Intravaginal misoprostol versus uterine curettage for missed abortion: A cost-effectiveness analysis.

PURPOSE: To evaluate the cost-effectiveness of a strategy based on direct-acting uterine curettage (UC) versus a pre-direct-acting misoprostol (1600 mg) in patients with missed abortion (MA), from the perspective of a National Health System. METHODS: An open prospective cohort study was carried out at Reina Sofía University Hospital (Córdoba, Spain) from January 1, 2019 to December 31, 2019 in 180 patients diagnosed with MA. The patients chose medical treatment with intravaginal misoprostol (800 µg/4 h) or UC after receiving complete and detailed information. The effectiveness, clinical characteristics of the patients, costs of treating and managing the disease, and satisfaction with the procedures were recorded. RESULTS: One hundred and forty-five patients (80.6%) chose misoprostol versus 35 patients (19.4%) who chose UC. The effectiveness of misoprostol has been 42% evaluated at 48 h; UC success rate has been 100%. The incidence of side effects is significantly higher in patients treated with misoprostol (p < 0.05); as well as the number of care received by the patient (p < 0.05). Satisfaction is higher in patients treated with UC (p < 0.05). However, the cost is almost 5-folds higher in patients treated with UC (p < 0.05). CONCLUSION: UC has a higher success rate, greater satisfaction, and a lower incidence of side effects, although significantly increases the cost compared to misoprostol in MA.

Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone. METHODS: MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 µg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/m2vs ≥35 kg/m2), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024. FINDINGS: Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups. INTERPRETATION: Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Cost-effectiveness of mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage: an economic evaluation based on the MifeMiso trial.

OBJECTIVE: To assess the cost-effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage. DESIGN: Within-trial economic evaluation and model-based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost-effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS). SETTING: Twenty-eight UK NHS early pregnancy units. SAMPLE: A cohort of 711 women aged 16-39 years with ultrasound evidence of a missed miscarriage. METHODS: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets. MAIN OUTCOME MEASURES: Cost per additional successfully managed miscarriage and quality-adjusted life years (QALYs). RESULTS: For the within-trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7-12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI -0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26-£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model-based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model-based evidence suggests that the intervention is a less effective but less costly strategy than surgical management. CONCLUSIONS: The within-trial analysis found that based on cost-effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage. TWEETABLE ABSTRACT: The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages.

Efficacy of mifepristone and misoprostol for medical treatment of missed miscarriage in clinical practice-A cohort study.

INTRODUCTION: It has been estimated that one out of every four women experience first-trimester miscarriage. Missed miscarriage is a common form of early miscarriage where the products of conception are not expelled from the uterus. It is diagnosed by ultrasound. The primary objective of this study was to evaluate the success rate of a combination treatment with mifepristone and misoprostol for missed miscarriage in clinical practice. The secondary objective was to identify significant factors influencing the rate of success. MATERIAL AND METHODS: A cohort of 941 consecutive women with an ICD-10 diagnosis of missed miscarriage who received treatment with 800 µg vaginal misoprostol and 2 repeat doses of 400 µg oral misoprostol after mifepristone pretreatment between 1 January 2012 and 31 December 2014 was analyzed. Women with a uterine size smaller than 12 weeks who were planned for medical treatment were included in the study. The exclusion criteria were primary surgical management or planned follow up outside the Stockholm County Council area. RESULTS: The success rate of medical treatment, defined as no need for surgical treatment, was 85.5% (805/941) in women with a uterine size of less than 12 weeks. However, for women with uterine size below 9 weeks the success rate was 88.9% (586/659). Indeed, uterine size of 9 gestational weeks or larger at time of treatment was identified as the only significant risk factor for surgical intervention. CONCLUSIONS: The medical regimen for missed miscarriage offered in this study appears to be safe and with high rates of success. Conclusions about which women to exclude from medical treatment could not be made. Medical treatment may therefore benefit all women with missed miscarriage who wish to avoid primary surgery.

Sublingual vs vaginal misoprostol for completion of first trimester missed abortion: a randomised controlled trial.

