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CLINICAL OBSTETRICS AND GYNECOLOGY

Volume 47, Number 1, 181202


2004, Lippincott Williams & Wilkins, Inc.

The TwinTwin
Transfusion Syndrome
VENU JAIN, MD, PhD and
NICHOLAS M. FISK, PhD, FRCOG
Center for Fetal Care, Queen Charlottes and Chelsea Hospital,
Institute of Reproductive and Developmental Biology, Imperial
College London, London, UK

Twintwin transfusion syndrome (TTTS) is


a complex cardiovascular disease affecting
monochorionic (MC) twin pregnancies. Although well characterized clinically, its etiopathogenesis remains poorly understood.
TTTS, which affects genetically-identical
structurally normal fetuses, primarily involves unbalanced transfusion of blood
from a net donor to a net recipient along one
or more placental arteriovenous anastomoses in absence of adequate compensatory
counter-transfusion along bi-directional superficial anastomoses. The resultant fetal
hemodynamic changes, and their associated
biochemical/humoral adaptations are responsible for the disparate phenotypic features found in the donor and recipient twins.
TTTS is arguably the oldest medical condition recorded. As described in the Bible
(Genesis 25:21-32), it appears that the twins
of Isaac and Rebekah who struggled together within her were afflicted with TTTS.
The first born, Esau, who came out red,

Correspondence: Dr. Venu Jain, Clinical Lecturer in Obstetrics and Gynaecology, Institute of Reproductive &
Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN,
United Kingdom. E-mail: venu.jain@imperial.ac.uk
CLINICAL OBSTETRICS AND GYNECOLOGY

was faint, and at the point to die, may


have been a recipient. Today, TTTS remains
one of the greatest challenges in modern fetal medicine for several reasons. Firstly, untreated, it is associated with extremely high
perinatal mortality ( 80%) and morbidity.
Secondly, not one but two babies are affected. Third, unlike many other fetal pathologies, these babies are entirely normal
structurally, thus with good potential for intact survival. Finally, the problem is an anatomic one in the placenta, which should, at
least theoretically, be amenable to surgical
cure. Because disease severity varies from
subclinical to life threatening, and because
of the multitude of treatment options available, clinical management of TTTS remains
challenging, despite considerable recent advances.

Clinical Features
TTTS occurs in approximately 15% of MC
diamniotic twins, affecting approximately 1
in 1600 pregnancies overall.1 It is not known
to occur in monoamniotic twins. TTTS can
also occur within MC twin pairs in triplet
and quadruplet pregnancies. TTTS is usually diagnosed on serial ultrasound indicated
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routinely in MC twins albeit may rarely present with polyhydramnios, preterm labor or
preterm premature rupture of membranes
(PPROM). Sonographic features of TTTS
usually manifest between 15 and 25 weeks,
although early 3rd trimester presentations
still occur. The net donor develops features
of anemia/hypovolemia including oliguria,
oligohydramnios, growth restriction, abnormal umbilical artery Dopplers and circulatory redistribution (Fig. 1). Anhydramnios
in the donor amniotic sac can lead to the
sonographic appearance of a stuck twin.
In contrast, the net recipient shows signs of
hypervolemia, including polyuria, polyhydramnios, visceromegaly, abnormal venous
Dopplers, cardiac enlargement/failure, and,
in extreme cases, hydrops (Fig. 1).
Before ultrasound, TTTS was diagnosed
in MC pregnancies based on growth discordance of 20% associated with a discordant fetal/neonatal hemoglobin of 5 g/dl.
However these diagnostic criteria are often
satisfied by discordant growth restriction
and are now considered unreliable for
TTTS. Paired fetal blood sampling has
shown hemoglobin discordance of 5 g/dl
in only 25% of 36 cases of TTTS, with a
mean hemoglobin difference of 3.6 g/dl.2
Discordant fetal growth (birth weight difference 20%) occurs as commonly in dichorionic as in MC twins.3
TTTS is now defined as presentation in
the mid-trimester with the oligopolyhydramnios sequence, the deepest vertical pool in the donor being 2 cm and in
the recipient 8 cm. Other supportive features are a small or non-visible bladder and
abnormal umbilical artery Doppler (absent
or reversed end-diastolic frequencies
[AEDF/REDF]) in the donor in association
with a large bladder, cardiac hypertrophy,
abnormal umbilical vein/ductus venosus
Dopplers and hydrops in the recipient (Fig.
1). Discordant intrauterine growth restriction (IUGR) can mimic the donors phenotype but should not be associated with the
recipients phenotypic features in the cotwin.

Pathophysiology of TTTS
ANATOMIC BASIS

Ex-vivo dye-injection studies have shown


that almost all MC placentae contain vascular anastomoses (Fig. 2).4 Thus, intertwin
transfusion is the norm in MC pregnancies.
This has been confirmed by in-vivo studies
examining markers including erythrocytes,
pancuronium, and microbubble contrast
agents injected in one twin for passage into
the co-twin.5,6
There are three types of interplacental
anastomosesarterio-arterial (AAA),
veno-venous (VVA) and arterio-venous
(AVA). AAAs (Fig. 2) and VVAs are superficial anastomoses that course entirely along
the chorionic plate. These are capable of bidirectional flow depending on alterations in
otherwise similar baseline hydrostatic pressures. In contrast, deep AVAs (Fig. 2) mediate unidirectional flow from one twin to the
other, but are not strictly anastomoses as
they do not bypass the capillary circulation.
Here, the artery from one twin enters the placental cotyledon from the chorionic plate
and forms the usual stem villous capillary
bed, but the corresponding vein that
emerges close to the feeding artery drains to
the co-twin. AVAs are present in almost all
MC placentae, AAAs in most and VVAs in
only approximately 25%.7,8
Although Schatz suggested more than a
century ago that TTTS is caused by unbalanced intertwin transfusion, the anastomotic
patterns responsible for such imbalance
have proved difficult to unravel.9 We have
hypothesized, that anastomoses arise in the
embryological stage of connection of embryonic and extra-embryonic circulations,
and that during placental growth, there is
random loss of these anastomoses, and
TTTS develops when this results in asymmetric flow resistance to net interplacental
transfusion.10 Deep anastomoses ie, AVAs
with net unidirectional blood flow in the absence of compensatory bidirectional superficial anastomoses ie, AAAs and VVAs
would result in an unbalanced intertwin

TwinTwin Transfusion

FIGURE 1. Ultrasound and Doppler findings in twintwin transfusion


syndrome (TTTS). Features of stage II TTTS include oligohydramniospolyhydramnios sequence with growth discordance and nonvisualization of
donor bladder (Panel A). Manifestations of hemodynamic compromise in
stage III TTTS include reversed end-diastolic frequencies (REDF) in umbilical artery of donor twin (Panel B), and pulsatile flow in umbilical vein
(Panel C), reversed flow in ductus venosus (Panel D) and marked tricuspid
regurgitation (Panel E) in recipient. Worsening cardiovascular dynamics in
recipient result in fetal hydrops ie, stage IV (Panel F).

