Original Paper

Fetal Diagn Ther 2012;31:30–34 Received: January 6, 2011

Accepted after revision: June 24, 2011
DOI: 10.1159/000330369
Published online: December 9, 2011

Fetoscopic Laser Surgery for

Twin-to-Twin Transfusion Syndrome
after 26 Weeks of Gestation
Dan V. Valsky a, b Elisenda Eixarch a Josep M. Martinez-Crespo a
Emilia-Ruthy Acosta a Liesbeth Lewi c Jan Deprest c Eduard Gratacós a
a
Department of Maternal-Fetal Medicine (Institut Clínic de Ginecologia, Obstetrícia i Neonatologia), Hospital
Clinic-IDIBAPS, University of Barcelona, and Centro de Investigación Biomédica en Red en Enfermedades Raras
(CIBER-ER), Barcelona, Spain; b Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical
Centers, Mt. Scopus, Jerusalem, Israel; c Department of Obstetrics and Gynecology, University Hospitals Leuven,
Leuven, Belgium

Key Words
Fetal therapy ⴢ Twin-to-twin transfusion syndrome ⴢ
Monochorionic twins ⴢ Laser ablation of anastomoses ⴢ
Fetoscopy complications
Abstract
Objective: To compare the outcomes of twin-to-twin trans-
fusion syndrome (TTTS) cases treated with fetoscopic laser
coagulation of vascular anastomoses before 25 + 6 weeks of
gestation and between 26 and 28 weeks of gestation. Mate-
rial and Methods: 28 consecutive cases of TTTS at Quintero
stages II–IV treated with laser therapy between 26 + 0 and
28 + 6 weeks of gestation were compared with 324 cases
treated between 15 + 0 and 25 + 6 weeks during a 3-year
period in two centers. The following data were recorded and
compared: duration of the fetoscopy, rate of complications
(preterm labor before 28 weeks and before 32 weeks, cho-
rioamnionitis, twin anemia-polycythemia syndrome and re-
current TTTS), gestational age at delivery and neonatal sur-
vival rate. Results: The study groups were similar as regards
Quintero staging and the frequency of anterior placental lo-
cation (50.0 vs. 47.8%, p = 0.85 in late and conventional laser,
respectively). There were no significant differences in the du-
ration of surgery (29 vs. 30, p = 0.27, respectively) and in the
rates of any of the complications evaluated. Gestational age
at delivery (33 vs. 33.3 weeks, p = 0.69) and neonatal survival
of at least one fetus (92.3 vs. 88.6%, p = 0.24) were also simi-
lar. Conclusion: Fetoscopic laser coagulation for TTTS per-
formed between 26 + 0 and 28 + 6 weeks of gestation was
associated with similar outcomes as those observed in cases
treated before 26 weeks. Copyright © 2011 S. Karger AG, Basel
Introduction
Twin-to-twin transfusion syndrome (TTTS) affects
10–15% of all MC pregnancies [1]. The syndrome results
from a chronic unbalance in intertwin blood volume ex-
change through the ever present anastomoses in the
monochorionic placenta, and if left untreated mortality
rates approach 100% [2]. The first-line treatment of severe
TTTS between 16 and 26 weeks is fetoscopic laser photo-
coagulation of placental anastomoses, which is associated
with reported survival rates for at least one twin ranging
75–85% [3, 4].

