Approximately 10-15% of monochorionic/diamniotic twin gestations are complicated by twin-twin transfusion syndrome (TTTS). Placental intertwin vascular anastomoses are present in essentially all monochorionic twins; it is thought that unbalanced blood flow through arteriovenous anastomoses leads to TTTS in some cases. Although several therapeutic options have been described for TTTS, most experts consider fetoscopic laser photocoagulation of placental anastomoses to be the best approach.

The severity of TTTS generally is reported by stage; the most commonly used system, which was developed by Quintero et al, includes 5 stages that range from mild disease (demonstrated by isolated discordance in amniotic fluid volumes) to severe disease (death of 1 or both twins). Severe disease is generally defined as Quintero stages II-V.

Two randomized trials have compared the efficacy of fetoscopic laser to serial large volume amnioreductions for the treatment of severe (stage II-IV) TTTS. In 2004, Senat et al published a randomized controlled trial (referred to as the Eurofetus trial) that demonstrated improved perinatal outcomes after laser ablation compared with amnioreduction in 142 women with a diagnosis of severe TTTS that had been diagnosed in the second trimester. This trial was stopped early after an interim analysis demonstrated improved perinatal outcomes in the laser group. In contrast, a second trial that was sponsored by the National Institute of Child Health and Human Development in which 3 large US centers participated found that the recipient twin mortality rate was significantly higher in the laser group than in the amnioreduction group. Because of this and poor patient recruitment, this trial was also terminated early. It is important to note that there has never been a randomized trial that has included a group of TTTS patients with stages II, III, and IV who were treated expectantly; it is likely that there never will be such a trial, given the very poor prognosis of TTTS without intervention.

In the previously mentioned studies, only pregnancies between 16 and either 24 (National Institutes of Child Health and Human Development trial) or 26 (Eurofetus trial) weeks’ gestation were included. Before 16 weeks’ gestation, it has been postulated that the surgical procedure may be more challenging; at >26 weeks’ gestation, less invasive approaches such as expectant management, serial amnioreduction, or preterm delivery are generally preferred. This is due at least in part to the hypothetic concern of laser-related injury to the fetal eyes when the lids are no longer fused, although this complication has not been reported. Given the inclusion criteria of the published trials, the Food and Drug Administration has approved the use of fetoscopic equipment for the treatment of TTTS only between 16-26 weeks’ gestation.

Two European studies have reported on a small series of fetoscopic laser therapy for TTTS at >26 weeks’ gestation. One showed improvement when compared with the amnioreduction group, and the other demonstrated no differences in perinatal outcome when compared with a larger group of “conventional” TTTS cases who were treated by laser photocoagulation at 16-26 weeks’ gestation. There have been no previous reports on laser photocoagulation for severe TTTS at <16 weeks’ gestation.

In this month’s Journal, Baud et al at Mount Sinai Hospital of the University of Toronto performed a retrospective chart review of 325 cases of severe TTTS who were treated with fetoscopic selective laser ablation of placental anastomoses over a 13-year study period. The focus was on the 24 cases who underwent early treatment (<17 weeks’ gestation) and 18 cases who underwent late treatment (>26 weeks’ gestation). There were only 8 cases treated at <16 weeks’ gestation, so data in this group were limited.

There were no differences in surgical technique or patient treatment in the “early” or “late” cases. Compared with the conventional group (17-26 weeks’ gestation), the TTTS stage, duration of surgery, and use of cerclage were similar among the groups. In the early group, there were no significant differences in survival at either 7 or 30 days of life for 1 or both twins, neonatal death within 7 days of birth, mode of delivery, or birthweight when compared with the conventional cases. There were, however, more cases of preterm premature rupture of membranes within 7 days of the laser surgery in the early group. However, this did not result in a higher rate of preterm delivery than that seen in the conventional group, although this may be due in part to the relatively small number of cases.

As might be expected, the TTTS stage was significantly higher in the late cases compared with the conventional cases, with a 33% rate of hydrops in the recipient twin in the late group. In monochorionic twins that are closely observed, it is unusual to experience TTTS at >24 weeks’ gestation. It is possible that many of these patients did not have close ultrasound surveillance and therefore presented with advanced stage disease. The authors reported no differences in either the duration or technical difficulty of laser surgery or in the rate of postoperative complications between the late and conventional groups. Furthermore, despite late cases presenting at a more advanced stage of TTTS, survival of at least 1 twin and dual survival were comparable in the late group and the conventional group. Although the authors state that survival was higher in the late group, this difference was not statistically significant ( P = .089).

The authors concluded that fetoscopic laser therapy for TTTS before 16-17 and at >26 weeks’ gestation was feasible, safe, and yielded similar outcomes to conventional cases treated between 17-26 weeks. Although early severe TTTS is a rare complication of monochorionic/diamniotic twin gestations, the authors present preliminary retrospective data that fetoscopic laser surgery is a viable option for this challenging situation. Although the rate of preterm premature rupture of membranes was higher in this group, this finding did not translate into an increased rate of prematurity. Furthermore, when severe TTTS occurs at >26 weeks’ gestation, good therapeutic options are limited, especially in the case of hydrops in which the perinatal mortality rate at <30 weeks’ gestation is extremely high.

The study of Baud et al is limited by its retrospective design and relatively small numbers of available cases. However, their data are encouraging and suggest that the conventional age limitations of 16-26 weeks’ gestation for laser treatment of severe TTTS should perhaps be reevaluated to include earlier and later gestational ages. Those cases that present very early or are not detected until late in gestation may represent the severe end of the spectrum and therefore be more likely to benefit from laser therapy. This issue could perhaps best be answered by a multicenter study that would involve the larger fetal treatment centers in the United States and Europe.