A total of 150 women in 3 equal groups, each using a different contraceptive method (group I used Norplant, group II used the IUD and group III used combined OC pills) were investigated for the presence of vaginal candidiasis before and at various time intervals (3, 6 and 12 months) after starting to use the particular contraceptive method. The incidence of vaginal Candida albicans infection increased significantly among pill and IUD users, but with a much lower intensity among the latter cases. In Norplant users the increase was slight and insignificant. The explanation of these findings within the context of changes in local vaginal milieu is discussed.

Bangladesh has achieved a considerable decline in fertility level in the past four decades through a strong family planning programme in spite of its poor social and economic growth. However, discontinuation of contraceptive methods and decline in the use of long-acting and permanent methods (LAPMs) are still the major concerns of the family planning programmes. This paper describes various factors that lead to the acceptance of the long-term method--Norplant and those that lead to early discontinuation. This descriptive, cross-sectional study was conducted in the Family Planning Association of Bangladesh (FPAB), Dinajpur, during March-June 2005 among 73 women who visited the clinic to remove their Norplant before its usual duration (5 years). The women were in the 25-31 years age-group--around two-thirds of them (57.5%) without formal education, and three-fourths of them (75.3%) were housewives. Most of them had been married for nine years, on average, and had two and/or more children. Sixty-seven percent of the women experienced regular menstruation, and 95% had used other contraceptive methods prior to using Norplant. Past users of Norplant were the single-most important source of information for about three-fourths of the women (74%); half of the women (51%) had discussed the method with their husbands, and majority (96%) of the husbands were informed about the women's decision on accepting the method before its implantation. All women were aware about the usual length of the effectiveness of Norplant. The most common reason for early removal of Norplant was menstrual disorder (59%), followed by desire for children (16%), husband's death, for abandonment or residing abroad (8%), anorexia, nausea, vomiting (7%), weight gain (4%), husband's objection (3%), and religious beliefs (3%). Service providers should properly counsel the couple before providing any contraceptive method, informing them about method-related side-effects and clearing any religious misconceptions. They should also explore the perception of women as well as their partners' desire for children; couples who would like to have a baby within a year or two can be encouraged to use a short-term method that can be more easily discontinued.

The objective of the study was to evaluate safety to infants whose mothers used Norplant levonorgestrel implants during breastfeeding. A nonrandomized clinical trial design was used. Participants were 220 and 222 healthy breastfed infants of mothers initiating use of Norplant or T-Cu IUD, respectively, at 55 days to 60 days postpartum. Infants were followed from birth through age 6 years. Breastfeeding pattern, infant growth, and disease events were recorded monthly in the first year, three-monthly in the second, and annually thereafter. Most mothers continued use of Norplant (96.4%) and T-Cu (94.1%) during lactation, and 2140 months of infant exposure to levonorgestrel were accumulated. Breastfeeding pattern and infants growth, from admission through age 6 years, were similar in both groups. In the first year, breastfed infants in the Norplant group had higher incidence rates (p < 0.05) of mild episodes of respiratory infections (adjusted RR 1.17, CI 1.08-1.27), skin conditions (adjusted RR 1.46, CI 1.20-1.79), and eye infections (unadjusted RR 1.49, CI 1.03-2.18) than the control group. Later on, a higher proportion of infants in the T-Cu group showed neurological conditions. Although breastfeeding patterns and infant growth is not affected by Norplant use during lactation, the effect on infants' health of steroidal contraception should be further evaluated.

BACKGROUND

Extending contraceptive implant duration of use increases accessibility by maximizing the lifetime of devices.

OBJECTIVE

To review the contraceptive efficacy during extended use of progestin implants.

METHODS

PubMed and EMBASE were searched for articles in any language, 1996-2017, utilizing terms for devices and contraceptive efficacy.

METHODS

Randomized clinical trials (RCTs), cohort studies, and case-control studies were included; abstracts, posters, and presentations were excluded. Studies evaluating Norplant and implants currently in pre-marketing trials were excluded.

METHODS

Titles and abstracts of articles were reviewed; those that met inclusion and exclusion criteria underwent full text review and data abstraction.

RESULTS

The search identified 2951 articles; six met inclusion and exclusion criteria. Five studies evaluated the etonogestrel implant (Implanon), and one the levonorgestrel implant (Jadelle). One RCT randomized to method, not duration; the remaining studies were prospective cohort studies. Three studies analyzed efficacy among women beyond currently approved duration separately. All studies were of poor to fair quality by United States Preventative Services Task Force (USPTF) grading. Limitations include lack of generalizability and control of important confounders.