© 2011 S. Karger AG, Basel Eduard Gratacós

1015–3837/12/0311–0030$38.00/0 Department of Maternal-Fetal Medicine (ICGON)
Fax +41 61 306 12 34 Hospital Clinic, Sabino de Arana 1
E-Mail karger@karger.ch Accessible online at: ES–08028 Barcelona (Spain)
www.karger.com www.karger.com/fdt Tel. +34 93 227 9946, E-Mail gratacos @ clinic.ub.es
 The appearance of TTTS beyond 26 weeks is rare but
possible and actually only very few cases after 25 weeks
have been reported in published series [1, 5, 6]. Histori-
cally laser therapy has been limited to 25 weeks and 6
days gestational age [3, 7, 8]. The original rationale behind
this limit was the invasive and (initially) experimental
nature of fetoscopic operations, which led to consider that
less-invasive therapeutic approaches, such as palliative
amnioreduction or even elective delivery, would be pref-
erable options once fetal viability was reached [9]. Almost
20 years after the first reports on fetoscopy for TTTS were
published, the procedure has gained wide acceptance and
there is good evidence that fetoscopy is generally a safe
procedure [3, 5, 10, 11]. In addition, the use of amniod-
rainage in TTTS is not devoid of complications [3, 12, 13]
and remains associated with a high rate of neurological
handicap in survivors of up to 29% [14], although it was
not separately evaluated for cases with late TTTS. Conse-
quently, an increasing number of fetoscopy centers have
introduced laser therapy for TTTS cases diagnosed be-
yond 26 weeks, particularly between 26 and 28 weeks.
However, there is still little evidence to support this prac-
tice. The rarity of TTTS after 26 weeks makes difficult for
single centers to make meaningful estimates. In a previ-
ous study, Middeldorp et al. [15] reported 10 patients
treated with laser therapy between 26 and 28 weeks of
gestation. The outcomes were compared with a similar
number of cases managed with amniodrainage. In spite
of the small size of the study, the outcomes reported were
similar to previous studies with either therapy conducted
at earlier gestational ages.
In this study, we report a consecutive group of 28 cas-
es of TTTS treated with laser coagulation between 26 + 0
and 28 + 6 weeks at two fetal therapy centers. Fetal ther-
apy was offered for those cases classified as Quintero
staging II–IV during the 3 years. We compared the surgi-
cal and pregnancy characteristics in these cases with
those of TTTS cases treated with laser earlier than 26
weeks during the same period.
Methods
The study group includes 28 cases of MC twin pregnancies
diagnosed as TTTS at Quintero stages II to IV, and treated by laser
ablation of inter-twin anastomoses after 26 + 0 weeks of gestation
in the period between December 2006 and December 2009 at
Hospital Clinic, Barcelona, Spain and the University Hospitals
Leuven, Belgium. The control group was composed by 324 MC
pregnancies treated during the same period by laser at gestation-
al age between 15 + 0 and 25 + 6 weeks. Gestational age was cal-
culated by last menstrual cycle and corrected by first trimester
Fetoscopic Laser Surgery for
Twin-to-Twin Transfusion Syndrome
ultrasound. The study was approved by the hospital Ethics Com-
mittee and patients provided written informed consent.
TTTS was defined according to the Eurofoetus criteria [9]. It
includes polyuric polyhydramnios in the recipient twin with the
deepest vertical amniotic fluid pocket of at least 8.0 cm before 20
weeks of gestation and 10.0 cm thereafter, together with oligohy-
dramnios in the donor twin with the deepest vertical amniotic
fluid pocket less than 2.0 cm and nonvisible bladder during most
of the examination. All cases were classified according to the se-
verity staging system proposed by Quintero et al. [16]. Exclusion
criteria were: (a) fetal death at diagnosis, (b) congenital malforma-
tions, and (c) chromosomal abnormalities.
Selective laser coagulation of the placental anastomoses on the
chorionic plate was performed as previously described [3] and in-
volved percutaneous insertion under local anesthesia of 1.2–2.0
mm endoscopes through operative trocars of 9–10 Fr, in the sac
of recipient fetus. Inter-twin anastomoses were identified and co-
agulated systematically along the inter-twin vascular equator
with a nontouch technique using a Nd/YAG or diode laser (30 W).
Amniotic fluid was drained subsequently until the deepest amni-
otic fluid pocket was below 8 cm on ultrasound examination. To-
colytic therapy (intravenous atosiban or presolat) was routinely
used in the late fetoscopy group, and was commenced before the
laser procedure.
After initial follow-up in the treatment center, patients were
referred back to their local physicians for further follow-up. In-
formation regarding pregnancy course and perinatal outcome
was retrieved prospectively in all cases from referring physicians
and patients, and written medical reports were available in most
cases. The following outcomes were considered in this study: du-
ration of surgery, preterm labor (PTL) ! 28 weeks and !32 weeks,
chorioamnionitis, recurrence of TTTS or development of twin
anemia-polycythemia syndrome, neonatal survival rate, gesta-
tional age at delivery and birth weight.
Statistical Analysis
Kruskal-Wallis test for independent samples and Fisher’s exact
test were used to compare quantitative and qualitative data with-
in the study group, respectively. All tests were two-tailed, and a
probability value of !0.05 was considered statistically significant.
Statistical calculations were performed using the Statistical Pack-
age for the Social Sciences (SPSS 15.0, SPSS Inc., Chicago, Ill.,
USA) software.
Results
Baseline characteristics, surgical data and clinical out-
come of the study groups are shown in table 1. The study
groups were similar in demographic parameters, distri-
bution of Quintero staging and frequency of anterior pla-
centa. The average difference in gestational age at therapy
was 6 weeks (26.3 weeks in cases vs. 20.3 weeks in con-
trols). Laser was successfully performed in all cases re-
ported in this study.
There were no significant differences in the duration
of surgery (29 vs. 30 min, p = 0.27 respectively), and in the
Fetal Diagn Ther 2012;31:30–34 31
 Table 1. Maternal characteristics, procedure data, surgical complications and perinatal outcome of the study
population treated by late laser between 26 + 0 and 28 + 6 weeks and before 26 + 0 weeks of gestation

