Early pregnancy termination with intravaginally administered sodium chloride solution-moistened misoprostol tablets: historical comparison with mifepristone and oral misoprostol

OBJECTIVE: The purpose of this study was to compare the abortifacient effect of intravaginally administered moistened misoprostol tablets with that of the combination regimen of mifepristone and oral misoprostol. STUDY DESIGN: One hundred women at 相似文献   

Efficacy of concurrent administration of mifepristone and misoprostol for termination of pregnancy

In this prospective randomized parallel group study, subjects with a pregnancy of less than 63 d were randomized to receive either (i) 200?mg oral mifepristone plus 400?μg misoprostol per vaginally concurrently (group A); (ii) or the administration of misoprostol after 48?h (group B). Transvaginal sonography was performed on the 14th day of misoprostol administration to confirm complete abortion. The primary outcome was to compare the rates of complete abortion in two groups. Secondary outcomes were to compare induction abortion interval, side effects and compliance. A total of 200 subjects included in the study were randomized into groups A and B (100 each). Both the groups were comparable for age, parity, gestational age and history of previous abortion. The complete expulsion rate in group A was 96% (95% confidence interval (CI) 95.1–98.2%) and group B was 95% (95% CI 93.0–96.8%) (p?>?0.100). A gestational age of more than 56 d was found to predict failure of treatment in both groups. The adverse effect profile in the two groups was the same. Efficacy of concurrent mifepristone and misoprostol in combination is similar to that when misoprostol is given 48?h later (ctri.nic.in CTRI/2010/091/001422).     

First trimester abortion with mifepristone and three doses of sublingual misoprostol: a pilot study

OBJECTIVE: To evaluate the efficacy and safety of a medical abortion regimen with multiple doses of sublingual misoprostol 24 h after mifepristone. METHODS: The regimen was designed on the basis of pharmacokinetics of various routes of administration of misoprostol. Forty women < or = 8 weeks' gestation were given mifepristone 200 mg orally, followed 24 h later by three doses of misoprostol 200 microgm sublingually 6 h apart. They were followed up on day 3 and day 14 with transvaginal ultrasound. Pain and bleeding were assessed using a visual analogue scale and acceptability, by a questionnaire. RESULTS: Abortion outcome was assessed in terms of onset of pain and vaginal bleeding, time of expulsion of products and duration of vaginal bleeding. Seventy-five per cent of women experienced pain within 2 h after first dose of misoprostol. Bleeding began at a mean of 1.41 h after pain and expulsion at a mean of 6.1 h after first dose of misoprostol. Complete expulsion was confirmed in all women (100%) by ultrasound on day 14. The longest duration of bleeding was 12 days (mean 7.2 days) with 87.5% bleeding for < 10 days. Acceptability was 100% but 70% perceived pain to be moderate and 67.5% bleeding to be light or slightly more than menses. CONCLUSIONS: Medical abortion using three doses of sublingual misoprostol administered 24 h after mifepristone appears to be the most appropriate in terms of pharmacokinetics of the drugs. This pilot study associates the regimen with a short abortion process, which appears to be safe, highly efficacious and acceptable.     

Second trimester medical abortion with mifepristone followed by unlimited dosing of buccal misoprostol in Armenia

Objectives: The aim of the study was to assess the efficacy and acceptability of a regimen using mifepristone and buccal misoprostol with unlimited dosing for second trimester abortion in Armenia.

Methods: Women seeking to terminate 13–22 week pregnancies were enrolled in the study. Participants swallowed 200?mg mifepristone in the clinic and were instructed to return to the hospital for induction 24–48?h later. During induction, women were given 400?μg buccal misoprostol every 3?h until the fetus and placenta were expelled. The abortion was considered a success if complete uterine evacuation was achieved without oxytocin or surgery.

