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Vaginal progesterone is as effective as cervical cerclage to prevent preterm birth in women with a singleton gestation, previous spontaneous preterm birth, and a short cervix: updated indirect comparison meta-analysis

  • Agustin Conde-Agudelo
    Affiliations
    Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI

    Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
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  • Roberto Romero
    Correspondence
    Corresponding author: Roberto Romero, MD, DMedSci.
    Affiliations
    Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI

    Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI

    Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI

    Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI
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  • Eduardo Da Fonseca
    Affiliations
    Departamento de Obstetrícia e Ginecologia, Hospital do Servidor Publico Estadual “Francisco Morato de Oliveira” and School of Medicine, University of São Paulo, São Paulo, Brazil
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  • John M. O’Brien
    Affiliations
    Department of Obstetrics and Gynecology, University of Kentucky, Lexington, KY
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  • Elcin Cetingoz
    Affiliations
    Department of Obstetrics and Gynecology, Turkish Red Crescent Altintepe Medical Center, Maltepe, Istanbul, Turkey
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  • George W. Creasy
    Affiliations
    Center for Biomedical Research, Population Council, New York, NY
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  • Sonia S. Hassan
    Affiliations
    Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI

    Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
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  • Offer Erez
    Affiliations
    Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI

    Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI

    Department of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Faculty of Health Sciences. Ben-Gurion University of the Negev, Beersheba, Israel
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  • Percy Pacora
    Affiliations
    Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI

    Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
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  • Kypros H. Nicolaides
    Affiliations
    Harris Birthright Research Center for Fetal Medicine, King’s College Hospital, London, United Kingdom
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Published:April 06, 2018DOI:https://doi.org/10.1016/j.ajog.2018.03.028

      Background

      An indirect comparison meta-analysis published in 2013 reported that both vaginal progesterone and cerclage are equally efficacious for preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic short cervix. The efficacy of vaginal progesterone has been challenged after publication of the OPPTIMUM study. However, this has been resolved by an individual patient-data meta-analysis (Am J Obstet Gynecol. 2018;218:161-180).

      Objective

      To compare the efficacy of vaginal progesterone and cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix.

      Data Sources

      MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to March 2018); Cochrane databases, bibliographies, and conference proceedings.

      Study Eligibility Criteria

      Randomized controlled trials comparing vaginal progesterone to placebo/no treatment or cerclage to no cerclage in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic cervical length <25 mm.

      Study Appraisal and Synthesis Methods

      Updated systematic review and adjusted indirect comparison meta-analysis of vaginal progesterone vs cerclage using placebo/no cerclage as the common comparator. The primary outcomes were preterm birth <35 weeks of gestation and perinatal mortality. Pooled relative risks (RRs) with 95% confidence intervals were calculated.

      Results

      Five trials comparing vaginal progesterone vs placebo (265 women) and 5 comparing cerclage vs no cerclage (504 women) were included. Vaginal progesterone, compared to placebo, significantly reduced the risk of preterm birth <35 and <32 weeks of gestation, composite perinatal morbidity/mortality, neonatal sepsis, composite neonatal morbidity, and admission to the neonatal intensive care unit (RRs from 0.29 to 0.68). Cerclage, compared to no cerclage, significantly decreased the risk of preterm birth <37, <35, <32, and <28 weeks of gestation, composite perinatal morbidity/mortality, and birthweight <1500 g (RRs from 0.64 to 0.70). Adjusted indirect comparison meta-analyses did not show statistically significant differences between vaginal progesterone and cerclage in the reduction of preterm birth or adverse perinatal outcomes.

      Conclusion

      Vaginal progesterone and cerclage are equally effective for preventing preterm birth and improving perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix. The choice of treatment will depend on adverse events and cost-effectiveness of interventions and patient/physician’s preferences.

