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.     

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 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.     

Use of Norplant implants in a New York City clinic population

Two-hundred-eight women attending family planning clinics in New York City who received the Norplant contraceptive system during the first sixteen months of Norplant implants insertions were evaluated. Within this clinic population, Norplant implants were a popular contraceptive choice and were removed from 64 of the 208 recipients. Reasons for removal included bleeding, weight gain, and headache, and were consistent with those found in the clinical trials. Prior satisfaction with oral contraceptives did not predict success or failure with Norplant implants. The rate of follow-up visits to the family planning clinics was low. However, evidence exists that these women did not lose contact with the medical center and continued to receive health care.     

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.     

Norplant皮下埋植避孕150例临床研究

目的:探讨Norplant皮下埋植避孕的效果。方法:选择Norplant皮下埋植避孕妇女150例作为治疗组,以宫内节育环避孕妇女150例作为对照组,比较两组使用情况、避孕效果和月经紊乱情况。结果:5年后随访,治疗组因不适取出32例,取出率为21.33%,其余118例全部达到避孕效果,有效率100.00%;期间出现月经紊乱58例,发生率为49.15%;对照组因不适取出或自行脱出10例,取出率为6.67%,其余140例中达到避孕效果115例,有效率82.14%,出现月经紊乱33例,发生率为23.57%。两组避孕效果、月经紊乱和不适失败率比较均具有统计学差异(P<0.01)。结论:对生育期要求避孕妇女行皮下Norplant埋植避孕手术可达到有效的避孕效果,但月经紊乱发生率相对较高,宫内节育环避孕有效率较皮下Norplant埋植避孕手术低,但月经紊乱发生率亦较治疗组低。使用Norplant埋植避孕如何减少月经紊乱,仍是今后值得探讨的一个问题。     

Norplant contraceptive implants: rods versus capsules

Norplant contraceptive implants are silastic implants containing levonorgestrel. When placed subcutaneously in the medial aspect of the upper arm, they release low levels of levonorgestrel in a constant manner over an extended period of time. Comparative studies of two silastic rods versus six capsules containing levonorgestrel were studied in 250 subjects for 4,464 months of use. Only one pregnancy occurred during the study. Side effect patterns were similar in both groups; the major side effect being irregular uterine bleeding. The bleeding, however, was well tolerated by subjects in both groups and discontinuation rate was very low. The two-rod system offers the advantages of easier insertion technique and shorter insertion time as well as ease of removal as compared to the six-capsule system. Norplant contraceptive implants offer a highly effective means of contraception which is particularly suited for women who are concerned about failure and compliance with oral contraceptives. This type of contraception should become well accepted, not only in underdeveloped countries, but in developed countries as well.     

Recent developments in contraceptive implants at the Population Council

Development of contraceptive implant methods, when based on established or on new synthetic chemical entities, is a decadal or multi-decadal process. The process often requires the cooperation of numerous investigators for laboratory work, for early Phase II trials, for dose-finding trials, and for Phase III clinical trials. The Phase III work also requires cooperation with a commercial manufacturer and potential distributor of the product. The Population Council has recently completed developmental work on two levonorgestrel-releasing implants, with filings to regulatory agencies that support extended use of Jadelle implants for 5 years and Norplant implants for 7 years. When the developmental process includes establishing the clinical properties of a molecule not yet approved by regulatory agencies, the minimum development time appears to be two decades. The status and rationale of studies of a new Nestorone-releasing, single implant developed by the Population Council for a period of use of 2 years are presented.     

Potential barriers to the removal of Norplant among family planning clinic patients.

OBJECTIVES: This study examined the prevalence and effects of potential barriers to removal of levonorgestrel implants (Norplant) among low-income women. METHODS: A sample of 687 women who received Norplant at hospital-based family planning clinics were interviewed before Norplant insertion and 6 months after Norplant insertion (or at Norplant removal if removal occurred earlier). Those who continued to use Norplant were reinterviewed at 2 years or at removal. RESULTS: In a multivariate analysis, only 1 of the 4 potential barriers--cost--significantly impeded Norplant discontinuation. CONCLUSIONS: Family planning clinics need to make clear that they follow a policy of Norplant removal on demand, regardless of the patient's ability to pay.     

