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.

Can risk factors, clinical history and symptoms be used to predict risk of ectopic pregnancy in women attending an early pregnancy assessment unit?

OBJECTIVE: To examine whether risk factors and symptoms may be used to predict the likelihood of ectopic pregnancy (EP) in women attending early pregnancy assessment units in the UK. METHODS: This was an observational cohort study of pregnant women under 12 weeks' gestation who were recruited from three London university hospitals between August 2012 and April 2013. One hospital continued recruitment between January and June 2015. A standardized information sheet incorporating patient demographics, medical history and symptoms was completed by patients and confirmed by examining clinicians. The outcome measure was final pregnancy location. RESULTS: There were 1320 eligible patients included in the analysis, with a total of 72 EPs (rate of 6%). Pelvic pain and diarrhea > three times in the previous 24 h were independent symptoms that increased the risk of EP, with relative risks of 2.4 (95% CI, 1.4-4.0; P = 0.002) and 2.2 (95% CI, 1.08-4.5; P = 0.03), respectively. The only other independent marker of risk of EP was duration of vaginal bleeding; the risk of EP increased by 20% (95% CI, 14%-27%) for every 1-day increment in duration (P < 0.001). A logistic regression model incorporating these factors demonstrated an area under the receiver-operating characteristics curve of 0.73 (95% CI, 0.67-0.79). The prevalence of EP was low when there was no pelvic pain, no diarrhea and the duration of bleeding was ≤ 3 days, with an EP rate of 2% (6/391). In the presence of a single risk factor, the EP rate increased to 5% (29/631) when only pelvic pain was present, 8% (1/12) when only diarrhea > three times in the previous 24 h was reported and 9% (9/103) when there was only vaginal bleeding with a duration > 3 days. Women with pelvic pain and vaginal bleeding of any severity for > 3 days had a high EP rate of 16% (23/146). In the nine women who also reported diarrhea > three times in the previous 24 h, two had EP. CONCLUSIONS: Only the presence of pelvic pain, diarrhea > three times in the previous 24 h and duration of bleeding were symptoms that significantly increased the risk for EP in women attending early pregnancy assessment units. Risk factors and symptoms alone could not be used to predict reliably an EP. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Functional linear discriminant analysis: a new longitudinal approach to the assessment of embryonic growth.

BACKGROUND: Functional linear discriminant analysis (FLDA) is a new growth assessment technique using serial measurements to discriminate between normal and abnormal fetal growth. We used FLDA to assess and compare growth in live pregnancies destined to miscarry with those remaining viable. METHODS: This was a prospective cohort study of women with ultrasound scans on at least two separate occasions showing live pregnancies. Serial crown-rump length (CRL), mean gestational sac diameter and mean yolk sac diameter measurements were recorded. The ability of FLDA to predict subsequent miscarriage was compared with that of a single CRL measurement. RESULTS: Of 521 included pregnancies, 493 (94.6%) remained viable at 14 weeks and 28 (5.4%) miscarried. The CRL growth rate was significantly lower in those that miscarried (one-sample t-test, P = 2.638E-22). The sensitivity of FLDA in predicting miscarriage from serial CRL measurements was 60.7% and specificity was 93.1% [positive predictive value (PPV) 33.3%, negative predictive value (NPV) 97.7%]. This was significantly better for predicting miscarriage than a single CRL observation of more than 2SD below that expected (sensitivity 53.6%, specificity 72.2%, PPV 9.9%, NPV 96.5%). CONCLUSIONS: FLDA discriminates between normal and abnormal growth to predict miscarriage with high specificity. FLDA predicts miscarriage better than a single observation of a small CRL.