Sex chromosome characteristics and recurrent miscarriage

ObjectiveTo investigate whether skewed X chromosome inactivation (XCI) and Y chromosome microdeletions are associated with recurrent miscarrige (RM).DesignA retrospective study.SettingUniversity hospital and genetic laboratory.Patient(s)Altogether, 46 women with a history of RM, defined as at least three miscarriages, and a control group of 95 women with no history of miscarriage were included in the XCI study. In the Y chromosome microdeletion study 40 male partners of women with RM were studied.Intervention(s)Blood samples for DNA extraction.Main Outcome Measure(s)X chromosome inactivation patterns in the females were analyzed using a methylation-sensitive assay. The DNA from males was tested for Y chromosome microdeletions by analyzing 37 sequence tagged sites.ResultsMildly skewed XCI (>85% inactivation of one allele) was detected in 4 of 43 (9.3%) patients, and 9 of 81 (11.1%) controls. Among these women, extremely skewed XCI (>90% inactivation of one allele) was detected in 2 of 43 (4.7%) patients, and 4 of 81 (4.9%) controls. No statistical differences could be shown between the groups. No microdeletions were found in the male partners.Conclusion(s)The frequency of both extremely and mildly skewed XCI was similar in patients and control women. Y chromosome microdeletions were not found in spouses of patients. Based on these results we conclude that skewed X inactivation and Y chromosome microdeletions are not associated with RM in our study couples.