title: X-chromosome inactivation in female newborns conceived by assisted reproductive technologies.
abstract: OBJECTIVE
  To investigate X-chromosome inactivation (XCI) skewing in female newborns conceived by intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), and naturally.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Research institution.
  
  
  METHODS
  A total of 185 female newborns, including 60 conceived by intracytoplasmic sperm injection (ICSI), 73 by in vitro fertilization (IVF), and 52 naturally conceived (NC).
  
  
  METHODS
  DNA was extracted from umbilical cord blood after birth.
  
  
  METHODS
  XCI skewing values determined by assaying allelic ratio of methylated alleles at the androgen receptor (AR), fragile X mental retardation 1 (FMR1), and DXS6673E loci.
  
  
  RESULTS
  In the comparison of the ICSI, IVF, and NC populations, the frequency of skewing ≥ 75% (7.0% vs. 5.7% vs. 2.0%, respectively) or ≥ 90% (0 vs. 1.4% vs. 2.0%, respectively) was not statistically significantly different. The mean level of skewing between the ICSI, IVF, and NC groups also did not differ (63.7% vs. 61.8% vs. 60.7%, respectively). Skewing variability was observed in the placentas of the two extremely skewed cases. The parental origin of the preferentially inactivated X chromosome in the extremely skewed IVF and NC cases were maternal and paternal, respectively.
  
  
  CONCLUSIONS
  The assisted reproductive technologies of ICSI and IVF do not appear to affect XCI skewing. Skewing variability within the placentas analyzed supports the theory that weaker selective pressures occur in the placenta that could result in skewed inactivation. Our study is the largest to date to investigate this epigenetic phenomenon in infants conceived by ICSI and IVF alongside age-matched NC controls.
authors.affiliation: Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Elizabeth X
authors.initials: EX
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Paloma
authors.initials: P
authors.lastname: Stanar
authors.affiliation: Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: sai@mail.ubc.ca.
authors.forename: Sai
authors.initials: S
authors.lastname: Ma
mesh_terms: D002170:Canada; D016022:Case-Control Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D005312:Fetal Blood / Q000737:chemistry; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008423:Maternal Age; D009687:Nuclear Proteins / Q000235:genetics; D011247:Pregnancy; D011944:Receptors, Androgen / Q000235:genetics; D012307:Risk Factors; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects; D049951:X Chromosome Inactivation
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009687:Nuclear Proteins; D011944:Receptors, Androgen; C410798:AR protein, human; C497683:FMR1 protein, human; C102796:ZMYM3 protein, human
keywords: Assisted reproductive technology; ICSI; IVF; X-chromosome inactivation; epigenetics