title: Pregnancy outcome in recurrent miscarriage patients with skewed X chromosome inactivation.
abstract: OBJECTIVE
  To analyze X inactivation in women with recurrent miscarriage to estimate whether skewed X inactivation is associated with recurrent miscarriage and whether it predicts next pregnancy outcomes.
  
  
  METHODS
  A multicenter study was performed. A power calculation determined that 101 patients were needed to detect a difference in skewed X inactivation between patients and controls. Patients were entered into a prospective trial of mononuclear-cell immunotherapy and subsequently tested for skewed X inactivation. Age-matched controls had one live birth and no prior miscarriages. Results from our X inactivation assay were compared with those from an independent genetics laboratory.
  
  
  RESULTS
  Greater than 75% skewing was seen in 22.6% of patients and 26.5% controls (P =.52). Greater than 90% skewing was seen in 6.6% of patients and 3.9% of controls (P =.77). There were 19.8% of primary aborters and 32% of secondary aborters with greater than 75% skewed X inactivation (P =.38). There were 4.9% of primary aborters and 12.0% of secondary aborters with greater than 90% skewed X inactivation (P =.27) Neither greater than 75% nor greater than 90% skewed X inactivation impacted next pregnancy outcomes (odds ratios = 0.87 [95% confidence interval (CI) 0.34, 2.3] and 1.4 [95% CI 0.27, 7.5], respectively). Results of the exchange of samples with an independent laboratory were highly correlated (alpha = 0.987, P <.001, coefficient of variation = 5.5%).
  
  
  CONCLUSIONS
  Skewed X chromosome inactivation is not associated with recurrent miscarriage. A patient's X chromosome inactivation status does not predict next pregnancy outcome. Our assay correlates with another experienced laboratory.
authors.affiliation: Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA. amy.sullivan@hsc.utah.edu
authors.forename: Amy E
authors.initials: AE
authors.lastname: Sullivan
authors.forename: Tracey
authors.initials: T
authors.lastname: Lewis
authors.forename: Mary
authors.initials: M
authors.lastname: Stephenson
authors.forename: Randall
authors.initials: R
authors.lastname: Odem
authors.forename: James
authors.initials: J
authors.lastname: Schreiber
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
authors.forename: D Ware
authors.initials: DW
authors.lastname: Branch
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic