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.     

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.     

Progress in the development of the Progestasert TM 65 progesterone therapeutic system for contraception

The primary objective in the design of the Progestasert 65 system, a progesterone uterine therapeutic system, has been to influence the intrauterine environment and produce fertility control by means of local steroid action. It has an average release rate of 65 mcg progesterone/day to the uterine lumen for a period of 400 days. Although the system was developed as a method of local steroid contraception rather than as an intrauterine device (IUD), information gained from experience with IUDs guided certain aspects of the design specifications; e.g., the T configuration was selected and modified for easier insertion. The progesterone core composition is contained within the verticle system of the T maintaining the flexibility and softness of this portion. The inserter is a smooth cylindrical unit, precurved and malleable so the angle can be changed if necessary. This inserter design has provided over 3000 insertions with no perforations. Clinical data come from 32 clinics. It is concluded that this development is a highly efficacious local hormonal system of contraception.     

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.     

The rise and fall and rise of the IUD

The history of IUD use, from the ring used by Richter in 1909 to the present, is described as 3 surges of popularity. The 1st IUDs were catgut rings with or without tails, and the Pust stainless and Ota rings. A worldwide pandemic or gonorrhea, and the population policies before and during World War II ended the popularity of IUDs temporarily. In 1959 IUDs re-emerged, proliferating to over 100 models, most of which were barium impregnated polyethylene, such as the Lippes Loop. Other models that had lesser success were several stainless springs that predisposed to embedding and perforations and the Majzlin spring with a multifilament tail that caused pelvic infection. The Dalkon shield, also bearing a multifilament nylon tail, brought the second wave of IUDs to a rapid end in the 1980s, because its multifilament tail increased risk of infection, midtrimester amnionitis, ectopic pregnancy, tubo-ovarian abscess, infertility, hysterectomy, and death. Robbins Company eventually recalled the Dalkon shield, and later became bankrupt from lawsuits. Other IUD makers, such as Searle, manufacturer of the well-tolerated and popular Copper-7, and Ortho, were subject to litigation, and removed their IUDs from the market, even though their products were still approved by the FDA. During this interim, several new copper bearing IUDs were being developed and tested. The TCU380A, like a Tatum-T with twice as much copper, developed and brought through FDA approval by the Population Council, was licensed and marketed by GynoPharma Corporation as the ParaGard. ParaGard is the most effective IUD to date for U.S. women, with pregnancy rates 1/100 after 2 years of use. Simultaneously, the Alza Corporation released Progestasert, a progesterone-releasing IUD. Progestasert has a 1.3% failure rate, and must be replaced yearly, but is the IUD of choice and therapeutic for women with dysmenorrhea or heavy menstrual flow. Progestasert appears to lessen tubal inflammation, but consequently permits more ectopic pregnancies than other IUDs.     

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.     

The effects of TCu-380A on cervicovaginal flora

Objective This study aims to identify the alterations in cervicovaginal flora after insertion of TCu 380A which is a popular type of copper IUD. Study design Among the women who visited the Department of Family Planning in our hospital during 1 month, 100 subjects who preferred IUDs for contraception and who had no history of local or systemic antibiotic use were considered eligible candidates. Results Anaerobic colonies, especially Gram-positive cocci and Gram-negative bacilli were isolated at significantly higher rates after the insertion of TCu-380A. Aerobic colonies were isolated relatively less. Conclusions It can be suggested that copper IUD causes the predominance of anaerobic species in the cervicovaginal flora, which is consistent with the literature. This clinically insignificant condition can be attributed to the copper content or threads of the IUDs. Yet there is no evidence that the prevalance of pelvic infections is influenced by the use of IUDs.     

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.     

