Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-10T19:30:18.510Z Has data issue: false hasContentIssue false

Chapter 11.4 - Twin-to-twin transfusion syndrome

treatment by fetoscopic laser ablation

from Section 2 - Fetal disease

Published online by Cambridge University Press:  05 February 2013

By
Gihad E. Chalouhi ,
Abdullah Al Ibrahim ,
Mohammed Essaoui  and
Yves Ville
Edited by
Mark D. Kilby ,
Anthony Johnson  and
Dick Oepkes
Mark D. Kilby
Affiliation:
Department of Fetal Medicine, University of Birmingham
Anthony Johnson
Affiliation:
Baylor College of Medicine, Texas
Dick Oepkes
Affiliation:
Department of Obstetrics, Leiden University Medical Center
Get access

Summary

Introduction

Monochorionic twin placentation occurs in 20% of spontaneous twin pregnancies and almost 5% of those are obtained by medically assisted reproduction [1]. Monochorionic diamniotic (McDa) twin fetuses have the unique characteristic of living upon one single placenta. This situation can lead to specific complications including twin-to-twin transfusion syndrome (TTTS) [2, 3], twin-anemia-polycythemia sequence (TAPS) [4, 5], and selective intrauterine growth retardation (s-IUGR) [6]. These complications are likely to explain most of the 6- to 12-fold increase in perinatal mortality in monochorionic twins compared to dichorionic twins [7–10].

TTTS, also called twin oligohydramnios-polyhydramnios sequence (TOPS), complicates around 15% of monochorionic pregnancies irrespective of the mode of conception [7]. It is a hemodynamic, and probably hormonal, discordance secondary to imbalanced blood flows through the vascular anastomoses aforementioned [11–14]. The natural history of untreated TTTS leads to intra- or perinatal death in as many as 90% of cases [15, 16]. Impaired neurological development is reported in up to 50% of survivor-twins as a consequence of prematurity or of the intrauterine fetal demise (IUFD) of the co-twin [17, 18]. It is hence crucial to diagnose and treat TTTS as early as possible and using the best-proven management strategy. In this chapter, we will mainly discuss its treatment options focusing on fetoscopic laser ablation of anastomoses. We will also discuss the benefits and risks associated with this treatment.

