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.     

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.     

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。     

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.     

A 5-year clinical evaluation of norplant® implants in senegal

The principal objective of this 5-year clinical study of Norplant® implants was to introduce these implants into the family planning program in Senegal and to determine their overall acceptability and safety in Senegalese acceptors. A total of 300 subjects were enrolled into the trial from August 1986 to July 1991. All the women were followed-up for 5 years or until the implants were removed. The pooled cumulative discontinuation rate was 40.8 ± 2.91 per 100 women resulting in a continuation rate of 59.2 ± 2.91 per 100 women. Thirteen subjects (4.3%) were lost during the follow-up. Seven pregnancies were reported throughout the 5 years leading to a cumulative pregnancy rate of 3.3 ± 1.25 per 100 women. Menstrual problems were the reason most often given for early removal during the first 2 years. After year 2, desire for another pregnancy was the main reason for implant removal. The results presented in this study show that the Norplant implant system is a safe, effective, and acceptable method that meets the needs of the Senegalese family planning program.     

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。     

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.     

Post-marketing surveillance of Norplant contraceptive implants: I. Contraceptive efficacy and reproductive health

The subject of this study to examine the safety and contraceptive efficacy of Norplant, we undertook a 5-year study of follow-up of women initiating use of Norplant, intrauterine device (IUD) or sterilization in eight developing countries. Women attending family clinics were enrolled if they consented and were medically eligible to use Norplant, IUD, or female sterilization. Women who chose to initiate use of IUDs or surgical sterilization served as controls and were frequency matched in 5-year age-bands with women who chose to use Norplant. At admission women had a physical examination, and their medical histories, demographic, and socio-economic characteristics were recorded. Follow-up visits were scheduled in the first 6 weeks after admission and semi-annually thereafter for 5 years irrespective of change of contraceptive method. Incidence rate ratios of health events were estimated for initial and current contraceptive method use. This paper reports reproductive health events and contraceptive efficacy. Altogether, 7,977 women initiating use of Norplant, 6,625 of IUD, and 1,419 of surgical sterilization were admitted. Their mean ages at initiation were 28.5, 28.5, and 29.6 years, respectively. More than 99% were married or cohabiting, and parous. Five-year follow-up was completed by 94.6% of the women. By the end of 5 years, the mean duration of first segment use per initiator was 4.16 years for Norplant, 4.10 years for IUDs, and 4.96 years for sterilization accounting for 39,337 woman-years for Norplant, 31,915 for IUDs, and 7,071 for sterilization. The study accumulated 78,323 woman-years of observation. Pearl pregnancy rates for Norplant, copper IUDs and female sterilization were 0.27, 0.88, and 0.17 per 100 woman-years, respectively. Users of Norplant, copper IUDs, and sterilization had rates of ectopic pregnancy of 0.30, 0.68, and 0.13 per 1,000 woman-years, respectively. Major health events related to the reproductive system were rare. Rates of acute PID were significantly lower among Norplant users than IUD users (p = 0.004). The rate of ovarian enlargement was significantly higher in Norplant users than controls (p <0.001), but not rates of hospitalization for this condition. Vaginitis and vaginal discharge, and low abdominal pain were significantly less frequent in Norplant users than in the other groups. Bleeding disturbances were more frequent among Norplant users than controls but not anemia. The study confirms the high contraceptive efficacy of Norplant, copper IUDs, and female sterilization. The incidence rates of major reproductive health problems were low. There was no significant excess of serious reproductive morbidity among users of Norplant compared to users of IUDs and sterilization.     

Efficacy and side effects of Norplant use in Thai women above the age of 35 years.

A prospective study of Norplant implant use in women aged above 35 years was conducted in Bangkok, Thailand. The purposes of this study were to evaluate the efficacy, menstrual patterns, and side effects of Norplant use in these women. A total of 100 women were recruited in a 1-year clinical study. Their mean age was 39.7 years. Most acceptors had completed secondary school. No accidental pregnancy occurred throughout the 1 year of use in this study. The most common menstrual pattern in these acceptors was amenorrhea followed by irregular bleeding. The major side effect was irregular bleeding. There was no significant change in systolic and diastolic blood pressure during the 1 year follow-up period. Thus, Norplant implant use in older women is a safe and effective contraceptive method. This should become another choice for contraception in women aged above 35 years who have contraindications for oral contraceptive use.     

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.     

