Implantable contraceptives for women: effectiveness, discontinuation rates, return of fertility, and outcome of pregnancies

Progestogen-only contraceptive implants are highly effective. In most studies, 5-year cumulative pregnancy rates are less than 1.5/100 women for Norplant and Norplant II. No study has yet reported any failures with Implanon. Weight over 70 kg and age at insertion under 25 years both increase the failure rate of Norplant and Norplant II; however, data are as yet lacking for Implanon. The effectiveness of other progestogen-only implants for which there are as yet few data are unlikely to be any different. Continuation rates are high compared with other hormonal methods and with the intrauterine device. In most cohorts at least 35% of women, and often many more, are still using Norplant by the end of 5 years. Rates vary according to a number of factors, including population studied, age, and parity. Menstrual disturbance is by far the most common reason for discontinuation, with headache, acne, weight gain, and desire for pregnancy accounting for other common reasons for implant removal. Fertility returns rapidly following implant removal, and pregnancy rates (76-100% 1 year after removal) are usually no different from those following discontinuation of any other contraceptive method. There is no increase in the risk of ectopic pregnancy, fetal malformation, or impaired infant health in pregnancies conceived either during implant use or after removal.     

A two-year study of acceptability, side effects, and effectiveness of NORPLANT and NORPLANT-2 implants in The People''s Republic of China

A large scale, phased investigation of NORPLANT^R contraceptive systems was conducted in the People's Republic of China. The first phase comprehended 1,200 women in four cities. Expanded trials included 11,918 women at 12 major centers and at sub-centers by 31 May 1987. At that date 4,676 NORPLANT^R capsule subjects and 1,089 rod subjects had completed one year of use, 1,381 capsule acceptors had completed two years as had 197 rod users. Gross pregnancy rates were less than 0.1 per 100 for each implant type both at one and at two years. Continuation rates were 94 per 100 for each implant type at one year, and were 82.0 and 83.6 per 100 among users of NORPLANT^R capsule and rod implants, respectively, at two years. Disruption of menstrual function was the dominant reason for termination, but mean hemoglobin levels increased in each of the nine centers reporting values at admission and at one year. First year gross cumulative termination rates for medical reasons were 1.2 to 1.3 per 100, reaching 3.8 and 5.6 per 100 for capsule and rod implants, respectively, at two years.

Microdose contraception with these levonorgestrel-releasing implants appears to be a highly acceptable and effective modality suitable for Chinese women. NORPLANT^R implants are now approved by the national drug regulatory agency for general use in China.     

4种新型宫内节育器使用5年临床效果评价

为较好掌握新型 IUD 的优点和特征,便于医务人员根据不同育龄妇女身体状况选择适当的 IUD 类型,本课题对2400例育龄妇女随机放置 TCu380A、三球头 TCu220C、MLCu375SL 和含药宫铜4种新型 IUD 使用5年间的终止原因进行临床多中心研究分析。结果表明:第二代活性 IUD具有安全、高效、长效的优点,其中尤以 TCu380A 具有较高续用率(78.1/100妇女),其妊娠率(带器妊娠及意外妊娠)为4.9/100妇女,脱落率也最低,为6.9/100妇女(P<0.05);MLCu375SL 城市组使用效果明显优于农村组,其5年续用率分别为80.54/100妇女和66.89/100妇女(P<0.05);农村组脱落率最高,为14.6/100妇女(P<0.05);含药宫铜 IUD 置器后月经量增加的症状明显减少,因症取出率最低,5年末为3.7/100妇女(P<0.01);;三球头 TCu220C 具有低因症取出率和低脱落率的优点,但带器妊娠率最高,为8.4/100妇女(P<0.01)。结果提示:T 铜 IUD 的脱落率相对较低;三球头 TCu220C 的球头和含药宫铜 IUD 所含的消炎痛在减少副反应方面有一定的作用;ML-Cu375SL 适合城市妇女使用。     

Norplant contraceptive implants: a new contraceptive for women

This article summarizes current knowledge on the mechanism of action, side effects, and effectiveness of Norplant contraceptive implants. The most common side effect of the implant method is its disruption of the menstrual cycle, especially in the 1st few months of use. Long intervals without frank bleeding may occur and be misinterpreted as pregnancy in women who have not been counseled about this possibility. The average annual continuation rate was 84/100 in a study of 324 women from several countries who were followed for 5 years after Norplant implantation. The net cumulative pregnancy rate for the 5-year study period was 0.6/100. Reasons for method termination included menstrual problems, other medical problems (headache, depression, fatique), planning pregnancy, and other personal reasons (change in marital status, change in residence). To provide training for doctors, nurses, and counselors, the Population Council has established a network of 5 training institutions. Within the next few years, drug regulatory agencies are expected to approve use of Norplant implants in many countries. Although at present the method is available only in Finland and Sweden, Thailand and Indonesia are considering the method and clinical trials are underway in India, China, Brazil, and the US. A consulting committee of the World Health Organization has concluded that Norplant implants are a suitable contraceptive method for use in family planning programs.     

