Reducing maternal mortality due to elective abortion: Potential impact of misoprostol in low-resource settings.

Over 99% of deaths due to abortion occur in developing countries. Maternal deaths due to abortion are preventable. Increasing the use of misoprostol for elective abortion could have a notable impact on maternal mortality due to abortion. As a test of this hypothesis, this study estimated the reduction in maternal deaths due to abortion in Africa, Asia and Latin America. The estimates were adjusted to changes in assumptions, yielding different possible scenarios of low and high estimates. This simple modeling exercise demonstrated that increased use of misoprostol, an option for pregnancy termination already available to many women in developing countries, could significantly reduce mortality due to abortion. Empirical testing of the hypothesis with data collected from developing countries could help to inform and improve the use of misoprostol in those settings.

Acceptability of manual versus electric aspiration for first trimester abortion: a randomized trial.

This study was conducted to compare the acceptability of manual and electric vacuum aspiration for first trimester elective abortion. Eighty-four women seeking abortions at less than 10 weeks gestation were randomized to abortion by manual or electric vacuum aspiration. Post-procedure questionnaires were administered to patients to assess pain, noise disturbance and overall satisfaction with the abortion procedure. Physicians reported procedural difficulty, their perceptions of patient discomfort and their overall acceptance of the procedure. Other outcomes included amounts of anesthesia required and complication rates. There were no significant differences in pain levels or satisfaction reported by patients; however, significantly more women in the electric group were bothered by noise (19% vs. 2%, p = 0.03). There were no differences in physician assessments of procedural difficulty; however, there were significantly more times in the electric group that physicians would have preferred manual aspiration (43% vs. 17%, p = 0.02). There were four crossovers from manual to electric, and none from electric to manual. It is concluded that physicians and patients find manual vacuum aspiration as acceptable as electric vacuum aspiration for elective abortions performed at less than 10 weeks gestation.

Implant contraception.

The experience of 6 million Norplant users has led to several more advanced implants. Implanon is a single-rod implant system containing a low androgenic progestin and requires 1 to 2 minutes for insertion and removal. Like other implants, Implanon prevents pregnancy by changing the character of the cervical mucus and interfering with luteal function. Unlike Norplant, though, Implanon is designed to prevent ovulation for the full duration of use. Implant contraception has several advantages over other types of contraception including high efficacy, minimal required maintenance, absence of estrogen, and rapid return of fertility after discontinuation. Implants can be a good choice for adolescents; women with hypertension, diabetes, anemia, endometriosis, or other medical problems; and women who are breast-feeding. Irregular bleeding is the most common adverse effect of implants and can be treated with several medication regimens. Preinsertion counseling, however, is the most important factor in ensuring satisfaction with implants. Unfortunately, no implant system is currently available in the United States since August 2000, but Implanon is expected to reach the U.S. market within the next 2 years.

Levonorgestrel concentrations during 7 years of continuous use of Jadelle contraceptive implants.

Serum levonorgestrel concentrations were assayed in a multicenter, 7-year study of 199 users of Jadelle rod implants. We examined drug levels, patterns of changes, factors affecting drug levels, and concentrations at which pregnancies occurred. Mean levonorgestrel concentrations declined from 435 pg/mL at 1 month of use to 64% of that value (280 pg/mL) at the end of 3 years. Between the end of the third and fifth years neither mean nor median serum levels varied markedly. At 5 years the mean concentration was again 64% of the first month's mean. Declining levels were observed thereafter through the end of 7 years when the mean, 224 pg/mL, was 52% of the 1-month value. Last measured drug concentrations of women who became pregnant during Jadelle use had mean and median values of 152 and 144 pg/mL, respectively, and a maximum value of 180 pg/mL. Analyses indicated ponderal index, body weight, duration of use, and a single clinical center were the most important variables affecting measured levonorgestrel levels. Approximately one-third of assays in the sixth and seventh years were found to be below 180 pg/mL, suggesting that Jadelle levonorgestrel implants would not maintain sufficiently high levels of effectiveness against pregnancy after 5 years and that heavier women would then be at greater risk of pregnancy.

Effects of a monthly injectable steroidal contraceptive, Mesigyna, on menstrual pattern, lipoproteins, and coagulation parameters.

