Comparison of the clinical performance, contraceptive efficacy and acceptability of levonorgestrel-releasing IUD and Norplant-2 implants in China

The levonorgestrel-releasing IUD (LNG-IUD, 20 μg/d) and the Norplant^R-2 implants were studied in a randomized comparative clinical trial with 200 women for one year. No pregnancy or expulsion occurred with the Norplant^R-2. In the LNG-IUD group, there was one pregnancy at the 12th month of use after an unnoticed expulsion. The net cumulative pregnancy and expulsion rates of LNG-IUD were 1.0 and 3.0. The removal rate due to menstrual disturbances in both LNG-IUD and Norplant^R-2 groups was 3.0. The use-related discontinuation rates were 9.0 and 3.0, and the continuation rates were 90.0 and 96.0, respectively. The differences were not statistically significant.

Menstrual disturbance was the main side effect. It was improved after long time use, especially in the LNG-IUD group. After one year, the percentages of women with amenorrhea were 18.9 for the LNG-IUD and 8.3 for the Norplant^R-2. The menstrual blood loss was statistically significantly reduced in the LNG-IUD group, and blood haemoglobin concentration increased in both groups. The LNG-IUD and Norplant^R-2 are highly effective, safe, long-acting, and well accepted by the Chinese women.     

Randomized clinical trial with intrauterine devices (levonorgestrel intrauterine device (LNG), CuT 380Ag, CuT 220C and CuT 200B). A 36-month study. Indian Council of Medical Research Task Force on IUD

A total of 1905 subjects were randomly allocated to four types of intrauterine devices (IUDs) and were observed for 45,683 woman-months of use. While no method failure was observed with levonorgestrel (LNG) IUD, 11 women became pregnant with other devices; 4 with Copper T 380Ag, 1 with Copper T 220C, and 6 while using Copper T 200B, indicating method failure rates of 1.0, 0.3 and 1.6, respectively, at 36 months of use. These rates were within acceptable range. Continuation rates were significantly lower with LNG IUD (74.5, 58.7, 38.8 at 1 year, 2 years and 3 years, respectively) as compared to other copper devices, which ranged between 82.4 to 84.4 at 1 year, 66.6 to 69.9 at 2 years and 45.4 to 50.4 at 3 years. The difference in continuation rates was mainly due to menstrual disturbances (e.g. amenorrhoea, irregular bleeding) which were higher with LNG IUD (27.9 per 100 users) as compared to the copper devices (13.4-15.4 per 100 users) at 36 months of use. The risk of expulsion ranged between 8.3 to 10.6 per 100 users and was comparable for all the devices. The observations from the present study based on 36 months of experience with different intrauterine devices do not indicate the need to replace CuT 200, the device currently in use in the National Programme.     

活性γ型宫内节育器的研究

活性γ型宫内节育器(IUD)结构分三层,以不锈钢丝为主要材料,呈γ形,带有铜丝及消炎痛。自1986年起经临床预试验49例扩大预试验249例及全国多中心试验1000例,定期随访结果表明,放置3年时的带器妊娠率为0.9/100妇女,脱落率1.61,因症取出率2.02,续放率93.73;对照组TCu220C相应为1.61、1.40、4.71和90.27/100妇女。放置前后月经血量测量,说明平均减少17％～25％;子宫内膜活检变化无特殊性,较带铜IUD有较少炎细胞浸润和间质较明显水肿;宫颈粘液铜离子含量测定,预期可释放10年以上;消炎痛体内、外释放量测定表明:适应临床IUD引起月经多的好发期在1年内。研究结果表明γ-IUD具有妊娠和脱落率低,出血副作用甚少,预期可长期放置的优点,是钢、铜、药相结合的新型IUD,值得推广。     

活性金属单环165推广试验研究

为进一步验证活性金单环165在推广中的临床效果,于1991.1～1992.8在上海市15个手术点作为常规放置活性金单环165共4998例,进行了3～6个月和12个月两次随访,随访结果:3～6月时续放率为95.91/100妇女,带器妊娠率0.42/100妇女,脱落率3.06/100妇女;因症取出率0.24/100妇女。12月时续放率为93.80/100妇女,带器妊娠率1.05/100妇女,脱落率4.26/100妇女,因症取出率为0.36/100妇女。3～6月随访时,有副反应人数占27.90％。12月随访时下降至14.98％,以上各指标均明显低于金单环。本研究结果提示该环临床效果明显高于金单环。上海市从1989年开始广泛放置该环,1990年人工流产率有显著下降,全年少做人工流产4万余人次。活性金单环165具有长期放置,随访方便,价格经济,放取技术易普及,推广中不需特殊培训,临床效果佳等优点,易为广大妇女所接受。     

