RESUMEN
OBJECTIVE: To study the influence of M2/ANXA5 for recurrent pregnancy loss (RPL), according to the timing of miscarriages and assess the male partner risk. DESIGN: Genetic association study. SETTING: Academic research center. PATIENT(S): Female patients from two academic centers in Germany and Bulgaria with two or more unexplained miscarriages were selected for this study. Male partners were available for a part of the German sample. Population controls were recruited from healthy individuals of respective populations. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence of M2 carriage and odds ratios were calculated between patient and control groups, and RPL risk was evaluated. RESULT(S): The M2 haplotype in ANXA5 was associated with greater overall RPL risk in German and in Bulgarian women, and a trend of higher prevalence was seen for male partners of German RPL patients. The highest relative risk of M2 carriage was observed in women of both populations with "early" fetal losses between the 10th and 15th gestational weeks, which was significant in the meta-analysis. CONCLUSION(S): M2 carriage seems to have an RPL risk role mostly for early abortions, gestational weeks 10-15. In the first phase of pregnancy this correlates with vascular remodeling to accomplish the transition from high- to low-resistance blood vessels.