Treatment continuation and satisfaction in women using combined oral contraception with nomegestrol acetate and oestradiol: a multicentre, prospective cohort study (BOLERO).

OBJECTIVE: The aim of the study was to examine treatment continuation and satisfaction over 1 year among women receiving nomegestrol acetate (NOMAC)/oestradiol (E2) combined oral contraception (COC) in real-world clinical practice. METHODS: The 17ß-Estradiol and Nomegestrol Acetate (BOLERO) Study is an observational, non-interventional, prospective, multicentre cohort study of premenopausal women (aged 18-50 years) who received prescription NOMAC/E2 (2.5 mg/1.5 mg) for contraception during routine clinical practice. Assessments were carried out at enrolment and at 3, 6 and 12 months. Probability of treatment continuation through 12 months (primary outcome) was examined using Kaplan-Meier survival analysis. Secondary outcomes included treatment satisfaction, menstrual cycle-related symptoms, libido and adverse events (AEs). RESULTS: Of 298 enrolled women, 292 were evaluable. The probability of NOMAC/E2 continuation through 12 months was 73.7% (95% confidence interval [CI] 68.0%, 78.5%). Satisfaction with NOMAC/E2 increased from 56.9% (37/65) of women at initial evaluation to 89.2% (58/65) of women at 12 months. Physician ratings at 12 months showed satisfactory to very satisfactory in 84.0% (168/200) of women. Libido was not affected. Menstrual cycle-related symptoms significantly declined from enrolment (6.04 ± 4.32) to 3 months (3.25 ± 3.05) and 12 months (2.62 ± 2.74; p < .0001). Treatment-related AEs were reported by 38.7% (113/292) of women. CONCLUSION: The real-world experience of women receiving NOMAC/E2 indicated very good treatment continuation, high satisfaction and significantly improved menstrual cycle-related symptoms.

Lack of an elevated risk of malignant melanoma in relation to oral contraceptive use.

Epidemiologic and laboratory data suggest an effect of oral contraceptives (OC) on the risk of malignant melanoma. This relationship was explored in a hospital-based case-control study of 160 women with malignant melanoma and 640 matched controls, all of whom were white and 20-59 years of age. A total of 63 cases (39%) had used OC compared with 270 controls (42%), yielding a relative risk estimate of 0.9 (95% confidence interval: 0.6-1.3). When a number of potential confounding factors were simultaneously controlled, the relative risk estimate was 0.8 (0.5-1.3). For use that lasted 5 or more years the estimate was 0.9 (0.5-1.6). The level of tumor invasion was not related to OC use. The evidence from this study suggests that OC, even when used for 5 or more years, do not increase the risk of malignant melanoma.

Six-month and 1-year continuation rates following postpartum insertion of implants and intrauterine devices.

OBJECTIVE: Studies show immediate postpartum (PP) insertion increases use of contraceptive implants and intrauterine devices (IUDs). Our objective was to compare the satisfaction and continuation rates of the two types of devices at 6 months and 1 year following PP insertion. STUDY DESIGN: We enrolled 133 women in a prospective cohort study following immediate PP insertion of an implant or IUD at two academic hospitals during 8 months of 2011. Subjects completed an enrollment survey during hospital admission and a follow-up phone survey 6 months and 1 year PP. RESULTS: At 6 months PP, 72% of subjects provided follow-up information. Implant users were more likely to be using the originally-placed device (40/41, 98% vs. 45/55, 82%, p=0.02); nine women reported IUD expulsions. When accounting for replacement of expelled IUDs, IUD continuation at 6 months was 89% yielding similar continuation rates between groups (p=0.12). At 1 year PP, 51% provided follow-up. Of those, 82% still had a LARC method in place with similar continuation by device type (84% for implants, 81% for IUDs, p=0.96). Overall, satisfaction was similarly high in both groups. CONCLUSION: Due to IUD expulsion, implants had a higher continuation rate than IUDs six months following immediate PP insertion. After replacement of expelled IUDs, continuation and satisfaction were similar for both devices at 6 months and 1 year. IMPLICATIONS: Placement of implants and IUDs immediately PP can lead to high satisfaction. Despite early IUD expulsions, continuation rates were similar to those placed outside of the immediate PP period.

Comparative study on the efficacy, acceptability, and side effects of a contraceptive pill administered by the oral and the vaginal route: an international multicenter clinical trial.