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Jain and Fisk

FIGURE 2. Vascular anastomoses in a


twin placenta from a monochorionicdiamniotic pregnancy. Vascular casting
has been used to delineate the vessels and
their anastomoses. The white arrow indicates an arteriovenous anastomosis
(AVA) with the transfusional direction
being from the artery on the left to the
vein on the right. The black arrow points
to an arterioarterial anastomosis (AAA).

transfusion, mediating a state of hypovolemia in the donor and hypervolemia in the recipient. Initial ex-vivo injection studies confirmed that TTTS placentae had more deep
than superficial anastomoses compared with
MC controls.4,7 Endoscopic studies, though
lacking histopathological confirmation,
confirm injection study evidence that the
majority of TTTS placentae show a higher
number of AVAs from donor to recipient
than in the opposite direction.11,12 Thrombosis of a previously compensatory reversedirected AVA from recipient to donor can
lead to rapid onset of TTTS in a previously
unaffected pregnancy.12 Notwithstanding
an endoscopic report of TTTS with no deep
anastomoses,13 ex-vivo studies show that
AVAs are present in all TTTS placentae as
opposed to 84% of controls.8 In addition,
78% pregnancies with one or more AVAs in
the absence of AAAs develop TTTS.8 The
largest ex-vivo placental injection study has
shown that AAAs are less frequent in TTTS
(24% versus 84% in controls) whereas the
frequency of AVAs and the rarer VVAs is
similar.14 In support of this, computer modeling has shown that unidirectional, or more
likely, asymmetrical bidirectional intertwin
transfusion results in hemodynamic, osmotic and physiological changes consistent
with the clinical features of TTTS.15,16
AAAs have a greater potential for hemodynamic counter balancing than VVAs by
virtue of their higher pressure differential.

The protective role of AAAs in MC twin


pregnancies has been validated by imaging
studies.14,17 AAAs can be ascertained antenatally by color Doppler from as early as 12
weeks gestation.18 Absence of AAAs is associated with an increased risk of TTTS
(61% versus 15%, odds ratio 8.6).14 Computer modeling studies confirm that AAAs
confer greater protection against TTTS than
oppositely-directed AVAs.19
Aberrant placentation and velamentous
cord insertion have also been implicated in
the development of TTTS.20,21 However, a
study of 90 MC placentae showed similar incidence of velamentous cord insertion in
TTTS placentae (53%) and in MC controls
(52%).21a However histology shows that the
donor territory, although showing slightly
edematous villi with small vessels, is more
similar to a normal than to a growth restricted singleton placenta, while the recipient placenta appears postmature, with a thin
trophoblast layer and numerous vasculosyncytial membranes.22
CARDIOVASCULAR
PATHOPHYSIOLOGY

Although anastomotic transfusion creates


the primary hemodynamic discordance,
adaptive/maladaptive secondary fetal physiological or placental responses contribute
toward disease manifestations.
Hypovolemia in the donor results in

TwinTwin Transfusion
growth restriction, redistribution of blood
flow, decreased renal perfusion and oligohydramnios. In advanced disease, increasing fetoplacental resistance manifests as
AEDF or REDF. In the donor kidney, degenerative changes and decreased mass of
the renal tubules may progress to renal tubular dysgenesis.23 Decreased glomerular filtration and renal perfusion in the donor may
be responsible for a renal defect which is
more likely a primary developmental defect rather than secondary to ischemia.23
Apoptosis-mediated loss of proximal and
medullary tubules is thought to be a precursor of more diffuse renal tubular atophy.24
In the recipient, phenotypic features have
largely been attributed to hypervolemia.
High atrial natriuretic peptide (ANP), secreted in response to fluid overload, along
with concomitant suppression of antidiuretic hormone (ADH) mediates the associated polyuria and polyhydramnios. 25
Amniotic pressure is raised in the polyhydramniotic sac and its amelioration by amnioreduction is associated with increased
uterine artery blood flow and improved fetal
acidbase status.2628 Hypervolemia also elevates cardiac preload. Findings of hypertension in the recipient indicate that elevated
afterload may also contribute to cardiovascular dysfunction.29 Implicated in this is endothelin, levels of which are raised in the recipient compared with the donor.30 Cardiac
failure is evident initially by venous Doppler
changes including AEDF/REDF in the ductus venosus, pulsatile flow in the umbilical
vein and tricuspid regurgitation, and later by
fetal hydrops (Fig. 1). Cardiac hypertrophy
secondary to raised afterload sometimes results in a functional right ventricular outflow
obstruction.31,32 Recipient kidneys are enlarged, congested and show hemorrhagic infarction, with glomerular and arterial
changes resembling polycythemia and hypertension.33
Disturbances of the renin-angiotensinaldosterone system (RAS) have been described in the donor as well as the recipient.33,34 There is overexpression of renin in

185

donor kidneys, presumably as a result of


chronic renal hypoperfusion. Though possibly beneficial for adaptation to hypovolemia, the associated increase in angiotensin II
can worsen the donors fetoplacental vasoconstriction thereby decreasing renal and
placental blood flow, promoting growth restriction, and worsening oliguria and oligohydramnios. This could be further aggravated by increased aldosterone production
by the fetal adrenal glands. Interestingly, hyperaldosteronism has been noted in women
with TTTS-affected pregnancies. Renin expression is significantly reduced in the recipients, probably in response to hypervolemia.33,34 However, paradoxical RAS activation due to transfer of effectors such as
renin and/or angiotensin II from the donor
through placental shunts could explain fetal
hypertension and cardiomyopathy in the recipient.33

Clinical Course
All MC pregnancies should be scanned every 2 to 4 weeks for early detection of
growth and amniotic fluid discordance,
Doppler abnormalities and other features of
TTTS. When minor amniotic fluid discordance is noted, scans should be done more
frequently. Fetal echocardiography is indicated in all MC twins in view of an increased
incidence of cardiac anomalies, (3.8% v
0.6% in singletons).32
Retrospective studies show that the median gestational age at diagnosis of TTTS is
around 21 weeks and 29 weeks at delivery.35,36 Preterm labor or PPROM occur
secondary to raised amniotic pressure with
polyhydramnios, but may also be a consequence of therapeutic procedures.37 Preterm
labor or PPROM is managed in the usual
fashion, and preterm delivery is associated
with the usual complications of prematurity.
However, preterm TTTS babies, especially
28 weeks, do much worse neonatally than
their singleton or non-TTTS twin counterparts. Cardiac dysfunction in the recipient is

