CONTEMPORARY EVALUATION AND MANAGEMENT
OF TWIN-TWIN TRANSFUSION SYNDROME*
Stephen R. Carr and Michael P. Plevyak
Division of Maternal-Fetal Medicine and
Program in Fetal Medicine
Brown Medical School and Women & Infants' Hospital of Rhode
*Reproduced with permission
from Medicine & Health/Rhode Island 2001;84:165-168.
The May 2001 issue of this journal was published
in conjuction with the 2nd Annual Frank G. DeLuca Lectureship
in Pediatric Surgical Sciences, entitled "The Smallest Patient:
Foundations in Fetal Medicine," organized by the Brown Medical
School Program in Fetal Medicine
Twinning rates vary by
twin type and location throughout the world. The rate of monozygotic
twinning is quite constant worldwide at 3.5/1000 deliveries while
dizygotic twinning rates range from 49/1000 deliveries in Nigerian
populations to 1.3/1000 deliveries in Japanese populations. Thirty
per cent of monozygotic twins result from division of the embryo
within the first 72 hours after fertilization and result in monochorionic-diamniotic
twins. These are the twins that are at risk for twin-twin transfusion
syndrome. Twin pregnancies evidence greater morbidity and mortality
than do singleton pregnancies, and among twin pregnancies monozygotic
twins have greater morbidity and mortality than do dizygotic
twins. The morbidities seen more commonly in monochorionic twins
include structural defects and twin-twin transfusion. Twin-twin
transfusion syndrome (TTTS) is the consequence of unbalanced
blood flow from one twin (the donor) to the other (the recipient)
across transplacental vascular communications and results in
the polyhydramnios/ oligo- hydramnios sequence and can include
growth discordance. These vascular communications (of which there
are four types) are present in nearly 100% of monochorionic twins
but occur only rarely in dichorionic twins.[1, 2] The diagnosis
of TTTS has in the past been based on neonatal findings, but
these findings are unreliable for the prenatal detection of the
syndrome. Current strategies use ultrasound to determine both
the presence and severity of prenatally diagnosed TTTS. Table
1 is a list of the salient points in ultrasound diagnosis of
Monochorionic twin gestation
1. Twins of same gender
2. Thin inter-twin membrane
3. Single placenta
B. Discordance in amniotic fluid volume
1. "Donor" twin with decreased fluid (deepest vertical
pocket < 2.0 cm is consistent with severe TTTS).
2. "Recipient" twin with increased amniotic fluid volume
(deepest vertical pocket > 8.0 cm is consistent with severe
C. Other ultrasound findings
1. Appearance of a "stuck" twin that does not change
intrauterine position regardless of maternal position.
2. Small or non-visualized bladder in the "donor" twin
3. Large bladder in the recipient twin
4. Abnormal Doppler findings
a. pulsatile umbilical venous blood flow
b. absent or reversed end-diastolic umbilical arterial blood
c. tricuspid valve regurgitation.
5. Hydrops: ascites, pleural or epicardial effusions
Table 1. Ultrasound
diagnosis of twin-twin transfusion syndrome (TTTS)
Once diagnosed, untreated
TTTS results in morbidity and mortality that exceeds 70%.
Despite enthusiasm for different modalities, treatment of TTTS
is associated with survival rates of only 60-70%. Even more troubling
is the increased incidence of cerebral palsy and other cerebral
impairment (from 20-40%) in the surviving co-twin when one of
a set of monochorionic twins dies in utero.[4, 5] Several treatment
modalities have been used to treat TTTS. Those receiving the
most attention include serial amnioreduction, septostomy, and
fetoscopic laser ablation of chorioangiopagus vessels (FLOC).
