Twin-Twin Transfusion Syndrome: APSA Prenatal Counseling Series

Guideline · Dec 2019 · 11 min read

In brief

Educational resource from APSA's Fetal Diagnosis and Treatment Committee providing prenatal counseling guidance for twin-twin transfusion syndrome. Designed to support clinicians in discussing diagnosis, treatment options, and outcomes with expectant families facing this high-risk monochorionic twin complication.

TTTS affects 10-15% of monochorionic twins; untreated mortality reaches 90%, requiring close q2-week ultrasound surveillance starting at 16 weeks
Diagnosis relies on polyhydramnios in recipient twin, oligohydramnios in donor twin, and Quintero staging (I-V) based on Doppler findings and hydrops
Donor twin develops hypovolemia with absent bladder and IUGR; recipient twin develops hypervolemia with large bladder and high-output heart failure
Worse prognosis when TTTS presents before 20 weeks, at higher Quintero stages, or with fetal growth discordance >30%
Echocardiography is essential for assessing AV valve regurgitation, ventricular hypertrophy, and myocardial performance index in staging disease severity

Written by the GCMD Library team from the guideline.

Definition and Etiology

Twin-twin transfusion syndrome (TTTS) occurs in 10-15% of monochorionic diamniotic twin pregnancies when unbalanced blood flow through shared placental vascular anastomoses causes hypervolemia in the recipient twin and hypovolemia in the donor twin. The donor twin develops oligohydramnios and absent bladder while the recipient develops polyhydramnios and cardiac complications. Untreated TTTS carries 90% mortality risk for one or both twins.

Prenatal Monitoring and Diagnosis

Monochorionic twins require first trimester chorionicity assessment followed by biweekly ultrasound surveillance starting at 16 weeks to evaluate amniotic fluid volumes and middle cerebral artery Doppler. Diagnosis is based on ultrasound findings of polyhydramnios in recipient and oligohydramnios in donor, with severity classified by Quintero staging (Stage 1-5) or supplemented by cardiovascular scoring systems including the Cincinnati modification and CHOP cardiovascular score. Echocardiography is recommended when TTTS is diagnosed to assess for cardiac complications.

Quintero Staging System

The Quintero staging system classifies TTTS severity from Stage 1 (fluid discordance with visible donor bladder) through Stage 5 (fetal demise). Stage 2 involves absent donor bladder, Stage 3 includes critically abnormal Doppler studies, and Stage 4 demonstrates hydrops in one or both twins. More severe presentation before 20 weeks and higher Quintero stages correlate with worse prognosis.

Cardiovascular Assessment Scores

Multiple cardiovascular scoring systems assess recipient twin cardiomyopathy severity including the Cincinnati cardiomyopathy staging (3a-3c based on AV regurgitation, ventricular thickness, and myocardial performance index), CHOP cardiovascular score (evaluating ventricular characteristics, valve function, venous Doppler, great vessels, and arterial Doppler), and Fetal Cardiovascular Profile Score (assessing hydrops, cardiomegaly, and cardiac function). These scores help prognosticate outcomes and guide treatment decisions.

Amnioreduction

Amnioreduction involves serial removal of excess amniotic fluid from the recipient twin to relieve polyhydramnios symptoms and potentially reverse early-stage TTTS. While frequently used for non-complicated cases or twins beyond 26 weeks gestation, it is not curative and carries risks including worsening TTTS, premature rupture of membranes, septostomy, and fetal loss. It may be therapeutic in early Quintero stages but has higher recurrence rates than laser therapy.

Fetoscopic Laser Ablation

Fetoscopic laser coagulation of placental vascular anastomoses is considered standard of care for advanced TTTS, typically performed between 16-26 weeks gestation. Techniques include non-selective ablation of all vessels crossing the intertwin membrane, selective ablation of specific connections, sequential ablation in a defined order, or the Solomon technique which ablates along the entire vascular equator to reduce recurrence. Laser therapy improves survival and reduces neurologic morbidity compared to amnioreduction but carries risks of PPROM, premature delivery, and treatment failure.

Alternative Treatment Options

Septostomy involves deliberate puncture of the intertwin membrane to equilibrate amniotic fluid volumes but risks cord entanglement and fetal loss. Selective fetal reduction via radiofrequency ablation of the diseased co-twin's umbilical cord may improve survival of the healthier twin in cases with significant anomalies, though it carries risk of neurologic injury to the surviving twin and PPROM.

