Korean J Obstet Gynecol.  2012 Oct;55(10):699-706.

Vaginal micronized natural progesterone treatment and reduced risk of recurrent preterm birth

• Seong LJ
• Kim MJ
• Lee Y
• Yoon SY
• Cha HH
• Kwak HM
• Choi SJ
• Oh SY
• Roh CR
• Kim JH

Abstract

OBJECTIVE
To evaluate whether the administration of vaginal natural micronized progesterone is associated with reduction of recurrent preterm birth (PTB) in women with prior history of spontaneous PTB.
METHODS
We retrospectively evaluated the obstetric and neonatal outcomes of all women with history of spontaneous PTB that delivered from January 2008 through April 2012. Spontaneous PTB was defined as PTB before 37 weeks of gestation due to spontaneous preterm labor or preterm premature rupture of membranes. Pregnancies with multiple gestation and those who received cerclage operation during previous or current pregnancy were excluded. Patients in the progesterone group were instructed to self-administer 100 or 200 mg vaginal micronized natural progesterone capsule. We evaluated the difference in recurrent PTB rate between the progesterone group (n = 73) and the non-user group (n = 158).
RESULTS
The incidence of recurrent spontaneous PTB before 37 weeks' gestation was significantly lower in the progesterone group than the non-user group (21.9% vs. 43.0%, P=0.002). Multivariate analysis showed that progesterone therapy was associated with a decrease in the incidence of recurrent PTB before 37 weeks' gestation (odds ratio, 0.382; 95% confidence interval, 0.169-0.863; P=0.021) independent of confounding variables.
CONCLUSION
Micronized vaginal progesterone supplement therapy was associated with a reduction of recurrent PTB risk in women with previous spontaneous PTB history.

Keyword

Progesterone; Preterm birth; Recurrence; Prevention

MeSH Terms

Female
Humans
Incidence
Membranes
Multivariate Analysis
Obstetric Labor, Premature
Pregnancy
Premature Birth
Progesterone
Recurrence
Retrospective Studies
Rupture
Progesterone

Reference

1. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008. 371:75–84.

2. Moster D, Lie RT, Markestad T. Long-term medical and social consequences of preterm birth. N Engl J Med. 2008. 359:262–273.

3. Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet. 2008. 371:261–269.

4. Koo YH, Kim SK, Skim JY, Won HS, Lee PR, Kim A. Analysis of preterm birth rate based on birth certificate data: from 1995 to 2003. Korean J Obstet Gynecol. 2006. 49:1855–1865.

5. Iams JD, Berghella V. Care for women with prior preterm birth. Am J Obstet Gynecol. 2010. 203:89–100.

6. Iams JD, Goldenberg RL, Mercer BM, Moawad A, Thom E, Meis PJ, et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. The preterm prediction study: recurrence risk of spontaneous preterm birth. Am J Obstet Gynecol. 1998. 178:1035–1040.

7. McManemy J, Cooke E, Amon E, Leet T. Recurrence risk for preterm delivery. Am J Obstet Gynecol. 2007. 196:576.e1–576.e6.

8. Mercer BM, Goldenberg RL, Moawad AH, Meis PJ, Iams JD, Das AF, et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. The preterm prediction study: effect of gestational age and cause of preterm birth on subsequent obstetric outcome. Am J Obstet Gynecol. 1999. 181:1216–1221.

9. Keirse MJ. Progestogen administration in pregnancy may prevent preterm delivery. Br J Obstet Gynaecol. 1990. 97:149–154.

10. How HY, Sibai BM. Progesterone for the prevention of preterm birth: indications, when to initiate, efficacy and safety. Ther Clin Risk Manag. 2009. 5:55–64.

11. da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003. 188:419–424.

12. Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003. 348:2379–2385.

13. Cetingoz E, Cam C, Sakalli M, Karateke A, Celik C, Sancak A. Progesterone effects on preterm birth in high-risk pregnancies: a randomized placebo-controlled trial. Arch Gynecol Obstet. 2011. 283:423–429.

14. DeFranco EA, O'Brien JM, Adair CD, Lewis DF, Hall DR, Fusey S, et al. Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007. 30:697–705.

15. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007. 357:462–469.

16. Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011. 38:18–31.

17. Rai P, Rajaram S, Goel N, Ayalur Gopalakrishnan R, Agarwal R, Mehta S. Oral micronized progesterone for prevention of preterm birth. Int J Gynaecol Obstet. 2009. 104:40–43.

18. Saghafi N, Khadem N, Mohajeri T, Shakeri MT. Efficacy of 17alpha-hydroxyprogesterone caproate in prevention of preterm delivery. J Obstet Gynaecol Res. 2011. 37:1342–1345.

19. Majhi P, Bagga R, Kalra J, Sharma M. Intravaginal use of natural micronised progesterone to prevent pre-term birth: a randomised trial in India. J Obstet Gynaecol. 2009. 29:493–498.

20. Society for Maternal Fetal Medicine Publications Committee. ACOG Committee Opinion number 419 October 2008 (replaces no. 291, November 2003). Use of progesterone to reduce preterm birth. Obstet Gynecol. 2008. 112:963–965.

21. Goffinet F. Primary predictors of preterm labour. BJOG. 2005. 112:Suppl 1. 38–47.

22. Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, et al. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network. The length of the cervix and the risk of spontaneous premature delivery. N Engl J Med. 1996. 334:567–572.

23. Grimes-Dennis J, Berghella V. Cervical length and prediction of preterm delivery. Curr Opin Obstet Gynecol. 2007. 19:191–195.

24. Honest H, Forbes CA, Duree KH, Norman G, Duffy SB, Tsourapas A, et al. Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling. Health Technol Assess. 2009. 13:1–627.

25. Dodd JM, Flenady VJ, Cincotta R, Crowther CA. Progesterone for the prevention of preterm birth: a systematic review. Obstet Gynecol. 2008. 112:127–134.

26. Rizzo G, Capponi A, Angelini E, Vlachopoulou A, Grassi C, Romanini C. The value of transvaginal ultrasonographic examination of the uterine cervix in predicting preterm delivery in patients with preterm premature rupture of membranes. Ultrasound Obstet Gynecol. 1998. 11:23–29.

27. O'Brien JM, Adair CD, Lewis DF, Hall DR, Defranco EA, Fusey S, et al. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, doubleblind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007. 30:687–696.

28. Glover MM, McKenna DS, Downing CM, Smith DB, Croom CS, Sonek JD. A randomized trial of micronized progesterone for the prevention of recurrent preterm birth. Am J Perinatol. 2011. 28:377–381.