Maria Lacarra

Rates and outcomes of planned pregnancy after use of norplant capsules, norplant II rods, or levonorgestrel-releasing or copper TCu 380Ag intrauterine contraceptive devices

OBJECTIVES The objectives were to measure rates of planned pregnancy and factors affecting these rates after use of very-long-acting contraceptive methods (Norplant or Norplant II implants, a levonorgestrel-releasing intrauterine contraceptive device, or the copper T (model TCu 380Ag) intrauterine contraceptive device. STUDY DESIGN The design was a concurrent, multicenter prospective study of 372 women who stopped contraception for planned pregnancy. Analysis was by life-table, log-rank, and standard chi 2 methods. RESULTS Pregnancy rates 12 and 24 months after cessation of contraceptive use were 82 and 89 per 100, respectively. Age at removal and family planning intentions at initiation of contraception were both significantly correlated with pregnancy rates (p less than 0.05), but former contraceptive regimen and duration of contraceptive use were not. Pregnancy outcomes did not deviate from normal limits and did not differ by contraceptive formerly used. CONCLUSION Contraceptive implants releasing 30 micrograms/day of levonorgestrel or intrauterine contraceptive devices releasing 20 micrograms/day of levonorgestrel or having copper surface areas of 380 mm2 are associated with normal fertility after use for women seeking pregnancy at termination. Durations of use do not affect pregnancy rates.

The use of transvaginal sonography for evaluation of postmenopausal ovarian size and morphology

Ultrasonic evaluation has been suggested as a possible screening tool for early changes in ovarian morphology. This study uses transvaginal sonography to evaluate the ovaries in postmenopausal women who were scheduled for gynecologic surgery unrelated to adnexal disease. The findings of ultrasonic ovarian examination are compared with the findings at surgery and the pathologic evaluation of the ovaries. Nine (17.3%) abnormal ovaries were identified by ultrasonography and at surgery and were confirmed at pathologic examination. Among the abnormal ovaries there were one malignancy (10%) and two neoplasms with known malignant potential (20%). One ovary that was identified to have microscopic areas of Brenner tumor cells at pathologic examination was described as normal by both ultrasound and surgical evaluation. The sensitivity (90%) and specificity (100%) of vaginal sonography were the same as that of gross examination of the ovary at the time of surgery. We conclude that vaginal sonography is a reliable tool in the detection of early abnormalities in the postmenopausal ovary.

Colposcopic evaluation of a vaginal gel formulation of iota-carrageenan

There is an urgent need to develop safe, effective, and acceptable vaginal products for the prevention of sexually transmitted infections. Preliminary in vitro results suggest that vaginal formulations of sulfated polysaccharides, including iota-carrageenan, have the potential to block mucosal transmission of human immunodeficiency virus (HIV). Twenty-five women in five sites participated in Phase I trials to evaluate the safety of a formulation containing iota-carrageenan (PC 213). The results of this study indicate that a 5 mL 2% gel formulation of iota-carrageenan is not associated with significant irritation of the female reproductive tract when administered once daily in the absence of sexual intercourse. Given the small number of participants in this initial study, careful observation for potential irritation must also be included in larger studies of this and other vaginal formulations.

Levonorgestrel concentrations during use of levonorgestrel rod (LNG ROD) implants

In a three-year randomized trial that included 398 women, blood samples were collected for the purpose of assaying levonorgestrel concentrations in women using a new two-rod contraceptive implant system or an earlier implant formulation, Norplant-2 implants. Sample collection was at 1, 3, 6, 9, and 12 months after placement and semiannually thereafter through three years. Resulting assays and analyses showed that levonorgestrel concentrations of each implant formulation decreased significantly with time after placement, with increasing body weight, and with ponderal index. In the third year, several measures indicated that concentrations of the contraceptive drug were higher in women using the LNG ROD implants than in users of the original formulation. No pregnancies occurred among women in either group in the three years. This study provides evidence that the minimum levonorgestrel concentration needed to protect against pregnancy is below 200 pg/ml, and possibly is below 175 pg/ml.

Long-term reversible contraception with levonorgestrel-releasing Silastic rods.

Subcutaneously placed Silastic capsules containing levonorgestrel are effective for 5 years and have a higher continuation rate than other methods of reversible contraception. Six 3 cm capsules are required to achieve satisfactory circulating levels of levonorgestrel. Two 4 cm covered Silastic rods containing levonorgestrel, which are easier to manufacture, insert, and remove than the capsules, produce similar in vitro release rates. This study compared clinical and metabolic effects as well as bleeding patterns in 23 women using either six capsules (n = 11) or two covered rods (n = 12). Serum levels of levonorgestrel, lipids, and lipoproteins as well as frequency of elevated progesterone levels were compared in serum samples obtained before treatment and 1, 6, 12, 18, and 24 months after insertion with the two systems. While bleeding patterns were similar for users of the two systems, rod users had slightly higher serum levels of levonorgestrel and a lower incidence of cycles with elevated progesterone levels. Therefore, rods could replace capsules as a long-term, reversible contraceptive method.

