X-chromosome inactivation in female newborns conceived by assisted reproductive technologies

Objective: To investigate X-chromosome inactivation (XCI) skewing in female newborns conceived by intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), and naturally. Design: Case-control study. Setting: Research institution. Patient(s): 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). Intervention(s): DNA was extracted from umbilical cord blood after birth. Main Outcome Measure(s): 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. Result(s): 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. Conclusion(s): 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. (C) 2014 by American Society for Reproductive Medicine.