H-Y antibody titers are increased in unexplained secondary recurrent miscarriage patients and associated with low male : female ratio in subsequent live births.
BACKGROUND
The birth of a boy is significantly more common than a girl prior to secondary recurrent miscarriage (SRM) and is associated with a poorer chance of a subsequent live birth. Children born after SRM are more likely to be girls. High-titer antisera specific for male antigens (H-Y) have been shown to arrest development of male bovine embryos efficiently. We consequently questioned the role of H-Y antibodies in women with SRM.


METHODS
Serum samples from patients with unexplained SRM (n = 84), unexplained primary recurrent miscarriage (PRM) (n = 12) and healthy women (n = 37) were obtained. The samples were taken during pregnancy (gestational weeks 4-5) for 77 (80%) of the patients. Enzyme-linked immunosorbent assay was used to detect immunoglobulin G antibodies that specifically recognized any of the five recombinant H-Y proteins (EIF1AY, RPS4Y1, ZFY, DDX3Y and UTY) and their H-X homologs.


RESULTS
H-Y-specific antibodies were more frequent in SRM patients (46%) compared with female controls (19%, P = 0.004) and PRM patients (8%, P = 0.01). The presence of H-Y antibodies in early pregnancy was associated with a low male: female birth ratio among the subsequent live births, as only 12% of children born to H-Y antibody-positive patients were boys compared with 44% boys born to H-Y antibody negative patients (P = 0.03).


CONCLUSIONS
The high frequency of H-Y antibody-positive SRM patients and the association between the presence of these antibodies in early pregnancy and the low number of male offspring, suggest that maternal immune responses against H-Y antigens can cause pregnancy losses. Further exploring these mechanisms may increase our understanding of unexplained SRM.
Nielsen
H S
HS
The Fertility Clinic 4071, University Hospital Copenhagen, Blegdamsvej 9, Rigshospitalet, Copenhagen Ø, Denmark. henriette.svarre.nielsen@rh.regionh.dk
Wu
F
F
Aghai
Z
Z
Steffensen
R
R
van Halteren
A G
AG
Spierings
E
E
Christiansen
O B
OB
Miklos
D
D
Goulmy
E
E
D000026:Abortion, Habitual / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006182:H-Y Antigen / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007518:Isoantibodies / Q000032:analysis*; D008297:Male; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D012744:Sex Ratio
D006182:H-Y Antigen; C051256:H-Y antibody; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies
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