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.     

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.     

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.     

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.     

Fertility control by intrauterine release of progesterone

The contraceptive effectiveness of small amounts of progesterone released in the uterine cavity via a silastic progesterone T IUD was studied. Over 1600 woman-months of use in 249 women were evaluated. The amount of progesterone remaining in 14 capsules revoved 161-200 days after insertion was variable, indicating a possible effect of individual uterine environment on release rates. No pregnancies occurred while devices releasing adequate amounts of progesterone were in situ. 7.9% of the devices were displaced or expelled. Serial plasma hormonal determinations showed no differences between patients with inert and progesterone IUDs. There was no inhibition of ovulation or change in cervical mucus. The mechanism of action is probably related to the decidual changes induced in the endometrial receptors.     

Analysis of minor complications in copper IUD wearers

Minor complications occuring after insertion of 3216 copper IUDs between October 1976 and December 1980 were studied. 1813 of the device were Cu 7 200s, 176 were Cu T 200s, 237 were ML Cu 250s, and 990 were Nova Ts. 133 partial and 71 total expulsions, 21 removals for bleeding, 24 for pain, 10 for bleeding and pain, and 115 for other causes were studied. 5.23% of Cu 7 200, 4.54% of Cu T 200, 2.53% of ML Cu 250, and 2.42% of Nova T devices were partially expelled, while 3.23% of Nova T, 1.87% of Cu T 200, 1.68% of ML Cu 250, and .56% of Cu T 200 devices were totally expelled. Considering all types of IUD, the frequency of expulsions declined with age, but great differences were not observed in relation to parity. 67.6% of total and 48.9% of partial expulsions occurred in the 1st 6 months of use. All total expulsions in the ML Cu 250 and the Cu T 200 occurred in the 1st 3 months. 58.14% of partially expelled IUDs which were reinserted presented no further problems. 16 of 21 IUDs removed for bleeding were Cu 7 200s, 2 each were ML Cu 250s and Nova Ts, and 1 was a Cu T 200. Slightly over 1/2 were removed in the 1st year of use. 20 fo the 24 IUDs removed for pain were Cu 7 200s, and 37.5% of them were used by nilliparas. 9 of the 10 removed for pain and bleeding wer Cu 7 200s, 40% of them in nulliparas. Psychological intolerance of the method (63.35%) and removal by other doctors (18.26%) were the other causes of removal. For the Cu 7 200, Cu T 200, ML Cu 250 and Nova T respectively, the Pearl indices of expulsion were 1.97, 2.22, 2.76, and 4.89, while for pain and/or bleeding they were 1.39, 1.33, 1.18, and .29.     

Duration of use of copper releasing IUDs and the incidence of copper wire breakage

The incidence of copper wire breakage for IUDs (Multiloads) using 0.3 and 0.4 mm diameter copper wire was evaluated by examining 969 devices that had been removed for various reasons. The IUDs were examined by light microscopy to determine the integrity of the copper wire. As expected, the incidence of breakage increased with increasing duration of IUD use. The cumulative breakage rate (life table) was significantly lower (p less than 0.05) for the Multiload 375 that used 0.4 mm diameter wire, compared to the Multiload 250 that used 0.3 mm diameter wire. The cumulative rates were 5.4 per 100 IUDs after 3 years for the Multiload 250, and 3.8 per 100 IUDs after 5 years for the Multiload 375. In only 1 (0.1%) of the 969 Multiloads examined, the breakage of the copper wire was sufficiently extensive to adversely affect the user's risk of pregnancy.     

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)     

Copper IUDs (author's transl)

Following initial development of the Grafenberg ring in the 1920's, IUDs fell into disuse until the late 1950s, when plastic devices inserted using new technology began to gain worldwide acceptance. Further research indicated that copper had a significant antifertility effect which increased with increasing surface area, and several copper IUDs were developed and adapted, including the Copper T 200, the Copper T 220C, and the Copper T 380 A, probably the most effective yet. The Gravigard and Multiload are 2 other copper devices developed according to somewhat different principles. Copper devices are widely used not so much because of their great effectiveness as because of their suitability for nulliparous patients and their ease of insertion, which minimizes risk of uterine perforation. Records of 2584 women using Copper IUDs for 7190 women-years and 956 women using devices without copper for 6059 women-years suggest that the copper devices were associated with greater effectiveness and fewer removals for complications. Research suggests that the advantages of copper IUDs become more significant with increased duration of use. Contraindications to copper devices include allergy to copper and hepatolenticular degeneration. No carcinogenic or teratogenic effect of copper devices has been found, but further studies are needed to rule out other undesirable effects. Significant modifications of copper devices in recent years have been developed to increase their effectiveness, prolong their duration of usefulness, facilitate insertion and permit insertion during abortion or delivery. The upper limit of the surface area of copper associated with increased effectiveness appears to be between 200-300 sq mm, and at some point increases in copper exposure may provoke expulsion of the IUD. The duration of fertility inhibition of copper IUDs is usually estimated at 2-3 years, but recent research indicates that it may be 6-8 years, and some devices may retain copper surface for as long as 20 years. Shorter and smaller versions of standard copper IUDs have been tested as they permit easier insertion, but high rates of pregnancy, expulsion, and removal have prevented their wider use. The discovery that the size of the uterine cavity is more important than its length has prompted the development of some promising uterine measuring instruments. Attempts to develop a device appropriate for postpartum use have been disappointing, and expulsion rates remain high. A few promising new forms of copper IUDs have been developed but not yet tested clinically.     

