TRAP Intervention STudy: Early Versus Late Intervention for Twin Reversed Arterial Perfusion Sequence

The investigators propose to conduct a multi-center open-label randomized controlled trial
to assess if early intervention (12.0-14.0 weeks) (study group) improves the outcome of TRAP
sequence as compared to late intervention (16.0-19.0 weeks) (control group). The
investigators will randomly assign women diagnosed with TRAP sequence diagnosed between 11.6
and 13.6 weeks (1:1) to an early or late intervention group, using a web-based application
(www.sealedenvelope.com) with a computer-generated list with random permuted blocks of sizes
2 or 4, stratified by gestational age at inclusion (11.6 -12.6 weeks versus 13.0-13.6
weeks). Analysis will be by intention-to-treat. Outcome will be adjudicated blinded to group
allocation.

All interventions will be done under local anaesthesia and/or conscious sedation in sterile
conditions by an experienced operator. They must be performed within 1 week after
randomisation and at the latest at 14.0 weeks in the early group and 19.0 weeks in the late
group. In the early group, only intrafetal coagulation will be used. Intrafetal ablation
will be performed under ultrasound guidance using an 18-gauge (1.27 mm) to 20-gauge (0.91
mm) needle with a free-hand technique. The needle is introduced into the pelvis/abdomen of
the TRAP mass close to the intra-abdominal portion of the feeding vessel, while avoiding
puncture of the placenta and pump twin sac. The procedure is considered successful when
there is complete cessation of reverse flow into the TRAP mass on intraoperative color-flow
mapping.

In the late intervention/control group either intrafetal coagulation or fetoscopic laser
coagulation will be performed of the cord and/or anastomosing vessels, unless the flow has
stopped spontaneously or demise of the pump twin has occurred in the meantime. Intrafetal
coagulation is done as described above by using a 17-gauge (1.47 mm) to 20-gauge needle.
Alternatively, fetoscopic laser coagulation of the cord or anastomosing vessels can be
performed through a 17-gauge to 7 French trocar with 1-1,3 mm fetoscope and 400 μm laser
fiber. The rationale not to standardize the technique in the late intervention group is that
several techniques have been reported for treatment after 16 weeks without any significant
differences in outcome. Also, it is usual for the surgeon to adapt the technique to the
requirements of each individual case, e.g. for a posterior placenta, the surgeon may prefer
fetoscopic rather than intrafetal coagulation. Not restricting the technique to only 1
option will therefore more truly represent current practice and increase the
generalizability of the trial's findings.

Patients will be discharged the same day or 1 day after the procedure. Management and
follow-up will be similar for the study and the control or current practice group. A
follow-up scan is usually performed 1 week after the intervention to check for fetal
well-being and exclude anemia. A detailed ultrasound scan will be arranged in a fetal
medicine center at 20 and 30 weeks to assess the heart and brain anatomy. Some centers may
offer an MRI scan at around 30 weeks as part of the protocol for monochorionic twin
pregnancies that underwent an intrauterine intervention. Antenatal, peripartum and postnatal
care of the mother will be similar to that of a singleton pregnancy and at the discretion of
the referring physician. Intrauterine intervention for TRAP sequence is not an indication
for cesarean or elective preterm birth.

Inclusion Criteria:

- TRAP sequence in a monochorionic diamniotic twin pregnancy diagnosed between 11.6 and
13.6 weeks, as determined by the crown-rump length of the pump twin in spontaneous
conceptions and by the date of insemination or embryonic age at replacement in
pregnancies resulting from subfertility treatment

- Women aged 18 years or more, who are able to consent

- Anatomically normal pump twin

- Provide written informed consent to participate in this randomized controlled trial,
forms being approved by the Ethical Committees

Exclusion Criteria:

- Contraindication for an intervention due to a severe maternal medical condition or
threatening miscarriage

- Inaccessibility of the acardiac twin due to a retroverted uterus, severe maternal
obesity, uterine fibroids, bowel or placental superposition

- A major anomaly in the pump twin, requiring surgery or leading to infant death or
severe handicap

- Spontaneous arrest of the reverse flow and/or pump twin demise at diagnosis