Post on 26-Aug-2018
Twin-twin transfusion syndrome
Michael Honigberg, HMS III
Gillian Lieberman, MD
March 2012
Michael Honigberg, HMS3
Gillian Lieberman, MD
Michael Honigberg, HMS3
Gillian Lieberman, MD
2
Understand the cause and consequences of twin-twin transfusion syndrome
Recognize the key diagnostic findings of twin-twin transfusion syndrome on ultrasound
Learn about management options for twin-twin transfusion syndrome
Objectives
Michael Honigberg, HMS3
Gillian Lieberman, MD
3
Early embryology: cell division in the Fallopian tube
http://www.patana.ac.th/secondary/science/IBtopics/IB%20Human(05)/pages/5.7.htm
Michael Honigberg, HMS3
Gillian Lieberman, MD
4
Early embryology: cell division in the Fallopian tube
http://www.patana.ac.th/secondary/science/IBtopics/IB%20Human(05)/pages/5.7.htm
Fimbriae
Infundibulum
Ampulla
Isthmus Interstitium
Michael Honigberg, HMS3
Gillian Lieberman, MD
5
Embryology of monozygotic twinning
Days 1-3 (morula)
Dichorionic diamniotic
~30% of monozygotic twin pregnancies
Days 4-8 (blastocyst)
Monochorionic diamniotic
~65% of monozygotic twin pregnancies
Days 8-12 (implanted blastocyst)
Monochorionic monoamniotic
~5% of monozygotic twin pregnancies
Days 13+ (formed embryonic disc)
Conjoined twins Rare
Images from http://en.wikipedia.org/wiki/File:Placentation.svg
Michael Honigberg, HMS3
Gillian Lieberman, MD
6
Complications of multiple gestation
General – Preterm delivery – Placental abruption – Growth abnormalities (e.g., IUGR, SGA) – 2-3x increased risk of preeclampsia, gestational
diabetes
Monochorionic diamniotic – Twin-twin transfusion syndrome – Twin reversed arterial perfusion – Twin anemia-polycythemia sequence
Monochorinoic monoamniotic – Cord entanglement
Michael Honigberg, HMS3
Gillian Lieberman, MD
7
Our patient
37-year-old G2P1001 with twin gestation at 17w 2d, here for second opinion about “low amniotic fluid”
Reports active fetal movement, no loss of fluid or vaginal bleeding
Prenatal course previously uncomplicated
How should we image her twins?
Michael Honigberg, HMS3
Gillian Lieberman, MD
Menu of tests for fetal imaging
Ultrasound
MRI
– Indications: Assessment of fetal CNS, fetal anomalies, placental anomalies (e.g., accreta)
– Safety studies have been performed at 1.5T
– Gadolinium not recommended (crosses placenta and remains in amniotic fluid)
8
Michael Honigberg, HMS3
Gillian Lieberman, MD
9
Our patient’s ultrasound: Twins A and B in sagittal view
PACS, BIDMC
Continue to view labeled images
Michael Honigberg, HMS3
Gillian Lieberman, MD
10
Our patient’s ultrasound: Labeled images
Uterus
Maxilla
Mandible
Anterior abdominal wall
Spine Umbilical cord
Uterus
PACS, BIDMC
Michael Honigberg, HMS3
Gillian Lieberman, MD
11
Our patient’s ultrasound: Discrepant amniotic fluid volumes
Anechoic amniotic fluid
PACS, BIDMC
Michael Honigberg, HMS3
Gillian Lieberman, MD
12
Concordant growth, but…
“The considerable discrepancy in amniotic fluid volumes suggests early appearance of twin-to-twin transfusion syndrome.”
Summary of ultrasound findings
Michael Honigberg, HMS3
Gillian Lieberman, MD
13
Twin-twin transfusion syndrome (TTTS)
Unbalanced blood flow through placental anastamoses from “donor” to “recipient,” possibly leading to hydrops, fetal death
Up to 20% of mono/di pregnancies (i.e., up to 4% of all twin pregnancies)
Responsible for 15-20% of total perinatal mortality in twins
Most commonly develops at 20-21 weeks – Can develop in 1st and 3rd trimesters
Acute onset in most cases
Cincotta and Fisk; Callen
Michael Honigberg, HMS3
Gillian Lieberman, MD
14
Pathophysiology of TTTS
Monochorionic placentas normally have multiple vascular connections
AA and VV are bidirectional while AV are unidirectional
“Classic” TTTS placenta: Single unidirectional AV anastamosis without compensatory AA/VV connections
Normal
TTTS
Modified from Cincotta and Fisk, Clin Obstet and Gynecol. 1997
Michael Honigberg, HMS3
Gillian Lieberman, MD
15
http://www.texaschildrens.org/carecenters/fetalsurgery/twin_twin_transfusion_syndrome.aspx
Placental anastamoses
AA/VV anastamoses are superficial
AV are deep
Courtesy Janneth Romero, MD
Anastamosis
Michael Honigberg, HMS3
Gillian Lieberman, MD
16
Pathophysiology of TTTS, continued
Increased blood flow to the recipient increased renal perfusion and increased ANP polyuria
Hypovolemia in the donor decreased renal perfusion increased ADH oliguria
Why doesn’t increased systemic pressure in the recipient halt shunting?
