Luteal Phase Support in in vitro Fertilization: Meta-Analysis of Randomized Trials

Nosarka, S; Kruger, Thinus F.; Siebert, Igno; Grové, D.

doi:10.1159/000084546

Cited by 76 publications

(35 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, we chose this route to deliver a greater proportion of the drug to the biologically relevant site (i.e., the uterus), 13,14 and the dose used (400 mg twice daily) represents a dose at the top end of the therapeutic window. 15 Some researchers have suggested that intramuscular preparations of progesterone may provide greater therapeutic benefit than vaginal preparations; however, data are lacking to support this contention, and previous trials of alternative progesterone preparations (including intramuscular progesterone) have shown varying results. 8,9 Furthermore, previous studies have shown the efficacy of vaginal progesterone in lowering the risk of preterm birth.…”

Section: Discussionmentioning

confidence: 99%

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

et al. 2015

View full text Add to dashboard Cite

BACKGROUNDProgesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. METHODSWe conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twicedaily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. RESULTSA total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, −4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. CONCLUSIONSProgesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages.

show abstract

Section: Discussionmentioning

confidence: 99%

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

et al. 2015

View full text Add to dashboard Cite

show abstract

“…For example, progesterone vaginal capsules are commonly used for luteal support in assisted conception at a treatment dose of 400 mg twice daily, with no specific safety concerns raised on this dose. 16,32 After evaluating the evidence, we considered the dosage of 400-mg vaginal progesterone twice daily to be an acceptable regimen to ensure a clinically effective dose, and to minimise the risk of a negative trial result from therapy with a suboptimal dose.…”

Section: Dosementioning

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

View full text Add to dashboard Cite

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.

show abstract

“…(18 РКИ) установлено, что пост-трансферная поддержка с использованием ХГ, мас-ляного раствора прогестерона и микронизированно-го прогестерона приводит к повышению эффектив-ности протоколов ЭКО. При этом более высокая ча-стота наступления беременности наблюдалась в про-токолах с использованием ХГ [24].…”

Section: почему эндометрий в протоколах стимуляции яич-ников часто явunclassified

Current scientific and practical luteal phase support strategies

Kogan¹,

Gerkulov²

2016

Probl. reprod.

View full text Add to dashboard Cite

Актуальные научно-практические направления в стратегии гормональной терапии в посттрансферном периоде И.Ю. КОГАН, Д.А. ГЕРКУЛОВ ФГБНУ «НИИ акушерства, гинекологии и репродукции им. Д.О. Отта» (дир. -акад. РАН Э.К. Айламазян), Санкт-Петербург, Россия, 199034 Проблема, сопровождающая все циклы стимуляции суперовуляции, -недостаточность лютеиновой фазы. Поддержка лютеиновой фазы (прежде всего назначение прогестерона) широко используется для увеличения частоты наступления имплантации, клинической беременности и родов. Однако внедрение в практическую деятельность новых стратегий, связанных с обеспечением безопасности протокола, а также острые конкурентные взаимоотношения на рынке фармакологических услуг ставят сегодня несколько вопросов научной обоснованности выбора того или иного варианта гормональной поддержки в посттрансферном периоде. The luteal phases of all stimulated IVF cycles are abnormal. Luteal phase support (mainly progesterone administration) is a common practice in infertility treatment to improve the implantation rate, clinical pregnancy rate, and delivery rate. However, new practical strategies aimed to improve protocol safety and commercial conflicts of interests between pharmacological companies necessitate to take desicion about methods of luteal phase support.

show abstract

Luteal Phase Support in in vitro Fertilization: Meta-Analysis of Randomized Trials

Cited by 76 publications

References 41 publications

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

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

Current scientific and practical luteal phase support strategies

Contact Info

Product

Resources

About