data from 27 Progestasert users show that none had salpingitis at the time of sterilization. Progestasert may also carry a lower risk of pelvic inflammatory disease associated with IUD use. A study in Helsinki found only 3 cases of pelvic inflammatory disease in 20,000 women years use of progestin (Levonorgestrel) impregnated IUDs, compared to the expected incidence (according to the Center for Disease Control) of 1/100 woman years. Additionally, in a study involving over 300 patients, the use of prophylactic antibiotics after insertion twice a day for 5 days and inserting Progestasert during the time ovulation rather at the time of menstruation produced no cases of the pelvic inflammatory conditions usually associated with the insertion procedure. Concerning the risks of ectopic pregnancy, evidence suggests that progestasert tends towards more ectopics when compared to the copper IUDs, but towards less when compared to not using any contraception. Although Progestasert is not contraindicated in nulliparous patients, caution should be taken with such patients.     

What we've learned about IUDs from the Women's Health Study

A new look at data from the Women's Health Study, done in 1976-1978, focuses on the outcomes of pelvic inflammatory disease (PID) and its determinants, and ectopic pregnancy, in IUD users. The advantage of this data set is that it does not suffer from bias resulting from the bad publicity that IUDs have since received. 657 cases of PID ascertained by discharge diagnosis were compared to 2566 sexually active controls with non-gynecological conditions. The overall data showed that the Dalkon shield conferred a relative risk of 8.3, and the risk was slightly elevated for Progestasert and Copper-7, compared to women using no method of contraception. Broken down by duration of use, most of the risk was limited to the 1st 4 months of use, and the highest risk was in the 1st month, 3.8. Regarding aspects of sexual behavior, the risks were computed for women claiming only one sexual partner. Single and previously married women had about twice the risk of married or cohabiting women. It is likely that this can be explained by a higher proportion of women whose partners were monogamous among married and cohabiting women, than among single or divorced women. The risk of ectopic pregnancy was 0.4 for IUD and traditional method users, and 0.1 for pill users, compared to non-contracepting women. Thus IUDs put women at a slightly higher risk of ectopic pregnancy, but at a low absolute risk, since they lower the overall change of pregnancy.     

Incidence of extrauterine pregnancies in IUD users (author's transl)

In January 1979 the Food and Drug Administration (FDA) Published a report indicating that experimental clinical studies had demonstrated that conception by progesterone-releasing IUD (Progestasert) entailed more risk of ectopic pregnancy than contraception with other types of IUDs, and that such risk was similar to that of women not utilizing any contraceptive method. In this article the authors show that such indication is not correct, and that comparative studies and new epidemiological data clearly demonstrate that all IUD types carry the same risk of ectopic pregnancy. The FDA statement was probably based on data gathered under different protocols, from different patient populations, in very dissimilar conditions of study, and from badly chosen samples. Moreover, it appears that the FDA statement did not take into consideration other factors predisposing to ectopic pregnancy, such as endometritis and uterine fibroma.     

Inserting IUDs safely

A comprehensive discussion of safe insertion of IUDs in the contemporary U.S. setting, when any IUD complication may provoke litigation, includes explanations of complications listed on package inserts, what to look for in the pelvic exam, now to handle the inserter, whether to give prophylactic antibiotics or a cervical block, follow-up management, and advice on safe sex and hygiene. The similarities and differences in listed contraindications for the ParaGard and Progestasert IUDs are analyzed. It is important to know these listed contraindications to avoid being the sole defendant in a court case. Neither explicitly rules out nulliparas, and some women who have completed childbearing may be willing to risk ectopic pregnancy. The physician must be sure to avoid any possible risks of pelvic infection, however. It is important to postpone IUD insertion if there is any suggestion of lower genital tract infection. Similarly, IUD insertion is intended to last for years, so a paracervical block is recommended if access is difficult. Tips for ensuring scrupulous asepsis are suggested. Women for whom prophylactic antibiotics are advised include diabetics, those with heart valve disease or transplants. IUD patients should be clearly identified when they call in with complaints, and seen urgently. Finally, a sexual history should be taken to avoid candidates who engage in anal sex practices.     

The end of IUD marketing in the United States: what does it mean for American women?

