Vaginal Administration Of Misoprostol Research Articles

O56 Pharmacokinetic profiles up to 12 h after administration of vaginal, sublingual and slow-release oral misoprostol

International Journal of Gynecology & ObstetricsVolume 107, Issue S2 p. S109-S109 Free communication (oral) presentations O56 Pharmacokinetic profiles up to 12 h after administration of vaginal, sublingual and slow-release oral misoprostol A. Aronsson, A. AronssonSearch for more papers by this authorC. Fiala, C. FialaSearch for more papers by this authorO. Stephansson, O. StephanssonSearch for more papers by this authorF. Granath, F. GranathSearch for more papers by this authorB. Watzer, B. WatzerSearch for more papers by this authorH. Schweer, H. SchweerSearch for more papers by this authorK. Gemzell-Danielsson, K. Gemzell-DanielssonSearch for more papers by this author A. Aronsson, A. AronssonSearch for more papers by this authorC. Fiala, C. FialaSearch for more papers by this authorO. Stephansson, O. StephanssonSearch for more papers by this authorF. Granath, F. GranathSearch for more papers by this authorB. Watzer, B. WatzerSearch for more papers by this authorH. Schweer, H. SchweerSearch for more papers by this authorK. Gemzell-Danielsson, K. Gemzell-DanielssonSearch for more papers by this author First published: 20 November 2009 https://doi.org/10.1016/S0020-7292(09)60428-8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume107, IssueS2Abstracts of XIX FIGO World Congress of Gynecology and ObstetricsOctober 2009Pages S109-S109 RelatedInformation

High-Dose Misoprostol as An Alternative Therapy After Failed Medical Abortion

The aim of this study was to determine the complete abortion rate for the vaginal administration of high-dose misoprostol after a failed medical abortion. When their medical abortions failed after the conventional oral administration of mifepristone and misoprostol, participants then received 1,000 microg of misoprostol vaginally. The efficacy and side effects of this treatment were evaluated. Twenty-seven women who failed to abort after the conventional administration of mifepristone and misoprostol were enrolled in this trial. Fourteen days after the vaginal administration of 1,000 microg misoprostol, the overall complete expulsion rate had reached 88.8% (24/27). Most adverse effects were mild to moderate and did not require treatment. The vaginal administration of 1,000 microg misoprostol as a salvage therapy after a failed medical abortion appears to be a safe and highly effective alternative to surgical intervention.

Vaginal Versus Oral Misoprostol for Second-Trimester Pregnancy Termination: A Randomized Trial

The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination. Sixty women in second trimester of gestation with indications for pregnancy termination were randomly assigned in two equal groups to receive either vaginal or oral misoprostol. The dosing regimen was 400 microg as the initial dose followed by 400 microg up to 3 doses (1200 microg) if needed in each group. Efficacy and side effects were compared. The percentage of women who delivered was significantly higher in vaginal group than the oral group (86.7 vs. 43.3 p = 0.0006). No significant differences in complication rates and induction to delivery interval were noted between the two groups. Vaginal administration of misoprostol resulted in a higher success rate for second trimester pregnancy termination, whereas, no significant differences in induction to delivery time and complication rates were noted between vaginal and oral groups.

Working to improve implantation

Working to improve implantation

A Multi-Center Prospective, Randomized, Double-Blind Trial Studying the Effect of Misoprostol on the Outcome of Intrauterine Insemination