NorplantR contraceptive subdermal implants: Two-year experience in Singapore

Norplant contraceptive implants are Silastic containing levonorgestrel implants. This study describes our two-year experience with 100 acceptors of Norplant implants in Singapore. No pregnancies occurred during the first two years of use. Desire for planned pregnancy and disruption of menstrual rhythm were the two main reasons for twenty implant removals during the two years. The continuation rate at the end of two years was 79%. The post-removal conception rate in women desiring pregnancy was 90% at the end of one year. It thus appears that the Norplant contraceptive system offers a highly effective, acceptable, reversible and safe method of contraception.     

国产18甲基炔诺酮皮下埋植剂的临床研究

666例40岁以下健康育龄妇女所参加的前瞻性多中心研究,经过一年观察,国产组333例中无妊娠,对照的Norplant-1组发生1例妊娠,妊娠率0.3/100妇女,二组的续用率同为94/100妇女。     

Norplant皮下埋植剂使用七年效果

对Norplant皮下埋植剂继续使用7年以上的效果作了多中心研究。3600余妇女使用满6年,2400余妇女使用满7年。第6、第7年的年妊娠率均为0.4/100妇女年。妊娠率随体重增加而增加(P<0.05),随年龄的增长而降低,第6、7年合并计算任何年龄组或体重组其年妊娠平均未超过1/100妇女年。     

A multicenter comparative study on the efficacy, safety, and acceptability of the contraceptive subdermal implants Norplant and Norplant-II

In order to assess efficacy, safety, and acceptability of the contraceptive subdermal implants Norplant^® and Norplant^®-II in Mexican women, a comparative phase III clinical trial was undertaken in eight clinics across the country. The study involved 1052 women who were followed-up trimonthly for three years. Cumulative pregnancy rates were 0.29% and 0.34% for Norplant and Norplant-II implants, respectively. Similar overall cumulative discontinuation rates were observed at three years: 50.38% for Norplant capsules, and 50.44% for Norplant-II rods. The main method-related reason for termination was endometrial bleeding irregularity which led to discontinuation rates of 11.94% and 11.62% for Norplant and Norplant-II contraceptive systems, respectively. In 15,279 woman-months of experience accumulated with Norplant implants and 14,092 with Norplant-II implants, there were few adverse events reported. No difference was found between the two groups in either difficulty for implants placement and removal or women's discomfort, even though the time required for insertion and removal of Norplant capsules was longer than for Norplant-II rods. It is concluded that during the first three years of use, both implants systems are equally effective, safe, and acceptable.     

Effective use of hormonal contraceptives: Part II: Combined hormonal injectables, progestogen-only injectables and contraceptive implants

Our objective in this systematic review was to evaluate evidence regarding controversial issues in the clinical management of women using injectable and implantable contraceptives. We searched MEDLINE and EMBASE for reports of primary research, published from 1966 through April 2005 in peer-reviewed journals, related to the initiation of combined or progestogen-only injectables and contraceptive implants, the effects of late contraceptive injections or the duration of levonorgestrel implant effectiveness. Results of the studies we reviewed showed that initiating injectable and implantable contraceptives through day 7 of the menstrual cycle suppresses follicular activity. Time to ovulation after study participants discontinued using injectables varied widely: from 4 to 8 weeks after the last administration of combined injectables, from 15 to 49 weeks after the last injection of depot medroxyprogesterone acetate and from 5 to 19 weeks after the last injection of norethisterone enanthate. Norplant implants left in place for up to seven completed years remained effective among women who weighed <70 kg at the time of implant insertion, but their effectiveness decreased among women weighing >or=70 kg.     

Tubal sterilization in women 15-24 years of age: demographic trends in the United States, 1970-1980.

Between 1970-1980, approximately 942,000 women 15-24 years of age underwent tubal sterilization in the United States. These women represented about 17 per cent of all women ages 15-44 years who underwent tubal sterilization in the United States during this 11-year period. During 1970-1980, sterilization rates rose steadily from three per 1,000 to 11 per 1,000 for women in the 20- to 24-year age group, but remained stable at less than one per 1,000 for women in the 15- to 19-year age group. For each year, rates for Black women were greater than those for White women. Sterilization rates increased over the time period for both currently and previously married women, but remained low for never-married women. Most tubal sterilizations were performed after delivery of an infant.     