CONCLUSIONS

These studies provide limited data for extended duration of contraceptive implants.

Available contraceptive implants appeal to women of diverse cultural and socioeconomic background because they offer long-term contraception, safety, effectiveness, reversibility and lack of estrogenic side-effects. Experience with Norplant I indicates that despite some side-effects the continuation rate is the highest for any reversible method of contraception. Disruption of the menstrual cycle is the main reason for discontinuation, hence research effort needs to focus on the mechanism of progestogen-induced endometrial bleeding and appropriate therapy. Implant service programs should have trained and skilled personnel who can provide adequate counseling that complements any public education effort and also provides effective services. Because contraceptive implants offer no protection against sexually transmitted infections, those who engage in high-risk sexual behavior should be encouraged to use condoms as well.

The objectives of this study were to evaluate the endometrial histology and cervical cytology of users of two contraceptive implants releasing etonogestrel/3-keto-desogestrel (Implanon) and levonorgestrel (Norplant) in West Midlands (UK) users. A 2-year prospective randomized design was used to study 60 implant users. Endometrial histology and cervical cytology were compared before insertion and after 12 and 24 months. At the end of 12 months, the majority of samples were inactive/weakly proliferative in both groups. At the end of 24 months, this remained unchanged in the Implanon group whereas the pattern was more diverse in the Norplant group. Endometrial thickness was significantly reduced in both groups during treatment. Cervical cytology remained unchanged. It is concluded that, after 2 years, there was no evidence of an increasing risk of endometrial hyperplasia, endometrial carcinoma, cervical intra-epithelial neoplasia or cervical carcinoma in either of the two groups of implant users.

This paper reports on a study in which the performances of physicians were compared to those of nonphysician health personnel in inserting and removing NORPLANT subdermal contraceptive implants. The study was conducted in Raden Saleh Clinic at the University of Indonesia, Jakarta, from September 1982 to August 1984. In a group of 828 women who accepted NORPLANT 285 insertions were performed by physicians and 543 by nonphysician health personnel. During the study period, 122 removals were performed (43 by physicians and 79 by nonphysicians). This small proportion of removals reflects the high continuation rate for NORPLANT. There was no significant difference between the two groups of acceptors regarding age, parity, education, or side effects. The average insertion times were 7.6 minutes for the physician group and 7.4 minutes for the nonphysician group (p greater than 0.1). The average removal times were 21.7 minutes for physicians and 21.8 minutes for nonphysicians (p greater than 0.9). Complications during and following insertion and removal were minimal for both groups, and no significant differences were found. It was concluded that nonphysician health personnel are qualified to administer the NORPLANT contraceptive implants.

A final evaluation of this longitudinal study involving 100 Singaporean women shows that, besides a significantly elevated bilirubin level, there is no other evidence of hepatocellular dysfunction with the use of Norplant implants. The elevated bilirubin levels remained significantly elevated six months after removal of the implant. Despite this, all values of bilirubin remained within the clinical range for the population studies. As regards lipid metabolism, total cholesterol, LDL-cholesterol and total triglycerides continued to remain below the pre-insertion mean at six months post-removal. The HDL-cholesterol showed a significant increase following removal of the implants. As a result, the HDL-cholesterol/(total cholesterol-HDL-cholesterol) ratio continued to remain above 0.200. This indicates that Norplant implants are not directly contributory to cardiovascular risk.

BACKGROUND

To evaluate the effects of Norplant (36 mg of levonorgestrel, six capsules) on serum cholesterol, triglycerides, alanine transaminase (ALT) and aspartate transminase (AST), we enrolled 465 healthy women from Zahedan, Iran, into a longitudinal study.

METHODS

Blood samples were collected after an overnight fast before implant insertion and after 3, 6, 9 and 12 months of use.

RESULTS

Total cholesterol and triglyceride levels did not significantly change during Norplant use. Although there were statistically significant increases in ALT and AST levels during Norplant use, the values were within the reference range.

The clinical evaluation of drugs used in fertility regulation is initially assessed in Phase I, II and III trials. The design of each phase and the investigative staff must be adequate. In Phase I, normal, healthy human volunteers meeting specific guidelines are usually studied. Numbers vary between 20 and 80 and the purpose is to determine the acute toxicity of the compound. In Phase II, efficacy and safety are examined in a clinical target population, and emphasis may be placed on pharmacological and mechanistic studies. Usually between 50 and 200 patients are involved. In Phase III, large-scale clinical studies for local registration and the introduction of drugs to various countries are included. This paper describes the evaluation of various drugs used in contraception, including NORPLANT implants, and considers the efficiency, safety and acceptability of such drugs. Phase IV studies are usually needed to reveal chronic toxicities or rare events.