Background: Because seminal prostaglandins play a role at natural fertilization, it was hypothesized that vaginal supplementation of prostaglandins at the time of intrauterine insemination (IUI) might enhance chances of conception. We investigated the effect of misoprostol, a prostaglandin analogue, on the success rate of IUI. Methods: A multi-center double-blind randomized controlled trial, using a cross-over design with alternating sequence, was designed. Vaginal tablets of misoprostol or placebo were used in conjunction to intrauterine insemination. In total, 199 women, comprising 466 cycles, were analyzed. Main outcome measures were pregnancy rate and prevalence of vaginal bleeding and uterine cramps. Results: The misoprostol group accounted for 146 cycles with 19 pregnancies, whereas the placebo group cycles totaled 164 cycles with 21 pregnancies (13.0 vs. 12.8%, not significant). There was a statistically significant increase in vaginal bleeding (12.3 vs. 1.8%; OR 7.55; 95% CI 2.31–24.48) and abdominal cramping rates (15.1 vs. 4.3%; OR 3.98; 95% CI 1.68–9.39) after application of misoprostol. Due to these severe adverse events the study was prematurely terminated. Conclusion: Although prostaglandins surely play a role in natural human reproduction, vaginal administration of misoprostol at the time of IUI is associated with a high rate of side effects and does not seem to enhance the outcome.

Vaginal administration of misoprostol has a significant effect on cervical ripening in premenopausal women undergoing operative hysteroscopy,

Vaginal administration of misoprostol has a significant effect on cervical ripening in premenopausal women undergoing operative hysteroscopy,

Möbius Syndrome in a Neonate After Mifepristone and Misoprostol Elective Abortion Failure

To report a case of a child born with Möbius syndrome following exposure in utero to mifepristone and misoprostol for elective abortion. In the seventh week of pregnancy, a woman was administered mifepristone 600 mg and, 2 days later, misoprostol 400 mug for abortion. One month later, despite significant metrorrhagia, an ultrasound examination showed ongoing gestation. At 33 weeks and 3 days of gestation, the woman gave birth to a male with left facial palsy, microretrognathia, and axial hypotonia related to Möbius syndrome. Möbius syndrome is characterized by unilateral or bilateral palsy of the abducens (VI) and facial (VII) cranial nerves. Other cranial nerves (eg, the hypoglossal [XII]), craniofacial or orofacial anomalies, and limb malformations are often associated. The etiology of the Möbius syndrome remains largely unknown and probably involves multiple factors. The most likely etiological hypothesis is disruption of the developing vascular system, with transient ischemia (particularly in the vertebral arteries) and fetal hypoxia. A teratogenic cause of Möbius syndrome has been suggested. The critical period for the development of Möbius syndrome following teratogen exposure appears to be 5-8 weeks of gestation. To date, mifepristone alone does not appear to have induced Möbius syndrome. In contrast, oral or vaginal misoprostol administration can lead to a significant increase in Doppler-measured uterine artery resistance and may induce uterine contractions. If these occur during the critical embryonic period, they may cause flexion in the areas of the sixth and seventh cranial nerves and decreased blood flow. Ineffective use of mifepristone and misoprostol in the first trimester of pregnancy may be associated with a risk of Möbius syndrome, primarily due to misoprostol activity. Women with ongoing pregnancy after failed abortion with misoprostol administration should be informed of this risk.

Efficacy of Vaginal Misoprostol Before Hysteroscopy for Cervical Priming in Patients Who Have Undergone Cesarean Section and No Vaginal Deliveries

We wanted to investigate the effect of misoprostol administered vaginally before operative hysteroscopy on cervical dilation, complications, and failure rates in patients who have undergone cesarean section and who have never delivered vaginally. Sixty patients who had undergone cesarean section, who had never delivered vaginally before, and were about to undergo hysteroscopy for various intrauterine lesions were included in this randomized controlled study. Thirty-two patients in the study group were given misoprostol 400 μg, and 28 patients in the control group were given placebo (hexetidine pill) vaginally twice, 6 and 12 hours before the procedure. Primary endpoints were cervical width detected with Hegar dilators and complication and failure rates. Mean cervical width was greater in patients in the study group (6.5 ± 0.8) than it was in patients in the control group (3.0 ± 0.6), (p = .0001). Complication and failure rates were lower in patients in the study group (p = .01). Administration of vaginal misoprostol before hysteroscopy proved to be effective in cervical ripening and in reducing complication and failure rates.

