Progesterone for preterm birth prevention

  • Miha Lucovnik Department of Obstetrics and Gynaecology, Division of Perinatology, University Medical Centre Ljubljana, Slovenia
  • Tanja Premru Sršen Department of Obstetrics and Gynaecology, Division of Perinatology, University Medical Centre Ljubljana, Slovenia
Keywords: progesterone, gestagens, preterm birth, pregnancy, uterine cervix

Abstract

Background: Progesterone is important in maintaining pregnancy. Progesterone supplementation may reduce risk of preterm birth in certain populations of pregnant women. The objective of this review was to develop evidence-based clinical recommendation for progesterone treatment in the prevention of preterm birth.

Methods: A search in the Medline database was performed using keywords: progesterone, pregnancy, preterm birth, preterm labour, preterm delivery, randomized trial, and randomized controlled trial. We only included studies of vaginal progesterone treatments for the prevention of preterm birth and excluded studies on 17-α-hydroksiprogesterone caproate.

Results: We report findings from twelve randomized trials conducted since 2003. These trials differ regarding inclusion criteria, progesterone dose, vehicle used, and duration of treatment. Inclusion criteria were: short uterine cervix (two trials), history of previous preterm birth (two trials), signs and symptoms of preterm labour (three trials), twin pregnancies (three trials), and multiple risk factors (among these history of previous preterm birth was the most common) (two trials). Six of these twelve trials showed a significant reduction in preterm birth in the progesterone groups.

Conclusions: Based on current evidence we recommend treatment with 200 mg of micronized progesterone daily, administered vaginally, in pregnant women found to have a short cervix (≤ 25 mm) at 19-24 weeks. The treatment should be continued until 37 weeks.

Downloads

Download data is not yet available.

Author Biographies

Miha Lucovnik, Department of Obstetrics and Gynaecology, Division of Perinatology, University Medical Centre Ljubljana, Slovenia

Doc. dr. Miha Lučovnik, dr. med.

KO za perinatologijo

Ginekološka klinika

Univerzitetni Klinični Center Ljubljana

Šlajmerjeva 3

Tanja Premru Sršen, Department of Obstetrics and Gynaecology, Division of Perinatology, University Medical Centre Ljubljana, Slovenia

Asist. dr. Tanja Premru Sršen, dr. med.

KO za perinatologijo

Ginekološka klinika

Univerzitetni Klinični Center Ljubljana

Šlajmerjeva 3

References

Hack M, Fanaroff AA. Outcomes of children of extremely low birthweights and gestational age in the 1990’s. Early Hum Dev 1999; 53: 193-218.

Slattery MM, Morison JJ. Preterm delivery. Lancet. 2002; 360: 1489-97.

Steer M. The epidemiology of preterm labor. BJOG. 2005; 122(Suppl 1): 1-3.

Muglia LJ, Katz M. The enigma of spontaneous preterm birth. N Engl J Med. 2010; 362: 529-35.

Gyetvai K, Hannah ME, Hodnett ED, Ohlsson A. Tocolytics for preterm labor: a systematic review. Obstet Gynecol. 1999;94:869-77.

Fox NS, Chervenak FA. Cervical cerclage: a review of the evidence. Obstet Gynecol Surv 2007; 63; 58-65.

Allen WM, Corner GW, Physiology of the corpus luteum. VII. Maintenance of pregnancy in rabbit after very early castration by corpus luteum extracts. Proc Soc Exp Biol Med. 1930; 27: 403.

Csapo IA. Progesterone “block”. Am J Anat. 1956; 98: 273-92.

Ruddock N, Shi S-Q, Jain S, Moore G, Hankins GDV, Romero R, Garfield RE. Progesterone, but not 17alpha hydroxyprogesterone caproate, inhibits human myometrial contractions. Am J Obstet Gynecol. 2008; 199: 391.e1-7.

Xu H, Gonzalez JM, Ofori E, Elovitz MA. Preventing cervical ripening: the primary mechanism by which progestational agents prevent preterm birth? Am J Obstet Gynecol. 2008; 198: 314.e1-314.e8.

Kelly RW. Pregnancy maintenance and parturition: the role of prostaglandin in manipulating the immune and inflammatory response. Endocr Rev. 1994; 15: 684-706.

Dodd JM, Flenady V, Cicotta R, Crowther CA. Prenatal administration of progesterone for preventing preterm birth. Cochrane Database Syst Rev. 2006; CD004947.

Northen AT, Norman GS, Anderson K, Moseley L, Divito M, Cotroneo M, et al. Follow-up of children exposed in utero to 17 alpha-hydroxyprogesterone caproate compared with placebo. Obstet Gynecol 2007; 110: 865-72.

Ness A, Dias T, Damus K, Burd I, Bergella V. Impact of the recent randomized trial on the use of progesterone to prevent preterm birth: a 2005 follow-up survey. Am J Obstet Gynecol 2005; 195: 1174-9.

Onsrud M, Paus E, Haug E, Kjorstad K. Intramuscular administration of hydroxyprogesterone caproate in patients with endometrial carcinoma. Pharmacocinetics and effects on adrenal function. Acta Obstet Gynecol Scand 1985; 64: 519-23.