The objective of this multicenter randomized clinical trial was to compare the efficacy, acceptability, and occurrence of side effects associated with the oral versus vaginal route of administration of contraceptive pills. Eight hundred nineteen healthy, parous women of reproductive age were recruited at family planning clinics and research centers, members of the South to South Cooperation in Reproductive Health, in seven countries of the developing world. These women were randomly assigned to use either oral or vaginal administration of the same contraceptive pill, which contained 250 micrograms levonorgestrel and 50 micrograms ethinyl estradiol. No statistically significant differences were found in discontinuation rates between the two groups after 1 year. Involuntary pregnancy rates after 1 year were not statistically significantly different between the two groups. The vaginal route of administration appears to be as acceptable and efficacious as the oral route.

PIP: The objective of this multicenter randomized clinical trail was to compare the efficacy, acceptability, and occurrence of side effects associated with the oral versus vaginal route of administration of contraceptive pills. This study started in June, 1987, and data collection extended up to April, 1992, at family planning clinics and research centers, members of the South to South Cooperation in Reproductive Health, in seven countries of the developing world. The 819 subjects were from 17 to 39 years of age, had already had at least one pregnancy, had had regular menstrual cycles for 3 months before, were exposed to the risk of pregnancy, and were not using any other method of contraception. 424 were randomly assigned to use the pills orally (which contained 250 mcg levonorgestrel and 50 mcg ethinyl estradiol), whereas 395 inserted the pills vaginally. 625 subjects completed at least 6 months of use, 326 used the pills orally and 299 used the pills vaginally. 385 subjects completed 1 year of pills use, 201 in the oral group and 184 in the vaginal group. The 1-year discontinuation rate per 100 subjects per year for the oral group was 34.71 +or- 2.42, while it was 36.35 +or- 2.53 for the vaginal group. This difference was not statistically significant. The only single reason of statistically significant difference for discontinuation was "desire for pregnancy" (p = 0.444). Paired value analysis of subjects completing 12 months of study showed that women in the oral group had a statistically significant increase in weight, from a mean of 55.8 kg at admission to a mean of 56.9 kg at 6 months (p 0.05) and 57.3 kg at 1 year (p = 0.05). The mean weight of the vaginal group increased from 56.52 kg to 57.22 kg (p = 0.036) at 12 months. Significantly more complaints of vaginal discharge were recorded in women using the pills by the vaginal route (p = 0.001). However, only one subject discontinued the pills because of vaginal discharge.

Comparative study on the efficacy and acceptability of two contraceptive pills administered by the vaginal route: an international multicenter clinical trial.

The efficacy and acceptability of two widely used oral contraceptive tablets, one containing 250 mg levonorgestrel and 50 micrograms ethinyl estradiol and the other containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol, administered by the vaginal route were compared in 1055 women studied over 12,630 woman-months of vaginal contraceptive pill use. This multicenter clinical trial was performed in nine countries of the developing world by the "South to South Cooperation in Reproductive Health," an organization founded by scientists from the Third World working in the area of reproductive health, and the study was developed and coordinated by one of these centers. The findings of this study confirm the efficacy of both these tablets when administered by the vaginal route. Involuntary pregnancy rates at 1 year of 2.78 for subjects in the levonorgestrel group and 4.54 for subjects the desogestrel group showed no statistically significant difference between the two groups. However, total discontinuation rates of 47.01 for subjects in the levonorgestrel group and 56.33 for subjects in the desogestrel group showed a statistically significant difference between the two groups, and discontinuation rates attributable to prolonged bleeding of 0.6 for subjects in the levonorgestrel group and 3.2 for subjects in the desogestrel group were also significantly higher in the group of subjects using the desogestrel vaginal contraceptive pill. Blood pressure remained at admission values throughout treatment. A statistically significant weight increase from admission values occurred in both groups of subjects.

