Feto–fetal transfusion syndrome

Feto–fetal transfusion syndrome. Management

Despite many unanswered questions on the pathophysiology of FFTS, different therapeutic approaches have been developed to treat ‘the visible part of the iceberg’. First, indomethacin has been successfully used in the treatment of polyuric polyhydramnios in singleton and in twin pregancies. However, the presumed beneficial effects to the recipient may be opposed to its potential adverse effects on the donor’s renal function and blood flow through the ductus arteriosus.

Digoxin was also used in 1985 to treat FFTS complicated by heart failure.39 Secondly, together with the early description of the ultrasonographic features of FFTS by Elliott et al,40 serial amnioreduction was proposed as a solution to treat amniotic fluid disparity by reducing the polyhydramnios in the recipient cavity. In 1980, Mills advocated that ‘as much fluid as possible must be removed as quickly as possible and the procedure being repeated as often as necessary’.41 This approach aimed initially at preventing preterm labor or preterm premature rupture of the membranes mediated by polyhydramnios, and therefore to prolong the pregnancy.


However, it also reduces intra-amniotic pressure and may therefore improve uterine and cord blood flows. This is the simplest and most inexpensive method but it needs to be serially performed in up to 80% of cases42 because of the lack of control of the underlying mechanism. Some cases of FFTS respond well to therapeutic amnioreduction, most do not. Bajoria43 postulated that the presence of bidirectional (AA or VV) anastomoses may prevent reaccumulation of amniotic fluid in the recipient’s sac following amnioreduction by compensating for hemodynamic imbalance set up by unidirectional vessels (AV).

Thirdly, the aim of deliberate septostomy was to allow amniotic fluid balance between the recipient’s and donor’s sacs. This approach was supported by a speculative ‘low incidence of FFTS in monoamniotic twins’. Disruption of the intertwin membrane was believed to allow correction of the polyhydramnios by filling the empty sac of the stuck twin. This technique was discovered unintentionally in 1995 by Hubinont and co-workers.44 They noted normalization of the amniotic fluid volume in both sacs a few days following septostomy together with an improvement in fetal umbilical artery blood flow. All these changes seem to be mediated through changes in amniotic fluid pressure.

Despite anecdotal good results, both groups treated with amniodrainage or septostomy achieved similar survival rates when looking at outcomes reported in a multicenter randomized controlled trial comparing septostomy against amnioreduction.45 Septostomy has since become obsolete. The initial postulate was then challenged by Quintero et al in 1998 and Hartung and co-workers,46 in 2000, who documented that amniotic fluid pressures prior to amniodrainage were equally high in both sacs. Umur and co-workers,47 using a mathematical model of twin–twin transfusion syndrome, demonstrated that septostomy allows amniotic fluid to be swallowed by the donor with minimal effects on donor growth and volemia.

In addition, specific complications, such as cord entanglement or amniotic bands through the defect in the intertwin membrane, have also been reported.48 Fourthly, based on the observation of the resolution of FFTS following spontaneous intrauterine death of one twin, selective feticide was suggested as a potential additional ‘therapy’.49 This, however, should be restricted to severe cases of FFTS in which one fetus demonstrates ominous signs of fetal demise. All techniques used must completely and permanently occlude all vessels in the umbilical cord in order to prevent acute exsanguination in the dead twin.

Several methods have already been described in this situation: umbilical cord embolization using Histoacryl, thrombogenic coils, bipolar cord coagulation, interstitial laser coagulation, cord ligation, and ultrasonic cord transection. However, the technique which has been most consistently reported to be efficient in most indications is ultrasound-guided cord coagulation using a bipolar forceps.50,51 Finally, the revival of fetoscopy for laser coagulation of intertwin anastomoses on the chorionic plate allowed a significant step towards a more causative treatment of FFTS with the aim of changing the placenta from mono- to dichorionic. The original technique was described by De Lia et al in 1990,52 and was only aimed at cases with a posterior placenta. It was performed under general anesthesia and required a maternal laparotomy to expose the uterus. A hysterotomy was then performed to insert the fetoscope. The approach was to coagulate only anastomotic vessels seen on the vascular equator of the placenta. In 1992,

Ville et al.53 modified the technique radically into a minimally invasive approach. The fetoscope and laser fiber were introduced percutaneously under local analgesia and ultrasound guidance. Both anterior and posterior placentas can be operated upon with this technique. The intertwin membrane was used as an anatomical landmark for the identification of the communicating vessels. All crossing vessels were then non-selectively photocoagulated.

This approach conferred the advantage of improving the reproducibility of the technique and the comparison of outcomes. However, the ‘non-selective’ photocoagulation of all crossing vessels could at least theoretically worsen placental vascular insufficiency of some donor twins, since the location of the dividing membrane on the surface of the placenta bears little relationship to the actual distribution of the vascular territories of the two fetuses and the cavity of the donor twin is often smaller. In order to preserve more of the non-shared cotyledons, in 1997 Quintero et al54 proposed a ‘selective’ approach. All vessels that cross the membrane are assessed systematically and followed into the territory of the recipient twin.

This technique has become the standard in all centers performing laser for TTTS. Machin et al.55 reported that AA anastomoses should be preserved, owing to their potential ability to prevent the development of FFTS. We believe that this could become an ‘historitical’ mistake. Indeed, any vessel left patent could favor the exsanguination of the survivor into its dead co-twin if surgery is followed by single fetal demise as happens in up to 33% of cases.56 The justification for using intrauterine surgery for TTTS had been questioned by the heterogeneous results reported with serial amnioreduction over the past 20 years.

Indeed, with survival ranging from 20 to 80%, the advantage of using fetoscopy, which requires specific skills and equipment, had to be established. This was achieved in 200457 with the coordination of the first randomized controlled trial showing a clear benefit of laser over amniocentesis benefit with fetal therapy. The advantages both in terms of improved survival as well as morbidity, is a milestone in the management of the disease. The future will hopefully be the development of reliable methods to achieve preoperative mapping of the placental angioarchitecture.

This is unlikely to come from ultrasound technology, which finds its limitation with the presence of polyhydramnios but possible rather from further developments of the magnetic resonance or other imaging (MRI) technologies. An improvement in the management of FFTS is also likely to result from better follow-up of treated cases with the recognition of preoperative risk factors.58,59 In addition, an understanding of postoperative complications such as feto–fetal chronic hemorrhage and its management is also likely to improve results.