Survival rates in pregnancies complicated by twin-to-twin transfusion syndrome undergoing laser therapy: a systematic review and meta-analysis: Survival rates in twin-to-twin transfusion syndrome.

Objectives: Twin-to-twin transfusion syndrome (TTTS) is associated with excess perinatal mortality and morbidity. Even though Quintero staging is commonly used to assess its severity, the limitations of its prognostic value have been highlighted by researchers over the years. Recent literature indicates that fetal survival, whether for both twins or at least one, following fetoscopic laser photocoagulation of the placental anastomoses is similar in TTTS Quintero stages I and II (combined) and III and IV (combined). In this context we perform a systematic review and meta-analysis of the published literature to elucidate the survival rate of twins according to the stage of TTTS and to compare the survival rates in pregnancies complicated by stage I and II (combined) vs those with stages III and IV (combined).

Data sources: Medline, Embase and Cochrane databases were searched.

Study eligibility criteria: The inclusion criteria were studies reporting the outcome of MCDA twin pregnancies with TTTS undergoing laser therapy according to the Quintero stage of the disease. The primary outcome was double survival at birth. The secondary outcomes were no survival, and survival of at least one twin. All the explored outcomes were reported according to the Quintero staging system. Furthermore, we aimed to compare all the observed outcomes in pregnancies complicated by TTTS affected by stage I and II vs those with stages III and IV.

Study appraisal and synthesis methods: Random-effect meta-analyses were used to combine data, and the results reported as pooled proportions or odd ratios (OR) with their 95% confidence intervals (CI).

Results: 26 studies were included. Survival of both fetuses was observed in 72.9% (95% CI 68.2-77.3) of pregnancies complicated by stage I, 67.9% (95% CI 62.3-73.3) with stage II, 48.1% (95% CI 42.5-53.8) with stage III, and 53.4% (95% CI 42.5-64.3) with stage IV TTTS (Table 3). At least one survivor was reported in 89.4% (95% CI 86.9-91.9) of cases with stage I, 87.1% (95% CI 82.9-90.7) with stage II, 77.3% (95% CI 71.7-82.5) with stage III, and 80.1% (95% CI 69.4-89.0) with stage 4. The corresponding figures for no survivors were 10.7% (95% CI 7.7-14.0), 11.4% (95% CI 7.8-15.6), 20.4% (95% CI 15.6-25.8), and 16.7% (95% CI 8.3-27.2), respectively. When comparing the different outcomes according to the different TTTS stages, there was no significant difference in the incidence of double survival (p=0.933), at least one survivor (p=0.688), and no survivors (p=0.866) between stages I and II TTTS. There was also no significant difference in the incidence of double survival (p=0.201), at least one survivor (p=0.380), and no survivors (p=0.947) between stages III and IV. Conversely, when comparing the outcome of pregnancies with stage I/II (combined) vs stages III/IV (combined), the incidence of double survival was significantly higher in pregnancies with stages I/II (OR 2.19; 95% CI 1.9-2.6, p<0.001) (Table 5). Likewise, the incidence of at least one survivor was significantly higher (OR 1.85, 95% CI 1.5-2.6, p<0.001) while that of no survivor (OR 0.56, 95% CI 0.4-0.7, p<0.001) significantly lower in pregnancies with stages I/II compared to III/IV.

Conclusion: Perinatal survival of MCDA twin pregnancies complicated by TTTS and treated with fetoscopic laser coagulation of placental anastomoses is not significantly different between stages I and II, or between stages III and IV, apart from a higher chance of one survivor in stage III compared to stage IV. The findings from this systematic review will be useful in individualised risk assessment of twin pregnancies complicated by TTTS and tailored counselling of the parents. It also highlights the need for studies aimed at better characterizing the prenatal risk factors for mortality in pregnancies complicated by TTTS.

Condensation: Perinatal survival of MCDA twin pregnancies complicated by TTTS and treated with fetoscopic laser coagulation of placental anastomoses is not significantly different between stages I and II, or between stages III and IV.