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Extended Embryo Culture and an Increased Risk of Preterm Delivery

OBJECTIVE: To estimate whether extended embryo culture is associated with preterm delivery, very preterm delivery, low birth weight, or a combination of these in neonates conceived through in vitro fertilization (IVF). METHODS: U.S. IVF live births were identified using the Society of Assisted Reproductive Technologies database (2004–2006). Associations were assessed in neonates born after extended embryo culture (day 5 to 6) as compared with cleavage-stage transfer (day 3). Analyses were stratified by singleton and twin birth. Subanalyses in neonates born to oocyte donation recipients and primiparous patients were performed. RESULTS: A total of 69,039 live births were identified; 46,288 neonates were born after cleavage-stage embryo transfer and 22,751 neonates after blastocyst transfer. Singleton IVF births conceived after blastocyst transfer, as compared with cleavage-stage transfer, were at an increased risk for preterm delivery (18.6% compared with 14.4%, respectively; adjusted odds ratio [OR] 1.39, P<.001) and very preterm delivery (2.8% compared with 2.2%, respectively; adjusted OR 1.35, P<.001), but not low birth weight (10.3% compared with 9.1%, respectively; adjusted OR 1.10, P=.06). Findings remained robust in subanalyses. In twin births, adverse outcome was more prevalent in both groups and an association of blastocyst transfer was noted for preterm delivery (67.3% compared with 60.5%; adjusted OR 1.81, P<.001) very preterm delivery (adjusted OR 14.0% compared with 12.0%; adjusted OR 1.75, P<.001), and low birth weight (71.1% compared with 68.6%, adjusted OR 1.19, P<.001). CONCLUSION: Extended culture of embryos from cleavage stage to blastocyst stage increases the risk of preterm delivery. Unless blastocyst transfer results in a reduction in multiple births, it may be contributing to the perinatal morbidity associated with IVF-assisted conception. LEVEL OF EVIDENCE: II