Eurofetus 2004.

Methods	Type of study: randomised controlled trial. Method of treatment allocation: computer‐generated random sequence with randomisation allocated by a web‐based system. Stratification: none stated. Sample size calculation: yes. Intention‐to‐treat analyses: yes. Losses to follow‐up: no. Funding: Biology, Medicine and Development contract, European Commission, Flemish Government, French Direction de la Recherche Clinique and the 5th framework Program of the European Commission.
Participants	Location: 6 countries, 122 women from France, 13 from Belgium, 3 from the Netherlands, 2 from Switzerland, 1 from Italy and 1 from the United States. Timeframe: January 1999 to March 2002. Inclusion criteria: women presenting between 15 and 26 weeks with polyuric polyhydramnios in the recipient twin, with a vertical pool of 8 cm at or before 20 weeks or 10 cm after 20 weeks with a distended fetal bladder. Oliguric oligohydramnios in the donor twin with a deepest pool measuring 2 cm. Exclusion criteria: fetal death, major fetal anomaly, ruptured membranes, maternal condition requiring delivery, and any previous invasive therapy for the syndrome. Total recruited: 142 women and 284 fetuses in both arms.
Interventions	Fetoscopic laser coagulation of vessels crossing the membranes. Amniotic fluid was drained through the cannula until the deepest pool was 5‐6 cm on ultrasonography. Amnioreduction of the polyhydramniotic sac under local analgesia, with an 18‐gauge needle and either syringe aspiration or wall suction. Amniotic fluid was drained until the deepest pool was 5‐6 cm. Amnioreduction was repeated whenever polyhydramnios recurred. Prophylactic tocolytics and antibiotics administered prophylactically. Women kept in hospital for 24‐48 hours after the procedure, then seen weekly for ultrasound follow‐up.
Outcomes	Primary outcomes: perinatal survival of at least 1 twin, survival of at least 1 twin to 7‐12 months and neurologic complications at 7‐12 months of age. Other outcomes: maternal complications (placental abruption, intra‐abdominal haemorrhage, or leakage of amniotic fluid with peritoneal irritation, chorioamnionitis, amniotic fluid embolus) and fetal complications.
Notes	Interim analyses: 2 planned (after the inclusion of 72 and 144 women) to evaluate the rates of survival of at least one twin to discharge from NICU ‐ an end point considered more clinically relevant than survival at 28 days. First interim analysis did not reveal any differences between the groups. The second showed a significantly higher rate of survival of at least one twin to discharge from NICU, so the trial was stopped according to the O'Brien‐Fleming stopping rule for discontinuing enrolment.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random sequence with randomisation allocated by a web‐based system.
Allocation concealment (selection bias)	Low risk	Computer‐generated random sequence with randomisation allocated by a web‐based system.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"For practical reasons the treating perinatologist was not blinded to therapy", however, the main survival outcomes are not likely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Outcomes were assigned by one neonatologist who had no knowledge of the assigned treatment."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Intention‐to‐treat analyses: yes. Losses to follow‐up: no.
Selective reporting (reporting bias)	Low risk	All pre‐specified outcomes reported.
Other bias	Low risk	This trial was stopped after the second interim analysis showed a higher rate of survival of at least one twin in the laser arm. The trial quoted the O'Brien‐Fleming rule for stopping.