Strong Evidence That Skewed X-chromosome Inactivation is Not Associated with Recurrent Pregnancy Loss: an Incident Paired Case Control Study

Background: Previous studies have reported conflicting results regarding recurrent pregnancy loss and skewed X-chromosome inactivation. Hence, we sought an association by carrying out a specifically designed incident paired case-control study with required statistical power.

Methods: Design incident 1:3 matched case-control study, from 2003 to 2007.

Setting: University Hospital of Brest.

Patients: Women, from the Brittany area, consecutively referred for at least two unexplained consecutive spontaneous abortions.

Controls: Women from the same geographic area, with no history of pregnancy loss and at least one normal pregnancy, recruited using electoral lists and then paired with cases, with respect to age, to within 1 year.

Intervention: Assessment of skewed X-chromosome inactivation.

Statistical Analysis: Comparison of the ratio of >90% skewed X-chromosome inactivation by conditional logistic regression.

Results: Five hundred and forty-three controls (mean age: 34.3 years) were paired within 1 year to 200 cases. The cases (mean age: 33.6 years) had experienced between 2 and 14 consecutive losses (median 3). The rate of >90% skewed X-chromosome inactivation was not statistically different (P = 0.33, odds ratio: 0.58, 95% confidence interval: 0.19-1.77) between cases and paired controls, 2.27% versus 4.1%, respectively.

Conclusions: We conclude that there is no association between skewed X-chromosome inactivation and recurrent pregnancy loss, defined as two or more unexplained consecutive spontaneous abortions.