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.

The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Caesarean scar pregnancy in the UK: a national cohort study.

OBJECTIVE: To estimate the incidence of caesarean scar pregnancy (CSP) and to describe the management outcomes associated with this condition. DESIGN: A national cohort study using the UK Early Pregnancy Surveillance Service (UKEPSS). SETTING: 86 participating Early Pregnancy Units. POPULATION: All women diagnosed in the participating units with CSP between November 2013 and January 2015. METHODS: Cohort study of women identified through the UKEPSS monthly mailing system. MAIN OUTCOME MEASURES: Incidence, clinical outcomes and complications. RESULTS: 102 cases of CSP were reported, with an estimated incidence of 1.5 per 10 000 (95% CI 1.1-1.9) maternities. Full outcome data were available for 92 women. Management was expectant in 21/92 (23%), medical in 15/92 (16%) and surgical in 56/92 (61%). The success rates of expectant, medical and surgical management were 43% (9/21), 46% (7/15) and 96% (54/56), respectively. The complication rates were 15/21 (71%) with expectant, 9/15 (60%) with medical and 20/56 (36%) with surgical management. Discharge from care (median number of days) was 82 (range 37-174) with expectant, 21 (range 10-31) with medical and 11 (range 4-49) with surgical management. CONCLUSIONS: Surgical management appears to be associated with a high success rate, low complication rate and short post-treatment follow up. TWEETABLE ABSTRACT: Surgery for CSP appears to be successful, with low complication rates and short post-treatment follow up.

Fallopian tube catheterization in the treatment of proximal tubal obstruction: a systematic review and meta-analysis.

Study question: What is the chance of clinical pregnancy when fallopian tube catheterization is used for proximal tubal obstruction? Summary answer: The pooled clinical pregnancy rate of tubal catheterization after proximal tubal obstruction is 27% (95% CI 25-30%). What is known already: Restoring fallopian tube patency by performing tubal catheterization has fallen out of favour since the increased availability of IVF. Our study is the first systematic review and meta-analysis to investigate reproductive outcomes following tubal catheterization for proximal tubal obstruction. Study design, size, duration: We undertook a systematic review and meta-analysis of 27 observational studies consisting of 1720 patients undergoing tubal catheterization for proximal tubal obstruction, who attempted to conceive naturally after the procedure. Participants/materials, setting, methods: Systematic literature searches were performed in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A total of 2195 titles and abstracts were reviewed. Only studies that reported outcomes when tubal catheterization was performed with no other tubal surgery were included. Twenty-seven cohort studies matched the inclusion criteria for the meta-analysis. Main results and the role of chance: The meta-analysis showed a pooled clinical pregnancy rate of 27% (95% CI 25-30%) after the use of tubal catheterization for unilateral or bilateral proximal tubal obstruction (27 studies, 1556 patients). In women with bilateral obstruction (14 studies, 617 patients), the clinical pregnancy rate was 27% (95% CI 23-32%). Our meta-analysis demonstrated that the pooled cumulative clinical pregnancy rates were 22.3% (95% CI 17.8-27.8%) at 6 months, 25.8% (95% CI 21.1-31.5%) at 9 months, 26.4% (95% CI 23.0-30.2%) at 12 months, 26.0% (95% CI 22.8-29.7%) at 18 months, 27.0% (95% CI 24.0-30.5%) at 24 months, 27.9% (95% CI 24.9-31.3%) at 36 months and 28.5% (95% CI 25.5-31.8%) at 48 months. The pooled live birth rate (14 studies, 551 patients) was 22% (95% CI 18-26%). The pooled ectopic pregnancy rate (27 studies, 1556 patients) was 4% (95% CI 3-5%). The included studies scored satisfactorily on the Newcastle-Ottawa quality assessment scale. Limitations, reasons for caution: The pooled clinical pregnancy rate after tubal catheterization was found to be almost comparable to that after IVF. However, included studies were small, non-comparative series with significant clinical heterogeneity in population characteristics, follow-up and surgical equipment, technique and experience. Wider implications of the findings: These findings suggest fallopian tube catheterization as an alternative strategy to IVF in patients presenting with proximal tubal obstruction. Further research should focus on comparing different surgical techniques of fallopian tube catheterization with IVF and provide cumulative reproductive outcomes over long-term follow-up. Study funding/competing interest(s): No funding was required and the authors have no competing interests to declare. Registration number: N/A.

