Twin-twin transfusion syndrome and related monochorionic disorders: historical perspectives, current controversies, and evidence-based opportunities.

Abstract

Twin-twin transfusion syndrome remains a major cause of morbidity and mortality in monochorionic twin pregnancies, arising from placental vascular anastomoses and representing a frequent indication for referral to fetal therapy centers. Despite advances in ultrasound assessment and fetoscopic laser therapy, variability in diagnostic thresholds, Doppler interpretation, and recognition of overlapping phenotypes-particularly twin anemia-polycythemia sequence and selective fetal growth restriction-continues to complicate clinical decision-making and limits meaningful comparison of outcomes across centers. Differences in the definition of polyhydramnios further contribute to this inconsistency, as traditional staging criteria remain widely applied, whereas gestational age-specific thresholds are commonly used in international studies. This expert review synthesizes current evidence regarding the placental vascular basis of twin-twin transfusion syndrome and related monochorionic phenotypes, including overlap phenotypes, and examines the evolution of diagnostic definitions, Doppler assessment, and treatment strategies. Ongoing uncertainty remains, particularly regarding prognostic heterogeneity in advanced-stage disease. This variability may partly reflect both heterogeneous Doppler abnormalities grouped within the same stage and overlap phenotypes involving twin anemia-polycythemia sequence and selective fetal growth restriction. An evidence-informed framework is presented that integrates placental vascular anatomy, Doppler findings, and overlap phenotypes with Quintero staging to improve interpretation and promote consistency in classification and clinical communication. Developed before the broader recognition of overlap phenotypes and contemporary approaches to Doppler and amniotic fluid assessment, the staging system continues to provide a structural foundation that can be interpreted in the context of emerging evidence. The proposed framework preserves that foundation while refining interpretation in light of evolving understanding of disease heterogeneity and overlap phenotypes. It is intended as a complementary and hypothesis-generating approach rather than a prescriptive management system; prospective validation is required.