Late laser group (n = 28) Early laser group (n = 324) p*

Maternal age, years 32.0 (21.0–42.9) 30.0 (17.3–47.0) 0.26

Nulliparity 64.3 (18) 50.9 (165) 0.24
Anterior placenta 50.0 (14) 47.8 (155) 0.85
GA at surgery, weeks 26.3 (26–29.3) 20.3 (15.3–25.6) 0.000
Cervical length, mm 20 (8–43) 34 (0–58) 0.001
TTTS stage
I – 16.4 (53) 1.34
II 35.7 (10) 34.8 (113) 2.79
III 53.6 (15) 41.7 (135) 1.02
IV 10.7 (3) 7.1 (23) 0.32
Length of surgery, min 29 (13–50) 30 (8–75) 0.27
Post-operative complicationsa 28.6 (8) 30.9 (100) 1.00
PTL <32 weeks 32.0 (8/25) 36.6 (82/232) 0.83*
PTL <28 weeks 24.0 (6/25) 14.7 (34/232) 0.81*
GA at delivery, weeks 33.0 (26.0–38.4) 33.3 (24.0–41.3) 0.69*
Donor weight at delivery, g 1,945 (460–2,730) 1,568 (200–3,645) 0.28*
Recipient weight at delivery, g 2,050 (750–3,040) 1,900 (235–3,800) 0.75*
Neonatal survival
At least one survivor 92.3 (24/26) 88.6 (273/308) 0.24
2 survivors 73.1 (19/26) 62.0 (191/308) 0.91
1 survivor 19.2 (5/26) 26.6 (82/308) 0.59
0 survivor 7.7 (2/26) 11.4 (35/308) 0.25

Results expressed as median (range) or percentage (number) as appropriate. GA = Gestational age.

* Miscarriages were excluded.
a Postoperative complications include: PTL <32 weeks, PPROM <32 weeks, chorioamnionitis, appearance of

twin anemia-polycytemia syndrome or recurrent TTTS.

rate of post-fetoscopy complications recorded (table  1).
There were no significant differences as well in terms of
neonatal survival of at least one fetus (92.3 vs. 88.6%, p =
0.24), gestational age at delivery (33.0 vs. 33.3 weeks, p =
0.69) and neonatal birth weight in late and conventional
laser groups, respectively (table 1).
Within the late laser group, there were no differences
in terms of placental location, Quintero stage, duration of
surgery and cervical length between cases with at least
one survivor and with no survivors.
Discussion
This study confirms and extends the results of previ-
ous reports [15] on fetoscopic laser ablation of inter-twin
anastomoses performed after 26 weeks of gestation. The
duration of fetoscopy, postoperative complications and
neonatal outcome in the late laser group were comparable
to those observed in TTTS cases treated before 26 weeks.
The control group of cases treated between 15 and 26
weeks of gestation in this study was comparable to previ-
ously published series in terms of gestational age at deliv-
ery, perinatal survival and rate of complications reported
[3, 4, 17]. The data support the notion that laser between
26 and 28 weeks of gestation is not associated with re-
markable differences in the rate of surgical and perinatal
complications, in comparison with laser ablation of anas-
tomoses performed earlier in pregnancy, although the
sample size may have prevented to observe significant
differences in some parameters.
The current case series including 28 cases had similar
outcomes to those described in the only previously pub-
lished report reporting the use of fetoscopic therapy after
26 weeks [15]. The outcome of 10 cases treated by late la-
ser was compared with 11 cases treated with amniodrain-
age. All infants treated by either therapy were born alive.
Neonates treated with fetoscopy had significantly longer

