Twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity rates. Placental vascular anastomoses, almost invariably present in monochorionic placentas, are the essential anatomical substrate for the development of TTTS. TTTS is thought to result from unbalanced inter-twin blood flow between the donor twin and the recipient twin through the vascular anastomoses, leading to hypovolemia and oligohydramnios in the donor and hypervolemia and polyhydramnios in the recipient. Despite significant developments in the diagnosis, staging and management of TTTS, the pathogenesis of TTTS is still poorly understood and, most importantly, perinatal mortality and morbidity in TTTS remain strikingly high. In this thesis, several studies on TTTS are presented regarding various aspects of this disease, including studies on monochorionic placentas to investigate the pathogenesis of TTTS, description of a new form of chronic TTTS and the short and long-term outcome in TTTS treated with fetoscopic laser surgery. In Chapter 2, an overview of the literature is presented. This review analyzes the possible pathophysiologic mechanisms involved, discusses the latest findings in diagnosis, therapy and prognosis, and focuses on neonatal and pediatric morbidity associated with TTTS. In Chapter 3 we describe a novel technique to calculate the net feto-fetal blood flow through placental arterio-venous anastomoses in a case of TTTS treated with laser surgery and subsequent intrauterine transfusion. In this study we determined that the net blood flow through the five unidirectional arterio-venous anastomoses was approximately 28 ml/24h, much lower than previously measured with Doppler ultrasound. This finding may also explain the inaccuracy of Doppler flow measurements, as such low flow velocities cannot possibly be detected with current Doppler techniques. Measurements of anastomotic blood flow are of major importance for the validation and development of accurate computer modeling in TTTS. In Chapter 4 we studied the role of velamentous cord insertion and discordant placental sharing in the pathogenesis of TTTS by comparing monochorionic placentas with and without TTTS. Previously, several studies reported an increased incidence of velamentous cord insertions in TTTS placentas and suggested a direct relation between velamentous cord insertion, unequal placental sharing and the development of TTTS. In this study we examined 76 monochorionic placentas with TTTS and 63 monochorionic placentas without TTTS. The incidence of velamentous cord insertion (per fetus) in the TTTS group and the no-TTTS group was 13% and 14% (p = 0.79), respectively. Placental sharing discordance in the TTTS group and the no-TTTS group was 20% in both groups (p = 0.83). In the TTTS group, donor twins had more often a velamentous cord insertion than recipient twins (24% and 3%, respectively, P 5 g/dL) were found in 65% (11/17) of cases with residual anastomoses and 20% (7/35) of cases without residual anastomoses (p LEI Universiteit LeidenKarl Storz BV, Stichting FEMAR, Viasys BV, Nycomed BVFoetale geneeskunde, in het bijzonder reproductieve immunologi