Salpingostomy in the treatment of hydrosalpinx: a systematic review and meta-analysis.

STUDY QUESTION: What is the chance of natural conception when salpingostomy is used to treat hydrosalpinx?. SUMMARY ANSWER: The natural clinical pregnancy rate following salpingostomy is 27%, in the hands of experienced surgeons who publish their results. WHAT IS KNOWN ALREADY: Tubal surgery is not commonly offered for women with hydrosalpinges since the advent of assisted conception treatment. This is the first systematic review to investigate natural conception rates following salpingostomy in the treatment of hydrosalpinx. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of 22 observational studies encompasses 2810 patients undergoing salpingostomy and attempting natural conception. PARTICIPANTS/MATERIALS, SETTING, METHODS: Literature searches were conducted to retrieve observational studies which reported salpingostomy for hydrosalpinx. Databases searched included MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL, with no language restriction. Only studies that focused on salpingostomy (rather than other tubal conserving surgeries) for the treatment of hydrosalpinx were included. A total of 22 studies matched the inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE: The pooled natural clinical pregnancy rate from the 22 observational studies (including 2810 patients) was 27% (95% confidence interval (CI): 25-29%) after salpingostomy was performed for hydrosalpinx. The cumulative clinical pregnancy rates were 8.7% (95% CI: 6.6-11.5%) at 6 months, 13.3% (95% CI: 10.6-16.7%) at 9 months, 20.0% (95% CI: 17.5-22.8%) at 12 months, 21.2% (95% CI: 18.6-24.1%) at 18 months and 25.5% (95% CI: 22.2-29.4%) at 24 months after salpingostomy. The pooled live birth rate (10 studies, 1469 patients) was 25% (95% CI: 22-28%) after salpingostomy was performed for hydrosalpinx. The pooled ectopic pregnancy rate (19 studies, 2662 patients) was 10% (95% CI: 9-11%). The pooled miscarriage rate (seven studies, 924 patients) was 7% (95% CI: 6-9%). The included studies scored well on the Newcastle Ottawa quality assessment scale. LIMITATIONS, REASONS FOR CAUTION: Strict inclusion criteria were used in the conduct of the systematic review. However, the studies included are clinically heterogeneous in many aspects including patient characteristics, surgical technique and duration of follow-up after salpingostomy. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this systematic review suggest that salpingostomy is an alternative treatment strategy to tubal clipping or salpingectomy in patients presenting to fertility services with hydrosalpinx. Further prospective, large and high quality studies are needed to identify the subpopulation that would most benefit from tube conserving surgery. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis.

BACKGROUND: Endometriosis is found in 0.5-5% of fertile women and 25-40% of infertile women. It is known that endometriosis is associated with infertility, but there is uncertainty whether women with endometriosis have adverse pregnancy outcomes in in vitro fertilisation (IVF) treatment. OBJECTIVES: To explore the association between endometriosis and IVF outcome. SEARCH STRATEGY: Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science (inception, December 2012) in all languages, together with reference lists of retrieved papers. SELECTION CRITERIA: Studies comparing IVF outcome in women with endometriosis with women without endometriosis. Patients were classified by stage of endometriosis. The outcomes were fertilisation, implantation, clinical pregnancy and live birth rates. Study selection was conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. DATA COLLECTION AND ANALYSIS: Data extraction was conducted independently by two reviewers. Relative risks from individual studies were meta-analysed. MAIN RESULTS: Twenty-seven observational studies were included, comprising 8984 women. Meta-analysis of these studies showed that fertilisation rates were reduced in stage I/II of endometriosis (relative risk [RR] = 0.93, 95% confidence interval [95% CI] 0.87-0.99, P = 0.03). There was a decrease in the implantation rate (RR = 0.79, 95% CI 0.67-0.93, P = 0.006) and clinical pregnancy rate (RR = 0.79, 95% CI 0.69-0.91, P = 0.0008) in women with stage III/IV endometriosis undergoing IVF treatment. CONCLUSION: The presence of severe endometriosis (stage III/IV) is associated with poor implantation and clinical pregnancy rates in women undergoing IVF treatment.

Pre-eclampsia is associated with, and preceded by, hypertriglyceridaemia: a meta-analysis.