32 Fetal Diagn Ther 2012;31:30–34 Valsky /Eixarch /Martinez-Crespo /

     

Acosta /Lewi /Deprest /Gratacós

       
treatment-to-delivery interval (31 vs. 9 days, p = 0.07),
significantly lower rate of major neonatal morbidity (0 vs.
27%, p = 0.02) and lower neonatal death rate (0 vs. 14%,
p = 0.23) than infants treated with amnioreduction. Ges-
tational age at birth was 29 [27–36] vs. 31[28–37] weeks in
the amniodrainage and laser surgery groups, respectively
(p = 0.17).
A relatively more benign evolution of TTTS after 26
weeks, technical challenges and potential maternal risks
are commonly mentioned as potential concerns to offer-
ing laser therapy beyond 26 weeks. Concerning the se-
verity of the disease, a substantial number of cases with
mere amniotic fluid discordance are often misclassified
as ‘late’ TTTS and this contributes to the long-standing
confusion about the benign evolution of such cases. True
TTTS after 26 weeks is indeed uncommon and it nor-
mally contains a number of cases with earlier onset but
delayed diagnosis. However, once clear criteria are met,
progression to severe disease is the rule and there is a
high risk of neurologic sequellae, as a consequence of
hemodynamic disturbances and/or severe prematurity.
Concerning technical challenges, indeed fetoscopic laser
at late gestational ages is normally more difficult in rela-
tion with earlier procedures. The amniotic fluid is often
turbid, hampering identification of the placental anasto-
moses. The uterine cavity and placenta are larger, which
may require important displacements of the endoscope,
and the diameter of the anastomoses increases accord-
ingly, which may render some vessels difficult to coagu-
late and increase the risk of hemorrhagic accident. Not-
withstanding, the results of this and the previously pub-
lished series [15] support that in experienced hands laser
treatment is feasible, with risks similar to fetoscopic pro-
cedures performed earlier in pregnancy. Finally, the risks
of fetal interventions after viability is reached must cer-
tainly be weighed against the potential benefits. Deci-
sions have to be carefully considered and agreed with
parents. However, once a consensus on active manage-
ment is reached, laser represents an etiological therapy
and achieves a definitive treatment with prolongation of
pregnancy. In addition, amniodrainage may offer clini-
cians a false reassuring impression of a low-risk associ-
ated procedure. However, in a large case series reported
by Mari et al. [13], the overall procedure-associated risk
of amniodrainage was 15% per procedure, including
bleeding, abruption placenta, chorioamnionitis, fetal
distress and fetal death in the infants who survived to 4
weeks after birth [13].
This study has several limitations. The small number
of cases of TTTS in later stages of pregnancy renders
Fetoscopic Laser Surgery for
Twin-to-Twin Transfusion Syndrome
gathering large sample sizes difficult. Although this case
series is the largest reported so far, sample size remains
limited to demonstrate statistical significance for small
differences if these existed. We acknowledge that the con-
trol group chosen for comparison is not ideal, since dis-
ease evolution could be different in early and late TTTS
cases. To compensate for this and ensure selection of cas-
es with clear disease progression, we selected only Quin-
tero stages II to IV. We acknowledge that a clinical trial
of late TTTS cases would be desirable to define the best
therapeutic approach, but such a trial does not seem real-
istic or is at best very difficult in view of the rarity of the
disease, clinical variability and parent’s preferences in re-
lation with management options. Ideally, international
registries or ad hoc studies with sufficient number of cen-
ters would help to add further evidence as to the safety
and perinatal outcomes with different therapy options,
although comparison between studies will always remain
limited by selection bias.
In conclusion, fetoscopic laser performed between 26