      Key words

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      References

        • Blencowe H.
        • Cousens S.
        • Oestergaard M.Z.
        • et al.
        National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications.
        Lancet. 2012; 379: 2162-2172
        • Martin J.A.
        • Hamilton B.E.
        • Osterman M.J.K.
        • Driscoll A.K.
        • Drake P.
        Births: final data for 2016.
        Natl Vital Stat Rep. 2018; 67: 1
        • United Nations Inter-Agency Group for Child Mortality Estimation (UN IGME)
        Levels and trends in child mortality: report 2017, estimates developed by the UN Inter-Agency Group for Child Mortality Estimation.
        United Nations Children’s Fund, New York2017
      1. Institute of Medicine, US Committee on Understanding Premature Birth and Assuring Healthy Outcomes.
        in: Behrman R.E. Butler A.S. Preterm birth: causes, consequences, and prevention. National Academies Press, Washington, DC2007
        • Saigal S.
        • Doyle L.W.
        An overview of mortality and sequelae of preterm birth from infancy to adulthood.
        Lancet. 2008; 371: 261-269
        • Mwaniki M.K.
        • Atieno M.
        • Lawn J.E.
        • Newton C.R.
        Long-term neurodevelopmental outcomes after intrauterine and neonatal insults: a systematic review.
        Lancet. 2012; 379: 445-452
        • Parkinson J.R.
        • Hyde M.J.
        • Gale C.
        • Santhakumaran S.
        • Modi N.
        Preterm birth and the metabolic syndrome in adult life: a systematic review and meta-analysis.
        Pediatrics. 2013; 131: e1240-e1263
        • Li S.
        • Zhang M.
        • Tian H.
        • Liu Z.
        • Yin X.
        • Xi B.
        Preterm birth and risk of type 1 and type 2 diabetes: systematic review and meta-analysis.
        Obes Rev. 2014; 15: 804-811
        • Manuck T.A.
        • Rice M.M.
        • Bailit J.L.
        • et al.
        Preterm neonatal morbidity and mortality by gestational age: a contemporary cohort.
        Am J Obstet Gynecol. 2016; 215: 103.e1-103.e14
        • Smith D.D.
        • Miller R.
        • Gyamfi-Bannerman C.
        Risk of cerebral palsy by gestational age epoch.
        Am J Obstet Gynecol. 2016; 214: S180
        • Chevallier M.
        • Debillon T.
        • Pierrat V.
        • et al.
        Leading causes of preterm delivery as risk factors for intraventricular hemorrhage in very preterm infants: results of the EPIPAGE 2 cohort study.
        Am J Obstet Gynecol. 2017; 216: 518.e1-518.e12
        • Romero R.
        Prenatal medicine: the child is the father of the man. 1996.
        J Matern Fetal Neonatal Med. 2009; 22: 636-639
        • Romero R.
        • Espinoza J.
        • Kusanovic J.P.
        • et al.
        The preterm parturition syndrome.
        BJOG. 2006; 113: 17-42
        • Romero R.
        • Dey S.K.
        • Fisher S.J.
        Preterm labor: one syndrome, many causes.
        Science. 2014; 345: 760-765
        • Asrat T.
        • Lewis D.F.
        • Garite T.J.
        • et al.
        Rate of recurrence of preterm premature rupture of membranes in consecutive pregnancies.
        Am J Obstet Gynecol. 1991; 165: 1111-1115
        • Ananth C.V.
        • Getahun D.
        • Peltier M.R.
        • Salihu H.M.
        • Vintzileos A.M.
        Recurrence of spontaneous vs medically indicated preterm birth.
        Am J Obstet Gynecol. 2006; 195: 643-650
        • Goldenberg R.L.
        • Andrews W.W.
        • Faye-Petersen O.
        • Cliver S.
        • Goepfert A.R.
        • Hauth J.C.
        The Alabama Preterm Birth Project: placental histology in recurrent spontaneous and indicated preterm birth.
        Am J Obstet Gynecol. 2006; 195: 792-796
        • Mazaki-Tovi S.
        • Romero R.
        • Kusanovic J.P.
        • et al.
        Recurrent preterm birth.
        Semin Perinatol. 2007; 31: 142-158
        • Esplin M.S.
        • O’Brien E.
        • Fraser A.
        • et al.
        Estimating recurrence of spontaneous preterm delivery.
        Obstet Gynecol. 2008; 112: 516-523
        • Crane J.M.
        • Hutchens D.
        Use of transvaginal ultrasonography to predict preterm birth in women with a history of preterm birth.
        Ultrasound Obstet Gynecol. 2008; 32: 640-645
        • Getahun D.
        • Strickland D.
        • Ananth C.V.
        • et al.
        Recurrence of preterm premature rupture of membranes in relation to interval between pregnancies.