活性金属单环165的临床研究

不锈钢环型节育器(金单环)在中国广为应用。为提高金单环的避孕效果,进行了金单环支撑力与脱落关系的研究,对200,165,135g不同支撑力进行比较性研究筛选出较为合理的支撑力为165g,其外形和金单环相似,分大、中、小三种型号,大号外径22mm,中号21mm,小号为20mm。外层为不锈钢丝螺旋簧,在螺旋环内相间置入纯铜丝(200mm2)和消炎痛硅橡胶各二段(消炎痛总含量5mg左右,现已改为10mg)。于1988年10月～1989年6月全国南北方7省市11所医院共放置1000例,经3年定期随访,12,24,36个月继续存放率各为92.5,88.99及85.94/100妇女年,36月累积带器妊娠率仅1.61/100妇女,脱落率比原金单环明显降低近40％,因症取出率为3.12。于放置前后进行月经血量测量24例,放置后3、6月各增加24.4％和27.4％。行子宫内膜“含铜含药组”和“有铜无药”组对照检查各11例,含药组炎症细胞略少。作宫颈粘液中铜离子含量测定,以6月内含量较高,6月后趋向平稳。消炎痛释放测定,1月内释放较快,一年后残留20％左右。经1249例临床观察,活性金单环165是一种不需特殊培训易于推广的、安全、经济并能长期放置的IUD。     

Performance of the Frameless IUD (Flexigard prototype inserter) and the TCu380A after six years as part of a WHO multicenter randomized comparative clinical trial in parous women

The clinical performance of the new Frameless IUD was compared with the TCu380A, the most widely used copper IUD in the world today. Insertions of the Frameless IUD were conducted with a prototype inserter (Flexigard). We report on the 6-year results from a randomized comparative clinical trial conducted at the Shanghai Institute of Planned Parenthood Research, as part of an international multicenter WHO clinical trial, involving 200 women, respectively recruited for use of each device. The cumulative 6-year pregnancy rates were 0.0 per 100 women for the Frameless IUD and 3.3 for TCu380A. Termination due to partial expulsion was significantly less for the Frameless IUD as compared with TCu380A (0.0 and 4.3 per hundred women, respectively). Complete expulsion, bleeding, pain, bleeding and pain and other medical reasons for termination did not differ significantly between the two devices. The net cumulative continuation rates at six years per 100 women were 80.8 for TCu380A, and 83.0 for the Frameless IUD.Both Frameless IUD and TCu380A are highly effective, safe and acceptable contraceptive devices, because of low pregnancy rates (per 100 women), and low termination rates due to expulsion, pain, bleeding, and bleeding and pain. Due to its anchoring, the Frameless IUD is significantly more effective than the TCu380A IUD as regards proper retention of the IUD in the uterine cavity. This may also explain its lower failure rate.     

Five years' experience with levonorgestrel-releasing IUDs

Two levonorgestrel-releasing IUDs and a copper-releasing IUD of the same shape were studied in a randomized comparative study over five years. The levonorgestrel-releasing IUDs released 20 micrograms or 30 micrograms per day. The Pearl index during the 10,600 woman-months of LNG-IUD use was 0.11. The control device releasing copper had a Pearl index of 1.6. The amount and duration of menstrual bleeding was greatly reduced, leading to a high incidence of oligo- or amenorrhea. The continuation rate in this pioneer trial was 53 per 100 users for the levonorgestrel-releasing IUD (LNG-IUDs) and 50 per 100 users for the copper-releasing IUD (Nova T). The removal rates for reasons other than amenorrhea were not significantly different. Discontinuation because of amenorrhea occurred during the first two years, the cumulative termination rate for this reason was 11.6 per 100 users at five years. The LNG-IUDs removed for investigation after five years of use revealed that the devices contained about 40 percent of the original load. The effective lifespan of the device has been demonstrated by this study to be five years; the residual steroid gives an additional safety period of two more years. The LNG-IUD is a highly effective reversible contraceptive method, which strongly reduced the amount and duration of bleeding. During the first two months there is scanty but frequent spotting which, like the high incidence of oligo- and/or amenorrhea, requires counselling of health personnel and women using LNG-IUDs.     