The decision to suspend sale of the copper 7 and Copper T 200 IUDs and the Lippes loop in the US will eventually affect most of the US women using them. Although the Progestasert, a progesterone-containing device manufactured by the Alza Corp, will still be available, the Progestasert accounted for only 3% of IUD sales in 1984 compared to 66% for the 2 copper devices and 31% for the Lippes loops. Ortho Pharmaceutical and Searle, the manufacturers of the discontinued devices, were motivated largely by their difficulty in obtaining liability insurance and their desire to avoid excessive financial risk resulting from lawsuits, especially in view of the large judgements against the makers of the Dalkon Shield. Ortho was also influenced by declining sales of the Lippes loop. The 198 National Survey of Family Growth (NSFG) estimated that in that year some 2,152,900 American women used IUDs, representing 7.3% of the 29.5 million contraceptive users in the US and 10.8% of users of reversible methods. 30% of IUD users had stopped oral contraceptive (OC) use on the advice of their physicians. Slightly over 1/2 of IUD users were 30 years old or over. 63% were currently married. 12.8% had no children. 21.2% had already had an unwanted pregnancy and 54.7% said they wanted no more children. OCs were contraindicated for 56.4% of the IUD users because of age, smoking, or medical conditions. Most IUD users thus belonged to the group for whom the method is most suitable: older married women who have already had children. Lippes loops are inert and users can continue indefinitely with the method, but copper IUDs require periodic replacement, usually after 3 years. Some physicians and family planning programs have advised women using Lippes loops or copper IUDs to have them removed at once. It is difficult to predict what method will be utilized in the future by current IUD users; the near total disappearance of a contraceptive method is unprecedented. 3 estimates of the percentage of current IUD users who will have unwanted pregnancies in the next year under different assumptions about contraceptive choices were compared to the proportion risking unwanted pregnancies assuming continued availability of their IUDs: 4.2%. If all IUD users chose the next most effective method available to them--sterilization for those not wanting more children, OCs for those with no contraindications who might want more children, and condoms for the rest--the pregnancy rate would be 2.4%. The other estimates were 9.2% assuming less resort to sterilization and more to diaphragms and spermicides, and 13.0% assuming that 15% of the women would use no other contraceptive. Current users of IUDs are faced with a difficult choice about future method use, and need clear and reliable information from their physicians and the media on the risks and advantages of other methods.     

Steroid intra-uterine contraception: progesterone-releasing devices. II. Insertion,clinical problems and contraceptive dependability

The advantages and disadvantages of the progesterone-releasing intrauterine device (IUD), Progestasert, are investigated, relying on the published literature and the authors' own experiences. Insertion of the Progestasert presents very few problems except in certain cases, particularly in nulliparous women. A complete gynecologic examination is indispensible before insertion to guarantee the absence of contraindications (e.g., pregnancy, anatomically abnormal uterus, tumors, pelvic inflammatory disease, acute cervicitis). Pain or discomfort at insertion appears infrequently, except among nulliparas. Similarly, pain after insertion is rare, but occurs most often in nulliparous women. Because of the insertion technique required for this IUD, cases of perforation of he uterus or cervix are virtually nonexistent. Expulsion of the Progestasert is very infrequent; it appears that incorrect insertion is the primary cause of expulsion. All studies verify a decrease in the expulsion rate after the 1st month of use. The incidence of pelvic inflammatory disease in Progestasert users is significantly lower than in users of other IUDs. This may be due, in part, to the shape of the device, which does not have wide surface areas and has no sharp or pointed edges which can become embedded in the endometrial wall. Additionally, the nature of the insertion device, guaranteeing lack of contact between the transverse arm of the IUD and the vagina, assures the sterility of the IUD even at the moment of introduction into the uterus, limiting the transport of bacteria into the cavity. Lack of sufficient data on ectopic pregnancies in Progestasert users impedes a complete evaluation and definition of the problem with this particular device. One of the most frequent reasons for discontinuing use of the IUD is distrubance of the menstrual cycle. Increase in menstrual blood loss, prolongation of the menstrual period, and intermenstrual bleeding are disturbances found in users of most IUDs. The Progestasert, however, appears to decrease menstrual bleeding and shorten the menstrual period in all cases. The advantages of the Progestasert are indisputable in treating dysmennorhea. All studies agree on the attributes of topical release of progesterone in treating this illness. Studies report disappearance of symptoms in 35% of dysmennorheic patients and a marked reduction of symptoms in 65%. Not enough data exist to draw any conclusions about the teratogenic action of the Progestasert. In normal pregnancies, however, natural progesterone is found in much higher levels than that released by the IUD. Theoretically, the hormone released by the IUD should not interfere with normal fetal development. The failure rate of Progestasert is equal to or lower than that of other IUDs. Overall, the Progestasert represents a remarkable improvement over conventional IUDs.     