Statement on Norplant subdermal contraceptive implant system

At its September 1985 meeting, the International Medical Advisory Panel of the International Planned Parenthood Federation drafted a statement concerning Norplant, the subdermal contraceptive implant system developed by the Population Council. The statement, intended for use by physicians, administrators, and other health personnel in the field of family planning, summarizes current knowledge of this means of fertility control. Norplant is particularly recommended for women who seek longterm protection from pregnancy, but either may desire another child in the future or do not wish to undergo sterilization. Insertion during the 1st 7 days after menstruation onset, or immediately postabortion or postpartum (in nonbreastfeeding women), is advised. Capsules should be removed after 5 years of use. Annual pregnancy rates range from 0.2-1.3/100 women/year, with a cumulative pregnncy rate of 5 years of 2.6. The most frequently reported side effect is irregular menstrual bleeding, especially during the 1st year of use. Continuation rates are 60-90% at the end of the 1st year, and about 50% after 5 years. Counseling, especially regarding bleeding irregularities, is critical to continued acceptability. 40% of women who request Norplant removal in order to conceive become pregnant within 3 months of removal, and 76% achieve pregnancy within 1 year. Epidemiologic studies of the longterm safety of Norplant implants are under way. It is noted that program use of Norplant poses several managerial challenges. Formal training in insertion and removal techniques, as well as the risks and benefits of the method, must be planned and back-up and referral facilities identified. Since Norplant is a new delivery system, a carefully designed public information system is also important.     

Prolonged effectiveness of Norplant(R) capsule implants: a 7-year study

Soft tubing Norplant(R) contraceptive implants were studied in 1210 women for 7 years to measure the duration of effectiveness and the magnitude of the pregnancy rates over that time. Mean age at enrollment was 27.4 years. Of the enrollees, 42% were US residents. One-sixth (16.1%) weighed >/=70 kg at the time of implant placement. At the end of 5 years, the cumulative pregnancy rate was 1.1/100; at the end of 7 years, it was 1.9/100. No pregnancies occurred to any of the 400 women who enrolled in the study at age >/=30 years and who weighed <100 kg. Among women aged 18-33 years, the 7-year Norplant pregnancy rates are comparable to the median pregnancy rates of tubal sterilization methods for women of the same age and duration of use. For women aged >/=34 years, without regard to weight at admission, the 7-year effectiveness of soft tubing Norplant equals or surpasses that of tubal sterilization. For continuing implant users, annual pregnancy rates <1.0/100 in years 6 and 7, together with low cumulative pregnancy rates, testify that Norplant capsule implants remain highly effective for 7 years.     

国产皮下埋植剂多中心研究

目的:评价两种国产皮下埋植剂的避孕效果、副反应和继续使用率。方法:分两期进行。第一期为国产Ⅰ型、Ⅱ型皮下埋植剂与Norplant进行前瞻性临床对比研究,各100例,共300例。第二期为国产皮下埋植剂扩大临床应用,接受合格对象Ⅰ型999例,Ⅱ型998例,共1997例。随访5年。结果:5年随访率为99.5％。第一期国产Ⅰ型、Ⅱ型皮下埋植剂和Norplant的5年累计妊娠率分别为0/百妇女、1.0/百妇女、0/百妇女,5年继续使用率分别为77％、80％、80％,差异均无统计学意义(P>0.05)。主要副反应为月经紊乱,月经卡分析显示3种埋植剂的出血模型相似。第二期国产Ⅰ型、Ⅱ型皮下埋植剂5年累计妊娠率分别为0.20/百妇女,2.10/百妇女,5年继续使用分别为84.47％、82.28％。使用埋植剂6个月Ⅰ型和Ⅱ型月经问题主诉发生率分别为50.88％、57.16％,差异有显著意义(P<0.01),但随着使用时间延长,月经紊乱主诉发生率逐渐下降,两组间无差异。结论:5年研究表明两种国产皮下埋植剂的避孕效果、副反应发生率和继续使用率与Norplant相似,也是一种高效,长效的避孕制剂。国产皮下埋植剂Ⅱ型使用至第5年避孕失败率明显增加,建议国产Ⅱ型皮下埋植剂使用期限在3～4年为好。     