PIP: Efficacy and acceptability of 2 combined oral contraceptive pills administered vaginally are summarized. This is the 1st collaborative trial published by the South to South Cooperation in Reproductive Health. 1055 women participated in 12,630 cycles, in 9 countries, from June 1988 to May 1991. The pills were commercially available tablets containing 50 mcg ethinyl estradiol and 250 mg levonorgestrel (Schering AG, Sao Paulo, Brazil), or 30 mcg ethinyl estradiol and 15 mcg desogestrel (Organon, Sao Paulo, Brazil). Subjects were aged 17-39 younger and of lower parity from Mexico and Dominican Republic and older from Egypt and China. All had at least 1 pregnancy. 675 participated for 6 months, 470 for 1 year, 364 for 18 months, and 210 for 2 years. The 1-year discontinuation rate averaged 47.01% for the levonorgestrel group and 56.33% for the desogestrel group (p = 0.0061); 2-year discontinuation rates were 48.01% and 69.36, respectively, explained in part by higher involuntary pregnancy rates and prolonged bleeding rates in the desogestrel group. The most common medical reasons for stopping contraception were unplanned pregnancy, vaginal or vulval irritation, nausea, vaginal discharge and headache. Vaginal irritation was reported by 1%, 9 in each group. There were 32 pregnancies, 14 in the levonorgestrel and 18 in the desogestrel group. 17 were in missed pill cycles and the rest were method failures, 6 in the levonorgestrel group and 9 in the desogestrel group. The Pearl index varied from 0 in Nigeria to 12.24 in Mexico, and was 2.45 for levonorgestrel vs. 3.74 for desogestrel. There was a wide variation in discontinuation rates by center: Brazil and China had few, while many women from Dominican Republic, Mexico and Zambia left the study. Bleeding problems were common complaints, more so in the desogestrel group. There were 363 women with intermenstrual bleeding (only once in 80%), 148 with spotting (only twice in 65%). Bleeding duration was significantly less in pill cycles than baseline, pressure. Women gained an average of 1 kg over 2 years, more in the desogestrel group. The pregnancy rate of 2.78 is within the range reported for levonorgestrel rings.

Factors affecting riboflavin requirements of oral contraceptive users and nonusers.

Riboflavin depletion has been identified in women on oral contraceptives (OC) but change in riboflavin nutriture has not been consistently demonstrated in all OC user groups studied. Discrepant findings in reports have been attributed to differences of pill formulation or riboflavin intake. Aims of this study were to compare the riboflavin requirements of healthy OC users and nonusers on diets prepared in a metabolic unit. A single daily menu and meal pattern was used. The basic diet providing riboflavin at a level of 0.6 mg/1000 kcal was used in the period of acclimation and period 1. In periods 2 and 3, the riboflavin content of the diet was increased to 0.8 and 1.0 mg/1000 kcal, respectively. The riboflavin status of subjects was monitored by erythrocyte glutathione reductase assay and urinary riboflavin excretion. Eight women on OC and 10 nonusers participated. Erythrocyte glutathione reductase assay values and urinary riboflavin excretion showed intersubject and interperiod differences but no significant group differences (OC versus non-OC) in erythrocyte glutathione reductase values or in urinary riboflavin per g creatinine. It was concluded that when dietary intake is controlled, OC do not significantly influence riboflavin status. Riboflavin needs were related to energy requirements of the subjects.

Levonorgestrel contraceptive implants in female patients 14 to 21 years old.

OBJECTIVE: To determine which factors are associated with duration of use of a levonorgestrel implant (Norplant) for contraception in adolescents and young adults. DESIGN: We retrospectively studied 144 young women (14 to 21 years of age) who chose a levonorgestrel contraceptive implant at Mayo Clinic Rochester between April 1990 and December 1993. MATERIAL AND METHODS: The following information was obtained at the time of insertion of the implant and from any follow-up visits: demographics, prior contraceptive experiences, frequency and management of complications, complications noted at removal of the implant, and subsequent contraceptive choice. The duration of use was examined. RESULTS: Of the 144 young women who underwent insertion of a Norplant system, 75 telephoned or made a medical appointment because of implant-related side effects. During the follow-up period, 64 patients had the Norplant system removed. The Kaplan-Meier estimate of the probability of the Norplant system remaining in place for at least 12 months was 83 % and for at least 24 months was 63 %. Duration of Norplant use was not found to differ with respect to age, prior contraceptive use, or timing of insertion, but it was significantly shorter among those with a prior pregnancy than in those who had never been pregnant. CONCLUSION: These findings suggest that a group of young women who are likely to continue use of a contraceptive implant (with or without treatment for side effects) are those who have never been pregnant.