Postnatal Outcomes and Complications

Average gestational age at delivery is 31-32 weeks with weekly ultrasound surveillance recommended after laser therapy to monitor for recurrent TTTS and twin anemia polycythemia sequence (TAPS). Complications include co-twin demise in 12-25% (higher in donor twins), neurodevelopmental impairment including cerebral palsy and developmental delay in both twins, cardiac complications from volume overload (ventricular hypertrophy, dysfunction, valvular defects), prematurity-related complications, and renal failure. Higher Quintero stage, advanced gestational age at laser therapy, and low birth weight increase risk of adverse neurodevelopmental outcomes.

Statements in this guideline

TTTS occurs in 10-15% of monochorionic twins.
EstablishedEtiology and Background
If untreated, TTTS can result in 90% mortality of one or both twins.
EstablishedEtiology and Background
Monochorionic diamniotic twin monitoring should include first trimester ultrasound assessment of chorionicity and nuchal translucency.
RecommendationPrenatal Consideration
Starting at 16 weeks, surveillance ultrasound should be performed every 2 weeks with amniotic fluid evaluation and middle cerebral artery peak systolic velocity.
RecommendationPrenatal Consideration
If a patient is diagnosed with TTTS, echocardiogram is recommended.
RecommendationPrenatal Consideration
Monthly fetal growth evaluations are recommended in monochorionic diamniotic twin pregnancies.
RecommendationPrenatal Consideration
Quintero Stage 1 is defined by polyhydramnios, oligohydramnios, and visible bladder of the donor twin.
EstablishedDiagnosis
Quintero Stage 2 is defined by non-critically abnormal Dopplers and non-visualized bladder in the donor twin.
EstablishedDiagnosis
Quintero Stage 3 is defined by abnormal Doppler studies in donor or recipient twin, including absent or reversed umbilical artery end diastolic flow, reversed ductus venosus a-wave, or pulsatile umbilical vein flow.
EstablishedDiagnosis
Quintero Stage 4 is defined by hydrops of one or both twins.
EstablishedDiagnosis
Quintero Stage 5 is defined by death of one or both twins.
EstablishedDiagnosis
Amnioreduction is frequently used if twins are greater than 26 weeks gestation.
RecommendationTreatment
Amnioreduction is often indicated for non-complicated TTTS and may potentially reverse TTTS in early Quintero stages.
RecommendationTreatment
Risks of amnioreduction include worsening of TTTS, bleeding, chorioamniotic membrane separation, premature rupture of membranes, fetal loss, neurologic impairment, septostomy, uterine bleeding, and chorioamnionitis.
EstablishedTreatment
Fetoscopic coagulation of vascular anastomoses (laser ablation) is considered standard of care for TTTS.
GuidelineTreatment
Laser ablation shows improved survival over amnioreduction.
ResearchTreatment
Laser ablation is indicated for advanced Quintero stages and is frequently performed during 16-26 weeks of gestation.
RecommendationTreatment
The Solomon method of laser ablation involves planned laser ablation between vascular connections along the vascular equator and decreases recurrence of TTTS and TAPS.
ResearchTreatment
Amnioreduction is frequently performed at the end of laser ablation procedures.
RecommendationTreatment
Laser ablation increases survival of both twins and decreases neurologic morbidities.
ResearchTreatment
Premature rupture of membranes is a contraindication to laser ablation.
RecommendationTreatment
Average gestational age at delivery after TTTS treatment is 31-32 weeks.
EstablishedPostnatal Considerations
After fetoscopic photocoagulation, weekly ultrasound surveillance and Doppler studies are recommended, particularly for recurrent TTTS and TAPS.
RecommendationPostnatal Considerations
The rate of co-twin demise after TTTS treatment is 12-25%.
ResearchPostnatal Considerations
There is a higher risk of death in the donor twin.
ResearchPostnatal Considerations
Neurologic injuries and neurodevelopmental impairment including cerebral palsy, quadriplegia, diplegia, hemiplegia, developmental delay, blindness, and hearing impairment can occur after TTTS.
EstablishedPostnatal Considerations
Higher risk of neurodevelopmental impairment is associated with advanced gestational age at time of laser therapy, high Quintero stage, low gestational age at birth, and low birth weight in both donor and recipient twins.
ResearchPostnatal Considerations
Worse prognosis occurs with more severe presentation when TTTS manifests before 20 weeks.
EstablishedEtiology and Background
Worse prognosis occurs with higher Quintero stage.
EstablishedEtiology and Background
Worse prognosis occurs with fetal growth discordance greater than 30% or intrauterine growth restriction in one or both fetuses.
EstablishedEtiology and Background