Results: A total of 120 women with a median gestational age of 18 weeks participated in the study. All women began misoprostol induction around 24?h after taking mifepristone. Complete uterine evacuation was achieved in 119 (99.2%) women. The median induction-to-abortion interval was 10.3?h (range 4–17.4) with a mean of 9.5?±?2.5?h. A median of four misoprostol doses (range 2–6) with a mean of 4?±?1 misoprostol doses were administered. The induction-to-abortion interval, number of misoprostol doses, pain score and analgesia use increased as gestational age advanced. Acceptability of the method was high among both patients and providers.

Conclusion: The medical abortion regimen of 200?mg mifepristone followed 24?h later by induction with 400?μg buccal misoprostol administered every 3?h, with no limit on the number of doses used for the termination of pregnancies of 13–22 weeks’ gestation is an effective and acceptable option for women.     

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

OBJECTIVE: To compare the efficacy, adverse effects and acceptability of the three most common misoprostol regimens used with mifepristone for medical abortion. DESIGN: Randomised nonblinded trial. SETTING: Three clinics associated with major research universities in Canada; two in major urban areas and one in a periurban area. POPULATION: Women of reproductive age. METHODS: 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. MAIN OUTCOME MEASURES: 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). RESULTS: 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. CONCLUSIONS: 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.     

Mifepristone and second trimester pregnancy termination for fetal abnormality in Western Australia: Worth the effort

Objective:  To determine the impact on the process of second trimester medical termination for fetal abnormality following the introduction of adjunctive mifepristone in an Australian tertiary hospital.
Methods:  All second trimester medical terminations for fetal abnormality between July 2006 and June 2009 were prospectively identified. Two temporal therapeutic cohorts were created: the first (1 July 2006 to 31 December 2007) using vaginal misoprostol alone and the second (1 January 2008 to 30 June 2009) using mifepristone priming prior to the administration of misoprostol. The primary outcome was to evaluate the impact of mifepristone priming upon the duration of pregnancy termination.
Results:  During the study period, 388 women with prenatally recognised fetal anomalies between 14 and 24 weeks gestation underwent medical termination: 189 with misoprostol alone and 199 with mifepristone priming followed by misoprostol. There was no difference between the groups for maternal age, parity or prior caesarean delivery. The median abortion duration was 15.5 h (interquartile ranges (IQR) 11.2–22.7) in the misoprostol group and 8.6 h (IQR 5.6–13.8) in the mifepristone primed group ( P  < 0.001). In both the groups, nulliparity and advancing gestation were associated with a significant prolongation of the abortion interval. Duration of hospitalisation was significantly longer in the misoprostol alone group (31.5 h (27–48.9) vs 27.2 h (22–31.5), misoprostol vs mifepristone priming, respectively, P  < 0.001).
Conclusions:  The introduction of mifepristone priming prior to second trimester medical termination with misoprostol has resulted in a significant reduction in the duration of the termination procedure and length of inpatient stay. These observed benefits of mifepristone provide objective support for the decision to permit use of this medication in Australia.     

Effects of a prolonged, 72 hours,interval between mifepristone and gemeprost in second trimester termination of pregnancy: a retrospective analysis

Objective: To evaluate if the 72 hours interval between mifepristone and gemeprost has a similar efficacy compared to the 48 hours interval for second trimester termination of pregnancy

Study Design: Two-hundred and fifteen consecutive pregnant women, admitted to our hospital, for second trimester TOP, were included in this retrospective analysis. Standard protocol was followed for all patients. On the first day of the procedure oral mifepristone 200?mg was administered. After 72 (group A, n?=?78) or 48 hours (group B, n?=?113) women were admitted for administration of gemeprost 1?mg pessary as per protocol. The induction to abortion time was defined as the interval between the insertion of the first gemeprost pessary and the expulsion of the fetus.

Results: There are no significant differences in the number of pessaries in the two groups. The induction to abortion interval was longer in group A than in group B. Twenty-one women required surgical evacuation of the uterus for retained placenta or incomplete abortion without difference between groups.

Conclusion: A 48-hours interval between mifepristone and gemeprost leads to better results than a 72-hours interval, with a shorter abortion length and represents the elective method for second trimester TOP.     

