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

Abstract

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.

M2/ANXA5 haplotype as a predisposition factor in Malay women and couples experiencing recurrent spontaneous abortion: a pilot study

“…On the other hand, uncertainties in the exact timing of conception allow for ±1 to 2 weeks difference, when recording the timing of pregnancy loss. Alternatively, M2/ ANXA5 might not only have a role in placental vascular remodelling but also in the process of embryonic implantation, as recently suggested (Fishel et al, 2014).…”

Evolution of embryo selection for IVF from subjective morphology assessment to objective time-lapse algorithms improves chance of live birth

“…Pituitary suppression for ovarian stimulation and oocyte maturation has been described previously (Fishel et al, 2014).…”

Maternal and paternal carriage of the annexin A5 M2 haplotype: a possible risk factor for recurrent implantation failure (RIF)

“…Matsubayashi et al demonstrated that RIF patients produce anti-ANXA5 significantly more often than controls (8.3% vs. 1.1%, p < 0.05) and consequently postulate anti-ANXA5 antibodies as risk factor for RIF [40]. Currently, there is only one multicenter study by Fishel et al analyzing the M2/ANXA5 haplotype in infertility couples undergoing ART procedure [41]. They reported a M2 carrier status of 44% in IVF couples (n = 157; one or both partners), 24% of females, 26% of males, and 37% of couples with unexplained infertility [41].…”

“…Currently, there is only one multicenter study by Fishel et al analyzing the M2/ANXA5 haplotype in infertility couples undergoing ART procedure [41]. They reported a M2 carrier status of 44% in IVF couples (n = 157; one or both partners), 24% of females, 26% of males, and 37% of couples with unexplained infertility [41]. In spite of these intruiging results, the relevance of M2/ANXA5 for RIF has not yet been studied.…”