+ 0 and 28 + 6 weeks of gestation had comparable out-
comes to those observed in TTTS cases treated before 26
weeks. From a clinical perspective, the decision about the
type of management in TTTS diagnosed between 26 and
28 weeks will always depend on a combination of factors,
including technical issues, parental wishes and coexis-
tence of obstetric or fetal complications, for instance se-
lective intrauterine growth restriction. However, in se-
lected cases of severe TTTS with clearly progressive dis-
ease, it may seem reasonable to offer laser as a first line
option.
References 1 Lewi L, Jani J, Blickstein I, Huber A, Guc-
ciardo L, Van Mieghem T, Doné E, Boes AS,
Hecher K, Gratacós E, Lewi P, Deprest J: The
outcome of monochorionic diamniotic twin
gestations in the era of invasive fetal therapy:
a prospective cohort study. Am J Obstet Gy-
necol 2008;199:514.
2 Haverkamp F, Lex C, Hanisch C, Fahnen-
stich H, Zerres K: Neurodevelopmental risks
in twin-to-twin transfusion syndrome: pre-
liminary findings. Eur J Paediatr Neurol
2001;5:21–27.
3 Senat MV, Deprest J, Boulvain M, Paupe A,
Winer N, Ville Y: Endoscopic laser surgery
versus serial amnioreduction for severe
twin-to-twin transfusion syndrome. N Engl
J Med 2004;351:136–144.
4 Roberts D, Gates S, Kilby M, Neilson JP: In-
terventions for twin-twin transfusion syn-
drome: a Cochrane review. Ultrasound Ob-
stet Gynecol 2008;31:701–711.
Fetal Diagn Ther 2012;31:30–34 33
5 Quintero RA, Dickinson JE, Morales WJ,
Bornick PW, Bermúdez C, Cincotta R, Chan
FY, Allen MH: Stage-based treatment of
twin-twin transfusion syndrome. Am J Ob-
stet Gynecol 2003;188:1333–1340.
6 Ville Y, Hecher K, Gagnon A, Sebire N, Hyett
J, Nicolaides K: Endoscopic laser coagulation
in the management of severe twin-to-twin
transfusion syndrome. Br J Obstet Gynaecol
1998;105:446–453.
7 Crombleholme TM, Shera D, Lee H, et al: A
prospective, randomized, multicenter trial
of amnioreduction vs selective fetoscopic la-
ser photocoagulation for the treatment of se-
vere twin-twin transfusion syndrome. Am J
Obstet Gynecol 2007;197:396.
8 Hecher K, Diehl W, Zikulnig L, Vetter M,
Hackelöer BJ: Endoscopic laser coagulation
of placental anastomoses in 200 pregnancies
with severe mid-trimester twin-to-twin
transfusion syndrome. Eur J Obstet Gynecol
Reprod Biol 2000; 92:135–139.
34 Fetal Diagn Ther 2012;31:30–34
9 Gratacos E, Deprest J: Current experience
with fetoscopy and the Eurofoetus registry
for fetoscopic procedures. Eur J Obstet Gy-
necol Reprod Biol 2000; 92:151–159.
10 Huber A, Diehl W, Bregenzer T, Hackeloer
BJ, Hecher K: Stage-related outcome in twin-
twin transfusion syndrome treated by feto-
scopic laser coagulation. Obstet Gynecol
2006;108:333–337.
11 Middeldorp JM, Sueters M, Lopriore E, et al:
Fetoscopic laser surgery in 100 pregnancies
with severe twin-to-twin transfusion syn-
drome in the Netherlands. Fetal Diagn Ther
2007;22:190–194.
12 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 1999;180:717–724.
13 Mari G, Roberts A, Detti L, Kovanci E, Stefos
T, Bahado-Singh RO, Deter RL, Fisk NM:
Perinatal morbidity and mortality rates in
severe twin-twin transfusion syndrome: re-
sults of the International Amnioreduction
Registry. Am J Obstet Gynecol 2001; 185:
708–715.
14 Rossi AC, D’Addario V: Laser therapy and se-
rial amnioreduction as treatment for twin-
twin transfusion syndrome: a meta-analysis
and review of literature. Am J Obstet Gyne-
col 2008;198:147–152.
15 Middeldorp JM, Lopriore E, Sueters M,
Klumper FJ, Kanhai HH, Vandenbussche FP,
Oepkes D: Twin-to-twin transfusion syn-
drome after 26 weeks of gestation: is there a
role for fetoscopic laser surgery? BJOG 2007;
114:694–698.
16 Quintero RA, Morales WJ, Allen MH, Bor-
nick PW, Johnson PK, Kruger M: Staging of
twin-twin transfusion syndrome. J Perinatol
1999;19:550–555.
17 Rossi AC, D’Addario V: Comparison of do-
nor and recipient outcomes following laser
therapy performed for twin-twin transfu-
sion syndrome: a meta-analysis and review
of literature. Am J Perinatol 2009;26:27–32.
Valsky /Eixarch /Martinez-Crespo /
Acosta /Lewi /Deprest /Gratacós