Amnioreduction is the
removal of large quantities of amniotic fluid from the polyhydramniotic
sac of the recipient twin. This is accomplished using an 18 or
20 gauge needle under ultrasound guidance and is performed from
one to several times. Although amnioreduction does not address
the postulated cause of TTTS, it is postulated to result in decreased
pressure on the transplacental vascular anastamoses, which increases
placental compliance, thus reducing the preload and afterload
in the hearts of both twins. The reduction in intrauterine
volume also appears to decrease the incidence of preterm labor,
a major contributor to the morbidity of TTTS. Proponents of amnioreduction
point to it's simplicity and success rates; one recent trial
of aggressive amnioreduction reported 57% survival of both twins
at 24 months of age and 70% survival at 24 months of age of at
least one twin. Preterm premature rupture of membranes complicates
8% of pregnancies treated with serial amnioreduction.
creation of a defect in the membrane separating the two twins)
has been proposed as a method to equalize the pressures in the
twins' amniotic sacs. In this technique a 20 or 22 gauge needle
is introduced to the uterine cavity using ultrasound guidance
in such a way as to deliberately breach the amniotic membrane
overlying the smaller oligohydramniotic sac. A recent study of
12 patients with severe TTTS treated with intentional septostomy
yielded 75% survival of both twins to delivery and 92% survival
of at least one twin. The authors, and others, postulate that
deliberate septostomy results in an equilibration of amniotic
fluid volumes around both twins as a result of hydrostatic pressure
differences between the sacs that may be too small to measure.
As in amnioreduction this technique does not directly address
the postulated cause of TTTS, the transplacental vascular anastamoses,
but offers temporizing measures in an attempt to prolong the
pregnancy to the point where survival ex utero is possible.
LASER ABLATION OF CHORIOANGIOPUS VESSELS (FLOC)
Fetoscopic laser ablation
of chorioangiopagus vessels (FLOC) is the only proposed intervention
for TTTS that directly addresses the postulated etiology of TTTS,
that is, the transplacental vascular communications. This technique,
first described by De Lia et al, uses a fetoscopically-directed
YAG-neodynium laser to photocoagulate those transplacental vascular
communications felt to be contributing to the TTTS. Initial use
of this technology involved ablation of all vessels crossing
the vascular equator of the placenta, but more recently there
has been more selective ablation involving only those vessels
thought to be contributing to the TTTS. Data from recent series
indicate 69% survival of both twins, 82% survival of at least
one twin, and 4.3% significant handicap in survivors of an in-utero
least 1 survivor
brain scan survivor(s)
Birth weight (donor)
Birth weight (recipient)
Comparison of FLOC and amnioreduction.
Direct comparison of
the efficacy of the different available interventions has not
been accomplished. Comparisons extant in the TTTS literature
typically compare case series using one intervention with case
series using a different intervention. One such recent comparison
 compared outcomes in 73 cases of severe TTTS treated with
FLOC in one center with 43 cases of severe TTTS treated with
serial amnioreduction in another center. (Table 2; * denotes
p < 0.05)
There are currently two randomized trials underway in attempts
to determine the most effective intervention for treatment of
TTTS. One is the EUROFETUS consortium (www.eurofetus.org) that
randomizes cases diagnosed with severe TTTS between serial amnioreduction
and FLOC. The other trial is coordinated at the University of
North Carolina  and is randomizing between serial amnioreduction
and septostomy. The relatively infrequent nature of severe TTTS
cases near any one center, and the (usually) strongly held opinions
of a given treatment team has rendered recruitment into these
trials more time-consuming than might have been originally anticipated.
Timing the intervention is of paramount importance in the treatment
of TTTS. As in any medical procedure, the risks of the procedure
itself must be weighed against the risk of the disease that is
being treated. The known risks of any of the interventions for
TTTS (preterm premature rupture of membranes, infection, preterm
labor, placental abruption, hemorrhage and fetal death) must
be acknowledged in deciding when to intervene. Quintero et al
 presented a classification schema based on their experience
(Table 3.) The group recently published their results following
FLOC using their staging schema. (Table 4.)
Consideration of the
morbidity following diagnosis and treatment of TTTS is of equal
importance to survival. In cases of TTTS treated with serial
amnioreduction that are complicated by in-utero demise of one
twin, neurological handicap is seen in approximately 30% of survivors
. Cases of TTTS treated with FLOC that are complicated by
in-utero demise of one twin experience neurological handicap
in 4.2%  (compared with the 18% incidence of neurological
handicap seen in singleton survivors following serial amnioreduction..
