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Curcumin: a potential vaginal contraceptive.

The purpose of this investigation was to evaluate the sperm-immobilizing effects of curcumin, a plant-derived diferuloylmethane compound. Washed human healthy sperm were suspended in Ham's F10 and exposed to varying concentrations of curcumin. Sperm motility was evaluated and changes in sperm mitochondrial transmembrane potential (MTP) was quantified by flow cytometry. Incubation of normal human sperm with curcumin resulted in a dose- and time-dependent loss of sperm motility. At lower concentrations (30 g/mL), curcumin produced a significant (20%) decrease in sperm motility within 30 min without significant effects on sperm viability. An instantaneous (>50%) loss of sperm motility was observed with higher concentrations (300 g/mL) of curcumin and a total loss of sperm motility was achieved within 60 min. A significant reduction in sperm MTP was found with all doses of curcumin tested. Our results indicate that curcumin has a selective sperm-immobilizing effect, in addition to a previously studied anti-HIV property. This compound may have potential clinical applications as a novel intravaginal spermicidal agent for contraception and HIV prevention.

Administration, Intravaginal↗

Outpatient misoprostol compared with dinoprostone gel for preinduction cervical ripening: a randomized controlled trial.

OBJECTIVE: To determine whether a single outpatient dose of intravaginal misoprostol (versus intracervical dinoprostone gel) reduces the oxytocin use for induction. Despite the numerous trials examining misoprostol for induction, the efficacy of a single outpatient dose of misoprostol followed by oxytocin induction is unknown. METHODS: Patients with a term, vertex, singleton pregnancy and a Bishop score of 6 or less were randomly assigned to receive misoprostol (n = 42, 0.25 microg intravaginally) or dinoprostone gel (n = 42, 0.5 mg intracervically) the evening before oxytocin induction. Patients were monitored for 3 hours after administration and discharged to home if fetal assessment was reassuring, for readmission the next morning for oxytocin. Primary outcomes were oxytocin dose, time, and dose intensity (dose divided by duration). Secondary outcomes were incidence of labor, uterine hyperstimulation, cesarean delivery, Apgar score. Statistics used were chi(2), Student t test, Mann-Whitney rank sum test, and Fisher exact test. P < .05 was accepted as statistically significant. RESULTS: A single dose of misoprostol significantly decreased the cumulative dose of oxytocin, the cumulative time of oxytocin administration, and the dose intensity of oxytocin (dose divided by time). Data are as follows (mean +/- standard error of the mean): oxytocin dose-dinoprostone 10,929 +/- 219 mU, misoprostol 6,081 +/- 170 mU, P = .008; oxytocin time-dinoprostone 798 +/- 11 minutes, misoprostol 531 +/- 11 minutes, P = .009; dose intensity-dinoprostone 11.3 +/- 0.1 mU/min, misoprostol 7.4 +/- 0.2 mU/min, P = .003. Misoprostol induced labor during the ripening period in 19 of 41 of patients, compared with 6 of 42 after dinoprostone (P = .002). There was no difference in cesarean delivery (dinoprostone, 8/42; misoprostol, 9/42; P = 1.00). There was no difference in short-term neonatal outcome. No patient had hyperstimulation or required cesarean delivery for nonreassuring fetal assessment during the ripening period. CONCLUSION: A single dose of misoprostol administered in the outpatient setting significantly decreases oxytocin use, largely due to labor within the ripening period.

Administration, Intravaginal↗

Experience with intravaginal misoprostol in the management of intra-uterine fetal death.

