Biochemical pregnancies—shall they count in the recurrent miscarriage diagnosis?

To investigate the expression of CD28 and CTLA-4, two costimulatory molecules involved in T-cell activation at the maternal–fetal interface in women with unexplained pregnancy loss.A total of 57 women, 39 with unexplained spontaneous abortion (SA) and 18 with unexplained recurrent spontaneous abortion (RSA), were enrolled in the study. A high-resolution spectratyping analysis of fluorescent bands was performed to detect CD28 and CTLA-4 expression in decidual tissues.The mean expression of CTLA-4 mRNA was significantly higher in women with SA than in controls (P < 0.05). Moreover, the expression of CTLA-4 was higher in SA patients with genotype AA and phenotype A+ (AA + AG) than in controls (P < 0.01). The expression of CTLA-4 was not significantly different in patients with RSA and in controls. The expression of CD28 was significantly decreased in patients with RSA (P < 0.01) and SA (P < 0.05) compared with controls. The mean ratios of CTLA-4/CD28 were significantly higher in patients with RSA (P < 0.01) and SA (P < 0.05) than in controls.This study suggests that an imbalance in CTLA-4/CD28 expression or suppressed T-cell activity at the maternal–fetal interface may confer susceptibility to unexplained pregnancy loss.