Keywords

twin-to-twin transfusion syndromelaser treatmentmaternal morbidityseptostomyfetoscopic laser coagulationamnioreductionanesthesia
Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
 , pp. 173 - 183
Publisher: Cambridge University Press
Print publication year: 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Salomon, LJ, Stirnemann, JJ, Bernard, JP, et al. Prenatal management of uncomplicated monochorionic biamniotic pregnancies. J Gynecol Obstet Biol Reprod 2009;38:S45–50.Google Scholar
Chalouhi, GE, Stirnemann, JJ, Salomon, LJ, et al. Specific complications of monochorionic twin pregnancies: twin-twin transfusion syndrome and twin reversed arterial perfusion sequence. Semin Fetal Neonatal Med 2010;15:349–56.Google Scholar
Bebbington, M. Twin-to-twin transfusion syndrome: current understanding of pathophysiology, in-utero therapy and impact for future development. Semin Fetal Neonatal Med 2010;15:15–20.Google Scholar
Lopriore, E, Middeldorp, JM, Oepkes, D, et al. Twin anemia-polycythemia sequence in two monochorionic twin pairs without oligo-polyhydramnios sequence. Placenta 2007;28:47–51.Google Scholar
Slaghekke, F, Kist, WJ, Oepkes, D, et al. Twin anemia-polycythemia sequence: diagnostic criteria, classification, perinatal management and outcome. Fetal Diagn Ther 2010;27:181–90.Google Scholar
Lewi, L, Gucciardo, L, Huber, A, et al. Clinical outcome and placental characteristics of monochorionic diamniotic twin pairs with early- and late-onset discordant growth. Am J Obstet Gynecol 2008;199:511.e1–7.Google Scholar
Sebire, NJ, Snijders, RJ, Hughes, K, Sepulveda, W, Nicolaides, KH. The hidden mortality of monochorionic twin pregnancies. Br J Obstet Gynaecol 1997;104:1203–7.Google Scholar
Hack, K, Derks, J, Elias, S, et al. Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study. BJOG 2008;115:58–67.Google Scholar
Lewi, L, Van Schoubroeck, D, Gratacos, E, et al. Monochorionic diamniotic twins: complications and management options. Curr Opin Obstet Gynecol 2003;15:177–94.Google Scholar
Hamilton, EF, Platt, RW, Morin, L, Usher, R, Kramer, M. How small is too small in a twin pregnancy? Am J Obstet Gynecol 1998;179:682–5.Google Scholar
Ville, Y. Monochorionic twin pregnancies: ‘les liaisons dangereuses’. Ultrasound Obstet Gynecol 1997;10:82–5.Google Scholar
Lewi, L, Jani, J, Cannie, M, et al. Intertwin anastomoses in monochorionic placentas after fetoscopic laser coagulation for twin-to-twin transfusion syndrome: is there more than meets the eye? Am J Obstet Gynecol 2006;194;790–5.Google Scholar
Quintero, RA, Morales, WJ, Allen, MH, et al. Staging of twin-twin transfusion syndrome. J Perinatol 1999;19:550–5.Google Scholar
Wee, LY, Fisk, NM. The twin-twin transfusion syndrome. Semin Neonatol 2002;7;187–202.Google Scholar
Weir, PE, Ratten, GJ, Beischer, NA. Acute polyhydramnios a complication of monozygous twin pregnancy. Br J Obstet Gynaecol 1979;86:849–53.Google Scholar
Robyr, R, Lewi, L, Salomon, LJ, et al. Prevalence and management of late fetal complications following successful selective laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome. Am J Obstet Gynecol 2006;194:796–803.Google Scholar
De Lia, JE. Surgery of the placenta and umbilical cord. Clin Obstet Gynecol 1996;39:607–25.Google Scholar
Haverkamp, F, Lex, C, Hanisch, C, Fahnenstich, H, Zerres, K. Neurodevelopmental risks in twin-to-twin transfusion syndrome: preliminary findings. Eur J Paediatr Neurol 2001;5;21–7.Google Scholar
Senat, MV, Deprest, J, Boulvain, M, et al. A randomized trial of endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome at midgestation. N Engl J Med 2004;351:136–44.Google Scholar
De Lia, J, Fisk, N, Hecher, K, et al. Twin-to-twin transfusion syndrome–debates on the etiology, natural history and management. Ultrasound Obstet Gynecol 2000;16:210–3.Google Scholar
