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PubMed1998

A population based case-control teratologic study of oral metronidazole treatment during pregnancy.

OBJECTIVE: To study human teratogenic risk of metronidazole. DESIGN: A case-control analysis of congenital abnormalities after oral metronidazole treatment during pregnancy grouped by months of gestation. The source of information concerning the use of drugs during pregnancy was the prospective data of the women's prenatal logbook and the retrospective data of a questionnaire filled in by mothers. SETTING: The large population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1991. PARTICIPANTS: The control group involved 30,663 pregnant women who had healthy babies; the response rate was 65%. The index group consisted of 17,300 pregnant women who had offspring with congenital abnormalities from the study pregnancy; data were available for 82% of these women. RESULTS: Of 30,663 pregnant women in the control group, 1041 (3.4%) were treated with metronidazole, 162 (0.53%) in the second to third month of gestation. Of 17,300 pregnant women in the index group, 665 (3.8%) were treated with metronidazole, 104 (0.66%) in the second to third months. McNemar analysis for case-matched control pairs indicated a somewhat higher maternal metronidazole treatment in the second-third months of gestation in nine cases with cleft lip with or without cleft palate, but it was not possible to exclude the recall bias. In addition, this finding was not confirmed by the comparison of cases with cleft lip with or without cleft palate and the total control group. CONCLUSION: Treatment with oral metronidazole during pregnancy presents no clinically important association with congenital abnormalities.

Abnormalities, Drug-Induced↗
PubMed1999

Nonsurgical mid-trimester termination of pregnancy: a review of 500 consecutive cases.

OBJECTIVE: To assess the effectiveness of a regimen comprising mifepristone followed by a combination of the vaginal and oral administration of misoprostol for mid-trimester medical termination of pregnancy. DESIGN: Retrospective analysis of prospectively collected data in women undergoing mid-trimester medical termination of pregnancy. SETTING: Aberdeen Royal Infirmary, Scotland. SAMPLE: A consecutive series of 500 women with pregnancies of 13-21 weeks of amenorrhea undergoing legally induced abortion in one Scottish NHS hospital. METHODS: Each woman received a single oral dose of mifepristone 200 mg and 36-48 h later vaginal misoprostol 800 microg. Three hours following the first dose of misoprostol, 400 microg doses were administered orally at three hourly intervals, to a maximum of four doses. Success was defined as abortion occurring with five doses of prostaglandin, or within 15 h of administration of the first dose of prostaglandin. RESULTS: Ninety-seven percent aborted successfully. The median dose of misoprostol required was 1200 microg and the median induction-to-abortion interval after first prostaglandin administration was 6.5 h. The median number of doses of misoprostol required to induce abortion, and the induction-to-abortion interval, was statistically significantly higher among women at gestations 17-21 weeks than among those at 13-16 weeks (P = 0.0001). A total of 9.4% required surgical evacuation of the uterus under general anaesthesia and 66.4% of the women were managed as day cases. CONCLUSIONS: The combination of oral mifepristone 200 mg followed by vaginally and orally administered misoprostol provides a noninvasive and effective regimen for second trimester termination of pregnancy.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

Misoprostol for induction of labour: a systematic review.