        Am J Obstet Gynecol. 2010; 202: 570.e1-570.e6
        • Manuck T.A.
        • Henry E.
        • Gibson J.
        • et al.
        Pregnancy outcomes in a recurrent preterm birth prevention clinic.
        Am J Obstet Gynecol. 2011; 204: 320.e1-320.e6
        • Gonzalez-Quintero V.H.
        • Cordova Y.C.
        • Istwan N.B.
        • et al.
        Influence of gestational age and reason for prior preterm birth on rates of recurrent preterm delivery.
        Am J Obstet Gynecol. 2011; 205: 275.e1-275.e5
        • Laughon S.K.
        • Albert P.S.
        • Leishear K.
        • Mendola P.
        The NICHD Consecutive Pregnancies Study: recurrent preterm delivery by subtype.
        Am J Obstet Gynecol. 2014; 210: 131.e1-131.e8
        • Drassinower D.
        • Običan S.G.
        • Siddiq Z.
        • Heller D.
        • Gyamfi-Bannerman C.
        • Friedman A.M.
        Does the clinical presentation of a prior preterm birth predict risk in a subsequent pregnancy?.
        Am J Obstet Gynecol. 2015; 213: 686.e1-686.e7
        • Yang J.
        • Baer R.J.
        • Berghella V.
        • et al.
        Recurrence of preterm birth and early term birth.
        Obstet Gynecol. 2016; 128: 364-372
        • Koullali B.
        • Ravelli A.C.J.
        • Kazemier B.M.
        • Pajkrt E.
        • Mol B.W.J.
        • Oudijk M.A.
        Recurrence rate of spontaneous preterm birth.
        Am J Obstet Gynecol. 2016; 214: S443-S444
        • Phillips C.
        • Velji Z.
        • Hanly C.
        • Metcalfe A.
        Risk of recurrent spontaneous preterm birth: a systematic review and meta-analysis.
        BMJ Open. 2017; 7: e015402
        • Andersen H.F.
        • Nugent C.E.
        • Wanty S.D.
        • Hayashi R.H.
        Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length.
        Am J Obstet Gynecol. 1990; 163: 859-867
        • Iams J.D.
        • Goldenberg R.L.
        • Meis P.J.
        • et al.
        The length of the cervix and the risk of spontaneous premature delivery.
        N Engl J Med. 1996; 334: 567-572
        • Goldenberg R.L.
        • Iams J.D.
        • Miodovnik M.
        • et al.
        The preterm prediction study: risk factors in twin gestations. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.
        Am J Obstet Gynecol. 1996; 175: 1047-1053
        • Imseis H.M.
        • Albert T.A.
        • Iams J.D.
        Identifying twin gestations at low risk for preterm birth with a transvaginal sonographic cervical measurement at 24 to 26 weeks’ gestation.
        Am J Obstet Gynecol. 1997; 177: 1149-1155
        • Wennerholm U.B.
        • Holm B.
        • Mattsby-Baltzer I.
        • et al.
        Fetal fibronectin, endotoxin, bacterial vaginosis and cervical length as predictors of preterm birth and neonatal morbidity in twin pregnancies.
        Br J Obstet Gynaecol. 1997; 104: 1398-1404
        • Berghella V.
        • Tolosa J.E.
        • Kuhlman K.
        • Weiner S.
        • Bolognese R.J.
        • Wapner R.J.
        Cervical ultrasonography compared with manual examination as a predictor of preterm delivery.
        Am J Obstet Gynecol. 1997; 177: 723-730
        • Grisaru-Granovsky S.
        • Farine D.
        • Barrett J.
        • et al.
        Is a single ultrasound measurement of cervical length a predictor of the risk of preterm delivery in multifetal pregnancy?.
        Am J Obstet Gynecol. 1998; 178: 191S
        • Hassan S.S.
        • Romero R.
        • Berry S.M.
        • et al.
        Patients with an ultrasonographic cervical length < or = 15 mm have nearly a 50% risk of early spontaneous preterm delivery.
        Am J Obstet Gynecol. 2000; 182: 1458-1467
        • Yang J.H.
        • Kuhlman K.
        • Daly S.
        • Berghella V.
        Prediction of preterm birth by second trimester cervical sonography in twin pregnancies.
        Ultrasound Obstet Gynecol. 2000; 15: 288-291
        • Guzman E.R.
        • Walters C.
        • O’Reilly-Green C.
        • et al.
        Use of cervical ultrasonography in prediction of spontaneous preterm birth in twin gestations.
        Am J Obstet Gynecol. 2000; 183: 1103-1107
        • Soriano D.
        • Weisz B.
        • Seidman D.S.
        • et al.
        The role of sonographic assessment of cervical length in the prediction of preterm birth in primigravidae with twin gestation conceived after infertility treatment.
        Acta Obstet Gynecol Scand. 2002; 81: 39-43
        • Vayssière C.
        • Favre R.
        • Audibert F.
        • et al.