Saade, GR, Belfort, MA, Berry, DL et al. Amniotic septostomy for the treatment of twin oligohydramnios-polyhydramnios sequence. Fetal Diagn Ther 1998;13(2):86–93.Google Scholar
Garry, D, Lysikiewicz, A, Mays, J, Canterino, J, Tejani, N. Intra-amniotic pressure reduction in twin-twin transfusion syndrome. J Perinatol 1998;18(4):284–6.Google Scholar
Moise, KJJ, Dorman, K, Lamvu, G, et al. A randomized trial of amnioreduction versus septostomy in the treatment of twin-twin transfusion syndrome. Am J Obstet Gynecol 2005;193:701–7.Google Scholar
Johnson, JR, Rossi, KQ, O’Shaughnessy, RW. Amnioreduction versus septostomy in twin-twin transfusion syndrome. Am J Obstet Gynecol 2001;185:1044–7.Google Scholar
Gilbert, WM, Davis, SE, Kaplan, C, et al. Morbidity associated with prenatal disruption of the dividing membrane in twin gestations. Obstet Gynecol 1991;78:623–30.Google Scholar
Feldman, DM, Odibo, A, Campbell, WA, Rodis, JF. Iatrogenic monoamniotic twins as a complication of therapeutic amniocentesis. Obstet Gynecol 1998;91:815–16.Google Scholar
Rujiwetpongstorn, J, Tongsong, T. Amniotic band syndrome following septostomy in management of twin-twin transfusion syndrome: a case report. J Perinatol 2008;28:377–9.Google Scholar
Cruz-Martinez, R, Van Mieghm, T, Lewi, L, et al. Incidence and clinical implications of early inadvertent septostomy after laser therapy for twin-twin transfusion syndrome. Ultrasound Obstet Gynecol 2011;37:458–62.Google Scholar
Winer, N, Salomon, LJ, Essaoui, M, et al. Pseudoamniotic band syndrome: a rare complication of monochorionic twins with fetofetal transfusion syndrome treated by laser coagulation. Am J Obstet Gynecol 2008;198:393.e1–5.Google Scholar
Hecher, K, Diehl, W, Zikulnig, L, et al. Endoscopic laser coagulation of placental anastomoses in 200 pregnancies with severe mid-trimester twin-to-twin transfusion syndrome. Eur J Obstet Gynecol Reprod Biol 2000;92:135–9.Google Scholar
Gray, PH, Cincotta, R, Chan, FY, Soong, B. Perinatal outcomes with laser surgery for twin-twin transfusion syndrome. Twin Res Hum Genet 2006;9:438–43.Google Scholar
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;450e1–7.Google Scholar
Roberts, D, Neilson, JP, Kilby, M, et al. Interventions for the treatment of twin-twin transfusion syndrome. Cochrane Database Syst Rev 2008;(1):CD002073.Google Scholar
Rossi, AC, D’Addario, V. Laser therapy and serial amnioreduction as treatment for twin-twin transfusion syndrome: a metaanalysis and review of literature. Am J Obstet Gynecol 2008;198:147–52.Google Scholar
Salomon, LJ, Ortqvist, L, Aegerter, P, et al. Long-term developmental follow-up of infants who participated in a randomized clinical trial of amniocentesis versus laser photocoagulation for the treatment of twin-to-twin transfusion syndrome (TTTS). Am J Obstet Gynecol 2010;203;444e1–7.Google Scholar
Benirschke, K, Kim, CK. Multiple pregnancy. N Engl J Med 1973;288:1276–84.Google Scholar
De Vore, G, Dixon, J, Hobbins, JC. Fetoscope-directed Nd:YAG laser: a potential tool for fetal surgery. Am J Obstet Gynecol 1983;143:379–80.Google Scholar
De Lia, JE, Cruikshank, DP, Keye, WR. Fetoscopic neodymium:YAG laser occlusion of placental vessels in severe twin-twin transfusion syndrome. Obstet Gynecol 1990;75:1046–53.Google Scholar
Ville, Y, Hyett, JA, Vandenbussche, FP, Nicolaides, KH. Endoscopic laser coagulation of umbilical cord vessels in twin reversed arterial perfusion sequence. Ultrasound Obstet Gynecol 1994;4:396–8.Google Scholar
Ville, Y, Hyett, J, Hecher, K, Nicolaides, K. Preliminary experience with endoscopic laser surgery for severe twin-twin transfusion syndrome. N Engl J Med 1995;332:224–7.Google Scholar