PIP: A retrospective study of 144 US women 14-21 years of age who requested and received the Norplant contraceptive implant system at the Mayo Clinic (Rochester, Minnesota) in 1990-93 analyzed the factors associated with duration of method use. Of the 124 women who reported past use of contraception, 94 (76%) had been pregnant at least once. The method most commonly used before Norplant was oral contraception (57%). The reasons for Norplant selection were its convenience (86%) and problems tolerating the pill (14%). Of the 130 Norplant users who either telephoned or made a clinic appointment after insertion, 60% reported side effects such as breakthrough bleeding, headache, and depression or mood swings. 64 women had the implants removed. The median duration of Norplant use was 29 months. The Kaplan-Meier estimate of the probability of the Norplant system remaining in place for at least 12 months was 83% and 63% for at least 24 months. Age, prior contraceptive use, and timing of insertion had no impact on duration of Norplant use. Multivariate analysis indicated that women with at least 1 prior pregnancy had a two-fold increased risk of Norplant removal compared to those who had never been pregnant. Larger studies are needed to identify additional factors associated with long-term use of injectable contraception among young women and to suggest interventions that would improve compliance with routine follow-up.

Oral contraceptive use and premenopausal breast cancer in Sweden and Norway: possible effects of different pattern of use.

Different use of oral contraceptives (OCs) in relation to reproductive histories and age might explain the conflicting results found in studies from different countries of OC use and premenopausal breast cancer. A population-based case-control study in Sweden and Norway has been analysed separately for the two countries. The study consists of 317 Swedish and 105 Norwegian cases diagnosed 1984-1985 with 317 Swedish and 210 Norwegian controls. The results for each country separately are consistent with the joint analysis showing increased risk for breast cancer with increased duration of OC use with the exception of that for women with more than 15 years since first use. The relative risk of breast cancer for more than four years of use among Norwegian women was 0.6 (95% confidence internal (Cl), 0.2-1.8). In both countries there was a non-significant higher risk associated with increasing duration of use before first full-term pregnancy. Analyses for surveillance bias show no evidence of bias as explanation for the association between total duration of OC use and breast cancer.

Tobacco use, alcohol consumption and infertility.

An epidemiological study of the association between alcohol consumption, tobacco use and subfecundity is presented. Study subjects were recruited for a case-control study whose primary objective was to examine the association between occupational exposures and subfecundity. All 1069 women treated for infertility at Odense University Hospital during the period 1977-1980 were eligible for participation as cases. A control group was chosen consisting of 4305 women who had each delivered a healthy child with a gestational age over 258 days at the same hospital in the period 1977-1979. Data regarding occupational exposures and smoking and drinking habits were collected by mailed questionnaires. A response rate of 87% was obtained for both case and control groups. Use of tobacco and alcohol was significantly higher in cases compared to controls. A within-group comparison of alcohol consumption among controls with delayed conception of more than one year with controls who conceived their children within one year failed to demonstrate a statistical association. However, a statistically significant association was observed between smoking and delayed conception among controls. On the basis of this finding, along with further analyses, the authors suggest that the statistical association between smoking and subfecundity may be real and ought to be studied further. Moderate alcohol consumption does not seem to play a role in the development of subfecundity. The paper provides a systematic review of possible sources of bias in the study.

PIP: An epidemiological study of the association between alcohol consumption, tobacco use, and subfecundity is presented. Study subjects were recruited for a case-control study whose primary objective was to examine the association between occupational exposures and subfecundity. All 1069 women treated for infertility at Odense University Hospital during 1977-80 were eligible for participation as cases. A control group was chosen consisting of 4305 women who had each delivered a healthy child with a gestational age over 258 days at the same hospital in the 1977-79 period. Data regarding occupational exposure and smoking and drinking habits were collected by mailed questionnaires. A response rate of 87% was obtained for both case and control groups. Use of tobacco and alcohol was significantly higher in cases compared to controls. A within-group comparison of alcohol consumption among controls with delayed conception of more than 1 year with controls who conceived their children within 1 year failed to demonstrate a statistical association. However, a statistically significant association was observed between smoking and delayed conception among controls. On the basis of this finding, along with further analyses, the authors suggest that the statistical association between smoking and subfecundity may be genuine and ought to be further examined. Moderate alcohol consumption does not seem to play a role in the development of subfecundity. The paper provides a systematic review of possible bias sources in the study.

Oral contraceptive use and risk of invasive cervical cancer.

