Evolution of Stage 1 Twin-to-Twin Transfusion Syndrome (TTTS): Systematic Review and Meta-Analysis

Objectives: The natural history of stage 1 Twin-to-twin transfusion syndrome (TTTS) remains unclear and its optimal management is yet to be established. The main aims of this meta-analysis were to quantify the incidence of progression in stage 1 TTTS and to ascertain survival in these pregnancies. Methods: MEDLINE, EMBASE, and The Cochrane Library were searched. Reference lists within each article were hand-searched for additional reports. The outcomes included incidence of progression and survival in stage 1 TTTS. Randomized controlled trials, cohort and case-control studies were included. Case reports, studies including three or fewer cases of stage 1 TTTS, and editorials were excluded. Proportion meta-analysis was used for analysis (Registration number: CRD42016036190). Results: The search yielded 3,085 citations; 18 studies were included in the review (172 pregnancies to assess progression and 433 pregnancies to assess the survival). The pooled incidence of progression in stage 1 TTTS was 27% [95% CI 16-39%]. The pooled overall survival, double survival and at least one survival in the pregnancies managed expectantly were 79% [95% CI 62-92%], 70% [95% CI 54-84%] and 87% [95% CI 69-98%], respectively. In those undergoing amnioreduction, the corresponding figures were 77% [95% CI 68-85%], 67% [95% CI 57-76%] and 86% [95% CI 76-94%], respectively. The survival rates were 68% [95% CI 54-81%], 54% [95% CI 36-72%], and 81% [95% CI 69-90%], when laser surgery was performed. Conclusions: The optimal initial management of stage 1 TTTS remains in equipoise. The ongoing randomized trial comparing immediate laser surgery versus conservative management should provide a definitive answer.