World Journal of Anemia

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VOLUME 2 , ISSUE 3and4 ( July-December, 2018 ) > List of Articles


Twin-to-twin Transfusion Syndrome: An Overview

Richa Saxena, Kanav Midha

Keywords : Dizygotic, Fetus, Gestation, Monozygotic, Twin–twin transfusion syndrome

Citation Information : Saxena R, Midha K. Twin-to-twin Transfusion Syndrome: An Overview. World J Anemia 2018; 2 (3and4):96-102.

DOI: 10.5005/jp-journals-10065-0041

License: CC BY-NC 4.0

Published Online: 01-04-2020

Copyright Statement:  Copyright © 2018; The Author(s).


Twin-to-twin transfusion syndrome (TTTS) is a severe problem that affects 10–15% of monochorionic (MC) multiple pregnancies. Connecting placental vessels on chorionic plate between donor and recipient twin is accountable for inequality of blood flow. There is an indication for the superiority of fetoscopic laser ablation over serial amnioreductions regarding survival and neurological outcome for stages II–IV TTTS. However, the optimal management of stage I is still debated. In this review, we discuss the basics of twin gestation, optimal management, pathophysiology, long-term neurodevelopmental outcome, and future aspects of TTTS.

  1. Armson BA, O'Connell C, Persad V, et al. Determinants of perinatal mortality and serious neonatal morbidity in the second twin. Obstet Gynecol 2006;108(3 Pt 1):556–564. DOI: 10.1097/01.AOG.0000227747.37184.0a.
  2. Bdolah Y, Lam C, Rajkumar A, et al. Twin pregnancy and the risk of preeclampsia: bigger placenta or relative ischemia? Am J Obstet Gynecol 2008;198(4):428.e1–428.e6. DOI: 10.1016/j.ajog.2007. 10.783.
  3. Bhide A, Thilaganathan B. What prenatal diagnosis should be offered in multiple pregnancy? Best Pract Res Clin Obstet Gynaecol 2004;18(4):531–542. DOI: 10.1016/j.bpobgyn.2004.04.012.
  4. Young BC, Wylie BJ. Effects of twin gestation on maternal morbidity. Semin Perinatol 2012;36(3):162–168. DOI: 10.1053/j.semperi.2012.02.007.
  5. Walker MC, Murphy KE, Pan S, et al. Adverse maternal outcomes in multifetal pregnancies. BJOG 2004;111(11):1294–1296. DOI: 10.1111/j.1471-0528.2004.00345.x.
  6. National Institute for Health and Clinical Excellence. (2011). Multiple Pregnancy: The Management of Twin and Triplet Pregnancies in the Antenatal Period. [online] Available from, Last Accessed November, 2019.
  7. Buhling KJ, Henrich W, Starr E, et al. Risk for gestational diabetes and hypertension for women with twin pregnancy compared to singleton pregnancy. Arch Gynecol Obstet 2003;269(1):33–36. DOI: 10.1007/s00404-003-0483-z.
  8. Obiechina NJ, Okolie V, Eleje G, et al. Twin versus singleton pregnancies: the incidence, pregnancy complications, and obstetric outcomes in a Nigerian tertiary hospital. Int J Women's Health 2011;3:227–230. DOI: 10.2147/IJWH.S22059.
  9. Campbell DM. Multiple pregnancy. Baillieres Clin Obstet Gynaecol 1990;4(1):109–127. DOI: 10.1016/S0950-3552(05)80215-9.
  10. Sperling L. Detection of chromosomal abnormalities, congenital abnormalities and transfusion syndrome in twins. Ultrasound Obstet Gynecol 2007;29(5):517–526. DOI: 10.1002/uog.3918.
  11. Dodd JM, Crowther CA. Reduction of the number of fetuses for women with a multiple pregnancy. Cochrane Database Syst Rev 2012;10:CD003932.
  12. Schmitz T, Carnavalet Cde C, Azria E, et al. Neonatal outcomes of twin pregnancy according to the planned mode of delivery. Obstet Gynecol 2008;111(3):695–703. DOI: 10.1097/AOG.0b013e318163c435.