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Jain and Fisk

the main additional problem, while renal


dysfunction and growth restriction are major
issues for the donor.
Untreated, TTTS is associated with a
perinatal loss rate 80% and frequent longterm morbidity in survivors especially neurologic sequelae.1,38 The donor is more
likely to die than the recipient, and neonatal
deaths outnumber fetal deaths by 2:1, although the latter may be attributed to late
gestational age at presentation in older series.3941 Where there are arterial Doppler
abnormalities ie, AEDF/REDF in the donor
umbilical artery or venous abnormalities in
the recipient, perinatal death of one or both
babies occurs in 65% of cases.17 Retrospective analysis of 136 fetuses diagnosed with
TTTS 28 weeks and managed expectantly
revealed an overall survival of 27% with
neurologic impairment in 25% of survivors.42
Death of one twin in utero complicates
about 30% of affected pregnancies.35,40,43,44
This may result in improvement of the condition in the surviving co-twin with resolution of TTTS due to cessation of the intertwin transfusion. However, there are substantial risks to the remaining twin including
a 25% risk of ischemic brain injury or renal
lesions in survivors and a comparable risk of
immediate co-twin fetal death.45,46 Fetal
blood sampling studies support the theory
that the increased risk of death or neurologic
injury in the surviving MC co-twins is due to
exsanguinatory intertwin transfusion from
the surviving twin into the dead twins vascular compartment. 44 This seems more
likely after recipient death in utero, but paradoxical exsanguination of the recipient into
the dead donor has also been reported.47 The
outcome for the survivor is poorer in the
presence of an AAA, presumably because of
more rapid mediation of agonal intertwin
transfusion.48 Notwithstanding this, AAAs
are less frequent in advanced stage TTTS,
and are usually associated with high double
survival in Stage IIII disease.49

Prediction of TTTS
Twins presenting with severe TTTS in the
mid-trimester may have hemodynamic imbalance from the first trimester manifest as
discordant increased nuchal transluscency
(NT) at 10 to 14 weeks.10,50 This is of relevance as NT is the primary screening test
for aneuploidy in multiple pregnancies. Sebire et al found that 32% of MC pregnancies
with increased NT subsequently developed
TTTS (likelihood ratio 3.5, 95% CI 1.96.2)
although only 28% of cases were predicted.50
Another finding associated with later
TTTS is folding of the intertwin membrane
at 1517 weeks. This is seen in 32% of MC
pregnancies, 43% of which subsequently
develop TTTS (likelihood ratio 4.2, 95% CI
3.06.0).50 However the utility of this subjective finding in predicting TTTS that remains debatable.
Doppler studies of placental anastomoses
have shown that TTTS develops in 15% of
patients with an AAA versus 61% without
an AAA (OR 8.6).14 Conversely however,
25%30% of TTTS placentae still have an
AAA, although, when TTTS develops in
the presence of AAAs, it is associated with
considerably higher perinatal survival.14
AAAs can be detected after 18 weeks using spectral and color Doppler with an 85%
sensitivity and 97% specificity, though
detection as early as 11 weeks is possible.14
Typically, the presence of an AAA is
revealed by a bidirectional speckled pattern on color or power Doppler (Fig. 3, panel
A).14,18 In a series of 105 patients with MC
pregnancies, 68 (65%) had an AAA confirmed by ex-vivo injection studies, 59
(56%) of which were identified in vivo by
Doppler.14 Computer modeling supports
varying bidirectional flow in the AAA,
the periodicity of which has been shown
to be a function of the difference in twins
heart rates (Fig. 3, panel B). 15 Further,
this bidirectional pattern transforms to
unidirectional flow in the event of intrauter-

TwinTwin Transfusion

187

FIGURE 3. The characteristic periodic bidirectional flow waveform of an


arterioarterial anastomosis (AAA). Panel
A: Demonstration of an AAA using
Doppler sonography on the chorionic
plate. The high frequency alternating bidirectional flow across this anastomosis
produces a speckled pattern on color
Doppler. Panel B: Computer modeling
using two fetal circulations in a model of
monochorionic diamniotic pregnancy
connected by an AAA as shown in the
upper right corner. The net direction and
amount of flow across this anastomosis
(lower trace) is determined by superimposition of oppositely directed flows
through the abdominal aortae (upper
trace) and umbilical arteries (middle
trace) of the two twins, being a function
of the difference between the two heart
rates (10% in this case). (From Taylor et
al. Mapping the monochorionic equatorthe new frontier. Ultrasound Obstet Gynecol 1999;14:372374. By permission
of John Wiley & Sons, Inc.)

ine demise of one twin.51 Interestingly,


cyclical changes in umbilical arterial flow
have been seen in growth restricted MC
twins (in the absence of TTTS), these are
secondary to retrograde transmission from
a large AAA.52 Factors that facilitate detection of AAAs are an anterior placenta, larger
diameter AAAs, gestational age 20 to 30
weeks, and serial scanning.14 Therefore,
absence of an AAA is a good predictor of
development of TTTS, and more significantly, of severe TTTS associated with poor
prognosis. Attempts should be made to identify AAAs on serial ultrasound between 14
and 28 weeks both to predict prognosis
as well as to select appropriate management.14,18,52 The main clinical issue with
this test is distinguishing a true negative result from a false negative due to early gestation.