Contraception with two levonorgestrel rod implants : A 5-year study in the United States and Dominican Republic

A 5-year trial of a two-rod contraceptive implant, which releases the progestin levonorgestrel (LNG rod), was conducted at four clinics with 594 women. Mean age and weight at admission were 25.5 years and 62.4 kg, respectively. Consent to continue through 5 years was sought and obtained when the 3-year cumulative pregnancy rate proved to be 0.8 per 100. No pregnancies occurred in the fourth or fifth years. The 5-year cumulative pregnancy rate was, therefore, 0.8 per 100 with an annual average pregnancy rate below 2 per 1000 women. Prolonged bleeding/spotting (8.2% of subjects) and irregular bleeding (5.6%) were the most frequently cited medical reasons for removal. Removals for headache (4.7%) and weight change (4.0%) were the next most frequent medical reasons. Between 1% and 2% of subjects during the 5-year trial sought removals for each of the following conditions: mood changes, lower abdominal pain, depression, or pain at the implant site. The mean annual continuation rate during the study was 77 per 100. Use per woman averaged 2.96 years. Mean removal time was 5.9 +/- 0.6 min. These data indicate that, for a 5-year period, the two LNG rod implants are equivalent to the six Norplant capsule implants with respect to safety and efficacy parameters, but permit easier and more rapid implant removal.

Early abortion with a single dose of the antiprogestin RU-486

RU-486 is a synthetic progesterone antagonist that is abortifacient in early pregnancy. This trial evaluated the effectiveness and safety of a single 600 mg oral dose given to 50 healthy women less than or equal to 49 days from their last menstrual period. Efficacy was inversely related to the initial beta-subunit of human chorionic gonadotropin level, ranging from 100% at less than 5000 mIU/ml to 81% at greater than 20,000 mIU/ml (p less than 0.05). Uterine bleeding was the most serious side effect. However, the mean change in the hemoglobin value 14 days after treatment was -0.4 gm/dl, and no patient required blood transfusion. This regimen appears to be simple, effective, and safe.

Termination of early gestation with the anti-progestin steroid RU 486: Medium versus low dose

RU 486 is a synthetic steroid which has antiprogesterone and antiglucocorticoid activity. In order to determine the optimal dosage of this drug to terminate early pregnancy, we treated 106 healthy women with normal pregnancies by real time ultrasound examination whose gestational duration was less than 49 days from onset of last menses with either a medium or low dose treatment regimen. A total of 66 patients received the medium dose regimen (100 mg/day X 7 days). Another 10 patients received ergonovine (0.2 mg/day X 6 doses) on Day 4 of the same RU 486 treatment regimen. In the first group, 48 (73%) aborted successfully and, of the second group, 6 (60%) aborted. Eighty percent of the subjects in this group of 76 patients reported side effects of nausea and vomiting, heavy bleeding, severe menstrual cramps or headache. All these side effects were successfully treated with analgesic and antiemetic medication. The remaining 30 subjects were treated with a low dose regimen (50 mg/day X 7 days). Of these 30, 15 (50%) aborted; this incidence was significantly less (p less than 0.05). Following the medium dose treatment regimen, the AM cortisol levels were significantly elevated on treatment Days 4 and 8, as compared to baseline (p less than 0.001), although the mean levels were still within the normal range. With the low dose, there was a non-significant rise in AM cortisol values. Thus the rise in cortisol was significantly greater in the former group than the latter (p less than 0.05). With the medium dose regimen, the women who aborted had significantly lower (p less than 0.05) pretreatment mean B-HCG and progesterone levels than the group that failed to abort. Mean serum levels of RU 486 were not significantly different between the group who aborted and those who did not. RU 486 is a promising agent for termination of early pregnancy.

Characteristics of ovarian follicular development in Norplant users

Daily transvaginal ultrasound (US) scanning of the ovaries to assess follicular development and daily blood sampling were performed on 19 Norplant (Leiras, Turku, Finland) subdermal contraceptive implant users who had regular menstrual cycles and on 10 normally cycling women. Three groups were identified in the implant users based on US finding. Six (31.6%) of the implant users had US findings that were consistent with a normal ovulatory pattern. However, their mean peak luteinizing hormone levels and peak midluteal phase progesterone (P) levels were significantly lower than control values. Eleven (57.9%) users had persistent follicles, and 2 users (10.5%) had no follicular development. These data suggest that after 2 to 4 years of use, about one third of Norplant users with regular bleeding patterns may ovulate but most have deficient luteal P levels. In this small study, the presence of persistent follicular enlargement in implant users was common.

A Medical Method of Early Pregnancy Termination Using Tamoxifen and Misoprostol

A study was undertaken to determine whether ingestion of the selective estrogen receptor modulator tamoxifen followed by vaginal administration of the prostaglandin misoprostol would be an effective medical method of elective termination of early pregnancy. A clinical trial was conducted with a study group of 100 healthy women with pregnancies of 56 days gestational age or less who desired elective pregnancy termination. Each subject ingested 20 mg of tamoxifen once daily for 4 days followed 4 days later by intravaginal placement of four 200 micrograms tablets of misoprostol. If abortion did not occur within the next 24 h a second dose of 800 micrograms of misoprostol was given. The main outcome measures were incidence of complete abortion, hemoglobin levels, duration of vaginal bleeding, and incidence of side effects. Complete abortion occurred in 92 (92%, 95% CI 86.7, 97.3%) of 100 subjects. Of these 92 women, four aborted after ingesting tamoxifen without use of misoprostol, 84 within 24 h after receiving a single dose of misoprostol, one 21 days following a single dose of misoprostol, and three after a second dose of misoprostol was administered. There were six (6.0%) complete treatment failures and two (2%) incomplete abortions that required a dilatation and curettage. The mean duration of uterine bleeding was 8.1 days (range 1-34 days) and there was a median decrease in hemoglobin level of 0.50 g/dL (+2.2 to -4.7 g/dL). Vomiting occurred in 28% of subjects and diarrhea in 8%. These initial data suggest that ingestion of tamoxifen followed by intravaginal misoprostol may be an effective, easily administered, and inexpensive method to electively induce complete abortion in pregnancies of 56 days gestational age or less. Additional studies are necessary to determine whether the addition of tamoxifen increases the success rate compared with that obtained with the use of vaginally administered misoprostol by itself.