Randomised controlled trial comparing the efficacy of same-day administration of mifepristone and misoprostol for termination of pregnancy with the standard 36 to 48 hour protocol

OBJECTIVE: To determine the efficacy of oral mifepristone followed by vaginal misoprostol 6 hours later compared with the standard 36- to 48-hour regimen for medical termination of pregnancy. DESIGN: Single centre, two arm, parallel, open randomised controlled trial. SETTING: Medical termination service at a teaching hospital. SAMPLE: Four hundred and fifty women undergoing medical termination of pregnancy at up to 63 days of gestation. METHODS: Eligible women were randomised to receive mifepristone 200 mg orally followed by vaginal misoprostol 800 micrograms either 6 hours (n=225) or 36-48 hours (n=225) later. All participants were invited to attend for a follow-up pelvic ultrasound scan within 7 days following the misoprostol administration. For those women in whom products of conception remained at the follow-up ultrasound scan, expectant management ensued with weekly follow-up ultrasound scans until the termination was complete. They could elect to undergo an evacuation of uterus at any stage following the scan. Those women with a nonviable gestation sac at the follow-up scan were offered a further dose of vaginal misoprostol 800 micrograms or suction termination of pregnancy. Women with a continuing pregnancy were managed with surgical termination. MAIN OUTCOME MEASURE: Successful medical abortion defined as no requirement for medical or surgical intervention beyond the initial dose of misoprostol. RESULTS: One hundred and sixty-five women (79%) in the 6-hour group and 197 women (92%) in the 36- to 48-hour group had a successful termination at first follow-up ultrasound or presumed on the basis of other considerations (those not seen for ultrasound but deemed successful by negative pregnancy test, products passed on ward or long-term assessment of notes). Twenty-two women (10%) in the 6-hour regimen required up to three further ultrasound scans after 7 days following the mifepristone administration in order to ensure that the termination process was complete. None of these women required a suction evacuation of uterus. In the 36- to 48-hour regimen, ten (5%) women had up to two further ultrasound scans to confirm a complete termination without the need for a surgical evacuation of uterus. Therefore, the overall successful termination rate in the 6-hour regimen was 89% (187/210) compared with 96% (207/215) in the 36- to 48-hour regimen (relative risk=0.92, 95% CI 0.84-0.98). Repeat administration of misoprostol or surgical treatment was required in 23 women (11%) in the 6-hour group and 8 women (4%) in the 36- to 48-hour group. A viable pregnancy was found in five women (2%) in the 6-hour group and in three women (1%) in the 36- to 48-hour group. CONCLUSIONS: Oral mifepristone 200 mg followed by vaginal misoprostol 800 micrograms after 6 hours is not as effective at achieving a complete abortion compared with the 36- to 48-hour protocol.     

Using telemedicine for termination of pregnancy with mifepristone and misoprostol in settings where there is no access to safe services

Women on Web is a service that uses telemedicine to help women access mifepristone and misoprostol in countries with no safe care for termination of pregnancy (TOP). This study reviews the telemedicine service. After an online consultation, women with an unwanted pregnancy of up to 9 weeks are referred to a doctor. If there are no contraindications, a medical TOP is conducted by mail. After maximising the follow up from 54.8 to 77.6%, 12.6% decided not to do the TOP and 6.8% of the women who did the medical TOP at home needed a vacuum aspiration. Telemedicine can provide an alternative to unsafe TOP. Outcomes of care are in the same range as TOP provided in outpatient settings.     

Sequential use of Foley catheter with misoprostol for second trimester pregnancy termination in women with and without caesarean scars: a prospective cohort study

Purpose: The aim of this study is to evaluate the effectiveness and safety of misoprostol and Foley catheter in second trimester termination in women with and without caesarean section (CS) scars.

