Patrick J. Rowe

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.

Assisted reproductive technology in developing countries: why should we care?

Although the provision of expensive ART services in resource-poor countries might appear to be incongruous, nevertheless, the number of ART clinics in such settings is on the rise. For example, in Latin America, the first baby conceived after IVF was born in 1984; by 1998, 84 centers were submitting data to the Latin American Registry (1). Similarly, in Egypt, where IVF was introduced in the late 1980s, at least 35 clinics currently provide a range of ART services (2). Since 1981, private clinics in India have offered ART procedures including IVF and intracytoplasmic sperm injection (ICSI), and 60 clinics have been registered by the Ministry of Health (3). China has also experienced a growth in infertility services since the early 1990s (4).

Clinical patterns and major causes of infertility in Mongolia.

Objective:  To determine the clinical patterns and major causes of infertility in Mongolia, based on the clinical and laboratory findings of both partners, and to compare the findings with data from the published World Health Organization (WHO) multicenter study.

Comparative multicentre trial of three IUDs inserted immediately following delivery of the placenta

A multinational comparative trial of three IUDs (Copper 7, Lippes loop size D and the Postpartum T) randomly inserted immediately following delivery of the placenta was conducted in six centres. A total of 841 women entered the study. As the predetermined termination indices for expulsions were exceeded at six months the trial was prematurely closed. An excess of expulsions during the first 48 hours following insertion was observed for the Lippes loop compared to the other devices. At six months the expulsion rate for the Lippes loop was significantly higher than that for the Copper 7. In addition, the discontinuation rate for the Lippes loop at 12 months was significantly higher than that for the Copper 7. There were no significant differences in either the expulsion rates or the discontinuation rate at six or twelve months between the postpartum T and the other devices. At 12 months the pregnancy rates with all three devices was high; there were no ectopic pregnancies. Considerable between-centre differences were observed, particularly for expulsion rates. Possible reasons for this are discussed and future research lines are suggested.

Precision intrauterine contraception may significantly increase continuation of use: a review of long-term clinical experience with frameless copper-releasing intrauterine contraception devices

Objective The purpose of this paper is to review the experience with the frameless, anchored, GyneFix copper-releasing intrauterine contraceptive devices (IUCDs/IUDs) (Contrel Europe, Belgium), and to demonstrate their high acceptability and low rate of discontinuation of use, which could contribute to current efforts that aim to reduce radically the high number of unintended pregnancies and induced abortions, particularly in young women. Materials and methods This paper is based on studies that examined the differences in uterine volume and cavity size, related to age and parity, and on original clinical research data and practical experience with frameless copper IUDs, as well as on literature data on the IUD–endometrial cavity relationship of conventional IUDs, with special reference to side effects and user discontinuation. Results The mean transverse diameter in nulliparous and parous women is significantly less than the length of the transverse arm of the TCu380A IUD (ParaGard, Duramed, NY, USA) or the levonorgestrel intrauterine system (Mirena, Bayer, Germany). Small, frameless, flexible, and unidimensional copper IUDs appear to be well tolerated, with less impact on menstrual bleeding, resulting in low discontinuation rates when compared with standard-size conventional IUDs, which often result in increased expulsion rates, complaints of pain and erratic or increased menstrual bleeding, and subsequent high rates of discontinuation, particularly in young women. Conclusion The unidimensional GyneFix IUDs fit the majority of uterine cavities. An IUD that fits is likely to result in increased tolerance and continued use of the method. As this would appeal to women, the logical result should be greater use of the method and fewer unintended pregnancies and induced abortions. Recommending the standard TCu380A (ParaGard) IUD or the Mirena levonorgestrel intrauterine system, primarily developed for use in parous women, for general use in nulliparous and adolescent women should be done with caution in the light of current scientific evidence, except if 3-D sonography indicates that the uterine cavity is sufficiently large.

