Efficacy of amnioreduction as a Therapy

Efficacy of amnioreduction as a Therapy in Twin–Twin Transfusion Syndrome

Amnioreduction has been employed as a primary or adjunctive therapy in TTTS for two decades. As discussed previously, this technique does not alter the underlying pathophysiology of unbalanced vascular anastomoses in monochorionic– diamniotic twin placentation, but appears to prolong gestation by reducing intra-amniotic pressure and improving uteroplacental perfusion. 

The available data on the efficacy of amnioreduction are based on two randomized controlled trials,16,35 one cohort comparative study,36 and many observational series of varying size and methodological quality.3,7–9,11,27,28,34,37–48 The initial data on outcomes for TTTS were derived from non-controlled institutional observational studies. 

As the experience of any single institution is numerically small, there is marked heterogeneity within these series and inter-study comparisons are almost impossible to make. In general, these data focus on perinatal survival with scant attention paid to neonatal morbidity or long-term developmental outcomes. 

These small institutional observational studies have, however, demonstrated that amnioreduction offers a benefit compared to non-interventional strategies and have prompted the conduct of larger studies. 

There have been two large observational series of TTTS treated with amnioreduction strategies published.27,28 The demography and outcomes of the pregnancies in these two registries was very similar, suggesting a fixed survival rate for amnioreduction strategies in TTTS (Table 8.1). The median gestation at diagnosis in each registry was 21 weeks and the median gestation at delivery 29 weeks, again emphasizing the very preterm delivery that characterizes amnioreduction as a therapy. 

Overall perinatal survival rates for TTTS treated with amnioreduction in two large observational studies has been approximately 60%.27,28 Two comparative cohort studies have been published comparing outcomes in non-randomized geographically separate populations treated with amnioreduction or placental laser techniques.36,47 Although perinatal survival rates were comparable in both series between the techniques (Table 8.2), there was a significant increase in the gestation at delivery in pregnancies managed with placental laser ablation. 

This increase in gestation at delivery was reflected with an increased birthweight and lower incidence of abnormal neonatal brain scans in survivors. There have been two randomized controlled clinical trials completed comparing amnioreduction with other techniques in TTTS.16,35 A third randomized controlled trial comparing amnioreduction with placental laser ablation, sponsored by the NIH, was commenced in the USA but abandonded secondary to recruitment difficulties. The first published randomized controlled trial of antepartum interventions in TTTS was that of Senat et al16 in 2004. 

This trial compared the perinatal outcomes of 142 pregnancies complicated with severe TTTS prior to 26 weeks’ gestation in which cases were randomly allocated to amnioreduction or placental laser ablation. Most cases were stage II (43.7%) or III (47.2%) disease at randomization. 

Placental laser ablation was associated with a significant increase in at least one survivor at 6 months of age compared with serial amnioreduction (76% (55/72) vs 51% (36/70), p = 0.002). Dual survival at 6 months of age occurred in 36% of cases treated with placental laser and 26% of cases treated with serial amnioreduction. In 24% of placental laser cases and 49% of amnioreduction cases there were no survivors. 

There was a significantly lower incidence of neurological complications at 6 months of age in those infants treated with placental laser (48% vs 69%, placental laser vs amnioreduction, respectively, p = 0.003). Similarly, periventricular leukomalacia was observed less frequently in those surviving infants treated antenatally with placental laser (6% vs 14%, placental laser vs amnioreduction, respectively, p = 0.02). 

When the data for cases randomized to amnioreduction in the Senat trial are scrutinized, there is one outstanding observation evident: how dismally amnioreduction performed as an intervention for TTTS. The outcomes for pregnancies randomized to amnioreduction are amongst the worst ever published. The performance of amnioreduction is even more concerning when scrutiny of the data demonstrates only one case in each treatment arm with stage IV disease. 

The reason for the amnioreduction outcome data is unclear and is most likely secondary to multiple phenomena such as pregnancy termination and individual research center management variations. The second completed clinical trial compared amnioreduction with microseptostomy as primary therapeutic interventions for TTTS.35 The study was concluded at the planned interim analysis after 73 women were enrolled. The survival of any fetus occurred in 78% of the pregnancies in the amnioreduction group vs 80% of pregnancies in the septostomy group (RR = 0.94, 95% CI 0.55, 1.61; p = 0.82). It is interesting to compare the difference in the perinatal outcomes of this clinical trial with those from the Senat trial amnioreduction arm outlined above. 

The birthweight of the donor fetus was greater in the septostomy group as compared to the amnioreduction group (1291 ± 731 vs 996 ± 408 g; p = 0.02) despite a similar gestational age at delivery. Women undergoing septostomy were more likely to require a single procedure for treatment than the amnioreduction group (64% vs 46%, p = 0.04). However, these outcome data demonstrate a high incidence of very preterm delivery in both treatments arms, presumably as neither treatment option addresses the underlying placental pathology. 

CONCLUSION 

Amnioreduction was the first therapy to alter the universally dismal prognosis for severe TTTS. There is an increasing body of scientific evidence to support the use of placental laser ablation of the vascular anastomoses as a definitive therapy; however amnioreduction will remain as an adjunct to placental laser and possibly as a primary therapy for early-stage disease. It is clear that therapeutic options for TTTS will continue to evolve as medical knowledge of the pathophysiology increases.