Risk of stillbirth and neonatal death in singletons born after fresh and frozen embryo transfer. Cohort study from the Committee of Nordic Assisted Reproduction Technology and Safety

OBJECTIVES: To investigate whether risks of stillbirth and neonatal death differ after fresh and frozen embryo transfer (fresh and frozen-ET) compared to singletons conceived without medical assistance. DESIGN: Population-based cohort. SETTING: Data linkage between the nationwide Medical Birth Registries in Denmark (1994-2014), Norway and Sweden (1988-2015), and national quality registries and databases on assisted reproductive technology. PATIENTS: 4,590,853 singletons, including 78,642 conceived by fresh transfer and 18,084 by frozen-ET. INTERVENTION: None MAIN OUTCOME MEASURES: Stillbirth (fetal death before and during delivery) and neonatal death (live born with death 0-27 days postpartum). RESULTS: Overall, 17,123 (0.37%) singletons were stillborn and 7,685 (0.17%) died neonatally. Compared to singletons conceived without medical assistance, the odds of stillbirth were similar after fresh and frozen-ET, while odds of neonatal death were higher after fresh (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.46-1.95) and frozen-ET (OR 1.51, 95% CI 1.08-2.10). Preterm birth (<37 gestational weeks) was more common after fresh (8.0%) and frozen-ET (6.6%) compared to singletons conceived without medical assistance (5.0%), and strongly associated with neonatal mortality across all conception methods. Within gestational age categories, risk of stillbirth and neonatal death was similar for all conception methods, except that singletons from fresh-ET had a higher risk of stillbirth during gestational week 22-27 (OR 1.85, 95% CI 1.51-2.26). CONCLUSION: Overall risk of stillbirth was similar after fresh and frozen-ET compared to singletons conceived without medical assistance, whereas neonatal mortality was higher, possibly mediated by the higher risk of preterm birth when compared to singletons conceived without medical assistance. Our results gave no clear support for choosing one treatment over the other.