Staging
Quintero et al developed an intuitive staging
system to categorize disease severity. 53
Stages I to V are based on progressivelyworsening clinical features: stage I,
oligo/polyhydramnios sequence only with
bladder visualized in the donor twin; stage
II, bladder not visualized in donor; stage III,
critically abnormal Dopplers (AEDF or
REDF in the donor umbilical artery, or reverse flow in the ductus venosus or pulsatile
flow in the umbilical vein in the recipient);
stage IV, hydrops in recipient; stage V, demise of one or both twins (Fig.1). This staging system for TTTS was designed to assist
with determination of prognosis, and to
standardize comparison of treatment results.53,54 However, attempts to validate
staging by outcome may be distorted by the
treatment paradox ie, improving outcomes

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Jain and Fisk

in presence of worse disease. In a recent


stage-dependent survival analysis of 52 consecutive cases with a median gestation at
presentation of 21 weeks and 29 weeks at
delivery, severe TTTS (stage III) was present in 63% at presentation.55 Excluding
elective terminations and stage V disease,
45% of TTTS cases progressed to a more advanced stage while 18% regressed to a lesser
stage. Of note, stage II was often temporary,
with 20% of cases progressing but 60% regressing to stage I. Notwithstanding this,
78% of cases were at least stage III at some
time during the pregnancy. Survival rates
were 58%, 60%, 42% and 43% for stages
IIV at presentation, respectively, with no
significant influence of stage on survival.
On the other hand, in terms of worst ever
stage, survival was 75%, 67%, 52% and
43% for stages IIV respectively. Survival
was poorer where stage increased (27% versus 94% when stage decreased). Thus, staging may be more useful for monitoring disease progression than for absolute risk assessment.55
At Queen Charlottes and Chelsea Hospital we now use a modified staging system
that incorporates the antenatal finding of an
AAA indicating improved prognosis into
the TTTS stage. If an AAA(s) is noted, stage
is post-scripted with an a as opposed to a
b when none is detected. Thus, stage III
disease is sub-staged as IIIa in presence of
an AAA and IIIb in its absence. In addition,
IIIb may be downstaged to IIIa if subsequent
scanning elicits the presence of an AAA. In
an analysis of 96 TTTS pregnancies, overall
survival was better in the presence of an
AAA on antenatal ultrasound (83%) than in
their absence (52%).49 Presence of an AAA
conferred a stage-dependent survival advantage to fetuses in stages I-III (Overall survival (stage at treatment): Ia 100%, Ib 63%,
IIa 100%, IIb 59%, IIIa 83%, IIIb 44%, IVa
25%, IVb 50%).49 Interestingly, survival is
actually better in stage IIIa compared with
Ib. Thus, our AAA modification of the
Quintero classification improves prognostic

stratification and seems an important variable in treatment selection.

Complications
In addition to the morbidity associated with
TTTS discussed above, some problems
merit further discussion.
NEUROLOGICAL COMPLICATIONS

TTTS is associated with an increased risk of


neurologic sequelae. There is a paucity of
long term follow up neurodevelopmental
cohort studies. Overall, there is an approximate 15% incidence of long-term neurologic sequelae in survivors.35,38,5659 Of
these, just over half involve cerebral
palsy.35,38,54,56,58,60 Neurologic morbidity
is the result of antenatal insults as well as
the sequelae of preterm birth such as periventricular leukomalacia (PVL) and intraventricular hemorrhage. The likely pathogenesis of antenatally-acquired lesions is
ischemia attributable to hemodynamic imbalance via placental vascular anastomoses.
Polycythemia and vascular stasis in the recipient and anemia and hypotension in the
donor are potential mechanisms for neurologic insults. Most series show equal distribution of neurologic lesions between donors and recipients.43,56,61,62 Death of one
twin is associated with an increased risk of
neurologic sequelae in the surviving cotwin.36,41,44,53 Despite initial claims of a decrease in neurologic sequelae after laser
treatment, recent studies have not been able
to confirm lower sequelae with any treatment modality, as discussed in the management section.
Neurologic sequelae have sometimes
been inferred from abnormalities on antenatal or early postnatal imaging studies.
However an ultrasound abnormality does
not necessarily equate with neurologic sequelae. On postnatal cranial ultrasound,
29% of TTTS survivors have abnormalities.35,36,38,43,60,61,63 In 12% of survivors,
these findings are PVL of antenatal origin.36,60 However, most ultrasound lesions
are minor, consisting of mild ventriculo-

TwinTwin Transfusion
megaly, subependymal pseudocysts, small
white matter cysts and basal ganglia echogenicity or lenticulostriate vasculopathy.36,61
Antenatally-acquired lesions should be differentiated from postnatally acquired ones
which include hemorrhages and PVL evident on delayed neonatal imaging.63 Surprisingly, in the absence of TTTS, 23% of
MC twin survivors also have abnormal postnatal ultrasound findings.62 In addition,
postnatal ultrasound studies in term infants
show an incidence of minor lesions as high
as 27%30%.64,65 However, none of these
infants had cerebral palsy or major developmental delay.64,65 The varying incidence of
ultrasound abnormalities in TTTS affected
survivors and control term infants in various
studies is also likely to be influenced by the
sensitivity of the imaging technique used in
different studies.
CARDIOVASCULAR COMPLICATIONS

Although MC twins have a six-fold increased risk of congenital cardiac anomalies, this is even higher in TTTS (6.9% with
versus 2.3% MC twins without TTTS).32
TTTS survivors are at increased risk of both
congenital and acquired cardiovascular lesions.31,32 All recipients manifest variable
degrees of biventricular hypertrophy and dilation, with tricuspid regurgitation and decreased ventricular function, while no specific acquired cardiac dysfunction occurs in
donors either in utero or after birth.29,31,32,66,67
Volume overloading and systemic hypertension in the recipient cause myocardial
hypertrophy.29 This hypertrophic cardiomyopathy can cause subvalvular stenosis resulting in right ventricular outflow tract obstruction necessitating valvotomy in infancy
in some cases.31,32 Though biventricular hypertrophy is frequent in recipients, an acquired right outflow tract anomaly has been
described in absence of systemic hypertension.68 Cardiac hypertrophy is associated
with subsequent cerebral palsy, although
this may simply be a function of disease
severity.60 Although 45% to 50% of recipients exhibit abnormal cardiac function in

189

the neonatal period; most of these changes


are reversible, however, 5% to 10% of
the recipients have long-term cardiac problems.31,32,43,66,67
Interestingly, follow up studies in offspring of TTTS pregnancies show abnormal
vascular function including reduced arterial
distensibility in donors versus recipients,
possibly due to vascular programming in
utero, with implications for cardiovascular
disease in adult life as proposed by Barker.69
Of note, these changes in vascular function
are absent in double survivors after laser, in
which ablation of anastomoses curtailed further intertwin transfusion in utero.70
OTHER COMPICATIONS

Acute neonatal renal failure occurs more


commonly in TTTS. A prospective cohort
study of 17 pregnancies described a 48% incidence of renal failure in survivors (donor >
recipient) compared with 14% in gestational
age-matched control twins.35 However, this
renal failure is often transient, long term renal sequelae occurring in only 3% of survivors.35,43,63 Abnormal perfusion in other
vascular beds may also result in fetal/neonatal
complications. Reduced splanchnic perfusion can lead to congenital intestinal perforation from ischemic necrosis. 35,43,63
Spontaneous lower extremity ischemia resulting in amputations have also been described.36,43,57