        Cervical length and funneling at 22 and 27 weeks to predict spontaneous birth before 32 weeks in twin pregnancies: a French prospective multicenter study.
        Am J Obstet Gynecol. 2002; 187: 1596-1604
        • Honest H.
        • Bachmann L.M.
        • Coomarasamy A.
        • Gupta J.K.
        • Kleijnen J.
        • Khan K.S.
        Accuracy of cervical transvaginal sonography in predicting preterm birth: a systematic review.
        Ultrasound Obstet Gynecol. 2003; 22: 305-322
        • Owen J.
        • Yost N.
        • Berghella V.
        • et al.
        Can shortened midtrimester cervical length predict very early spontaneous preterm birth?.
        Am J Obstet Gynecol. 2004; 191: 298-303
        • Gibson J.L.
        • Macara L.M.
        • Owen P.
        • Young D.
        • Macauley J.
        • Mackenzie F.
        Prediction of preterm delivery in twin pregnancy: a prospective, observational study of cervical length and fetal fibronectin testing.
        Ultrasound Obstet Gynecol. 2004; 23: 561-566
        • Sperling L.
        • Kiil C.
        • Larsen L.U.
        • et al.
        How to identify twins at low risk of spontaneous preterm delivery.
        Ultrasound Obstet Gynecol. 2005; 26: 138-144
        • Fait G.
        • Har-Toov J.
        • Gull I.
        • Lessing J.B.
        • Jaffa A.
        • Wolman I.
        Cervical length, multifetal pregnancy reduction, and prediction of preterm birth.
        J Clin Ultrasound. 2005; 33: 329-332
        • Arabin B.
        • Roos C.
        • Kollen B.
        • van Eyck J.
        Comparison of transvaginal sonography in recumbent and standing maternal positions to predict spontaneous preterm birth in singleton and twin pregnancies.
        Ultrasound Obstet Gynecol. 2006; 27: 377-386
        • To M.S.
        • Skentou C.A.
        • Royston P.
        • Yu C.K.
        • Nicolaides K.H.
        Prediction of patient-specific risk of early preterm delivery using maternal history and sonographic measurement of cervical length: a population-based prospective study.
        Ultrasound Obstet Gynecol. 2006; 27: 362-367
        • To M.S.
        • Fonseca E.B.
        • Molina F.S.
        • Cacho A.M.
        • Nicolaides K.H.
        Maternal characteristics and cervical length in the prediction of spontaneous early preterm delivery in twins.
        Am J Obstet Gynecol. 2006; 194: 1360-1365
        • Crane J.M.
        • Hutchens D.
        Transvaginal sonographic measurement of cervical length to predict preterm birth in asymptomatic women at increased risk: a systematic review.
        Ultrasound Obstet Gynecol. 2008; 31: 579-587
        • Klein K.
        • Gregor H.
        • Hirtenlehner-Ferber K.
        • et al.
        Prediction of spontaneous preterm delivery in twin pregnancies by cervical length at mid-gestation.
        Twin Res Hum Genet. 2008; 11: 552-557
        • Fox N.S.
        • Saltzman D.H.
        • Klauser C.K.
        • Peress D.
        • Gutierrez C.V.
        • Rebarber A.
        Prediction of spontaneous preterm birth in asymptomatic twin pregnancies with the use of combined fetal fibronectin and cervical length.
        Am J Obstet Gynecol. 2009; 201: 313.e1-313.e5
        • Honest H.
        • Forbes C.A.
        • Durée K.H.
        • 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
        • Domin C.M.
        • Smith E.J.
        • Terplan M.
        Transvaginal ultrasonographic measurement of cervical length as a predictor of preterm birth: a systematic review with meta-analysis.
        Ultrasound Q. 2010; 26: 241-248
        • Conde-Agudelo A.
        • Romero R.
        • Hassan S.S.
        • Yeo L.
        Transvaginal sonographic cervical length for the prediction of spontaneous preterm birth in twin pregnancies: a systematic review and metaanalysis.
        Am J Obstet Gynecol. 2010; 203: 128.e1-128.e12
        • Lim A.C.
        • Hegeman M.A.
        • Huis In ’T Veld M.A.
        • Opmeer B.C.
        • Bruinse H.W.
        • Mol B.W.
        Cervical length measurement for the prediction of preterm birth in multiple pregnancies: a systematic review and bivariate meta-analysis.
        Ultrasound Obstet Gynecol. 2011; 38: 10-17
        • Barros-Silva J.
        • Pedrosa A.C.
        • Matias A.
        Sonographic measurement of cervical length as a predictor of preterm delivery: a systematic review.
        J Perinat Med. 2014; 42: 281-293
        • Conde-Agudelo A.
        • Romero R.
        Prediction of preterm birth in twin gestations using biophysical and biochemical tests.
