Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix

A multicenter, randomized, double-blind, placebo-controlled trial

S. S. Hassan, R. Romero, D. Vidyadhari, S. Fusey, J. K. Baxter, M. Khandelwal, J. Vijayaraghavan, Y. Trivedi, P. Soma-Pillay, P. Sambarey, A. Dayal, V. Potapov, J. O'Brien, V. Astakhov, O. Yuzko, W. Kinzler, B. Dattel, H. Sehdev, L. Mazheika, D. Manchulenko & 5 others M. T. Gervasi, L. Sullivan, A. Conde-Agudelo, J. A. Phillips, G. W. Creasy

Research output: Contribution to journalArticle

483 Citations (Scopus)

Abstract

Objectives Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat. Results Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n = 235; placebo, n = 223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n = 21) vs 16.1% (n = 36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P = 0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P = 0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P = 0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P = 0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P = 0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P = 0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P = 0.01). There were no differences in the incidence of treatment-related adverse events between the groups. Conclusions The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.

Original languageEnglish (US)
Pages (from-to)18-31
Number of pages14
JournalUltrasound in Obstetrics and Gynecology
Volume38
Issue number1
DOIs
StatePublished - Jul 2011

Fingerprint

Premature Birth
Cervix Uteri
Progesterone
Placebos
Foams and Jellies Vaginal Creams
Pregnancy
Intention to Treat Analysis
Lost to Follow-Up
Random Allocation
Birth Weight
Rupture
Morbidity
Safety
Membranes
Mortality
Incidence

Keywords

  • pregnancy
  • preterm delivery
  • preterm labor
  • progestins
  • progestogens
  • respiratory distress syndrome
  • transvaginal ultrasound
  • uterine cervix
  • vaginal administration

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Reproductive Medicine
  • Medicine(all)

Cite this

Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix : A multicenter, randomized, double-blind, placebo-controlled trial. / Hassan, S. S.; Romero, R.; Vidyadhari, D.; Fusey, S.; Baxter, J. K.; Khandelwal, M.; Vijayaraghavan, J.; Trivedi, Y.; Soma-Pillay, P.; Sambarey, P.; Dayal, A.; Potapov, V.; O'Brien, J.; Astakhov, V.; Yuzko, O.; Kinzler, W.; Dattel, B.; Sehdev, H.; Mazheika, L.; Manchulenko, D.; Gervasi, M. T.; Sullivan, L.; Conde-Agudelo, A.; Phillips, J. A.; Creasy, G. W.

In: Ultrasound in Obstetrics and Gynecology, Vol. 38, No. 1, 07.2011, p. 18-31.

