Double-Blind Trial of a Progestin in Habitual Abortion

Goldzieher, Joseph W.

doi:10.1001/jama.1964.03060330031008

Cited by 76 publications

(6 citation statements)

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“…However, the results are not yet available. There have only been one trial of progesterone implants [5], one trial of medroxyprogesterone acetate [6] and one on intramuscular injection of 17 hydroxyprogesterone [7]. In order to assess safety, all 13 studies were assessed.…”

Section: Discussionmentioning

confidence: 99%

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A systematic review of dydrogesterone for the treatment of recurrent miscarriage

Carp

2015

Gynecological Endocrinology

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The objective of this systematic review was to assesses whether the orally acting progestagen, dydrogesterone lowers the incidence of subsequent miscarriage in women with recurrent miscarriage. A computerized search was performed in Medline, Embase and Ovid Medline for original reports with the product name "Duphaston" or "dydrogesterone" and limited to clinical human data. Thirteen reports of dydrogesterone treatment were identified. Two randomized trials and one non-randomized comparative trial were identified, including 509 women who fulfilled the criteria for meta-analysis. The number of subsequent miscarriages or continuing pregnancies per woman was compared in women receiving dydrogesterone compared to standard bed rest or placebo intervention. There was a 10.5% (29/275) miscarriage rate after dydrogesterone administration compared to 23.5% in control women (odds ratio for miscarriage 0.29 [confidence interval 0.13-0.65] and 13% absolute reduction in the miscarriage rate). The adverse and side effects were summarised in all 13 reports, and seemed to be minimal. Although all the predictive and confounding factors could not be controlled for, the results of this systematic review show a significant reduction of 29% in the odds for miscarriage when dydrogesterone is compared to standard care indicating a real treatment effect.

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Section: Discussionmentioning

confidence: 99%

“…Each used a different progesterone regimen. The meta-analysis icluded trials of progesterone implants [5], medroxyprogesterone acetate [6] or intramuscular injections of 17 hydroxyprogesterone [7]. These trials came from the 1950s and 1960s, when there was no early ultrasound available, hence no matching for the presence of a foetal heart.…”

Section: Introductionmentioning

confidence: 99%

A systematic review of dydrogesterone for the treatment of recurrent miscarriage

Carp

2015

Gynecological Endocrinology

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“…A total of 94 RCTs were included in the review (Table S1). The PRISMA flow chart in Supporting Information Figure S1 shows study selection. Table displays the study characteristics for the included papers.…”

Section: Resultsmentioning

confidence: 99%

Outcomes in prevention and management of miscarriage trials: a systematic review

Smith

Dhillon-Smith

O’Toole

et al. 2018

BJOG

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Background There is a substantial body of research evaluating ways to prevent and manage miscarriage, but all studies do not report on the same outcomes. Objective To review systematically, outcomes reported in existing miscarriage trials. Search strategy MEDLINE, Embase, CINAHL, and Cochrane were searched from inception until January 2017. Selection criteria Randomised controlled trials (RCTs) reporting prevention or management of miscarriage. Miscarriage was defined as a pregnancy loss in the first trimester. Data collection and analysis Data about the study characteristics, primary, and secondary outcomes were extracted. Main results We retrieved 1553 titles and abstracts, from which 208 RCTs were included. For prevention of miscarriage, the most commonly reported primary outcome was live birth and the top four reported outcomes were pregnancy loss/stillbirth (n = 112), gestation of birth (n = 68), birth dimensions (n = 65), and live birth (n = 49). For these four outcomes, 58 specific measures were used for evaluation. For management of miscarriage, the most commonly reported primary outcome was efficacy of treatment. The top four reported outcomes were bleeding (n = 186), efficacy of miscarriage treatment (n = 105), infection (n = 97), and quality of life (n = 90). For these outcomes, 130 specific measures were used for evaluation. Conclusions Our review found considerable variation in the reporting of primary and secondary outcomes along with the measures used to assess them. There is a need for standardised patient‐centred clinical outcomes through the development of a core outcome set; the work from this systematic review will form the foundation of the core outcome set for miscarriage. Tweetable abstract There is disparity in the reporting of outcomes and the measures used to assess them in miscarriage trials.

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“…Four randomised trials [7][8][9][10] were identified. There were 14 trials assessing the effects of progesterone in miscarriages including spontaneous (one-time) events 2 but these trials should not be confused with trials assessing the effects of progesterone in RM.…”

Section: Effectiveness Of Progesterone In Recurrent Miscarriagesmentioning

confidence: 99%

PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages – a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation

Coomarasamy

Williams

Truchanowicz

et al. 2016

Health Technol Assess

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Background and objectivesProgesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted.Design and settingA randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites).Participants and interventionsWomen with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan®, Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks).Main outcome measuresLive birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6–8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use.MethodsParticipants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth.ResultsA total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body mass index, maternal ethnicity, smoking status and parity) of the participants were comparable in the two arms of the trial. The follow-up rate to primary outcome was 826 out of 836 (98.8%). The live birth rate in the progesterone group was 65.8% (262/398) and in the placebo group it was 63.3% (271/428), giving a relative risk of 1.04 (95% confidence interval 0.94 to 1.15;p = 0.45). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Economic analysis suggested a favourable incremental cost-effectiveness ratio for decision-making but wide confidence intervals indicated a high level of uncertainty in the health benefits. Additional sensitivity analysis suggested the probability that progesterone would fall within the National Institute for Health and Care Excellence’s threshold of £20,000–30,000 per quality-adjusted life-year as between 0.7145 and 0.7341.ConclusionsThere is no evidence that first-trimester progesterone therapy improves outcomes in women with a history of unexplained RM.LimitationsThis study did not explore the effect of treatment with other progesterone preparations or treatment during the luteal phase of the menstrual cycle.Future workFuture research could explore the efficacy of progesterone supplementation administered during the luteal phase of the menstrual cycle in women attempting natural conception despite a history of RM.Trial registrationCurrent Controlled Trials ISRCTN92644181; EudraCT 2009-011208-42; Research Ethics Committee 09/H1208/44.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 41. See the NIHR Journals Library website for further project information.

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Double-Blind Trial of a Progestin in Habitual Abortion

Cited by 76 publications

References 3 publications

A systematic review of dydrogesterone for the treatment of recurrent miscarriage

A systematic review of dydrogesterone for the treatment of recurrent miscarriage

Outcomes in prevention and management of miscarriage trials: a systematic review

PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages – a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation

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