A randomised comparative study on sublingual versus vaginal administration of misoprostol for termination of pregnancy between 13 to 20 weeks

Misoprostol is the drug of choice for medical abortion worldwide but consensus is yet to be reached regarding its preferred route of administration. To compare the outcome of sublingual with vaginal administrations of misoprostol for induction of second trimester abortion. A randomised comparative trial where 300 women at 13-20 weeks gestation, requiring medical abortion, were randomly assigned to sublingual or vaginal route for misoprostol administration with a dose schedule of 400 microg three-hourly, up to a maximum five doses over 24 h. The same doses were repeated for another 24 h in non-responders. Primary outcome measure was complete abortion rate at 24 and 48 h, and the secondary outcome measures were induction-abortion interval, failure rate, side-effects and patients' preference to the route. No statistically significant differences in the complete abortion rates were observed at 24 h (64.03% vs 61.59%, P = 0.767) and at 48 h (79.14% vs 82.01%, P = 0.651) when sublingual and vaginal groups were compared. Mean induction-abortion intervals in sublingual and vaginal groups were 14.1 and 14.5 h, respectively (P = 0.066). Other outcome measures were also more or less similar in both groups. Differences in the incidence of side-effects were also statistically insignificant when both groups were compared. Sublingual administration of the drug was preferred by most of the women as compared to vaginal administration (P < 0.0001). Both sublingual and vaginal administrations of misoprostol are equally effective in inducing medical abortion during second trimester but sublingual route was preferred by the patients.

A randomised comparison between sublingual, oral and vaginal route of misoprostol for pre‐abortion cervical ripening in first‐trimester pregnancy termination under local anaesthesia

To compare efficacy of sublingual (S/L), oral and vaginal routes of misoprostol administration for cervical priming before suction evacuation (SE) under local anaesthesia. In a prospective randomised clinical trial, 200 women in the first trimester of pregnancy were randomised into four groups of 50 each. Patients in control group did not receive any medication before SE while other treatment groups received 400 microg of misoprostol three hours prior to SE either by sublingual/oral or by vaginal route. Main outcome measure was basal cervical dilatation while the secondary outcome measures were operative blood loss, time duration of surgery, patient satisfaction, pain perception and adverse effects. Sublingual group had a higher dilatation (9.9 +/- 2.1 mm; P < 0.001) and lower time duration of surgery (3.6 +/- 1.0 min; P < 0.01) as compared to oral (8.2 +/- 2.6 mm, 4.9 +/- 1.7 min) or vaginal routes (7.6 +/- 2.6 mm, 5.2 +/- 1.8 min). Mean pain score of the sublingual group was significantly lower (2.4 + 1.3; P < 0.001) as compared to oral (3.4 +/- 1.3) or vaginal routes (3.6 +/- 1.2). Patient acceptability was higher for sublingual (53 of 150) and oral routes (62 of 150) as compared to vaginal (35 of 150) route. Sublingual route was significantly more effective than oral or vaginal administration of misoprostol for cervical dilatation. To the best of our knowledge, this is the first study to simultaneously compare the efficacy of sublingual, oral and vaginal routes of misoprostol for cervical priming before SE.

Cervical ripening before operative hysteroscopy in premenopausal women: a randomized, double-blind, placebo-controlled comparison of vaginal and oral misoprostol