– Donor placental vascular vasoconstriction helps maintain pressure gradient
– Global fetoplacental vascular derangement
Galea, Jain, and Fisk
Michael Honigberg, HMS3
Gillian Lieberman, MD
17
Companion patient #1: TTTS on ultrasound
http://www.bwhct.nhs.uk/fetalmedicine-home/fmc-procedures/fmc-tts.htm
Michael Honigberg, HMS3
Gillian Lieberman, MD
18
Companion patient #1: TTTS on ultrasound, labeled
http://www.bwhct.nhs.uk/fetalmedicine-home/fmc-procedures/fmc-tts.htm
Amniotic membrane
Oligohydramnios Polyhydramnios
Fetal hand
Fetal arm
Michael Honigberg, HMS3
Gillian Lieberman, MD
19
Diagnosis of TTTS
Demonstration of polyhydramnios/oligohydramnios sequence
– Polyhydramnios: Maximum vertical fluid pocket > 8 cm before 20 weeks, > 10 cm after 20 weeks
– Oligohydramnios: Maximum vertical fluid pocket < 2 cm
Monochorionic placentation
Fetuses of the same sex
(Usually fetal size discordance > 20%)
Michael Honigberg, HMS3
Gillian Lieberman, MD
20
Differential diagnosis of TTTS
Genitourinary tract abnormality in oligohydramniotic twin
Isolated IUGR of one fetus (if growth discrepancy < 15%)
Dichorionic twin pregnancy with fused placentas and growth restriction of one fetus
Michael Honigberg, HMS3
Gillian Lieberman, MD
21
TTTS staging: Quintero scale
I: Poly/oligohydramnios
II: “Absent bladder” in donor
III: Abnormal Doppler
IV: Hydrops
V: Demise
– Thought to reflect typical disease progression
– Appears to correlate with prognosis in patients undergoing treatment
Quintero et al., J. Peritnatol 1999
Survival in patients treated with laser photocoagulation of the communicating vessels
Michael Honigberg, HMS3
Gillian Lieberman, MD
Let’s view several ultrasounds, applying the Quintero stages.
Michael Honigberg, HMS3
Gillian Lieberman, MD
Companion patient #2: Evaluation of the fetal bladder (Stage II)
23
http://www.fetalultrasound.com/online/text/9-092.htm
Umbilical arteries
Bladder (normal)
“Absent” bladder
Michael Honigberg, HMS3
Gillian Lieberman, MD
24
Fetal circulation
Image from Up-to-Date
Michael Honigberg, HMS3
Gillian Lieberman, MD
25
Normal fetal Doppler evaluation Umbilical artery waveform
should always be antegrade
Ductus venosus has the highest-velocity flow in the fetal venous system and should also be antegrade throughout the cycle – Absent/reversed waveform in
DV always abnormal
– Flow reversal in atrial systole normal in IVC/SVC
Umbilical vein flow should be non-pulsatile
Images from Up-to-Date
Peak systolic flow
End-diastolic
flow
Systolic peak
Diastolic peak
Atrial systole
Michael Honigberg, HMS3
Gillian Lieberman, MD
26
Doppler evaluation of TTTS: Findings in Stage III
Normal TTTS
Umbilical artery
Ductus venosus
Umbilical vein
Donor UA shows absent end-
diastolic flow1
Recipient DV shows flow
reversal in atrial systole2
Pulsatile recipient UV3
1Kim et al.; 2Wee and Fisk; 3http://www.centrus.com.br/DiplomaFMF/SeriesFMF/doppler/capitulos-html/chapter_11.htm
Michael Honigberg, HMS3
Gillian Lieberman, MD
27
Companion patient #3: “Stuck twin” on MRI and Doppler US
Courtesy Deborah Levine, MD
Michael Honigberg, HMS3
Gillian Lieberman, MD
28
Companion patient #3: “Stuck twin” on MRI and Doppler US, labeled
Courtesy Deborah Levine, MD
Absent end-diastolic flow in the umbilical
artery
T2 MRI
Coronal view of “stuck twin”
(donor)
Enlarged ventricles
Sagittal view of recipient
Lateral ventricle
Arm
Michael Honigberg, HMS3
Gillian Lieberman, MD
Companion patient #4: Fetal hydrops (Stage IV) on US
29
Femur
Courtesy Carolynn DeBenedectis, MD
Massive skin and
soft tissue edema
Ascites
Pleural and pericardial effusions
Polyhydramnios
Skin edema (late finding)
Michael Honigberg, HMS3
Gillian Lieberman, MD
30
Companion patient #5: Progression of TTTS on US, recipient fetus, sagittal view
20w 0d 21w 3d 24w 3d
Courtesy Janneth Romero, MD
Michael Honigberg, HMS3
Gillian Lieberman, MD
31
Companion patient #5: Polyhydramnios in TTTS on 20w US, sagittal view, labeled
20w 0d 21w 3d 24w 3d
Courtesy Janneth Romero, MD
Leg Abdomen Head
Michael Honigberg, HMS3
Gillian Lieberman, MD
32