A case-control study of 759 invasive cervical cancer patients and 1430 controls in Panama, Costa Rica, Colombia and Mexico enabled an evaluation of risk in relation to oral contraceptive use. Overall use was associated with a 21% nonsignificant elevation in risk, with some further increases in risk for more extensive durations of use. Although risks were similar for recent and non-recent users (RRs = 1.3 versus 1.2), recent long-term users were at highest risk (RR for 5+ years use = 1.7, 95% Cl 1.1-2.6). Relationships were similar for women with and without a recent Pap smear, arguing against detection bias. There was little evidence that other risk factors, including smoking and detection of human papillomaviruses (HPV), altered the effects of oral contraceptives. The risk associated with oral contraceptives was significantly increased for adenocarcinomas (RR = 2.2), whereas for squamous cell tumours the effect was minimal (RR = 1.1). These results provide some support for an adverse effect of oral contraceptives on cervical cancer risk, although possibly limited only to a subpopulation of cases.

Long-acting hormonal contraceptives for women.

Following the development and widespread use of oral hormonal contraceptives, it became evident that alternative long-acting delivery systems would be required to improve contraceptive practice in some cultural settings where injectable or subdermal routes of administration are preferred. Nowadays, long-acting contraceptives constitute an important option in family planning services in many parts of the world. Indeed, two long-acting injectable contraceptives containing just a synthetic progestogen (depot-medroxyprogesterone acetate (DMPA) and norethisterone enantate (NET-EN)) have been in clinical practice for more than 20 years. The World Health Organization's (WHO) Special Programme of Research in Human Reproduction, in collaboration with the U.S. National Institute of Child Health and Human Development (NICHD) and universities primarily in developing countries undertook a synthesis programme aimed at producing an improved injectable preparation by developing new derivatives of known steroids. One such compound (levonorgestrel 17-butanoate) is now at the stage of Phase II clinical testing. In addition, the Special Programme has developed and improved once-a-month injectable formulations and assessed their safety and efficacy in different countries worldwide. After large scale clinical testing, at least two progestogen-estrogen combinations have reached the point of introductory trials.

PIP: A survey of recent trials of new injectable hormonal contraceptives, progestogen-only, levonorgestrel esters, and once monthly injectables, follows a brief review of all the experimental long-acting contraceptive modalities, injectables, implants, vaginal rings, and hormone-releasing IUDs. Currently medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN) are being used by 7 million women. WHO is conducting dose reduction trials and studies of bioavailability in various national populations. Even though a dose of 100 mg DMPA every 3 months has been satisfactory for contraception, 150 mg is still recommended until further pharmacodynamic data are available. Some populations, notably Thais and Mexican women, have higher peaks and more rapid elimination rates of DMPA, while Chinese women show slower elimination and higher blood levels of NET-EN. Extensive studies of new synthetic esters of levonorgestrel have proceeded to Phase II clinical trials with levonorgestrel butanoate. This ester is an effective contraceptive for 3 months at 12.5 mg, or 5-6 months at a dose of 25 or 50 mg. Trials of combined estrogen and progestogen injectables once-monthly have been ongoing for 10 years. The ratio of the 2 components is as important as the amounts. 2328 women from 12 countries participated in trials of DMPA 25 mg-estradiol cypionate 5 mg, and NET-EN 50 mg-estradiol valerate 5 mg. The continuation rate was better than that for 3-monthly progestogen-only injectables, because of less irregular bleeding. A combined injectable called Cyclofem, DMPA 25 mg-estradiol cypionate is being introduced in several countries. The steadily increasing demand for long-acting injectables prompts development of better formulations.

Contraception with progestogens and progesterone during lactation.

The growth and development of breastfed infants whose mothers used the contraceptive implants Norplant containing levonorgestrel and the injectable containing norethisterone enanthate were studied. Each group comprised of 120 women who initiated the use during the 5th to 7th week postpartum and were compared with a similar number of IUD using mothers. The breastfeeding performance did not differ between groups. The infants of the three groups performed similarly as regards their physical growth and health as well as the time of acquisition of the various milestones of psychomental development. A vaginal ring releasing 10 mg of the "natural" progesterone per 24 h was tested in breastfeeding mothers. The continuous use of the ring produced a serum level of progesterone around 4 ng/ml. This was effective in augmenting lactational infertility even through the later phases of breastfeeding when such an effect starts to wane off. The use of the ring proved to be acceptable and had no ill-effect on breastfeeding or infant growth or health. Using the natural progesterone as a contraceptive adds a new measure of safety, since the amount of the steroid secreted in the mother's milk will not be effectively absorbed from the infant's gut. These studies suggest the possibility of using two new methods for breastfeeding mothers; Norplant and the progesterone vaginal contraceptive ring. These can be initiated early postpartum, whenever this is considered needed.