To compare the effectiveness of oral and vaginal misoprostol for preoperative cervical ripening in premenopausal women before hysteroscopic surgery. Placebo-controlled, double blind, randomized trial. University hospital. Eighty-six premenopausal women eligible for operative hysteroscopy were recruited. Nine women were excluded from the study. Patients were randomly assigned to receive 400 microg of misoprostol orally (n = 39) or vaginally (n = 38), 10-12 hours before operative hysteroscopy. Extent of initial cervical width, percentage of patients requiring cervical dilatation, duration of cervical dilatation and surgical procedure, complications during procedure, and associated side effects. Mean cervical widths in the vaginal and oral misoprostol groups after treatment were 7.3 +/- 1.6 mm and 6.0 +/- 1.5 mm, respectively, which was a statistically significant difference. Time required for cervical dilatation (98.6 +/- 88.7 s vs. 49.1 +/- 34.9 s) and duration of surgery (14.5 +/- 6 vs. 7.7 +/- 4.0 min) was statistically significantly shorter in the vaginal misoprostol group. The percentage of women with an initial cervical width of 9 mm was statistically significantly higher in the vaginal misoprostol group (36.8% vs. 5.1%). Uterine perforation occurred in two patients in the oral misoprostol group and in none in the vaginal misoprostol group. Side effects were comparable between the two treatment groups. Vaginal administration of misoprostol is more effective than the oral route for preoperative cervical ripening in premenopausal women.

Pharmacokinetic profiles up to 12 h after administration of vaginal, sublingual and slow-release oral misoprostol

It has been shown that the route of administration of misoprostol has a strong impact on the pharmacokinetic profile and result in different clinical efficacy. No study has so far evaluated the pharmacokinetics beyond 6 hours. Furthermore a new slow-release misoprostol formulation was included in the study. Pharmacokinetics of a novel slow-release (SR) oral misoprostol was compared during 12 h after administration to conventional misoprostol administered vaginally or sublingually. Thirty-three women requesting surgical abortion up to 12 weeks were randomly allocated to groups receiving a single dose of 400 microg conventional misoprostol administered vaginally or sublingually or 800 microg SR oral misoprostol. Blood samples were taken before (0 h) and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 h after misoprostol administration. Misoprostol acid (MPA) was determined in serum samples using liquid chromatography/tandem mass spectrometry. Three women did not complete the study. Serum concentrations reached their highest level following sublingual misoprostol (P<0.0001) and the time to peak concentration was shortest for this group (P=0.0094). The area under the curve (AUC) up to 12 h was greater following sublingual treatment than for the other alternatives (P<0.0001) and lowest for SR misoprostol. Cumulative serum levels of MPA did not increase beyond 6 h following sublingual and vaginal administration, while they continued to increase up to 12 h following SR misoprostol. The new SR form of misoprostol demonstrated lower peak levels and a lower AUC but longer lasting elevation in serum levels when compared to conventional misoprostol administered sublingually or vaginally. SR misoprostol may offer an alternative to repeated administration of conventional misoprostol.

Concurrent Use of Mifepristone and Misoprostol for Early Medical Abortion

This study was designed to evaluate the efficacy of using mifepristone and misoprostol concurrently for early medical abortion. A total of 90 women with undesired pregnancies <or= 49 days' gestation were enrolled. All women concurrently received oral mifepristone 200 mg and vaginal misoprostol 800 microg. Follow-up evaluation with transvaginal ultrasonography was performed 4 days and 2 weeks after treatment. The complete abortion rate was 97.8% (88/90 women). The mean induction to abortion interval was 5.5 hours. The mean bleeding duration was 11.8 days. Patients found the side effects acceptable and reported a 91.1% (82 patients) satisfaction rate. Concurrent administration of oral mifepristone and vaginal misoprostol is an efficacious regimen for medical abortion of pregnancies <or= 49 days of gestation.

P-454: Office hysteroscopy is the best treatment option in cases with severe cervical stenosis

Office hysteroscopy is used outpatient procedure for endoscopic examination of the uterine cavity. Advantages of this procedure are decreased medical expenses and less requirement of sedation or anesthesia. However, some patients require dilatation of the cervical canal before investigation of the uterine cavity. Suggested methods for dilatation of the canal are laminaria placement, oral or vaginal misoprostol administration, application of Hegar dilators, or fluoroscopic guidance. In cases where severe cervical stenoses exist, the forceful use of Hegar dilators may lead to a creation of false passage and in some cases perforation of the endocervical canal or uterine cavity.