  13. Wimalasundera RC, Trew G, Fisk NM. Reducing the incidence of twins and triplets. Best Pract Res Clin Obstet Gynaecol 2003;17(2):309–329. DOI: 10.1016/S1521-6934(02)00135-9.
  14. Hack KE, Derks JB, Elias SG, et al. Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study. BJOG 2008;115(1):58–67. DOI: 10.1111/j.1471-0528.2007.01556.x.
  15. Consensus views arising from the 50th study group: multiple pregnancy. In: Kilby M, Baker P, Critchley H, et al. Multiple Pregnancy. London: RCOG Press; 2006. pp. 283–286.
  16. De Paepe ME, Luks FI. What—and why—the pathologist should know about twin-to-twin transfusion syndrome. Pediatr Dev Pathol 2013;16:237–251. DOI: 10.2350/13-03-1315-MISC.1.
  17. De Lia JE, Kuhlmann RS. Twin-to-twin transfusion syndrome—30 years at the front. Am J Perinatol 2014;31(Suppl 1):S7–S12. DOI: 10.1055/s-0034-1376184.
  18. Baschat A, Chmait RH, Deprest J, et al. Twin-to-twin transfusion syndrome (TTTS). J Perinat Med 2011;39:107–112.
  19. Simpson LL. Society for maternal-fetal medicine (SMFM). Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013;208:3–18. DOI: 10.1016/j.ajog.2012.10.880.
  20. Diehl W, Diemert A, Glosemeyer P, et al. OP06. 02: development of survival rates after intrauterine laser therapy for severe mid-trimester twin–twin transfusion syndrome: experience with 600 cases. Ultrasound Obst Gyn 2010;36:67. DOI: 10.1002/uog.7974.
  21. Zhao DP, de Villiers SF, Slaghekke F, et al. Prevalence, size, number and localization of vascular anastomoses in monochorionic placentas. Placenta 2013;34(7):589–593. DOI: 10.1016/j.placenta.2013.04.005.
  22. Harkness UF, Crombleholme TM. Twin–twin transfusion syndrome: Where do we go from here? Semin Perinatol 2005;29(5):296–304. DOI: 10.1053/j.semperi.2005.10.001.
  23. Quintero RA, Morales WJ, Allen MH, et al. Staging of twin-twin transfusion syndrome. J Perinatol 1999;19(8 Pt 1):550–555. DOI: 10.1038/
  24. Michelfelder E, Gottliebson W, Border W, et al. Early manifestations and spectrum of recipient twin cardiomyopathy in twin-twin transfusion syndrome: relation to quintero stage. Ultrasound Obstet Gynecol 2007;30(7):965–971. DOI: 10.1002/uog.5211.
  25. Rychik J, Tian Z, Bebbington M, et al. The twin-twin transfusion syndrome: spectrum of cardiovascular abnormality and development of a cardiovascular score to assess severity of disease. Am J Obstet Gynecol 2007;197(4):392.e1–408.e1. DOI: 10.1016/j.ajog.2007.06.055.
  26. Wohlmuth C, Gardiner HM, Diehl W, et al. Fetal cardiovascular hemodynamics in twin-twin transfusion syndrome. Acta Obstet Gynecol Scand 2016;95(6):664–671. DOI: 10.1111/aogs.12871.
  27. Wohlmuth C, Boudreaux D, Moise Jr KJ, et al. Cardiac pathophysiology in twin-twin transfusion syndrome: new insights into its evolution. Ultrasound Obstet Gynecol 2018;51(3):341–348. DOI: 10.1002/uog.17480.
  28. Yamamoto M, Essaoui M, Nasr B, et al. Three-dimensional sonographic assessment of fetal urine production before and after laser surgery in twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 2007;30(7):972–976. DOI: 10.1002/uog.5218.
  29. Akkermans J, Peeters SH, Klumper FJ, et al. Twenty-five years of fetoscopic laser coagulation in twin-twin transfusion syndrome: a systematic review. Fetal Diagn Ther 2015;38:241–253. DOI: 10.1159/000437053.
  30. Stirnemann J, Chalouhi G, Essaoui M, et al. Fetal brain imaging following laser surgery in twin-to-twin surgery. BJOG 2016;125(9):1186–1191. DOI: 10.1111/1471-0528.14162.
