title: Independent association of the M2/ANXA5 haplotype with recurrent pregnancy loss (RPL) in PCOS patients.
abstract: OBJECTIVE
  The 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.
  
  
  METHODS
  100 PCOS patients, 500 fertile women and 533 random population controls were genotyped for M2/ANXA5.
  
  
  RESULTS
  M2 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.
  
  
  CONCLUSIONS
  M2/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.
authors.affiliation: Division of Gynecological Endocrinology and Reproductive Medicine, Department of Gynecology and Obstetrics, Klinikum der Ludwig-Maximilians-Universität, Munich, Campus Grosshadern, D-81377 Munich, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Rogenhofer
authors.forename: Laura
authors.initials: L
authors.lastname: Engels
authors.forename: Nadja
authors.initials: N
authors.lastname: Bogdanova
authors.forename: Frank
authors.initials: F
authors.lastname: Tüttelmann
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Thaler
authors.forename: Arseni
authors.initials: A
authors.lastname: Markoff
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology / Q000235:genetics*; D000328:Adult; D017304:Annexin A5 / Q000235:genetics*; D015331:Cohort Studies; D016001:Confidence Intervals; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D016017:Odds Ratio; D010920:Placenta / Q000473:pathology; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology; D055815:Young Adult
chemical_list: D017304:Annexin A5; D004247:DNA
keywords: AF; ANXA5; Annexin A5; DNA; M2 haplotype of ANXA5; M2/ANXA5; PCOS; Polycystic ovarian syndrome; RPL; Recurrent miscarriage; Risk factor; allele frequency; annexin A5 gene or protein; deoxyribonucleic acid; polycystic ovarian syndrome; recurrent pregnancy loss