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Do We Know How To Effectively Treat Twin-Twin Transfusion
Syndrome?
T.M. Crombleholme
The Center for Fetal Diagnosis and Treatment at The Children's Hospital of Philadelphia and the University of
Pennsylvania School of Medicine, Philadelphia, PA, U.S.A.
The natural history of severe TTTS is well established with mortality approaching 100% if left
untreated, especially when it presents at less than 20 weeks' gestation (1-3). As a result,
numerous treatments have been proposed including selective fetocide, cord coagulation, sectio
parva, placental blood letting, maternal digitalis, indocin, serial amnioreduction,
microseptostomy of the intertwin membrane, and nonselective or selective fetoscopic laser
photocoagulation. However, in the United States serial amnioreduction has been the standard
therapy of TTTS.
Amnioreduction was first employed as a means to control polyhydramnios in the hope of
prolonging the pregnancy (4). In uncontrolled series, serial amnioreduction appeared to improve
survival. Moise, in a review of 26 reports dating from the 1930s of 252 fetuses, found an overall
survival of 49% (5). However, the survival in more recent series with more consistently
aggressive serial amnioreduction to reduce amniotic fluid volume to normal have ranged widely
from as low as 37% to as high as 83% (1,6,7). However, these retrospective series are comprised
of small numbers of patients from a range of gestational ages as well as a broad spectrum of
severity of TTTS. The severity of TTTS clearly varies with the gestation age at which it presents,
and this may have a profound impact on the observed mortality with any treatment strategy
employed. The earlier in gestation TTTS presents the worse the prognosis and, conversely, the
later in gestation TTTS presents the better the prognosis as data from the Amnioreduction
Registry shows (7). Experience with patients presenting with advanced TTTS prior to 22 weeks
gestation and absent end diastolic flow in the recipient umbilical artery, survival with aggressive
serial amnioreduction was only 13% and with absent end diastolic flow in the donor umbilical
artery was 33% (8).
The paradoxical resolution of oligohydramnios after a single amnioreduction was first suggested
by Saade to be due to puncture of the intertwin membrane(8). This intertwin septostomy was
proposed as a treatment for TTTS to restore amniotic fluid dynamics without the need for
repeated amnioreduction. In a small multicenter series of 12 patients, Moise et al., reported an
81% survival with microseptostomy(9). One objection to this approach is the possibility it would
result in a large septostomy creating an essentially monoamniotic sac with the attendent risk of
cord entanglement (10). For this reason, a "microseptostomy" has been proposed to prevent this
complication. However, not only was the series small and uncontrolled, there was no report of
neurologic or cardiac morbidity. In a direct comparison, albiet a small retrospecitve single
institution series, of serial amnioreduction vs microseptostomy Johnson et al observed no
survival advantage with either therapy (11). But microseptostomy did appear to prolong
pregnancy compared to amnioreduction. In our experience with microseptostomy performed in
severe TTTS presenting prior to 20 weeks gestation this treatment was able to restore amniotic
fluid dynamics in almost every case. However, in two thirds of the cases there was hemodynamic
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evidence of progression of TTTS necessitating either fetoscopic cord coagulation or selective
fetoscopic laser photocoagulation to salvage the twins.
The first treatment for TTTS that attempted to treat the underlying chorioangiopagus was
reported by DeLia et al (12,13). Fetoscopic laser was used to photocoagulate vessels crossing the
intertwin membrane. In the first series of cases of TTTS, DeLia reported a survival of 53% in 26
patients (12). While survival was not significantly better than previous reports with serial
amnioreduction, the neurologic outcome was: 96% of survivors had normal neurologic outcome.
Other groups from Europe have reported similar survival with fetoscopic laser photocoagulation.
Ville et al, reported 53% survival with a non-selective laser technique which was better than the
survival observed with historical controls at the same center with serial amnioreduction (37%)
(13). There also appeared to be an improved neurologic outcome in fetuses treated by laser. Nonselective fetoscopic laser photocoagulation of all vessels crossing the intertwin membrane may
be problematic as the intertwin membrane often bares no relation to the vascular equator of the
placenta. This may result in sacrifice of vessels not responsible for the TTTS, resulting in a
higher death rate of the donor twin from acute placental insufficiency. More recently a selective
laser photocoagulation technique has been reported with survival of 73% (14). The selective
technique does not photocoagulate every vessel crossing the intertwin membrane, but only direct,
arterial-arterial and veno-venous, connections are photocoagulated along with any unpaired
artery going to a cotyledon with the corresponding vein (and vice versa) going to the opposite
umbilical cord. In a non-randomized comparison of patients treated by serial amnioreduction at
one center and selective laser photocoagulation at another the overall survival was not
statistically significantly different (61% for laser vs 51% for serial amnioreduction) (15).
However the survival of at least one twin with laser photocoagulation was 79% while survival of
at least one twin with serial amnioreduction was only 60% (15). Unfortunately, this was not a
controlled trial and patients were not randomized.
