17-hydroxyprogesterone caproate for twin pregnancy: a double-blind, randomized clinical trial


      We sought to determine whether prophylactic treatment with 17-alpha-hydroxyprogesterone caproate (17Pc) in twin pregnancy will reduce neonatal morbidity (primary outcome) by prolonging pregnancy (secondary outcome).

      Study Design

      This was a double-blind, randomized clinical trial. Mothers carrying dichorionic-diamniotic twins were randomly assigned (in a 2:1 ratio) to weekly injections of 250 mg of 17Pc or placebo, starting at 16-24 weeks and continued until 34 weeks.


      In all, 160 women were randomized to 17Pc and 80 to placebo. Composite neonatal morbidity occurred with similar frequency in the 17Pc and placebo groups (14% vs 12%, respectively, P = .62). Mean gestational age at delivery was not affected by 17Pc (35.3 vs 35.9 weeks, P = .10), but a 3-day difference in median gestational age favored placebo (P = .02). There were no perinatal deaths with 17Pc and 3 with placebo.


      In twin pregnancy, prophylactic treatment with 17Pc did not prolong gestation or reduce neonatal morbidity.

      Key words

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        • Martin J.A.
        • Hamilton B.E.
        • Sutton P.D.
        • et al.
        Births: final data for 2007.
        Natl Vital Stat Rep. 2010; 58.24: 1-125
        • Mathews T.J.
        • MacDorman M.F.
        Infant mortality statistics from the 2006 period linked birth/infant death data set.
        Natl Vital Stat Rep. 2010; 58.17: 1-32
        • Meis P.J.
        • Klebanoff M.
        • Thom E.
        • et al.
        Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.
        N Engl J Med. 2003; 348: 2379-2385
        • da Fonseca E.B.
        • Bittar R.E.
        • Carvalho M.H.B.
        • 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
        • Majhi P.
        • Bagga R.
        • Kalra J.
        • Sharma M.
        Intravaginal use of natural micronized progesterone to prevent pre-term birth: a randomised trial in India.
        J Obstet Gynaecol. 2009; 29: 493-498
        • Fonseca E.B.
        • Celik E.
        • Parra M.
        • Singh M.
        • Nicolaides K.H.
        Progesterone and the risk of preterm birth among women with a short cervix.
        N Engl J Med. 2007; 357: 462-469
        • DeFranco E.A.
        • O'Brien J.M.
        • Adair C.D.
        • 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
        • Borna S.
        • Sahabi N.
        Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial.
        Aust N Z J Obstet Gynaecol. 2008; 48: 58-63
        • American College of Obstetricians and Gynecologists
        Use of progesterone to reduce preterm birth.
        American College of Obstetricians and Gynecologists, Washington, DC2003
        • Hartikainen-Sorri A.L.
        • Kauppila A.
        • Tuimala R.
        Inefficacy of 17alpha-hydroxyprogesterone caproate in the prevention of prematurity in twin pregnancy.
        Obstet Gynecol. 1980; 56: 692-695
        • Combs C.A.
        • Garite T.
        • Maurel K.
        • Das A.
        • Porto M.
        Failure of 17-hydroxyprogesterone to reduce neonatal morbidity or prolong triplet pregnancy: a double-blind, randomized clinical trial.
        Am J Obstet Gynecol. 2010; 203: 248.e1-248.e9
        • American College of Obstetricians and Gynecologists
        Special problems of multiple gestation.
        American College of Obstetricians and Gynecologists, Washington, DC1998
        • Garite T.J.
        • Clark R.H.
        • Elliott J.P.
        • Thorp J.A.
        • Pediatrix/Obstetrix Perinatal Research Group
        Twins and triplets: the effect of plurality and growth on neonatal outcome compared with singleton infants.
        Am J Obstet Gynecol. 2004; 191: 700-707
        • Rouse D.J.
        • Caritis S.N.
        • Peaceman A.M.
        • et al.
        A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins.
        N Engl J Med. 2007; 357: 454-461
        • Briery C.M.
        • Veillon E.W.
        • Klauser C.K.
        • et al.
        Progesterone does not prevent preterm births in women with twins.
        South Med J. 2009; 102: 900-904
        • Norman J.E.
        • Mackenzie F.
        • Owen P.
        • et al.
        Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis.
        Lancet. 2009; 373: 2034-2040
        • Caritis S.N.
        • Rouse D.J.
        • Peaceman A.M.
        • et al.
        Prevention of preterm birth in triplets using 17 alpha-hydroxyprogesterone caproate: a randomized controlled trial.
        Obstet Gynecol. 2009; 113: 285-292
        • Food and Drug Administration, Center for Drug Evaluation and Research
        Summary minutes of the advisory committee for reproductive health drugs, August 29, 2006.
        (Accessed Aug. 17, 2009)
        • Berghella V.
        • Figueroa D.
        • Szychowski J.M.
        • et al.
        17-alpha-hydroxyprogesterone caproate for the prevention of preterm birth in women with prior preterm birth and a short cervical length.
        Am J Obstet Gynecol. 2010; 202 (e1-6): 351
        • Dodd J.M.
        • Flenady V.
        • Cincotta R.
        • Crowther C.A.
        Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth.
        Cochrane Database Syst Rev. 2006; 1: CD004947
        • Iams J.D.
        • Berghella V.
        Care for women with prior preterm birth.
        Am J Obstet Gynecol. 2010; 203: 89-100
        • 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
        • O'Brien J.M.
        • Adair C.D.
        • Lewis D.F.
        • 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: 687-696
        • Facchinetti F.
        • Paganelli S.
        • Comitini G.
        • Dante G.
        • Volpe A.
        Cervical length changes during preterm cervical ripening: effects of 17-α-hydroxyprogesterone caproate.
        Am J Obstet Gynecol. 2007; 196 (e1-4): 453
        • Keeler S.M.
        • Kiefer D.
        • Rochon M.
        • Quinones J.N.
        • Novetsky A.P.
        • Rust O.
        A randomized trial of cerclage vs 17-alpha-hydroxyprogesterone caproate for treatment of short cervix.
        J Perinat Med. 2009; 37: 473-479
        • Alexander G.R.
        • Himes J.H.
        • Kaufman R.B.
        • Mor J.
        • Kogan M.
        A United States national reference for growth.
        Obstet Gynecol. 1996; 87: 163-168