Materials and methods: Women with an indication for pregnancy termination between 14 and 22 completed weeks of gestation were included to the study. Enrolled women were allocated into three groups: (1) women with no history of CS, (2) women with one CS and (3) women with ≥2 CS. Study consisted 337 patients (233 group 1, 88 group 2 and 16 group 3). Misoprostol and Foley catheter were used sequentially. The primary outcome was the induction to abortion interval. Secondary outcomes were the successful vaginal abortion rate, the percentage of abortions in 24?h and the rates of surgical removal of the placenta, Foley catheter use and major maternal complications (transfusions, thromboembolic events, uterine rupture and death).

Results: Demographic characteristics were comparable. All study outcomes were statistically similar among groups. There was no major maternal complication among all patients.

Conclusions: Sequential use of misoprostol and Foley catheter is safe and effective in second trimester pregnancy termination for patients with and without CS scars.     

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

OBJECTIVE: To compare efficacy of sublingual (S/L), oral and vaginal routes of misoprostol administration for cervical priming before suction evacuation (SE) under local anaesthesia. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Analgesic effects of acetaminophen,diclofenac and hyoscine N-butylbromide in second trimester pregnancy termination: a prospective randomized study

Objectives: This prospective, randomized study aimed to compare the analgesic effects of acetaminophen, diclofenac and hyoscine-N-butylbromide (HnBB) in cases of second trimester pregnancy termination.

Methods: In 60 women with indications for second trimester pregnancy termination, three analgesic agents were randomized into three groups: group 1, acetaminophen; group 2, diclofenac; and group 3, HnBB. A visual analog scale (VAS) used for the evaluation of pain perception. The primary outcome of the study was mean VAS score during the procedure and last VAS score before the completion of termination. The secondary outcomes were the induction-to-abortion interval, the percentage of aborted cases within the first 24?h and finally the need for parenteral analgesia.

Results: Demographic characteristics were similar among the groups. The mean VAS and last VAS scores before termination did not differ among the groups (p?=?0.3 and 0.2, respectively). The need for parenteral analgesia did not differ among the groups (p?=?0.3). Although a shorter induction-to-abortion interval and greater number of cases with successful termination before 24?h were found in the HnBB group, the differences were not statistically significant (p?=?0.6 and 0.5, respectively).

Conclusions: Our study did not demonstrate a difference in pain perception among second trimester pregnancy termination cases using acetaminophen, diclofenac and HnBB.     

Dosing interval of 24 hours versus 48 hours between mifepristone and misoprostol administration for mid-trimester termination of pregnancy

Objective

To compare the efficacy of a shorter interval (24 hours) between misoprostol and mifepristone administration with that of the conventional dosing interval (48 hours) for second-trimester termination of pregnancy (TOP).

Methods

This was a prospective randomized, controlled, open-label study of 98 healthy women opting for mid-trimester TOP. The women were randomized to receive 200 mg mifepristone orally, followed 24 hours (Group 1) or 48 hours (Group 2) later by misoprostol (800 μg, then 400 μg every 3 hours). The primary outcome measure was the percentage of successful abortions within 24 hours. Secondary outcome measures were the induction-to-abortion interval (measured from misoprostol administration) and the frequencies of complications and adverse effects.

Results

The rate of successful abortions was similar with the 24-hour and 48-hour dosing intervals (95.8% and 93.6%, respectively; P = 0.38). The mean induction-to-abortion interval was also comparable between the 2 groups (8.6 ± 4.1 hours versus 8.7 ± 3.9 hours; P = 0.37). Nulliparous women and women with a pregnancy duration of 16 weeks or more had a longer induction-to-abortion interval in both groups.

Conclusion

The 24-hour dosing interval between misoprostol and mifepristone administration seems to be as effective as the 48-hour dosing interval for second trimester TOP.Clinical Trial Registry India: CTRI/2011/05/001770.     

Mifepristone combined with misoprostol versus intra-amniotic injection of ethacridine lactate for the termination of second trimester pregnancy: a prospective, open-label, randomized clinical trial

Objectives

To compare the effectiveness and safety of mifepristone/misoprostol versus intra-amniotic injection of ethacridine lactate for the termination of second trimester pregnancy.