The objective of this study was to determine the effects of a once-monthly injectable contraceptive (Mesigyna) on menstrual pattern, lipoproteins, and coagulation parameters. Thirty-six women aged 18-35 years requesting monthly injectable contraception were included. Before injecting estradiol valerate 5 mg and norethisterone enanthate 50 mg, coagulation, lipoprotein, and liver function parameters were determined. After the 3- and 6-month injections, the same coagulation and serum lipid measurements and liver function tests were repeated, and women were questioned about their menstrual patterns and side effects. Thirty women who completed 6 months were evaluated. At the end of 3 months, two-thirds of the 30 women had normal menstrual patterns; at the end of 6 months, 80% of the women had normal menses. Serum LDL, total cholesterol, and triglyceride levels did not change significantly, while HDL and VLDL decreased significantly (p = 0.032 and p = 0.039, respectively) at 6 months. PT and aPTT measures did not change at the end of 6 months, while fibrinogen levels were significantly lower (p = 0.013). Serum total bilirubin levels increased (p = 0.022) and albumin levels decreased (p = 0.022) at the end of 6 months. Mesigyna was well tolerated and side effects and menstrual abnormalities were acceptable. There were no clinically significant changes in lipoprotein, coagulation, or hepatic parameters.

Cervical neoplasia risk in women provided hormonal contraception without a Pap smear.

The study was conducted to determine whether women using a demonstration program providing hormonal birth control without concurrent pelvic examination (First Stop) are at higher risk of cervical neoplasia compared to women using traditional family planning clinics. Using retrospective ion of medical charts, we compared risk factors for cervical neoplasia among 400 First Stop clients and 400 traditional site clients matched on age, race, and contraceptive method. We determined prevalence of these factors: previous abnormal cervical smear, <16 years at first intercourse, multiple sexual partners, high parity, history of sexually transmitted infections, and current cigarette smoking. First Stop clients were not at greater likelihood of having any risk factor for cervical neoplasia except high parity. First Stop clients who failed to follow through on a referral to a traditional clinic were not more likely to be of higher risk than those who did follow through. Of 13 First Stop clients with the highest risk profiles (previous abnormal cervical smear plus one other risk factor), one did not follow through with referral. First Stop clients choosing hormonal contraception without a pelvic examination do not appear to be at substantially higher risk of cervical neoplasia. Future research should quantify more precisely the risks and benefits of the general application of this strategy on a population level.

Provision of hormonal contraceptives without a mandatory pelvic examination: the first stop demonstration project.

CONTEXT: First Stop, an 18-month demonstration project that operated in 1996-1997, was designed to offer low-income adult women in California hormonal contraceptives without requiring a pelvic examination. METHODS: An evaluation was undertaken to assess the contraceptives adopted by First Stop clients, compare health risks of these women with risks among women using traditional family planning clinics and assess clients'satisfaction. Data on 2,065 First Stop clients and 1,507 women attending traditional clinics were collected through several self- and clinician-administered instruments, including questionnaires, a telephone survey and medical chart abstractions. RESULTS: After the initial First Stop visit, 38% of women adopted a more effective method than they had used at last sex, 4 7% remained with the same method, 12% switched to a less-effective method and 3% accepted no method. Of clients who were referred for additional medical care, 73% followed through on their referrals. Compared with clients at traditional clinics, First Stop clients were less likely to have a regular source of health care, but more likely to have made a health care visit in the past year. Most First Stop clients valued the project's services; 76% said it was important to be able to receive pills or injections without a pelvic examination. CONCLUSIONS: Programs that provide hormonal contraceptives without requiring a pelvic examination can expand low-income women's access to these methods and improve the chances that they will obtain other reproductive health services.

Digoxin to facilitate late second-trimester abortion: a randomized, masked, placebo-controlled trial.

OBJECTIVE: To examine the efficacy of digoxin for decreasing operative time, difficulty, and pain of late second-trimester surgical abortions. METHODS: We performed a randomized, double-masked, placebo-controlled trial of intra-amniotic digoxin for second-trimester dilation and evacuation (D&E) involving 126 consecutive women at an inner-city public hospital. Eligible women had gestational ages of 20-23.1 weeks, spoke English or Spanish, and were at least 16 years old. Digoxin (1 mg) or saline was injected intra-amniotically 24 hours before the procedure, at cervical laminaria insertion. The primary outcome was procedure duration. Sample size was based on 80% power to detect a difference of 3.5 minutes between groups. RESULTS: The two groups were similar in demographic factors, obstetric histories, and gestational duration. The average gestational length was 22.5 weeks. There was no difference in procedure duration (mean +/- standard deviation) between groups (placebo 14.7 +/- 7.0, digoxin 15.4 +/- 8.0). There were no differences in blood loss estimated by surgeons, pain scores, procedure difficulty scores, or complications between groups. Vomiting was significantly more common in those who received digoxin (placebo 3.1%, digoxin 16.1%). Most subjects (91%) reported that they preferred their fetuses were dead before the abortions. CONCLUSION: Although digoxin did not increase efficacy of late second-trimester abortion, patient preference might justify its use.