OBJECTIVE: The study aimed to compare the efficacy and safety of sublingual and vaginal misoprostol for termination of pregnancy in women with first trimester missed abortion. METHODS: A single-blind, parallel group, randomised clinical trial (ClinicalTrials.gov NCT02686840) was conducted in a university hospital between 1 February 2016 and 31 January 2017. All women who presented with first trimester missed abortion were invited to participate in the study and were randomised to one of two groups: one group received sublingual misoprostol in three doses of 800 µg every 4 h, while a second group received vaginal misoprostol in the same dosage regimen. The primary outcome of the study was the rate of complete abortion within 7 days after initiation of treatment. RESULTS: The study included 200 women (100 in each arm). By day 7, successful complete abortion was significantly more frequent in the sublingual misoprostol group (71.4%) than in the vaginal misoprostol group (51.5%) (p = .006). By day 30, the rate of complete abortion was higher in the sublingual misoprostol group (90.6%) than in the vaginal misoprostol group (83.9%), but with no statistically significant difference (p = .164). The mean length of the induction-expulsion interval in the sublingual misoprostol group was significantly shorter compared with the vaginal misoprostol group (12.3 ± 3.1 h vs 16.4 ± 4.2 h, respectively; p = .001) and the sublingual misoprostol group had a smaller drop in haemoglobin level (p = .001). The side effects of misoprostol were significantly more frequent in the sublingual group compared with the vaginal group. CONCLUSION: Sublingual misoprostol is more effective than vaginal misoprostol in completing first trimester missed abortion, with a shorter induction-expulsion time. Sublingual misoprostol is, however, associated with more side effects, such as unpleasant taste, gastrointestinal symptoms and fever, compared with vaginal misoprostol.

Medical management of first trimester missed miscarriage: the efficacy and complication rate.

Our aim of the study was to evaluate the efficacy and complication rate of our inpatient medical management protocol for missed miscarriages. Three-hundred and ninety women hospitalised at our tertiary centre because of a missed miscarriage/anembryonic pregnancy in 2012-2013 were included in this retrospective study. The women underwent either a low (until 9 + 0 weeks of gestation) or high gestational age (from 9 + 1 until 15 + 6 weeks of gestation) management protocol. The success rate, curettage in the first 48 hours after the procedure, the complication rate and the factors that might influence these outcomes were evaluated. The overall success rate was 83.3%. The curettage in the first 48 hours after the procedure was performed in 7.4% of the patients and was more often in the high gestational age protocol. Complications that required another outpatient visit or hospitalisation occurred in 9% of the patients. Higher beta-hCG values 14 days after the procedure and the absence of evacuation of products of conception during hospitalisation were associated with a higher complication rate. IMPACT STATEMENT What is already known on this subject? As much as 10-20% of clinically recognised pregnancies end in a spontaneous abortion. A missed miscarriage and a blighted ovum represent a form of spontaneous abortion, which has long been treated with surgical evacuation. However, nowadays, medical management represents a well-established alternative with very high success rates and is considered as an equivalent and safe method that is also very well accepted by patients. What do the results of this study add? According to our results, a medical management of a first trimester missed miscarriage and a blighted ovum is very effective with an overall success rate of 83.3% and a very low percentage of curettage in the first 48 hours after the procedure (7.4%). Our study was also able to identify higher beta-hCG values 14 days after procedure and absence of evacuation of products of conception during hospitalisation as risk factors for complication occurrence. What are the implications of these findings for clinical practice and/or further research? Our study helps to identify patients who are at greater risk for developing complications after the medical management of a first trimester missed miscarriage.

Association between uterine position and transvaginal misoprostol treatment for early pregnancy failure.

AIM: We aimed to determine the importance of uterine position as a predicting factor of success rate in medically treated early pregnancy failure (EPF). METHODS: We carried out a retrospective cohort study at the Obstetrics and Gynecology Department of a tertiary medical center between January 2011 and June 2012. We included women diagnosed with EPF, which we defined as women diagnosed with missed abortion up to 13 gestational weeks. Patients were treated with one or two doses of 800 µg of misoprostol vaginally in accordance with the department's protocol. Demographic, clinical, and treatment success data were collected from patient electronic records. RESULTS: A total of 255 women were included in our study. The success rate after treatment with misoprostol for the anterior uterine group was 78.7% as compared to the non-anterior uterine group, which achieved a success rate of 88.1%. This difference was not statistically significant (P = 0.180). In a multivariate analysis comparing patients for whom treatment with misoprostol was successful as opposed to patients for whom treatment failed, only embryonic sac size showed a statistically significant difference, measuring shorter in the success group. CONCLUSION: Uterine position has no effect on success rate of misoprostol treatment for EPF.