Research output: Contribution to journalArticle

Hassan, SS, Romero, R, Vidyadhari, D, Fusey, S, Baxter, JK, Khandelwal, M, Vijayaraghavan, J, Trivedi, Y, Soma-Pillay, P, Sambarey, P, Dayal, A, Potapov, V, O'Brien, J, Astakhov, V, Yuzko, O, Kinzler, W, Dattel, B, Sehdev, H, Mazheika, L, Manchulenko, D, Gervasi, MT, Sullivan, L, Conde-Agudelo, A, Phillips, JA & Creasy, GW 2011, 'Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: A multicenter, randomized, double-blind, placebo-controlled trial', Ultrasound in Obstetrics and Gynecology, vol. 38, no. 1, pp. 18-31. https://doi.org/10.1002/uog.9017
Hassan, S. S. ; Romero, R. ; Vidyadhari, D. ; Fusey, S. ; Baxter, J. K. ; Khandelwal, M. ; Vijayaraghavan, J. ; Trivedi, Y. ; Soma-Pillay, P. ; Sambarey, P. ; Dayal, A. ; Potapov, V. ; O'Brien, J. ; Astakhov, V. ; Yuzko, O. ; Kinzler, W. ; Dattel, B. ; Sehdev, H. ; Mazheika, L. ; Manchulenko, D. ; Gervasi, M. T. ; Sullivan, L. ; Conde-Agudelo, A. ; Phillips, J. A. ; Creasy, G. W. / Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix : A multicenter, randomized, double-blind, placebo-controlled trial. In: Ultrasound in Obstetrics and Gynecology. 2011 ; Vol. 38, No. 1. pp. 18-31.
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abstract = "Objectives Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat. Results Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n = 235; placebo, n = 223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9{\%} (n = 21) vs 16.1{\%} (n = 36); relative risk (RR), 0.55; 95{\%} CI, 0.33-0.92; P = 0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95{\%} CI, 0.31-0.91; P = 0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1{\%} vs 10.3{\%}; RR, 0.50; 95{\%} CI, 0.25-0.97; P = 0.04) and 35 weeks (14.5{\%} vs 23.3{\%}; RR, 0.62; 95{\%} CI, 0.42-0.92; P = 0.02), respiratory distress syndrome (3.0{\%} vs 7.6{\%}; RR, 0.39; 95{\%} CI, 0.17-0.92; P = 0.03), any neonatal morbidity or mortality event (7.7{\%} vs 13.5{\%}; RR, 0.57; 95{\%} CI, 0.33-0.99; P = 0.04) and birth weight < 1500 g (6.4{\%} (15/234) vs 13.6{\%} (30/220); RR, 0.47; 95{\%} CI, 0.26-0.85; P = 0.01). There were no differences in the incidence of treatment-related adverse events between the groups. Conclusions The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45{\%} reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.",
keywords = "pregnancy, preterm delivery, preterm labor, progestins, progestogens, respiratory distress syndrome, transvaginal ultrasound, uterine cervix, vaginal administration",
author = "Hassan, {S. S.} and R. Romero and D. Vidyadhari and S. Fusey and Baxter, {J. K.} and M. Khandelwal and J. Vijayaraghavan and Y. Trivedi and P. Soma-Pillay and P. Sambarey and A. Dayal and V. Potapov and J. O'Brien and V. Astakhov and O. Yuzko and W. Kinzler and B. Dattel and H. Sehdev and L. Mazheika and D. Manchulenko and Gervasi, {M. T.} and L. Sullivan and A. Conde-Agudelo and Phillips, {J. A.} and Creasy, {G. W.}",
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TY - JOUR

T1 - Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix

T2 - A multicenter, randomized, double-blind, placebo-controlled trial

AU - Hassan, S. S.

AU - Romero, R.

AU - Vidyadhari, D.

AU - Fusey, S.

AU - Baxter, J. K.

AU - Khandelwal, M.

AU - Vijayaraghavan, J.

AU - Trivedi, Y.

AU - Soma-Pillay, P.

AU - Sambarey, P.

AU - Dayal, A.

AU - Potapov, V.

AU - O'Brien, J.

AU - Astakhov, V.

AU - Yuzko, O.

AU - Kinzler, W.

AU - Dattel, B.

AU - Sehdev, H.

AU - Mazheika, L.

AU - Manchulenko, D.

AU - Gervasi, M. T.

AU - Sullivan, L.

AU - Conde-Agudelo, A.

AU - Phillips, J. A.

AU - Creasy, G. W.

PY - 2011/7

Y1 - 2011/7

N2 - Objectives Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat. Results Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n = 235; placebo, n = 223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n = 21) vs 16.1% (n = 36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P = 0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P = 0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P = 0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P = 0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P = 0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P = 0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P = 0.01). There were no differences in the incidence of treatment-related adverse events between the groups. Conclusions The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.

AB - Objectives Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat. Results Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n = 235; placebo, n = 223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n = 21) vs 16.1% (n = 36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P = 0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P = 0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P = 0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P = 0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P = 0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P = 0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P = 0.01). There were no differences in the incidence of treatment-related adverse events between the groups. Conclusions The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.

KW - pregnancy

KW - preterm delivery

KW - preterm labor

KW - progestins

KW - progestogens

KW - respiratory distress syndrome

KW - transvaginal ultrasound

KW - uterine cervix

KW - vaginal administration

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