Assessment of the performance of a copper intrauterine device: MLCu 375

Between November 1977 and May 1978, 120 Multiload Cu 375 (ML Cu 375) IUDs were inserted to be used for periods of 24 months in 24 women or 36 months in 96 women. 4 patients were aged 24 years or younger, 38 were 25-29, 40 were 30-34, 21 were 35-39, 13 were 40-44, and 4 were 45 or over. 9 were nulliparous, 30 were primaparous, and 81 were multiparous. 35 women had used another type of IUD and 5 had expelled another model. At 12, 24 and 36 months respectively there were 1, 2, and 0 pregnancies; 3, 4 and 0 expulsions; 5, 3, and 4 removals for pain; 0, 2, and 1 removal for other medical reasons; 0, 1, and 1 removals for personal reasons; and 2, 4, and 3 removals because of desire for pregnancy. The number of cycles included at 12, 24, and 36 months respectively were 1354, 2454, and 3081, and a total of 20 patients were lost to follow-up over 36 months. The small sample size and limited number of cycles of use prohibit a complete evaluation of the ML Cu 375, but the author's experiences confirm the simplicity of insertion, efficacy, good retention and acceptable tolerance of the device. A review of the literature suggests that IUDs with large doses of copper, such as the ML Cu 375, offer contraceptive efficacy that will be difficult to improve, at least with copper devices.     

Analysis of bioactive intrauterine devices using high energy proton induced X-Rays (Pixe) and scanning microscopy (Sem) (Author's transl)

It has been amply demonstrated that the effectiveness of copper IUDs is superior to that of inert IUDs. The decreased risk of pregnancy depends not only on the mechanical action on the endometrium, but on modification of the biochemical environment. Goal of this study is to analyze the physico-chemical process which intervenes on the surface of copper IUDs, using high energy proton induced X-rays and scanning microscopy. The devices examined were removed during routine examinations from patients who had worn them for periods going up to 3 years. Data gathered showed that there are 2 phases in the physico-chemical process. During the first 8 months of use a deposit of a granular structure and rich in potassium, chlorine, calcium, and probably sulphur, appears on the copper wire; during the same period the emission of copper is very important, whence the increased contraceptive effectiveness. During the second phase, going from 1 to 3 years, there is a marked process of calcification which induces a progessive and irreversible neutralization of the contraceptive action of bioactive IUDs.     

Trailing and treating the wandering IUD

Suggestions on how to manage a missing IUD for current practitioners in the U.S., who may not have any IUD experience, are recommended. It is important to realize that IUDs do not perforate the uterus on their own: they do so at insertion. No one who inserts enough IUDs will never perforate a uterus: the average perforation rate is 3 per 1000. Ultrasound cannot find a lost IUD without reference to some structure, especially if the IUD is free-floating. The best way to ensure that the IUD is not in the uterus use hysteroscopy. Any cystoscope can be converted to a hysteroscope by attaching a glass adaptor, and no distension medium is necessary. If the IUD is not found in the uterus, it can be located in the abdominal cavity by x-ray of the abdomen, including a lateral views. An anterior-posterior view of the pelvis may suggest that the IUD is in the uterus when it is not. If the IUD is in the abdominal cavity, the safest, and most acceptable way to remove it is by laparoscopy. Most lawsuits concerning perforated IUDs were prompted by laparotomy or colpotomy. IUDs in the abdomen, especially copper IUDs, will develop adhesions, any may bear bacteria from the insertion process. Perforated copper IUDs should be removed as soon as possible.     

