Postpartum hemorrhage is an important cause of maternal mortality and morbidity. Especially uterine atony is the most common cause of postpartum hemorrhage. Conventional method to control postpartum uterine atonic bleeding is based on the use of oxytocin and ergot preparations. Prostaglandin F2alpha analogue such as carboprost can be used to promote contraction when these agents fail to produce uterine contraction. Prostaglandin E1 analogue, misoprostol has uterotonic effect by oral or vaginal administration. They are used to induce labor and first or mid trimester abortion. In postpartum uterine atonic bleeding, misoprostols cannot be used via oral or vaginal route. Recently we have experienced that postpartum uterine atonic bleedings unresponsive to conventional methods were controlled by rectal misoprostols. So we report these cases with a brief review of literatures.
Administration, Intravaginal ; Alprostadil ; Carboprost ; Dinoprost ; Hemorrhage* ; Maternal Mortality ; Misoprostol* ; Oxytocin ; Postpartum Hemorrhage ; Postpartum Period* ; Uterine Contraction ; Uterine Inertia

Our purpose was to compare the safety and efficacy of intravaginal misoprostol versus dinoprostone vaginal tablet for induction of labor at term pregnancies. Two hundred three patients with indications for induction of labor at term were randomly assigned to receive either intravaginal misoprostol or dinoprostone vaginal tablet. Fifty micrograms of misoprostol was placed in the posterior vaginal fornix every six hours, with a potential maximum of four doses. 3 milligrams of dinoprostone vaginal tablet was placed in the posterior vaginal fornix every eight hours, with a potential maximum of three doses. Further medication was withheld with the occurrence of spontaneous rupture of membrane, entry into adequate contraction pattern(twenty second sustained with two or more frequent uterine contraction in 10 minutes), nonreassuring FHR tracing, or delivery. Artificial membrane rupture with both study protocol was done at the discretion of the attending physician. After membrane rupture, in the cases of failure of active labor or arrest of dilation, oxytocin was administerated. Among those evaluated, 100 received misoprostol and 102 received dinoprostone. The average interval from start of induction to vaginal delivery was shorter in the misoprostol group(784.7 +/- 389.3 min) than in the dinoprostone group(988.3 +/- 369.5 min)(p<0.01). There was no significant difference in change of Bishop score between the two groups. No statistically significant differences were noted between two groups in case of need for oxytocin and oxytocin total dose, but significant difference was noted between two groups in case of indication for oxytocin augmentation. There were no significant differences in the routes of delivery. Intravaginal administration of misoprostol appears to be as effective as dinoprostone vaginal tablet for labor induction at full term pregnancies. Complications associated with prostaglndin administration were not statistically different between the two treatment groups.
Administration, Intravaginal ; Dinoprostone* ; Humans ; Membranes ; Membranes, Artificial ; Misoprostol* ; Oxytocin ; Pregnancy* ; Rupture ; Rupture, Spontaneous ; Uterine Contraction ; Vaginal Creams, Foams, and Jellies*

BACKGROUNDIn China, no multicenter double-blinded prospective randomized controlled study on labor induction has been conducted till now. This study is to evaluate the efficacy and safety of intravaginal accurate 25-μg misoprostol tablets for cervical ripening and labor induction in term pregnancy in nulliparous women.

METHODSThis was a double-blinded, prospective randomized controlled study including nulliparous women from 6 university hospitals across China. Subjects were randomized into misoprostol or placebo group with the sample size ratio set to 7:2. Intravaginal 25-μg misoprostol or placebo was applied at an interval of 4 h (repeated up to 3 times) for labor induction. Primary outcome measures were the incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h. Safety assessments included the incidences of maternal morbidity and adverse fetal/neonatal outcomes.

RESULTSA total of 173 women for misoprostol group and 49 women for placebo were analyzed. The incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h was higher in the misoprostol group than in the placebo (64.2% vs. 22.5%, relative risk [RR]: 2.9, 95% confidence interval [CI]: 1.4-6.0). The incidence of onset of labor within 24 h was significantly higher in the misoprostol group than in the placebo group (48.0% vs. 18.4%, RR: 2.6, 95% CI: 1.2-5.7); and the induction-onset of labor interval was significantly shorter in the misoprostol group (P = 0.0003). However, there were no significant differences in the median process time of vaginal labor (6.4 vs. 6.8 h; P = 0.695), incidence (39.3% vs. 49.0%, RR: 0.8, 95% CI: 0.4-1.5) and indications (P = 0.683) of cesarean section deliveries, and frequencies of maternal, fetal/neonatal adverse events between the groups.

CONCLUSIONIntravaginal misoprostol 25 μg every 4 h is efficacious and safe in labor induction and cervical ripening.

