Vaginal misoprostol for cervical priming before dilatation and curettage in postmenopausal women: a randomized controlled trial

AIM: To investigate the efficacy of vaginal misoprostol for cervical priming before dilatation and curettage in postmenopausal women. METHODS: Forty-four postmenopausal women with indication for dilatation and curettage were randomly assigned to receive either 400 micro g of misoprostol or placebo vaginally 6 h before dilatation and curettage. The main outcome measures were the number of women who required cervical dilatation, cervical width, time taken to dilate to Hegar 6 and other complications. RESULTS: The mean cervical diameter (4.59 millimeters in the misoprostol group vs 4.41 millimeters in the placebo group) was comparable between the two groups. A similar number of women in the misoprostol group and in the placebo group required cervical dilatation (12 vs 16, P = 0.35). The operative times for both groups were similar. The incidence of side-effects was comparable in both groups. There were two uterine perforations in the misoprostol group (2 vs 0). CONCLUSION: There was no significant benefit from applying 400 micro g vaginal misoprostol 6 h prior to dilatation and curettage in postmenopausal women.     

Utility of misoprostol for labor induction in severe pre-eclampsia and eclampsia

OBJECTIVES: To determine the effectiveness and safety of misoprostol in severe pre-eclampsia and eclampsia patients with unripe cervix. METHODS: A prospective observational study was carried out in 135 severe pre-eclampsia and eclampsia patients who required termination of pregnancy at the Department of Obstetrics and Gynecology, Khulna Medical College Hospital, Khulna, Bangladesh during January 2002 to October 2003. Fifty micrograms of misoprostol was used every 4 h in cases of unripe cervix (Bishop score < or = 6) in severe pre-eclampsia and eclampsia patients. Maternal and perinatal outcome as well as any complications were recorded. RESULTS: In severe pre-eclampsia and eclampsia patients vaginal delivery occurred in 79.3 and 80.5% of cases, and cesarean section was performed in 20.6 and 19.4% of cases, respectively. The maximum required responsive dose was 50-150 microg. Oxytocin augmentation was required in 29.3 and 35% of cases, respectively. Induction to delivery time was median 8 h, interquartile ranges 4.2-8.2 h in the severe pre-eclampsia group, and median 9 h, interquartile ranges 6.8-12.5 h in the eclampsia group, and average hospital stay was 3.4 +/- 1.8 and 3.7 +/- 1.7 days, respectively. The only maternal complications were hyperstimulation which occurred in 6.8 and 5.1% of cases, respectively. Neonatal death occurred in five (11.3%) and eight cases (12.1%), respectively. CONCLUSION: Intravaginal misoprostol is well tolerated and very effective for the induction of labor in severe pre-eclampsia and eclampsia patients with unripe cervix.     

Misoprostol in labour induction of term pregnancy: a meta-analysis

Objective To evaluate the efficacy and safety of misoprostol in term labour induction. Data sources Data from published English and Chinese literatures about misoprostol in term labour induction were identified from Medline and CBMdisk (using the search terms “misoprostol” and “labour induction”) before 2001; hand searches of reference lists of original studies and reviews (including meta-analyses) and contact with investigators in this field before 2001. Study selection Studies were included if they had data on misoprostol and labour induction. Altogether 623 articles were found and 124 were admitted, including 19 287 cases. Data extraction Data were collected on efficacy and incidence of side-effects of misoprostol and oxytocin. Data were checked for consistency within the published articles and converted into a standard format for incorporation into a central database. Data synthesis The average successful induction rate, rates of caesarean section; incidence of tachysystole, hypertonus of uterus and precipitous labour, and rates of meconium stained amniotic fluid between the misoprostol and oxytocin groups were significantly different (P&lt;0.05). There were no significant differences between the two groups concerning the average interval from the administration of misoprostol and oxytocin to the onset of labour, duration of the total stage of labour, incidence rate of foetal distress, neonatal asphyxia (1-minute Apgar score≤7), postpartum haemorrhage or amount of blood loss in postpartum.Conclusions Misoprostol is a superior agent over oxytocin on the induction of term labour, but its application might increase the risk of precipitatous labour, abnormal uterine contractions or meconium stained amniotic fluid. Therefore, the doasges and regimens of the agent need further investigation.     