两种国产皮下埋植避孕剂临床多中心比较研究

目的:对两种国产皮下埋植避孕剂的长期应用效果及副反应进行评价。方法:采用前瞻性临床多中心对比研究,共在5省58个分中心进行了7941例长达5年的临床应用和随访研究。结果:两种埋植剂5年的净累积妊娠率仅为0.257/百妇女(Ⅰ型)和1.569/百妇女(Ⅱ型),两者间有极显著差异;5年累积续用率高达76.23/百妇女(Ⅰ型)和77.98/百妇女(Ⅱ型);主诉副反应的发生率开始较高,随应用时间延长而逐年降低,由开始的近50％降至第5年时的15％左右,最主要的副反应是月经异常,占终止人数的74.8％,月经副反应发生率和因月经异常的停用率Ⅰ型埋植剂明显高于Ⅱ型。结论:两种国产皮下埋植避孕剂均是高效、长效、可接受性较好的新型避孕药。     

Recovery of fertility and outcome of planned pregnancies after the removal of NORPLANT subdermal implants or Copper-T IUDs

The recovery of fertility after discontinuation of NORPLANT^R implant use was assessed in ninety women who stated a desire for a new child at the time of removal. Three subjects were lost to follow-up after removal. The cumulative probability of conception in the remaining 87 women was 25, 49, 73 and 86 percent at one, three, six and twelve months after removal, respectively. Nine observations were censored either because of the use of a contraceptive method soon after removal of the implants (n = 7) or separation (n = 2). All other cases were pregnant at the end of two years with exception of three subjects where a male factor for infertility was present. There was no significant correlation between the length of NORPLANT^R use and the length of the interval from removal to conception. A significantly higher frequency of intervals longer than 6 months was observed among women older than 30 years as compared to younger women. Pathology during pregnancy was cholestasia (n = 5), hypertension (n = 1) and gestational diabetes (n = 1). The outcome was term delivery in 59 cases, premature delivery in 4 cases, and spontaneous abortion in 7 cases. One woman is still pregnant and the outcome is unknown in 4 cases. One premature infant died. A contemporary control group of Copper Tusers enrolled under the same criteria as NORPLANT^R implant users provided 44 women who had the device removed to become pregnant. The cumulative probability of pregnancy was 27, 69, 84 and 89 at one, three, six and twelve months and all were pregnant by the end of the second year. Six censored observations occurred because of the use of another contraceptive method after removal (n = 3) or loss to follow-up (n = 3). The outcome of pregnancy was term delivery in 23 cases and abortion in 7 cases. Recovery of fertility occurred at a normal rate after NORPLANT^R implant removal and the incidence of problems detected in the ensuing pregnancy were within the expected range for Chilean women.     

A study on the contraceptive effectiveness of a newly designed IUD "FD-1" in Japan

A newly designed IUD, FD-1, was inserted in 671 women for a total of 9624.5 months of use. The IUD is ready-loaded in its insertion so no folding or loading of the IUD before insertion is necessary. The net cumulative termination rates at the end of 23 months using the life-table techniques are as follows: pregnancy 4.0, expulsion 2.1, removal due to bleeding and pain 2.7, other medical reason 0.8, planning pregnancy 1.0, and other personal reason 0.4, per 100 women. This clinical experience has demonstrated that this IUD has a high contraceptive effectiveness with a low expulsion rate and high acceptability.     

Five-year clinical experiences with NOVA T 380 copper IUD

In an open, single-group, phase III clinical trial of 5 years, the clinical performance of NOVA T 380 was investigated in three centers. The device having a higher copper surface of 380 mm(2) is a modification of NOVA T. A total of 400 voluntary women were enrolled in the study. The mean age was 31.4 years (SD 5.5) with the minimum of 18 and the maximum of 44 years. At the end of the study, 211 women had passed the 60-month visit. Cumulative discontinuation rates at the end of the first and the fifth year calculated by Kaplan-Meier estimates, were respectively as follows: pregnancy 0.5 and 1.9, expulsion 1.3 and 4.1, bleeding 4.4 and 14.0, pain 1.3 and 4.2, removal for other medical reason 1.4 and 6.4, planning pregnancy 0.8 and 13.5, and removal for other personal reason 2.4 and 11.9 per 100 users. Neither ectopic pregnancies nor episodes of pelvic inflammatory diseases (PIDs) occurred. One perforation was recorded; the calculated rate is 0.3 per 100 women (first year). The continuation rate was 88.3 and 52.5 at 1 and 5 years, respectively. In conclusion, the 5-year performance of NOVA T 380 was good compared to other "high-loaded" copper devices. Safety was acceptable over the entire study period.     