BACKGROUND: Elevated triglycerides are a feature of the metabolic syndrome, maternal obesity, maternal vasculitis (i.e. systemic lupus erythematosus) and diabetes mellitus. These conditions are all known risk factors for pre-eclampsia. Hypertriglyceridaemia therefore may be associated with pre-eclampsia and indeed this may precede the presence of overt disease. OBJECTIVE: In this study we determine the association between hypertriglyceridaemia and pre-eclampsia in pregnant women. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Web of Science, Excerpta Medica Database, ISI Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library from inception until June 2012 and reference lists of relevant studies. SELECTION CRITERIA: Two reviewers independently selected studies on pregnant women where triglycerides were measured and women were followed up until the development of pre-eclampsia or selected on the basis of presence of pre-eclampsia and compared with controls. DATA COLLECTION AND ANALYSIS: We collected and meta-analysed the weighted mean differences (WMDs) of triglyceride levels from individual studies using a random effects model. MAIN RESULTS: We found strong evidence from meta-analysis of 24 case-control studies (2720 women) that pre-eclampsia is associated with higher levels of serum triglycerides (WMD 0.78 mmol/l, 95% confidence interval 0.6-0.96, P < 0.00001). This finding is also confirmed in five cohort studies, that recruited 3147 women in the second trimester before the onset of pre-eclampsia, which proves that hypertriglyceridaemia precedes the onset of pre-eclampsia (WMD 0.24 mmol/l, 95% confidence interval 0.13-0.34, P < 0.0001). AUTHOR'S CONCLUSIONS: Hypertriglyceridaemia is associated with and precedes the onset of pre-eclampsia. Further research should focus on defining the prognostic accuracy of this test to identify women at risk and the beneficial effect of triglyceride-lowering therapies in pregnancy.

Dexamethasone reduces pain, vomiting and overall complications following tonsillectomy in adults: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Tonsillectomy is one of the most common surgical procedures, but there is debate whether systemic steroids should be used to reduce pain and post-operative complications. OBJECTIVE OF REVIEW: To determine whether peri-operative steroids reduce post-tonsillectomy pain and complications in adults. TYPE OF REVIEW: Systematic review and meta-analysis of randomised controlled trials. SEARCH STRATEGY: We searched MEDLINE (1950-2010), EMBASE (1980-2010), CINAHL (1981-2010), Web of Science, ProQuest, metaRegister, Conference Proceedings Citation Index, the Cochrane Library and reference lists of relevant studies. EVALUATION METHOD: Two reviewers independently selected trials and extracted data on their quality, characteristics and results. Trials included adults (age >16 years) undergoing elective tonsillectomy where peri-operative steroids were used, and the results were compared with control or placebo. RESULTS: There were seven randomised controlled trials (580 patients) reporting post-operative pain. Meta-analysis demonstrates that dexamethasone in adults reduces the pain level experienced in the first post-tonsillectomy day [standard mean difference (SMD): -0.63, 95% CI: -1.13 to -0.12] with significant heterogeneity (I(2) = 84%, P < 0.00001). Sub-group analysis to explore heterogeneity demonstrated this reduction in pain was mostly with high total dose steroids (total >10 mg over first 24 h post-operatively; SMD: -1.48, 95% CI: -2.17 to -0.79, P < 0.00001), especially when given both intra-operatively and post-operatively. There was no significant effect with low doses (SMD: -0.12, 95% CI: -0.36 to 0.13, P = 0.35). There were three trials (231 patients) that reported post-operative nausea and vomiting, three other trials (270 patients) reporting on bleeding and three trials (401 patients) reporting other complications (infections and odynophagia). There was a significant reduction in post-operative nausea and vomiting (RR: 0.53, 95% CI: 0.36 to 0.80, P = 0.002, I(2) = 26%) and bleeding (RR: 0.45, 95% CI: 0.25 to 0.80, P = 0.007, I(2) = 0%), but the reduction in the other complications did not reach statistical significance (RR: 0.69, 95% CI: 0.48 to 1.01, P = 0.06, I(2) = 0%). Pooling of these complications (post-operative nausea and vomiting, bleeding, infections and odynophagia) shows that in six trials (501 patients), the use of dexamethasone significantly reduced post-operative complications following tonsillectomy in adults (RR: 0.59, 95% CI: 0.49 to 0.71, P < 0.00001, I(2) = 0%), when compared with placebo or control. CONCLUSIONS: Dexamethasone reduces pain, post-operative nausea and vomiting, bleeding and overall post-operative complications in adults undergoing tonsillectomy. However, the effect of the dose of dexamethasone on post-operative pain and whether dexamethasone reduces bleeding require further research.