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

Ogwulu, CB Okeke; Goranitis, Ilias; Devall, AJ; Cheed, Versha; Gallos, Ioannis D; Middleton, LJ; Harb, HM; Williams, H James; Eapen, Abey; Daniels, JP; Ahmed, Ali; Bender-Atik, Ruth; Bhatia, Kalsang; Bottomley, C.; Brewin, Jane; Choudhary, Meenakshi; Deb, Shilpa; Duncan, W. Colin; Ewer, Andrew K; Hinshaw, Kim; Izzat, Feras; Johns, Jemma; Lumsden, Mary-Ann; Manda, Padma; Norman, Jane E.; Nunes, Natalie; Overton, Caroline; Kriedt, Kathiuska; Quenby, Siobhán; Rao, Sandhya; Ross, Jackie; Shahid, Anupama; Underwood, Martyn; Vaithilingham, Nirmala; Watkins, Linda R.; Wykes, Catherine; Horne, Andrew W; Coomarasamy, Arri; Roberts, Tracy

doi:10.1111/1471-0528.16068

Cited by 9 publications

(5 citation statements)

References 25 publications

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“…To conclude, Coomarasamy et al demonstrated, in a subgroup analyses of the PRISM and PROMISE trials, that in women presenting with dual risk factors of early pregnancy bleeding and a history of one or more previous miscarriages, progesterone has a beneficial role by increasing LBR by 5%, whereas women with at least 3 previous miscarriages benefit the most by progesterone supplementation [69 ▪ ]. A Cochrane review suggested that progesterone may improve LBRs [70], however, the cost efficiency of progesterone in the treatment of RM has been questioned [71 ▪ ,72 ▪▪ ].…”

Section: Unexplained Recurrent Miscarriagesmentioning

confidence: 99%

Management of recurrent miscarriages: an overview of current evidence

Tsonis

Balogun

Adjei³

et al. 2021

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of review Recurrent miscarriage (RM) or recurrent pregnancy loss (RPL) is defined as the consecutive loss of two or more pregnancies before the age of viability. The exact prevalence of RM is unknown, but it has been reported between 1% and 2%. The objective of this review is to provide a critical summary of the latest evidence for the investigation and management of women with RM. Recent findings RMs are associated with multiple factors including increased female age and lifestyle habits, as well as genetic factors, hereditary and acquired thrombophilia and infections. Metabolic and endocrine factors, in addition to anatomical causes such as uterine malformations have also been suggested as a causative factors of RM. Summary The management of RM would be expected to cause specific, however, in the majority of the cases no cause is identified, and the factors associated with RM may not be causally related with the condition.

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Section: Unexplained Recurrent Miscarriagesmentioning

confidence: 99%

Management of recurrent miscarriages: an overview of current evidence

Tsonis

Balogun

Adjei³

et al. 2021

Current Opinion in Obstetrics &Amp; Gynecology

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“…Reproduced from Okeke Ogwulu et al 52 During the antenatal period, women allocated to the progesterone arm had, on average, a higher frequency of antenatal and DAU visits but a smaller number of emergency room visits and hospital admissions than women in the placebo arm. During the postnatal period, women in the progesterone arm utilised similar services more than those in the placebo arm except for emergency hospital visits, which were the same for both arms.…”

Section: Resource Use and Costsmentioning

confidence: 99%

“…Cost-effectiveness plane for the primary analysis using hospital-related costs for the participants. Reproduced from Okeke Ogwulu et al52 © 2020 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.…”

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confidence: 99%

“…Mean resource use across treatment groups Mean resource use across treatment groups (continued ) Note The primary care mean values were calculated for only participants with complete primary care data. Reproduced from Okeke Ogwulu et al52 © 2020 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.…”

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confidence: 99%

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Progesterone to prevent miscarriage in women with early pregnancy bleeding: the PRISM RCT

Coomarasamy

Harb

Devall

et al. 2020

Health Technol Assess

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Background Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage. Objectives (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding. Design A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding. Setting A total of 48 hospitals in the UK. Participants Women aged 16–39 years with early pregnancy bleeding. Interventions Women aged 16–39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation. Main outcome measures The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective. Results A total of 4153 women from 48 hospitals in the UK received either progesterone (n = 2079) or placebo (n = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p = 0.08). A significant subgroup effect (interaction test p = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p = 0.004). A significant post hoc subgroup effect (interaction test p = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval –£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation. Conclusions Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets. Trial registration Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 33. See the NIHR Journals Library website for further project information.

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“…[10,11,15] About 30-50% [8,16,17] of VB-affected deliveries end in a miscarriage. [18][19][20] The long-term risk of cancer in women with a pregnancy complicated by vaginal bleeding within 20 gestational weeks is unknown. A previous Danish study showed that VB in pregnancy is not a marker of occult cancer.…”

Section: Introductionmentioning

confidence: 99%

Association between having a pregnancy complicated by vaginal bleeding and risk of cancer

Dudukina

Horváth‐Puhó

Sørensen

et al. 2022

Preprint

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Objective: To investigate an association of vaginal bleeding-affected deliveries with the long-term risk of cancer as compared with vaginal bleeding-unaffected deliveries and pregnancies ending in a termination or miscarriage. Design: Registry-based cohort study in Denmark, 1995-2017. Setting: Danish health and administrative registries. Participants: Deliveries (N=37,085) affected by vaginal bleeding (VB) within 20 gestational weeks among 35,517 women, VB-unaffected deliveries (N=1,362,760) among 783,020 women, pregnancies ending in a termination (N=324,395) among 239,729 women or miscarriage (N=137,040) among 121,303 women. Main outcome measures: Incidence rates (IR) per 10,000 person-years and cumulative incidence of cancer at the end of up to 24 years of follow-up, hazard ratios (HR) with 95% confidence intervals (CIs) adjusted for age, calendar year, reproductive history, history of chronic conditions, medication use, and socioeconomic factors using Cox proportional hazards regression. Results: We observed 1,725 cancer events (IR=32.1, 95% CI: 30.6-33.6) following VB-affected deliveries, 52,620 events (IR=31.5, 95% CI: 31.2-31.7) following VB-unaffected deliveries, 12,925 events (IR=30.1, 95% CI: 29.6-30.6) following a termination and 6,080 events (IR=34.3, 95% CI: 33.4-35.1) following a miscarriage. We found no association between VB and any cancer in comparison with VB-unaffected deliveries (HR=0.98, 95% CI: 0.93-1.03), terminations (HR=1.00, 95% CI: 0.94-1.06) and miscarriages (HR=1.04, 95% CI: 0.94-1.14). Specifically, there was no increase in relative risk of breast (HR=0.94, 95% CI: 0.86-1.03), cervical (0.94, 0.77-1.14), ovarian and fallopian tube (1.16, 0.81-1.66), uterine cancer (0.78, 0.46-1.33) and other site-specific cancers across all comparisons and in sensitivity analyses. Conclusions: Having a VB-affected pregnancy ending in a delivery was not associated with an increased risk of cancer in women in comparison with having a VB-unaffected pregnancy ending in a delivery, termination or miscarriage.

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

Cited by 9 publications

References 25 publications

Management of recurrent miscarriages: an overview of current evidence

Management of recurrent miscarriages: an overview of current evidence

Progesterone to prevent miscarriage in women with early pregnancy bleeding: the PRISM RCT

Association between having a pregnancy complicated by vaginal bleeding and risk of cancer

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