Consequences of uterine blood loss caused by various intrauterine contraceptive devices in South American women

Increased menstrual blood loss (MBL) associated with intrauterine device (IUD) use may precipitate or aggravate iron deficiency anaemia, adversely affecting the health of women particularly those from developing countries. Studies were conducted to define the association of MBL and iron status in South American women; to determine the level of MBL induced by IUD use which would result in iron depletion, the length of time for this depletion to occur and, comparing various IUDS, to determine if any currently tested IUDs are suited to long-term use in South American women. A total of 395 women received one of 5 types of IUDs in Santiago, Chile, and Juiz de Fora, Brazil: Lippes Loop, Multiload-250 and Multiload-375 were used in both centres; in Santiago some subjects received the Copper-7 or ProgestasertR devices and in Juiz de Fora, the TCu 200 and the T-Chloroquin IUDs were also tested. MBL and haemoglobin (HGB) were measured for 3 menstrual cycles before insertion, and following insertion, at one, two, four, six, nine, twelve, eighteen and twenty-four months in the majority of cases. Serum ferritin was measured before insertion and at intervals of six months. Mean values of MBL prior to IUD insertion in both centres varied from 21-30 ml. As with previous publications, the use of the Lippes Loop was associated with the greatest increase in MBL which was sustained throughout the 24 months of observation. Women who had one of the two types of Multiload devices inserted also had increased MBL and reduced ferritin for at least 12 months of use. TCu 200 and Copper-7 IUD users had an initial increase in MBL of 1 to 17 ml in the first six months of observation returning to normal levels beyond six months. Serum ferritin levels were lower for one year and then returned to admission values. ProgestasertR users confirmed previous reports of a reduction of 40-50% in MBL and an increase in serum ferritin. Few significant changes in haemoglobin (HGB) concentrations were found. Serum ferritin levels on admission ranged from 7.1 to 16.4 ng/ml in Santiago and from 15.8 to 23.2 ng/ml in Juiz de Fora. Many women were in a marginal state of iron balance as evidenced by lower serum ferritin values. Changes in serum ferritin were very closely related to those in MBL.(ABSTRACT TRUNCATED AT 400 WORDS)

The frameless copper IUD (GyneFix) and the TCu380A IUD: results of an 8-year multicenter randomized comparative trial.

BACKGROUND Clinical performance of the frameless copper IUD (GyneFix), designed to reduce side effects related to the frame of conventional IUDs, and TCu380A was compared. STUDY DESIGN Randomized Multicenter randomized comparative trial. Parous women requesting and eligible to use IUD were admitted in 21 centers in eight countries in 1989-1993 and followed-up for up to 8 years. RESULTS Two thousand twenty-seven women were randomized to the frameless IUD and 2036 to TCu380A; 43 insertions of the frameless IUD failed and none for TCu380A. First-year expulsion rate of the frameless IUD was 5.3 (95% CI: 4.4-6.4) per 100 and 2.5 (95% CI: 1.9-3.3) for the TCu380A; second- through eighth-year expulsion rates were not different. First-year pregnancy rates for the frameless IUD and TCu380A were 1.3 (95% CI: 0.9-2.0) and 0.5 (95% CI: 0.3-0.9), respectively; second- through eighth-year cumulative pregnancy rates were 1.2 (95% CI: 0.7-1.9) and 2.5 (95% CI: 1.8-3.4), respectively. The 8-year cumulative rates of ectopic pregnancy and IUD removal for pain were lower for the frameless IUD than for TCu380A. Removals for other reasons were not different. CONCLUSIONS The frameless IUD had more insertion failures, expulsions and pregnancies in the first year than TCu380A, but fewer pregnancies from the second through the eighth year, and by 8 years had fewer ectopic pregnancies and removals for pain.

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.

Repeated vaginal administration of 15-methyl PGF2α methyl ester for termination of pregnancy in the 13th–20th week of gestation

Abstract In a comparative multicentre trial, vaginal suppositories containing 1.5 mg 15-methyl prostaglandin F 2α methyl ester were administered at 3-hour intervals to 310 patients. Abortion of the fetus occurred within 24 hours in 274 patients (88.4%) and within 30 hours in 285 patients (91.9%). The mean induction-abortion interval was 14.2 hours. Abortion was complete in 49.9 per cent of the cases. The most common side effects were vomiting and diarrhoea. The mean frequency of vomiting and diarrhoea was 2.8 episodes per patient for both types of side effects, while temperature elevation above 38 °C occurred in 11.7 per cent of the cases. Repeated vaginal administration of 15-methyl PGF 2α methyl ester is an effective, noninvasive method for termination of second trimester pregnancy. Further development of suppositories should achieve a longer action combined with a decrease in gastrointestinal side effects.

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.