Five-year experience with Norplant

At Klinik Raden Saleh, Department of Obstetrics and Gynaecology, University of Indonesia, from 1 May until 31 August, 1981, Norplant contraceptive implants were inserted into 437 Indonesian women. The continuation rates of Norplant at first, second, third, fourth and fifth year were, respectively, 96%, 92%, 88%, 82% and 78%. Bleeding problems were the most common cause for removal. The cumulative five-year net pregnancy rate for Norplant was 1.8 per 100 women. The Norplant contraceptive system is thus seen to combine the highest acceptability as measured by its continuation rate with the highest long-term effectiveness among the available temporary contraceptive methods.     

皮下埋植避孕剂临床多中心对比研究

对两种国产皮下埋植避孕剂与 Norplant 进行前瞻性临床对比研究,以了解在避孕效果、临床副反应及续用率方面有无差异。全国10个省市分别承担国产Ⅰ型、Ⅱ型和 Norplant 各100例,采用前瞻性、随机化的临床对比研究。根据统一的科研计划、记录表格和定期随访,资料集中统计和处理。共接收国产Ⅰ型1 001例,国产Ⅱ型1001例,Norplant 998例。一年时的随访率为99.3%,1年内避孕失败1例,因各种原因的终止率分别为每百名妇女3.9、3.7和3.9,因月经问题而终止者分别占总终止的79%、73%和77%,一年末的续用率分别为96.1%、96.3%和96.1%,三组之间均无差异。两种国产皮下埋植剂均为一种高效的避孕方法,副反应发生率、因症终止率和续用率均与 Norplant 相似,在全国不同地区、不同群体之间和 Norplant 一样具有较高的可接受性,可供广大育龄妇女选用。     

Long-term contraception by a single silastic implant-D containing norethindrone acetate in women: a clinical evaluation

876 women were followed over a 3975-woman-month period after implantation of a single silastic capsule containing 40 mg of norethindrone acetate. Data were analyzed by a life-table method with 3 cut-off dates. Net cumulative pregnancy rate until 7 months was 2.3/100, whereas it rose to 3.9/100 after 8 months of implantation. Net cumulative termination rates rose from .7-10.9 at the end of 7 months and reached 13.6 after 8 months. Removal rates for planned pregnancy, personal, and medical reasons after 8 months were .6, 1.2, and 5.7, respectively. 1.4/100 requested implant removals in preparation for sterilization procedures. Expulsion occurred at a rate of .8/100 at the end of 8 months. The continuation rate was 86.4/100 after 8 months. Menstrual pattern abnormalities showed a reduction with time. This implant seems an acceptable long-term contraception alternative.     

Probability of pregnancy after sterilization: a comparison of hysteroscopic versus laparoscopic sterilization

Objective

To compare the expected probability of pregnancy after hysteroscopic versus laparoscopic sterilization based on available data using decision analysis.

Study design

We developed an evidence-based Markov model to estimate the probability of pregnancy over 10 years after three different female sterilization procedures: hysteroscopic, laparoscopic silicone rubber band application and laparoscopic bipolar coagulation. Parameter estimates for procedure success, probability of completing follow-up testing and risk of pregnancy after different sterilization procedures were obtained from published sources.

Results

In the base case analysis at all points in time after the sterilization procedure, the initial and cumulative risk of pregnancy after sterilization is higher in women opting for hysteroscopic than either laparoscopic band or bipolar sterilization. The expected pregnancy rates per 1000 women at 1 year are 57, 7 and 3 for hysteroscopic sterilization, laparoscopic silicone rubber band application and laparoscopic bipolar coagulation, respectively. At 10 years, the cumulative pregnancy rates per 1000 women are 96, 24 and 30, respectively. Sensitivity analyses suggest that the three procedures would have an equivalent pregnancy risk of approximately 80 per 1000 women at 10 years if the probability of successful laparoscopic (band or bipolar) sterilization drops below 90% and successful coil placement on first hysteroscopic attempt increases to 98% or if the probability of undergoing a hysterosalpingogram increases to 100%.

Conclusion

Based on available data, the expected population risk of pregnancy is higher after hysteroscopic than laparoscopic sterilization. Consistent with existing contraceptive classification, future characterization of hysteroscopic sterilization should distinguish “perfect” and “typical” use failure rates.

Implications

Pregnancy probability at 1 year and over 10 years is expected to be higher in women having hysteroscopic as compared to laparoscopic sterilization.