A Success Story of Modern Obstetrics

Twin–Twin Transfusion Syndrome: A Success Story of Modern Obstetrics

The Twin–Twin Transfusion Syndrome was first described by Schatz in Germany in 1882, when he reported three cases of twin gestations with vascular anastomoses in the placenta. Schatz attributed the phenotype of the twins to the hemodynamic consequences of the vascular anastomoses which he termed ‘the third circulation’.

Since that time, the Twin–Twin Transfusion Syndrome has remained a challenge in obstetrics, a condition requiring fundamental definition, diagnosis, classification, and treatment. Major developments in imaging and operative endoscopy have now allowed important breakthroughs in all these areas, and the diagnosis and treatment of Twin–Twin Transfusion Syndrome has become one of the success stories of modern obstetrics. Imaging with ultrasound allowed the development of diagnostic criteria in the prenatal period, and several investigators contributed to the recognition of the importance of amniotic fluid volume (polyhydramnios and oligohydramnios) in the diagnosis.


The next major contribution was the generation of a staging system that took into account the state of the bladder, Doppler velocimetry of the umbilical artery, vein and ductus venosus. Implicit in this staging system was that the disease was both heterogenous and dynamic. The lethality rate of fetuses with Stage IV (with hydrops) without treatment was approximately 95%, while those in Stage I (amniotic fluid volume abnormalities with a visible bladder and normal Doppler) was only 5%. This seminal observation had profound implications in the assessment of risk, and allowed examination of interventions on a rational basis. After the introduction of the staging system, not all Twin–Twin Transfusion Syndromes were the same.

A critical question of this fascinating and unique disease of pregnancy is its pathophysiology. The view that the syndrome is due to an imbalance of blood exchange between fetuses through vascular anastomoses in the placenta was a central hypothesis for more than a century. Moreover, even among those who accepted this mechanism of disease, the precise role of superficial and deep anastomoses remained unclear.

Laser photocoagulation was first introduced in the late 1980s for the treatment of this condition in the United States. However, the question of what vessels should be obliterated to cure the disease was unanswered. Some surgeons used the dividing membranes as a landmark to identify the vessels to be photocoagulated. This method identified many vessels suspected to participate in the process. This nonselective approach, however, could also result in the obliteration of vessels not participating in the disease process.

A major step forward was the development of criteria to identify, during the course of an endoscopic procedure, the anastomotic from the non-anastomotic vessels. This was central to the major breakthrough: the development of selective photocoagulation for the treatment of the syndrome.

A multicenter European randomized clinical trial led by Professor Yves Ville of the Université Paris, France, demonstrated the superiority of selective laser photocoagulation over amnioreduction for the treatment of the syndrome.

Photocoagulation was associated with improved neonatal survival and reduced neurologic injury. The results of this historical and pioneering trial have implications not only for patient care, but also provide evidence that “the third circulation” is responsible for the disease, as originally proposed by Schatz in 1882.

The challenges presented by the disease now include early diagnosis, refinement of the surgical technique, improving the pathophysiologic understanding and long-term prognosis of affected fetuses, as well as the training of a generation of fetal endoscopic surgeons capable of offering this treatment to patients worldwide.

Dr Ruben Quintero, now Director of Maternal-Fetal Medicine at the University of South Florida in Tampa, played a pioneering role in this success story. Therefore, it is fitting that he has undertaken editing a monograph designed to share with the biomedical community the information that talented investigators around the world have developed for the diagnosis, evaluation, and treatment of this syndrome.

This landmark contribution approaches the subject in a comprehensive manner and will be a reference point in the history of this disease.

Roberto Romero MD Chief

Perinatology Research Branch

Program Director for Obstetrics and Perinatology

Intramural Division, NICHD, NIH, DHHS

Professor of Molecular Obstetrics and Genetics

Center for Molecular Medicine and Genetics

Wayne State University School of Medicine

Bethesda, Maryland and Detroit, Michigan USA