Current issues in contraception

Some controversies regarding currently used contraceptive methods are reviewed. There are no newly available estrogens for oral contraceptives (OCs), but 2 progestins are coming into use: cyproterone acetate, which has a potent antiandrogenic action, and desogestrel, which combines a strong inhibitory effect on ovulaion and a marked peripheral progestin activity with very weak androgenic and anabolizing activity. New systems of administration will be used in the future to avoid the serum "peaks" observed in oral administration. The lack of agreement on the effects and secondary effects of various progestins will be a continuing source of discussion. 2 aspects of combined OCS, residual ovarian activity and androgenicity, are attracting increasing attention. Among new preparations, the combination of 2 mg cyproterone acetate and 50 mcg of ethinyl estradiol (EE) has been shown in multicenter European studies to have good effects on acne and satisfactory acceptance despite some hyperestrogenic secondary effects, which may be improved by a new dosage schedule. Triphasic preparations have given good results with significantly reduced steroid doses. There have been few recent findings concerning risks of OCs. The triphasic formulations and those containing desogestrel are too recent to have been subjected to epidemiologic study. The noncontraceptive benefits of OCs are becoming more apparent; they include protection against ovarian and endometrial cancer, functional ovarian cyst, ectopic pregnancy, salpingitis, benign breast disease, dysmenorrhea, rheumatoid arthritis, menorrhagia, and premenstrual syndrome. Improved knowledge of the mechanisms of action and local effects of IUDs permitted improved utilization. Ultastructural studies and endometrial exploration have show that non-fundally located IUDs entail greater risk of failure and complications. The question of early pregnancy with IUD use is still unresolved. Copper IUDs are now the most widely used type, but there are differences of apinion about whether the copper content should be increased or whether silver should be added to the core of the copper thread. IUDs with natural or synthetic progesterone may reduce bleeding and have other beneficial effects. Currently it is impossible to identify 1 particualr IUD as superior. IUD performance is improved by careful patient selection, choice of IUDs, and follow-up to identify and treat problems at an early stage. Improved spermicides such as Benzalkonjum chloride attracted greater attention to vaginal methods. The posibility of increased risk of toxic shock syndrome and teratogenic effects remain to be evaluated. Post-coital contraception continues to be important as yet no satisfactory new male methods have been developed. The US office of Technology Assessment has published a list of contraceptive developments or improvements expected by the year 2000.     

The effect of copper in vivo on specific progesterone binding by human endometrial cytosol.

Copper has been shown to interfere with specific progesterone binding by human endometrial and myometrial cytosol in vitro. These results suggested that one possible mode of action of the copper-bearing intrauterine devices (IUDs) is through interference with the action of progesterone at its target sites. A prospective study was carried out to determine whether the proposed mode of action of copper-bearing IUDs could be demonstrated in vivo. The results of this study revealed a significant difference in specific progesterone-binding capacity between proliferative and secretory endometria (P less than 0.001). However, when secretory endometria of the controlled subjects were compared with those of the copper-bearing IUD wearers, no significant difference was observed in the specific progesterone-binding capacity (P greater than 0.2). These data suggested that copper released from copper-bearing IUDs in vivo may not interfere with the binding of progesterone to its receptors in vitro. It is doubtful that the contraceptive effectiveness of copper-bearing IUDs could be due to the ability of copper to prevent progesterone from exerting its full effects on the endometrium.     

The effect of intrauterine contraceptive devices on the endometrium

Insertion of an IUD into the uterine cavity is associated with an inflammatory cellular response of the endometrium, which initially is common to all IUDs as the endometrial tissue reacts to the presence of a foreign body. Other types of morphologic modifications specific to different types of IUDs are then observed and may be important in understanding the mode of action of the device and in explaining bleeding patterns associated with IUDs. The endometrial response to inert and copper IUDs is quite similar. The part of the endometrial surface in contact with an inert or copper IUD loses its outer layer of epithelial tissue, exposing the lower layer of basal membrane. The rest of the epithelium in contact with the IUD appears flattened, and some epithelial cells lose their microvilli. Ultrastructural studies have demonstrated a reduction in number of ciliated cells and an alteration of the secretory activity of the surface epithelium and to a lesser degree of the glandular epithelium in reaction to the IUD. Diffuse interstitial bleeding with migration of erythrocytes between the interepithelial spaces has frequently been seen. Ultrastructural studies clearly show that inert IUDs induce lesions and later secondary modifications of the surface epithelium, the superficial vascular epithelium, the glandular epithelium, and to a lesser extent other endometrial cells. With copper IUDs, surface erosions of endometrial epithelium are seen, with much more cellular destruction and signs of bleeding in the part in contact with the copper. As with inert IUDs, the adjacent basal membrane is usually intact. A notable finding in the endometrium is the existence of microthrombosis of stromal capillaries, especially in the portion exposed to the copper. There appears to be a direct relationship between the amount of copper and the degree of ultrastructural modification. The effects of progesterone-releasing IUDs on the surface epithelium, the glands, the stroma, and the vascularization vary as a function of the dose and type of progestin, the proximity of the tissue and the part of the IUD treated, and the time elapsed since insertion.     