Implantable contraception.

Although levonorgestrel contraceptive implants have been available for over 15 years, innovations have only recently led to a wider choice. These new implants offer easier insertion and removal and other advantages depending on the type of progestin. Implants prevent pregnancy by several mechanisms, including inhibition of ovulation and luteal function and alteration of cervical mucus and the endometrium. The high efficacy and ease of maintenance make implants an ideal contraceptive for many women, including adolescents, a population that uses implants infrequently but reports high satisfaction. Implants are appropriate for women who are breastfeeding, who have contraindications to estrogen, or who have diseases such as diabetes, hypertension, sickle cell anemia, or an HIV infection because implants have few metabolic or hematologic effects. Long-term use has not been associated with a decrease in BMD and generally leads to increased blood levels and iron stores. Women who wish to space their pregnancies appreciate the nearly immediate onset of action with insertion and the rapid termination of all effects with removal. All types of implants lead to menstrual changes and other side effects in some women. Adverse effects that occur in implant users more than the general population include headaches and acne. Women must be thoroughly counseled regarding the potential for menstrual alteration, side effects, and sexually transmitted infections if they do not use condoms. Despite their initial high cost, implants are a cost-effective method over several years, even when discontinued before the life of the implant.

Ovarian steroid and cytokine modulation of human endometrial angiogenesis.

A key mechanism underlying the cyclical growth of the endometrium is its ability to regenerate a vascular capillary network. In normal cycling human endometrium, angiogenesis is influenced by both endocrine and paracrine factors. Hormonal manipulation of the endometrium, such as that occurring during the use of steroidal contraception, appears to result in capillary proliferation and fragility. As a consequence of these vascular changes, contraceptive users may be predisposed to unpredictable uterine bleeding, which is responsible for the high frequency of contraceptive discontinuation. In this paper we address mechanisms responsible for vascular endothelial cell proliferation in normal and contraceptive steroid-exposed endometria. We propose that regulation of endometrial angiogenesis is mediated indirectly, via steroid and cytokine actions on vascular endothelial growth factor (VEGF), and we present data indicating that VEGF expression in normal endometrial stromal cells is increased by oestrogens and progestins. Three proinflammatory cytokines with angiogenic effects in other systems (i.e. interleukin-1beta, tumour necrosis factor-alpha and interferon-gamma) do not appear to up-regulate VEGF expression in normal endometrial stromal cells. Well-characterized in-vitro models in conjunction with immunohistochemistry provide useful experimental systems to study endometrial neovascularization under physiological conditions and in those potentially perturbed via the use of contraceptive steroids.

Knowledge and willingness to use emergency contraception among low-income post-partum women.

We performed a multivariate analysis to determine factors associated with knowledge and willingness to use emergency contraception in a consecutive sample of 371 post-partum women from an inner-city public hospital. Women were queried about previous contraceptive use, pregnancy history including abortions and unplanned pregnancies, and demographic characteristics. Outcomes included knowledge of emergency contraception and willingness to use it. Questionnaires were conducted in person, in English or Spanish.Of 371 women, 3% had used emergency contraception, 36% had heard of it, and 7% knew the correct timing for use. Two-thirds of the population indicated a willingness to use emergency contraception in the future. Factors positively associated with knowledge included being a teenager or more than 30 years old, prior use of condoms, and history of an elective abortion. Being multiparous, monolingual Spanish-speaking, or Asian were negatively associated with knowledge. Willingness to use emergency contraception was positively associated with being multiparous and negatively associated with a higher income, moral or religious objections to the use of emergency contraception, a belief that it is unsafe or a perception that it is an abortificient. Knowledge about emergency contraception, especially correct timing, remains low. Multiparous women should receive increased education given their lack of knowledge but willingness to use emergency contraception. In order to increase the acceptability of emergency contraception, educational efforts must include accurate information about its mechanism of use and safety.

Early surgical abortion: an alternative to and backup for medical abortion.

Surgical abortion by vacuum aspiration is one of the most commonly reported surgical procedures in the United States. The developments of highly sensitive urinary pregnancy tests and transvaginal ultrasonography have encouraged the application of surgical abortion methods at earlier gestational ages. Manual vacuum aspiration with a handheld syringe safely accomplishes early abortion in a variety of settings, from elective abortion in the office or clinic setting to emergency care of a patient with an incomplete abortion. As a wider range of clinicians expresses interest in offering medical abortion, the appropriate use and technique of surgical backup are crucial in safely providing medical abortion. This article reviews vacuum aspiration during the first few weeks of pregnancy, with special attention to manual vacuum aspiration, both for elective surgical abortion and when intervention is required after medical abortion.

