From Amniocentesis to Selective Laser Coagulation

If one baby dies in utero, the placental anastomoses that cause TTTS in the first place—that is, the open vessel connections that exist between the twins—carry an additional danger. In artery-to-artery and vein-to-vein anastomoses, the direction of blood flow is determined by the difference in blood pressure on either side. If one twin dies, the resultant drop in blood pressure causes the surviving twin to lose a large amount of blood volume across the connecting vessels and into the dying twin. This puts the surviving twin at risk of hemorrhagic shock and a heart attack or stroke.

It is estimated that the risk for white-matter injury in the surviving twin at the time of birth may be as high as 50% following such an intrauterine event. The fates of both twins are thus essentially linked to each other through their placental anastomoses.

Although exact contributors still need to be determined, it is well established that, compared with nonidentical twins, identical twins have a higher incidence of cerebral palsy and other anomalies, and a higher rate of developmental delay at 2 years. Because the development of TTTS is one well-recognized contributor to these statistics, perinatal interventions in monochorionic pregnancies have primarily focused on its treatment.

Evolution of Management

It's most interesting to look at the evolution of management from a historical perspective. When TTTS was clinically recognized, before the days of multivessel Doppler assessment, patients would most often present with a massively distended uterus and preterm labor.

The natural management approach was amnioreduction, which involved the removal of large volumes of amniotic fluid in an effort to relieve uterine distention and prevent preterm delivery. Physicians recognized the need for serial amnioreduction, as the procedure leaves anastomoses open and does nothing to address the underlying problem.

This approach was often satisfactory when it was started at 26–27 weeks' gestation because chances to prolong pregnancy to 32–34 weeks with repeated drainage were reasonable. The patients who presented with massive polyhydramnios and severe TTTS at 20 weeks, however, were another story. Their outcomes with serial amnioreduction were poor; in fact, many physicians would offer pregnancy termination under these circumstances.

In the late 1990s several groups began to address the underlying problem by closing the problem vessels. Dr. Julian De Lia, at that time practicing in Utah, was the first to describe fetoscopic laser ablation of placental anastomoses. He and the team of Prof. Kypros Nicolaides in Europe used a nonselective technique that involved ablating blood vessels and the placental mass along a dividing line between the twins—essentially making the placenta functionally dichorionic—and then draining the amniotic fluid.

Developmental research on the equipment and modification of the technique proceeded. In 1999, Dr. Rubén A. Quintero in Florida published a five-stage classification system for the progression of TTTS, with stages I and II characterized primarily by imbalances in blood volume, stages III and IV signified by cardiovascular compromise, and stage V signified by the death of one or both twins.

This staging system marked a significant step in the management of TTTS because it established a unified diagnostic approach that was based on prenatal criteria. Until this point, the definitions of TTTS were based on an extrapolation of pediatric diagnostic criteria that were used at birth. The application of Dr. Quintero's staging system allowed a more objective comparison of treatment strategies, but required familiarity with arterial and venous Doppler techniques.

Dr. Quintero also argued that a nonselective approach with the laser—one that coagulates vessels that do not contribute to TTTS, as well as those that do—can rob one or both twins of placental territory that is vital for their survival. He developed a selective laser technique that involves identification and coagulation of the vessels that pass from one twin to the other, leaving normal placental territory and noncontributing vessels untouched.

In the meantime, the Eurofetus research consortium had formed in Europe, and had begun designing a trial to compare laser therapy with amnioreduction, with one of their premises being that laser therapy would most benefit twin pregnancies that are complicated by TTTS before 26 weeks' gestation. Perinatal mortality for untreated severe TTTS, they knew, was as high as 90%, with significant handicap in the survivors.

Results of the multicenter randomized study were published in 2004 (N. Engl. J. Med. 2004;351:136-44). Complication rates were basically comparable (approximately 9% in each arm), but the rates of survival of at least one twin at 28 days and at 6 months of age were significantly better in the group that underwent selective laser coagulation than in the amnioreduction group (76% vs. 56% at 28 days, and 76% vs. 51% at 6 months).