Julien Stirnemann1, Femke Slaghekke2, Nahla Khalek3, Norbert Winer4, Anthony Johnson5, Liesbeth Lewi6, Mona Massoud7, Laurence Bussieres8, Philippe Aegerter9, Kurt Hecher10, Marie-Victoire Senat11, Yves Ville8. 1. Department of Obstetrics and Maternal-Fetal Medicine, Hôpital Necker-Enfants Malades, AP-HP and EA7328, Université de Paris, Paris, France. Electronic address: julien.stirnemann@aphp.fr. 2. Department of Obstetrics and Fetal Therapy, Leiden University Medical Center, Leiden, the Netherlands. 3. Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA. 4. Department of Obstetrics and Gynecology, NUN, INRAE, UMR 1280, PhAN, University Hospital of Nantes, Nantes, France. 5. The Fetal Center, University of Texas Health Science Center, Houston, TX. 6. Department of Obstetrics and Gynecology, University Hospitals Leuven and Department of Development and Regeneration, Biomedical Sciences, Katholieke Universiteit Leuven, Leuven, Belgium. 7. Fetal Medicine Unit, Hôpital Femme Mère Enfants, Hospices Civils de Lyon, Lyon, France. 8. Department of Obstetrics and Maternal-Fetal Medicine, Hôpital Necker-Enfants Malades, AP-HP and EA7328, Université de Paris, Paris, France. 9. Department of Public Health, UMR 1168, UVSQ INSERM, GIRCI IdF-UFR Médecine Paris-Ile-de-France-Ouest, Université de Versailles St-Quentin-en-Yvelines, Versailles, France. 10. Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany. 11. Department of Gynecology-Obstetrics, Hôpital Bicêtre AP-HP and Université Paris-Sud, Paris-Saclay Medical School and CESP Centre for Research in Epidemiology and Population Health, Université Paris-Saclay, Université Paris-Sud, UVSQ, INSERM, Villejuif, France.
Abstract
BACKGROUND:Selective fetoscopic laser coagulation of the intertwin anastomotic chorionic vessels is the first-line treatment for twin-twin transfusion syndrome. However, in stage 1 twin-twin transfusion syndrome, the risks of intrauterine surgery may be higher than those of the natural progression of the condition. OBJECTIVE: This study aimed to compare immediate surgery and expectant follow-up in stage 1 twin-twin transfusion syndrome. STUDY DESIGN: We conducted a multicentric randomized trial, which recruited from 2011 to 2018 with a 6-month postnatal follow-up. The study was conducted in 9 fetal medicine centers in Europe and the Unites States. Asymptomatic women with stage 1 twin-twin transfusion syndrome between 16 and 26 weeks' gestation, a cervix of >15 mm, and access to a surgical center within 48 hours of diagnosis were randomized between expectant management and immediate surgery. In patients allocated to immediate laser treatment, percutaneous laser coagulation of anastomotic vessels was performed within 72 hours. In patients allocated to expectant management, a weekly ultrasound follow-up was planned. Rescue fetoscopic coagulation of anastomoses was offered if the syndrome worsened as seen during a follow-up, either because of progression to a higher Quintero stage or because of the maternal complications of polyhydramnios. The primary outcome was survival at 6 months without severe neurologic morbidity. Severe complications of prematurity and maternal morbidity were secondary outcomes. RESULTS: The trial was stopped at 117 of 200 planned inclusions for slow accrual rate over 7 years: 58 women were allocated to expectant management and 59 to immediate laser treatment. Intact survival was seen in 84 of 109 (77%) expectant cases and in 89 of 114 (78%) (P=.88) immediate surgery cases, and severe neurologic morbidity occurred in 5 of 109 (4.6%) and 3 of 114 (2.6%) (P=.49) cases in the expectant and immediate surgery groups, respectively. In patients followed expectantly, 24 of 58 (41%) cases remained stable with dual intact survival in 36 of 44 (86%) cases at 6 months. Intact survival was lower following surgery than for the nonprogressive cases, although nonsignificantly (78% and 71% following immediate and rescue surgery, respectively). CONCLUSION: It is unlikely that early fetal surgery is of benefit for stage 1 twin-twin transfusion syndrome in asymptomatic pregnant women with a long cervix. Although expectant management is reasonable for these cases, 60% of the cases will progress and require rapid transfer to a surgical center.
RCT Entities:
BACKGROUND: Selective fetoscopic laser coagulation of the intertwin anastomotic chorionic vessels is the first-line treatment for twin-twin transfusion syndrome. However, in stage 1 twin-twin transfusion syndrome, the risks of intrauterine surgery may be higher than those of the natural progression of the condition. OBJECTIVE: This study aimed to compare immediate surgery and expectant follow-up in stage 1 twin-twin transfusion syndrome. STUDY DESIGN: We conducted a multicentric randomized trial, which recruited from 2011 to 2018 with a 6-month postnatal follow-up. The study was conducted in 9 fetal medicine centers in Europe and the Unites States. Asymptomatic women with stage 1 twin-twin transfusion syndrome between 16 and 26 weeks' gestation, a cervix of >15 mm, and access to a surgical center within 48 hours of diagnosis were randomized between expectant management and immediate surgery. In patients allocated to immediate laser treatment, percutaneous laser coagulation of anastomotic vessels was performed within 72 hours. In patients allocated to expectant management, a weekly ultrasound follow-up was planned. Rescue fetoscopic coagulation of anastomoses was offered if the syndrome worsened as seen during a follow-up, either because of progression to a higher Quintero stage or because of the maternal complications of polyhydramnios. The primary outcome was survival at 6 months without severe neurologic morbidity. Severe complications of prematurity and maternal morbidity were secondary outcomes. RESULTS: The trial was stopped at 117 of 200 planned inclusions for slow accrual rate over 7 years: 58 women were allocated to expectant management and 59 to immediate laser treatment. Intact survival was seen in 84 of 109 (77%) expectant cases and in 89 of 114 (78%) (P=.88) immediate surgery cases, and severe neurologic morbidity occurred in 5 of 109 (4.6%) and 3 of 114 (2.6%) (P=.49) cases in the expectant and immediate surgery groups, respectively. In patients followed expectantly, 24 of 58 (41%) cases remained stable with dual intact survival in 36 of 44 (86%) cases at 6 months. Intact survival was lower following surgery than for the nonprogressive cases, although nonsignificantly (78% and 71% following immediate and rescue surgery, respectively). CONCLUSION: It is unlikely that early fetal surgery is of benefit for stage 1 twin-twin transfusion syndrome in asymptomatic pregnant women with a long cervix. Although expectant management is reasonable for these cases, 60% of the cases will progress and require rapid transfer to a surgical center.