Full text

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome TM from the Fetal Diagnosis and Treatment Committee of the American Pediatric Surgical Association Editor-in-Chief: Ahmed I. Marwan, MD Special thanks to Niti Shahi, MD, Nicholas Behrendt, MD, and Jill Stein, MD ©2019, American Pediatric Surgical Association

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome 2 Twin-Twin Transfusion Syndrome Definition TTTS: shift of intravascular volume between twins with a shared placenta Etiology and Background • Mainly diagnosed in monochorionic (1 placenta), diamniotic (2 amniotic sacs) gestations who share a common placenta • The donor and recipient twins also share multiple vascular connections/anastomoses (1) o Vascular anastomoses include artery-to-artery connections (AA ), vein-to-vein connections (VV ), and veno-arterial connections (VA ) • Progression of disease: Unbalanced blood flow in vascular anastomoses in the shared placenta resulting in unequal volume balances between both fetuses➞ hypervolemia in recipient twin and hypovolemia in donor twin➞ increased mortality risk, organ failure, cardiac complications and neurodevelopmental impairment (1) • Incidence: 10-15% of monochorionic twins (2) o If untreated, TTTS can result in 90% mortality of one or both twins (2) • Donor versus recipient twin: Figure 1. Schematic of Twin-Twin Trasnfusion Syndrome. Courtesy of the Colorado Fetal Care Center. Donor Twin Recipient Twin Mechanism Volume shunted away from donor twin➞ persistent hypovolemia➞ oligohydramnios Volume shunted to recipient twin➞ persistent hypervolemia➞ polyhydramnios US findings Oligohydramnios, absent bladder, abnormal Doppler blood flow Polyhydramnios, large bladder Complications IUGR, hydrops, death (1) Increased mortality rate in donor twin (3) hydrops (pleural effusions, ascites, skin edema, & pericardial effusions), high output CHF , death

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome 3 Figure 2 Figure 3 Figure 2: Transverse grayscale ultrasound image of the fetal pelvis in a donor twin shows lack of fluid within the urinary bladder. Figure 3: Transverse color Doppler ultrasound image of the the fetal pelvis in the same donor twin shows lack of fluid within the urinary bladder with expected location between the umbilical arteries. Figure 4: Longitudinal ultrasound of a donor twin demonstrates lack of fluid within the urinary bladder. Courtesy of Jill Stein, MD – Colorado Fetal Care Center Figure 4 • Associated anomalies: o IUGR in 20% of cases (2) o Chromosomal abnormalities (4) o Congenital cardiac defects (5-10) o Cerebral lesions (5-10) • Worse prognosis with the following: o More severe presentation when it manifests <20 weeks (1, 11) o Higher Quintero stage o Fetal growth discordance >30% (3, 10), IUGR in one or both fetuses

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome 4 Figure 5. 3-Dimensional Anatomical model of Twin-twin Transfusion Syndrome. Courtesy of Christine Castillo, Nicholas Behrendt, MD and Rony Marwan, MD, Colorado Fetal Care Center Differential Diagnosis (2) 1) IUGR (selective intrauterine growth restriction) 2) TAPS (twin anemia polycythemia sequence) 3) Discordant twins secondary to anomaly 4) Subjective fluid discordance 5) Dichorionic twin gestation with fluid discordance 6) Discordant twins secondary to infection Prenatal Consideration • Monoamniotic Dichorionic twin monitoring: (2) o 1st trimester ultrasound assessment: chorionicity, nuchal translucency o Starting at 16 weeks, q2 week surveillance with ultrasound: amniotic fluid evaluation, middle cerebral artery (MCA) peak systolic velocity (increased frequency if abnormal) o If patient is diagnosed with TTTS, recommend echocardiogram o Monthly fetal growth evaluations

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome 5 Diagnosis • Based on current ultrasound surveillance and echocardiography • Current staging systems: (12) o Quintero staging for TTTS: (2, 4, 11) o Cincinnati modification of the Quintero staging: incorporates echo findings of A V valve function, ventricular hypertrophy and ventricular function (13) o CHOP cardiovascular score in TTTS (14-17) o Cardiovascular Profile Score (CVPS) for fetal hydrops (18) Quintero Staging for TTTS Stage 1 Polyhydramnios, oligohydramnios, bladder of donor visible Stage 2 Dopplers are not critically abnormal, bladder is not visualized in donor twin Stage 3 Abnormal Doppler studies in donor or recipient twin (i.e. absent or reversal umbilical artery end diastolic flow, reversal of ductus venosus a-wave, and/or pulsatile umbilical vein flow) Stage 4 Hydrops of one or both twins Stage 5 Death of one or both twins Figure 6. Normal umbilical arterial spectral Doppler waveform pattern in a donor twin with brisk systolic upstroke and positive diastolic flow. Courtesy of Jill Stein, MD – Colorado Fetal Care Center