Study design

210 women requesting voluntary termination of pregnancies at between 16 and 24 weeks of gestation were randomly assigned into two groups. Group 1 (MM) received a single oral dose of 200 mg mifepristone and, 36-48 h later, 400 μg of misoprostol vaginally, with up to three additional oral doses of 400 μg misoprostol every 12 h. Group 2 (EL) received an intra-amniotic injection of 100 mg ethacridine lactate. The primary outcome was successful abortion rate. Secondary outcomes included the difference in the induction-to-abortion interval and the frequency of adverse events.

Results

Both MM and EL regimens were effective, with successful abortion rates of 96.19% and 94.29%, respectively (P = 0.746). The complete abortion rates were 68.57% and 70.48%, respectively. The induction-to-abortion interval was longer in the MM group than in the EL group (50.57 ± 6.80 h vs. 43.02 ± 8.74 h, respectively, P < 0.001). Both treatments were safe, although there was a significant difference in rates of gastrointestinal and fever adverse events between the two groups.

Conclusions

Both MM and EL regimens were effective with high success rates and were safe for the termination of second trimester pregnancy.     

米非司酮配伍米索前列醇终止8～16周妊娠有效性及安全性的临床研究

目的：探讨米非司酮配伍不同用药途径（口服或阴道给药）的米索前列醇终止8~16周妊娠的有效性和安全性。方法采用随机、开放、多中心研究,于2011年1月至2012年10月间对复旦大学附属妇产科医院等11个研究中心纳入的625例观察对象进入数据分析,口服组417例,其中孕8~9周198例、孕10~16周219例;阴道组208例,其中孕8~9周99例、孕10~16周109例。第1、2天分别顿服米非司酮100 mg,距首次口服米非司酮36~48 h后,口服组予米索前列醇400μg口服,间隔3 h重复给药400μg,最多4次;阴道组予米索前列醇600μg阴道放置,间隔6 h重复给药400μg,最多4次。主要评价指标为流产有效率,其他评价指标包括胚胎或胎儿排出时间、阴道流血情况、月经复潮时间及安全性等。结果（1）流产有效率阴道组[98.1%（202/206）]优于口服组[94.0%（390/415）],两组比较,差异有统计学意义（P=0.023）。按孕周分层,孕8~9周流产有效率口服组为95.9%（189/197）,阴道组99.0%（96/97）;孕10~16周流产有效率口服组为92.2%（201/218）,阴道组97.2%（106/109）;两组分别比较,差异均无统计学意义（P=0.156、0.073）。（2）胚胎或胎儿排出时间按孕周分层,孕8~9周口服组为（4.3±7.9）h,阴道组（3.8±2.5）h;孕10~16周口服组为（6.2±4.8）h,阴道组（5.5±3.8）h;两组分别比较,差异均无统计学意义（P=0.238、0.273）;孕8~9周平均为（4.1±6.6）h,孕10~16周平均为（6.0±4.5）h。（3）孕8~9周观察对象胎盘娩出2 h内阴道流血量口服组平均为（63±46）ml,多于阴道组的（55±45）ml,两组比较,差异有统计学意义（P=0.047）;孕10~16周胎盘娩出2 h内阴道流血量口服组为（76±52）ml,与阴道组的（76±61）ml比较,差异无统计学意义（P=0.507）。（4）月经复潮时间两组均在37 d左右。（5）研究期间发生5例严重不良事件,其中2例与药物相关;其他不良事件均为轻中度;口服组胃肠道症状恶心、呕吐的发生率分别为57.2%（239/417）、36.3%（151/417）,高于阴道组的45.4%（94/208）、26.1%（54/208）,两组比较,差异均有统计学意义（P=0.005、0.011）。结论米非司酮配伍米索前列醇终止8~16周妊娠,无论口服还是阴道给药均安全有效,这种非侵入性终止妊娠的方法值得临床推广应用。