Administration, Intravaginal ; Adult ; Cervical Ripening ; drug effects ; Double-Blind Method ; Female ; Humans ; Labor, Induced ; methods ; Misoprostol ; administration & dosage ; therapeutic use ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, Third ; Young Adult

OBJECTIVE: To evaluate the predictive factors associated with the success of medical abortion by misoprostol monotherapy within 24 hours in the first trimester of pregnancy. METHODS: The records of 228 women with miscarriage up to 11 weeks of gestational age who underwent medical abortion by intravaginal misoprostol monotherapy were reviewed. Success of abortion was defined as complete expulsion of the conceptus without the need for surgical intervention. Outcomes of interest were success of abortion within 24 hours following administration of misoprostol. RESULTS: Among 222 women who continued the process of medical abortion for 24 hours, 209 (94.1%) had a successfully completed abortion. Multivariate logistic regression showed that serum β-human chorionic gonadotropin (β-hCG) above 40,000 mIU/mL is significantly associated with failed medical abortion within 24 hours (odds ratio [OR], 7.13; 95% confidence interval [CI], 1.60–37.32; P=0.011). The area under the receiver operating characteristic curve of β-hCG level associated with successful abortion within 24 hours was 0.705 (95% CI, 0.63–0.77; P=0.007). Previous vaginal delivery seems to be significantly associated with successful abortion within 24 hours on univariate analysis (P=0.037), but the association was lost in multivariate analysis. CONCLUSION: Misoprostol monotherapy has a high success rate for first trimester abortion. Women with serum β-hCG less than 40,000 mIU/mL are likely to achieve a successful abortion within 24 hours after intravaginal administration of misoprostol.
Abortion, Spontaneous ; Administration, Intravaginal ; Chorionic Gonadotropin ; Female ; Gestational Age ; Humans ; Logistic Models ; Misoprostol* ; Multivariate Analysis ; Pregnancy ; Pregnancy Trimester, First ; ROC Curve

Obstetrical hemorrhage is one of the deadly triad, along with hypertensive disorder in pregnancy and infection. Postpartum hemorrhage is the major cause of obstetrical hemorrhage. Uterine atony is the most common cause of postpartum hemorrhage, and resulted from poor uterine contraction after delivery of the fetus and placenta. Initial management to control postpartum uterine atonic bleeding is based on the use of uterotonics such as well known oxytocin and ergot preparations together with uterine massage. Prostaglandin E2 analogue, sulprostone can be used next when these agents are failed to produce uterine contraction. The woman unresponsive to non-surgical managements requires surgical interventions including emergency hysterectomy. Recently prostaglandin E1 analogue, misoprostol, has been known to elicit potent uterine contraction and cervical ripening after oral, vaginal or rectal administration. We have experienced two cases of postpartum uterine atonic bleedings which were unresponsive to oxytocin, ergot, or prostaglandin E2, but were successfully controlled by rectal administration of misoprostols.
Administration, Rectal ; Alprostadil ; Cervical Ripening ; Dinoprostone ; Emergencies ; Female ; Fetus ; Hemorrhage* ; Humans ; Hysterectomy ; Massage ; Misoprostol* ; Oxytocin ; Placenta ; Postpartum Hemorrhage ; Postpartum Period* ; Pregnancy ; Uterine Contraction ; Uterine Inertia

OBJECTIVE: This study was conducted to determine the effectiveness and safety of medical treatment with sublingual misoprostol (MS) in the 1st trimester miscarriage under the approval by Health Insurance Review and Assessment Service (HIRA) for off-label usage by the single medical center in Korea. METHODS: A retrospective cohort study was performed in one institution between April 2013 and June 2016. Ninety-one patients diagnosed with miscarriage before 14 weeks of gestation and wanted to try medical treatment were included. A detailed ultrasound scan was performed to confirm the diagnosis. Patients took 600 microgram (mcg) of MS sublingually at initial dose, and repeated the same dose 4–6 hours apart. Successful medical abortion was defined as spontaneous expulsion of gestational products (including gestational sac, embryo, fetus, and placenta). If gestational products were not expelled, surgical evacuation was performed at least 24 hours later from the initial dose. Information about side effects was obtained by medical records. RESULTS: About two-thirds of patients had a successful outcome. The median interval time from pill to expulsion was 18 hours in the successful medical treatment group. There was no serious systemic side effect or massive vaginal bleeding. Presence or absence of vaginal spotting before diagnosis of miscarriage, uterine leiomyomas, subchorionic hematoma, or distorted shape of gestational sac on ultrasound scan were not statistically different between the two groups. CONCLUSION: Medical treatment with sublingual MS can be a proper option for the 1st trimester miscarriage, especially for the patient who want to avoid surgical procedure. We can reduce the unnecessary sedation or surgical intervention in the patients with the 1st trimester miscarriage.
Abortion, Incomplete ; Abortion, Missed ; Abortion, Spontaneous* ; Administration, Sublingual ; Cohort Studies ; Diagnosis ; Embryonic Structures ; Female ; Fetus ; Gestational Sac ; Hematoma ; Humans ; Insurance, Health ; Korea* ; Leiomyoma ; Medical Records ; Metrorrhagia ; Misoprostol* ; Off-Label Use* ; Pregnancy ; Retrospective Studies ; Ultrasonography ; Uterine Hemorrhage