OBJECTIVE: To determine, from the best available evidence, the effectiveness and safety of misoprostol administered vaginally or orally for third trimester cervical ripening or induction of labour. METHODS: Clinical trials of misoprostol used for cervical ripening or labour induction in the third trimester were identified from the register of randomised trials maintained by the Cochrane Pregnancy and Childbirth Group. All identified trials were considered for inclusion in the review according to a prespecified protocol. Primary outcomes were chosen to address clinical effectiveness (delivery within 24 hours) and safety (uterine hyperstimulation, caesarean section, serious maternal and neonatal morbidity) and were determined a priori. All meta-analyses were based on the intention-to-treat principle. In the absence of heterogeneity the summary statistics have been expressed as typical relative risk (RR) and 95% confidence interval (CI). RESULTS: Vaginal misoprostol: one small study showed that the use of misoprostol results in more effective cervical ripening and reduced need for oxytocin when compared with placebo. When compared with oxytocin, vaginal misoprostol was more effective for labour induction. The relative risk of failure to achieve vaginal delivery within 24 hours was 0.48 (95% CI 0.35 to 0.66). However, the relative risks for uterine hyperstimulation with and without fetal heart rate abnormalities were 2.54 (95% CI 1.12 to 5.77) and 2.96 (95% CI 2.11 to 4.14), respectively. In three out of four trials which studied women with intact membranes and unfavourable cervices, failure to achieve vaginal delivery within 24 hours was reduced with misoprostol when compared with other prostaglandins (RR 0.71, 95% CI 0.62 to 0.81). Vaginal misoprostol was associated with increased uterine hyperstimulation both without fetal heart rate changes (RR 1.67, 95% CI 1.30 to 2.14) and with associated fetal heart rate changes (RR 1.45, 95% CI 1.04 to 2.04). There was also an increase in meconium stained amniotic fluid following vaginal misoprostol (RR 1.38, 95% CI 1.06 to 1.79). Oral misoprostol: one small trial suggests that, when compared with placebo, oral misoprostol reduces the need for oxytocin and shortens the time between induction and delivery. Compared with other prostaglandins one small trial showed a reduced need for oxytocin with oral misoprostol. Two trials compared oral with vaginal misoprostol using different doses. No significant differences were evident. CONCLUSIONS: Overall, misoprostol appears to be more effective than conventional methods of cervical ripening and labour induction. Although no differences in perinatal outcome were shown, the studies were not sufficiently large to exclude the possibility of uncommon serious adverse effects. In particular the increase in uterine hyperstimulation with fetal heart rate changes following misoprostol is a matter for concern. It is possible that, if sufficient numbers are studied, an unacceptably high number of serious adverse events including uterine rupture and asphyxial fetal deaths may occur. The data at present are not robust enough to address the issue of safety. Thus, though misoprostol shows promise as a highly effective, inexpensive and convenient agent for labour induction, it cannot be recommended for routine use at this stage. Lower dose misoprostol regimens should be investigated further.

Administration, Intravaginal↗
PubMed2001

A comparison of oral and vaginal misoprostol for induction of labour at term: a randomised trial.

OBJECTIVE: To compare the efficacy of oral with vaginal misoprostol for induction of labour at term. DESIGN: Randomised trial. SETTING: Tertiary Care hospital. PARTICIPANTS: One hundred and sixty-seven women requiring induction of labour. METHODS: The women were randomised to receive 50 microg of misoprostol orally or vaginally every 6 h until the cervix was favourable for amniotomy, spontaneous rupture of membranes, or active labour occurred. Sample size was calculated with a two-tailed alpha of 0.05 and a power of 95% to detect a 5 h difference in induction-to-delivery time. Student's t test was used for comparison of normally distributed continuous variables and the Mann-Whitney U test was used for non-Gaussian distributed continuous variables. Fisher' s exact and chi2 tests were used for comparison of categorical variables. The main outcome measure was induction to delivery time. RESULTS: The median induction to delivery time was significantly shorter with vaginal misoprostol (15.7 h range 4.3-55.7), compared with oral misoprostol (23.0 h range 3.2-141.7, P = 0.0013). The median number of doses was also significantly less in the vaginal misoprostol group, 1 (range 1-3), compared with the oral group, 2 (range 1-8), (P < 0.0001). The significant differences in outcome held true when nulliparous and multiparous women were analysed separately. There were no differences between the two routes of administration with respect to rates of hyperstimulation or neonatal asphyxia. There were more caesarean sections in the vaginal misoprostol group, but the difference was not statistically significant. CONCLUSIONS: Compared with oral misoprostol, vaginal misoprostol for induction of labour at term results in a shorter induction-to-delivery time, with fewer doses required per patient. Vaginal misoprostol may be associated with higher rates of caesarean section than oral misoprostol.

Administration, Intravaginal↗
PubMed2001

A comparison of oral and vaginal misoprostol tablets in induction of labour at term.