This collaborative study between the departments of Obstetrics and Gynaecology of the University College Hospital, Ibadan and Federal Medical Centre, Abeokuta assessed the value of intravaginal misoprostol in the management of intra-uterine fetal death. Fifty-six women at gestational ages between 17 weeks and term admitted for intra-uterine death with no contraindications to misoprostol received 400mcg of misoprostol administered intravaginally 12-hourly, until the establishment of effective uterine contractions. The mean gestational age was 27.9 weeks+/-7.1(SD) and the mean Bishop score was 2.7+/-2.4(SD). The mean duration of onset of contractions was 5.0 hours+/-8.4 (SD); the mean induction-delivery interval was 17.5 hours+/-6.3(SD). Ninety three percent of the women had expelled within 48 hours. Successful induction was achieved in all women. Prophylactic vacuum aspiration was performed (lower gestation only) in 19.6% of cases. Fever, nausea and vomiting were the commonest side effects (7.1%). Neither gestational age nor the cervical score significantly affected the insertion-contraction or induction-delivery intervals. Intra-vaginal Misoprostol at the dosage administered is safe, effective and reduces staff workload.

Abortifacient Agents, Nonsteroidal↗

Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis.

OBJECTIVE: Efficacy study of suppressive vaginal metronidazole in reducing recurrent symptomatic episodes of bacterial vaginosis. STUDY DESIGN: Multicenter prospective study with initial 10-day open-label metronidazole gel in which asymptomatic responders randomly assigned to receive twice weekly metronidazole vaginal gel or placebo for 16 weeks and off therapy for 12 weeks. RESULTS: Of 157 eligible women with recurrent bacterial vaginosis, 112 of 127 returning evaluable women (88.2%) responded clinically and were randomly assigned. During suppressive therapy, recurrent bacterial vaginosis occurred in 13 women (25.5%) receiving metronidazole and 26 (59.1%) receiving placebo (MITT analysis, relative risk [RR] 0.43, CI = 0.25-0.73, P = .001). During the entire 28-week follow-up, recurrence occurred in 26 (51.0%) on treatment compared with 33 (75%) on placebo (RR 0.68, CI = 0.49-0.93, P = .02). Probability for remaining cured was 70% for metronidazole compared with 39% on placebo, which declined to 34% and 18%, respectively, by 28 weeks follow-up. Adverse effects were uncommon; however, secondary vaginal candidiasis occurred significantly more often in metronidazole-treated women (P = .02). CONCLUSION: Suppressive therapy with twice-weekly metronidazole gel achieves a significant reduction in the recurrence rate of bacterial vaginosis; however, secondary vaginal candidiasis is common.

Administration, Intravaginal↗

Microbicides--evaluating multiple formulations of C31G.

Despite a significant worldwide need for effective microbicides to reduce sexually transmitted diseases (STD) and HIV transmission, none is currently available. C31G, a surface active anti-infective agent that is active in vitro against bacterial and viral STD pathogens, was evaluated in a 3-day, once-daily dosing clinical trial designed to assess multiple formulations for safety and acceptance. The trial used a scoring algorithm that was based on relevant subject reported symptoms and signs observed at follow-up. Differences in tolerance and acceptability between the formulations were demonstrated, as was consistency with the results from a previous 7-day trial that involved two of the formulations (1.2% HEC gel, 2.0% N-9). The 1.0% C31G co-polymer gel was the best tolerated, most acceptable formulation, and will be advanced to longer, more comprehensive trials. Thus, formulation differences are relevant to microbicide tolerance and acceptability, and the 3-day trial design validated in this study can be used to assess formulations.

Administration, Intravaginal↗

Intracervical misoprostol and prostaglandin E2 for labor induction.

