Independent association of the M2/ANXA5 haplotype with recurrent pregnancy loss (RPL) in PCOS patients

Abstract

ObjectiveThe aim of this study was to analyze the contribution of the M2 haplotype of ANXA5 gene, previously identified as a risk factor for RPL and thrombophilia related pregnancy complications, to repeated miscarriage observed in PCOS patients. Patients/Methods100 PCOS patients, 500 fertile women and 533 random population controls were genotyped for M2/ANXA5. ResultsM2 haplotype carriers faced a 3.4 fold elevated RPL risk (odds ratio 5.3, 95% confidence interval 3–9.2) compared to female fertile controls and 2.1 (odds ratio 2.6, 95% confidence interval 1.6–4.3) compared to population controls. The relative population risks in subgroups of PCOS patients with primary and secondary RPL were 2.3 (odds ratio 2.5, 95% confidence interval 1.2–5) and 3.3 (odds ratio 3.6, 95% confidence interval 1.5–8.4) respectively. As compared to the fertile women group, the relative risks equaled 4 (odds ratio 5, 95% confidence interval 2.3–10.8) and 6 (odds ratio 7.2, 95% confidence interval 3–17.7). Estimated relative risks for M2 carriers among PCOS RPL patients matched the values previously obtained for repeated miscarriage populations. The essential phenotypes, clinically defining PCOS, associated neither with RPL in their diagnostically relevant combinations, nor with M2 carriage as RPL risk factor in the PCOS RPL subgroups. ConclusionsM2/ANXA5 seems an independent RPL risk factor in PCOS patients that progressively correlates with the number of first trimester pregnancies. From our pilot study in PCOS women it appears relevant to offer M2/ANXA5 diagnostic analysis to such patients with RPL complications, to possibly guide proper therapeutic decisions.