Emergency contraception: advance provision in a young, high-risk clinic population.

OBJECTIVE: To assess whether advance provision of emergency contraception increases its use and whether it has secondary effects on regular contraceptive use. METHODS: We conducted a controlled trial of female clients, aged 16-24 years, who attended a publicly funded family planning clinic. Women were systematically assigned to receive an advance provision of emergency contraception and education (treatment) or education only (control). Among 263 participants enrolled (133 treatment, 130 control), follow-up was completed in 213 (111 treatment, 102 control). The main outcome measures were emergency contraception knowledge and use, frequency of unprotected sex, and pattern of contraceptive use in the past 4 months. RESULTS: Participants were aware of emergency contraception at follow-up, but the treatment group was three times as likely to use it (P =.006). Although the treatment group did not report higher frequencies of unprotected sex than the control group, women in the treatment group (28%) were more likely than those in the control group (17%) to report using less effective contraception at follow-up compared with enrollment (P =.05). The proportion of women in both groups who reported consistent pill use increased from enrollment to follow-up (34% versus 45%); however, the control group (58%) was more likely than the treatment group (32%) to report consistent pill use at follow-up (P =.03). CONCLUSION: Use of emergency contraception was increased by providing it in advance, but not by education alone. Changes to less effective contraceptive methods and patterns of pill use were potentially negative effects that need to be explored in relation to observed benefits.

Prolonged effectiveness of Norplant(R) capsule implants: a 7-year study.

Soft tubing Norplant(R) contraceptive implants were studied in 1210 women for 7 years to measure the duration of effectiveness and the magnitude of the pregnancy rates over that time. Mean age at enrollment was 27.4 years. Of the enrollees, 42% were US residents. One-sixth (16.1%) weighed >/=70 kg at the time of implant placement. At the end of 5 years, the cumulative pregnancy rate was 1.1/100; at the end of 7 years, it was 1.9/100. No pregnancies occurred to any of the 400 women who enrolled in the study at age >/=30 years and who weighed <100 kg. Among women aged 18-33 years, the 7-year Norplant pregnancy rates are comparable to the median pregnancy rates of tubal sterilization methods for women of the same age and duration of use. For women aged >/=34 years, without regard to weight at admission, the 7-year effectiveness of soft tubing Norplant equals or surpasses that of tubal sterilization. For continuing implant users, annual pregnancy rates <1.0/100 in years 6 and 7, together with low cumulative pregnancy rates, testify that Norplant capsule implants remain highly effective for 7 years.

Safety of intra-amniotic digoxin administration before late second-trimester abortion by dilation and evacuation.

OBJECTIVE: The purpose of this study was to determine the safety of intra-amniotic digoxin injection before late second-trimester pregnancy termination by dilation and evacuation through an assessment of maternal systemic digoxin absorption, cardiac rhythm, and coagulation parameters. STUDY DESIGN: Pregnant women at between 19 and 23 weeks' gestation received 1.0 mg digoxin through intra-amniotic injection and then had serum digoxin levels determined for 48 hours and Holter cardiac monitoring performed for 24 hours. Clotting parameters were assessed before digoxin injection and 24 hours later, at the time of the dilation and evacuation procedure. RESULTS: Eight patients completed the study. The mean (+/-SD) serum digoxin peak concentration was 0.81 +/- 0.22 microg/L (range, 0.5-1.1 microg/L). The mean (+/-SD) time to peak digoxin concentration was 11.0 +/- 5.55 hours (range, 4-20 hours). Ambulatory cardiac monitoring showed no rhythm or conduction abnormalities associated with digoxin. Prothrombin time, partial thromboplastin time, and fibrinogen levels did not change significantly between determinations before and after the dilation and evacuation procedure (11.5 to 11.4 seconds, 24.1 to 24.4 seconds, and 441 to 475 mg/dL, respectively). CONCLUSION: The maximum digoxin concentration peak achieved after intra-amniotic injection was in the low therapeutic range. No rhythm or conduction abnormalities associated with digoxin were noted by Holter monitoring. Coagulation parameters did not change significantly. On the basis of the limited systemic absorption and the absence of clinically significant cardiac or clotting effects, intra-amniotically administered digoxin may be considered safe for use before late second-trimester pregnancy terminations.

Implantable contraception.

