Multiple Pregnancies

The purpose of this study was to evaluate the prognostic value of sonographic and clinical parameters to develop a staging classification of twin-twin transfusion syndrome (TTTS). Severe TTTS was defined as the presence of polyhydramnios (maximum vertical pocket of > or = 8 cm) and oligohydramnios (maximum vertical pocket of < or = 2 cm). Nonvisualization of the bladder in the donor twin (-BDT) and absence of presence of hydrops was also noted. The middle cerebral artery, umbilical artery, ductus venosus, and umbilical vein in both fetuses were assessed with pulsed Doppler. Critically abnormal Doppler studies (CADs) were defined as absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein. TTTS was staged as follows: stage I, BDT still visible; stage II, BDT no longer visible, no CADs; stage III, CADs; stage IV, hydrops; stage V, demise of one or both twins. Laser photocoagulation of communicating vessels (LPCV) or umbilical cord ligation was performed depending on the severity of the condition. The study was approved by the Institutional Review Board of St. Joseph's Hospital in Tampa and by the Fetal Therapy Board at Hutzel Hospital, Detroit, and all patients gave informed consent. A total of 80 of 108 referred patients met criteria for surgery, but only 65 were treated surgically: 48 with LPCV and 17 with umbilical cord ligation. Complete Doppler data were obtainable in 41 of 48 LPCV patients. Survival rates by stage for one or two fetuses were statistically different (chi-squared analysis = 12.9, df = 6, p = 0.044). Neither percent size discordance nor gestational age at diagnosis were predictive of outcome. Staging of TTTS using the proposed criteria has prognostic significance. This staging system may allow comparison of outcome data of TTTS with different treatment modalities.

Recent data in humans and animals suggest that assisted reproductive technology (ART) might affect the epigenetics of early embryogenesis and might cause birth defects. We report the first evidence, to our knowledge, that ART is associated with a human overgrowth syndrome-namely, Beckwith-Wiedemann syndrome (BWS). In a prospective study, the prevalence of ART was 4.6% (3 of 65), versus the background rate of 0.8% in the United States. A total of seven children with BWS were born after ART-five of whom were conceived after intracytoplasmic sperm injection. Molecular studies of six of the children indicate that five of the six have specific epigenetic alterations associated with BWS-four at LIT1 and one at both LIT1 and H19. We discuss the implications of our finding that ART is associated with human overgrowth, similar to the large offspring syndrome reported in ruminants.