Quantitative studies on menstrual blood loss in IUD users

Despite the introduction of new intrauterine devices (IUDs), the most important complication involving their use continues to be excessive menstrual bleeding. IUD use in developing countries with women who are already depleted in body iron stores may prove to be deleterious to their health. Mean amounts of menstrual blood loss (MBL) for women not using contraception in the western world is about 32 ml. This mean is increased to 52-72 ml with use of the Lippes loop and other non-medicated devices up to 24 months after insertion. For the Copper-7 and Copper-T-200 devices this mean increase is to 37-40 ml in the first month, decreasing to 30-38 ml at 12 months after IUD insertion. In the users of the Multiload-250 IUD at one month post-insertion the MBL is from 56 to 63 ml and from 36 to 39 ml at 24 months of use. The mean Multiload-375 device users at one month after insertion lose a mean of 45-73 ml at 24 months, 35-50 ml. With the progestogen-releasing IUD mean MBL is 27-36 ml at 1 month and 9-13 ml at 12 months post-insertion. Intermenstrual blood loss is significant only in the first month of use for all IUDs. Discontinuation rates for pain and bleeding with non-medicated IUDs are from 11.0-19.6 per 100 women per year, and for the copper IUDs 4.4 to 6.8 per 100 women in the first year of use. The main problem with prolonged menstrual bleeding is depletion of the body iron stores; this is highly significant with non-medicated devices, less important with copper devices and conversely, iron stores are increased in users of progestogen-releasing devices. This is based on serum ferritin measured up to 24 months after insertion. The ferritin values correlated well with the volumes of MBL. It is suggested, especially for women with low body iron stores, that there is an order of preference for IUDs to be used. This should be: firstly, the progestogen-releasing devices; secondly, the Copper-T and Copper-7 IUDs; thirdly the larger surface copper devices (Cu-T-220C, Multiload 250 and 375, Cu-T-380). Non-medicated devices are not to be recommended for these women.     

Phase II randomized comparative clinical trial of Norplant (six capsules) with Norplant-2 (two covered rods) subdermal implants for long-term contraception: report of a 24-month study. National Programme of Research in Human Reproduction

In a randomized clinical study, contraceptive efficacy and bleeding patterns were studied in a group of healthy, regularly menstruating, non-lactating women (n = 84) using two 4.4 cm covered silastic rods containing levonorgestrel, Norplant(R)-2, and compared with another group of women (n = 88) using six 3.4 cm capsules also containing levonorgestrel, Norplant(R). The silastic rods or capsules were placed subdermally in the medial aspect of the upper arm. No method failure was reported up to 24 months of use in this study with either of the device. The bleeding pattern was also similar for both devices as indicated by average episode length, number of bleeding runs and number of spotting days. The continuation rates with both devices were over 80 per 100 users at the end of 12 months and over 65 per 100 users at the end of 24 months. Discontinuations due to expulsion of the device, bleeding problems or personal reasons were few and similar for both devices. The results suggest that silastic-covered rods, Norplant(R)-2, which are comparatively easier to insert and remove and have similar clinical effect, could replace capsules, Norplant(R), as a long-term reversible subdermal contraceptive.     

The clinical performance of NORPLANT implants over time: a comparison of two cohorts

This paper reports on a study that compared the clinical performance of NORPLANT implants in two separate but similar cohorts: 200 NORPLANT users from 1975 through 1978, when the method was first introduced in the clinic, and 212 users in the same population from March 1982 through December 1983. Two different cohorts of Copper T IUD users were included as controls. Continuation rates, at one and two years of use, were significantly higher in the second group of NORPLANT users (88.1 vs. 60.5 and 76.5 vs. 40.8, respectively). Statistically significant differences between the NORPLANT cohorts were observed in discontinuation due to bleeding, amenorrhea, other medical causes, total medical causes, and personal reasons. No differences in clinical performance of the IUD were observed between the two control groups. The higher continuation rate in the second group of implant users is attributed to greater confidence and experience among the clinic staff between 1982 and 1983, and greater knowledge of and familiarity with the method among those in the target population. The study also shows that the first clinical trials of a new contraceptive method may not provide an accurate picture of that method's ultimate performance.     