In vitro sperm penetration tests and PCTs in fertile women wearing different medicated IUDs (Cu and progesterone)

In order to evaluate the sperm-cervical mucus interactions in women wearing different intrauterine devices (IUDs), a longitudinal study of over 27 months in 7 selected normally fertile couples was made. In vitro sperm penetration tests and PCTs, in the same woman, were carried out in basal conditions and after insertion of IUDs (copper IUD before and progesterone IUD after). The copper IUD induces little modification on the "in vitro" and "in vivo" sperm passage and on the characteristics of the cervical mucus. In contrast, the progesterone IUD is more effective than the copper IUD in inhibiting sperm penetration even with little modofication of the characteristics of the ovulatory cervical mucus. It appears, therefore, that the cervical mucus modifications are less relevant than the toxic effect on the spermatozoa in the mechanism of activity of progesterone IUDs.     

Obstetrician-gynecologists and the intrauterine device: a survey of attitudes and practice

OBJECTIVE: To assess obstetrician-gynecologists' clinical use of the intrauterine device (IUD), their attitudes toward the IUD and how they select IUD candidates, and to test the hypotheses that limited residency training in IUDs, fear of litigation, and a belief that IUDs cause pelvic inflammatory disease decrease IUD use. METHODS: We performed a national mailed survey of 811 practicing obstetrician-gynecologists obtained from systematic sampling of ACOG membership listings to assess use of and attitudes toward the IUD. RESULTS: The survey response rate was 50%. Most respondents agreed that the copper IUD is safe (95%) and effective (98%). However, 20% of respondents had not inserted an IUD in the past year, and of those who had, most (79%) reported inserting 10 or fewer. Fear of litigation and a belief that IUDs cause pelvic inflammatory disease were associated with lower IUD use; the number of IUDs inserted during residency was not. In selecting IUD candidates, respondents were most restrictive about patient monogamy. Having less conservative criteria for selecting IUD candidates was associated with greater IUD use. Respondents with liberal criteria inserted a mean of nine IUDs in the past year, whereas those with conservative criteria inserted four. CONCLUSIONS: Because most obstetrician-gynecologists are inserting few IUDs, educational programs should target these physicians to expand their IUD use. Such programs should highlight modern IUD safety and the rarity of litigation. The number of IUDs inserted in residency may be less important than the development of less restrictive, more evidence-based criteria for selecting IUD candidates.     

The benefit of endometrial biopsy before IUD insertion

131 patients aged 25-35 followed from 1969-84 underwent endometrial biopsies under antibiotic cover preliminary to insertion of IUDs. 125 subsequently had IUDs inserted, including 10 Dalkon Shields, 50 Gravigards, and 66 copper 200, Gyne-T, or Nova T devices. All IUDs were inserted in the 1st 10 cycle days under a 3-day antibiotic cover. The 131 biopsies revealed 18 simple endometrial hyperplasias, 1 glandulo- cystic hyperplasia, and 5 endometrial polyps. The hyperplasias were treated with a progestin on cycle days 15-25 for 3-6 months and a curettage was performed for the polyps. No cases of endometritis were found in nulligestes. The 11 patients with latent endometritis were treated with antibiotics for 10 days and were vaccinated with an antipyogenic. A repeat endometrial biopsy was done to confirm disappearance of the endometritis before the IUD was inserted. The 126 IUD users were followed for 6 years on average. 2 cases of salpingitis and an adnexal reaction were observed. 2 of the 3 were treated with antibiotics and had no complications. The 3rd underwent tubal microsurgery after which she became pregnant. The IUD was removed in all 3 cases at the onset of symptoms. 1 of the 3 patients did not have a preliminary endometrial biopsy before the IUD was inserted. Despite the small sample size, it appears that a preliminary endometrial biopsy can reduce the infection rate among IUD users to that of the general female population.     

The effect of a copper IUD and various "inert" Iuds on the histological picture of the rabbit endometrium during early pseudopregnancy and pregnancy.

