A. Andrade

Microdose intravaginal levonorgestrel contraception: A multicentre clinical trial

A multicentre clinical trial, including 19 centres in 13 countries, assessed the contraceptive efficacy and clinical acceptability of a Silastic 382 vaginal ring releasing 20 micrograms of levonorgestrel for at least 90 days. A total of 1005 women entered the study and 8176.74 woman-months of experience was gathered. The rate of intrauterine pregnancy at one year of use was 3.6 per 100 women (95% confidence interval 2.2-5.0), and of ectopic pregnancy, 0.2% (one case). The principal reasons for discontinuation were menstrual disturbances (17.2% at one year), vaginal symptoms (6.0%) and repeated expulsion of the ring (7.1%). The pregnancy rate with this 20 micrograms levonorgestrel-releasing vaginal ring compares favourably with that of a low estrogen combination oral contraceptive tested by WHO and is less than half that of a progestogen-only oral contraceptive in a WHO randomized study. It is concluded that the WHO intravaginal ring releasing an average of 20 micrograms of levonorgestrel per 24 hours is an effective method of contraception for at least one year of use.

Microdose intravaginal levonorgestrel contraception: A multicentre clinical trial: II. Expulsions and removals

This paper investigates the relationship between expulsions and removals, and demographic characteristics of 1005 women from 19 centres using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. Emphasis is placed on discontinuations of method use due to expulsions, on the number and rate of expulsions, and the time at which the first expulsion occurred. The overall life-table discontinuation rate due to expulsion was 7.1% at one year. Life-table discontinuation rates increased with parity and were highest in Asian and lowest in European women. In respect to the number of expulsions experienced by women (expulsions did not necessarily lead to discontinuation), the women of high parity and those from Asia and Europe have the highest rates. The life-table first expulsion rate is 29% at one year. Such rates are highest in Chinese and Asian women. Following a first expulsion, the second expulsion rate is 45% by the end of the subsequent six months. The majority of first expulsions occur at defaecation (134 or 57% of 234 women), urination (12%) and during menstruation (17%). Rings were removed by 121 (12%) women on 201 occasions and for a variety of reasons. The main medical reasons were vaginal discharge and irritation, bleeding pain and dyspareunia. Others removed the ring during defaecation, intercourse or because the ring came out of place. Women also removed rings for curiosity, to show their husbands and to clean.

The ‘frameless’ intrauterine system for long‐term, reversible contraception: A review of 15 years of clinical experience

Aim:  The development of the ‘frameless’ intrauterine system (IUS) is a response to the growing need to develop high‐performing, long‐acting, reversible, and acceptable contraceptives with a high continuation of use.

Microdose intravaginal levonorgestrel contraception: A multicentre clinical trial: III. The relationship between pregnancy rate and body weight

This paper investigates the relationship between pregnancy rates and body weight of 1005 women using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. While the overall pregnancy rate at one year was 3.7%, it was found that women have an increasing risk of pregnancy with increasing body weight. For example, a woman of 40 kg has an estimated pregnancy rate of 1.7% in contrast to 9.8% for a woman of 80 kg weight.

Microdose intravaginal levonorgestrel contraception: A multicentre clinical trial: IV. Bleeding patterns

A multicentred clinical trial was conducted in 12 countries to assess the contraceptive efficacy and side effects of a low-dose levonorgestrel-releasing vaginal ring. Contraceptive efficacy and side effects, expulsions and removals, and the relation between pregnancy rate and admission body weight of the women have been reported previously. The effect of ring use on vaginal bleeding patterns as observed from daily menstrual diaries kept by the women is the object of this paper. A total of 1005 women were fitted with the ring and 702 of them provided a menstrual diary suitable for analysis. The description of the bleeding patterns is made using a 90-day reference period approach and following the guidelines published by WHO. In addition the longest bleeding/spotting episode and longest bleeding/spotting-free interval are calculated over the entire diary length. Half of the ring users have vaginal bleeding patterns similar to normal untreated patterns. A quarter experience irregular bleeding, 10% have prolonged cycles and 10% have shortened cycles. Over one year of continuous use, there appears to be no significant trend in these patterns. Users with the worst bleeding patterns tend to discontinue first during the clinical trial and are influenced by their more recent experience of vaginal bleeding irregularities. Life-table analysis of discontinuation rates gives an underestimation of the true incidence of bleeding irregularities. Some comments are made on the limitations of the methods of analysis of menstrual diaries.