Vaginal Misoprostol Administration for Cervical Ripening and Labor Induction

Intravaginal misoprostol has been shown to be an effective agent for cervical ripening and induction of labor. Vaginal application of misoprostol has been reported in over 9000 women worldwide and seems to have safety profile similar to that of endocervically and intravaginally administered dinoprostone. Concern arises with the use of higher doses of intravaginal misoprostol (50 mcg or more) and the association with uterine contractile abnormalities and for this reason, use of low-dose misoprostol regimen has been recommended by the American College of Obstetricians and Gynecologists. The recommendation is use of a 25-mcg dose of misoprostol inserted into the posterior vaginal fornix and repeated every 3 to 6 hours as needed. Misoprostol administration to women with prior cesarean births seems to increase the likelihood of uterine scar disruption and should not be used in these women. There are reports of uterine rupture in women with unscarred uteri treated with vaginally applied misoprostol. Therefore, all patients need to be monitored adequately after misoprostol administration. Although there is a growing body of data regarding the ambulatory use of intravaginal misoprostol for cervical ripening, its use for this purpose cannot be recommended outside of investigational protocols at this time because of concerns for maternal and neonatal safety.

Nova formulação de misoprostol sublingual na indução do trabalho de parto

To determine effectiveness and safety of sublingual misoprostol in tablets of 25 mcg, given every 6 hours for induction of labor in high-risk pregnant women hospitalized in two teaching hospitals in the Northeast of Brazil. An open, non-randomized clinical trial was conducted, including 40 women with high-risk pregnancies hospitalized at "Maternidade-Escola Assis Chateaubriand" and "Instituto Materno-Infantil de Pernambuco". All of them had gestational age >or= 37 weeks, alive fetus with good vitality and Bishop scores <or= 7. A tablet of 25 mcg of misoprostol was administered every 6 hours, up to a maximum of 4, until active labor. Statistical analysis was performed using the public domain software Epi-Info 3.2.2. Active labor occurred in 100% of cases after misoprostol administration. The mean (+/-SD) induction-to-labor interval was 4.8(+/-3.8 hours. Interval from induction-to-delivery varied from 8 to 31 hours with 95% of the deliveries occurring in the first 24 hours with 75% of vaginal deliveries. The frequency of tachysystole was 12.5%. The women did not present relevant side effects neither were there any neonatal complications. The sublingual tablet of misoprostol of 25 mcg was shown to be effective for induction of labor in high-risk pregnant women. The efficacy and acceptability of this new route should be compared to vaginal administration of misoprostol in future prospective randomized clinical trials.

Sublingual versus vaginal misoprostol (400 μg) for cervical priming in first-trimester abortion: a randomized trial

Objective Our objective was to compare the sublingual administration and the vaginal administration of misoprostol for cervical priming before first-trimester surgical abortion. Design We used an open, multicenter, randomized trial. Locations We conducted the study in four clinics (in Valencia, Castelló, Murcia and Murcia Capital) in Spain. Participants A total of 1424 healthy pregnant women with amenorrhea of ≤84 days who voluntarily decided to terminate their pregnancy participated in the study. Methods Women were randomly assigned to receive a single dose of 400 μg of misoprostol either sublingually or vaginally 1–3 h before aspiration. Outcome Measures The outcome measures assessed were cervical dilation before surgery and surgical time needed for aspiration. The incidence of side effects, such as nausea, vomiting, diarrhea, fever/chills and paresthesia, was evaluated. Results The mean cervical dilation achieved was 6.8±0.8 and 6.7±0.9 mm for the sublingual and vaginal groups, respectively. The mean surgical time was 7.0±2.8 and 7.4±2.5 min for the sublingual and vaginal groups, respectively. Nausea, vomiting and diarrhea were more frequent in the sublingual group. Conclusions Both regimens had equal efficacy; however, the sublingual route caused more side effects.