Taken at face value, these data suggest that while overall survival
appears to differ little between the different interventions,
there is a lesser risk of neurologic morbidity in survivors following
FLOC than in survivors following serial amnioreduction.
There have also been reports of limb reduction anomalies and
intestinal atresia associated with TTTS. Table 5 summarizes published
cases of structural anomalies associated with monochorionic twinning.
The etiology of these defects remains unclear. Hecher et al 
suggested that polycythemia and an arterial steal syndrome were
the probable etiology of necrotic toes detected prior to FLOC
for severe TTTS. Margono et al  suggested that their findings
of thrombosis of the transplacental vascular connections and
necrosis of the right foot of the surviving twin were consistent
with a thromboembolic phenomenon. Lundvall et al  found necrosis
in the right lower leg of the recipient twin 27 days after FLOC.
Post mortem examination found a thrombus in the right common
iliac artery, "presumably the result of polycythemia".
Scott and Evans  documented a case of severe TTTS managed
with serial amnioreduction that resulted in 2 live twins. At
time of delivery the recipient twin was found to have left lower
leg necrosis that was associated with polycythemia (Hb 26.8 g/dL,
Ht 89%). The authors concluded that the necrosis was the result
of hyperviscosity due to polycythemia. Dawkins et al  reported
a pregnancy with severe TTTS managed with amnioreduction x 6
over a nine week period. Delivery was at 32 weeks. The recipient
twin was born with Hb 25.9 g/dL, Ht 72% and gangrene of the left
lower leg. Arul et al  presented two cases of severe TTTS
treated with FLOC. In both cases there was demise of the donor
twin and in both survivors ileal atresia was noted after birth.
The authors suggest three possible etiologies for these findings:
hypoperfusion or hyperviscosity associated with TTTS could cause
mesenteric ischemia; death of the donor could affect the hemodynamics
of the survivor, causing mesenteric hypoperfusion; a shower of
emboli or thromboplastins could be released into the fetal circulation.
Van Allen et al  described two sets of monochorionic twins.
The first case documented a singleton demise at 12 weeks EGA.
At birth the surviving twin had cleft lip and palate and terminal
limb reduction with ring constrictions of the left hand and both
feet. In the other case singleton demise was documented at 18
weeks EGA. At birth the survivor was found to have ring constrictions
of the left hand digits and left big toe. There was no evidence
of amniotic bands in either case. The authors suggest that these
findings were the result of vascular disruption in the co-twin.
In our case TTTS was first diagnosed at 14 weeks and was treated
with serial amnioreduction x 7. FLOC was performed at 23+ weeks
EGA. Preterm premature rupture of membranes occurred at 26+ weeks
EGA and cesarean delivery was at 28+ weeks. At time of delivery
necrosis of the left lower extremity of the recipient was seen.
The toe-heel length of the necrotic limb of 3.2 cm is consistent
with 19 weeks 4 days gestation, which is prior to either the
FLOC or the amnioreductions. Polycythemia was not universally
seen in these cases, but is the most common finding among these
pregnancies with severe TTTS affected with structural anomalies.
Polycythemia could result from the elevated atrial natriuretic
protein found in recipient twins and the resulting diuresis,
and would lead to hyperviscosity. This hyperviscosity would result
in greater incidence of thrombosis. It remains unclear why the
lower extremities are more affected by such a thrombotic diathesis.
Monochorionic twins present
unique challenges above and beyond those associated with multiple
gestation. There have been several developments in the evaluation
and treatment of twin-twin transfusion syndrome, but these twins
remain at high risk. In spite of these advances, these twins
are at continued risk for anomalies that appear to result from
hypoperfusion. These anomalies have been seen in monochorionic
twins that have undergone serial amnioreductions, FLOC or no
intervention at all. This suggests that the tendency towards
these defects is intrinsic to monochorionic twins suffering from
TTTS, and is not related to the interventions that have been
used in attempts to mitigate the impact of TTTS. The care of
monoamniotic twins affected by TTTS continues to require coordinated
care by a team of highly trained individuals.
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