While much attention has focused on the effect of treatment on survival in TTTS the morbidity
among survivors has been under appreciated. Among the most important is the severe neurologic
morbidity that is observed in 18-26% of survivors (12-15). Due to the shared placental
circulation, with death of one co-twin an acute fall in blood pressure may cause the placental
resistance to fall resulting in decrease in the cerebral perfusion pressure and ischemic injury to
the brain of the other twin. Brain injury can occur in TTTS even in the absence of co-twin
demise, however (7). The incidence of neurologic injury with serial amnioreduction varies from
18% to 26%. In contrast, fetoscopic laser photocoagulation has demonstrated lower incidence of
neurologic morbidity (defined as sonographic abnormality) of 4-6% (12-15). However, none of
these abnormal ultrasound findings have been correlated with long-term neurodevelopmental
outcome. In addition, because ultrasounds may not be obtained in the immediate postnatal
period, it is not possible to determine if the neurologic morbidity is due to events in utero or due
to perinatal or postnatal events in this high risk group of premature infants. Long-term
neurologic outcome in TTTS has never been evaluated.
All of the treatments discussed above have anecdotal evidence suggesting that they improve
survival in TTTS. It is not clear which therapy is best under what circumstances. In most centers
the current standard of care in the United States is serial amnioreduction. Microseptostomy is
practiced by few and a prospective study has yet to be completed evaluating its efficacy.
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Fetoscopic laser photocoagulation is available in only a few centers and the lack of controlled
trials has limited enthusiasm for this more invasive therapy.
At present it is not known which therapy for TTTS is best for specific patients, for either survival
or neurodevelopmental outcome. Crombleholme et al, have begun an NIH sponsored multicenter
prospective randomized controlled trial comparing aggressive serial amnioreduction with
selective fetoscopic laser photocoagulation for severe twin-twin transfusion syndrome presenting
prior to 22 weeks gestation. It is hoped that this controlled trial will address many of the
questions that remain unanswered about the treatment of severe TTTS (16).
References
1.
Cheung VY, Becking AD, Dasilva OP: Preterm discordant twins: what birth weight
difference is significant? Am J Obstet Gynecol 172: 955-959, 1995
2.
Weir PE, Ratten GJ, Beischer NA: Acute polyhydramnios- a complication of
monozygous twin pregnancy. Br J Obstet Gynaecol 86: 849-853, 1979
3.
Saade GR, Ludomirsky A, Fisk NM: Feto-fetal transfusion. In Fetal Therapy Invasive
and transplacental. Fisk NM, Moise KJ Jr (ed). Cambridge University Press, Cambridge
UK, pp 225-251, 1997
4.
Moise KJ Jr: Polyhydramnios: problems and treatment. Semin Perinatol 17: 197-209,
1993
5.
Rodestal A, Thomassen PA: Acute polyhydramnios in twin pregnancy. A retrospective
study with special reference to therapeutic amniocentesis. Acta Obstetricia et
Gynecologica Scandinavic 69: 297-300, 1990
6.
Urig MA, Clewell WH, Elliott J: Twin-twin transfusion syndrome. Am J Obstet Gynecol
163: 1522-1526, 1990
7.
Mari G, Roberts A, Detti L, Kovanci E, Deter RL, Fisk NM: Perinatal morbidity and
mortality in severe twin-twin transfusion syndrome: results of the international
amnioreduction registry. (in press)
8.
Saade GR, Olson G, Belfort MA, Moise KJ: Amniotomy: a new approach to the “stuck
twin” syndrome. Am J Obstet Gynecol 172: 429-434, 1995
9.
Saade GR, Belfort MA, Berry DL, Bori T-H, Montgomery LD, Johnson A, D’Day M,
Olson GL, Lindholm H, Garoff L, Maise KJ Jr. Amniotic septostomy for the treatment of
twin oligohydramnios-polyhydramnios sequence. Fetal Diagn Ther 13: 86-93, 1998
10.
Feldman DM, Odibo A, Campbell WA, Rodis JF: Iatrogenic monoamniotic twins as a
complication of therapeutic amniocentesis. Obstet Gynecol 91: 815-816, 1998
11.
Johnson JR, Rossi KQ, O'Shaughnessy RW: Amnioreduction versus septostomy in twintwin transfusion syndrome. Am J Obstet Gynecol 185: 1044-1047, 2001
12.
De Lia JE, Kuhlmann RS, Harstad TW, Cruikshank DP: Fetoscopic laser ablation of
placental vessels in severe twin-twin transfusion syndrome. Am J Obstet Gynecol 172:
1202-1211, 1995
13.
Ville Y, Hyett J, Hecher K, Nicolaides KH: Preliminary experience with endoscopic laser
surgery for severe twin-twin transfusion syndrome. N Engl J Med 332: 224-227, 1995
14.
Quintero RA, Morales WJ, Mendoza G, Allen M, Lalter C, Giannina G, Angel JL:
Selective photocoagulation of placental vessels in twin-twin transfusion syndrome:
Evaluation of a surgical technique. Obstet Gynecol Survey 53: 597-603, 1998
15.
Hecher K, Plath H, Bregenzer T, Hansmann M, Hackeloer BJ: Endoscopic laser surgery
versus serial amniocenteses in the treatment of severe twin-twin transfusion syndrome.
Am J Obstet Gynecol 180: 717-724, 1999
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16.
Crombleholme TM, et al: Twin-Twin Transfusion Syndrome Trial 1RO1-HD41149-01