Mechanism of recurrent spontaneous abortions in women with mosaicism of X-chromosome aneuploidies

Abstract

Objective: To investigate the mechanism of recurrent miscarriages in women with mosaicism of X-chromosome aneuploidies.

Design: Prospective case-control study.

Setting: University-based reproductive clinic housed in a medical center with genetic laboratories.

Patient(s): Eighteen women who experienced recurrent miscarriages and had mosaicism of X-chromosome aneuploidies; two control groups, one with a balanced structural autosomal rearrangement and the other without chromosomal abnormalities.

Intervention(s): Criteria were established for the diagnosis of low-grade X-chromosome mosaicism by using peripheral blood lymphocytes. Patients were evaluated for the pathogenesis of recurrent miscarriages. Their abortion rate was assessed, and each abortus was karyotyped.

Main outcome measure(s): Abortion rate and karyotype of the abortus.

Result(s): In comparison with patients with X-chromosome mosaicism with a balanced structural autosomal rearrangement, patients with X-chromosome mosaicism without a balanced autosomal structural rearrangement had a significantly higher incidence of diminished ovarian reserve (DOR) and had a somewhat higher prevalence of uterine anomalies. In comparison with controls without chromosomal abnormalities, the patients with a balanced autosomal structural rearrangement also had higher incidence of both conditions, but the differences were not statistically significant. At least two factors are implicated in recurrent miscarriages in women with X-chromosome mosaicism. Among them, DOR is the most prevalent (occurring in 44.4% of cases), followed by uterine anomalies (16.7% of cases). Cases with DOR had a higher abortion rate than did those without (68.6% vs. 44.1%). Cases with DOR also had a slightly higher rate of abnormal karyotypes in the abortus than did those without (73.7% vs. 42.9%).

Conclusion(s): The oocytes of women with X-chromosome mosaicism are in a suboptimal state of development and are prone to embryonic lethality.