Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis

Pedro Melo; Adam Devall; Andrew H Shennan; Manu Vatish; Christian M Becker; Ingrid Granne; Aris T Papageorghiou; Ben W Mol; Arri Coomarasamy

doi:10.1111/1471-0528.17705

Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis

Pedro Melo^* (Corresponding Author), Adam Devall, Andrew H Shennan, Manu Vatish, Christian M Becker, Ingrid Granne, Aris T Papageorghiou, Ben W Mol, Arri Coomarasamy

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

1 Citation (Scopus)

Abstract

BACKGROUND: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored.

OBJECTIVES: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP.

SEARCH STRATEGY: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023.

SELECTION CRITERIA: We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications.

DATA COLLECTION AND ANALYSIS: We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology.

MAIN RESULTS: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I 2 = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I 2 = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I 2 = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I 2 = 0%; low-certainty evidence).

CONCLUSIONS: Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.

Original language	English
Journal	BJOG : an international journal of obstetrics and gynaecology
Early online date	8 Nov 2023
DOIs	https://doi.org/10.1111/1471-0528.17705
Publication status	E-pub ahead of print - 8 Nov 2023

Bibliographical note

ACKNOWLEDGEMENTS
The investigators thank all trial authors who provided information about their own studies, including Zarko Alfirevic, Ana Luisa Areia, Camil Castelo-Branco, Ozlem Erdem, Fabio Facchinetti, Luke McLindon, Ben Willem Mol, Kypros Nicolaides and Ariel Weissman.

FUNDING INFORMATION
We did not seek funding for the completion of this work. PM is supported by an NIHR Academic Clinical Lectureship grant.

Keywords

Hypertensive disorders of pregnancy
pre-eclampsia
progesterone

Access to Document

10.1111/1471-0528.17705Licence: CC BY-NC-ND

Cite this

Melo, P., Devall, A., Shennan, A. H., Vatish, M., Becker, C. M., Granne, I., Papageorghiou, A. T., Mol, B. W., & Coomarasamy, A. (2023). Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis. BJOG : an international journal of obstetrics and gynaecology. Advance online publication. https://doi.org/10.1111/1471-0528.17705

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title = "Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis",

abstract = "BACKGROUND: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored.OBJECTIVES: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP.SEARCH STRATEGY: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023.SELECTION CRITERIA: We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications.DATA COLLECTION AND ANALYSIS: We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology.MAIN RESULTS: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I 2 = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I 2 = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I 2 = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I 2 = 0%; low-certainty evidence). CONCLUSIONS: Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.",

keywords = "Hypertensive disorders of pregnancy, pre-eclampsia, progesterone",

author = "Pedro Melo and Adam Devall and Shennan, {Andrew H} and Manu Vatish and Becker, {Christian M} and Ingrid Granne and Papageorghiou, {Aris T} and Mol, {Ben W} and Arri Coomarasamy",

note = "ACKNOWLEDGEMENTS The investigators thank all trial authors who provided information about their own studies, including Zarko Alfirevic, Ana Luisa Areia, Camil Castelo-Branco, Ozlem Erdem, Fabio Facchinetti, Luke McLindon, Ben Willem Mol, Kypros Nicolaides and Ariel Weissman. FUNDING INFORMATION We did not seek funding for the completion of this work. PM is supported by an NIHR Academic Clinical Lectureship grant.",

year = "2023",

month = nov,

day = "8",

doi = "10.1111/1471-0528.17705",

language = "English",

journal = "BJOG : an international journal of obstetrics and gynaecology",

issn = "1470-0328",

publisher = "John Wiley & Sons, Ltd (10.1111)",

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TY - JOUR

T1 - Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy

T2 - A systematic review and meta-analysis

AU - Melo, Pedro

AU - Devall, Adam

AU - Shennan, Andrew H

AU - Vatish, Manu

AU - Becker, Christian M

AU - Granne, Ingrid

AU - Papageorghiou, Aris T

AU - Mol, Ben W

AU - Coomarasamy, Arri

N1 - ACKNOWLEDGEMENTS The investigators thank all trial authors who provided information about their own studies, including Zarko Alfirevic, Ana Luisa Areia, Camil Castelo-Branco, Ozlem Erdem, Fabio Facchinetti, Luke McLindon, Ben Willem Mol, Kypros Nicolaides and Ariel Weissman. FUNDING INFORMATION We did not seek funding for the completion of this work. PM is supported by an NIHR Academic Clinical Lectureship grant.

PY - 2023/11/8

Y1 - 2023/11/8

N2 - BACKGROUND: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored.OBJECTIVES: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP.SEARCH STRATEGY: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023.SELECTION CRITERIA: We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications.DATA COLLECTION AND ANALYSIS: We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology.MAIN RESULTS: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I 2 = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I 2 = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I 2 = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I 2 = 0%; low-certainty evidence). CONCLUSIONS: Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.

AB - BACKGROUND: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored.OBJECTIVES: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP.SEARCH STRATEGY: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023.SELECTION CRITERIA: We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications.DATA COLLECTION AND ANALYSIS: We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology.MAIN RESULTS: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I 2 = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I 2 = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I 2 = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I 2 = 0%; low-certainty evidence). CONCLUSIONS: Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.

KW - Hypertensive disorders of pregnancy

KW - pre-eclampsia

KW - progesterone

U2 - 10.1111/1471-0528.17705

DO - 10.1111/1471-0528.17705

M3 - Review article

C2 - 37941309

SN - 1470-0328

JO - BJOG : an international journal of obstetrics and gynaecology

JF - BJOG : an international journal of obstetrics and gynaecology

ER -

Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis

Abstract

Bibliographical note

Keywords

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