From Amniocentesis to Selective Laser Coagulation

The differences existed in both the early and later stages of TTTS, although fetuses in the Quintero stages I or II had better outcomes than did those with higher stages in both treatment groups. (The study had been concluded early, after 72 women had been assigned to the laser group and 70 to the amnioreduction group, when an interim analysis demonstrated significant benefits.)

Gestational ages at the time of delivery were also significantly different: Patients in the laser group delivered, on average, at 33 weeks, whereas those in the amnioreduction group delivered at 29 weeks.

An intermediate-term look at neurologic outcomes favored laser surgery as well: At 6 months of age, infants in the laser group were more likely than those in the amnioreduction group to be free of neurologic deficits (52% vs. 31%, respectively).

At the center for advanced fetal care at the University of Maryland, Baltimore, which has served for almost a decade as a referral resource for minimally invasive fetal therapy, I have applied the identical technique utilized in the Eurofetus trial using a selective approach. Our treatment results have consistently mirrored the published statistics.

Our research, which we presented at the annual meeting of the Society for Maternal-Fetal Medicine, confirms that successful laser ablation corrects the abnormal blood volume distribution. This effect is first apparent for the donor twin and clinically presents with the reappearance of bladder filling, often on the day after the procedure.

Urination gradually normalizes in the recipient twin, typically over 1–2 weeks after the procedure. The mother feels better immediately after the procedure and continues to improve as fetal status normalizes.

Longer-term follow-up of neurologic abnormalities in the Eurofetus trial is underway. For now, however, an analysis of a series of patients who received intrauterine laser treatment for TTTS has shown that 78% of 89 surviving children had a normal neurodevelopmental status at about 2 years of age, whereas 11% had minor neurologic deficiencies and 11% had major neurologic deficits (Am. J. Obstet. Gynecol. 2003;188:876-80).

Although comparisons of patients managed in the randomized trial are pending, these rates of neurologic handicap compare favorably with those seen after amnioreduction.

Two large series indicate that severe TTTS is associated with poor neurodevelopment, and that up to 27% of survivors may have abnormal brain ultrasounds at the time of delivery. It is therefore widely accepted that the neuroprotective benefit of laser therapy is most marked in early onset TTTS (prior to 26 weeks), and that the difference in outcomes is attributable to lower rates of preterm delivery and prematurity-associated complications as well as to the elimination of the risks of ongoing TTTS.

Moving Into the Future

In Europe, the randomized trial basically brought the controversy over optimal treatment for TTTS to a close. In the United States, there are some who still lean toward performing an initial amnioreduction and moving on to laser surgery if necessary.

There are disadvantages to such an approach. An initial amnioreduction removes the amniotic fluid pocket that is necessary to successfully maneuver the fetoscope. Decompression of the placenta not only unpredictably affects shunt dynamics but also can create placental “valleys” that can impair visualization of anastomoses. Potential bleeding from the procedure, as well as advancing gestational age until a suitable fluid pocket has reestablished, can also make the fluid cloudier.

Investigators who have looked at the factors that influence outcomes of selective laser coagulation of placental anastomoses have reported that those who do poorly have more advanced TTTS; have shorter cervical length, and thus a higher incidence of preterm labor; have a history of prior amnioreduction; and have technically difficult laser procedures with poor visualization of anastomoses as contributing factors.

Amnioreduction still has a role, however, particularly for patients who present with TTTS beyond 26 weeks' gestation. These patients are not candidates for laser therapy because the efficacy and safety of the procedure at this gestational age has not been studied.

Even with the improved outcomes, the therapies are still not optimal, and our knowledge of TTTS is still full of gaps and differences in opinion. Some experts believe, for instance, that with selective laser therapy there is a risk of recurring TTTS—that is, as visible anastomoses are closed, intravascular pressures are diverted to very small vessels that are barely visible at the time of the laser procedure. Over time, it is believed, these vessels may expand and therefore become hemodynamically relevant contributors to recurring TTTS.

At this time, I believe it's important to keep an open mind after presumably successful laser therapy, and to follow the fetuses closely after surgery for TTTS. Continued evaluation of bladder filling, amniotic fluid volumes, and placental and venous Doppler studies may be necessary over extended periods of time.