IUD expulsion solved with implant technology

In an attempt to minimize the problem of IUD expulsion, implantation technology has been developed and tested. The trials have extended from 1985 until the present time for interval as well as for immediate postabortal and post-placental insertion and fixation of the CuFix IUD (Gyne-Fix). The present article reports on an ongoing study with GyneFix interval insertion, with an improved inserter, in 820 women, observed up to 3 years, of whom 213 (25.9%) are nulligravid/nulliparous. The cumulative expulsion rate is 0.6 per 100 women-years at 3 years and is not significantly higher in the nulligravid/nulliparous group. The cumulative pregnancy rate is 0.6 and the cumulative removal rate for medical reasons 3.2 at 3 years. The total experience in this multicenter study covers approximately 14,000 woman-months. It is concluded that the design characteristics of the GyneFix (fixed, frameless, and flexible) explain the low expulsion, high efficacy and high acceptability rates. The implantation technology is very effective and the improved inserter allows easy insertion and optimal anchoring.

The Femilis LNG-IUS: contraceptive performance-an interim analysis.

Objective To provide an update on the experience with the Femilis® levonorgestrel-releasing intrauterine system (LNG-IUS) used for up to five years by parous and nulliparous women, particularly with regard to its contraceptive performance. Study design An interim, open, prospective non-comparative study of the Femilis® LNG-IUS releasing 20 μg of levonorgestrel/day. Results Two-hundred and eighty insertions were carried out in women with a mean age of 35.7 years (range 17–48), 60% of whom were parous and 40% nulliparous. Twenty-four women with uterine pathology (e.g., fibroids, menorrhagia) were included in the study. The cumulative gross discontinuation life table rates were determined. The total observation period was 8,028 woman-months. The LNG-IUS was easy to insert in 95.7% of the cases, and no perforations occurred. No pregnancies were observed and only one expulsion took place (rate 0.4/100 women at five years). The cumulative total use-related discontinuation rate was 14.7/100 at five years. There were nine removals because of pain, six of which were in nulliparous women. Four women requested removal of the IUS for bleeding problems. Fourteen removals were done for ‘other’ medical reasons among which mood disturbances (five cases) were the most frequent, and 12 for non-medical reasons. Fifteen removals were requested for pregnancy wish. Twelve of these women became pregnant within one year and all had uneventful pregnancies. The Femilis® LNG-IUS was equally well accepted by nulliparous as by parous women. Most women with heavy menstrual bleeding prior to insertion, whether associated with fibroids or not, reported much less bleeding, scanty bleeding or even no bleeding at all after insertion. Conclusion This study suggests that the Femilis® LNG-IUS, which releases 20 μg LNG/d, is a highly effective, well tolerated and well retained contraceptive both in parous and nulliparous women. The shorter crossarm of the LNG-IUS has simplified its insertion technique, which may contribute to its safety. This could promote use by non specialist providers and enhance the application of the method.

Review of clinical experience with the frameless LNG-IUS for contraception and treatment of heavy menstrual bleeding.

Objective. Review the clinical experience with the frameless FibroPlant® levonorgestrel intrauterine system (FP-LNG-IUS). Study design. An open, prospective non-comparative contraceptive 5-year study; a 1-year MBL study in women with heavy menstrual bleeding (HMB), using a PBAC and a 2-year MBL study in women with HMB and with normal menstruation using the quantitative alkaline hematin method. A literature review on perforation rate with the frameless GyneFix® and FibroPlant®. Results. 304 insertions were performed with the FP-LNG-IUS. The total observation period was 11,299 woman-months. Only one pregnancy occurred. There were two expulsions and two uterine perforations at insertion during the first year. In the first 1-year MBL study, the median MBL decreased by more than 90%. In the second 2-year MBL study, MBL reduced drastically and 80% had amenorrhoea after 24 months. The ferritin values increased significantly. On a total of approximately 17,000 insertions, the perforation rate was between 1.2 and 2.0/1000 insertions. Conclusion. The frameless FP-LNG-IUS is an effective and well-tolerated long-acting reversible contraceptive and is also highly effective for the treatment of HMB. The perforation rate is similar to traditional copper and levonorgestrel-releasing intrauterine devices and systems. Strict adherence to the manufacturers insertion instructions is recommended.