OBJECTIVE: To compare the efficacy of equivalent doses of orally administered with vaginally administered misoprostol in induction of labour at term. DESIGN: A non-blinded randomised controlled trial. SETTING: Induction and labour wards of a UK teaching hospital. PARTICIPANTS: Two hundred and forty-five pregnant women at term, with medical or obstetric indications for labour induction and unfavourable cervices. METHODS: The women were randomly assigned to receive 50 microgm of misoprostol orally or vaginally four hourly to a maximum of five doses. MAIN OUTCOME MEASURES: Interval from induction to vaginal delivery, mode of delivery, oxytocic and analgesic requirements in labour, neonatal outcome, patient satisfaction and acceptability. RESULTS: The mean induction to vaginal delivery interval was significantly shorter in the vaginal group compared with the oral group (17.8h vs 27.9h: mean difference 10.1 hrs, 95% CI 5.8-14.4). More women were delivered within 24 hours (80% vs 46.3%; RR 1.7, 95% CI 1.3-2.1) and fewer women needed oxytocin augmentation (39% vs 58.2%; RR 0.67, 95% CI 0.5-0.9) in the vaginal group. There was no difference in the mode of delivery, analgesic requirements or neonatal outcomes in the two groups. There was a higher incidence of uterine hyperstimulation in the vaginal group (4.9% vs 0.8%, RR 6, 95% CI 0.07-48.7) and more caesarean sections were performed for fetal distress in this group (13% Vs 2.4%, RR 5.3, 95% CI 1.6-17.7), although the overall operative delivery rate was similar in the two groups. CONCLUSION: Misoprostol effectively induces labour, with the vaginal route of administration having a faster action than the oral route in equivalent doses. However, the more frequent occurrence of hyperstimulation and the higher intervention rate for fetal distress in the vaginal group could mean that the preferred route might be oral. More trials are needed to find the right oral dosage that combines efficacy with safety.

Administration, Intravaginal↗
PubMed2001

Titrated oral misoprostol solution for induction of labour: a multi-centre, randomised trial.

OBJECTIVES: To determine the effects of titrated oral misoprostol solution, compared with vaginal dinoprostone. STUDY DESIGN: Open, randomised clinical trial. SETTING: Academic hospitals in South Africa and Liverpool, UK. METHODS: Women undergoing induction of labour after 34 weeks of pregnancy were allocated by randomised, sealed opaque envelopes, to induction of labour with titrated oral misoprostol solution, or two doses of vaginal dinoprostone (2mg) administered six hours apart. Failure to deliver within 24 hours of randomisation was the primary outcome on which the sample size was based. The data were analysed by intention-to-treat. RESULTS: Six hundred and ninety-five women were randomly allocated: 346 to oral misoprostol and 349 to vaginal dinoprostone. There were no significant differences in substantive outcomes. Vaginal delivery within 24 hours was not achieved in 38% of women in the oral misoprostol group and 36% in the vaginal dinoprostone group (RR 1.08; 95% CI 0.89-1.31). The caesarean section rates were 16% and 20%, respectively (RR 0.80; 95% CI 0.58-1.11). Hyperstimulation with fetal heart rate changes occurred in 4% of women in the oral misoprostol group and 3% after vaginal dinoprostone (RR 1.32, 95% CI 0.59-2.98). The response to induction of labour in women with unfavourable cervices was somewhat slower with misoprostol when membranes were intact, and with dinoprostone when membranes were ruptured. There were no differences in neonatal outcome between the two groups. CONCLUSIONS: This new approach to oral misoprostol administration was successful in minimising the risk of uterine hyperstimulation, which has been a feature of misoprostol use for induction of labour, at the expense of a somewhat slower response in women with intact membranes and unfavourable cervices. Misoprostol is not registered for use in pregnant women, and further research is needed to confirm optimal and safe dosages.

Administration, Intravaginal↗
PubMed2002

Medical management of early fetal demise using sublingual misoprostol.

The aim of this study was to determine the efficacy of mifepristone in combination with sublingual misoprostol for the medical management of early fetal demise. Fifty-six consecutive women were studied prospectively. The mean (SD) gestation at diagnosis was 9.6 weeks (1.84). Four women had complete miscarriage with mifepristone alone. The overall success rate was 83.9% and the median induction-miscarriage interval was 8.19 hours (range 0.83 to 37.50 hours). Of those women who had a successful outcome, 91.5% were satisfied with the regimen. Sublingual misoprostol in combination with mifepristone is an effective and safe alternative to vaginal or oral misoprostol in the management of early fetal demise.