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome 6 Figure 7 . Abnormal umbilical arterial spectral Doppler waveform pattern in a recipient twin with absent diastolic flow. Courtesy of Jill Stein, MD – Colorado Fetal Care Center Figure 8. Demonstration of polyhydramnios in Recipient twin on Ultrasound. Courtesy of Nicholas Behrendt, MD – Colorado Fetal Care Center

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome 7 Cardiomyopathy Variable Mild (Stage 3a) Moderate (Stage 3b) Severe (Stage 3c) A V regurgitation Mild Moderate Severe RV /L V thickness Mild Moderate Severe MPI (myocardial performance index) >2+ Z-score > +3 Z-score > +4 Z-score L V-MPI > 0.43 to 0.48 > +4 Z-score > 0.53 RV-MPI > 0.48 to 0.56 > 0.56 to 0.64 > 0.64 CHOP Cardiovascular Score- Recipient Twin Score 0 1 2 3 Ventricular characteristics Cardiac enlargement None Mild Moderate- Severe Ventricular hypertrophy None Mild Moderate- Severe Systolic dysfunction None Mild Moderate- Severe Valve function Tricuspid regurgitation None Mild Moderate- Severe Mitral regurgitation None Mild Moderate- Severe Venous Doppler Characteristics Tricuspid valve inflow 2 peaks 1 peak Mitral valve inflow 2 peaks 1 peak Ductus venosus Forward Decreased atrial contraction Reversal of flow Umbilical vein pulsation None + Great Vessel Analysis Outflow tracts PA>Aorta PA= aorta PA<Aorta RV outflow obstruction Pulmonary insufficiency None + Arterial Doppler Characteristics Normal Decreased diastolic flow No flow or reversal of diastolic flow

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome 8 Fetal Cardiovascular Profile Score 2 1 0 Hydrops None Ascites, pleural effusion or pericardial effusion Skin edema Cardiomegaly (cardiac area/thoracic area) >0.2 to 0.35 0.35 to 0.50 <0.2 OR >0.5 Cardiac function Normal, diastolic filling Holosystolic TR Holosystolic MR, monophasic diastolic filling Arterial umbilical Doppler Venous Doppler (umbilical vein and ductus venosus) Treatment 1) Amnioreduction a. Definition: removal of excess amniotic fluid from recipient twin, can be done serially b. Usually not a curative procedure, potential for persistence/recurrence (19-21) c. Frequently used if twins >26 weeks gestation (1) d. Indication: often for non-complicated TTTS, potentially reverses TTTS in early Quintero stages e. Advantages: decreases the side effects of polyhydramnios in recipient twin, may be therapeutic f. Risks: worsening of TTTS, risk of bleeding, chorioamniotic membrane separation, premature rupture of membranes (PROM)➞ prematurity, fetal loss, neurologic impairment, septostomy (rupture of amniotic membrane increased need for additional procedures), uterine bleeding, chorioamnionitis, etc. (1, 2) 2) Septostomy a. Definition: deliberate puncture into the intertwin membrane to allow for equilibration of amniotic fluid volumes (21, 22) b. Risks: cord entanglement, fetal loss

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome 9 3) Ultrasound or fetoscopic-guided radio frequency ablation (selective fetal reductions) a. Definition: selective radiofrequency ablation of the cord of the diseased co-twin or co-twin with significant anomaly in effort to improve the survival of the other twin b. Risks: neurologic injury of surviving twin, PPROM (21) 4) Fetoscopic coagulation of vascular anastomoses (laser ablation) a. Considered standard of care (3), improved survival over amnioreduction b. Indication: Advanced Quintero stages, frequently during 16-26 weeks of gestation c. Methods: (24-27) i. Non-selective: Coagulation of all placental vessels that cross the intertwin membrane/membranous equator, decreased donor survival ii. Selective: Coagulation of selective connections iii. Sequential: The order of ablation is as follows: donor artery-recipient vein anastomosis, recipient artery-donor vein anastomosis, V-A, and lastly A-A. iv. Solomon method: Planned laser ablation between vascular connections along the vascular equator; decreased recurrence of TTTS and TAPS (24) d. Amnioreduction frequently performed at the end of the procedure e. Advantages: increased survival of both twins, decreased neurologic morbidities (2) f. Risks: PROM, premature delivery, chorionic membrane septation, treatment failure (may miss vascular anastomoses), and fetal demise (2, 3) g. Contraindication: PPROM (1) Figure 9. Before and after Fetoscopic Coagulation of Vascular anastomose. Courtesy of Nicholas Behrendt, MD – Colorado Fetal Care Center

