title: Increased risk of large-for-gestational age birthweight in singleton siblings conceived with in vitro fertilization in frozen versus fresh cycles.
abstract: BACKGROUND
  Children born from fresh in vitro fertilization (IVF) cycles are at greater risk of being born smaller and earlier, even when limited to singletons; those born from frozen cycles have an increased risk of large-for-gestational age (LGA) birthweight (z-score ≥1.28). This analysis sought to overcome limitations in other studies by using pairs of siblings, and accounting for prior cycle outcomes, maternal characteristics, and embryo state and stage.
  
  
  METHODS
  Pairs of singleton births conceived with IVF and born between 2004 and 2013 were identified from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database, matched for embryo stage (blastocyst versus non-blastocyst) and infant gender, categorized by embryo state (fresh versus frozen) in 1st and 2nd births (four groups).
  
  
  RESULTS
  The data included 7795 singleton pairs. Birthweight z-scores were 0.00-0.04 and 0.24-0.26 in 1st and 2nd births in fresh cycles, and 0.25-0.34 and 0.50-0.55 in frozen cycles, respectively. LGA was 9.2-9.8 and 14.2-15.4% in 1st and 2nd births in fresh cycles, and 13.1-15.8 and 20.8-21.0% in 1st and 2nd births in frozen cycles. The risk of LGA was increased in frozen cycles (1st births, adjusted odds ratios (AOR) 1.74, 95% CI 1.45, 2.08; and in 2nd births when the 1st birth was not LGA, AOR 1.70, 95% CI 1.46, 1.98 for fresh/frozen and 1.40, 1.11, 1.78 for frozen/frozen).
  
  
  CONCLUSIONS
  Our results with siblings indicate that frozen embryo state is associated with an increased risk for LGA. The implications of these findings for childhood health and risk of obesity are unclear, and warrant further investigation.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, 965 Fee Road, East Fee Hall, Room 628, East Lansing, MI, USA. lukeb@msu.edu.
authors.forename: Barbara
authors.identifier: http://orcid.org/0000-0002-0405-8133
authors.initials: B
authors.lastname: Luke
authors.affiliation: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Morton B
authors.initials: MB
authors.lastname: Brown
authors.affiliation: Redshift Technologies, Inc, New York, NY, USA.
authors.forename: Ethan
authors.initials: E
authors.lastname: Wantman
authors.affiliation: Department of Obstetrics and Gynecology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors.forename: Judy E
authors.initials: JE
authors.lastname: Stern
authors.affiliation: Atlanta Center for Reproductive Medicine, Atlanta, GA, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Toner
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Mayo Clinic, Rochester, MN, USA.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Coddington
mesh_terms: D001724:Birth Weight; D015925:Cryopreservation; D004624:Embryo Transfer / Q000379:methods*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D005615:Freezing; D005865:Gestational Age; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth; D027724:Reproductive Techniques, Assisted; D035781:Siblings
keywords: Assisted reproductive technology; Birth outcomes; Fresh and thawed cycles; Siblings