Utility of ßhCG monitoring in the follow-up of medical management of miscarriage.

OBJECTIVE: To evaluate the percentage change in total ßeta-unit human chorionic gonadotropin (ßhCG) levels (%ΔßhCG) in the prediction of treatment outcomes following intravaginal misoprostol for missed miscarriage before 13 weeks. METHODS: A secondary analysis of a randomised controlled study of medical management of miscarriage was performed. Total ßhCG levels were collected before misoprostol (baseline) and after a planned seven day interval (follow-up), when a transvaginal ultrasound (TVUS) reported a gestational sac as present or not. If no sac at TVUS, surgery was indicated on clinical criteria. %ΔßhCG ((baseline ßhCG - follow-up ßhCG)/baseline ßhCG × 100) was evaluated in the prediction of a sac at TVUS and surgery on clinical criteria. RESULTS: %ΔßhCG was calculated for cases with ßhCG levels within two days of misoprostol and TVUS; calculation interval determined case number. The median %ΔßhCG for 24 cases with a persistent sac (6-9 day interval) was significantly lower than for 145 with no sac (58.75% (interquartile range (IQR): 37.59-76.69; maximum 86.54) vs 97.65% (IQR: 95.44-98.43); P < 0.0001). The median %ΔßhCG for eight cases needing surgery on clinical criteria (5-9 day interval) was significantly lower than for 140 cases with no sac not needing surgery (79.68% (IQR: 64.63-91.15; maximum 94.06) vs 97.68% (IQR: 95.61-98.50); P < 0.0001). The area under the receiver-operator curve was 0.975 for prediction of a persistent sac and 0.944 for prediction of surgery on clinical criteria, respectively. %ΔßhCG > 87% predicted no sac at TVUS. %ΔßhCG > 94.5% predicted no surgery on clinical criteria. CONCLUSION: %ΔßhCG calculation over one week reliably predicted treatment outcomes after medical management of missed miscarriage.

Sublingual misoprostol for management of empty sac or missed miscarriage: The first two years' experience at a metropolitan Australian hospital.

BACKGROUND: Misoprostol management of miscarriage is only now becoming widely used in Australia. AIMS: To review the efficacy, safety and the popularity of outpatient sublingual misoprostol in empty sac/missed miscarriage management over its first two years of availability in a metropolitan Australian hospital. MATERIALS AND METHODS: A retrospective cohort review was undertaken of women choosing sublingual misoprostol 600 µg (three tablets) × three doses for miscarriage management. Principal outcomes assessed were miscarriage resolution without the need for curettage and complications. Additionally, the relative popularity of misoprostol versus surgery by place of birth and over time, and the return of pregnancy tissue for histology were analysed. RESULTS: Between 1 December 2012 and 30 November 2014, 279 women chose sublingual misoprostol for nonurgent miscarriage management, while 420 chose surgery (40 and 60%, respectively). Of the misoprostol cohort, 269 had complete data; 239 of 269 (88.8%) had resolution without curettage, nine (3.3%) had acute curettage, 21 (7.8%) had nonacute curettage, 30 (11.15%) had unplanned emergency department presentation, 11 (4.1%) had unplanned admission, three (1.1%) had blood transfusion and one (0.4%) had an infection requiring admission. Misoprostol was as popular with Australian-born as overseas-born women; 53.5% of patients returned histopathology specimens; one (0.7%) demonstrated partial hydatidiform mole. CONCLUSIONS: Outpatient management of missed/empty gestational sac miscarriage using sublingual misoprostol is associated with a high rate of avoiding curettage and the low rate of complication. It is equally popular with Australian-born and overseas-born women. Just over 50% returned pregnancy tissue for analysis.

The medical management of missed miscarriage: outcomes from a prospective, single-centre, Australian cohort.