PIP: Weight gain and psychomotor development of breastfed infants of Egyptian mothers using Norplant, Cu T-380A IUDs, norethisterone enanthate injectables (NET-EN), Depo Provera and a levonorgestrel minipill were compared in 2 trials. First, groups of 120 women using Norplant and NET-EN were compared to a control group using IUDs, beginning 5-7 weeks postpartum. There were no differences in infant weight gain, mid-arm circumference, triceps-skin-fold thickness, or timing of motor milestones. The mean growth curve of all 3 groups were close to that of the 50th percentile for Egyptian infants. While timing of initiation of supplements was similar in the 3 groups, complete weaning occurred first in the IUD group, second in the Norplant group, and last in the NET-EN users. A second trail compared progesterone implants injected with a trocar that resulted in a blood level of 3 ng/ml for 5 months, with Population Council vaginal rings releasing 10 progesterone/24 hours, and CuT-380A IUDs. Serum progesterone in the ring users averaged 5.2 ng/ml for the 1st 2 weeks, then leveled off at about 4 ng/ml for about 2 months, falling to about 3 ng/ml for the last 3 weeks of use. Each women used 4 rings per year. Evidence of ovulation by ultrasonic vaginal probe and assay of estradiol and progesterone was apparent in 25% of vaginal ring users, compared to 55.9% of controls in the 2nd 6 months postpartum. There was 1 pregnancy in a ring users. The continuation rates were 66.6% for rings and 85.5% for IUDs. The reasons for discontinuation in vaginal ring continuation were logistical problems and unfamiliarity.

Experience with the Dalkon Shield as a contraceptive device.

PIP: 291 woman recieved Dalkon shields for 2143 woman-months of cummulative use. The failure rate was 6.2% (18 pregnancies). 4.5% of these pregnancies occurred during the first year of use, and 6.8% during the second year. The overall pregnancy rate was 10.1 per 100 woman years, with no discernable diminution with the passage of time. The pregnancy rate rose rapidly during the first 6 months of usage and remained high thereafter. The expulsion rate was 1.7% and expulsions occurred only within the first 6 months after insertion. Removals totaled 19.2% for bleeding, pain, and/or infection. There was a "moderate degree of difficulty" in removing the device. The institution in which this study occurred recommended discontinuing use of the Dalkon shield because of its unacceptably high pregnancy rate.^ieng

Depo-medroxyprogesterone acetate as a contraceptive.

PIP: To test its effectiveness as a contraceptive, 150 mg of depo-medroxyprogesterone acetate (DMPA) was administered every 3 months to 752 women for 44 consecutive cycles. Side effects were similar to those seen with other contraceptive agents, the major one being irregular bleeding. During the course of this experiment, ethinyl was administered orally for 7 days of each month. This treatment improved the regularity of bleeding cycles. Although 450 women discontinued usage of DMPA for both drug-related and non-drug-related reasons, this study still showed DMPA to be an effective contraceptive. Only one method-failure occurred during 10,000 months of use; 75% of the women conceived within 12 months after discontinuing DMPA; 1 patient developed a questionable case of thrombophlebitis, but no cases of thromboembolic phenomenon were reported. DMPA, then, is regarded as an effective contraceptive that appears to inhibit the pituitary release of gonadotropins, and to alter the cervical mucus.^ieng

Contraceptive therapy following therapeutic abortion: an analysis.

PIP: Presented is a follow-up study of 823 women who were offered a contraceptive method after a therapeutic abortion. The 520 women who elected an oral contraceptive were started on the regimen the day of the abortion, and 93% were maintaining the therapy 6 weeks later. Postabortal bleeding ceased by Day 7 in 58% of the oral contraceptive users and in 59% of the control group. Virtually all bleeding had stopped by Day 28 (97%, 98%). 42% of the patients inserted with IUDs on the day of abortion had stopped bleeding by Day 7, and 85% had stopped by Day 28. About 80% of the oral contraceptors and 30% of the control group returned to menses within 28 days of the abortion. It is recommended that oral contraceptive therapy, if chosen, be initiated the day of the abortion.^ieng

Canadian county-sponsored family planning. 3. A second survey.