Ovarian cysts in users of Implanon and Jadelle subdermal contraceptive implants

OBJECTIVE: To evaluate the prevalence of ovarian cysts in users of two contraceptive implants compared to users of intrauterine contraceptive (IUC). MATERIALS AND METHODS: A total of 344 women were enrolled at 3 months of use of the etonogestrel-releasing implant (Implanon), the levonorgestrel-releasing implant (Jadelle) or the TCu380A IUC. Bimanual pelvic examination and vaginal ultrasound were performed during routine 3-, 6- and 12-month visits of asymptomatic women. Women with ovarian cysts (or enlarged ovarian follicles > or = 25 mm) were assessed weekly until disappearance or reduction of the image [including estradiol (E2) and progesterone (P) measurement], and women with no ovarian enlargement underwent the same evaluation for the same period of time. RESULTS: Ovarian cysts were detected in 5.2%, 13.0% and 1.9% of users of Implanon, Jadelle and IUC, respectively, at 3 months. At 6 months of use, prevalence was 7.2%, 8.0% and 2.1%, whereas 12-month rates were 26.7%, 14.6% and 1.2% in the three groups, respectively. E2 levels were significantly higher among users with ovarian cysts than controls. The time until disappearance of the ovarian cyst was similar in all three groups. There were more cases of menorrhagia in users of implants who had ovarian cysts than in those with no ovarian enlargement. CONCLUSIONS: The finding of ovarian cysts or enlarged ovarian follicles during the first year of use of Implanon and Jadelle implants is common and transient and should not be interpreted as a pathologic ovarian cyst. No further medical interventions are necessary.     

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.     

A comparison of the clinical performance, contraceptive efficacy, reversibility and acceptability of Norplant implants and Ortho Gynae T380 intrauterine copper contraceptive device

In this comparative study, the five-year continuity rate of 53.7% in the Norplant implants group was comparable to that of 52.7% in the copper IUD group. The difference was not statistically significant. Only one accidental pregnancy occurred during the five years of copper IUD use.Desire for future pregnancy was the main reason for removal in the Norplant implants group (35.9%) while expulsion of the IUD (13.2%) was the main reason for removal of the copper IUD. Menstrual disturbance was not a major side-effect in either group.The post-removal conception rates of 78.6% in the Norplant implants group and 75.0% in the copper IUD were good and comparable.Both the Norplant implants and copper IUD are acceptable and effective contraceptive methods in Singapore.     

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.     

Location and removal of non-palpable Implanon implants with the aid of ultrasound guidance

BACKGROUND: Implanon insertion appears to be an easy procedure, but in a small minority of cases difficulties have been encountered with removal if the rod is impalpable. METHODS: Patients were referred to the contraceptive and sexual health service with non-palpable Implanon. Following a clinical assessment and examination of the arm where the implant had been inserted, an ultrasound examination was carried out to identify and locate the implant. These implants were subsequently removed, some under general anaesthesia and others under local anaesthesia. RESULTS: Twenty-seven patients were referred to the unit with impalpable Implanon rods. In four cases the rods were palpable and were removed in the clinic setting without the need for further intervention. Positive identification of the implants was achieved in 21 of the remaining 23 cases using ultrasound. No implant was detected in two cases and etonogestrel was not demonstrated serologically in either woman, suggesting non-insertion. All 21 Implanon rods identified by ultrasound were successfully removed. In just over 52% of women a previous attempt at removal had been undertaken prior to referral. CONCLUSIONS: It is possible to identify and locate impalpable Implanon rods with the aid of ultrasound, facilitating their subsequent safe removal. Although previous reports have identified the position of 'lost' implants using ultrasound, this is the first case series to discuss measuring the skin/implant depth. This parameter, together with the precise position of the implant (in muscle or fat), aids removal. All health professionals inserting and removing contraceptive implants should have been appropriately trained.     