This article reviews the advantages and disadvantages of progestogen-only contraceptive implants in light of the development of Implanon, a new, single-rod, etonogestrel-releasing system. Implants rapidly produce serum progestogen levels sufficient to ensure contraception for 1-5 years. The steady release ofprogestogen avoids the peaks and troughs associated with oral contraceptives, the profound ovarian suppression observed with depot injections and the need for user compliance. Implants have few serious complications. Ectopic pregnancy rates are low, and follicular hypertrophy is generally self-limiting. The principal acceptability limitation to both users and providers of Norplant is insertion and removal. Implanon is easy to insert and remove with minimal complications and pain. The main adverse event causing discontinuation of implants is a change in bleeding pattern. However, with good counselling, this is well tolerated by most women. Implants thus provide an effective, safe, economical and convenient alternative to oral, injectable or intrauterine contraceptives. Implanon is an extremely effective single-rod implant with a Pearl index of 0. It employs a new polymer and a less androgenic progestogen. These features provide easier insertion and removal for both users and clinicians, a more stable release rate and potentially fewer adverse androgenic effects compared with existing formulations.

A comparative study of two contraceptive vaginal rings releasing norethindrone acetate and differing doses of ethinyl estradiol.

Two combined contraceptive vaginal rings (CVR) each releasing approximately 1 mg norethindrone acetate (NET-Ac) and either 20 micrograms or 15 micrograms ethinyl estradiol over 24 h were tested at three clinic sites in Los Angeles, San Francisco, and Sydney. A total of 61 women were enrolled to use the ring on a schedule of 3 weeks in/1 week out for four treatment cycles. Serum estradiol, progesterone, norethindrone (NET), and ethinyl estradiol (EE) levels were assayed twice weekly in all four treatment cycles. Both CVR performed well, with no pregnancies occurring and only one cycle of luteal activity suggestive of ovulation (serum progesterone > 32 nmol/L) occurring with each ring (0.9% of cycles with the 1/15 ring and 1.2% of cycles with the 1/20 ring). Although there was significantly more luteal activity in women using the 1/15 CVR (5.9% compared with 1.2% of cycles), only three cycles with a marked degree of luteal activity (progesterone > 10 nmol/L) occurred among compliant women. Serum levels of NET and EE were consistently elevated during use of both rings. There was no significant difference between serum levels with the two rings because of wide interindividual variations, although both NET and EE levels tended to be higher with the 1/20 ring. However, there was a significant difference in EE levels between the women in Los Angeles and Sydney using the same dose rings. Total cholesterol, HDL, and LDL cholesterol values were not significantly changed during treatment. Triglycerides increased but remained within the normal range. Overall cycle control was good with both formulations, but there was slightly more cycle disturbance with the lower dose ring. There was no change in mean body weight during the study, and individual weight changes appeared to be idiosyncratic. Side effects were infrequent and similar to those reported with other steroidal contraceptive methods. Three women complained of vaginal discharge, one with accompanying itch and one with a vaginal Candida infection in cycle 1. Overall, both of these EE/NET-Ac rings performed well, with only minor and mainly nonsignificant differences in effect on serum EE, NET, E2, and progesterone levels and lipids, and on vaginal bleeding patterns.

PIP: This study compares the performance of 2 combined contraceptive vaginal rings (CVRs) releasing 1 mg norethindrone acetate (NET-Ac) and either 20 or 15 mcg ethinyl estradiol (EE) over 24 hours. 61 women selected at 3 clinic sites in Los Angeles, San Francisco and Sydney were included. The performance of the 2 CVRs was determined by luteal activity, menstrual bleeding patterns, sum levels of EE and NET-Ac, and effects on serum lipoproteins. Results showed that both CVRs worked effectively: no pregnancies occurred, and there was only 1 cycle of luteal activity suggestive of ovulation (serum progesterone 32 nmol/l) with each ring (0.9% of cycles with the 1/15 ring and 1.2% of cycles with the 1/20 ring). Although there was more luteal activity in 1/15 CVR users, only 3 cycles with a significant level of luteal activity (progesterone 10 nmol/l) occurred among compliant users. Consistent elevation in serum levels of NET and EE was observed during use of both rings. A significant difference in EE levels was observed between women in Los Angeles and Sydney using the same dose of rings. There were no significant changes in the total cholesterol, HDL and LDL cholesterol values during treatment. The increase in triglycerides remained within the normal range while mean body weight showed no change. Side effects were infrequent and were similar to those associated with other steroidal contraceptives. Overall, both CVRs performed well, showing only minor and mainly nonsignificant differences in effect on serum EE, NET, E2, on progesterone levels and lipids, and on vaginal bleeding patterns.