PIP: Information for the Norfolk-Haldimand County Health Unit is family planning clinic from May 1967 through October 1968 (160 new applicants) is presented and compared with the data of the original applicants (163) from May 1966 through April 1967. The pregnancy rate of women applicants age 19-25 was significantly less in the later survey group. There were 27.4% fewer IUD insertions in the second group and a concomitant rise in the number of women receiving oral contraceptives. The overall expulsion rate for the IUD was 11%. During the time covered in the study the overall continuation rate for oral contraceptives was 80%. Over the first 28 months of operation there was a 50% increase in the number of teenagers age 18 and under who had a pregnancy and subsequently requested contraceptive advice. Practically 92% of all applicants attending the clinic had 2 or more children. 90% of patients attending the clinic are women over 18 requesting permanent birth control and since continuation rates for the pill and the IUD are inadquate, sterilization for these women is suggested.^ieng

Contraceptive practice before and after therapeutic abortion. II. Use-effectiveness of oral contraceptives and intrauterine devices.

Of 180 women who underwent therapeutic abortion in a certain period in 1977, 71.7% were unmarried and 63.9% were unmarried primigravidas. At the first follow-up visit 3 to 6 weeks postabortion 55.0% of the unmarried primigravidas chose oral contraceptives and 43.2% chose intrauterine devices (IUDs). Of the unmarried women, 25.7% chose oral contraceptives and 65.7% chose IUDs. For unmarried primigravidas the 1-year continuation rates for oral contraceptives and IUDs were 83.6% and 93.8%, respectively. For married women the figures were 55.6% for oral contraceptives and 91.3% for IUDs. The differences between use of oral contraceptives and use of IUDs in the two groups of women was not statistically significant. We recorded no contraceptive failure, but three episodes of pelvic inflammatory disease occurred among unmarried primigravidas. The results indicate a high motivation for reliable methods and a high continuation rate following therapeutic abortion. The results may also indicate that oral contraceptives and IUDs represent equivalent methods for both parous and nulliparous women.

PIP: 195 women undergoing therapeutic abortion in a clinic were included in this study of the efficacy of various forms of contraception postabortion. 180 women were followed for the complete study; of these, 71.7% were unmarried and 63.9% were unmarried primigravidas. 3-6 weeks postabortion, the patients were offered a choice of contraception; 55% of the unmarried primas chose oral contraceptives, whereas 43.2% chose IUDs. Among the married population, 25.7% chose oral contraceptives, and 65.7% requested IUDs. Continuation rates for 1 year were calculated. Unmarried primas had continuation rates of 83.6% for oral contraceptives and 93.8% for IUDs. Married women had continuation rates of 55.6% and 91.3%, respectively, for oral contraceptives and IUDs. None of these rates showed statistical significance. Motivation for reliable contraception postabortion is very high, as judged by these continuation rates. There were no contraceptive failures; however, 3 cases of acute pelvic inflammatory disease were reported among the unmarried primas. The results indicate that either method is efficacious for both parous and ulliparous clients.

Clinical experience with LEM, an intrauterine contraceptive device.

PIP: The larger model LEM IUD was studied in a group of 464 women of which 63% were nulliparous and 37% were parous. The nulliparous group showed pregnancy rate of 12.5% at 12 months and the parous group showed rates of 5% at 12 months and 9.3% at 24 months. Expulsions in the nulliparous group increased from 5.3% at 3 months to 12.7% at 12 months and the parous group rate increased from 1.2% at 3 months to 5.9% at 12 months eventually reaching 7.3% at 24 months. Removal rates were 19.8% in the nulliparous group and 11.8% in the parous group. Figures for the entire group showed a rate of accidental pregnancy of 13.5%, expulsion 11%, removal 33%, and a continuation rate of 42 per 100 first insertions. Though the LEM is easily inserted and has relatively few complications, the pregnancy and expulsion rates do not recommend the device.^ieng

Experience with two different medicated intrauterine devices: a comparative study of the Progestasert and Nova-T.

A comparative study of the Progestasert (UPS) and the Nova-T in 326 randomly selected women was carried out. The observation period was 1 year. The over-all continuation rates for the two types of intrauterine devices (IUDs) were similar. The expulsion rate for the Nova-T (9.2%) was considerably higher (P = 0.001) than that for the UPS (1.2%). Medical removals for bleeding/pain were more frequent (P = 0.028) for the UPS (15.4%) as compared with the Nova-T (6.1%). The pregnancy rate for the UPS (Pearl index = 4.8) was insignificantly higher than that for the Nova-T (Pearl index = 2.8). Two of the pregnancies in the UPS group were ectopic. No significant changes in the reactive immunoglobulins (IgA, IgG, or IgM) were observed in either of the groups. Our results indicate that neither of these two IUDs is preferable to the already existing medicated IUDs, such as the Copper T or the Copper 7.