        Am J Obstet Gynecol. 2014; 211: 583-595
        • Li Q.
        • Reeves M.
        • Owen J.
        • Keith L.G.
        Precocious cervical ripening as a screening target to predict spontaneous preterm delivery among asymptomatic singleton pregnancies: a systematic review.
        Am J Obstet Gynecol. 2015; 212: 145-156
        • Conde-Agudelo A.
        • Romero R.
        Predictive accuracy of changes in transvaginal sonographic cervical length over time for preterm birth: a systematic review and metaanalysis.
        Am J Obstet Gynecol. 2015; 213: 789-801
        • Pagani G.
        • Stagnati V.
        • Fichera A.
        • Prefumo F.
        Cervical length at mid-gestation in screening for preterm birth in twin pregnancy.
        Ultrasound Obstet Gynecol. 2016; 48: 56-60
        • Kindinger L.M.
        • Poon L.C.
        • Cacciatore S.
        • et al.
        The effect of gestational age and cervical length measurements in the prediction of spontaneous preterm birth in twin pregnancies: an individual patient level meta-analysis.
        BJOG. 2016; 123: 877-884
        • Melamed N.
        • Pittini A.
        • Hiersch L.
        • et al.
        Serial cervical length determination in twin pregnancies reveals 4 distinct patterns with prognostic significance for preterm birth.
        Am J Obstet Gynecol. 2016; 215: 476.e1-476.e11
        • Vandermolen B.I.
        • Hezelgrave N.L.
        • Smout E.M.
        • Abbott D.S.
        • Seed P.T.
        • Shennan A.H.
        Quantitative fetal fibronectin and cervical length to predict preterm birth in asymptomatic women with previous cervical surgery.
        Am J Obstet Gynecol. 2016; 215: 480.e1-480.e10
        • Melamed N.
        • Pittini A.
        • Hiersch L.
        • et al.
        Do serial measurements of cervical length improve the prediction of preterm birth in asymptomatic women with twin gestations?.
        Am J Obstet Gynecol. 2016; 215: 616.e1-616.e14
        • Moroz L.A.
        • Brock C.O.
        • Govindappagari S.
        • Johnson D.L.
        • Leopold B.H.
        • Gyamfi-Bannerman C.
        Association between change in cervical length and spontaneous preterm birth in twin pregnancies.
        Am J Obstet Gynecol. 2017; 216: 159.e1-159.e7
        • Esplin M.S.
        • Elovitz M.A.
        • Iams J.D.
        • et al.
        Predictive accuracy of serial transvaginal cervical lengths and quantitative vaginal fetal fibronectin levels for spontaneous preterm birth among nulliparous women.
        JAMA. 2017; 317: 1047-1056
        • Brock C.
        • Moroz L.
        • Gyamfi-Bannerman C.
        Is cervical length similarly predictive of preterm birth across races in twin gestation?.
        Am J Obstet Gynecol. 2017; 216: S264-S265
        • Iams J.D.
        • Goldenberg R.L.
        • Mercer B.M.
        • et al.
        The Preterm Prediction Study: recurrence risk of spontaneous preterm birth.
        Am J Obstet Gynecol. 1998; 178: 1035-1040
        • Owen J.
        • Yost N.
        • Berghella V.
        • et al.
        Mid-trimester endovaginal sonography in women at high risk for spontaneous preterm birth.
        JAMA. 2001; 286: 1340-1348
        • Romero R.
        • Nicolaides K.
        • Conde-Agudelo A.
        • et al.
        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.e1-124.e19
        • Conde-Agudelo A.
        • Romero R.
        • Nicolaides K.
        • et al.
        Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis.
        Am J Obstet Gynecol. 2013; 208: 42.e1-42.e18
        • Romero R.
        • Yeo L.
        • Miranda J.
        • Hassan S.S.
        • Conde-Agudelo A.
        • Chaiworapongsa T.
        A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix.
        J Perinat Med. 2013; 41: 27-44
        • Romero R.
        • Yeo L.
        • Chaemsaithong P.
        • Chaiworapongsa T.
        • Hassan S.S.
        Progesterone to prevent spontaneous preterm birth.
        Semin Fetal Neonatal Med. 2014; 19: 15-26
        • International Federation of Gynecology and Obstetrics Working Group on Best Practice In Maternal-Fetal Medicine; International Federation of Gynecology and Obstetrics
        Best practice in maternal-fetal medicine.
        Int J Gynaecol Obstet. 2015; 128: 80-82
      2. National Institute for Health and Care Excellence. Preterm labor and birth. NICE guideline 25. 2015. Available at: https://www.nice.org.uk/guidance/ng25/evidence/full-guideline-2176838029. Accessed Jan. 30, 2018.