皮下埋植避孕剂用于临床避孕的疗效研究

目的:对皮下埋植剂避孕剂避孕的临床疗效及安全性进行研究,对其临床应用的前景进行展望。方法:对2007年4月～2008年4月在东台市计划生育指导站实行避孕术的妇女进行回顾性分析,选取98例符合标准者,观察组使用皮下埋植避孕剂进行避孕,对照组使用宫内节育器进行避孕。对两组研究对象避孕效果、术后阴道出血、月经情况、放置率、患者满意率等临床数据进行比较。结果:术后对患者随访5年,观察组有效率为97.9%,较对照组91.3%有优势。观察组出现不良反应4例,不良反应率为8.5%;对照组出现不良反应11例,不良发应率为23.9%,观察组不良反应率低于对照组(P<0.05)。观察组在放置率及患者满意率明显优于对照组。结论:皮下埋植避孕剂在临床避孕的使用中,具有避孕率高,不良发应少,放置率高等优势,受到临床医患的认可,适于推广使用。     

Norplant® implants in the UK: First year continuation and removals

Norplant^® implants are a long-term, reversible hormonal method of contraception consisting of six flexible capsules placed subdermally in the inner aspect of the nondominant arm. Norplant implants were introduced into the UK in October 1993 although they had been used previously in some countries for up to ten years. The insertion and removal techniques require skills training and therefore it is important to assess early experience with the method.

This survey looks at the first year continuation rate of Norplant implants in the UK from a total of 2,129 insertions. From these insertions, 133 removals were documented and described, using a checklist of features. The continuation rate for Norplant implants use was 96.5% at six months and 85.2% at one year. None of the reasons for discontinuation were of a serious nature. The most common reason given was menstrual change (50.4% of all removals, 3% of all women included in the survey), which is in line with other reported studies.

Of the removals, 71.5% were reported as straightforward (of these 65.6% were completed within 20 minutes). In the first year of use, Norplant implants were associated with high continuation rates and the removal procedure was, in the majority of cases, completely straight-forward.     

Norplant as a Contraceptive Device in Enugu, Eastern Nigeria

This paper is an evaluation of acceptability and use-experience with the contraceptive device Norplant at the University of Nigeria Teaching Hospital, Enugu, Eastern Nigeria. Over a period of 36 months, 173 women (8% of the clinic population) accepted the implant. Use of Norplant was concentrated among high-parity women, and the proportion of Norplant users was highest among women aged 30–34 years. Comparing Norplant and IUD users, we found Norplant users to be significantly less highly educated with <1% of Norplant users having tertiary education compared to 25% of new IUD users. The continuation rate with Norplant was 89% at three years, suggesting this method has the potential for improving the low contraceptive prevalence in this region.     

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.     

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.     

Local side effects observed among long-term users of norplant contraceptive implants

The prevalence of local signs and symptoms related to the site of insertion of implants, and the association of these signs and symptoms with time of use, skin color and body mass index (BMI) was evaluated among users of the Norplant implant system. Three hundred and three Norplant users attending at the reproductive health clinic of PROFAMILIA in Santo Domingo, Dominican Republic, were asked if they had ever had any discomfort at the site/arm of implant insertion and the implant insertion area was examined and hyperpigmentation and hollowing of the surface was recorded. Half of the subjects reported either pain or paresthesia or both, in almost equal numbers, some time since insertion. Hyperpigmentation was observed in 35.6% and hollowing in 22.4% of the subjects. Report of pain and paresthesia was inversely associated to time of use and to BMI. Hyperpigmentation was directly associated to time of use and darker skin, and hollowing of the arm surface in the implants area with time of use and BMI. Local signs and symptoms were more frequent than previously reported, although they were of mild nature and appeared not to worry most of the users.