Should the recommended number of IUD revisits be reduced?

This study uses data from clinical trials of intrauterine devices to examine the effect of reducing the recommended number of IUD follow-up visits. Over 11,000 follow-up forms were analyzed to estimate the number of health problems that would have escaped detection if women with no or mild symptoms had not made recommended revisits. Less than one percent of woman-visits with no or only mild symptoms had an underlying health risk that could have gone undetected if the follow-up visits that were made in the clinic trial setting had not been made. The results from this analysis suggest that a reduction in the number of recommended follow-up visits is safe, when measured according to selected conditions. Additional research is necessary to determine whether any revisits should be recommended in the absence of signs or symptoms.

PIP: International Program in Population and Family Planning, Pathfinder International, and other organizations providing support to family planning organizations in developing countries, generally recommend that women who use intrauterine devices (IUDs) go for an initial revisit at four to six weeks postinsertion, a second revisit at one year, and subsequent revisits at yearly intervals. However, ministries of health and family planning organizations in developing countries generally recommend more frequent revisits. This study examined the effect of reducing the recommended number of IUD follow-up visits using data from clinical trials of the TCu380A and other widely used IUDs conducted by Family Health International (FHI) during 1986-89. The clinical studies were conducted in 13 clinics in 9 countries (Cameroon, Egypt, El Salvador, Mexico, Pakistan, Peru, Philippines, Sri Lanka, and Venezuela) among sexually active and healthy women aged 18-40. Over 11,000 follow-up forms were analyzed to estimate the number of health problems that would escape detection if women with no or mild symptoms had not made recommended visits. Less than 1% of woman-visits with no or only mild symptoms had an underlying health risk that could have gone undetected if the follow-up visits that were made in the clinic trial setting had not been made. Results suggest that a reduction in the number of recommended follow-up visits is safe, when measured according to selected conditions. Clinic policy and practice in family planning probably could move toward encouraging fewer recommended follow-up visits, while simultaneously encouraging those who feel they need assistance to seek medical attention. Additional research is, however, needed to determine whether any revisits should be recommended in the absence of sign and symptoms.

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.

PIP: From February 1985 to February 1986, researchers enrolled 600 18-40 year old women at the Dhaka Medical College and Hospital, the Institute of Postgraduate Medicine and Research, and the Mohammadpur Fertility Services and Training Centre in a 5-year clinical trial to evaluate the contraceptive efficacy, safety, and acceptability of Norplant subdermal implants in Bangladesh. They scheduled the women to return for follow-up visits 1, 3, and 6 months after insertion and every 6 months thereafter until removal or at the end of 5 years. No pregnancies after insertion occurred during the study. The gross cumulative continuation rate was 93.9% at 1 year and 72.3% at 2 years. The 5-year cumulative continuation rate was 41.2% which was much lower than that in other Asian countries (e.g., 52.3% in Sri Lanka and 78.2% in Indonesia). The 5-year cumulative discontinuation rate for menstrual problems was 30.7% which was higher than that of other studies. It may have been higher because Bangladeshi women do not tolerate well and accept changes in bleeding patterns, especially since menstrual bleeding prevents them from prayer and taking part in sexual activity. 45.3% of all women requesting early Norplant removal complained of menstrual problems, especially prolonged heavy bleeding (75% of women requesting removal for menstrual problems). Most menstrual problem removals took place during the 2nd year and fell thereafter. Desired pregnancy was the second most common reason for removal (18.6%). The gross discontinuation rate for nonmenstrual side effects was just 2.2%, the main side effect being headaches. 97.5% of women who completed the 5-year study considered their experience with Norplant favorable. The leading reason for a favorable rating for Norplant was its duration of use (64.5%). Menstrual changes comprised the least favorable component of Norplant among women who completed the study (63.3%). 33% of women still wanting to use contraception after 5 years of Norplant use said they would use Norplant again.

Distribution of initial and persistent 2-acetylaminofluorene-induced DNA adducts within DNA loops.

The intranuclear distribution of initial and persistent DNA adducts induced in vivo after four weekly injections of the hepatocarcinogen 2-acetylaminofluorene was examined in rat liver by using a protocol that fractionates chromatin from various regions of each of the multiple nuclear DNA loops. Ten hours after the initial dose, two acetylated [(N-acetyl-N-(deoxyguanosin-8-yl)-2-aminofluorene and 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene] and one deacetylated [N-(deoxyguanosin-8-yl)-2-aminofluorene] adduct were detected by a 32P-labeling assay and were found to have a random genomic distribution, as evident by their relative concentrations in various chromatin fractions. These data suggest that all regions of the DNA loops are equally susceptible to adduct formation. A nonrandom persistence of the deacetylated adduct in the regions where the DNA loops are constrained by the nuclear matrix was evident by 6 days after the last dose and was markedly apparent by 60 days. In contrast, all chromatin fractions had equally inefficient removal of the N2-acetylated adduct by 6 days as well as 60 days but had complete removal of the C8-acetylated adduct. These findings suggest that pronounced regional differences in adduct repair along the DNA loops may play a role in chemically induced hepatocarcinogenesis.

Formation and removal of DNA adducts in rat liver treated with N-hydroxy derivatives of 2-acetylaminofluorene, 4-acetylaminobiphenyl, and 2-acetylaminophenanthrene.

Formation and removal of hepatic DNA adducts was studied in male Sprague-Dawley rats following single injections of two hepatocarcinogens, N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and a nonhepatocarcinogen, N-hydroxy-2-acetylaminophenanthrene (N-OH-AAP) at 0.5 h, 1.5 h, 4 h, 24 h, 9 d and 29 d. Using a previously described 32P-postlabeling assay, maximal DNA binding of these compounds was observed at approximately 1.5 h, 0.5 h and 24 h, respectively. In addition to the formation of three already known C8- and N2-acetylated and C8-deacetylated guanine derivatives and several minor unknown adducts with N-OH-AAF, a set of four new major adducts was also detected. These comprised approximately 50% of the total adducts during the first 4 h. The three known adducts amounted to 58, 16 and 6% of the 1.5-h value after 24 h, 9 d and 29 d, respectively, while the bulk (greater than 84%) of the new major adducts were removed from the DNA within 24 h and found only in traces after 9 d. N-OH-AABP formed several unknown minor adducts, in addition to the one major C8-deacetylated and two minor C8- and N2-acetylated guanine derivatives; only the C8-deacetylated and N2-acetylated adducts were detected after 29 d. In the case of N-OH-AAP, two major and several minor adducts were detected, most of which were found to be deacetylated, and as much as 60% of the adducts measured at 24 h were still present after 9 d treatment. These data indicate that certain DNA adducts are repaired rapidly, while others persist for long periods.