Cervical mucus granulocyte macrophage colony stimulating factor and interleukin-2 soluble receptor in women using copper intrauterine contraceptive devices

The objectives of this study were to evaluate the bleeding patterns and clinical performance during the first 2 years of use of an intrauterine system releasing 20 microg/day of levonorgestrel (LNG-IUS, Mirena). Two-hundred-fifty-six women accepted use of Mirena from April 1998 through September 1998. The gross cumulative discontinuation rate due to pregnancy and expulsion were significantly higher in women who used the device because of heavy bleeding. There was one pregnancy at the 15th month of use after an inadvertent expulsion of the device. The continuation rate was 66.2 at the end of the second year. Forty-four percent of women reported amenorrhea at the 6th month of use. This rate maintained stability at 50% after 12 and 24 months of use. Spotting was present in 25% of the users at 6 months, decreasing to 8% and 11% at 18 and 24 months, respectively. Oligomenorrhea was described by one-quarter of women and was similar at each observation period. Removals due to menstrual bleeding problems were concentrated in the first 6 months of use and mostly due to amenorrhea or menorrhagia. In conclusion, LNG-IUS showed a high contraceptive efficacy and a good continuation rate up to 2 years. In addition, a reduction of blood loss was observed a few months after insertion.     

Long-term use of intrauterine devices

Analysis was performed of data relative to 10,001 IUD insertions (mostly Lippes Loop D and C) in 8091 women in Slovenia between 1965 and 1972. Data were gathered on sociodemographic characteristics of the users; cumulative life-table rates per 100 women for removals due to pregnancy, expulsion, bleeding/pain, other medical reasons, and personal reasons as well as continuation rates and the rate of follow-up; and the proportion of women with bleeding, spotting, vaginitis, and pelvic inflammatory disease (PID) at 1-, 5-, and 10-year follow-up. The most frequent reason for removal was bleeding. Increased duration of IUD use was associated with a smaller number of women with bleeding and PID episodes. Of those with first insertions, 608 were hospitalized for IUD-related complications (49% for bleeding requiring curettage and 20% with PID). IUD use for more than five years carried a relative risk of 3.9 for a severe episode when PID developed. Of the women who terminated use of their first IUD because of expulsions, pregnancy, or bleeding, 28% asked for reinsertion. Over the 15 years of IUD use, 853 pregnancies occurred with an IUD in situ. If the IUD was removed after conception, the pregnancy outcome did not differ from women without IUDs. If the IUD was not removed, there was an increased risk of spontaneous abortion, preterm labor, and intrauterine fetal infection. While the IUD users experienced the same risk of ectopic pregnancy as noncontraceptors, if the IUD user did become pregnant, their risk of ectopic pregnancy was twice as high as that faced by those who did not use IUDs. Duration of IUD use and type of IUD had no effect on time from removal to desired conception. This duration was increased, however, in women with a history of PID and in older women. Women over 40 tolerated the IUD better than younger women but as women approached 50, removals for bleeding became more frequent. In conclusion, the IUD is a very safe contraceptive agent and is well tolerated if users are selected carefully, are motivated, and receive help with side effects.     

Comparative evaluation of contraceptive efficacy of norethisterone oenanthate (200 mg) injectable contraceptive given every two or three monthly. Indian Council of Medical Research Task Force on Hormonal Contraception

