Gary Sondermann Grubb

Regret after decision to have a tubal sterilization

To determine characteristics associated with regretting sterilization that can be determined preoperatively, we analyzed data from the Collaborative Review of Sterilization (CREST), a multicenter, prospective, observational study. Of 5022 women, 2.0% regretted having had a tubal sterilization at 1 year after the procedure and 2.7% did so after 2 years. Using a multivariate analysis to identify risk factors for regret, we found that almost all characteristics were more closely associated with regret at 1 year than at 2 years postoperatively. Of the characteristics we examined that could be objectively determined preoperatively, we considered only age less than 30 years and (for whites) a concurrent cesarean section to be risk factors for regret at 2 years after sterilization. However, in absolute terms, less than 10% of women with both those risk factors regretted having the procedure.

Case-fatality rates for tubal sterilization in U.S. hospitals, 1979 to 1980

To update a 1977 to 1978 case-fatality estimate for tubal sterilization in U.S. hospitals, we reviewed the medical records of women reported by the Commission on Professional and Hospital Activities to have died after tubal sterilization procedures in 1979 or 1980. We project that the most reasonable case-fatality rate estimate is slightly greater than 9 per 100,000 sterilizations if all deaths associated with the procedure are considered. Rate estimates that assume minimum and maximum numbers of all associated deaths in our sample are approximately 6 per 100,000 and 10 per 100,000 sterilizations, respectively. However, when only deaths that can be attributed to sterilization per se are considered, the most reasonable case-fatality rate is estimated at between 1 and 2 per 100,000 procedures, a lower rate than previously reported. Rate estimates that assume minimum and maximum numbers of attributable deaths in our sample are approximately 1 per 100,000 and 5 per 100,000 sterilizations, respectively. These results further indicate that death attributable to tubal sterilization is rare.

Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial☆

BACKGROUND This Phase 3, randomized, open-label, multicenter study conducted at 44 sites in Europe evaluated the safety and efficacy of a continuous, daily regimen of levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg compared with a 21-day, cyclic LNG 100 mcg/EE 20 mcg regimen. STUDY DESIGN Three hundred twenty-three healthy women were randomized to continuous LNG 90 mcg/EE 20 mcg and 318 subjects to cyclic LNG 100 mcg/EE 20 mcg for 1 year (13 pill packs). Pearl index, adverse event (AE) incidence and bleeding profiles were assessed. RESULTS No pregnancies occurred with the continuous oral contraceptive (OC) (Pearl index=0.00). As the study progressed, the percentage of women who achieved amenorrhea during each 28-day pill pack increased: 40% at pill pack 7, 53% at pill pack 13. The percentage of women with no bleeding [with or without spotting (defined as not requiring sanitary protection)] was 50%, 69% and 79% at pill packs 3, 7 and 13, respectively. The incidence of AEs was similar to that of the cyclic OC (except for metrorrhagia and vaginal bleeding in the first 6 months). CONCLUSIONS Continuous LNG 90 mcg/EE 20 mcg was shown to be a safe and effective OC in this direct comparison to a cyclic OC. Suppression of menses and the potential for no bleeding requiring sanitary protection may be provided by this continuous, low-dose OC.

Return to fertility after cessation of a continuous oral contraceptive.

OBJECTIVE To evaluate the return to fertility among women planning to become pregnant after the use of a continuous regimen of levonorgestrel 90 microg and ethinyl E(2) 20 microg. DESIGN Descriptive analysis of pregnancy outcomes after participation in a contraceptive trial. SETTING Multicenter trial. SUBJECT(S) Participants in a phase 3 contraceptive trial who discontinued to become pregnant. INTERVENTION(S) Eligible subjects were contacted at 3 and 12 months after treatment discontinuation to determine if and when they had conceived. MAIN OUTCOME MEASURE(S) Kaplan-Meier analysis displaying the time until conception after oral contraceptive discontinuation. RESULT(S) In the phase 3 trial, 34 of 2,134 subjects cited a desire for pregnancy as a reason for discontinuation. Of these, 4 were already pregnant before stopping treatment, 4 initiated other contraception, and 5 were lost to follow-up. Of the remaining 21 subjects at risk of pregnancy, the pregnancy rate was 57% at 3 months, 81% at 12 months, and 86% (18 of 21) (95% confidence interval 64% to 97%) at 13 months after discontinuation of treatment. CONCLUSION(S) These findings suggest that a continuous oral contraceptive with levonorgestrel 90 microg and ethinyl E(2) 20 microg does not delay the return to fertility.

Ovarian activity and safety of a novel levonorgestrel/ethinyl estradiol continuous oral contraceptive regimen

BACKGROUND A continuous regimen of oral levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg was evaluated for inhibition of ovulation, time to return to ovulation after stopping treatment and safety. STUDY DESIGN This open-label study was conducted in healthy women aged 18-35 years. Ovulation was documented before treatment, and then participants received oral tablets containing LNG 90 mcg/EE 20 mcg to be taken continuously for three 28-day intervals. Ovarian activity was assessed three times per week during the treatment period with transvaginal ultrasound scans and measurements of serum 17beta-estradiol, progesterone, follicle-stimulating hormone and luteinizing hormone concentrations. Safety assessments included physical examinations, laboratory evaluations and adverse event records. RESULTS Thirty-seven of the 58 subjects who received treatment met predefined criteria for efficacy analysis. No on-treatment ovulations occurred in the efficacy or intent-to-treat population. There was evidence of ovulation within 37 days of stopping treatment for 46 (98%) of 47 subjects evaluated posttreatment. The final subject with a history of polycystic ovarian syndrome ovulated by Day 66. The safety profile observed during this 84-day continuous regimen was similar to that seen with other low-dose oral contraceptives administered in a cyclic regimen. CONCLUSIONS The continuous LNG/EE regimen completely inhibited ovulation, with little evidence of follicular development and with rapid return of ovulatory capacity after stopping treatment.

Safety and bleeding profile of continuous levonorgestrel 90 mcg/ethinyl estradiol 20 mcg based on 2 years of clinical trial data in Canada

BACKGROUND The study was conducted to evaluate bleeding profile and safety of continuous oral contraceptive (OC) containing levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg. STUDY DESIGN Healthy women who participated at seven Canadian sites in 1-year open-label study of LNG 90 mcg/EE 20 mcg daily were eligible for this second-year extension study. Primary end points included bleeding profile and adverse events. RESULTS Seventy-nine women enrolled without interrupting pill taking; 62 (78.5%) completed. Adverse events were comparable to cyclic OC regimens, except unscheduled vaginal bleeding. Amenorrhea and absence of bleeding increased to about 80% and 90%, respectively, by Pill Pack 18. Mean (median) number of bleeding days for the last two 90-day intervals was 1.1 (0) and 0.7 (0) days, respectively. CONCLUSIONS Continuous LNG 90 mcg/EE 20 mcg had a safety profile similar to low-dose cyclic OCs. Short-term safety profile remained excellent, with increasing rates of amenorrhea and decreasing incidence of unscheduled bleeding and/or spotting.