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. ManchulenkoM. T. Gervasi, L. Sullivan, A. Conde-Agudelo, J. A. Phillips, G. W. Creasy

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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.

Original languageEnglish (US)
Pages (from-to)18-31
Number of pages14
JournalUltrasound in Obstetrics and Gynecology
Volume38
Issue number1
DOIs
StatePublished - Jul 1 2011

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Keywords

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

ASJC Scopus subject areas

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

Cite this

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., ... Creasy, G. W. (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, 38(1), 18-31. https://doi.org/10.1002/uog.9017