King's College London

Research portal

Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence

Research output: Contribution to journalReview article

Standard

Micronized vaginal progesterone to prevent miscarriage : a critical evaluation of randomized evidence. / Coomarasamy, Arri; Devall, Adam J.; Brosens, Jan J.; Quenby, Siobhan; Stephenson, Mary D.; Sierra, Sony; Christiansen, Ole B.; Small, Rachel; Brewin, Jane; Roberts, Tracy E.; Dhillon-Smith, Rima; Harb, Hoda; Noordali, Hannah; Papadopoulou, Argyro; Eapen, Abey; Prior, Matt; Di Renzo, Gian Carlo; Hinshaw, Kim; Mol, Ben W.; Lumsden, Mary Ann; Khalaf, Yacoub; Shennan, Andrew; Goddijn, Mariette; van Wely, Madelon; Al-Memar, Maya; Bennett, Phil; Bourne, Tom; Rai, Raj; Regan, Lesley; Gallos, Ioannis D.

In: American Journal of Obstetrics and Gynecology, Vol. 223, No. 2, 08.2020, p. 167-176.

Research output: Contribution to journalReview article

Harvard

Coomarasamy, A, Devall, AJ, Brosens, JJ, Quenby, S, Stephenson, MD, Sierra, S, Christiansen, OB, Small, R, Brewin, J, Roberts, TE, Dhillon-Smith, R, Harb, H, Noordali, H, Papadopoulou, A, Eapen, A, Prior, M, Di Renzo, GC, Hinshaw, K, Mol, BW, Lumsden, MA, Khalaf, Y, Shennan, A, Goddijn, M, van Wely, M, Al-Memar, M, Bennett, P, Bourne, T, Rai, R, Regan, L & Gallos, ID 2020, 'Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence', American Journal of Obstetrics and Gynecology, vol. 223, no. 2, pp. 167-176. https://doi.org/10.1016/j.ajog.2019.12.006

APA

Coomarasamy, A., Devall, A. J., Brosens, J. J., Quenby, S., Stephenson, M. D., Sierra, S., Christiansen, O. B., Small, R., Brewin, J., Roberts, T. E., Dhillon-Smith, R., Harb, H., Noordali, H., Papadopoulou, A., Eapen, A., Prior, M., Di Renzo, G. C., Hinshaw, K., Mol, B. W., ... Gallos, I. D. (2020). Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence. American Journal of Obstetrics and Gynecology, 223(2), 167-176. https://doi.org/10.1016/j.ajog.2019.12.006

Vancouver

Coomarasamy A, Devall AJ, Brosens JJ, Quenby S, Stephenson MD, Sierra S et al. Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence. American Journal of Obstetrics and Gynecology. 2020 Aug;223(2):167-176. https://doi.org/10.1016/j.ajog.2019.12.006

Author

Coomarasamy, Arri ; Devall, Adam J. ; Brosens, Jan J. ; Quenby, Siobhan ; Stephenson, Mary D. ; Sierra, Sony ; Christiansen, Ole B. ; Small, Rachel ; Brewin, Jane ; Roberts, Tracy E. ; Dhillon-Smith, Rima ; Harb, Hoda ; Noordali, Hannah ; Papadopoulou, Argyro ; Eapen, Abey ; Prior, Matt ; Di Renzo, Gian Carlo ; Hinshaw, Kim ; Mol, Ben W. ; Lumsden, Mary Ann ; Khalaf, Yacoub ; Shennan, Andrew ; Goddijn, Mariette ; van Wely, Madelon ; Al-Memar, Maya ; Bennett, Phil ; Bourne, Tom ; Rai, Raj ; Regan, Lesley ; Gallos, Ioannis D. / Micronized vaginal progesterone to prevent miscarriage : a critical evaluation of randomized evidence. In: American Journal of Obstetrics and Gynecology. 2020 ; Vol. 223, No. 2. pp. 167-176.

Bibtex Download

@article{4da8fb84240a4ea6bc35940170ae9c0b,
title = "Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence",
abstract = "Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of. 08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03–1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08–1.51; P=.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making.",
keywords = "bleeding, luteal phase deficiency, meta-analysis, recurrent miscarriage, threatened miscarriage, vaginal micronized progesterone",
author = "Arri Coomarasamy and Devall, {Adam J.} and Brosens, {Jan J.} and Siobhan Quenby and Stephenson, {Mary D.} and Sony Sierra and Christiansen, {Ole B.} and Rachel Small and Jane Brewin and Roberts, {Tracy E.} and Rima Dhillon-Smith and Hoda Harb and Hannah Noordali and Argyro Papadopoulou and Abey Eapen and Matt Prior and {Di Renzo}, {Gian Carlo} and Kim Hinshaw and Mol, {Ben W.} and Lumsden, {Mary Ann} and Yacoub Khalaf and Andrew Shennan and Mariette Goddijn and {van Wely}, Madelon and Maya Al-Memar and Phil Bennett and Tom Bourne and Raj Rai and Lesley Regan and Gallos, {Ioannis D.}",
year = "2020",
month = aug,
doi = "10.1016/j.ajog.2019.12.006",
language = "English",
volume = "223",
pages = "167--176",
journal = "American Journal of Obstetrics and Gynecology",
issn = "0002-9378",
publisher = "Mosby Inc.",
number = "2",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Micronized vaginal progesterone to prevent miscarriage

T2 - a critical evaluation of randomized evidence

AU - Coomarasamy, Arri

AU - Devall, Adam J.

AU - Brosens, Jan J.

AU - Quenby, Siobhan

AU - Stephenson, Mary D.

AU - Sierra, Sony

AU - Christiansen, Ole B.

AU - Small, Rachel

AU - Brewin, Jane

AU - Roberts, Tracy E.

AU - Dhillon-Smith, Rima

AU - Harb, Hoda

AU - Noordali, Hannah

AU - Papadopoulou, Argyro

AU - Eapen, Abey

AU - Prior, Matt

AU - Di Renzo, Gian Carlo

AU - Hinshaw, Kim

AU - Mol, Ben W.

AU - Lumsden, Mary Ann

AU - Khalaf, Yacoub

AU - Shennan, Andrew

AU - Goddijn, Mariette

AU - van Wely, Madelon

AU - Al-Memar, Maya

AU - Bennett, Phil

AU - Bourne, Tom

AU - Rai, Raj

AU - Regan, Lesley

AU - Gallos, Ioannis D.

PY - 2020/8

Y1 - 2020/8

N2 - Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of. 08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03–1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08–1.51; P=.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making.

AB - Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of. 08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03–1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08–1.51; P=.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making.

KW - bleeding

KW - luteal phase deficiency

KW - meta-analysis

KW - recurrent miscarriage

KW - threatened miscarriage

KW - vaginal micronized progesterone

UR - http://www.scopus.com/inward/record.url?scp=85087113894&partnerID=8YFLogxK

U2 - 10.1016/j.ajog.2019.12.006

DO - 10.1016/j.ajog.2019.12.006

M3 - Review article

C2 - 32008730

AN - SCOPUS:85087113894

VL - 223

SP - 167

EP - 176

JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

SN - 0002-9378

IS - 2

ER -

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454