OBJECTIVES: To compare the safety and efficacy of misoprostol with PGE(2) for induction of labor by intracervical administration. METHODS: Eighty-six women with indications for labor induction at term were randomly assigned to two groups. Each woman received either 50 microg of misoprostol or 0.5 mg of prostaglandin E(2) intracervically. If labor was not initiated after 4 h, the same dose was repeated every 4 h to a maximum of 200 microg of misoprostol or 1.5 mg of PGE(2) until adequate labor was achieved. RESULTS: Forty-three women were allocated to the misoprostol group and 43 to the prostaglandin E(2) group. Misoprostol was more effective than PGE(2) in producing cervical changes (P<0.025). Delivery within 12 h after the first administration occurred more often in the misoprostol group than in the PGE(2) one (85% vs. 56%, P<0.05). Less patients in the misoprostol group required oxytocin augmentation than in the PGE(2) one (16.3% vs. 39.5%, P<0.05). Uterine tachysystole and hyperstimulation occurred more frequently in the misoprostol group (44.1%) than in the PGE(2) group (18.7%) (P<0.05). Nevertheless, no statistically significant differences were noted between the two groups including mode of delivery and neonatal or maternal adverse outcome. The interval from induction to vaginal delivery was significantly shorter in the misoprostol group (480+/-172 min vs. 657+/-436 min, P<0.01). CONCLUSIONS: Compared with prostaglandin E(2), intracervical misoprostol is more effective in cervical ripening and labor induction at term. The higher frequency of uterine hypercontractility associated with the use of misoprostol did not increase the risk of adverse intrapartum and neonatal outcomes.

Administration, Intravaginal↗

[Premature termination of pregnancy in the 2nd and 3rd trimester. Serial administration of 1 mg gemeprost vaginal suppositories versus intravenous sulproston].

Comparison of 1 mg Gemeprost-Vaginal Suppositories Serial Application versus Sulproston i.v.: Three different regimens for the termination of second and third trimester pregnancies by the use of prostaglandins (PG) were compared in a retrospective analysis. In group A (n = 16) terminations were attempted by continuous i.v. Infusion of Sulproston 9 hours after administration of a 3 mg-PGE2-vaginal tablet overnight. In group B (n = 22), i.v. Sulproston was started 2 hours after priming with 1 mg Gemeprost-vaginal suppositories. The outcome of these two regimens was compared with that of repeated administration of 1 mg Gemeprost-vaginal suppositories at 6-hourly intervals (group C, n = 25). In each group. If uterine contractions failed to appear after one day, the treatment was discontinued for a sleep rest over night and then resumed. Genetic disorders or fetal malformations were the most frequent reasons for termination. Patients with intrauterine fetal demise, rupture of the membranes, preterm labour or a ripe cervix (Bishop Score > 3) were excluded. Median time intervals from induction to abortion were 33 hours in group A and 23 hours in each Group B and C. The rate of fetal expulsions within 12, 24 and 36 hours in groups B and C were similar. Women of parity > or = 1 showed significantly shorter intervals than nulliparae in groups A and C. Only one woman (in group A) failed to expel after induction, in four other cases (in groups A and B) complications (local thrombophlebitis, bronchospasm) were noted. The serial administration of 1 mg Gemeprost-vaginal suppositories at 5-hourly intervals showed fewer side effects and seems to be as efficient as sulproston i.v. after cervical ripening.

Abortifacient Agents, Nonsteroidal↗

Self-administration of vaginal misoprostol after mifepristone for termination of pregnancy: patient acceptability.

This was a questionnaire survey involving women who self-administered vaginal misoprostol in the hospital setting following oral mifepristone for medical termination of pregnancy. The sample number was 89 with a median gestational age of 9 weeks; median dose of misoprostol used was 1600 mug and median induction abortion interval was 5.3 h. The success rate was 100% with the majority finding it easy to self-administer vaginal misoprostol and two-thirds did not mind doing this. Only one-third experienced adverse effects of the medication and 83% were satisfied with the procedure. Only one-third was willing to try it at home in future if necessary. Self-administration of vaginal misoprostol for termination of pregnancy in the hospital is safe and effective. Although women were comfortable in self administering the pessaries in the hospital, they do not appear to be keen to do it at home without any supervision. However, as this is the first study in the UK involving women expressing their views regarding this issue, added research in this area is required.

Abortifacient Agents↗

Vaginal ring delivery of hormone replacement therapy--a review.