A total of 2388 subjects, 1181 for 60 +/- 5-day and 1207 for 90 +/- 5-day treatment regimen with norethisterone oenanthate (NET OEN) 200 mg injection, were observed for 24 months, constituting 28,513 woman-months. This clinical trial represents the largest clinical trial undertaken on NET OEN. The observations indicated that NET OEN given at 60 +/- 5-day intervals provides adequate contraceptive protection. However, as compared to the published studies elsewhere, higher method failures were seen during the first six months of NET OEN usage, when all women were receiving the drug at 60 +/- 5-day intervals. The reasons for this discrepant observation in the present study cannot be explained. The higher method failures reported with 90 +/- 5-day regimen were mainly during the third month following the injection, suggesting reduced contraceptive efficacy of the drug during this period. Thin build women (body weight less than or equal to 40 kg) were at higher risk of involuntary pregnancy. Disrupted menstrual pattern was the major reason for discontinuation ranging between 42-43 per 100 users at the end of 24 months. Amongst these, amenorrhoea was the commonest reason for discontinuation. No change in blood pressure was observed during contraceptive usage. The majority of NET OEN users did not show any change in body weight. The overall continuation rates with NET OEN were lower than those observed in similar conditions with Cu-T 200 mm2 IUCD.     

WHO 86925 Norplant上市后监测(中国部分)

本课题研究目的是对Norplant皮下埋植剂潜在副作用进行监测,以进一步证实其安全性。对使用Norplant和IUD或绝育术的妇女进行比较随访研究。每半年随访一次,详细记录所有健康情况,共随访5年。随访率达99.9％。结果:Norplant组及对照组IUD和绝育术的5年继续使用率分别为76.25、80.89、98.10/100使用者。Norplant的5年累计妊娠率为0.6/100使用者,远低于IUD的8.11/100使用者,宫外孕发生率为0.46/1000妇女年,低于IUD的1.24/1000妇女年,但宫外孕和妊娠之比在Norplant组为31.6:100,远高于IUD的6.7:100,如发生妊娠,要警惕宫外孕的可能。月经问题是Norplant的主要终止使用原因,但使用5年者,其血红蛋白均值上升,和接收时相比P<0.001,而IUD使用5年者,其血红蛋白均值下降,和接收时相比P<0.01。在观察5年中胆囊炎胆石症、纤维囊性乳腺病在Norplant使用者中的发病率高于对照组,P<0.05～0.001,但未发现重大健康问题。Norplant使用5年是安全的。     

三种国产宫内节育器临床多中心比较性研究——八年随访总结

全国9省市16个单位,对不锈钢金属单环(金单)、VCu200及TCu220C三种宫内节育器(IUD)进行随机临床多中心比较性研究。自1983年7月1日至1984年3月31日共接受对象4490例。八年末随访率为90.33％。三种IUD间每百妇女累积续用率的差别后期有随使用时间的增长而缩小的趋势,但96个月时仍以金单为最低,47.08％,VCu200和TCu220C各为54.05％和61.14％。VCu20O和TCu220C的妊娠率分别为10.35％和8.94％,它们间差异较前期增大,并显著地低于金单的24.14％。96个月时,金单、VCu200和TCu220C的脱落率分别为21.69％、13.05％和7.48％,三者间呈显著性差异。因出血和/或疼痛取器,八年中金单最低,前期VCu200略低于TCu220C,96个月时仍以金单为最低,VCu200略高于TCu220C,但二种带铜IUD间无差别。三种IUD使用情况城市与农村比较,城市的累积续用率均高于农村;妊娠、脱落和个人原因停用农村均高于城市。用COX比例风险模型和似然比检验分析,发现妊娠和脱落均受年龄、过去使用IUD、本次IUD类型和孕次的影响,显示了两种带铜IUD的妊娠和脱落风险远小于金单;出血和/或疼痛受孕次和本次IUD类型的影响,金单的出血和/或疼痛风险小于两种带铜IUD,总的失败风险受年龄、本次IUD类型、过去使用IUD和孕次的影响,显示了直至使用八年金单的失败风?     

5种IUD使用3年的临床效果分析

目的:观察5种宫内节育器(IUD)放置3年的临床效果。方法:回顾性分析放置爱母环、元宫220型、宫铜、TCu 380型、母体乐等5种IUD的672例观察对象,追踪使用IUD 3年的临床随访观察效果。结果:3年的随访结果表明,元宫220型的续用率最高(97.89%),妊娠率最低(0.70%),脱落率(0%)最低,异常出血(5.63%)和疼痛(3.52%)的发生率最低(P<0.05)。TCu 380型的续用率最低,妊娠率最高,脱落率以爱母环和元宫220型最低,TCu380型和母体乐最高。结论:活性元宫220型IUD较其他4种IUD具有副作用小、续用率高、避孕效果好等优点,可在临床广泛应用。     