        • Conde-Agudelo A.
        • Romero R.
        Vaginal progesterone to prevent preterm birth in pregnant women with a sonographic short cervix: clinical and public health implications.
        Am J Obstet Gynecol. 2016; 214: 235-242
        • Romero R.
        • Nicolaides K.H.
        • Conde-Agudelo A.
        • et al.
        Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study.
        Ultrasound Obstet Gynecol. 2016; 48: 308-317
        • O’Brien J.M.
        • Lewis D.F.
        Prevention of preterm birth with vaginal progesterone or 17-alpha-hydroxyprogesterone caproate: a critical examination of efficacy and safety.
        Am J Obstet Gynecol. 2016; 214: 45-56
        • Vintzileos A.M.
        • Visser G.H.
        Interventions for women with mid-trimester short cervix: which ones work?.
        Ultrasound Obstet Gynecol. 2017; 49: 295-300
        • Romero R.
        • Conde-Agudelo A.
        • Da Fonseca E.
        • et al.
        Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data.
        Am J Obstet Gynecol. 2018; 218: 161-180
        • Campbell S.
        Prevention of spontaneous preterm birth: universal cervical length assessment and vaginal progesterone in women with a short cervix: time for action!.
        Am J Obstet Gynecol. 2018; 218: 151-158
        • Berghella V.
        • Rafael T.J.
        • Szychowski J.M.
        • Rust O.A.
        • Owen J.
        Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth: a meta-analysis.
        Obstet Gynecol. 2011; 117: 663-671
        • Berghella V.
        Cerclage decreases preterm birth: finally the level I evidence is here.
        Am J Obstet Gynecol. 2011; 205: 89-90
        • Society for Maternal-Fetal Medicine Publications Committee, with assistance of Vincenzo Berghella
        Progesterone and preterm birth prevention: translating clinical trials data into clinical practice.
        Am J Obstet Gynecol. 2012; 206: 376-386
        • American College of Obstetricians and Gynecologists. Committee on Practice Bulletins–Obstetrics
        Prediction and prevention of preterm birth. ACOG Practice bulletin no. 130.
        Obstet Gynecol. 2012; 120: 964-973
        • American College of Obstetricians and Gynecologists
        Cerclage for the management of cervical insufficiency. ACOG Practice bulletin no.142.
        Obstet Gynecol. 2014; 123: 372-379
        • McIntosh J.
        • Feltovich H.
        • Berghella V.
        • Manuck T.
        • Society for Maternal-Fetal Medicine (SMFM)
        The role of routine cervical length screening in selected high- and low-risk women for preterm birth prevention.
        Am J Obstet Gynecol. 2016; 215: B2-B7
        • Berghella V.
        The power of meta-analysis to address an important clinical question in obstetrics.
        Am J Obstet Gynecol. 2017; 216: 379.e1-379.e4
        • Ionescu A.C.
        • Gheorghiu D.
        • Pacu I.
        • Davitoiu B.
        • Dimitriu M.
        • Haradja H.
        Randomized trial of cerclage and progesterone to prevent spontaneous preterm birth in high-risk women with a short cervix.
        J Perinat Med. 2011; 39 (Abstract 008)
        • Chandiramani M.
        • Seed P.T.
        • Orsi N.M.
        • et al.
        Limited relationship between cervico-vaginal fluid cytokine profiles and cervical shortening in women at high risk of spontaneous preterm birth.
        PLoS One. 2012; 7: e52412
        • Norman J.E.
        • Marlow N.
        • Messow C.-M.
        • et al.
        • for the OPPTIMUM study group
        Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomized, double-blind trial.
        Lancet. 2016; 387: 2106-2116
        • Song F.
        • Altman D.G.
        • Glenny A.M.
        • Deeks J.J.
        Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses.
        BMJ. 2003; 326: 472
        • Sutton A.
        • Ades A.E.
        • Cooper N.
        • Abrams K.
        Use of indirect and mixed treatment comparisons for technology assessment.
        Pharmacoeconomics. 2008; 26: 753-767
        • Song F.
        • Harvey I.
        • Lilford R.
        Adjusted indirect comparison may be less biased than direct comparison for evaluating new pharmaceutical interventions.
        J Clin Epidemiol. 2008; 61: 455-463
        • Wells G.A.
        • Sultan A.
        • Chen L.
        • Khan M.
        • Coyle D.
        Indirect evidence: indirect treatment comparisons in meta-analysis.
        Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada2009
        • Edwards S.J.
        • Clarke M.J.
        • Wordsworth S.
        • Borrill J.
        Indirect comparisons of treatments based on systematic reviews of randomized controlled trials.
        Int J Clin Pract. 2009; 63: 841-854
        • Song F.
        • Xiong T.
        • Parekh-Bhurke S.
        • et al.
        Inconsistency between direct and indirect comparisons of competing interventions: meta-epidemiological study.
        BMJ. 2011; 343: d4909
        • Abdelhamid A.S.
        • Loke Y.K.
        • Parekh-Bhurke S.
        • et al.
        Use of indirect comparison methods in systematic reviews: a survey of Cochrane review authors.
        Res Synth Methods. 2012; 3: 71-79
        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.
        BMJ. 2009; 339: b2700
        • Stewart L.A.
        • Clarke M.
        • Rovers M.
        • et al.
        Preferred reporting items for systematic review and meta-analyses of individual participant data: the PRISMA-IPD statement.
        JAMA. 2015; 313: 1657-1665
        • Donegan S.
        • Williamson P.
        • Gamble C.
        • Tudur-Smith C.
        Indirect comparisons: a review of reporting and methodological quality.
        PLoS One. 2010; 5: e11054
      3. Higgins J, Altman D, Sterne J. Chapter 8: Assessing risk of bias in included studies. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration; 2011.