Management
The range of therapeutic options includes
expectant management, serial amnioreduction, septostomy, laser photocoagulation of
placental shunts, and selective feticide. Because of the high untreated perinatal mortality and morbidity, expectant management
will only be appropriate in a few mild cases.
MEDICAL THERAPY

Some empiric medical treatments have been


tried. However, none to date have proven to
be of benefit. With a view to improving cardiac function in the recipient, maternal di-

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Jain and Fisk

goxin therapy has been used with anecdotal


success.71 However, the ability of digoxin to
cross the placenta and reach the recipient in
therapeutic concentrations, especially in the
presence of hydrops, is questionable. Indomethacin to control polyhydramnios in the
recipient is contraindicated in view of its exacerbating effect on the already compromised donors renal function.
AMNIOREDUCTION

Serial amnioreduction to normalize amniotic fluid volume is the earliest and arguably
the simplest and most accessible of the various treatments advocated in TTTS.37 The
most obvious mechanism by which amnioreduction works is decreased fluid volume
reducing the risk of preterm labor and
PPROM.72 Patients with polyhydramnios
have raised amniotic pressure and its reduction is associated with improvement in fetal
status.27 Polyhydramnios is associated with
impaired uteroplacental perfusion as suggested by an inverse correlation between the
degree of hydramnios and impairment in fetal blood gases.73 Amnioreduction leads to a
74% increase in uterine arterial flow, which
suggests a further mechanism for the beneficial effects of amnioreduction.26 PPROM in
TTTS may paradoxically improve outcome
by a similar mechanism.
Amniocentesis is indicated when amniotic fluid index (AFI) is >40 cm or the deepest vertical pool >12 cm, the threshold for
increased amniotic pressure. Each liter of
fluid reduces AFI by about 10 cm. Previously, the goal was to lower the AFI to <25
cm,37 but increasingly, targets of <15 or <10
cm are used in an attempt to prolong the interval between procedures.74 Procedurerelated risks include PPROM (approximately 6%), chorioamnionitis and placental
abruption though the incidence is low.37,43
In a retrospective analysis, in cases with severe TTTS before 28 weeks gestation, serial
amnioreduction led to an improvement in
perinatal survival to 60% (versus <20%
without treatment), which included a 50%
double and 20% single survival.1 However,

half the treated pregnancies still have at least


one perinatal death while neurologic lesions
are found on ultrasound in 18% of survivors.43 Importantly, although amnioreduction controls polyhydramnios, it does not
address the underlying pathophysiology of
TTTS.
SEPTOSTOMY

The aim of septostomy is to allow excess


fluid in the recipient sac to pass into the donor sac where, by absorption and swallowing, it may reduce the oligo/polyhydramnios
sequence as well as restore euvolemia in the
donor. It arose following a case of inadvertent puncture of the intervening membrane
in TTTS which was followed by normalization of amniotic fluid volume in both sacs,
and improved Dopplers and growth in the
donor.75 Indeed, some argue that clinical
improvement seen after amnioreduction can
be explained by inadvertent iatrogenic septostomy by transgression of the flattened donors sac during insertion of the amnioreduction needle into the recipients sac. Of
relevance, TTTS is rare in monoamniotic
twins, which have a similar incidence of placental anastomoses but lack a dividing
membrane.
Saade et als early series of needling the
septum with a 20g to 22 g needle in 12 cases
(9 of which underwent septostomy without
amnioreduction) reported an 83% overall
survival.76 A subsequent smaller study reported a similar overall perinatal survival of
71% in patients treated with septostomy
(versus 64% with amnioreduction), with a
trend toward a higher double survival in the
former (57% versus 43%).77 Others have reported poorer outcomes with septostomy despite improved relative amniotic volumes,
mostly due to PPROM and preterm labor.
Because septostomy is associated in small
case series with a mean fetal survival rate of
78%,7678 a multicentre randomised controlled trial has compared septostomy
against amnioreduction. The report of that
trial in abstract form showed no difference
in overall survival (70%).79 However, one

TwinTwin Transfusion
reported benefit was a decrease in need for
repeat procedures with septostomy (40%
versus 70% with amnioreduction). In terms
of technique, Nd:YAG laser can be used as
an alternative to needling to create the defect
in the intertwin membrane, though without
any significant advantages.75 The procedure
has at least a theoretical risk of intertwin
cord entanglement through extension of the
defect in the dividing membrane, though the
hole created is usually small (microseptostomy).
Despite its ameliorative effects, it is again
difficult to see how septostomy addresses
the underlying transfusional basis of the disease. In this light, computer modeling has
shown that merging of the two amniotic
compartments to allow swallowing of the redistributed fluid by the donor has minimal
effect on donor blood volume or growth.80,81
LASER ABLATION

Laser ablation is the only treatment that addresses the primary basis of the disease; cessation of intertwin transfusion. Laser ablation entails photocoagulation of anastomotic
vessels between the two chorionic circulations under direct vision. Typically, an endoscope is introduced transabdominally into
the uterine cavity under ultrasound guidance
and Nd:YAG laser applied via a 400600
m optic fiber introduced thorough the side
channel.82,83
Non-Selective Laser Ablation
In this initial technique, all vessels approaching or crossing the membrane between the twins were ablated.84 However,
this approach met with limited success.
Ville et al carried out laser ablation of placental anastomoses in a series of 132 patients with severe TTTS at a median gestational age of 21 weeks. Overall fetal survival
was 55%, and the number of pregnancies
with at least 1 survivor was 73%.58 De Lia
reported a 69% overall survival and 82% of
pregnancies had at least 1 survivor in a series
of 74 patients, though 7 patients were excluded from analysis due to pre- or intraop-

191

erative complications.57 A meta-analysis of


TTTS presenting before 28 weeks concluded that outcomes from non-selective laser ablation were similar to serial amnioreduction with a 58% overall survival and at
least one survivor in 74 versus 70% of pregnancies.1
A likely explanation for the lack of improved survival with non-selective laser ablation is that since the intertwin membrane
bears little relationship to the vascular equator between the two fetoplacental circulations, a number of non-anastomotic vessels
are also obliterated; devitalizing some normal cotyledons.72,85 The excessive placental insult is substantiated by findings of full
thickness placental necrosis postpartum.82
Such an insult is more detrimental to the donor with a lesser a priori placental share.
This explains the high procedure related fetal loss rate, which was as high as 42% in the
first series though subsequently decreased to
15-20%.58,84 In keeping with this hypothesis, two thirds of donors die if AEDF is present prior to laser. Other complications include PPROM, chorioamnionitis, preterm
labor, and continued or even reversed
TTTS.86 Rare findings including aplasia cutis, limb necrosis, amniotic bands, and microphthalmia, have been described, but their
causal relationship to the procedure rather
than TTTS has not been established.57,87
Anecdotal reports of maternal complications such as pulmonary edema, adult respiratory distress syndrome and maternal death
are of concern, although the contribution of
laser as opposed to the concomitant amnioreduction is unclear.
Selective Laser Ablation
To minimize the high procedure related loss
rate of non-selective ablation, several
groups developed selective photocoagulation targeting only those AVAs involved in
the donor-to-recipient transfusion.11,39,40,59,88
Vessels near the intertwin membrane are
carefully examined endoscopically to identify AVAs. All AVAs including reverse
ones from the recipient to donor are photo-