Companion patient #5: Progressive hydrops with fetal ascites at 24w3d on US, recipient fetus on sagittal view
20w 0d 21w 3d 24w 3d
Courtesy Janneth Romero, MD
Ascites Worsening
ascites
Hepatomegaly
Michael Honigberg, HMS3
Gillian Lieberman, MD
33
Complications of TTTS
Polyhydramnios uterine distention respiratory/abdominal discomfort, (PP)ROM, preterm labor, abruption
Fetal cardiac complications, especially the recipient: – Heart failure leading to hydrops – Cardiomyopathy – Mitral and/or tricuspid regurgitation – Right ventricular outflow tract obstruction (8%)1
Pulmonary hypoplasia (donor) Anemia of donor, polycythemia of recipient
1Callen
Michael Honigberg, HMS3
Gillian Lieberman, MD
34
Complications of TTTS, continued
Demise of one or both twins – Exsanguination of surviving twin via AA/VV
anastamoses if present – Disseminated intravascular coagulation following
co-twin demise – Twin embolization syndrome
Neurologic and renal disease also common in survivors
Michael Honigberg, HMS3
Gillian Lieberman, MD
35
Options for managing TTTS
Laser photocoagulation of the placental vessels*
Amnioreduction – Reduces uterine distention and improves
placental perfusion – Often performed serially because underlying
abnormality persists – Complications: PPROM, chorio, abruption
Septostomy – Introduce connection in inter-twin membrane to
equalize volumes of amniotic fluid – Creation of monoamniotic sac risk of cord
entanglement
Michael Honigberg, HMS3
Gillian Lieberman, MD
36
Options for managing TTTS, continued
Expectant management – Stage I: 10-50% worsen – Stage II+: 70% perinatal mortality1
Selective termination – If one fetus abnormal or other measures fail – Laser coagulation – Bipolar forceps coagulation – Radiofrequency ablation
Delivery if past age of viability
1Berghella and Kaufmann
Michael Honigberg, HMS3
Gillian Lieberman, MD
37
Laser coagulation of placental vessels
Significantly better outcomes than other methods – Considered first-line but only
performed at specialized centers – 65-85% survival of at least one
twin, 35-50% of both1
Fetoscope introduced under U/S, placental equatorial plate visualized
Vessels mapped and selectively coagulated
Complications: – PPROM (17%) – Bleeding – Chorioamnionitis – Abruption
Images from Up-to-Date
Donor artery
Recipient vein
Laser
Post-ablation
1Chalouhi et al.
Michael Honigberg, HMS3
Gillian Lieberman, MD
Let’s take a brief look at another related condition.
Michael Honigberg, HMS3
Gillian Lieberman, MD
39
Twin reversed arterial perfusion (TRAP)
Acardiac twin perfused by viable pump twin via AA anastamoses – 70% of acardiac masses have two-vessel cord,
suggesting underlying genetic abnormality
Diagnosis: Reversed umbilical artery flow in acardiac twin on Doppler – Lower half of acardiac twin develops because it
is perfused via the iliac arteries
Pump twin is at risk for heart failure and preterm birth
Michael Honigberg, HMS3
Gillian Lieberman, MD
40
Companion patient #6: TRAP, Twin A, axial view of the chest on US
Courtesy Carolynn DeBenedectis, MD
Michael Honigberg, HMS3
Gillian Lieberman, MD
41
Companion patient #6: TRAP, Twin A, axial view of the chest on US, labeled
Courtesy Carolynn DeBenedectis, MD
LA
RA
RV
LV Polyhydramnios
Michael Honigberg, HMS3
Gillian Lieberman, MD
42
Companion patient #6: TRAP, Twin B, axial view of the chest on US, labeled
Courtesy Carolynn DeBenedectis, MD
Involuted cardiac mass
Michael Honigberg, HMS3
Gillian Lieberman, MD
43
Companion patient #6: TRAP, Twin B, axial view of the chest with Doppler
Courtesy Carolynn DeBenedectis, MD
Reversal of flow in the umbilical artery
Michael Honigberg, HMS3
Gillian Lieberman, MD
44
Options for managing TRAP
Coagulation of acardiac twin cord and/or AA anastamosis – Laser coagulation – Bipolar forceps coagulation – Radiofrequency ablation
? Higher success and reduced complications with RFA
Expectant management – High risk of heart failure in pump twin (55%
perinatal mortality)
Delivery if past age of viability
Michael Honigberg, HMS3
Gillian Lieberman, MD
Let’s return to our patient.