Ville, Y, Hecher, K, Gagnon, A, et al. Endoscopic laser coagulation in the management of severe twin-to-twin transfusion syndrome. Br J Obstet Gynaecol 1998;105:446–53.Google Scholar
Klaritsch, P, Albert, K, Van Mieghem, T et al. Instrumental requirements for minimal invasive fetal surgery. Br J Obstet Gynaecol 2009;116:188–97.Google Scholar
Nizard, J, Barbet, JP, Ville, Y. Does the source of laser energy influence the coagulation of chorionic plate vessels? Comparison of Nd:YAG and Diode Laser on an ex-vivo placental model. Fetal Diagn Ther 2007;22:33–7.Google Scholar
Van Peborgh, P, Rambaud, C, Ville, Y. Effect of laser coagulation on placental vessels: histological aspects. Fetal Diagn Ther 1997;12:32–5.Google Scholar
Deprest, JA, Van Schoubroeck, D, Van Ballaer, PP, et al. Alternative technique for Nd: YAG laser coagulation in twin-to-twin transfusion syndrome with anterior placenta. Ultrasound Obstet Gynecol 1998;11:347–52.Google Scholar
Huber, A, Baschat, AA, Bregenzer, T, et al. Laser coagulation of placental anastomoses with a 30 degrees fetoscope in severe mid-trimester twin-twin transfusion syndrome with anterior placenta. Ultrasound Obstet Gynecol 2008;31:412–16.Google Scholar
Quintero, RA, Bornick, PW, Allen, MH, Johson, PK. Selective laser photocoagulation of communicating vessels in severe twin-twin transfusion syndrome in women with an anterior placenta. Obstet Gynecol 2001;97:477–81.Google Scholar
Middeldorp, JM, Lopriore, E, Sueters, M, et al. Laparoscopically guided uterine entry for fetoscopy in twin-to-twin transfusion syndrome with completely anterior placenta: a novel technique. Fetal Diagn Ther 2007;22:409–15.Google Scholar
De Lia, JE, Kuhlmann, RS, Harstad, TW, Cruikshank, DP. Fetoscopic laser ablation of placental vessels in severe previable twin-twin transfusion syndrome. Am J Obstet Gynecol 1995;172:1202–8.Google Scholar
Stirnemann, JJ, Nasr, B, Quarello, E, et al. A definition of selectivity in laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome and its relationship to perinatal outcome. Am J Obstet Gynecol 2008;198:62.e1–6.Google Scholar
Quintero, RA, Comas, C, Bornick, PW, et al. Selective versus non-selective laser photocoagulation of placental vessels in twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 2000;16:230–6.Google Scholar
Martinez, JM, Bermudez, C, Becerra, C, et al. The role of Doppler studies in predicting individual intrauterine fetal demise after laser therapy for twin–twin transfusion syndrome. Ultrasound Obstet Gynecol 2003;22:246–51.Google Scholar
Quintero, RA, Martinez, JM, Lopez, J, et al. Individual placental territories after selective laser photocoagulation of communicating vessels in twin-twin transfusion syndrome. Am J Obstet Gynecol 2005;192:1112–18.Google Scholar
Crisan, LS, Kontopoulos, EV, Quintero, RA. Appraisal of the selectivity index in a cohort of patients treated with laser surgery for twin-twin transfusion syndrome. Am J Obstet Gynecol 2010;202:157.e1–5.Google Scholar
Lopriore, E, Slaghekke, F, Middeldorp, JM, et al. Residual anastomoses in twin-to-twin transfusion syndrome treated with selective fetoscopic laser surgery: localization, size, and consequences. Am J Obstet Gynecol 2009;201:66e1–4.Google Scholar
Sago, H, Hayashi, S, Saito, M, et al. The outcome and prognostic factors of twin-twin transfusion syndrome following fetoscopic laser surgery. Prenat Diagn 2010;30:1185–91.Google Scholar
Salomon, LJ, Nasr, B, Nizard, J, et al. Emergency cerclage in cases of twin-to-twin transfusion syndrome with a short cervix at the time of surgery and relationship to perinatal outcome. Prenat Diagn 2008;28:1256–61.Google Scholar
