TTTS 1 trial: A cluster randomized controlled trial comparing a conservative management and primary laser surgery in stage 1 TTTS.

Giant leaps have been made in the last decades in the treatment of twin-to-twin
transfusion syndrome (TTTS). Overall, the emerging best first-line treatment of
severe TTTS is percutaneous laser surgery as demonstrated by the only completed
randomized controlled trial (RCT) so far in the field comparing laser surgery
to amnioreduction. Although these results were convincing as to the overall
superiority of laser over amnioreduction, indications for invasive treatment
may deserve refining.
There has been growing concerns that percutaneous laser surgery may not be
indicated in early or stage 1 TTTS. This idea arose from the belief that stage
1 TTTS may not warrant immediate invasive treatment and may just be followed
conservatively, thus reducing the iatrogenic complications of invasive therapy
in non-progressive disease as demonstrated by small retrospective studies of
early TTTS. However, advocates of immediate laser surgery would argue that
postponing surgery would increase the rates of spontaneous fetal demise and
secondary neurological morbidity, as well as preterm premature rupture of the
membranes (PPROM) and very preterm birth. Indeed, Quintero staging is not the
only potential prognostic factor after laser surgery and management should also
encompass gestational age at diagnosis and cervical length.

This study aims to compare two management strategies by an international
randomized controlled trial: the first relies on the overall conclusion from
the Eurofoetus trial and advocates immediate percutaneous fetoscopic surgery
for all stages of TTTS including stage 1 disease; the second is a conservative
strategy, in which patients are monitored weekly until delivery or until
progression warranting laser surgery. The primary end-point for this comparison
encompasses both survival and neurological morbidity in a composite outcome,
using a cluster-designed trial allowing the use of a per-fetus outcome rather
than a per-pregnancy outcome.

A multi- centre, randomized controlled trial.

Foetscopic laser treatment (percutaneous)

The potential benefits of conservative management is that some patients may not
require invasive laser- treatment. For patients randomized to primary laser,
they may benefit from definitive treatment of early TTTS avoiding progression
to more advanced stages of the syndrome.

The potential risks of conservative management are an increased risk of intra-
uterine fetal demise (IUFD), early rupture of membranes (PPROM), miscarriage
and preterm birth. The risk of progressive disease has been associated to a
worsening of overall pregnancy outcome. Progression rates are estimated between
30 and 45% in pregnancies managed conservatively. For patients randomized to
primary laser, the establishes risks encompass IUFD, PPROM, chorio- amnionitis,
preterm birth, placental abrubtion, miscarriage and surgical failure defined as
recurrence of TTTS or post- operative fetal anemia.