Dose- and age-dependent ectopic pregnancy risks with intrauterine contraception

Analyses of randomized trials of copper intrauterine devices (IUDs) substantiate three hypotheses: 1) Ratios of ectopic to total pregnancies conceived during copper IUD use did not differ among devices; 2) pregnancy rates per 1000 woman-years varied inversely with copper surface area; and 3) ectopic pregnancy rates consequently varied inversely by copper surface area. Randomized trials also demonstrated that progestin-only IUDs had a markedly higher ratio of ectopic to total pregnancies, 171 per 1000, than did copper IUDs, at 39 per 1000 (P less than .001). Ectopic pregnancy rates per 1000 woman-years with progestin-only IUDs varied inversely with dose, notably for levonorgestrel-releasing devices. In a large United States IUD cohort study, ectopic pregnancy ratios of copper IUDs varied significantly (P less than .05) with age, as they do in the general population. Copper and non-medicated IUDs in the United States and the United Kingdom had age-specific ectopic pregnancy ratios six times those of non-contraceptors in the United States population during 1970-1978. The estimated rate of ectopic pregnancy for users of IUDs having 200 mm2 of copper was four-tenths that of non-contraceptors in the United States during 1970-1978. For users of devices with 350 mm2 or more of copper, ectopic pregnancy rates were one-tenth those of non-contraceptors. Rates for users of devices releasing 65 micrograms/day of progesterone are estimated to have been 50-80% above those of non-contraceptors. Devices releasing 20 micrograms/day of levonorgestrel have had ectopic pregnancy rates estimated to be 0.1 of those of non-contraceptors. Most IUDs protect against ectopic pregnancy.     

IUD litigation: the Planned Parenthood experience

This review of the IUD litigation experience of Planned Parenthood in the U.S. from 1977-1988 involved 18 injuries allegedly caused by the plaintiff's use of an IUD. These 18 IUD cases represent 9.8% of the total malpractice lawsuits involving Planned Parenthood in the period. 7 were dismissed, 8 were settled, 1 was decided in favor of the defense, and 2 were decided in favor of the plaintiff. While the disposition of these cases is similar to the overall malpractice experience nationally, it is unusual in that twice as many verdicts were for the plaintiff. It is likely that the public perception that IUDs are dangerous made it difficult to select an impartial jury. Pelvic inflammatory disease (PID) was the most common alleged injury, 15 of 18. Even though the scientific evidence predicts otherwise, 15 of the 16 cases of PID occurred over 4 months after insertion. 8 of 15 cases involves Copper-7 IUDs, 4 Dalkon shields, 1 a Progestasert, and 2 Saf-T-Coils. The other 2 cases were 1 uterine perforation and 1 pregnancy. Of the 8 cases that were settles, the mean payment was $20,912, and the median $10,000. These payments are about 25% higher than average non-IUD cases. Payments by insurance companies averaged $21,644 in the late 1970s for IUD claims. In jury cases involving IUDs and Planned Parenthood, the average jury award was $50,000. It is recommended that providers take care especially to comply fully with an IUD manufacturer's protocol, and obtain full and complete informed consent with documentary proof to decrease the possibility of an adverse outcome in potential litigation.     

活性γCu380 IUD与TCu380A IUD多中心比较性研究

本研究通过增加原γCu2 0 0 IUD的铜表面积至 380 mm2 ,以期在不增加副反应的基础上进一步降低带器妊娠率 (包括异位妊娠 ) ,而达到与 TCu380 A IUD相似的避孕效果 ,并保持原来的低副反应发生率。方法 :1 998年 1～ 5月由全国五个中心参加的随机比较性研究 ,共随访 1 2个月。每个中心分别放置γCu380与 TCu380 A IUD各 1 0 0例 ,共 1 0 0 0例。结果 :1 2个月末 γCu380与 TCu380 A IUD脱落率每百妇女分别为 0 .80和 1 .99(P>0 .0 5)。带器妊娠率每百妇女均为 0 .2 0。异位妊娠率每百妇女分别为 0 .2 0和 0 .0 0 (P>0 .0 5)。因症取出率每百妇女分别为 1 .0 0和 2 .6 0 (P>0 .0 5)。结论 :γCu380 IUD临床效果与 TCu380 A IUD相似 ,而 γCu380 IUD副反应发生率明显低于 TCu380 A IUD。本研究结果证实载高铜面积 γCu380 IUD是一种优质的 IUD。     