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome 10 Postnatal Considerations • Average gestational age at delivery 31-32 weeks (28) • After fetoscopic photo coagulation, recommend weekly ultrasound surveillance and Doppler studies, particularly for recurrent TTTS and TAPS (1) • Complications: (2) o Twin anemia polycythemia sequence (TAPS) o Selective fetal intrauterine growth restriction (sIUGR) o Recurrent TTTS o Fetal demise ■ Rate of co-twin demise 12-25% (14) ■ Higher risk of death in donor twin o Neurologic injuries and/or neurodevelopment impairment including cerebral palsy, quadriplegia/diplegia/hemiplegia, developmental delay, blindness and hearing impairment (5) ■ Higher risk of neurodevelopment impairment with advanced gestational age at time of laser therapy, high Quintero stage, low gestational age at birth and low birth weight (limitation: only teen mother population) in both donor and recipient twins (no difference between donor and recipients) (28) o Prematurity and associated complications o Cardiac complications from volume overload such as ventricular hypertrophy, ventricular dysfunction, valvular defects and heart failure (6, 17 , 29, 30) o Respiratory complications o Renal failure

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome 11 References 1. Mutatore CS, Feltis B. Twin-to-Twin Transfusion Syndrome In: NaT (Not a Surgical T extbook). © 2019 American Pediatric Surgical Association and Unbound Medicine, Inc; 2018. 2. Marwan R, Feltis B, Zaretsky M. MultipleGestation, Twin-TwinTransfusionSyndrome (TTTS) and Twin Reversed Arterial Perfusion (TRAP)Sequence. In: NaT (Not a T extbook). American Pediatric Surgical Association and Unbound Medicine, Inc. 3. Hoffman M, Habli M, Donepudi R, Boring N, Johnson A, Moise KJ, et al. Perinatal Outcomes of Single Fetal Survivor after Fetal Intervention for Complicated Monochorionic Twins. Prenat Diagn. 2018. 4. T ownsend R, Khalil A. Ultrasound screening for complications in twin pregnancy. Seminars in Fetal and Neonatal Medicine; Elsevier; 2018. 5. Sommer J, Nuyt A, Audibert F , Dorval V , Wavrant S, Altit G, et al. Outcomes of extremely premature infants with twin–twin transfusion syndrome treated by laser therapy. Journal of Perinatology. 2018;38(11):1548. 6. Van Mieghem T , Lewi L, Gucciardo L, Dekoninck P , Van Schoubroeck D, Devlieger R, et al. The Fetal Heart in Twin-to-Twin Transfusion Syndrome. Int J Pediatr. 2010;2010:10.1155/2010/379792. Epub 2010 Aug 8. 7 . Pruetz JD, Sklansky M, Detterich J, Korst LM, Llanes A, Chmait RH. Twin–twin transfusion syndrome treated with laser surgery: postnatal prevalence of congenital heart disease in surviving recipients and donors. Prenat Diagn. 2011;31(10):973-7 . 8. Wee L Y , Fisk NM. The twin-twin transfusion syndrome. Semin Neonatol. 2002 Jun;7(3):187- 202. 9. Quarello E, Molho M, Ville Y . Incidence, mechanisms, and patterns of fetal cerebral lesions in twin-to-twin transfusion syndrome. The Journal of Maternal-Fetal & Neonatal Medicine. 2007;20(8):589-97 . 10. Snowise S, Moise KJ, Johnson A, Bebbington MW , Papanna R. Donor Death After Selective Fetoscopic Laser Surgery for Twin–Twin Transfusion Syndrome. Obstetrics & Gynecology. 2015;126(1):74-80. 11. Quintero RA, Morales W J, Allen MH, Bornick PW , Johnson PK, Kruger M. Staging of twin- twin transfusion syndrome. Journal of Perinatology. 1999;19(8):550. 12. Villa C, Habli M, Votava‐Smith J, Cnota J, Lim F , Divanovic A, et al. Assessment of fetal cardiomyopathy in early-stage twin–twin transfusion syndrome: comparison between commonly reported cardiovascular assessment scores. Ultrasound in Obstetrics & Gynecology. 2014;43(6):646-51. 13. Harkness UF , Crombleholme TM. Twin–twin transfusion syndrome: where do we go from here? Seminars in perinatology; Elsevier; 2005. 14. Stirnemann J, 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 in Obstetrics & Gynecology. 2010;36(1):52-7 . 15. Rychik J, Tian Z, Bebbington M, Xu F , McCann M, Mann S, et al. The twin-twin transfusion syndrome: spectrum of cardiovascular abnormality and development of a cardiovascular score to assess severity of disease. Obstet Gynecol. 2007;197(4):392. e1,392. e8.