Thilaganathan, B, Gloeb, DJ, Sairam, S, Tekay, A. Sono-endoscopic delineation of the placental vascular equator prior to selective fetoscopic laser ablation in twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 2000;16:226–9.Google Scholar
Ierullo, AM, Papageorghiou, AT, Bhide, A, et al. Severe twin-twin transfusion syndrome: outcome after fetoscopic laser ablation of the placental vascular equator. BJOG 2007;114:689–93.Google Scholar
Morris, RK, Selman, TJ, Harbidge, A, Martin, WL, Kilby, MD. Fetoscopic laser coagulation for severe twin-to-twin transfusion syndrome: factors influencing perinatal outcome, learning curve of the procedure and lessons for new centres. BJOG 2010;117;1350–7.Google Scholar
Sepulveda, W, Wong, AE, Dezerega, V, Devoto, JC, Alcalde, JL. Endoscopic laser surgery in severe second-trimester twin-twin transfusion syndrome: a three-year experience from a Latin American center. Prenat Diagn 2007;27:1033–8.Google Scholar
Yamamoto, M, Barki, G, Ville, Y. Direct visual control on cord coagulation using a fetoscopy-guided bipolar forceps. Description of a new technique. Prenat Diagn 2010;30:156–8.Google Scholar
Robyr, R, Lewi, L, Yamamoto, M, Deprest, J, Ville, Y. Permanent feto-fetal transfusion from the recipient to the donor twin: a complication of laser surgery in twin-to-twin transfusion syndrome. Am J Obstet Gynecol 2004;191:42.Google Scholar
Ville, Y, Hecher, K, Gagnon, A, et al. Endoscopic laser coagulation in the management of severe twin-to-twin transfusion syndrome. Br J Obstet Gynecol 1998;105:446–53.Google Scholar
Yamamoto, M, El Murr, L, Robyr, R, et al. Incidence and impact of perioperative complications in 175 fetoscopy-guided laser coagulation of chorionic plate anastomoses in fetofetal transfusion syndrome before 26 weeks of gestation. Am J Obstet Gynecol 2005;193:1110–16.Google Scholar
Merz, W, Tchatcheva, K, Gembruch, U, Kohl, T. Maternal complications of fetoscopic laser photocoagulation (FLP) for treatment of twin-twin transfusion syndrome (TTTS). J Perinat Med 2010;38:439–43.Google Scholar
Habli, M, Bombrys, A, Lewis, D, et al. Incidence of complications in twin-twin transfusion syndrome after selective fetoscopic laser photocoagulation: a single-center experience. Am J Obstet Gynecol 2009;201:417.e1–7.Google Scholar
Grannum, PA, Copel, JA. Invasive fetal procedures. Radiol Clin North Am 1990;28:217–26.Google Scholar
Deprest, JA, Van Ballaer, PP, Evrard, VA, et al. Experience with fetoscopic cord ligation. Eur J Obstet Gynecol Reprod Biol 1998;81:157–64.Google Scholar
Quintero, RA. Treatment of previable premature ruptured membranes. Clin Perinatol 2003;30:573–89.Google Scholar
Harrison, MR, Mychaliska, GB, Albanese, CT, et al. Correction of congenital diaphragmatic hernia in utero IX: fetuses with poor prognosis (liver herniation and low lung-to-head ratio) can be saved by fetoscopic temporary tracheal occlusion. J Pediatr Surg 1998;33:1017–22.Google Scholar
Liekens, D, Lewi, L, Jani, J, et al. Enrichment of collagen plugs with platelets and amniotic fluid cells increases cell proliferation in sealed iatrogenic membrane defects in the foetal rabbit model. Prenat Diagn 2008;28(6):503–7.Google Scholar
Devlieger, R, Millar, LK, Bryant-Greenwood, G et al. Fetal membrane healing after spontaneous and iatrogenic membrane rupture: a review of current evidence. Am J Obstet Gynecol 2006;195;1512–20.Google Scholar
Lopriore, E, Lewi, L, Oepkes, D, et al. In utero acquired limb ischemia in monochorionic twins with and without twin-to-twin transfusion syndrome. Prenat Diagn 2008;28:800–4.Google Scholar
Lopriore, E, Middeldorp, JM, Oepkes, D, et al. Residual anastomoses after fetoscopic laser surgery in twin-to-twin transfusion syndrome: frequency, associated risks and outcome. Placenta 2007;28:204–8.Google Scholar