OBJECTIVE: To report the prospective outcomes of medical management of missed miscarriage before 13 weeks' gestation from an Australian cohort. DESIGN: Descriptive study of a cohort selected out of a randomised controlled trial. SETTING: Outpatient management at a maternity hospital between 1 May 2007 and 28 July 2010. PARTICIPANTS: 264 women requesting medical management of missed miscarriage. MAIN OUTCOME MEASURES: Number of doses of misoprostol required, unscheduled visits for care, findings at ultrasound follow-up, requirement for surgical management, number of cases of gestational trophoblastic disease (GTD), and self-reported patient experience. RESULTS: 107 women (40.5%) received a repeat dose of misoprostol, and 79 women (29.9%) made unscheduled visits for care. Among the 241 women with Day 7 ultrasound follow-up, a gestational sac was found in 32 women (13.3%), indicating failure of medical management. Complete miscarriage was induced without the need for surgery in 206 women (78.0%). Surgery was performed as an emergency in 13 women (4.9%). Twelve women (4.5%) had surgery for ongoing bleeding after medical management, and four of these did not have chorionic villi on histopathological examination. Five women (1.9%) had GTD, which was managed incidentally under the protocol. Among those who returned patient questionnaires, 73.0% participants (116/159) indicated that they would recommend medical management of miscarriage to other women, while 18.2% (29/159) indicated that they would undergo surgery next time. CONCLUSION: The medical management of missed miscarriage on an outpatient basis is safe and effective. TRIAL REGISTRATION: ACTRN12612000150842.

The association between serum progesterone and outcome of medical management of early fetal demise: a pilot study.

The study objective was to determine the relationship between serum progesterone level and the outcome of mifepristone-misoprostol regimen for medical management of missed miscarriage up to 12 weeks. A blood sample was collected just before mifepristone administration for serum progesterone assay. After 48 h, misoprostol 800 µg was administered vaginally; further 400 µg was administered 4 h later if necessary. Treatment was classed as a success if retained tissues were expelled within 72 h (Group 1), and a failure if this did not occur (Group 2). Of 52 analysed cases, complete medical evacuation occurred within 72 h in 40 (76.9%) women (serum progesterone ranged 13-90 nmol/l). Serum progesterone between the two groups were statistically significant (p < 0.001), by Mann-Whitney test. Of the 12 patients who did not respond, nine (75%) women had serum progesterone < 10 nmol/l. We found mifepristone-misoprostol regimen is less effective in missed miscarriage when serum progesterone is < 10 nmol/l.

The management of missed miscarriage in an outpatient setting: 800 versus 600 µg of vaginal misoprostol.

BACKGROUND: Many misoprostol regimens have been used to treat early pregnancy loss as an alternative to surgical evacuation, with differing adverse event and success rates. AIMS: This study sought to compare the effectiveness and adverse effects of 800 and 600 µg of misoprostol administered vaginally for the treatment of early pregnancy failure in an outpatient setting. METHODS: A retrospective, observational study of 946 women with a missed miscarriage <12 weeks' gestation was performed: 487 women received 800 µg (group 1) and 459 women received 600 µg (group 2) of vaginal misoprostol every 24 h for two days. The first follow-up was seven days after treatment. Women were asked about symptoms, and a transvaginal ultrasound was performed. If an incomplete miscarriage or gestational sac was still found, then an additional dose of intravaginal misoprostol was prescribed, and a second follow-up visit was arranged for seven days later. Surgical evacuation was scheduled for women who did not wish to continue medical treatment after the first or second follow-up visit. RESULTS: The total rate of complete miscarriage was 90.6% after 800 µg and 87.8% after 600 µg of intravaginal misoprostol. The percentage of women who underwent surgical evacuation after medical treatment was 9.4% for group 1 and 12.2% for group 2. CONCLUSIONS: Complete uterine evacuation after a missed miscarriage was effectively induced by both 600 and 800 µg of misoprostol. The overall success of medical treatment with intravaginal misoprostol demonstrates that the treatment is safe in an outpatient setting.

Factors Affecting the Success of Repeated Misoprostol Course for the Treatment of Missed Abortion.