Sustained Intravesical Drug Delivery Using Thermosensitive Hydrogel

PURPOSE: Direct instillation of drug solutions into the bladder through a urethral catheter (i.e., intravesical therapy) evades systemic adverse effects of drugs used for bladder diseases. However, conventional vehicles for these drugs fail to extend duration of drug exposure in the bladder beyond the first voiding of urine postinstillation. The current study seeks to overcome the aforementioned inherent limitation of intravesical drug administration by using thermosensitive hydrogel as a matrix for sustained intravesical drug delivery. METHODS: Under halothane anesthesia, normal adult female Sprague-Dawley rats were catheterized with PE-50 tubing to instill either 0.02% w/v solution of fluorescein isothiocyanate (FITC) or the same amount of FITC in a 30% w/v dispersion of thermosensitive [Poly(ethylene glycol)-Poly[lactic acid-co-glycolic acid]-Poly(ethylene glycol)) (PEG-PLGA-PEG) polymer in a 0.1 M phosphate buffer. After instillations, rats were kept in metabolic cages for urine collection. Fluorescence emanating from FITC was measured in the urine at various time points up to 24 h after instillation. A rat model of cyclophosphamide-induced cystitis was chosen for the efficacy study using misoprostol as a model drug entrapped in the thermosensitive hydrogel in place of FITC. Efficacy of hydrogel containing misoprostol was compared against rat groups instilled with saline, hydrogel, and misoprostol independently. RESULTS: Prolonged drug exposure to the bladder afforded by hydrogel was evident from the time course of FITC elimination in the urine and by the green fluorescence of FITC seen at the bladder surface when isolated 24 h after instillation. Rats instilled with free FITC voided almost all of the fluorescence in the urine within the first 8 h, whereas rats instilled with hydrogel encapsulated FITC showed sustained release up to 24 h after instillation. Using a cyclophosphamide-induced cystitis model, rats instilled with misoprostol, a synthetic PGE1 analog, showed significantly reduced frequency of urine voiding (p < 0.05) as compared to the rats instilled with saline. Histological examination of the urothelium showed near normal morphology in rats instilled with misoprostol in hydrogel, whereas extensive tissue damage was observed in rats instilled with saline. CONCLUSION: Our study showed that PEG-PLGA-PEG polymer could be used as a viable sustained drug delivery system for intravesical therapy of diseases of the bladder such as cystitis using misoprostol.     

A novel approach to intertriplet birth weight discordance

OBJECTIVE: This study was undertaken to evaluate intertriplet birth weight discordance. STUDY DESIGN: Birth weight discordance greater than 25% was evaluated in a cohort of 2804 US live-born triplets. Symmetric and high- and low-skew sets were defined by the rank of the middle triplet between the heavier and the lighter triplets. Frequencies of discordance level and type were analyzed by gestational age, parity, and total triplet birth weight. RESULTS: Discordance of 25.1% to 35% and greater than 35% was found in 19.4% and 9.5% of the triplets analyzed, respectively. Frequencies of greater than 25% discordant sets demonstrated polynomial relationship to gestational age (R (2) = 0.94, P <.001) total triplet birth weight deciles (R (2) = 0.97, P <.001). Frequencies of discordance type are unchanged throughout gestation. CONCLUSION: Birth weight discordance in triplets is frequent and large and implies exhaustion of fetal growth potential despite a uterine environment that appears to perform at maximal effort in these pregnancies.     

Use of a single preoperative dose of misoprostol is efficacious for patients who undergo abdominal myomectomy

OBJECTIVE: To investigate the effectiveness of a single preoperative dose of misoprostol in abdominal myomectomies. DESIGN: Placebo-controlled randomized prospective study. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): Twenty-five women with symptomatic uterine leiomyomas. INTERVENTION(S): Among patients undergoing abdominal myomectomies, an hour before the operation women in the study group (n = 13) were given a single dose of vaginal misoprostol (400 microg); those in the control group (n = 12) were given placebo. MAIN OUTCOME MEASURE(S): Intraoperative blood loss, duration of operation, duration of postoperative hospitalization, and the need for blood transfusion were compared between the control and study groups. RESULT(S): Blood loss, operation time, and need for postoperative blood transfusion were significantly reduced in the group given vaginal misoprostol. No difference was observed among patients in terms of the time of hospitalization. CONCLUSION(S): A single preoperative dose of vaginal misoprostol is a simple, reliable method for reducing intraoperative blood loss and need for postoperative blood transfusion after abdominal myomectomies.     

Inhibition of progesterone secretion with trilostane for mid-trimester termination of pregnancy: randomized controlled trials

