Randomized Controlled Trial Comparing a Conservative Management and Laser Surgery

Although we demonstrated the overall benefit of fetoscopic laser surgery as first-line
treatment in twin-twin transfusion syndrome (TTTS), indications in early stage TTTS are
controversial. Indeed, a conservative management with close follow-up is offered in some
centers as first-line management for QUINTERO stage 1 TTTS, although this strategy has not
been formally compared to first-line fetoscopic placental surgery. The objective of this
trial is to compare both strategies for patients with stage 1 TTTS and favorable obstetrical
parameters in an international randomized controlled trial. Patients randomized to a
conservative management will be followed on a weekly basis as long as the syndrome remains
stable using obstetrical and fetal parameters and until an adequate gestational age is
reached allowing delivery. Cases progressing to stage ≥ 2 or with a worsening of obstetrical
parameters during follow-up in this group will be actively treated by percutaneous laser
coagulation. Patients allocated to the "immediate laser" group will be treated by fetoscopic
laser surgery within 24 h following randomization. The primary end-point encompasses survival
and neurological morbidity at the age of 6 months for each foetus randomized. Analyses and
power computations use a cluster-trial methodology that accounts for the inter-twin
correlation, with many benefits over more traditional designs using a per-pregnancy outcome.
With proportions of 60% and 75% meaning a clinically relevant difference of 15% between the
groups, 200 fetuses or equivalently 100 pregnancies would be needed in each arm to reach a
power of 80% with an alpha-risk of 5%, allowing 2 interim analyses based upon LAN-DEMETS
boundaries and an O'Brien-Fleming function. Inclusion criteria, interventions and
randomisation were investigated through a preliminary survey across potential participating
centers. Based on this survey, it is anticipated that 3 years will be needed to achieve the
requested number of patients. This trial will answer an important question and will help in
the management and tailoring of surgical indications in stage 1 TTTS.

Inclusion Criteria:

- TTTS stage 1 (Euro foetus criteria)

- Gestational age > 16 and < 26 weeks

- Age > 18

- Informed consent

Exclusion Criteria:

- Therapeutic amniocentesis prior to referral

- Short cervix < 15 mm on transvaginal US

- Severe maternal discomfort:Dyspnea and orthopnea, Abdominal pain > 4 on a 10-level
visual analogic pain scale, Contractions > 1 per hour

- PPROM

- Fetal malformations unrelated to TTTS

- Follow-up is impossible