OBJECTIVE: To assess the rates of success of the second dose of Misoprostol administration and to evaluate the parameters that affect the success of this approach. STUDY DESIGN: This retrospective cohort study was performed using institutional database of Carmel Medical Center between the dates of 1/11/2012-1/11/2017. Patients with ultrasound proven intrauterine abnormal pregnancy, treated for missed abortion or blighted ovum by two doses of intravaginal Misoprostol were included. The primary outcome was the treatment success rate of repeated Misoprostol treatment, and factors affecting this outcome. RESULTS: Overall, 97 patients were included in the study. The success of repeated dose of Misoprostol was noted in 46 cases (47.4%). A higher success rate was noted in symptomatic women - 64.3% vs. 35.7% in asymptomatic patients (Odds Ratio 2.6, 95% Confidence Interval 1.1-6.5). In addition, marginal significance was noted for pregnancies with an embryonic pulse previously observed (66.7% in the success group vs. 33.3% in failed treatment, p=0.051). DISCUSSION: Efficacy of a repeated Misoprostol course was shown to have a success rate of 47%%. This success rate is slightly increased in women presenting symptoms of bleeding before first administration. This information is highly important in the clinical discussion with each patient prior choosing a possible treatment.

[Mifepristone in primary care: no impediments against its use in management of missed miscarriage]. / Prescriptie van mifepriston in de eerste lijn?

In the Netherlands, medical treatment to women with a non-vital pregnancy is provided in secondary care. In a Dutch pilot study, it has been shown that treatment of a missed miscarriage with misoprostol in primary care is an acceptable alternative. However, there are clear indications that medical treatment in women with a non-vital pregnancy is greatly improved when mifepristone is prescribed in addition to misoprostol. The authors state that this treatment is also justified in primary care.

Evaluation of the introduction of a new treatment for the termination of pregnancy in The Netherlands.

All hospital-based gynecologists in The Netherlands were sent a questionnaire on the termination of pregnancy with off-label drugs in the absence of treatment protocols. Response was received from 93.2% of the teaching hospitals and 87.9% of the non-teaching hospitals, thus representing practice of nearly all gynecologists working in The Netherlands. More than 40 different regimens were used for five different indications. Gynecologists embarked on a large number of different regimens of which a distressing number do not have any merits to be found in studies or guidelines illustrating that, without clear protocols or guidelines, the implementation of new medical treatments is potential haphazard and based on personal preference. Suboptimal treatment regimens will frustrate patients and doctors and deprive future patients from the most efficacious and patient friendly treatment regimes available.

Sublingual versus vaginal misoprostol for the management of missed abortion.

AIM: To evaluate the efficacy of two routes of misoprostol administration (sublingual and vaginal) for the treatment of missed abortion. METHODS: Two hundred and twenty women with confirmed missed abortion who received 400 microg/6 h misoprostol either sublingually or vaginally, were included in this randomized control trial. All women were admitted to hospital for follow-up care for 2 days. If the pregnancy was not completely evacuated during this time, the patient underwent immediate surgical completion. Efficacy was defined as the percentage of women discharged from the study without the need for surgical intervention. RESULTS: The effectiveness was high in the sublingual group and statistically different (sublingual 84.5%, vaginal 46.4% P = 0.000 RR = 0.54 95%CI = 0.442-0.681). The groups differed in terms of complications like bleeding (88.2% vs 65.5%), pain (85.5% vs 56.4%), diarrhea (69.1% vs 36.4%) and fever (23.6% vs 13.3%) in the sublingual group versus the vaginal group, but the mean time to expulsion was shorter (9.68 h SD = 5.51 95%CI = 8.61-10.57) in the sublingual group than the vaginal group (16.64 h SD = 14.01 95%CI = 13.8-19.48), P = 0.000. Women in the sublingual group were highly satisfied with the method. CONCLUSION: Sublingual misoprostol for the medical management of missed abortion is more effective and more acceptable than the vaginal route. However, it showed more adverse effects.

Early pregnancy failure: factors affecting successful medical treatment.