B超监测下放置吉妮IN IUD的临床效果观察

目的:观察B超监测放置吉妮IN IUD宫内节育器的临床效果。方法:多中心随机分组在B超监测下放置吉妮IN IUD289例,TCu380A IUD 303例,分别于术后1、3、6、12、24、36个月行妇科及B超随访,以生命表方法统计结果并行显著性检验。结果:①术后疼痛TCu380A组明显高于吉妮IN组(P<0.05);术后6~36月,月经紊乱以TCu380A组为高(P<0.05)。②两组带器妊娠率均较低(吉妮IN组1.04/100妇女,TCu380A组1.32/100妇女,P>0.05);脱落率TCu380A组(6.60/100妇女)高于吉妮IN组(4.84/100妇女,P<0.05);吉妮IN组因出血和疼痛的终止率(2.77/100妇女)较TCu380A组(5.61/100妇女)低(P<0.05)。结论:吉妮INIUD具有与TCu380A IUD同样高的避孕效率,其在降低脱落率、因症取出率及副反应发生率方面优于TCu380A IUD。     

Copper surface area and clinical performance of the copper-bearing T intrauterine device

The concept of a parallel increase of surface area of copper and effectiveness with the T IUD was tested in 1,313 women during 11,581 months of use, divided in 4 groups inserted with T bearing 30, 120, 200 and 340 mm² of copper. No correlation between copper surface area on the T and clinical performance was observed.     

Premenopause contraception with monthly injectable Mesigyna with special emphasis on serum lipid and bone density patterns

This 2-year study compared Mesigyna(R) administered to 49 pre-menopausal women between 38 and 50 years, to 99 women fitted with an IUD (Nova-T). A complete lipoprotein assessment was carried out before treatment and at 6, 12, and 24 months of treatment. A bone densitometry was performed on half of the women, and an endometrial biopsy was taken from half of the Meisgyna group before and at the end of the first and second year. No pregnancy occurred with Mesigyna use while three pregnancies were observed with the IUD. The incidence of bleeding anomalies was higher in the Mesigyna group, with a discontinuation rate for these reasons of 20% versus 4% for IUD (p <0.05). The duration of bleeding days as well as dysmenorrhea were less with Mesigyna. No differences were seen in the pattern of intermenstrual bleeding and spinal bone density between both groups. No patient developed endometrial hyperplasia after treatment, thus endometrial risk seemed not to be increased. Total and LDL cholesterol, and apolipoproteins did not show modifications. A slight decrease in total triglycerides, HDL and HDL(2) cholesterol, and IDL lipoproteins was observed with Mesigyna. The present study appears to be the first using a monthly injectable hormonal contraceptive and monitoring its influence on lipid patterns in premenopausal women. Mesigyna proved to be a highly effective and low risk agent for premenopausal users.     

Reasons for contraceptive discontinuation in women 20-39 years old in New Zealand.

To estimate the frequency and the medical and nonmedical reasons for discontinuation of oral contraceptive (OC), intrauterine device (IUD), and injectable depot medroxyprogesterone acetate (DMPA) use, data from a cohort of experienced contraceptive users in New Zealand are reported. The current analysis consists of 2469 OC, 2072 IUD, and 1721 DMPA users followed over a period of 5 years. The percentage of women who discontinued the use of the method within 24 months after entry into the cohort were 42%, 44%, and 48%, respectively, for OC, IUD, and DMPA; these differences were not statistically significant. The most common reasons given for discontinuing a contraceptive method, regardless of which method was in use, were the desire to conceive, patient preference, no longer needing contraception, and vasectomy. Among the medical reasons, menorrhagia and intermenstrual bleeding were the reasons for discontinuing use of the method in 1.5 and 1.1 times per 100 women-years among DMPA users and in 1.8 and 4.7 times per 100 women-years among OC users. Pelvic pain and infection were reasons for discontinuing contraceptive method, respectively, 4.4 and 4.3 times per 100 women-years among IUD users. In conclusion, the present study confirms, in this New Zealand population, the high discontinuation rate of contraceptive methods reported elsewhere. In contrast with previous suggestions, in this study, irregular bleeding was not an important medical reason for discontinuation of DMPA use.