American Pediatric Surgical Association Prenatal Counseling Series Twin-Twin Transfusion Syndrome 12 16. Michelfelder E, Gottliebson W , Border W , Kinsel M, Polzin W , Livingston J, et al. Early manifestations and spectrum of recipient twin cardiomyopathy in twin–twin transfusion syndrome: relation to Quintero stage. Ultrasound in Obstetrics and Gynecology: The Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2007;30(7):965-71. 17 . Habli M, Michelfelder E, Cnota J, Wall D, Polzin W , Lewis D, et al. Prevalence and progression of recipient‐twin cardiomyopathy in early‐stage twin–twin transfusion syndrome. Ultrasound in obstetrics & gynecology. 2012;39(1):63-8. 18. Hofstaetter C, Hofstaetter C, Hansmann M, Eik-Nes SH, Huhta JC, Luther SL. A cardiovascular profile score in the surveillance of fetal hydrops. The Journal of Maternal- Fetal & Neonatal Medicine. 2006;19(7):407-13. 19. Senat M, Deprest J, Boulvain M, Paupe A, Winer N, Ville Y . Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome. N Engl J Med. 2004;351(2):136-44. 20. Mari G, Detti L, Oz U, Abuhamad AZ. Long-term outcome in twin-twin transfusion syndrome treated with serial aggressive amnioreduction. Obstet Gynecol. 2000;183(1):211-7 . 21. Roberts D, Neilson JP , Kilby MD, Gates S. Interventions for the treatment of twin‐twin transfusion syndrome. Cochrane Database of Systematic Reviews. 2014(1). 22. Moise Jr KJ, Dorman K, Lamvu G, Saade GR, Fisk NM, Dickinson JE, et al. A randomized trial of amnioreduction versus septostomy in the treatment of twin-twin transfusion syndrome. Obstet Gynecol. 2005;193(3):701-7 . 23. Roman A, Papanna R, Johnson A, Hassan S, Moldenhauer J, Molina S, et al. Selective reduction in complicated monochorionic pregnancies: radiofrequency ablation vs. bipolar cord coagulation. Ultrasound in Obstetrics & Gynecology. 2010;36(1):37-41. 24. Ruano R, Rodo C, Peiro J, Shamshirsaz A, Haeri S, Nomura M, et al. Fetoscopic laser ablation of placental anastomoses in twin–twin transfusion syndrome using ‘Solomon technique’. Ultrasound in Obstetrics & Gynecology. 2013;42(4):434-9. 25. Baschat AA, Barber J, Pedersen N, Turan OM, Harman CR. Outcome after fetoscopic selective laser ablation of placental anastomoses vs equatorial laser dichorionization for the treatment of twin-to-twin transfusion syndrome. Obstet Gynecol. 2013;209(3):234. e1,234. e8. 26. De Lia J, Kuhlmann R, Lopez K. Treating previable twin-twin transfusion syndrome with fetoscopic laser surgery: outcomes following the learning curve. J Perinat Med. 1999;27(1):61-7 . 27 . Chalouhi G, Essaoui M, Stirnemann J, Quibel T , Deloison B, Salomon L, et al. Laser therapy for twin‐to‐twin transfusion syndrome (TTTS). Prenat Diagn. 2011;31(7):637-46. 28. Lopriore E, Nagel HT , Vandenbussche FP , Walther F J. Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome. Obstet Gynecol. 2003;189(5):1314-9. 29. Delabaere A, Leduc F , Reboul Q, Fuchs F , Wavrant S, Dubé J, et al. Factors associated to early intrauterine fetal demise after laser for TTTS by pre-operative fetal heart and Doppler ultrasound. Prenat Diagn. 2018. 30. Fisk N, Duncombe G, Sullivan M. The basic and clinical science of twin–twin transfusion syndrome. Placenta. 2009;30(5):379-90.

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