Is immune system activation/systemic inflammation a prerequesite for successful reproduction? association of immune system activation with embryo quality during in vitro fertilization (IVF)

Abstract

Requiring implantation and tolerance of semi-allograft, pregnancy mandates complex immunological processes. Degree of immune system activation has been associated with pregnancy complications. Effects of immune system activation on embryo quality has, however, never been investigated. Cohort study. 125 infertile women underwent 169 IVF cycles. Embryo quality was defined as good (4-cell d-2; 8-cell d-3, Grade 4-5), poor (arrested or degenerated, Grade ≤ 2) or fair (all embryos in between). Immune system activation was tested utilizing immune parameters, demonstrated effective in prior studies in identifying immune system activation with good sensitivity: thyroid antibodies (peroxidase, thyroglobulin, thyroid receptor antibodies), total immunoglobulins (IgG, IgM, IgA, IgE), antiphospholipid antibodies (β2 glycoprotein, anticardiolipin, antiphosphatidylserine, lupus anticoagulant), antinuclear antibody, anti-adrenal antibody (21-hydroxylase) and anti-ovarian antibodies. Any positive finding was considered indicative of immune activation. Patient age was 38.9 ± 5.5 years. Immune system activation was associated with significantly better embryo quality (P=0.008). This association persisted after adjustment for age and repeat IVF cycles (P=0.006). Observed improvement in embryo quality derived mostly from better embryo grade (3.7 ± 0.05 vs. 3.4 ± 0.07, P=0.002). This is the first report associating improved embryo quality with maternal immune system activation. These data relate to recent report from our center that normal androgen levels appear associated with immune system activation, while low androgen levels fail to show such activation (Gleicher et al ESHRE 2013/Reprod Biol Encocrinol 2013; In press). Combined, these data suggest that immune system activation/systemic inflammation, possibly via androgen effects on follicle maturation, contributes to embryo quality and pregnancy success with IVF.