Twin-to-twin transfusion syndrome occurs when unborn identical twins have different sacs in the womb but share the same placenta. This may result in blood flow from one twin to the other through connections between blood vessels in the shared placenta. The volume of fluid around the twins can also become uneven. This procedure uses laser to separate the shared blood vessels in the placenta.

The National Institute for Health and Clinical Excellence is examining intrauterine laser ablation of placental vessels for the treatment of twin-to-twin transfusion syndrome and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. The Institute's Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about intrauterine laser ablation of placental vessels for the treatment of twin-to-twin transfusion syndrome.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

• comments on the preliminary recommendations
  
• the identification of factual inaccuracies
  
• additional relevant evidence.

Note that this document is not the Institute's formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that the Institute will follow after the consultation period ends is as follows.

• The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
  
• The Advisory Committee will then prepare draft guidance which will be the basis for the Institute's guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from the Institute's website (www.nice.org.uk/ipprogrammemanual).

Closing date for comments: 26 September 2006
Target date for publication of guidance: January 2007

Note that this document is not the Institute's guidance on this procedure. The recommendations are provisional and may change after consultation.

Current evidence on the safety and efficacy of intrauterine laser ablation of placental vessels for the treatment of twin-to-twin transfusion syndrome (TTTS) appears adequate to support the use of this procedure provided that the normal arrangements are in place for clinical governance.

Clinicians wishing to undertake intrauterine laser ablation of placental vessels for the treatment of TTTS should ensure that parents understand that in spite of intrauterine laser ablation treatment, there is still a risk of serious abnormalities in the development of the nervous system among survivors of TTTS. Clinicians should provide parents with clear written information. Use of the Institute's Information for patients ('Understanding NICE guidance') is recommended (available from www.nice.org.uk/IPG XXX publicinfo). [[details to be completed at publication]]

Clinicians should consider case selection carefully because there are uncertainties about the stages of TTTS for which this procedure is appropriate (particularly the early stages).

This procedure should only be performed in centres specialising in invasive fetal medicine and in the context of an appropriate multidisciplinary team.

Clinicians are encouraged to collaborate on longer term data collection across the centres performing intrauterine laser ablation for the treatment of TTTS. The Institute may review the procedure upon publication of further evidence.

Approximately 70% of monozygotic twins are monochorionic/diamniotic (one placenta with two amniotic sacs). TTTS affects approximately 15% of these pregnancies and perinatal mortality is up to 80% if the syndrome is left untreated. TTTS results from shunting of blood between the circulations of the unborn twins through anastomoses of the vessels of the shared placenta. Blood is transfused from the donor twin, whose growth becomes restricted and who develops oligohydramnios or anhydramnios, to the recipient, who usually develops circulatory overload, cardiac compromise and polyhydramnios. The combination of polyhydramnios in the recipient and oligo/anhydramnios in the donor squashes the donor twin against the wall of the uterus. The syndrome is associated with high morbidity and mortality for both twins. Morbidity among survivors includes cardiac, renal and serious neurological impairment, such as cerebral palsy. About 15% of survivors have long-term neurological sequelae.

The options for managing TTTS include expectant medical management, amniodrainage, septostomy, laser ablation, and selective fetal termination using techniques such as umbilical cord occlusion. In some cases the treatment aim is to enable one twin to survive, as the chances for both surviving are extremely poor. Some parents may choose to terminate the pregnancy because of the high risk of perinatal morbidity and mortality in both twins and the risks of serious long-term morbidity in survivors.

In a systematic review that included ten studies assessing laser ablation (both non-selective and selective) for the treatment of TTTS, overall perinatal survival ranged from 61% (87/142) to 70% (210/300); rates for survival of at least one twin ranged from 61% (11/18) to 83% (79/95). In a systematic review that included a single randomised controlled trial of selective laser ablation versus amniodrainage, the likelihood of at least one twin surviving to 28 days was higher with laser ablation than with amniodrainage: 76% (55/72) versus 51% (36/70; p = 0.002). This difference was also maintained to 6 months of age (p = 0.01).

Postnatal neurological sequelae were reported in eight of the ten studies included in the systematic review. The incidence of postnatal neurological morbidity ranged from 1% (1/87) to 8% (2/26). Two additional case series that specifically evaluated long-term neurological sequelae reported major neurological abnormities in 6% (10/167) and 11% (10/89) of twins treated with laser and followed up postnatally for a median of 22 and 38 months, respectively. In the randomised controlled trial it was reported that babies in the laser ablation group were more likely to be free of neurological complications at 6 months of age than those treated with amnioreduction (52% [75/144] vs 31% [44/140]; p = 0.003).. For more details, refer to the sources of evidence (see appendix).

Only one study (n = 101) reported recurrence of TTTS following the procedure - in 14 (14%) of pregnancies.

The Specialist Advisers commented that there are some uncertainties about whether the procedure improves long-term neurodevelopmental outcomes, and the degree of selectivity required when performing laser ablation. They also expressed uncertainty as to the best treatment for early-stage TTTS.

The most common maternal complication following laser surgery was premature rupture of the membranes, which occurred in 28% of women (49/175) in a case series evaluating the perioperative complications of laser ablation; 43% (21/49) occurred within 3 weeks of the procedure. In the randomised controlled trial, premature rupture of the membranes within 28 days of the procedure occurred equally in the two groups (9%). Placental abruption and pregnancy loss (miscarriage) occurred in 2% (3/175) and 7% (12/175) of women, respectively, in the case series; and in 1 of 69 pregnancies (1%) in the laser ablation group and in 2 of 68 (3%) in the amniodrainage group in the randomised controlled trial. In the randomised controlled trial, pregnancy loss within 7 days after the procedure occurred in 8/69 (12%) of women in the laser ablation group and 3% (2/68) in the amniodrainage group (p = 0.1). Other complications reported in the studies included amniotic fluid leakage and vaginal bleeding. For more details, refer to the sources of evidence (see appendix).

The Specialist Advisers listed potential complications as premature rupture of the membranes, infection (chorioamniitis), pregnancy loss, iatrogenic intrauterine death of the donor twin, and sometimes of the recipient twin, persistent TTTS, and reverse transfusion. The Specialist Advisers also noted that there was a risk of maternal death, although this risk has been reduced with improvements in the technique.

The Institute is developing interventional procedures guidance on amnioreduction using septostomy with or without amniodrainage for the treatment of TTTS (www.nice.org.uk/ip_337).

The following document, which summarises the evidence, was considered by the Interventional Procedures Advisory Committee when making its provisional recommendations.

• 'Interventional procedure overview of Intrauterine laser ablation of placental vessels for the treatment of twin to twin transfusion syndrome', March 2006.