  31. van Klink JM, Koopman HM, van Zwet EW, et al. Improvement in neurodevelopmental outcome in survivors of twin-twin transfusion syndrome treated with laser surgery. Am J Obstet Gynecol 2014;210(6):e541–e547. DOI: 10.1016/j.ajog.2014.01.002.
  32. Schou KV, Lando AV, Ekelund CK, et al. Long-term neurodevelopmental outcome of monochorionic twins after laser therapy or umbilical cord occlusion for twin-twin transfusion syndrome. Fetal Diagn Ther 2019;46(1):20–27. DOI: 10.1159/000491787.
  33. van Klink JM, Koopman HM, Rijken M, et al. Long-term neurodevelopmental outcome in survivors of twin-to-twin transfusion syndrome. Twin Res Hum Genet 2016;19(3):255–261. DOI: 10.1017/thg.2016.26.
  34. Lenclen R, Paupe A, Ciarlo G, et al. Neonatal outcome in preterm monochorionic twins with twin-to-twin transfusion syndrome after intrauterine treatment with amnioreduction or fetoscopic laser surgery: comparison with dichorionic twins. Am J Obstet Gynecol 2007;196(5):e451–e457. DOI: 10.1016/j.ajog.2007.01.036.
  35. Lopriore E, Ortibus E, Acosta-Rojas R, et al. Risk factors for neurodevelopment impairment in twin-twin transfusion syndrome treated with fetoscopic laser surgery. Obstet Gynecol 2009;113(2 Pt 1): 361–366. DOI: 10.1097/AOG.0b013e318195873e.
  36. Herberg U, Bolay J, Graeve P, et al. Intertwin cardiac status at 10-year follow-up after intrauterine laser coagulation therapy of severe twin-twin transfusion syndrome: comparison of donor, recipient and normal values. Arch Dis Child Fetal Neonatal Ed 2014;99(5): F380–F385. DOI: 10.1136/archdischild-2013-305034.
  37. Bebbington M. Twin-to-twin transfusion syndrome: current understanding of pathophysiology, in-utero therapy and impact for future development. Semin Fetal Neonatal Med 2010;15(1):15–20. DOI: 10.1016/j.siny.2009.05.001.
  38. Zikulnig L, Hecher K, Bregenzer T, et al. Prognostic factors in severe twin-twin transfusion syndrome treated by endoscopic laser surgery. Ultrasound Obstet Gynecol 1999;14(6):380–387. DOI: 10.1046/j.1469-0705.1999.14060380.x.
  39. Gratacós E, Van Schoubroeck D, Carreras E. Impact of laser coagulation in severe twin-twin transfusion syndrome on fetal doppler indices and venous blood flow volume. Ultrasound Obstet Gynecol 2002;20(2):125–130. DOI: 10.1046/j.1469-0705.2002.00749.x.
  40. Mackie FL, Hall MJ, Morris RK, et al. Early prognostic factors of outcomes in monochorionic twin pregnancy: systematic review and meta-analysis. Am J Obstet Gynecol 2018;219(5):436–446. DOI: 10.1016/j.ajog.2018.05.008.
  41. Stagnati V, Zanardini C, Fichera A, et al. Early prediction of twin-to-twin transfusion syndrome: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2017;49(5):573–582. DOI: 10.1002/uog.15989.
  42. Akkermans J, Peeters SH, Middeldorp JM, et al. A worldwide survey of laser surgery for twin-twin transfusion syndrome. Ultrasound Obstet Gynecol 2015;45(2):168–174. DOI: 10.1002/uog.14670.
  43. Taylor MJ. The management of multiple pregnancy. Early Hum Dev 2006;82(6):365–370. DOI: 10.1016/j.earlhumdev.2006.03.008.
  44. Perry H, Duffy JMN, Umadia O, et al. Outcome reporting across randomized trials and observational studies evaluating treatments for twin-twin transfusion syndrome: systematic review. Ultrasound Obstet Gynecol 2018;52(5):577–585. DOI: 10.1002/uog. 19068.
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