Regimens of misoprostol with mifepristone for early medical abortion: a randomised trial

To compare the efficacy, adverse effects and acceptability of the three most common misoprostol regimens used with mifepristone for medical abortion. Randomised nonblinded trial. Three clinics associated with major research universities in Canada; two in major urban areas and one in a periurban area. Women of reproductive age. Consenting women presenting for abortion services with gestations less than 56 days and who met inclusion criteria were given 200 mg mifepristone orally and then randomised into three misoprostol study groups: (group I) 400 micrograms of oral misoprostol, (group II) 600 micrograms of oral misoprostol, and (group III) 800 micrograms of vaginal misoprostol. Misoprostol was self-administered at home 24-48 hours following mifepristone, and participants were instructed to take a second similar misoprostol dose at 24 hours after the initial dose if bleeding was less than a normal menstrual period. Successful abortion without surgery was 94.1%, with no significant differences across the three study groups (94.7% in group I, 93.4% in group II, and 94.3% in group III; P= 0.975). Efficacy and adverse effects did not differ significantly across the three study groups. Pain increased significantly across the study and the gestational age groups and was associated with lower acceptability. There appears to be a range of safe and effective options for early medical abortion with mifepristone including a choice between oral and vaginal administration of misoprostol.

Induction of second trimester abortion (12–20 weeks) with mifepristone and misoprostol: a review of 386 consecutive cases

Design A retrospective analysis of 386 women who underwent termination of pregnancy between 12 and 24 weeks' gestation. Methods Each woman received 200 mg mifepristone orally followed by vaginal misoprostol 800 μg 36 to 48 h later. Three hours after the initial misoprostol administration, 400-μg doses of vaginal misoprostol were administered every 3 h, to a maximum of four doses in 24 h. If abortion failed, 200 mg mifepristone is given again 3 h after the last misoprostol dose, followed by 12 h of rest before vaginal misoprostol administration is repeated as per previous course of treatment. Results Overall, 97.9% and 99.5% of the women aborted within 24 and 36 h, respectively. The median induction-to-abortion interval was 6.7 h (range: 1.4–73.8 h), and nulliparous women took significantly longer time to abort (6.0 h in multiparous women compared to 7.6 h in nulliparous women; p<.0001). One woman failed to abort within 48 h. Surgical evacuation of the uterus was performed in 5% of women for incomplete abortion or retained placenta. Multiparous women were less likely to need analgesic administration for pain relief, and to experience vomiting and diarrhea, than nulliparous women. Conclusion The combination of 200 mg mifepristone and vaginally administered misoprostol is a safe, effective and noninvasive regimen for termination of pregnancy between 12 and 20 weeks.

Simultaneous very low dose mifepristone and vaginal misoprostol for medical abortion

Objective This pilot study was designed to evaluate the outcome of medical abortion following simultaneous mifepristone (100 mg) and misoprostol (800 μg). Methods Enrollees had gestational ages up to 56 days and desired a medical abortion. They received 100 mg of mifepristone orally and 800 μg of misoprostol vaginally. Follow-up examination occurred in 2–7 days. A phone call 3 weeks later assessed symptoms and acceptability. A 95% success rate, as seen in higher dose studies, gives a 95% confidence interval of 88–100% for 40 subjects. Results Forty women were enrolled; 39 women had follow-up visits. Completed medical abortion was confirmed for 35 (90%) of 39 women. Four women had uterine aspiration. Two patients required repeat misoprostol. Median time from medication to abortion was 7 h. Most women (92%) strongly preferred taking all medications in the clinic. Conclusions The simultaneous administration of vaginal misoprostol with 100 mg of oral mifepristone had the outcome of completed abortion within the predicted confidence interval. In addition, simultaneous dosing was highly acceptable.