Clinopodium chinense, a traditional folk medicinal herb, has been used to treat abnormal uterine bleeding(AUB) for many years. Saponins and flavonoids are the main active components in C. chinense. To study the pharmacokine-tics of multiple components from the total extract of C. chinense(TEC), we established a sensitive and rapid method of ultra-perfor-mance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS) for simultaneous determination of five compounds in the plasma of AUB rats. After validation, the AUB model was established with SD female rats which got pregnant on the same day by gavage with mifepristone(12.4 mg·kg~(-1)) and misoprostol(130 μg·kg~(-1)). The established method was applied to the detection of hesperidin, naringenin, apigenin, saikosaponin a, and buddlejasaponin Ⅳb in AUB rats after the administration of TEC. The pharmacokinetic parameters were calculated by DAS 2.0. The five compounds showed good linear relationship within the detection range. The specificity, accuracy, precision, recovery, matrix effect, and stability of the method all matched the requirements of biolo-gical sample detection. The above 5 compounds were detected in the plasma of AUB rats after the administration of TEC. The C_(max) va-lues of hesperidin, naringenin, apigenin, saikosaponin a, and clinoposide A were 701.6, 429.5, 860.7, 75.1, and 304.1 ng·mL~(-1), respectively. All the compounds owned short half-life and quick elimination rate in vivo, and the large apparent volume of distribution indicated that they were widely distributed in tissues. Being rapid, accurate, and sensitive, this method is suitable for the pharmacokinetic study of extracts of Chinese herbal medicines and provides a reference for the study of pharmacodynamic material basis of C. chinense in treating AUB.
Administration, Oral ; Animals ; Apigenin/analysis* ; Chromatography, High Pressure Liquid/methods* ; Chromatography, Liquid ; Drugs, Chinese Herbal/chemistry* ; Female ; Flavonoids/analysis* ; Hesperidin ; Lamiaceae ; Mifepristone ; Misoprostol ; Oleanolic Acid/analogs & derivatives* ; Plant Extracts/chemistry* ; Rats ; Saponins ; Tandem Mass Spectrometry/methods* ; Uterine Hemorrhage

OBJECTIVETo evaluate the effect and risk of misoprostol for stimulating cervical maturity in women with post-term pregnancy negative for insulin-like growth factor binding protein-1 (IGFBP-1) in cervical secretion with modified Bishop score less than 3.

METHODSSeventy-one women with post-term pregnancy randomized into misoprostol group (n=37) and control group (n=34) received misoprostol placement at the posterior vaginal fornix and routine intravenous oxytocin infusion, respectively, to stimulate cervical maturity. Failure to respond to the treatment within the initial 24 h necessitated a repeated administration for no more than 3 times in all. Modified Bishop score was recorded and fetal heart monitored once every 24 h, and IGFBP-1 in the cervical secretion was detected at 24 and 48 h after drug administration.

RESULTSThe misoprostol group showed better effect of cervical maturity stimulation than the control group (P<0.001), and the positivity rates of IGFBP-1 24 and 48 h after drug administration were significantly higher than that of the control group (P<0.01 and 0.001). The number of cases with indication for cesarean section was significant higher in the control group (P<0.001). There were no significant differences in postpartum hemorrhage, excessive uterine contraction, incidence of fecal contamination of the amniotic fluid or Apgar score of the newborn between the two groups (P>0.05).

CONCLUSIONSMisoprostol is safe and effective for stimulating cervical maturity in women with post-term pregnancy who have modified Bishop score lower than 3 and are negative for IGPBF-1 in cervical secretion. Oxytocin is not advised for use in such gravida for stimulating cervical maturity. IGFBP-1 in cervical secretion may serve as an important index for evaluating the cervical maturity.

Abortifacient Agents, Nonsteroidal ; administration & dosage ; adverse effects ; therapeutic use ; Administration, Intravaginal ; Adult ; Cervical Ripening ; drug effects ; Cervix Uteri ; drug effects ; metabolism ; Female ; Heart Rate, Fetal ; drug effects ; Humans ; Insulin-Like Growth Factor Binding Protein 1 ; metabolism ; Misoprostol ; administration & dosage ; adverse effects ; therapeutic use ; Pregnancy ; Pregnancy, Prolonged ; drug therapy ; Treatment Outcome

BACKGROUND/AIMS: The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. METHODS: We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 microg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. RESULTS: Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258). CONCLUSIONS: Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.
Adult ; Aged ; Alanine/administration & dosage/adverse effects/*analogs & derivatives ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Anti-Ulcer Agents/*administration & dosage/adverse effects ; Arthritis/drug therapy ; Butanones/adverse effects ; Diclofenac/adverse effects/analogs & derivatives ; Double-Blind Method ; Drug Administration Schedule ; Gastric Mucosa ; Humans ; Middle Aged ; Misoprostol/*administration & dosage/adverse effects ; Quinolones/*administration & dosage/adverse effects ; Stomach Ulcer/chemically induced/*prevention & control ; Thiazines/adverse effects ; Thiazoles/adverse effects ; Treatment Outcome