BACKGROUND: Progesterone is central to the maintenance of pregnancy, and is thus the ideal target for fertility regulation. Two mechanisms by which progesterone can be targeted are: receptor blockade and reduction of progesterone production through enzyme inhibition. Mifepristone, a receptor blocker, is usually given as 'pretreatment' prior to prostaglandin administration in mid-trimester termination of pregnancy (TOP). Unfortunately, there are difficulties accessing mifepristone in developing countries, and TOP is therefore performed using prostaglandins alone, which results in unacceptably long induction-to-abortion intervals. Trilostane is a 3beta-hydroxysteroid dehydrogenase inhibitor which reduces progesterone production. In these mid-trimester studies it is evaluated as a method of pretreatment prior to misoprostol administration. METHODS: Three consecutive randomized controlled trials comparing different trilostane regimens for pretreatment were performed. In study 1, trilostane was compared with placebo; in study 2, two doses of trilostane were compared (1080 mg and 720 mg); in study 3, the effect of adding danazol to trilostane as combination therapy was evaluated. The primary outcome in all the studies was the induction-to-abortion interval. Serum progesterone, estradiol and cortisol were measured serially during treatment. RESULTS: In study 1, 48 women were randomized. The median induction-to-abortion interval was 9 h in the trilostane group and 18.5 h in the placebo group (P < 0.0001). Progesterone and estradiol production was significantly reduced in the women receiving trilostane, with maintenance of diurnal cortisol variation. Twenty-eight women were randomized in study 2, which demonstrated that there was no significant difference in the induction-to-abortion interval using 1080 mg and 720 mg trilostane when compared with the higher doses used in study 1. Study 3, in which 40 women were included, failed to show any additional benefit using combination therapy with danazol and trilostane. CONCLUSIONS: Trilostane is an effective pretreatment agent in mid-trimester TOP.     

Misoprostol in the treatment of trigeminal neuralgia associated with multiple sclerosis

Multiple sclerosis can be associated with trigeminal neuralgia which is often difficult to treat in this specific condition. We performed an open prospective trial on the efficacy and safety of the prostaglandin-E1-analogue misoprostol (600 μg per day) in the reduction of attack frequency and pain intensity in patients with refractory trigeminal neuralgia associated with multiple sclerosis. Eighteen patients completed the study period and 14 of them showed a reduction of more than 50 % in attack frequency and intensity beginning five days after treatment onset. There were only mild and transient drug related side effects in three patients. One patient stopped taking misoprostol after the study period because of severe menorrhagia. Our results suggest that misoprostol is effective and safe in the treatment of this specific type of refractory trigeminal neuralgia. Received: 11 September 2002, Received in revised form: 13 November 2002, Accepted: 21 November 2002 Correspondence to Stefan Evers, MD, Department of Neurology, University of Münster, Albert-Schweitzer-Str. 33, 48129 Münster, Germany, Fax: +49-251/8348181, E-Mail: everss@uni-muenster.de The DMKG study group (The members of the study group contributing to this work are listed in the appendix.)     

早孕7-9周药物流产的临床观察

目的:探讨提高孕7-9周药物流产的有效性药物剂量。方法:因非意愿妊娠要求终止早孕的孕7-9周妇女256例,随机分为二组,A组(109例)和B组(147例)。d1-2分别分次口服米非司酮150mg或200mg;d3口服米索前列醇600μg,4h后无论胚囊是否排出,均加服米索400μg。结果:A组完全流产率为91.2%,B组为92.5%,P>0.05。药物流产后阴道出血时间、出血量、转经时间、经期及经量二组均无统计学差异。结论:两种方法的完全流产率均达到90%以上,200mg米非司酮配伍米索前列醇,可能减少孕囊排出时的出血量,对孕7-9周的妇女不失为一种安全的药物流产手段。     

Methotrexate and misoprostol used alone or in combination for early abortion

The purpose of this study was to compare the outcome and side effects of using the drugs methotrexate and misoprostol, alone or in combination, to induce abortion. A total of 108 subjects who had requested elective termination of pregnancy and medical abortion at 9 weeks gestation or less were randomized into three groups. The first group received 50 mg/m² intramuscular (IM) methotrexate on day 1 and, if the hCG level had risen by >50% of the initial level on day 4, a second dose was given. They were then followed-up at weekly intervals up to day 21. Group 2 received 800 μg vaginal misoprostol on day 1 and, if ultrasound showed a gestational sac on day 4, they received a repeat dose and were re-examined on day 7. Group 3 received 50 mg/m² methotrexate intramuscularly followed 3 days later by 800 μg vaginal misoprostol and were re-examined on day 7. Complete abortion occurred in 25 (69%) of the 36 subjects in group 1, 21 (58%) of the 36 subjects in group 2, and 32 (89%) of the 36 subjects in group 3. The complete abortion rate in group 3 was significantly higher than that of both group 1 and group 2 (p <0.05). The incomplete abortion rate was significantly higher in group 2 as compared with both of the other groups (p <0.05). There were significant differences between the mean gestational age of the successful abortions and the failures in group 1 (no abortion occurred at more than 49 days gestation), but not in groups 2 or 3. Vaginal bleeding in subjects who successfully aborted began within 16 ± 4 days in group 1 after the first dose, and within 24 h in 18 (86%) of the 21 subjects in group 2 and 27 (84%) of the 32 subjects in group 3 after the misoprostol dose. The drugs caused no serious or prolonged side effects. The combination of methotrexate and misoprostol is a more effective abortifacient regimen than when either drug is used alone.