The influence of a copper IUD and two "inert" IUDs on the histological picture of the rabbit endometrium during early pseudopregnancy and early pregnancy was studied. The copper IUD markedly inhibited the endometrial maturation during the first five days of both pseudopregnancy and pregnancy. The "inert" IUDs had no such effect. The copper IUD prevented the normal response of the rabbit uterus to 17-beta-estradiol in castrated animals. The observed effects of the copper IUD might seriously interfere with the normal process of implantation.     

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.     

IUD-related anatomical,cytological and pathological modifications in the uterine tract (author's transl)

This paper presents a study of the anatomical, cytological, and pathological reactions of the vaginal, cervical, and endometrial mucosa in 445 women wearing inert IUDs, copper IUDs, and progesterone-releasing IUDs. Vaginal cytology does not seem to be affected by any type of IUD. Cervical cytology shows with time increased levels of leuko-histiocytosis and at 18 months cellular alterations are evident; in the series presented here after 24 months there were 2% of cases of light or moderate dysplasia. Endometrial cytology shows cellular inflammation, which worsens with time. Endometrial histology shows: 1) for inert IUDs and after 3-4 years of use, a histio-leukocytic action is evident; 2) for copper IUDs there is no particular alteration for the 1st months; after 18-24 months papillary metaplasia is evident; and 3) for progesterone-releasing IUDs a lympho-plasmocytic infiltration is visible in the 1st month of use, with typical hormonal reactions. This study shows that the uterine mucosa is not affected by an IUD for the 1st 2 years of use, after which the signs of inflammatory reaction are minor and common to any IUD type. The regeneration of the mucosa is very quick after IUD removal.     

A fundamental study of Copper-T (intrauterine device). Part 1 (author's transl)]

Copper IUDs and polyethylene IUDs were inserted in Clauberg rabbits. Proliferation of endometrium caused by exogenous progesterone was markedly inhibited in the rabbits with the copper IUD. Maximum proliferation was seen in the contralateral uterine horn of the rabbits with polyethylene IUDs. The concentration of Cu-ion in the endometrium in the horn with Cu-IUD showed a higher level as 19.5 ug/g wet wt. than that in the control horn, 2.5 ug/g wet wt. This effect corresponds to the addition of Cu-ion in a concentration of higher dosage to the endometrium of the control horn. In the case of women with normal menstrual cycles, the increase in a concentration of Cu-ion in the endometrium with Cu-IUD was lower than 10-5M; in the control women the concentration was 1.6 ug/g wet wt. of endometrium. The histological dating of endometrial specimens (E-B date) with Cu-IUD was examined and compared with expected date of the cycle determined by BBT date. Cu-IUD did not induce any significant discrepancy in both dating. The mechanism of increasing contraceptive effect with Cu-ion was considered to be a little different than in rabbits. (Author's Modified)     

Modification of the cervical flora by IUCD

The study objective was to examine the cervical flora during the insertion of an IUD and to determine whether the presence of the device in utero modified this flora. A secondary objective was to determine whether the colonization of the cervix with (occasionally) pathogenic bacteria warrants a prophylactic antibiotic treatment. IUDs were inserted in a group of 20 women, ranging in age from 23-40 years, at the Family Planning Clinic of Meir Hospital in Kfar Saba, Israel. The cervical bacterial flora was examined during insertion and again after a period of 3-12 months with the IUD in situ. None of the women received antibiotic or antifungal treatment for 3 months prior to or 12 months after insertion. The women were divided into 2 groups according to the type of IUD used. Group A consisted of 22 women with nonmedicated IUDs and Group B included 28 women with IUDs medicated with copper. A cervical swab was collected during insertion of the IUD and at 3-12 months afterwards. Of the 50 cervical cultures collected during the insertion, 48 (84%) were sterile, but only 27 of the cultures collected after 3-12 months with the IUD in utero were sterile. The medicated IUD had a more intense bacteriostatic effect on the bacterial cervical flora than the other devices. Among the copper IUDs the best results were obtained with the Nova T type and secondly with the Copper 7 (Gravigard). It is possible that the pathogenic organisms enter the uterine cavity and tubes from the cervix during insertion of the IUD. It may be concluded that during IUD insertion prophylactic treatment with a broad spectrum antibiotic would be indicated, but the study showed that this was not the case. The organisms isolated in the women studied were those normally found in the upper vagina and cervix and only occasionally became pathogenic. Medicated IUDs are preferable because of the bacteriostatic activity of the copper and to the fact that they are normally left in utero for a shorter time than the unmedicated IUDs.