Abortifacient Agents, Nonsteroidal↗
PubMed2002

Oral versus intra-vaginal imidazole and triazole anti-fungal agents for the treatment of uncomplicated vulvovaginal candidiasis (thrush): a systematic review.

OBJECTIVES: To compare the relative effectiveness, cost effectiveness and safety of oral versus intra-vaginal anti-fungal treatments for uncomplicated vulvovaginal candidiasis (thrush) and establish patient preference for the route of anti-fungal administration. DESIGN: A systematic review of studies comparing oral and intra-vaginal anti-fungal treatments for uncomplicated vulvovaginal candidiasis. Standard Cochrane Collaboration methods were used. DATA SOURCES: The following sources were searched: the Cochrane Controlled Trials Register; the Cochrane Sexually Transmitted Disease review group Specialised Register of Controlled Trials; EMBASE (January 1980 to January 2000); and MEDLINE (January 1985 to May 2000). The reference list of each trial was checked for additional references. The manufacturers of anti-fungal treatments in the UK were asked for information on trials fulfilling the inclusion criteria. METHODS: There was duplicate, independent examination and selection of the electronic search results followed by duplicate data abstraction. Disagreements regarding inclusion status and data abstraction were resolved by discussion between reviewers and the editor of the Cochrane Sexually Transmitted Disease group. Randomised controlled trials conducted worldwide and published in any language were included. The primary outcome measure was clinical cure. Mycological cure, patient preference and safety were secondary outcome measures. RESULTS: Seventeen trials were included in the review, reporting 19 oral versus intra-vaginal anti-fungal treatment comparisons. No statistically significant differences were shown between oral and intra-vaginal anti-fungal treatment for clinical or mycological cure. All 10 trials that reported a preference favoured oral treatment (compared with intra-vaginal or no preference). No trials presented cost data. CONCLUSIONS: There is no difference between the relativeeffectiveness of oral and intra-vaginal anti-fungal treatment for thrush.

Acute Disease↗
PubMed2002

Intrauterine 10 microg and 20 microg levonorgestrel systems in postmenopausal women receiving oral oestrogen replacement therapy: clinical, endometrial and metabolic response.

OBJECTIVE: The clinical and endometrial efficacy and lipid response of two different doses of intrauterine levonorgestrel were assessed in comparison with sequential oral medroxyprogesterone acetate in postmenopausal women receiving continuous oral E2-valerate. DESIGN: One-year prospective multicentre randomised control trial. SETTING: Four outpatient clinics in Oulu, Helsinki and Jyväskylä, Finland. POPULATION: A total of 163 healthy volunteer postmenopausal women with climacteric complaints or already using hormone replacement therapy (HRT). INTERVENTIONS: Subjects were randomly allocated to receive a new intrauterine system releasing 10 microg of levonorgestrel daily or an established intrauterine system (Mirena) releasing 20 microg of levonorgestrel daily or sequential oral medroxyprogesterone acetate (5mg/day, 14/30 days). All three regimens were combined with an oral daily dose of 2mg of E2-valerate. MAIN OUTCOME MEASURES: Bleeding patterns were assessed by diaries kept by the subjects. Endometrial effects were evaluated by histologic biopsies taken at the baseline and after six and 12 months of therapy. Serum concentrations of total, HDL and LDL cholesterol, triglycerides and lipoprotein(a) were determined at the baseline and after six and 12 months of therapy. RESULTS: Insertion of the smaller 10 microg levonorgestrel system was easy in 70% and difficult in 4% and that of Mirena was easy in 46% and difficult in 21% of the subjects. After six months of therapy, 43 (95.6%) of the 47 subjects receiving 10 microg levonorgestrel and 54 (98.2%) of the 55 subjects receiving 20 microg levonorgestrel had no bleeding, while the sequential medroxyprogesterone acetate regimen produced typical cyclic withdrawal bleedings. Endometrial hyperplasia was not observed in any of the treatment groups during the 12-month study. After 12 months of therapy, strong endometrial suppression was found in 46/47 and 55/55 of the subjects receiving 10 microg and 20 microg of levonorgestrel, respectively, while the endometrium was proliferative in 18/47 of the subjects in the medroxyprogesterone acetate group. Serum total cholesterol decreased in all treatment groups. HDL cholesterol increased in women receiving medroxyprogesterone acetate or the smaller intrauterine dose of levonorgestrel. CONCLUSIONS: Both intrauterine doses of levonorgestrel provided good endometrial protection in postmenopausal women on oestrogen replacement therapy. The advantage of the 10 microg system with a smaller size is the easier insertion of the system and a minimal attenuation of the favourable effects of oral oestrogen on the serum lipid profile.