Michael Honigberg, HMS3
Gillian Lieberman, MD
46
Our patient: Clinical course continued
Declined fetal surgery, opted for reassessment in one week
One week later, reported increased abdominal pressure
In-office ultrasound showed Twin A with multiple amniotic fluid pockets >10 cm, Twin B with almost no amniotic fluid
Patient opted to wait one more week before deciding on treatment
One week later, returned for ultrasound
Michael Honigberg, HMS3
Gillian Lieberman, MD
47
Our patient: Repeat US at 19w 2d (Twin A, recipient)
PACS, BIDMC
Michael Honigberg, HMS3
Gillian Lieberman, MD
48
Our patient: Repeat US at 19w 2d (Twin A, recipient), labeled
Arm
Edematous skin consistent with
hydrops
Lack of Doppler activity within
the chest
PACS, BIDMC
Arm
Chest Pelvis
Michael Honigberg, HMS3
Gillian Lieberman, MD
49
Our patient: Repeat US at 19w 2d (Twin B, donor)
PACS, BIDMC
Michael Honigberg, HMS3
Gillian Lieberman, MD
50
Our patient: Repeat US at 19w 2d (Twin B, donor), labeled
Lack of Doppler activity within
the chest
M-mode: No heart beat
Diagnosis: Demise of both twins
PACS, BIDMC
Michael Honigberg, HMS3
Gillian Lieberman, MD
51
Summary
TTTS is a serious complication of monochorionic diamniotic pregnancy with high morbidity/mortality
Key diagnostic features are polyhydramnios/ oligohydramnios, absent donor fetal bladder, Doppler abnormalities, and hydrops
Management options include laser photocoagulation, amnioreduction, septostomy, selective termination, expectant, and delivery
Michael Honigberg, HMS3
Gillian Lieberman, MD
52
Acknowledgements
Carolynn DeBenedectis, MD
Deborah Levine, MD
Janneth Romero, MD
Joe Reardon, Grant Smith, Christian Strong
Claire Odom
Gillian Lieberman, MD
Michael Honigberg, HMS3
Gillian Lieberman, MD
53
References
Baschat AA. Venous Doppler for fetal assessment. Up-to-Date.
Berghella V, Kaufmann M. Natural history of twin-twin transfusion syndrome. J Reprod Med. 2001;46(5):480.
Callen PW. Ultrasonography in Obstetrics and Gynecology. 5th edition. Saunders: Philadelphia, 2007.
Cincotta RB, Fisk NM. Current thoughts on twin-twin transfusion syndrome. Clin Obstet and Gynecol. 1997;40(2):290.
Galea R, Jain V, Fisk NM. Insights into the pathophysiology of twin-twin transfusion syndrome. Prenat Diagn 2005;25:777.
Holland MG, Mastrobattista JM, Lucas MJ. Diagnosis and management of twin reversed arterial perfusion (TRAP) sequence. Up-to-Date.
Kim JA, Cho JY, Lee YH, et al. Complications arising in twin pregnancy: Findings of prenatal ultrasonography. Korean J Radiol. 2003;4(1):54.
Moise KJ, Johnson A. Pathogenesis and diagnosis of twin-twin transfusion syndrome. Up-to-Date.
Moise KJ, Johnson A. Management of twin-twin transfusion syndrome. Up-to-Date.
Quintero RA, Morales WJ, Allen MH, et al. Staging of twin-twin transfusion syndrome. J Perinatol 1999;19(8):550.
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 Gyncol 2000;16:230.
Russell Z, Quintero RA, Kontopoulos EV. What is the definition of pulsatile umbilical venous flow in twin-twin transfusion syndrome? Am J Obstet Gynecol 2008;199:634.
Wee LY, Fisk NM. The twin-twin transfusion syndrome. Semin Neonataol 2002;7:187.