title: Secondary recurrent miscarriage and H-Y immunity.
abstract: BACKGROUND
  Approximately half recurrent miscarriage (RM) cases remain unexplained after standard investigations. Secondary RM (SRM) is, in contrast to primary RM, preceded by a birth, which increases the transfer of fetal cells into the maternal circulation. Mothers of boys are often immunized against male-specific minor histocompatibility (H-Y) antigens, and H-Y immunity can cause graft-versus-host disease after stem-cell transplantation. We proposed the H-Y hypothesis that aberrant H-Y immunity is a causal factor for SRM.
  
  
  METHODS
  This is a critical review of the H-Y hypothesis based on own publications and papers identified by systematic PubMed and EMBASE searches.
  
  
  RESULTS
  SRM is more common after the birth of a boy and the subsequent live birth rate is reduced for SRM patients with a firstborn boy. The male:female ratio of children born prior and subsequent to SRM is 1.49 and 0.76 respectively. Maternal carriage of HLA-class II alleles presenting H-Y antigens to immune cells is associated with a reduced live birth rate and increased risk of obstetric complications in surviving pregnancies in SRM patients with a firstborn boy. In early pregnancy, both antibodies against HLA and H-Y antigens are increased in SRM patients compared with controls. Presence of these antibodies in early pregnancy is associated with a lower live birth rate and a low male:female ratio in subsequent live births, respectively. Births of boys are also associated with subsequent obstetric complications in the background population.
  
  
  CONCLUSIONS
  Epidemiological, immunogenetic and immunological studies support the hypothesis that aberrant maternal H-Y immune responses have a pathogenic role in SRM.
authors.affiliation: The Fertility Clinic 4071, University Hospital Copenhagen, Blegdamsvej 9, Rigshospitalet, Copenhagen Ø, Denmark. henriette.svarre.nielsen@rh.regionh.dk
authors.forename: Henriette Svarre
authors.initials: HS
authors.lastname: Nielsen
mesh_terms: D000026:Abortion, Habitual / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D006182:H-Y Antigen / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology / Q000276:immunology; D011256:Pregnancy Outcome; D012307:Risk Factors
chemical_list: D006182:H-Y Antigen; D000949:Histocompatibility Antigens Class II