A five-year clinical evaluation of NORPLANT contraceptive subdermal implants in Bangladeshi acceptors

A non-comparative study of the Norplant contraceptive subdermal implant system was conducted in Dhaka, Bangladesh. The study was designed to evaluate the contraceptive efficacy, safety and overall acceptability of Norplant implants. Six hundred women were enrolled in the clinical trial, which began in 1985 at three study sites. Follow-up visits were scheduled at 1, 3, and 6 months after Norplant implant insertion, and every six months thereafter until removal or at the end of five years. There were no post-insertion pregnancies during Norplant implant use in this study. After five years of Norplant implant use, there was no clinically significant change in body weight, systolic or diastolic blood pressure. Less than 3% of the women ever reported having any significant medical problems such as migraine, respiratory or cardiac problems during the study. The gross cumulative continuation rate was 41.2 per 100 women at the end of five years. The two most frequently reported reasons for discontinuation during the study were menstrual problems and desired pregnancy. Of the women who completed the five-year user satisfaction questionnaire, the majority of the women (86.3%) planned to continue using contraception after study completion. Of these women, approximately one-third said they planned to use another Norplant set. The findings presented suggest that the Norplant system is a highly effective, safe and acceptable method among Bangladeshi women.     

Introduction of the injectable contraceptive NET-EN into family planning clinics in Bangladesh

In preparation for introducing the injectable contraceptive norethisterone enanthate (NET-EN) into the national family planning program, a field study was conducted in 6 family planning clinics in Bangladesh. 3 of the clinics were located in Dhaka, the capital city, 1 was located in a town approximately 15 kilometers from Dhaka, and the other 2 clinics were located several hundred kilometers from Dhaka. A total of 913 women were chosen to receive injections of NET-EN every 8 weeks for 6 months and every 12 weeks thereafter. The mean age of the subjects was 26.8 years, and the mean number of live births was 3.4. The overall cumulative discontinuation rates were 26.3/100 women at 6 months, 37.3/100 at 12 months, and 42.9/100 at 18 months. The most common reason for discontinuing was a disturbance in bleeding. Heavy and/or prolonged bleeding was the single most frequent reason (6.3/100 women at 12 months), but amenorrhea was not uncommon (5.1/100 women at 12 months), while irregular bleeding or spotting was given as a reason somewhat less frequently (3.9/100 women). 3 women became pregnant during the study, giving a cumulative pregnancy rate of 0.4/100 women at 18 months. A variety of complaints fell within the category of "other medical reasons," the most common being fatigue, headache, and dizziness. The overall discontinuation rates varied markedly by center, as did the reasons for discontinuation. The lowest discontinuation rate of 14.7/100 women at 12 months was seen in the Mohammedpur Fertility Services and Training Center. This rate was considerably lower than that in any other center. The highest discontinuation rate was found by the Bangladesh Association for Voluntary Sterilization -- 52.0/100 women at 12 months. The variation in rate of discontinuation because of bleeding disturbances was most dramatic, with relatively high rates at the Bangladesh Association for Voluntary Sterilization, markedly low rates in the Mohammedpur Fertility Services and Training Centre, and intermediate rates elsewhere. Neither the overall discontinuation rate, nor the individual reasons for discontinuation varied much by age group. The most notable finding regarding discontinuation of NET-EN was the marked difference between centers. This is particularly notable given the lack of any major differences with respect to age, parity, residence, and history of contraception of the subjects. These findings suggest that the specific approach used in each clinic had a considerable impact on continuation rates and acceptance of NET-EN.     

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。     

19301例吉妮IUD5年使用效果观察

目的:了解吉妮IUD长期使用的有效性。方法:通过门诊和电话随访方式,调查了山东省19个中心19301例使用吉妮IUD满5年妇女。结果:调查对象绝大多数来自农村,置器时哺乳妇女居多(69.8%),术者均为县级计划生育服务站医生。5年续用率87.89/百妇女年,与IUD使用相关的终止率为4.47/百妇女年(带器妊娠0.93/百妇女年、脱落1.29/百妇女年、因出血/疼痛2.10/百妇女年),吉妮IUD长期使用是安全、有效的,特别是对农村哺乳妇女作为间隔生育或长期避孕有很好的可接受性。     