活性γCu380IUD与TCu380AIUD临床比较性研究

本研究通过增加原γCu 2 0 0 IUD的铜表面积至 3 80 mm2 ,其目的为了进一步降低带器妊娠率 (包括异位妊娠 ) ,以期达到 TCu3 80 A IUD相似的避孕效果 ,而其副反应发生率明显低于 TCu3 80 A IUD。方法 :1 995年 8月～ 1 996年 6月由三个中心参加的随机比较性研究 ,共随访 2 4个月。每个中心分别放置γCu 3 80与 TCu 3 80 A IUD各 1 0 0例 ,共 6 0 0例。结果 :2 4个月末 γCu3 80与 TCu3 80 A IUD脱落率每百妇女分别为 0 .997和 2 .4 70 (P>0 .0 5)。带器妊娠率每百妇女分别为 0 .3 3 2和 2 .4 59(P<0 .0 5)。异位妊娠率每百妇女分别为 0 .1 6 1和 0 .3 3 0 (P>0 .0 5)。因症取出率每百妇女分别为 1 .6 6 1和 5.4 95(P<0 .0 5)。结论 :γCu 3 80 IUD临床避孕效果明显优于 TCu 3 80 A IUD;两种 IUD的异位妊娠率相似 ;γCu3 80 IUD的副反应发生率明显低于 TCu3 80 A IUD。本研究结果证实高铜面积 γCu3 80 IUD是一种优质的 IUD。     

The new IUDs

This brief review mentions 3-dimensional IUDs and large surface IUDs and discusses progesterone and copper-containing IUDs. The 3-dimensional IUDs (Corolle, Basquet, and Majzlin spring) were expelled easily and were poorly tolerated. The large area Dalkon shield was difficult to insert and remove but permitted few expulsions; the failure rate of less than 1% claimed by its inventors has not been confirmed in French and British studies. IUDs with progesterone capsules or with auxiliary daily pills are on trial. Copper T and 7 shaped IUDs have proved to be more effective, seldom expelled, and rarely responsible for severe bleeding. The IUDs with 300 sq. mm copper release about 50 mcg copper /day, not enough to affect blood levels. They seem to prevent implantation by attracting leukocytes and macrophages, by modifying mucosa enzymes such as acid phosphatase, and by preventing sperm from penetrating cervical mucus.     

Insertion forces with intrauterine devices: implications for uterine perforation

The force required to insert a Copper 7, Multiload Copper or Nova T IUD was measured in 197 successful and 25 unsuccessful insertion attempts. These forces were compared with the forces required to perforate freshly obtained uterine specimens with a metal uterine sound and Dalkon shield device, as well as with the clinically tested devices. The mean insertion forces for the Copper 7, Nova T and Multiload Copper devices were 1.502 N, 2.134 N and 4.041 N respectively, while the mean insertion pressures (N/mm2) were 0.203, 0.209 and 0.122 respectively. The mean in vitro fundal perforation forces with metal sounds was 20.7 N and with the Dalkon shield 31.6 N. The Copper 7, Multiload Copper and Nova T IUDs achieved mean in vitro forces of 5.75 N, 9.2 and 8.1 N respectively, without causing perforation. Primary uterine perforation at the time of insertion of these devices appears unlikely.     

Will progesterone save the IUD?

In 1971 we began studying pelvic inflammatory disease (PID) in IUD users by examining fallopian tube specimens obtained after elective female sterilization. We studied four groups: 175 nonhormonal-IUD users, 22 Progestasert users, 1,500 non-IUD users and 100 non-IUD users who had had IUDs in the past. We found histologically detectable salpingitis in 49% of the nonhormonal-IUD users, none of whom had symptoms of PID. Culture of 100 specimens from these nonhormonal-IUD specimens proved to be sterile. Viewing the inflammation as predisposing the tissues to bacterial infection would help explain the higher frequency of PID among IUD users than among nonusers. All the Progestasert users lacked histologically detectable salpingitis; the difference was statistically significant (p < 10(-6). This finding suggests that women using progesterone-releasing IUDs have a lower risk of developing PID than do users of other kinds of IUDs.     

