Effect of vaginal progesterone in combination with cervical cerclage on improved gestational age and perinatal outcome in twin pregnancy: A prospective randomized study
Keywords:Cerclage M, Preterm birth, Twin gestation, Vaginal progestrone
Background: Prematurity is the second leading cause of death in the first month of life. Objective of present study was to evaluate the effectiveness of vaginal progesterone and cervical cerclage each alone and in combination in improving gestational age in twin pregnancy and its subsequent impact on perinatal outcome.
Methods: A sample size of seventy-five patients has been calculated out of those recruited from outpatient clinic at menoufia university hospital. All fulfilled eligibility criteria of having a twin pregnancy with a history of spontaneous preterm labour, or with a sonographic short cervical length <25mm in mid trimester. The participants were randomly assigned to three groups. Group 1 (N-25): received vaginal progesterone supplementation of 200 mg from 20 weeks until 34 weeks of gestation. Group2 (N-25): were remedied with cervical cerclage of Mc Donald type at 14-16 weeks of gestation Group 3 (N-25): received both vaginal progesterone as well as cervical cerclage. The primary outcome measure was spontaneous delivery between 34-37 weeks of gestation. Secondary outcomes were delivery prior 34 weeks of gestation as well as some parameters of neonatal morbidity and mortality.
Results: There was a statistically significant higher gestational age in combination group when compared to progesterone group or cerclage group (P<0.001). Comparison between progesterone and cerclage groups did not reach statistical significance(P=-0.85). Both progesterone and cerclage groups demonstrated significantly lower birth weights, lower Apgar scores and a higher NICU admission rate than in combination group(P<0.001), while such significant difference did not exist between progesterone and cerclage groups.
Conclusions: Combination of vaginal progesterone and cervical cerclage can improve gestational age at delivery as well as some parameters of perinatal morbidity and mortality in twin pregnancy.
Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385:430-40.
Romero R, Nicolaides K, Conde-Agudelo A, Tabor A, O’Brien JM, Cetingoz E et al. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the mid trimester decreases preterm delivery and neonatal morbidity: a systematic review and meta analysis of individual patient data. Am J Obstet Gynecol. 2012;206:124 e1-19.
Berghella V, Seibel-Seamon J. Contemporary use of cervical cerclage. Clini Obstet Gynecol. 2007;50(2):468-77.
Jarde A, Lutsiv O, Park CK, Barrett J, Beyene J, Saito S, Dodd JM et al. Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis. BJOG. BJOG. 2017;124(8):1163-73.
Rafael TJ, Berghella V, Alfirevic Z. Cervical stitch (cerclage) for preventing preterm birth in multiple pregnancy. Cochrane Database Syst Rev. 2014;10;(9):CD009166.
Martin JA, Hamilton BE, Osterman MJK. Three decades of twin births in the United States, 1980-2009. NCHS Data Brief, no 80.2012; Hyattsville, MD: National Center for Health Statistics.
Goldenberg RL, Iams JD, Miodovnik M, Van Dorsten JP, Thurnau GS 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;175:1047-53.
Conde-Agudelo A, Romero R, Hassan SS, Yeo L. Transvaginal sonographic cervical length for the prediction of spontaneous preterm birth in twin pregnancies: a systematic review and meta analysis. Am J Obstet Gynecol. 2010;203:128 e1-12.
Berghella V, Odibo AO, To MS, Rust OA, Althuisius SM. Cerclage for short cervix on ultrasonography: meta-analysis of trials using individual patient-level data. Obstet Gynecol. 2005;106:181-9.
Brubaker SG, Gyamfi C. Prediction and prevention of spontaneous preterm birth in twin gestations. Semin Perinatol. 2012;36:190-4.
Newman RB, Krombach RS, Myers MC, MCGee DL. Effect of cerclage on obstetrical outcome in twin gestations with a shortened cervical length. Am J Obstet Gyncol. 2002;186:634-40.
Berghella V, Seibel-Seamon J. Contemporary use of cervical cerclage. Clin Obstet Gynecol. 2007;50(2):468-77.
Houlihan C, Poon LCY, Ciarlo M, Kim E, Guzman ER. Cervical cerclage for preterm birth prevention in twin gestation with short cervix: a retrospective cohort study. Ultrasound Obstet Gynecol. 2016;48(6):752-6.
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 randomised, double-blind, placebo-controlled study and meta-analysis. Lancet. 2009;373(9680):2034-40.
Zacharakis D, Daskalakis G, Papantoniou N. Is treatment with cervical pessaries an option in pregnant women with a mid trimester short cervix? J Maternal Fetal Neonatal Med. 2012;25:52.
Brubaker SG, Pessel C, Zork N, Gyamfi-Bannerman C, Ananth CV. Vaginal progesterone in women with twin gestations complicated by short cervix: a retrospective cohort study. BJOG. 2015;122(5):712-8
El-refaie W, Abdelhafez MS, Badawy A. Vaginal progesterone for prevention of preterm labor in asymptomatic twin pregnancies with sonographic short cervix: a randomized clinical trial of efficacy and safety. Arch Gynecol Obstet. 2016;293(1):61-7.
Romero R , Conde-Agudelo A , El-Refaie W, Rode L. 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(3):303-14.
Rode L, Klein K, Nicolaides KH, Krampl-Bettelheim E, Tabor A. 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.
Combs CA, Garite T, Maurel K, Das A, Porto M. Obstetrix Collaborative Research Network. 17-hydroxyprogesterone caproate for twin pregnancy: a double-blind, randomized clinical trial. Am J Obstet Gynecol. 2011;204(3):221.e1-8.
Schuit E, Stock S, Rode L, Rouse DJ, Lim AC, Norman JE et al. Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis. BJOG. 2015;122(1):27-37.
Roman A, Rochelson B, Fox NS, Hoffman M, Berghella V, Patel V et al. Efficacy of ultrasound-indicated cerclage in twin pregnancies. Am J Obstet Gynecol. 2015;212(6):788.e1-6.
Vilchez G, Dai J, Maulik E, Sokol L. A retrospective cohort analysis of cerclage in Twin pregnancies: perinatal outcomes and gestational age at delivery. Am J Obstet Gynecol. 2017;216(1):S538-9.
Chavan MS, Jassawalla MJ. Comparison of perinatal outcome in twin pregnancy with and without cervical cerclage. Int J Reprod Contracept Obstet Gynecol. 2016;5(11):3924-30.
Bernabeu A, Goya M, Martra M, Suy A, Pratcorona L. Physical examination-indicated cerclage in singleton and twin pregnancies: maternal–fetal outcomes. J Maternal Fetal Neonatal Med. 2016;29(13):2109-13.