192

Jain and Fisk

coagulated to prevent any reversal of the


transfusional phenotype.89 The anastomotic
configuration can be variable making correct identification challenging and in this
light, endoscopically identified AVAs have
not been validated against gold standard placental injection studies. Visual examination
under optimal ex vivo conditions identified
only two-thirds of AVAs demonstrated by
placental injection.21a AVAs can be identified in vivo using color Doppler and 3D ultrasound which may facilitate planning of
selective laser ablation and result in shorter
procedure times, although the sensitivity of
this technique to date remains < 50% (unpublished observations).90,91
There are a number of technical challenges with both types of laser treatment.
Access to an anterior placenta is a particular
problem. A lateral entry, use of flexible
curved or sidefiring scope and even a minilaparotomy to insert the cannula directly
into the uterus have been used in attempts to
overcome this problem.58,87,88 Access may
also be facilitated by adequate maternal anesthesia, such as under epidural or general,
although not all groups find this necessary.
Prior septostomy may occasionally render
access to the chorionic plate problematic due
to chorioamniotic separation, while intraamniotic bleeding secondary to vessel disruption may necessitate amnioexchange to
restore visualization.
Treatment is followed by improvement in
fetal hemodynamics including restoration of
normal ductus venosus flow in the recipient
and normal umbilical artery flow in the donor.86 However, the donor may show signs
of a transient hydrops, which may be the result of normalization of a previously hypodynamic circulation.86 Around 13% of patients require a repeat procedure.40,58 An anecdotal report of a superselective laser
ablation procedure describes identification
and ablation of a single donor-to-recipient
AVA.92 However, when selective ablation
of anastomoses from the donor to the recipient is undertaken, the possibility of reversal

of TTTS along residual anastomoses directed from recipient to donor needs to be


kept in mind.89
Using the selective laser, Quintero et al
reported survival of at least one fetus in 83%
of patients versus 61% in a non-selective laser group and 67% in a serial amniocentesis
group managed in the same center. 54,59
Similarly, Hecher et al showed an improved
overall survival of 68% with selective laser
(versus 61% in a non-selective laser group
and 51% in non-contemporaneous amniodrainange control group from another center) with survival of at least one fetus in 81%
(versus 79% and 60%, respectively).39,40
However, a double survival of only 54%, indicates that even with the best treatment option available, almost half of affected pregnancies still lose one or more fetuses.40
In terms of neurologic sequelae, Quintero
et al suggested that selective laser led to a
decrease in the incidence of neurologic morbidity (4% versus 24% in the non-selective
group), though without differentiating between cranial ultrasound abnormalities and
neurologic handicap.54 Hecher et al also
suggested a lower incidence of abnormal
cranial ultrasound findings with selective laser treatment (6% versus 18% in an amnioreduction group managed elsewhere). 39
However, a formal neurodevelopmental follow up study of 89 TTTS survivors at 14 to
33 months by the same group subsequently
showed a 22% incidence of neurologic sequelae in the selective laser treated group including an 11% incidence of cerebral
palsy.56 The incidence was similar in donors
and recipients. However, it was increased in
single survivors after an intrauterine death
(27% versus 8% in double survivors), in
which case it was more likely to be in recipients (23% versus 14% in donors) as compared with double survivors (3% in recipients versus 13% donors).56 In the absence of
formal long term neurologic follow up, Ville
et al also reported a seemingly low neurologic handicap rate of 4% with non-selective
laser.58 However, detailed neurodevelopmental follow up by the same group at 6

TwinTwin Transfusion
months to 3 years showed a 9% incidence of
cerebral palsy.93 Considering all the data, it
appears that the incidence of cerebral palsy
with non-selective and selective laser is
comparable to the overall incidence of cerebral palsy in TTTS (8%) and argues against
an obvious improvement in neurologic outcome with laser therapy. However, Sutcliffe
et al found no cases of cerebral palsy in
single survivors following non-selective laser treatment, suggesting that non-selective
laser may result in single intrauterine death,
the resultant functionally dichorionic placentae protect against agonal transfusional
sequelae.93 An alternative explanation could
be that this treatment modality improves
overall survival merely by salvaging fetuses
that have already suffered a neurologic insult.
SELECTIVE FETICIDE

In contrast to other treatments which attempt


to salvage both fetuses, with selective feticide one fetus is killed by cord litigation to
improve the chance of survival in the other.
Due to its inherent procedure related mortality of at least 50%, feticide was initially reserved for cases where other treatments
failed, and in particular where one fetus was
deemed preterminal. More recently it has
been offered to patients with severe TTTS
(Stage III or IV) as an alternative to selective
laser ablation with the surmise that a better
intact prognosis for one twin may be preferable to a guarded prognosis for both. After
the decision has been made to proceed, the
question that arises is which fetus to terminate. Initially, donors were selected based
on the assumption that a donor with AEDF
has defective placentation impairing its subsequent intrauterine longevity. In addition,
the recipient was felt less likely to exsanguinate into the donor against the net AVA
transfusional direction. Both assumptions
have been proven to be incorrect. Postprocedure survival and growth velocities of
spared recipient and donor co-twins have
been similar, making the recipient and the
donor equally appropriate choices for cord

