title: 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.
authors.affiliation: CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham NG8 6PZ, United Kingdom. Electronic address: simon.fishel@carefertility.com.
authors.forename: Simon
authors.initials: S
authors.lastname: Fishel
authors.affiliation: CARE Manchester, 108-112 Daisy Bank Road, Victoria Park, Manchester M14 5QH, United Kingdom.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Patel
authors.affiliation: CARE Manchester, 108-112 Daisy Bank Road, Victoria Park, Manchester M14 5QH, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Lytollis
authors.affiliation: CARE Northampton, 67 The Avenue, Cliftonville, Northampton NN1 5BT, United Kingdom.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Robinson
authors.affiliation: CARE Nottingham, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham NG8 6PZ, United Kingdom.
authors.forename: Mary
authors.initials: M
authors.lastname: Smedley
authors.affiliation: CARE Sheffield, 24-26 Glen Road, Sheffield S7 1RA, United Kingdom.
authors.forename: Paula
authors.initials: P
authors.lastname: Smith
authors.affiliation: CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham NG8 6PZ, United Kingdom.
authors.forename: Craig
authors.initials: C
authors.lastname: Cameron
authors.affiliation: CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham NG8 6PZ, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Thornton
authors.affiliation: CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham NG8 6PZ, United Kingdom.
authors.forename: Ken
authors.initials: K
authors.lastname: Dowell
authors.affiliation: CARE Manchester, 108-112 Daisy Bank Road, Victoria Park, Manchester M14 5QH, United Kingdom.
authors.forename: Glenn
authors.initials: G
authors.lastname: Atkinson
authors.affiliation: CARE Sheffield, 24-26 Glen Road, Sheffield S7 1RA, United Kingdom.
authors.forename: Adel
authors.initials: A
authors.lastname: Shaker
authors.affiliation: CARE Nottingham, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham NG8 6PZ, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Lowe
authors.affiliation: CARE Northampton, 67 The Avenue, Cliftonville, Northampton NN1 5BT, United Kingdom.
authors.forename: Rahnuma
authors.initials: R
authors.lastname: Kazem
authors.affiliation: CARE Dublin, Beacon CARE Fertility, Beacon Court, Sandyford, Dublin 18, Ireland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Brett
authors.affiliation: CARE Dublin, Beacon CARE Fertility, Beacon Court, Sandyford, Dublin 18, Ireland.
authors.forename: Anna
authors.initials: A
authors.lastname: Fox
mesh_terms: D000026:Abortion, Habitual / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D017304:Annexin A5 / Q000235:genetics*; D005260:Female; D005307:Fertilization in Vitro; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D019851:Thrombophilia / Q000453:epidemiology / Q000235:genetics
chemical_list: D017304:Annexin A5
keywords: ANXA5; infertility; miscarriage; recurrent pregnancy loss; thrombophilia