Vaginal ring delivery systems are a highly promising approach to hormone replacement therapy (HRT). The vagina is an excellent route for steroid absorption. Menopausal vaginal rings can be designed to allow very low dose local delivery of oestrogen to the vagina for the large percentage of postmenopausal women experiencing urogenital atrophy, or can be modified to deliver much higher doses sufficient for systemic oestrogen replacement therapy, with or without simultaneous progestogen release. Clinical studies of ultra-low dose rings have shown them to be as efficacious as established treatments of urogenital atrophy (creams, pessaries) and to be preferred by most users. Pharmacokinetic and limited clinical studies of vaginal rings designed to deliver systemic doses of HRT (oestrogen alone or combined) have also been highly promising. Vaginal ring delivery of HRT offers women convenient, long-acting therapy (>/= 3 months) that is under their own personal control.

Administration, Intravaginal↗

[Vaginal estriol administration in treatment of postmenopausal urinary incontinence].

In an open, prospective, multicenter, controlled study, 629 female subjects suffering from stress and urgency urinary incontinence were treated with vaginally administered estriol at a dose of 0.01 g daily for 3 weeks, and 0.01 g bi-weekly for a further 3 weeks. All data of 552 patients were available at follow-up after 6 weeks of treatment. The subjective improvement in symptoms of stress urinary incontinence (SUI) was 82% for grade 1, 77% for grade 2, and 69% for grade 3. Voluntary urinary control and symptoms of urgency were improved in more than 80% of patients. Frequency was reduced in almost 50%. Compared with conditions at the outset of the study, after 6 weeks, vaginal lubrication is normal in 77%, and intercourse is no longer painful for 88%. Objective parameters were: no change in existing descent of the anterior vaginal wall, and normal cytoscopic findings in 66% of the patients in whom these were previously pathologic. Vaginal atrophy improved in approximately 40% of cases. A quality of life score revealed improvement in 72%, no change in 20% and worsening in 9% of patients compared with conditions at the start of therapy. During therapy, symptoms worsened in 1%; 2% of patients suffered from the adverse effects, with vaginal itching and burning sensations. Our results confirm the value of topical estrogen application as a cornerstone of efficient treatment of stress and/or urge incontinence in the postmenopausal patient.

Administration, Intravaginal↗

Maternal intravaginal prostaglandin E2 gel before elective caesarean section at term to induce catecholamine surge in cord blood: randomised, placebo controlled study.

OBJECTIVE: To test the hypothesis that the application of intravaginal prostaglandin E(2) gel before elective caesarean section (ECS) will induce a catecholamine surge in umbilical arterial blood. DESIGN: Randomised, double blind, placebo controlled trial. SETTING: A regional perinatal referral centre. PATIENTS: Mothers booked for ECS at or above 38 weeks gestation. INTERVENTIONS: Thirty six consenting mothers were randomly allocated to receive either 2 mg intravaginal prostaglandin E(2) gel (study group; n = 18) or an equal volume of K-Y jelly as a placebo (control group; n = 18) 60 minutes before the ECS. Computer generated random numbers contained in coded, sealed envelopes were used for allocation. The obstetric and neonatal teams were blinded to the randomisation status of enrolled mothers. MAIN OUTCOME MEASURES: Catecholamine concentrations in the umbilical arterial blood samples collected at delivery. RESULTS: The median (interquartile range) neonatal gestation and birth weight were 271 (269-274) days and 3605 (3072-3970) g for the study group and 271 (270-273) days and 3340 (3000-3622) g for the control group. Median (interquartile range) noradrenaline (norepinephrine) concentrations in the umbilical arterial blood were significantly higher in the study group than the control group (15.9 (9.8-28.92) v 4.6 (1.65-14.4) ng/l, p = 0.03). Adrenaline (epinephrine) concentrations did not differ significantly between the two groups (1.6 (< 0.5-3.1) v 1.4 (< 0.5-2.75) ng/l, p = 0.6). No treatment related complications occurred. CONCLUSION: A labour related catecholamine surge could be simulated by intravaginal prostaglandin E(2) gel.

Administration, Intravaginal↗