title: Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group.
abstract: OBJECTIVE
  What are the risks of adverse outcomes in singletons born after frozen-thawed embryo transfer (FET)?
  
  
  CONCLUSIONS
  Singletons born after FET have a better perinatal outcome compared with singletons born after fresh IVF and ICSI as regards low birthweight (LBW) and preterm birth (PTB), but a worse perinatal outcome compared with singletons born after spontaneous conception.
  
  
  BACKGROUND
  Previous studies have shown a worse perinatal outcome in children born after IVF in general compared with children born after spontaneous conception. In singletons born after FET, a lower rate of PTB and LBW and a higher rate of large for gestational age (LGA) compared with singletons born after fresh IVF have been shown.
  
  
  METHODS
  A retrospective Nordic population-based cohort study of all singletons conceived after FET in Denmark, Norway and Sweden until December 2007 was performed.
  
  
  METHODS
  Singletons born after FET (n = 6647) were compared with a control group of singletons born after fresh IVF and ICSI (n = 42 242) and singletons born after spontaneous conception (n = 288 542). Data on perinatal outcomes were obtained by linkage to the national Medical Birth Registries. Odds ratios were calculated for several perinatal outcomes and adjustments were made for maternal age, parity, year of birth, offspring sex and country of origin.
  
  
  RESULTS
  Singletons born after FET had a lower risk of LBW (adjusted odds ratio (aOR) 0.81, 95% confidence interval (CI) 0.71-0.91), PTB (aOR 0.84, 95% CI 0.76-0.92), very PTB (VPTB; aOR 0.79, 95% CI 0.66-0.95) and small for gestational age (SGA; aOR 0.72, 95% CI 0.62-0.83), but a higher risk of post-term birth (aOR 1.40, 95% CI 1.27-1.55), LGA (aOR 1.45, 95% CI 1.27-1.64), macrosomia (aOR 1.58, 95% CI 1.39-1.80) and perinatal mortality (aOR 1.49, 95% CI 1.07-2.07) compared with singletons born after fresh IVF and ICSI. Compared with children conceived after spontaneous conception, singletons born after FET had a higher risk of LBW (aOR 1.27, 95% CI 1.13-1.43), very LBW (aOR 1.69, 95% CI 1.33-2.15), PTB (aOR 1.49, 95% CI 1.35-1.63), VPTB (aOR 2.68, 95% CI 2.24-3.22), SGA (aOR 1.18, 95% CI 1.03-1.35), LGA (aOR 1.29, 95% CI 1.15-1.45), macrosomia (aOR 1.29, 95% CI 1.15-1.45) and perinatal (aOR 1.39, 95% CI 1.03-1.87) neonatal (aOR 1.87, 95% CI 1.23-2.84) and infant mortality (aOR 1.92, 95% CI 1.36-2.72). When analyzing trends over time, the risk of being born LGA increased over time for singletons born after FET compared with singletons born after fresh IVF and ICSI (P = 0.04).
  
  
  CONCLUSIONS
  As in all observational studies, the possible role of residual confounding factors and bias should be considered. In this study, we were not able to control for confounding factors, such as BMI, smoking and reason for, or length of, infertility.
  
  
  CONCLUSIONS
  Perinatal outcomes in this large population-based cohort of children born after FET from three Nordic countries compared with fresh IVF and ICSI and spontaneous conception were in agreement with the literature.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Gothenburg, Gothenburg, Sweden. ulla-britt.wennerholm@vgregion.se
authors.forename: Ulla-Britt
authors.initials: UB
authors.lastname: Wennerholm
authors.forename: Anna-Karina Aaris
authors.initials: AK
authors.lastname: Henningsen
authors.forename: Liv Bente
authors.initials: LB
authors.lastname: Romundstad
authors.forename: Christina
authors.initials: C
authors.lastname: Bergh
authors.forename: Anja
authors.initials: A
authors.lastname: Pinborg
authors.forename: Rolv
authors.initials: R
authors.lastname: Skjaerven
authors.forename: Julie
authors.initials: J
authors.lastname: Forman
authors.forename: Mika
authors.initials: M
authors.lastname: Gissler
authors.forename: Karl Gösta
authors.initials: KG
authors.lastname: Nygren
authors.forename: Aila
authors.initials: A
authors.lastname: Tiitinen
mesh_terms: D000328:Adult; D001755:Blastocyst; D015331:Cohort Studies; D015925:Cryopreservation; D004624:Embryo Transfer / Q000009:adverse effects*; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects; D005317:Fetal Growth Retardation / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007233:Infant, Postmature; D007234:Infant, Premature; D007236:Infant, Small for Gestational Age; D008297:Male; D054238:Perinatal Mortality; D047928:Premature Birth / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D012042:Registries; D012189:Retrospective Studies; D012306:Risk; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects
keywords: IVF; assisted reproduction technology; cryopreservation; perinatal outcome; singletons