        • Tierney J.F.
        • Vale C.
        • Riley R.
        • et al.
        Individual participant data (IPD) meta-analyses of randomized controlled trials: guidance on their use.
        PLoS Med. 2015; 12: e1001855
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BM. 2003; 327: 557-560
        • Altman D.G.
        Confidence intervals for the number needed to treat.
        BMJ. 1998; 317: 1309-1312
        • Bucher H.C.
        • Guyatt G.H.
        • Griffith L.E.
        • Walter S.D.
        The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials.
        J Clin Epidemiol. 1997; 50: 683-691
        • Glenny A.M.
        • Altman D.G.
        • Song F.
        • et al.
        Indirect comparisons of competing interventions.
        Health Technol Assess. 2005; 9: 1-134, iii-iv
        • Fonseca E.B.
        • Celik E.
        • Parra M.
        • Singh M.
        • Nicolaides K.H.
        • 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
        • 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
        • Cetingoz E.
        • Cam C.
        • Sakallı 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
        • Hassan S.S.
        • Romero R.
        • Vidyadhari D.
        • et al.
        PREGNANT Trial. 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
        • Rust O.A.
        • Atlas R.O.
        • Reed J.
        • van Gaalen J.
        • Balducci J.
        Revisiting the short cervix detected by transvaginal ultrasound in the second trimester: why cerclage therapy may not help.
        Am J Obstet Gynecol. 2001; 185: 1098-1105
        • Althuisius S.M.
        • Dekker G.A.
        • Hummel P.
        • Bekedam D.J.
        • van Geijn H.P.
        Final results of the Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): therapeutic cerclage with bed rest vs bed rest alone.
        Am J Obstet Gynecol. 2001; 185: 1106-1112
        • To M.S.
        • Alfirevic Z.
        • Heath V.C.
        • et al.
        Cervical cerclage for prevention of preterm delivery in women with short cervix: randomised controlled trial.
        Lancet. 2004; 363: 1849-1853
        • Berghella V.
        • Odibo A.O.
        • Tolosa J.E.
        Cerclage for prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination: a randomized trial.
        Am J Obstet Gynecol. 2004; 191: 1311-1317
        • Owen J.
        • Hankins G.
        • Iams J.D.
        • et al.
        Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length.
        Am J Obstet Gynecol. 2009; 201: 375.e1-375.e8
        • van Os M.A.
        • van der Ven A.J.
        • Kleinrouweler C.E.
        • et al.
        Preventing preterm birth with progesterone in women with a short cervical length from a low-risk population: a multicenter double-blind placebo-controlled randomized trial.
        Am J Perinatol. 2015; 32: 993-1000
        • Azargoon A.
        • Ghorbani R.
        • Aslebahar F.
        Vaginal progesterone on the prevention of preterm birth and neonatal complications in high risk women: a randomized placebo-controlled double-blind study.
        Int J Reprod Biomed (Yazd). 2016; 14: 309-316
        • Crowther C.A.
        • Ashwood P.
        • McPhee A.J.
        • et al.
        Vaginal progesterone pessaries for pregnant women with a previous preterm birth to prevent neonatal respiratory distress syndrome (the PROGRESS study): a multicenter, randomized, placebo-controlled trial.
        PLoS Med. 2017; 14: e1002390
        • Otsuki K.
        • Nakai A.
        • Matsuda Y.
        • et al.
        Randomized trial of ultrasound-indicated cerclage in singleton women without lower genital tract inflammation.
        J Obstet Gynaecol Res. 2016; 42: 148-157
        • 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: 351.e1-351.e6
        • Jo B.
        Statistical power in randomized intervention studies with noncompliance.
        Psychol Methods. 2002; 7: 178-193
        • Alfirevic Z.
        • Stampalija T.
        • Medley N.
        Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy.
        Cochrane Database Syst Rev. 2017; 6: CD008991
        • Grobman W.A.
        • Thom E.A.
        • Spong C.Y.
        • et al.
        17 Alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm.
        Am J Obstet Gynecol. 2012; 207: 390.e1-390.e8
        • Winer N.
        • Bretelle F.
        • Senat M.V.
        • et al.
        17 Alpha-hydroxyprogesterone caproate does not prolong pregnancy or reduce the rate of preterm birth in women at high risk for preterm delivery and a short cervix: a randomized controlled trial.
        Am J Obstet Gynecol. 2015; 212: 485.e1-485.e10
        • Roeckner J.T.
        • Sanchez-Ramos L.
        The comparative efficacy of cervical pessary, cerclage, vaginal and parenteral progesterone for the prevention of preterm birth in women with a sonographic short cervix and a singleton gestation: a systematic review and network meta-analysis.
        Am J Obstet Gynecol. 2017; 216: S382
        • Dodd J.M.
        • Jones L.
        • 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. 2013; 7: CD004947
        • Dodd J.M.
        • Grivell R.M.
        • O’Brien C.M.
        • Dowswell T.
        • Deussen A.R.
        Prenatal administration of progestogens for preventing spontaneous preterm birth in women with a multiple pregnancy.
        Cochrane Database Syst Rev. 2017; 10: CD012024
        • Romero R.
        • Conde-Agudelo A.
        • El-Refaie W.
        • et al.
        Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta-analysis of individual patient data.
        Ultrasound Obstet Gynecol. 2017; 49: 303-314
        • O’Brien J.M.
        • Steichen J.J.
        • Phillips J.A.
        • Creasy G.W.
        Two year infant outcomes for children exposed to supplemental intravaginal progesterone gel in utero: secondary analysis of a multicenter, randomized, double-blind, placebo-controlled trial.
        Am J Obstet Gynecol. 2012; 206: S223
        • McNamara H.C.
        • Wood R.
        • Chalmers J.
        • et al.
        STOPPIT Baby Follow-up Study: the effect of prophylactic progesterone in twin pregnancy on childhood outcome.
        PLoS One. 2015; 10: e0122341