Gembruch, U, Viski, S, Bagamery, K, Berg, C, Germer, U. Twin reversed arterial perfusion sequence in twin-to-twin transfusion syndrome after the death of the donor co-twin in the second trimester. Ultrasound Obstet Gynecol 2001;17:153–6.Google Scholar
Quarello, E, Stirnemann, J, Nassar, M, et al. Outcome of anaemic monochorionic single survivors following early intrauterine rescue transfusion in cases of feto-fetal transfusion syndrome. BJOG 2008;115;595–601.Google Scholar
Maschke, C, Diemert, A, Hecher, K, Bartmann, P. Long-term outcome after intra-uterine laser treatment for twin-twin transfusion syndrome. Prenat Diagn 2011;31:647–53.Google Scholar
Quintero, RA, Morales, WJ, Allen, M, et al. Treatment of iatrogenic previable premature rupture of membranes with intra-amniotic injection of platelets and cryoprecipitate (amniopatch): preliminary experience. Am J Obstet Gynecol 1999;181:744–9.Google Scholar
Young, BK, Roman, AS, MacKenzie, AP, et al. The closure of iatrogenic membrane defects after amniocentesis and endoscopic intrauterine procedures. Fetal Diagn Ther 2004;19:296–300.Google Scholar
Quintero, RA, Morales, WJ, Bornick, PW, Allen, M, Garabelis, N. Surgical treatment of spontaneous rupture of membranes: the amniograft – first experience. Am J Obstet Gynecol 2002;186:155–7.Google Scholar
Baumgarten, K, Moser, S. The technique of fibrin adhesion for premature rupture of the membranes during pregnancy. J Perinat Med 1986;14:43–9.Google Scholar
Sciscione, AC, Manley, JS, Pollock, M, et al. Intracervical fibrin sealants: a potential treatment for early preterm premature rupture of the membranes. Am J Obstet Gynecol 2001;184:368–73.Google Scholar
O’Brien, JM, Milligan, DA, Barton, JR. Gelatin sponge embolization. A method for the management of iatrogenic preterm premature rupture of the membranes. Fetal Diagn Ther 2002;17:8–10.Google Scholar
O’Brien, JM, Barton, JR, Milligan, DA. An aggressive interventional protocol for early midtrimester premature rupture of the membranes using gelatin sponge for cervical plugging. Am J Obstet Gynecol 2002;187:1143–6.Google Scholar
Chang, J, Tracy, TF Jr, Carr, SR, et al. Port insertion and removal techniques to minimize premature rupture of the membranes in endoscopic fetal surgery. J Pediatr Surg 2006;41:905–9.Google Scholar
Mallik, AS, Fichter, MA, Rieder, S, et al. Fetoscopic closure of punctured fetal membranes with acellular human amnion plugs in a rabbit model. Obstet Gynecol 2007;110:1121–9.Google Scholar
Papadopoulos, NA, Kyriakidis, DI, Schillinger, U, et al. Successful anatomic repair of fetoscopic access sites in the mid-gestational rabbit model using amnion cell engineering. In Vivo 2010;24:745–50.Google Scholar
Papanna, R, Molina, S, Moise, KY, Moise, KJ, Johnson, A. Chorioamnion pluging and the risk of preterm premature rupture of membranes after laser surgery in twin-twin transfusion syndrome. Ultrasound Obstet Gynecol 2010;35:337–43.Google Scholar
Taylor, MJ, Govender, L, Jolly, M, et al. Validations of the Quintero staging system for twin–twin transfusion syndrome. Obstet Gynecol 2002;100:1257–65.Google Scholar
Dickinson, JE, Evans, S. The progression of disease stage in twin–twin transfusion syndrome. J Matern Fetal Neonatal Med 2004;16:95–101.Google Scholar
Stirnemann, JJ, Nasr, B, Proulx, F, Essaoui, M, Ville, Y. Evaluation of the CHOP cardiovascular score as a prognostic predictor of outcome in twin–twin transfusion syndrome after laser coagulation of placental vessels in a prospective cohort. Ultrasound Obstet Gynecol 2010;36:52–7.Google Scholar
Stamilio, DM, Fraser, WD, Moore, TR. Twin-twin transfusion syndrome: an ethics-based and evidence-based argument for clinical research. Am J Obstet Gynecol 2010;203:3–16.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×