Titrated low-dose vaginal and/or oral misoprostol to induce labour for prelabour membrane rupture: a randomised trial.

OBJECTIVE: To evaluate the clinical effectiveness and safety of titrated low-dose misoprostol for induction of labour (IOL) in the presence of prelabour rupture of membranes (PROM). DESIGN: Randomised controlled trial. SETTING: Maternity units in the UK (9) and Egypt (1). POPULATION: Women >34 weeks of gestation with PROM, singleton viable fetus and no previous caesarean section. METHODS: Subjects randomised to IOL with a titrated low-dose misoprostol regimen (oral except if unfavourable cervix, where initial dose vaginal) or a standard induction method, namely vaginal dinoprostone followed by intravenous oxytocin if the cervix was unfavourable or intravenous oxytocin alone if the cervix was favourable. MAIN OUTCOME MEASURES: Primary outcome measures were caesarean section and failure to achieve vaginal delivery within 24 hours. Analysis was by intention to treat. RESULTS: The trial did not achieve the planned sample size of 1890 due to failure in obtaining external funding. Seven hundred and fifty-eight women were randomised (375 misoprostol and 383 standard). There were less caesarean section (14 versus 18%, relative risk [RR] 0.79; 95% CI 0.57-1.09) and less women who failed to achieve vaginal delivery within 24 hours in the misoprostol group (24 versus 31%, RR 0.79; 95% CI 0.63-1.00), but the differences were not statistically significant. Subgroup analysis showed that with unfavourable cervix, misoprostol may be more effective than vaginal dinoprostone. There was no difference in hyperstimulation syndrome. There were more maternal adverse effects with misoprostol, but no significant differences in maternal and neonatal complications. CONCLUSIONS: Titrated low-dose misoprostol may be a reasonable alternative for IOL in the presence of PROM, particularly in women with an unfavourable cervix. Safety and rare serious adverse events could not be evaluated in a trial of this size.

Effect of 21-day and 24-day oral contraceptive regimens containing gestodene (60 microg) and ethinyl estradiol (15 microg) on ovarian activity.

OBJECTIVE: To compare ovulation inhibition and ovarian activity with 21-day and 24-day regimens of a low-dose combined oral contraceptive (COC) containing 60 microg of gestodene and 15 microg of ethinyl estradiol. DESIGN: Interventional observational study. SETTING: Reproductive medicine unit. PATIENT(S): Fifty-eight healthy volunteers aged 18-35 years. INTERVENTION(S): Ovarian activity was monitored every other day with the use of ultrasound to measure the diameters of follicle-like structures and blood samples to measure serum concentrations of 17beta-E2 and progesterone. Subjects were observed for five cycles: pretreatment and posttreatment control cycles and three cycles in which the COC was administered for either 21 or 24 days of each cycle. MAIN OUTCOME MEASURE(S): Occurrence of ovulation and evidence of ovarian activity. RESULT(S): The study was completed by 27 (90%) of the 30 subjects who received the 24-day regimen and by 24 (79%) of the 28 subjects who received the 21-day regimen. Ovulation was inhibited in all cycles in the 24-day group and in 74 of 75 cycles in the 21-day group. Luteinized unruptured follicles were seen in no cycles with the 24-day regimen and in 6 (8%) of 75 cycles with the 21-day regimen. Mean ovarian follicular development and serum 17beta-E2 and progesterone levels were lower in the 24-day group. CONCLUSION(S): The 24-day regimen is an innovative strategy for maintaining effective ovulation inhibition at ultra-low doses of contraceptive steroids.

Why do women volunteer to participate in clinical studies?

The purpose of this study was to determine why young women volunteer to participate in clinical studies. Questionnaires were sent to 126 healthy fertile women, who during 1 year had undertaken contraceptive pill trials in the Reproductive Medicine Unit, of the University Hospital of South Manchester. An 85% response rate was obtained. Most of these women worked, were married and had children. Study recruitment was most effective by 'word of mouth', posters within the hospital not attracting many volunteers. They volunteered to take part because of the perceived financial gain from 'reasonable expenses' payable. Only 11.2% expressed a desire to assist in medical research or have their own health checked. The sex of the study investigator was not crucial to their participation; 94.4% were willing to participate in future pill trials. Therefore, when planning a clinical study requiring healthy volunteers, reasonable expenses are an essential compensation to aid the recruitment process.

Advances in oral hormonal contraception.

PIP: Researchers continue to search for newer oral contraceptive (OC) formulations that retain the pill's beneficial effects while minimizing side effects. Changes in the clinical profile of OCs since their introduction in 1960 have enhanced their safety and acceptability. Most notable has been a trend toward the reduction of the pill's estrogen dose to 15-20 mcg of ethinyl estradiol and the consequent decline in cardiovascular risks attributable to thromboembolic processes. In addition, research has been directed toward the identification of selective gonane progestins that do not have the same atherogenetic impact as their predecessors. The low-dose gonane progestins may provide protection against cardiovascular disease through their beneficial impact on lipid profile. New regimes currently under study include a 23-24-day/month use pattern to reduce follicular ripening, use of estradiol rather than ethinyl estradiol, and the identification of progestins with special anti-androgenic effects. Also under investigation is the contraceptive potential of antiprogestogens such as RU-486. At present, the non-contraceptive benefits of OC use include reductions in ovarian and endometrial cancer, fewer ovarian cysts, less benign breast disease, a lower incidence of pelvic inflammatory disease, and less menorrhagia.^ieng