A case of neuropathy in the medial antebrachial cutaneous nerve of the forearm following a Norplant(R) removal is described. The incidence of this problem is uncertain. The suggested sitting of the contraceptive implants directly over the bicipital groove is questioned.

The results of Norplant subdermal implants in 10,718 women receiving Norplant-6 and 1,208 women accepted Norplant-2 were analyzed. Up to May 31, 1988, the 3-year cumulative pregnancy rate was 0.2 per 100 acceptor for Norplant-6 and 0.1 per 100 acceptor for Norplant-2 and the continuation rate was 78.6 and 73.1 per 100 acceptor respectively. Menstrual disturbance constituted the majority (70%) of terminations. Cumulative termination rate for medical reasons was only 4.2 and 6.3 per 100 acceptor for Norplant-6 and Norplant-2 respectively. It is concluded preliminarily that the Norplant subdermal implantable contraceptive system is a safe and acceptable to the Chinese women.

Time-release pellets of levonorgestrel (LNG), the progestogenic hormone contained in the contraceptive system Norplant, were implanted subdermally in mice, after the animals had mated and ovulated but before uterine implantation of embryos would have occurred, to examine whether the hormone could reduce the number of embryos that subsequently implanted and, if so, when it had to be administered in the postcoital period to achieve that effect. Hybrid female mice (C57BL x CBA) were paired with breeder males (CD-1) and LNG pellets were implanted on day 0, the day on which copulation plugs were found, or on day 2 or day 3 in the postcoital period. Mice in some groups were sacrificed on day 14 of the gestation period, and numbers of fetuses and/or resorption sites were counted, while mice in other groups were allowed to go to term. When LNG pellets were implanted subdermally on day 0 of the postcoital period, pellets designed to release 1.5 mg of hormone in 21 days failed to exhibit a contraceptive effect, but pellets designed to release 5 mg of hormone in 90 days were totally effective in preventing uterine implantation of embryos. Although the 5 mg pellets did not prevent embryos from implanting in all cases when administered on day 2, they prevented pregnancies from going to term by causing resorption of those embryos that did implant. When the pellets were implanted as late as day 3 in the postcoital period, uterine implantation of embryos occurred and fetuses were carried to term. Results of the study indicate that subdermal implants of LNG inserted postcoitally can prevent uterine implantation of embryos in mice, and thereby prevent pregnancy, despite fertilization of oocytes having occurred, if the hormone implants are inserted before day 3 of the postcoital period.

This study on birth control methods used, and HIV infection protection of the HIV infected pregnant women in the obstetrics-gynecology department of Chonburi Hospital from 1 January 1990 to 31 December 1993 revealed that there were 27 HIV infected women with less than 24 weeks gestational age, using birth control methods as such 12 women (44.44%) had tubal resection after abortion, 8 women (29.62%) oral contraceptive pills, 5 women (15.51%) injectable contraception, and 2 women (7.40%) norplants. The 106 HIV infected women with more than 24 weeks gestational age were allowed to deliver. The birth control methods were as follows: 19 women (17.92%) tubal resection, 38 women (35.84%) oral contraceptive pills, 49 women (46.22%) injectable contraception. They were all encouraged to use a condom while having sexual intercourse. Only 40 women of this group are still seen in the follow-up clinic and all are found to be healthy, the birth control is effective and HIV infection is in the early stage. The new born babies were not allowed to be breast fed and were followed-up periodically to 18 months old. Twenty five babies received HIV blood test; 7 babies (28%) were found to be HIV infected. The birth control and HIV infection protection used in this study demonstrate no adverse effects on the disease, and the unexpected problems of these women, as well as the health personnel concerned are reduced both economically and socially. This study provides the guidelines of good care for HIV infected pregnant women.

This Memorandum reviews the results of research undertaken in animals and human subjects on the implantable contraceptive, Norplant, and where relevant, its components, levonorgestrel and Silastic. Results from clinical trials, including effectiveness and side-effects, are evaluated and service delivery aspects commented on. The Memorandum concludes with a statement regarding the use of Norplant as an option for long-term reversible contraception.

High maternal mortality rates coupled with poor socioeconomic conditions in developing countries indicate the need for those truly dedicated to improvement of maternal well-being to investigate advances in methods of pregnancy regulation and to implement those found to be effective and acceptable. In a trial involving 100 patients at Tygerberg Hospital that commenced in December 1993, Norplant was found to be highly acceptable and easy to use. It is strongly recommended that the acceptability of Norplant to the general South African population be evaluated further and then, hopefully, made available to all our people without undue delay.