Murray JL. Natural progesterone: what role in women’s heatlh care? Women’s Health Primary Care 1998; 1: 671-87.

Fonseca EB, Bittar RE, Carvalho MHB, 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: 419-24.

Cetingoz E, Cam C, Sakalh 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: 423-9.

Majhni P, Bagga R, Kalra J, Sharma M. Intravaginal use of natural micronized progesterone to prevent pre-term birth: A randomized trial in India. J Obstet Gynecol 2009; 29: 493-8.

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, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2007; 30: 687-96.

Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med 2007; 357: 462-9.

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

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.

Norman JE, Mackenzie F, Owen P, Mactier H, Hanretty K, Cooper S, et al. Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomized, double-blind, placebo-controlled study and meta-analysis. Lancet 2009; 373: 2034-40.

Rode L, Klein K, Nicolaides KH, Krampl-Bettelheim E, Tabor A; PREDICT Group. Prevention of preterm delivery in twin gestations (PREDICT): a multicenter, randomized, placebo-controlled trial on the effect of vaginal micronized progesterone. Ultrasound Obstet Gynecol 2011; 38:272-80.

Serra V, Perales A, Meseguer J, Parrilla JJ, Lara C, Bellver J, Grifol R, Alcover I, Sala M, Martínez-Escoriza JC, Pellicer A. Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double-blind multicentre trial. BJOG 2013; 120:50-7.

Rouse DJ, Caritis SN, Peaceman AM, Sciscione A, Thom EA, Spong CY, et al. A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. N Engl J Med 2007; 357: 454-61.

Romero R, Nicolaides K, Conde-Agudelo A, Tabor A, O'Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Klein K, Rode L, Soma-Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS.Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol 2012; 206: 124.e1-19.

Fuchs F, Stakemann G. Treatment of threatened premature labor with large doses of progesterone. Am J Obstet Gynecol. 1960; 79: 172-6.

Erny R, Pigne A, Prouvost C, Gamerre M, Malet C, Serment H, et al. The effects of oral administration of progesterone for premature labor. Am J Obstet Gynecol 1986; 154: 525-9.

Noblot G, Audra P, Dargent D, Faguer B, Mellier G. The use of micronized progesterone in the treatment of menace of preterm delivery. Eur J Obstet Gynecol Reprod Biol 1991; 40: 203-9.

Borna S, Sahabi N. Progesterone for maintenance tocolytic therapy after threatened preterm labour: A randomised controlled trial. Aust N Z J Obstet Gynecol 2008; 48: 58-63.

Sharami SH, Zahiri Z, Shakiba M, Milani F. Maintenance therapy by vaginal progesterone after threatened idiopathic preterm labor: a randomized placebo-controlled double-blind trial. Int J Fertil Steril 2010; 4: 45-50.

Martinez de Tejada B, Karolinski A, Ocampo M, Laterra C, Hösli I, Fernández D, et al. Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial. BJOG 2014[Epub ahead of print].

Hendrickx AG, Korte R, Leuschner F, Neumann BW, Poggel A, Binkerd P, et al. Embriotoxicity of sex steroidal hormones in nonhuman primates: II. Hydroxyprogesterone caproate, estradiol valerate. Teratology 1987; 35 :129.

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: 2379-85.

Keirse MJNC. Progestogen administration in pregnancy may prevent preterm delivery. BJOG 1990; 97: 149-54.

Hobel CJ, Ross MG, Bemis RL, Bragonier JR, Nessim S, Sandhu S, et al. The West Los Angeles Preterm Birth Prevention Project. I. Program impact on high risk women. Am J Obstet Gynecol. 1994; 170: 54-62.

Rode L, Langhoff-Roos J, Andersson C, Dinesen J, Schou Hammerun M, Mohapeloa H, et al. Systematic review of progesterone for the prevention of preterm birth in singleton pregnancies. Acta Obstet Gynecol Scand. 2009; 88: 1180-9.

Rebarber A, Istwan NB, Russo-Stieglitz K, Cleary-Goldman J, Rhea DJ, Stanziano GJ, et al. Increased incidence of gestational diabetes in women receiving prophylactic 17alpha-hydroxyprogesterone caproate for prevention of preterm delivery. Diabetes Care 2007; 30: 2277-80.

Rai P, Rajaram S, Goel N, Gopalakrishnan RA, Agarwal R, Mehta S. Oral micronized progesterone for prevention of preterm birth. Int J Gynaecol Obstet 2009; 104: 40-3.

De Ziegler D, Bulletti C, De Monstier B, Jaaskelainen A-S. The first pass uterine effect. Ann N Ann N Y Acad SciY Acad Sci 1997; 828: 291–9.

Published
2015-10-06
How to Cite
1.
Lucovnik M, Premru Sršen T. Progesterone for preterm birth prevention. ZdravVestn [Internet]. 6Oct.2015 [cited 23Aug.2019];84(9). Available from: https://vestnik.szd.si/index.php/ZdravVest/article/view/1272
Section
Review