193

ligation.94 In addition, preprocedural Doppler abnormalities normalize postprocedure


in surviving donors.94 Current evidence suggests that the recipient may be a better candidate for termination for several reasons.
Technically, targeting the cord in the recipient sac with polyhydramnios is easier. The
cord can be occluded well away from the
uterine wall decreasing the risk of maternal
injury. In addition, recipients are more likely
to develop hydrops and cardiac dysfunction,
and may have a higher incidence of neurologic sequelae.31,38,60,61,6668 Nonetheless,
there remain indications for selective feticide of the donor eg, severe brain lesions or
cardiac defects in donor or increased cord
thickness in the recipient (>26 weeks or with
hydrops) rendering cord occlusion problematic. One disadvantage with selecting the
donor is that amnioinfusion is often required
to access the cord.94
Any technique used must ensure that all
vessels in the umbilical cord are occluded,
failure of which can lead to acute intertwin
transfusion. Ultrasound-guided sclerosant
injection techniques95,96 occlude only one
vessel which explains the failure rate of 67%
reported using alcohol or enbucrilate.97 Laser coagulation of the cord is usually not feasible after 18 to 20 weeks because of a
higher failure rate with increasing vessel diameter.98 A fetoscopic approach has been
used to place a suture knot around the cord
with success rates as high as 84%.99101
Overall survival (of the surviving twin) with
fetoscopic suture ligation of the cord is 63%
to 71% with an associated risk of preterm
rupture of membranes as high as 30% to
40%.99,101 Suture ligation of the cord can
also be done entirely under ultrasound guidance.102
The preferred method for selective feticide
in MC twins is now the simpler ultrasoundguided approach with bipolar diathermy.94
A single 3.3 mm port is introduced into the
amniotic cavity under local anesthesia (Fig.
4) and 3 mm bipolar diathermy forceps advanced under ultrasound guidance to grasp
a free loop of cord away from the both the

194

Jain and Fisk

FIGURE 4. Instruments and technique


for bipolar diathermy of umbilical cord.
A 3 mm diathermy forceps (Everest)
(Panel A) is used to grasp the umbilical
cord under ultrasound guidance after
identification of the cord with color
Doppler (Panel B). Diathermy is applied
(Panel C), the cord is released and absence of blood flow through the cord is
confirmed with color Doppler (Panel D).
Panel E shows the appearance of the umbilical cord of a selectively terminated
recipient (cord occlusion by bipolar diathermy at 20 weeks) at delivery of the
surviving donor at 35 weeks. (From Taylor et al. Ultrasound-guided umbilical
cord occlusion using bipolar diathermy
for Stage III/IV twintwin transfusion
syndrome. Prenat Diagn 2002;22:70
76. By permission of John Wiley & Sons,
Inc.)

fetus and the uterine wall. Serial applications of coagulation lasting 60 seconds are
used with incremental power as needed (20
to 50 W) until the bubbling stops. Cessation
of blood flow is confirmed by color Doppler.
Advantages include use of a single port, a
high success rate in achieving cord occlusion, a shorter procedure duration, a 76% to
93% survival of the remaining twin, and a
lower albeit substantial (12% to 20%) incidence of PPROM.94,103,104 An important
aspect of this treatment is the varying legal
status of termination of pregnancy after viability. This option may be feasible after 24
weeks in jurisdictions such as the United
Kingdom, France and Israel but is not
widely available in other countries including
most of the United States.
A novel recently developed interstitial laser procedure is useful for selective termination in the early mid trimester (<16 to 17
weeks).105 This technique involves introducing a 20 gauge needle into the abdomen
of the selected twin close to the vitelline arteries and intrahepatic vein under ultrasound
guidance.105 Then a 400 mm to 600 mm la-

ser fiber is advanced through the needle,


protruding 4 mm beyond the needle tip and
short bursts of Nd:YAG laser (10 to 20 W)
fired until the area becomes intensely echogenic. Again cessation of umbilical blood
flow is confirmed on Doppler. The operator
skills required for this technique are the
same as any other intrauterine needling procedure. Other advantages are reduction of
risks to the surviving twin due to limitation
of any hemorrhage within the body of the
selected twin and the applicability of selective termination to earlier gestations, especially since cases are increasingly diagnosed
in the early mid-trimester. However, ensuring coagulation of all the cord vessels within
the fetal abdomen can be challenging, and
accordingly this method is restricted to earlier gestations. We currently use interstitial
laser before 16 to 17 weeks, bipolar cord occlusion thereafter until 27 weeks, after
which selective feticide is rarely carried out
by ultrasound guided suture ligation. One
difficulty in restricting the procedure to preterminal situations is timing, especially
given the understandable reluctance of par-

TwinTwin Transfusion
ents to countenance termination of a structurally normal fetus, along with the natural
tendency of clinicians to delay such a procedure until it becomes absolutely necessary,
which obviously can result in an unexpected
fetal loss.
MANAGEMENT OF SINGLE
INTRAUTERINE DEATH

In the event of death of one twin, the TTTS


phenotype may resolve, but close monitoring of the surviving co-twin is essential to
detect acute transfusional sequelae. Fetal
blood sampling has been carried out followed by intrauterine blood transfusion to
correct anemia in an attempt to improve survival and perhaps reduce neurologic disease
in survivors.46 However, emergency transfusion seems too late to prevent neurologic
injury and may lead to increased survival of
brain damaged fetuses. Similarly, immediate delivery does not improve outcome for
the surviving fetus, presumably because the
insult has already occurred.45 In contrast
conservative management with ultrasonography and magnetic resonance imaging
(MRI) allows detection of significant neurologic injury. Abnormal cranial ultrasound
findings are reported in 50% of survivors.36 When imaging suggests a major risk
of neurologic sequelae, termination of pregnancy can be considered within the local
gestational and legal constraints. Clearly,
prevention of the first intrauterine death and
its sequelae is the preferable goal; thus careful monitoring of TTTS pregnancies is crucial to facilitating a diagnosis of impending
fetal death rather than fetal death itself.
When intrauterine death is imminent, delivery, laser or at least occlusive feticide may
prevent these devastating complications.
Finally, despite anecdotal reports of subclinical coagulopathy in the mother after intrauterine death of one twin, there is no evidence to implicate disseminated intravascular coagulation as a sequelae of single MC
intrauterine death.45

195

DELIVERY

After viability, delivery becomes an option,


keeping in mind the poorer fetal outcome at
gestations <28 weeks in TTTS. Our unit has
used fetal blood sampling between 28 to 30
weeks to assist in decision making regarding
further therapy and /or timing of delivery.
The greater the interfetal haemoglobin discordance, the higher is the likelihood of intracranial abnormalities.43 Unless earlier intervention is indicated on other grounds, we
recommend routine delivery in TTTS at 32
to 33 weeks after administration of steroids
for fetal lung maturation. Cesarean section is
indicated in view of high likelihood of fetal
intolerance of labor, and the possibility of
acute intrapartum intertwin transfusion.
RANDOMIZED CONTROLLED TRIALS