Recovery of the intrauterine contraceptive device from the sigmoid colon. Three case reports

3 cases of copper IUDs recovered during laparotomy from the sigmoid colon are presented. One woman was a 24-year old mother of 5 who had had 2 cesarean sections since the disappearance of her Cu-7 IUD in 1980. She had right upper quadrant abdominal pain for 1 year with gall bladder stones. The IUD was found lying 80% in the gut lumen. After colotomy she recovered. The 2nd woman was 31 years old, pregnant for the 4th time after failure of her IUD. She was experiencing a constant left iliac fossa ache. The IUD was shown to be extrauterine by ultrasound, could not be seen at laparoscopy, and was removed by colotomy. The 3rd woman was a 37-year old mother of 5, 19 weeks' pregnant, having a septic miscarriage on admission. She had labor induced, but the IUD was not expelled. Her pain worsened, and fever and tachycardia persisted. Emergency laparotomy revealed a perforated posterior uterine wall with the Cu-7 eroding the serosa of the sigmoid colon. It was removed but the defect was not repaired. She required a subtotal hysterectomy, and a second laparotomy with a temporary colostomy, and her recovery was complicated by pulmonary embolism and cardiac failure. These cases draw attention to the importance of proper management of patients with no visible IUD thread. Ultrasound, and if necessary x-rays and laparoscopy should precede laparotomy. Expulsion of an IUD is rarely unnoticed, nor should pregnancy with an IUD be assumed to be due to an expelled device.     

Intrauterine contraception

Approximately 60 million women worldwide use IUDs. Despite worldwide distribution, the total number of IUD carriers has barely increased since 1970. Due to its risks and side effects there is a retrograding tendency both in West Germany and the US. To generate positive development, 3 basic trends have emerged: 1) Restrictive usage of the pharmacologically inactive, 1st generation IUDs such as the Lippes Loop or the Saf-T-Coil, 2) the increasing usage of small plastic IUDs with bioactive alloys to decrease failure rates such as the copper (2nd generation) or hormone-releasing IUDs, and 3) improvements made by changing its design to reduce side effects without loss of contraceptive effectiveness. Almost all IUDs increase monthly blood loss by 50-100%. The risk of illness for women with IUDs is 2-3 times higher than for a woman without or with other contraceptive methods. About 20% of all expulsions occur unnoticed. There are 2 kinds of perforations: primary (iatrogenic), at time of insertion, and secondary, some time after insertion. The IUD failure rate is about 1-3 pregnancies/100 woman years. In case of pregnancy, the IUD must be removed immediately. IUD insertion requires consent of the woman and can be made to women from 16 years on, presupposing moral maturity. IUD insertion after a miscarriage or abortion does not lead to risks or complications. Due to its corrosive quality, the copper IUD can only remain inside the uterus for a limited time. IUDs could become an excellent contraceptive method if it were possible to decrease bleeding, design easily-removeable IUDs, and prolong their potential for duration in the body.     

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.     

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.     

Post-partum and post-abortal use of IUDs (author's transl)

The search for an IUD that could be safely inserted in the immediate postpartum period and retained as long as desired led the Population Council to undertake a 13-center study of Lippes loop insertion during the 1st 10 postpartum days. The expulsion rate of 20.5% in the 1st 3 months following insertion was considered too high, despite apparently lower risks of perforation and infection. In 1975 the International Fertility Research Program (IFRP) began a program to modify existing IUDs for immediate postpartum and postabortal insertion. Several approaches were explored using biodegradable materials to avoid expulsion, and a modified Lippes loop with catgut sutures gave good results. A case study undertaken by the IFRP attempted to evaluate too many factors with too little attention to the qualifications of participating physicians, resulting in highly variable experiences in different centers. A program recently initiated in 10 collaborating centers in Turkey promises to yield interesting results; preliminary indications are that success rates vary between institutions and depend partly on the enthusiasm of the program director. 1 Turkish center solved the difficult problem of follow-up by adding a clinic where the newborns received check-ups. In 1 month, with 100% follow-up, over 100 IUDs were inserted and only 1 of the last 50 was expelled. Many IUDs inserted postpartum are expelled because they are not placed sufficiently deeply in the uterine cavity. The IFRP believes that with appropriate training of personnel and a better tool for insertion, a high rate of retention can be achieved. Within 6 months the IFRP expects to begin clinical testing of a 2nd generation postpartum IUD with improved sutures. Despite variable success in the past, development of a satisfactory postpartum IUD would be a valuable addition to many national family planning programs.     

缓慢释放孕酮宫内节育器的体内释药研究及对垂体—卵巢轴影响的探讨

本文依据雌性家兔及人体内使用9%乙烯醋酸乙烯(9%Ethylene Vinyl Acetate,简称EVA)共聚物作为释药系统,含一定量孕酮的宫内节育器,经过使用不同时间后分别取出测定剩余的孕酮量,观察本释药系统在体内的药物释放情况。测定结果证明家兔体内释放符合零级动力学,即恒速释放,释放速度为46.6μg/cm~2/天。在人体内也达到恒速释放,释药速度为29μg/cm~2/天。此外对四名育龄妇女进行上环前一个周期及上环后九个月至一年的基础体温、宫颈粘液、阴道脱落细胞成熟指数及血清促黄体生成激素、促卵泡激素、雌二醇和孕酮的放射免疫测定的系统纵向观察,结果证明受试者上环后每个周期均有排卵,释放孕酮量为29μg/cm~2/天的宫内节育器对机体垂体-卵巢轴无显著影响。