国产皮下埋植避孕方法多中心研究

本研究在全国11个省100个分中心对国产Ⅰ型和Ⅱ型皮下埋植剂进行临床多中心比较研究,共接收合格对象19673例,目前已完成二年随访。二年随访率94.29％,累计继续使用率分别为88.89,％(Ⅰ型)和89.93％(Ⅱ型),Ⅱ型显著高于Ⅰ型,二年累积妊娠率Ⅰ型和Ⅱ型分别为每百妇女0.0462和0.281,其间呈显著性差异。Ⅰ型埋植剂无异位妊娠发生,Ⅱ型埋植剂发生异位妊娠3例,发生率为0.163/1000妇女年。副反应的发生率有随时间增长而减少的趋势。主要副反应为月经失调,占副反应的90％以上。月经异常中月经频发、不规则出血和点滴出血的发生率高于月经稀发/量少和闭经。闭经和月经稀发/量少的发生率Ⅰ型高于Ⅱ型。二年观察中,因月经问题而终止使用者占总终止人数的78％,与月经问题有关的二年累积终止率Ⅰ型为每百妇女8.96,Ⅱ型为7.84,差别有显著性。二年观察研究表明,两种国产皮下埋植剂的副反应发生率和避孕效果以及二年的续用率与Norplant相似。     

A five-year clinical trial of levonorgestrel silastic implants (Norplant™)

Silastic implants containing the progestin, levonorgestrel, were tested as a long-term contraceptive system in 101 women. During five full years of use, no pregnancies occurred. The 5-year continuation rate was 54%. Menstrual irregularities were the most frequent reason for termination of use but only during the first year. More than half of the terminations for this reason were in the first year. Some of the subjects elected to continue use of the implants beyond 5 years, allowing release rate data to be obtained through 6 years.From the second through the sixth year of use, the implants delivered a constant 30 micrograms per day of levonorgestrel to the subjects, and even after six years 57% of the original steroid content remained in the capsules.Return of fertility following removal was essentially immediate and not related to time of use. Medical reasons for removal were infrequent and no pattern was discernible.     

Two-year performance of a Nestorone-releasing contraceptive implant: a three-center study of 300 women

A 2-year trial of a single Nestorone (NES) rod implant was conducted at three Latin American centers, each enrolling 100 women. We studied the safety, effectiveness and acceptability of this progestin-releasing contraceptive implant. Three pregnancies occurred, the last at 18 months of use. Because no pregnancies were expected in the first 18 months, the trial was halted. At that time, 224 women had completed at least 18 months of use, and 99 women had used the implant for more than 24 months. Few participants used adjunctive contraception between the time the study was halted and the time they had their implant removed. No additional pregnancies occurred before the removal of the last implant. The 2-year cumulative pregnancy rate was 1.7 per 100 with a Pearl index of 0.6 per 100 for the 2-year period. The 1-year and 2-year continuation rates were 80.5 and 66.7 per 100, respectively. Menstrual and medical disturbances were the principal reasons for discontinuation, followed by planned pregnancy. Headache and weight gain frequently led to discontinuation. The NES implant had little important effect on most clinical chemistry and lipid parameters. Over the study course, the mean change in hemoglobin was <1%. Slight modification of the design of this single 2-year implant, restoring features previously examined in clinical trials, is likely to improve its effectiveness. A single NES implant appears to provide acceptable contraception for women.     

Return of fertility after the removal of Nova T or Copper T 200

The return of fertility after removal of Nova T or Copper T 200 IUDs was studied in 150 women who had a removal for planning pregnancy in a study performed for the comparison of the clinical performance of these IUDs in Denmark, Finland and Sweden. There was no significant difference in the return of fertility of women having used either device. The cumulative probability of pregnancy per 100 women after the removal of the IUD, as a net rate, was 77.3 at one year, 88.9 at two years and 92.4 at three years.The return of fertility was analyzed separately for those women who had used their IUD for less than two years and for two or more years. The duration of the use had no significant effect on the return of fertility. The outcome of pregnancy, the birth weight, the condition at delivery and the sex ratio of the newborns were normal in the participating countries.     

Efficacy and continuation rates of Norplant in Pakistan.

A total of 265 women who had the Norplant system inserted were followed for 5 years. The present study is based on 11,435 women-months of use, describing the continuation rates and efficacy of Norplant among these women. The 5-year cumulative continuation rate was 45.7 per 100 continuing users. The continuation rates were age-dependent. The women > or = 35 years of age consistently maintained higher continuation rates at all time intervals as compared with those of younger women. During 5 years of follow-up, five women became pregnant. Three pregnancies occurred in year 2, one in year 3, and one in year 5. The 5-year cumulative pregnancy rate was 2.5 per 100 continuing users. The weight of the user did not influence the pregnancy rate. The continuation rates, as well as the pregnancy rates, are comparable to those reported from other countries in the region.