IUDs and ectopic pregnancy

Recent data indicate that the number of ectopic pregnancies in the US has quadrupled since 1965, while the frequency has tripled, from 38/100,000 women aged 15-44 in 1965 to 113/100,000 in 1981. The frequency of ectopic pregnancies in Sweden has also increased significantly, while in England and Wales a less marked but still notable increase has also occurred. The finding in the 1970s of a correlation between ectopic pregnancy and IUD use raises questions about the causal factors involved which are addressed in this article through an examination of the relevant literature. It has been noted in previous work that rates of ectopic pregnancy associated with inert or copper IUD use in the US are not different from rates associated with use of barrier contraceptives or in the absence of contraception. Comparison of rates of ectopic pregnancy among women using IUDs with those of women using combined oral contraceptives (OCs) sterilization, or sexually inactive are methodologically questionable. In 1981, the Women's Health Study, a large case control study, demonstrated that current IUD use protected against ectopic pregnancy when the control group was composed of women who had never used an IUD. Current IUD users had a relative risk of .4 when compared with women using no contraception. Users of barrier methods had a relative risk very similar to that of IUD users, while women on OCs had a relative risk of .1. Differences in the rates of ectopic pregnancy among users of barrier methods in England and the US are largely explained by the much higher failure rates of barrier methods in the US. The relative risk of ectopic pregnancy among IUD users was also under 1 in a Swedish study. The single study with data on the relative risk of previous IUD users indicates a relative risk of 1.4 compared to women who never used the IUD, but a risk of about .7 compared to women currently at risk of conception but using no method. The 3 large studies analyzing risk of ectopic pregnancy by duration of IUD use yielded conflicting results and have been challenged on methodological grounds. Supplementary proof of a correlation from prospective studies is needed. Studies of the rates of ectopic pregnancy for different types of IUD are difficult to plan and conduct. In general they indicate that inert and copper devices are not associated with an increased risk, although progesterone-releasing devices elevate the risk significantly. It is concluded that there is no causal relationship between use of a nonmedicated or copper bearing IUD and ectopic pregnancy, although OCs and effective barriers afford better protection against ectopic pregnancy than do IUDs.     

Was the Dalkon Shield a safe and effective intrauterine device? The conflict between case-control and clinical trial study findings.

OBJECTIVE: To compare the findings of the case-control and cohort studies used to indict the Dalkon Shield (A.H. Robins Company, Inc., Richmond, VA) with the findings of the Dalkon Shield clinical trials. DATA IDENTIFICATION: All published reports on the Dalkon Shield were identified through MEDLARS system (United States National Library of Medicine) searches and by cross checking all references in these reports. The same approach was used to identify all case-control and cohort studies of the purported relationship between intrauterine devices (IUDs) and pelvic inflammatory disease (PID). STUDY SELECTION: Only studies of interval patients that included 50 or more women and 6 or more months of follow up that computed standard IUD event rates (rates of pregnancy and expulsion and removal for pain and bleeding) were selected for this study. All case-control and cohort studies identified were included except two case-control studies that included women with sterile chronic salpingitis. RESULTS: The 16 case-control and 2 cohort studies found or suggested that the Dalkon Shield increased the risk of PID. The 71 clinical trials of the Dalkon Shield show that when this device is inserted by an experienced clinician it is a safe and effective contraceptive method, comparable with other IUDs used at the time. There was no evidence of an increased risk of PID found in these clinical trials. CONCLUSIONS: This study offers convincing evidence that the indictment of the Dalkon Shield was a mistake. Additionally, this study shows that physician skill and experience is far more important to successful IUD insertion than previously recognized, a finding with considerable implications for IUD study designs and for marketing strategies.     

The intrauterine device, pelvic inflammatory disease, and infertility: the confusion between hypothesis and knowledge.

An earlier editorial made many false claims against the IUD and women. In many cases, the author extrapolated experience from the Dalkon Shield to today's IUDs. He even said the modern contraception has not reduced fertility, but data from at least 7 developing countries clearly refute that statement. Moreover he claims that the most female ambition is motherhood. Thus he blamed women for high fertility rates without acknowledging that women in developing countries have little control over fertility. Husbands determine when and how often to have intercourse and whether to use contraceptives or not. Women do not always have access to contraceptives. The author boldly stated that the IUD poses a threat to future fertility because it causes pelvic infections. The real threat is intercourse by which upper genital tract infections are transmitted. It is these sexually transmitted diseases that cause pelvic infections. The studies the author quoted have been found to have considerable bias and/or methodologic flaws. Some studies used as the comparison group women using contraceptive which lower the pelvic infection risk. Contemporary studies find no increased risk of infertility in copper and hormone IUD users, but instead show increased risk for multiple sex partners. Some studies do indicate an increased risk shortly after insertion which is due to insertion instrumentation used. The author even claimed that a Swedish study concluded that IUDs promote pelvic infection in patients with gonorrhea and chlamydia. But the Swedish study found no difference in pelvic infection risk between IUD and non-IUD, nonhormonal contraceptive users. Based on hundreds of millions of woman-years of worldwide experience, WHO claims modern copper and hormone releasing IUDs, when used as directed, may be the most effective and reliable reversible contraceptive method. This editorial based on flawed conclusions and misinformation does an injustice to the IUD and to women.