Administration, Intravaginal↗
PubMed2004

A randomised comparison of oral misoprostol and vaginal prostaglandin E2 tablets in labour induction at term.

OBJECTIVE: To compare the efficacy of 100 microg of oral misoprostol with 3 mg prostaglandin E2 vaginal tablets in term labour induction. DESIGN: A non-blinded, randomised, controlled trial. SETTING: A tertiary level, teaching Scottish Hospital. POPULATION: Two hundred women at term with indications for labour induction and modified Bishop's cervical score of less than 8. METHODS: The women were randomly allocated to receive either 100 microg of misoprostol orally (which could be repeated 4 hourly to a maximum of five doses if indicated), or a 3 mg tablet of prostaglandin E2 vaginally (which could be repeated in 6 hours, according to routine departmental protocol). MAIN OUTCOME MEASURE: The number delivering vaginally within 24 hours of the induction. RESULTS: Seventy-five women delivered vaginally in the misoprostol group and 73 in the PGE2 group. Of these, 50.7% in the misoprostol group and 54.8% in the PGE2 group delivered within 24 hours of the induction (RR 0.92, 95% CI 0.7 to 1.3). More women in the misoprostol group were given oxytocin, but this was not statistically significant (60%vs 47%, RR 1.3, 95% CI 0.98 to 1.7). Two women in the misoprostol group had uterine hyperstimulation. The neonatal outcomes were not significantly different in the two groups. There was a pound 1100 saving on direct drug costs in the misoprostol group. CONCLUSIONS: Oral misoprostol (100 microg) has similar efficacy to vaginal PGE2 tablets, and may be an option to consider for term labour induction.

Administration, Intravaginal↗
PubMed2004

A prospective randomised comparison of sublingual and vaginal misoprostol in second trimester termination of pregnancy.

OBJECTIVE: To compare the efficacy, side effects and acceptability of sublingual and vaginal misoprostol for second trimester medical abortion. DESIGN: Prospective randomised controlled trial. SETTING: Tertiary referral unit and a teaching hospital. POPULATION: Two hundred and twenty-four women at 12 to 20 weeks of gestation. METHODS: The women were randomised to receive either sublingual or vaginal misoprostol 400 microg every 3 hours for a maximum of five doses. The course of misoprostol was repeated if the woman did not abort within 24 hours. MAIN OUTCOME MEASURES: The success rate at 48 hours, induction-to-abortion interval and the side effects. RESULTS: There was no significant difference in the success rate at 48 hours (sublingual: 91%; vaginal: 95%). However, the success rate at 24 hours was significantly higher in the vaginal group (85%) compared with the sublingual group (64%). There was no difference in the median induction-to-abortion interval (sublingual: 13.8 hours; vaginal: 12.0 hours). Significantly more women in the sublingual group preferred the route to which they were assigned when compared with the vaginal group. The incidence of fever was also less in the sublingual group. CONCLUSION: The use of vaginal misoprostol for second trimester medical abortion resulted in a higher success rate than sublingual misoprostol at 24 hours but the abortion rate was similar at 48 hours. Vaginal misoprostol should be the regimen of choice but sublingual misoprostol is also an effective alternative.

Abortifacient Agents, Nonsteroidal↗
PubMed2005

Oral versus vaginal misoprostol administered one hour before surgical termination of pregnancy: a randomised controlled trial.