BACKGROUND: The results of medical treatment for early pregnancy failure are conflicting. OBJECTIVES: To determine whether gestational sac volume measurement as well as other variables can predict the success rate of medical treatment for early pregnancy failure. METHODS: The study group comprised 81 women diagnosed with missed abortion or anembryonic pregnancy who consented to medical treatment. Demographic data were collected and beta-human chorionic gonadotropin level was documented. Crown-rump length and the sac volume were measured using transvaginal ultrasound. TVU was performed 12-24 hours after intravaginal administration of 800 micro g misoprostol. If the thickness of the uterine cavity was less than 30 mm, the women were discharged. If the sac was still intact or the thickness of the uterine cavity exceeded 30 mm, they were offered an additional dosage of intravaginal misoprostol or surgical uterine evacuation. RESULTS: Medical treatment successfully terminated 32 pregnancies (39.5%), 30 after one dose of misoprostol and 2 after two doses (group A); 49 underwent surgical evacuation (group B), 47 following one dose of misoprostol and 2 following two doses. There were no significant differences between the groups in age and gestational week. Gestational sac volume did not differ between groups A and B (10.03 and 11.98 ml respectively, P = 0.283). Parity (0.87 and 1.43, P = 0.015), previous pregnancies (2.38 and 2.88, P = 0.037), and betahCG concentration (6961 and 28,748 mlU, P = 0.013) differed significantly between the groups. CONCLUSIONS: Gestational sac volume is not a predictor of successful medical treatment for early pregnancy failure. Previous pregnancies and deliveries and higher betahCG concentration negatively affect the success rate of medical treatment.

Sublingual versus vaginal misoprostol in the management of missed miscarriage.

OBJECTIVE: To compare the efficacy of sublingual and vaginal misoprostol in the medical management of missed miscarriage. METHODS: Fifty women diagnosed as having missed miscarriage of gestational age less than 20 weeks were assigned randomly to receive 400 microg of either sublingual or vaginal misoprostol every three hours, up to a maximum of five doses. The primary outcome measures were, complete evacuation of products of conception, mean induction to delivery time and the occurrence of side effects. RESULTS: There was no significant difference in complete evacuation rates between the sublingual misoprostol and the vaginal misoprostol groups (52% vs. 48%, p = 0.571) mainly within the first 24 hours. Mean induction to delivery time was also similar for both groups (13.07 +/- 6.95 hours for sublingual versus 13.29 +/- 5.63 hours for vaginal group) as was the total number of doses required (4.44 +/- 1.04 for sublingual versus 4.52 +/- 0.96 for vaginal misoprostol). Side effects were seen in 18 women (72%) in the sublingual group compared to 5 women (20%) in the vaginal group (p < 0.001). The incidence of unpleasant taste was significantly higher in the sublingual group than in the vaginal group (60% versus 4%, p = < 0.001). CONCLUSION: Sublingual misoprostol is as effective as vaginal misoprostol for medical management of missed miscarriage but is associated with an increased risk of side effects especially an unpleasant taste.

Effect of misoprostol with and without letrozole on the induction of abortion for women with first-trimester missed abortion.

OBJECTIVE: To determine whether addition of letrozole to a misoprostol-based abortion regimen can increase the rate of complete abortion. METHODS: The randomized, placebo-controlled, double-blind trial enrolled women with missed abortion in the first trimester of pregnancy attending Sadooghi Hospital, Isfahan, Iran, from 2016 to 2018. The women were randomly assigned to the study group, which received 10 mg of letrozole daily for 3 days, followed by two doses of 800 µg of vaginal misoprostol at a 4-hour interval, or the control group, which received a placebo, followed by the same dose of misoprostol. Sonography was performed to check the abortion status. RESULTS: In total, 120 women completed the study: 60 in the misoprostol plus letrozole group, and 60 in the misoprostol only group. Complete abortion was documented for 93 (77.5%) women: 48 (80.0%) in the misoprostol plus letrozole group and 45 (75.0%) in the misoprostol only group (P=0.80). The mean duration of induction in the misoprostol plus letrozole and misoprostol only groups was 7.35 ± 3.54 hours and 8.2 ± 3.8 4hours, respectively (P=0.21). CONCLUSION: Administration of misoprostol alone was found to be as effective as the administration of misoprostol plus letrozole for first-trimester missed abortion.

The use of misoprostol in obstetrics and gynaecology.

Misoprostol, although originally introduced as a therapy for gastric ulcers, is now widely used in reproductive health. For some indications it is now the optimal choice, whilst for others it provides an important alternative, especially in low-resource settings. The optimal dose varies widely from 20 to 600 mcg depending on the indication and gestation. Use of the correct dose is important, too low a dose will be ineffective and overdosage can be dangerous for mother and baby. Evidence-based information about the safest regimens for multiple pregnancy indications are therefore provided in this review.