        • Vedel C.
        • Larsen H.
        • Holmskov A.
        • et al.
        Long-term effects of prenatal progesterone exposure: neurophysiological development and hospital admissions in twins up to 8 years of age.
        Ultrasound Obstet Gynecol. 2016; 48: 382-389
        • van ’t Hooft J.
        • Cuijpers C.
        • Schneeberger C.
        • et al.
        Preventing preterm birth with progesterone in women with short cervical length, outcomes in children at 24 months of age.
        Am J Obstet Gynecol. 2017; 216: S492
        • Murray S.R.
        • Stock S.J.
        • Norman J.E.
        Long-term childhood outcomes after interventions for prevention and management of preterm birth.
        Semin Perinatol. 2017; 41: 519-527
        • Cahill A.G.
        • Odibo A.O.
        • Caughey A.B.
        • et al.
        Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.
        Am J Obstet Gynecol. 2010; 202: 548.e1-548.e8
        • Werner E.F.
        • Han C.S.
        • Pettker C.M.
        • et al.
        Universal cervical-length screening to prevent preterm birth: a cost-effectiveness analysis.
        Ultrasound Obstet Gynecol. 2011; 38: 32-37
        • Werner E.F.
        • Hamel M.S.
        • Orzechowski K.
        • Berghella V.
        • Thung S.F.
        Cost-effectiveness of transvaginal ultrasound cervical length screening in singletons without a prior preterm birth: an update.
        Am J Obstet Gynecol. 2015; 213: 554.e1-554.e6
        • Einerson B.D.
        • Grobman W.A.
        • Miller E.S.
        Cost-effectiveness of risk-based screening for cervical length to prevent preterm birth.
        Am J Obstet Gynecol. 2016; 215: 100.e1-100.e7
        • Crosby D.A.
        • Miletin J.
        • Semberova J.
        • Daly S.
        Is routine transvaginal cervical length measurement cost-effective in a population where the risk of spontaneous preterm birth is low?.
        Acta Obstet Gynecol Scand. 2016; 95: 1391-1395
        • Pizzi L.T.
        • Seligman N.S.
        • Baxter J.K.
        • Jutkowitz E.
        • Berghella V.
        Cost and cost effectiveness of vaginal progesterone gel in reducing preterm birth: an economic analysis of the PREGNANT trial.
        Pharmacoeconomics. 2014; 32: 467-478
        • Jain S.
        • Kilgore M.
        • Edwards R.K.
        • Owen J.
        Revisiting the cost-effectiveness of universal cervical length screening: importance of progesterone efficacy.
        Am J Obstet Gynecol. 2016; 215: 101.e1-101.e7
        • Page J.
        • Emerson J.
        • Cahill A.
        • et al.
        The impact of cervical length on the cost-effectiveness of vaginal progesterone as a preterm birth intervention. ACOG Practice bulletin no. 126.
        Am J Obstet Gynecol. 2013; 208: S66
        • Brown S.
        • Mozurkewich E.
        Cost analysis of universal cervical length screening and progesterone therapy in remote populations. ACOG Practice bulletin no. 397.
        Am J Obstet Gynecol. 2014; 210: S201
        • Fonseca E.B.
        • Nishikawa A.M.
        • Paladini L.
        • Clark O.A.
        Cervical assessment with progesterone in the prevention of preterm birth: a strategy based on cost-effectiveness.
        Value Health. 2014; 17: A510
        • Son M.
        • Grobman W.A.
        • Ayala N.K.
        • Miller E.S.
        A universal mid-trimester transvaginal cervical length screening program and its associated reduced preterm birth rate.
        Am J Obstet Gynecol. 2016; 214: 365.e1-365.e5
        • Temming L.A.
        • Durst J.K.
        • Tuuli M.G.
        • et al.
        Universal cervical length screening: implementation and outcomes.
        Am J Obstet Gynecol. 2016; 214: 523.e1-523.e8
        • Green P.M.
        • Argyelan A.
        • Mutual F.
        • Nynas J.
        • Williams J.
        • Keeton K.
        Implementation of universal cervical length screening is associated with a reduction in the rate of spontaneous preterm delivery in a low-risk cohort.
        Am J Obstet Gynecol. 2017; 216: S10
        • Newnham J.P.
        • White S.W.
        • Meharry S.
        • et al.
        Reducing preterm birth by a statewide multifaceted program: an implementation study.
        Am J Obstet Gynecol. 2017; 216: 434-442
        • Miller E.
        • Grobman W.A.
        Cost-effectiveness of cervical length screening to prevent recurrent preterm birth.
        Am J Obstet Gynecol. 2011; 204: S191
        • Eke A.
        • Buras A.
        • Drnec S.
        • Woo J.
        Vaginal progesterone vs cervical cerclage for the prevention of preterm births in women with a sonographically short cervix—a cost effectiveness and decision analysis.
        Am J Obstet Gynecol. 2015; 212: S367-S368
        • Gray L.
        • Seligman N.
        • Ozcan T.
        • Berghella V.
        Transvaginal cervical length ultrasound: a cost analysis of screening and treatment strategies in high-risk women.
        Am J Obstet Gynecol. 2015; 212: S253
        • Society for Maternal-Fetal Medicine (SMFM) Publications Committee
        The choice of progestogen for the prevention of preterm birth in women with singleton pregnancy and prior preterm birth.
        Am J Obstet Gynecol. 2017; 216: B11-B13

      Linked Article

      • Vaginal progesterone is an alternative to cervical cerclage in women with a short cervix and a history of preterm birth
        American Journal of Obstetrics & GynecologyVol. 219Issue 1
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          Preterm birth continues to be an important and global obstetrical problem. An estimated 15 million preterm births occur throughout the world annually, resulting in approximately 1 million deaths.1 In addition to the high mortality rate, preterm birth is associated with short- and long-term adverse effects.2–6 During their early years, infants born prematurely have high rates of cerebral palsy, sensory deficits, learning disabilities, and respiratory illnesses.7–9 Later in life, these individuals have an increased incidence of diabetes, hypertension, metabolic syndrome, and other adult chronic diseases.
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