OBJECTIVE: To assess the efficacy of oral and vaginal misoprostol as cervical priming agents administered 1 hour before first trimester surgical termination of pregnancy. DESIGN: A randomised controlled trial. SETTING: Chelsea and Westminster Hospital, London. POPULATION: Pregnant women of 10 weeks or less gestation attending the termination of pregnancy clinic. METHODS: Ninety eligible women were recruited to the study during September 2001 and September 2002. Women were randomised to one of the three groups: misoprostol administered orally (400 microg), misoprostol administered vaginally (800 microg) and standard care (no cervical priming agent) administered prior to surgical termination of pregnancy. Under general anaesthesia, and prior to the operation, a cervical tonometer was used to determine the main outcome measures. MAIN OUTCOME MEASURES: Baseline cervical dilatation and the cumulative force required to dilate the cervix from 3 to 9 mm. RESULTS: There was no significant difference in the mean baseline cervical dilation (P= 0.16) or the cumulative force required to dilate the cervix (P= 0.12) between the three randomised groups. CONCLUSION: No cervical priming effects were detectable with oral or vaginal misoprostol administered 1 hour before first trimester surgical termination of pregnancy.

Abortifacient Agents, Nonsteroidal↗
PubMed2005

A randomised controlled trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion up to 13 weeks of gestation.

OBJECTIVE: To assess women's acceptability, the efficacy and side effects of sublingual versus vaginal administration of misoprostol in combination with mifepristone for medical abortion up to 13 weeks of gestation. DESIGN: Randomised controlled trial. SETTING: Aberdeen Royal Infirmary. POPULATION: Women undergoing medical abortion under the terms of the 1967 Abortion Act. METHODS: Mifepristone (200 mg) was given orally followed 36-48 hours later by misoprostol administration (sublingual: 600 microg; vaginal: 800 microg). A second dose of misoprostol 400 microg was given 3 hours later (sublingually or vaginally). Women between 9 and 13 weeks of gestation received a further (third) dose of misoprostol 400 microg (sublingually or vaginally), 3 hours later if abortion had not occurred. MAIN OUTCOME MEASURES: Women's acceptability, efficacy of the regimen and side effects experienced. RESULTS: A total of 340 women were recruited (171 sublingual and 169 vaginal). A total of 70% of women in the sublingual group expressed satisfaction with the route of misoprostol administration; 18% answered 'Don't know' while 12% were dissatisfied, compared with 68%, 28% and 4%, respectively, in the vaginal group (P= 0.02). There was no significant difference in the need for surgical evacuation for women in the sublingual (3/158, 1.9%) and vaginal groups (4/156, 2.6%) (P= 0.70). Women receiving misoprostol sublingually were more likely to experience diarrhoea (P < 0.01), shivering (P < 0.01) and unpleasant mouth taste (P < 0.01). CONCLUSIONS: Sublingual administration of misoprostol is an effective alternative to vaginal administration for medical abortion up to 13 weeks of gestation. The prevalence of prostaglandin-related side effects, however, was higher with this route of administration.

Abortifacient Agents, Nonsteroidal↗
PubMed2006

Oral versus self-administered vaginal misoprostol at home before surgical termination of pregnancy: a randomised controlled trial.