Comparison of outcomes between treatment


modalities is difficult in the absence of randomised trials. However, 2 such trials have
been completed and are awaiting publication, although results have been presented in
abstract form. Saade et als multicenter randomized-controlled trial comparing serial
amnioreduction with septostomy, the first
randomized trial of any invasive treatment
in fetal medicine, showed no difference in
overall survival, as discussed above.79 The
Eurofetus trial compared serial amnioreduction with laser coagulation in pregnancies
with TTTS <26 weeks.106 In this study, survival, gestational age at delivery and birthweight were significantly higher and PVL
lower in the laser treated group compared
with amnioreduction, although power endpoints for morbidity were not reached. The
chief finding of the trial however was the
poor results in both groups. Double intact
survival was achieved in only a third of
cases with the better of the treatments. An
NIH trial comparing serial amnioreduction
and laser ablation in stage IIIV TTTS is underway in the USA.
STAGE-BASED TREATMENT

Pending the above, the optimal treatment


strategy for TTTS remains unclear. Staging

196

Jain and Fisk

is increasingly used to guide management,


with simpler relatively safe but possibly less
effective procedures like amnioreduction
and septostomy preferred for good prognosis cases. Technically-challenging procedures like cord occlusion and endoscopic laser ablation, which are seemingly more effective but with a higher intrinsic risk of
fetal loss, being employed in poor prognosis
cases. There are now strong arguments for a
stage-based approach to therapy. Quintero
et al in a multicenter cohort comparison of
survival by stage recently reported results
which showed that laser had a higher perinatal death rate compared with serial amnioreduction (29% versus 13%, OR 2.7 (95% CI
1.1-7.0), P = 0.02) in early disease with fluid
balance changes only (stage I and II) (Fig.
5). In contrast, in advanced disease with cardiovascular manifestations (stage III and
IV), laser had a lower perinatal death rate
(45% versus 65%, OR 0.4 (95% CI 0.20.9),
P < 0.02). The double survival rate in stage I
and II was similarly higher for amnioreduction (79% versus 55% for laser, OR 3.1

(95% CI 1.28.3), P = 0.02). Thus, the number needed to treat (NNT) for amnioreduction versus laser in early stage disease indicated an extra double survival for every four
or five cases treated by amnioreduction
compared with laser. Since some cases with
AR will progress, if this analysis had been
done for worst rather than initial stage, the
survival advantage in early disease may be
even greater in favor of amnioreduction.
Analysis of another useful parameter to assess pregnancy outcome, any (or at least
one) survival rate, was higher for laser in
stage III and IV (82% versus 45% for amnioreduction, OR 2.8 (95% CI 1.716.7), P
< 0.01). Thus, in advanced disease, the NNT
for laser versus amnioreduction indicated
that every third patient treated with laser resulted in an extra pregnancy with at least 1
survivor. In conclusion, serial amnioreduction and/or septostomy is associated with
better outcomes in stage I or II disease, while
selective laser ablation is associated with
better outcomes in advanced disease (stage
III/IV).

FIGURE 5. Categorical reanalysis of survival data from twin-twin transfusion syndrome (TTTS)-affected pregnancies treated with amnioreduction
or selective laser (Quintero et al, Am J Obstet Gynecol 2003;188:1333
1340). Panel A: Perinatal (overall), double (both twins) and any (at least one)
survival rates in mild (combined stage I and II) TTTS. Panel B: Survival
rates in severe (combined stage III and IV) TTTS. *versus amnioreduction,
P < 0.05.

TwinTwin Transfusion
Our suggested sub-categorization of
Quintero stage, in which the presence or absence of an antenatally-detected AAA is denoted a and b respectively, not only allows identification of good from bad prognosis cases within each stage, but also an
AAA-positive subgroup within Stage III
(IIIa) which is associated with better perinatal and double survival than AAA-negative
Stage I and II (Ib and IIb) cases.49 Incorporation of AAA into a modified TTTS staging
system should improve prediction of perinatal survival, and may facilitate treatment selection to optimize outcome. Stages Ia, IIa
and IIIa form a group with good survival
prognosis, which can be managed conservatively or with temporizing measures such as
amnioreduction and/or septostomy, and
then delivered electively by 32 to 34 weeks.
Stages Ib and IIb comprise a group with intermediate survival prognosis. While amnioreduction is associated with better perinatal survival than laser ablation for Stage
III,54 some of this group nevertheless progress to more advanced stage disease, eventually requiring definitive treatment. Stages
IIIb and IV form the group with the poorest
survival, in which more invasive albeit definitive treatment such as selective laser or
cord occlusion appear indicated. Selective
laser ablation of anastomotic vessels has
been shown to result in higher perinatal,
double and any survival rates than amniocentesis procedures for stage IV disease,54
while cord occlusion in Stage III/IV disease
is associated with empirically higher survival than amnioreduction.94
Notwithstanding this, there are some arguments against a stage based approach to
treatment. Firstly, little information is available on neurologic sequelae by stage, and future studies will now be needed to stratify by
modified stage. Next a proportion of patients with early stage disease will progress
to require more definitive treatment, and
membranous detachment after septostomy
or intra-amniotic bleeding after amnioreduction may render laser technically difficult, reducing the chances of success. Fi-

197

nally, in Stage IV disease, the rare presence


of an AAA seems to worsen prognosis, presumably by allowing acute transfusion with
its sequalae when one twin dies in utero.48,49

Conclusion
TTTS is a common disease process affecting
monochorionic diamniotic pregnancies.
Though the pathophysiology is poorly understood, interplacental anastomoses and
unbalanced intertwin transfusion form the
etiologic basis. Several therapeutic options
are available including amnioreduction,
septostomy, laser ablation of vascular anastomoses, and selective feticide. With these
modern treatment modalities, overall perinatal survival rates have improved from
20% to around 60% to 70%. However, the
majority of affected pregnancies will still
lose at least one baby, with significant long
term neurologic morbidity in about 10% of
the survivors. Thus, outcomes, though substantially improved by intervention, remain
suboptimal, partly due to poor understanding of the underlying pathophysiology and
partly because of poor case selection for intervention. Current evidence supports a
stage-based approach to treatment, with a
further survival advantage conferred by the
presence of an AAA. Conservative treatment such as amnioreduction and septostomy are favored for early stage disease. In
advanced disease, with a <50% probability
of survival of one or both twins, selective
laser or cord ligation confer better outcomes.
With all treatment modalities, timely intervention in a tertiary referral center that routinely undertakes these procedures is essential.

Acknowledgments
We acknowledge programme funding for
our work on twintwin transfusion syndrome from the Richard and Jack Wiseman
Trust.

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