PIP: This study 1) compared the efficacy and continuation rates for the Progestasert (UPS) and Nova-T (Y-shaped, copper-medicated, 200 sq. mm., with flexible arms) and 2) determined the serum immunoglobulin response to women wearing 1 of these 2 differently medicated IUDs. Overall continuation rates for the 2 types of IUDs over a 1-year observation period (UPS must be changed yearly) were similar. Expulsion rate for Nova-T (9.2%), however, was considerably higher (P=.001) than for the UPS (1.2%). Pregnancy rate for the UPS by the Pearl index was 4.8 and was insignificantly higher than that for Nova-T (Pearl index=2.8). 2 UPS pregnancies were ectopic. Removals for bleeding/pain (i.e., medical removals) were more frequent (P=.082) for UPS (15.4%) than for Nova-T (6.1%). No significant changes in reactive immunoglobins (Igs), i.e., IgA, IgG, or IgM, were observed in either IUD group. Results suggested that neither IUD was preferable to already existing medicated IUDs.

Norplant implants: the mechanism of contraceptive action.

OBJECTIVE: To determine if fertilization occurs unnoticed among Norplant users who are ovulatory. DESIGN: Serial blood samples were obtained during 1 month from sexually active Norplant users experiencing regular menstrual bleeding patterns and a control group of noncontracepting women trying to conceive. The sequential blood samples were assayed for the presence of human chorionic gonadotropin (hCG). SETTING: All samples were obtained from women receiving contraceptive service and health care at the Center for Research and Services in Human Reproduction and Contraception, Santo Domingo, The Dominican Republic. Assays for hCG were performed at the Department of Biomedical Sciences, University of Tampere, Finland. PATIENTS, PARTICIPANTS: A total of 32 women using Norplant implants were enrolled in the treatment group, and 20 women of proven fertility who were attempting to conceive served as a control group. INTERVENTIONS: Duration of Norplant use was as follows: 4 in the 2nd year of use, 13 in the 3rd year, 11 in the 4th year, 3 in the 5th year, and 1 in the 7th year. MAIN OUTCOME MEASURE: The determination of pregnancy was based on the presence of hCG in the luteal phase, using a sensitive and specific immunoenzymatic assay that can detect dimeric hCG as early as 7 days after ovulation. RESULTS: Nine pregnancies were detected. All were in the control group trying to conceive. Six of these advanced to clinical pregnancies, and three did not proceed beyond the next expected menses. None of the Norplant users had evidence of hCG production, whether the observed cycles were anovulatory or ovulatory. The probability of finding no pregnancies in the ovulatory months at risk among Norplant users is between 1 in 50 and 1 in 150,000. The null hypothesis that Norplant users conceive at a natural rate can be rejected at the 0.05 level. CONCLUSION: Interruption of early pregnancy (menstrual abortion) does not play a role in the mechanism of action of Norplant contraceptive implants.

PIP: This study sought to determine if fertilization can occur unnoticed among Norplant users who are ovulatory. Serial blood samples were obtained during a 1-month period from women receiving contraceptive service and healthcare at the Center for Research and Services in Human Reproduction and Contraception, Santo Domingo, The Dominican Republic. These women were all sexually active Norplant users who experienced regular menstrual bleeding patterns, and their sequential blood samples were assayed for the presence of human chorionic gonadotropin (hCG) at the Department of Biomedical Sciences at the University of Tampere, Finland. There was also a control group of 20 noncontracepting women included who were trying to conceive. Duration of Norplant was as follows: 4 in the 2nd year of use, 13 in the 3rd year, 11 in the 4th, 3 in the 5th year, and 1 in the 7th year. Pregnancy determination was based on the presence of hCG in the luteal phase by use of a sensitive and specific immunoenzymatic assay that can detect dimeric hCG as early as 7 days postovulation. 9 pregnancies were detected, all in the control group who were trying to conceive. 6 of these advanced to clinical pregnancies and 3 terminated spontaneously at the next menstrual period. None of the Norplant users evidenced and hCG production, whether or not the observed cycles were ovulatory. The probability of finding no pregnancies in the ovulatory months at risk among Norplant users is between 1/50 and 1/150,00. The null hypotheses that Norplant users conceive at a natural rate can be rejected at the 0.05 level. Thus, interruption of early pregnancy (menstrual abortion) does not play a role in the mechanism of action of Norplant contraceptive implants.