OBJECTIVE: To compare the impact of 400 mug oral versus self-administered vaginal misoprostol at home on pre-operative cervical priming in both primigravid and multigravid women prior to first trimester surgical abortion. DESIGN: Randomised controlled trial. SETTING: Norwegian University Teaching Hospital. SAMPLE: Three hundred and thirty-eight women undergoing surgical abortion between 7 and 12 weeks of gestation. METHODS: The women were randomised to either 400 microg of oral misoprostol the evening before or 400-microg of self-administered vaginal misoprostol at home the same day as vacuum aspiration. Main outcome measures Pre-operative cervical dilatation, complications and acceptability. RESULTS: The median cervical dilatation was 6.2 mm (range 0-11 mm) for the women in the 400 mug oral misoprostol and 6.5 mm (range 0-11 mm) in the 400-microg vaginal misoprostol groups. The median pre-operative dilatation was larger in multigravidae (6.4 and 6.7 mm for the oral and vaginal routes, respectively) than in primigravidae (5.8 and 6.0 mm, respectively). In primigravidae, 19% achieved a pre-operative dilatation of > or = 7 mm, with no significant difference between oral and vaginal dosage. In multigravidae, 52% achieved a pre-operative dilatation of > or = 7 mm with vaginal dosage, compared with 36% with oral dosage (P = 0.03). There was no difference between non-immigrant versus immigrant women in pre-operative cervical dilatation. The 400-microg oral dosage group had a higher risk of bleeding, compared with the group receiving 400-microg vaginal misoprostol [odds ratio (OR) = 10.4; confidence interval (CI) 5.2-20.8]. There was no difference between non-immigrant and immigrant women in acceptability of self-administered vaginal misoprostol; almost all women found this administration route acceptable. Complications were minor and were distributed equally between the two dosage groups. CONCLUSIONS: The vaginal route will result in a satisfactory dilatation in about half of multigravidae but is much less effective in primigravidae. The oral route does not lead to satisfactory dilatation in either group and is associated with a higher occurrence of pre-operative bleeding. Self-administered vaginal misoprostol at home is highly acceptable.

Abortifacient Agents, Nonsteroidal↗
PubMed2006

Sublingual compared with vaginal misoprostol for labour induction at term: a randomised controlled trial.

OBJECTIVE: To compare the efficacy and safety of 50 microg of sublingual misoprostol with 25 microg of vaginal misoprostol administered for labour induction at term. Design Double-blinded, randomised controlled trial. Setting University Hospital, Kaunas, Lithuania. Sample A total of 140 women at term with indications for labour induction. Methods Women were randomised to receive either 50 microg of sublingual misoprostol with vaginal placebo (n = 70) or sublingual placebo with 25 microg of vaginal misoprostol (n = 70) every 4 hours (maximum six doses). Main outcome measures The number of women delivering vaginally within 24 hours of labour induction. Results Fifty-eight women (83%) in the sublingual misoprostol group and 53 (76%) in the vaginal misoprostol group delivered vaginally within 24 hours [relative risk (RR) 1.1, 95% confidential interval (CI) 0.9-1.3]. However, the induction to vaginal delivery time was significantly shorter in the sublingual group (15.0 +/- 3.7 hours) compared with the vaginal group (16.7 +/- 4.1 hours, P = 0.03). The incidence of tachysystole was more than three-fold higher in the sublingual than in the vaginal group (14 versus 4.3%; RR 3.3, 95% CI 0.9-11.6), but this was not statistically significant. There were no significant differences in the incidence of hypertonus or hyperstimulation syndrome, mode of delivery, interventions for fetal distress or neonatal outcomes between the two groups. Conclusion A 50 microg of sublingual misoprostol 4 hourly for labour induction at term seems to have similar efficacy as 25 microg of vaginal misoprostol. Further studies on safety with larger numbers of women need to be conducted before routine sublingual misoprostol use in this setting.

Administration, Intravaginal↗
PubMed2006

Misoprostol compared with prostaglandin E2 for labour induction in women at term with intact membranes and unfavourable cervix: a systematic review.

