Multicentre study of the clinical relevance of screening IVF patients for carrier status of the annexin A5 M2 haplotype

Reprod Biomed Online. 2014 Jul;29(1):80-7. doi: 10.1016/j.rbmo.2014.03.019. Epub 2014 Apr 12.


Thrombophilia and impaired placental vasculature are a major cause of adverse pregnancy outcome. In 2007, a new hereditary factor for obstetric complications and recurrent pregnancy loss (RPL) was identified as a sequence variation in the core promoter of the annexin A5 gene, ANXA5, called the M2 haplotype. M2 carriership has been demonstrated in couples with recurrent miscarriage and its origin is embryonic rather than specifically maternal, confirmed by subsequent papers. The M2 haplotype is the first report of a hereditary factor related to pregnancy pathology caused by embryonic-induced anticoagulation. It has been demonstrated that couples with RPL had equal and significantly increased M2 carriership and that maternal and paternal carriership confers equal risk. Given its importance for patients with RPL, and potentially implantation failure, this study assessed the incidence of carrier status for the M2 ANXA5 haplotype in both the male and female of couples attending five CARE IVF centres. In 314 patients (157 couples), 44% of couples (one or both partners), 24% of females, 26% of males and 37% of couples with unexplained infertility were M2 carriers. This high incidence has provoked further urgent studies on specific patient populations and on the value of post embryo-transfer therapy.

Keywords: ANXA5; infertility; miscarriage; recurrent pregnancy loss; thrombophilia.

Publication types

  • Multicenter Study

MeSH terms

  • Abortion, Habitual / epidemiology
  • Abortion, Habitual / genetics*
  • Adult
  • Annexin A5 / genetics*
  • Female
  • Fertilization in Vitro
  • Genetic Carrier Screening
  • Haplotypes
  • Heterozygote*
  • Humans
  • Male
  • Middle Aged
  • Promoter Regions, Genetic
  • Thrombophilia / epidemiology
  • Thrombophilia / genetics


  • Annexin A5