BACKGROUND: Misoprostol is a commonly used prostaglandin to induce labour. A potential risk of induction, however, is caesarean delivery, especially in women with an unfavourable cervix. OBJECTIVES: To evaluate the use of misoprostol, compared with prostaglandin E2 (PgE2), for labour induction in women at term with an unfavourable cervix and intact membranes. SEARCH STRATEGY: PubMed, Medline, EMBASE and the Cochrane Library were searched for articles published in any language from January 1987 to December 2005, using the keywords 'misoprostol', 'labour/labor' and 'induction'. SELECTION CRITERIA: We identified randomised trials of women at term (> or =37 weeks of gestation) with intact membranes and unfavourable cervix, undergoing labour induction with misoprostol, orally, vaginally, sublingually or buccally, compared with PgE2 vaginally or intracervically. DATA COLLECTION AND ANALYSIS: Caesarean delivery was the primary outcome, with tachysystole and hyperstimulation as secondary outcomes. The primary analysis compared any misoprostol with any PgE2 for all women, with a subgroup analysis for nulliparous women. Secondary analyses compared different routes and doses of misoprostol (oral or vaginal and 25 microgram or >25 microgram) and PgE2 (intracervical or vaginal). Relative risks (RR) and 95% confidence intervals (CI) were calculated using random effects models. Main results Fourteen of 611 articles identified met the criteria for systematic review, with three providing information for nulliparous women. There was no difference in the risk of caesarean delivery between misoprostol and PgE2 groups (RR = 0.99, 95% CI = 0.83-1.17). Any misoprostol was associated with higher risks of tachysystole and hyperstimulation compared with any PgE2 (RR = 1.86, 95% CI = 1.01-3.43 and RR = 3.71, 95% CI = 2.00-6.88, respectively). There was a higher rate of vaginal delivery within 24 hours among all vaginal deliveries with any misoprostol compared with any PgE2 (RR = 1.14, 95% CI = 1.00-1.31), and among all deliveries, a lower rate of oxytocin use (RR = 0.71, 95% CI = 0.60-0.85) but a trend towards increased meconium staining was observed (RR = 1.22, 95% CI = 0.96-1.55). The use of misoprostol at starting dosages >25 microgram had similar findings to the primary analysis. Studies of lower misoprostol dosing (starting dose of 25 microgram) did not show any differences in the outcomes of interest, but the sample size of this secondary analysis was small (304 women, 155 receiving misoprostol). AUTHOR'S CONCLUSIONS: Although misoprostol in women at term with an unfavourable cervix and intact membranes was more effective than PgE2 in achieving vaginal delivery within 24 hours, misoprostol does not reduce the rate of caesarean delivery either in all women or in the subgroup of nulliparous women, and it increases the rates of tachysystole and hyperstimulation. Further studies of misoprostol using a starting dose of 25 microgram may be warranted.

Administration, Intravaginal↗
PubMed1980

Evidence for the metabolic activation of non-steroidal antioestrogens: a study of structure-activity relationships.

1 The oestrogenic and antioestrogenic activities of tamoxifen and monohydroxytamoxifen have been compared with those of para-methoxy, -methyl, -fluoro, and -chloro tamoxifen in the 3 day immature rat uterine weight test.2 The oestrogenic activity of mestranol, a steroid with low oestrogen receptor binding affinity which is believed to be demethylated to ethinyl oestradiol before exerting its effects, was less potent than ethinyl oestradiol when assayed in the 3 day immature rat uterine weight test. Similarly, para-methoxytamoxifen was less active than monohydroxytamoxifen in oestrogenic and antioestrogenic tests.3 The introduction of a para-methoxy group into tamoxifen did not affect oestrogenic or antioestrogenic activity.4 All the derivatives of tamoxifen were partial oestrogen agonists when compared with oestradiol benzoate in the 3 d immature rat uterine weight test. All test compounds inhibited the uterotrophic activity of oestradiol benzoate (0.16 mug daily) in a dose-related manner. The order of potency was: monohydroxytamoxifen > tamoxifen identical with methoxytamoxifen > p-fluoro identical with p-chloro identical with p-methyltamoxifen.5 Tamoxifen was approximately equiactive with its p-methyl, p-fluoro and p-chloro derivatives in the ability to inhibit [(3)H]-oestradiol binding to rat uterine oestrogen receptors in vitro.6 Tamoxifen was approximately equiactive with its p-methyl and p-fluoro derivatives in the ability to inhibit vaginal cornification of ovariectomized rats upon intravaginal administration with oestradiol (3.2 ng total dose).7 Since tamoxifen in vivo was more active as a partial oestrogen agonist and antagonist than the para substituted fluoro, chloro and methyl derivatives that cannot undergo metabolic hydroxylation to monohydroxytamoxifen, whereas the antioestrogenic activity of the compounds upon local application in the vaginal cornification test was equivalent as was their ability to inhibit [(3)H]-oestradiol-17beta binding to the oestrogen receptor in vitro, it is suggested that at low doses; i.e. over the range of the partial agonist dose-response curve, the biological activity of tamoxifen is the net result of the activities of the parent compound and its metabolites.8 The results demonstrate that metabolic activation of non-steroidal antioestrogens is only an advantage and not a requirement for antioestrogenic activity.

Animals↗