Elevated Preconception CD56+16+ and/or Th1:Th2 Levels Predict Benefit from IVIG Therapy in Subfertile Women Undergoing IVF

Abstract

We sought to answer two questions: First, is there a group of patients who benefit from intravenous immunoglobulin (IVIG) in IVF? Second can this group of patients be identified by preconception blood testing? A total of 202 IVF cycles in subfertile women were divided into four groups. Group I: 62 cycles with preconception Th1:Th2 ratio and/or % CD56(+) cell elevation using IVIG; Group II: 27 cycles with similar Th1:Th2 and/or % CD56(+) cell elevation not using IVIG; Group III: 71 cycles with normal Th1:Th2 and/or % CD56(+) cell levels using IVIG; Group IV: 42 cycles with normal Th1:Th2 and % CD56(+) levels not using IVIG. These groups were similar with regard to patient age, diagnosis, and past failure history. The implantation rate (number of gestational sacs per embryo transferred, with an average of two embryos transferred per cycle) was 45% (55/123), 22% (12/54), 54% (75/139), and 48% (40/84) for Groups I-IV, respectively. The clinical pregnancy rate (fetal heart activity per IVF cycle started) was 61% (38/62), 26% (7/27), 69% (49/71), and 71% (30/42), respectively. The live birth rate was 58% (36/62), 22% (6/27), 61% (43/71), and 71% (30/42), respectively, and the live birth per embryo transferred was 40% (49/123), 13% (7/24), 43% (60/139), and 48% (40/84), respectively. There was a significant improvement in implantation, clinical pregnancy, live birth rate and live birth rate per embryo transferred for Group I versus Group II (P = 0.0032, 0.0021, 0.0017, and 0.0002, respectively) and for Group II versus Group IV (P = 0.0021, 0.0002, <0.0001 and <0.0001, respectively). There was no significant difference in success rates between Groups I and III (P = 0.085, 0.23, 0.45, 0.34, respectively) and between Groups III and IV (P = 0.22, 0.48, 0.17, 0.31, respectively). In subfertile women with preconception Th1:Th2 and/or % CD56(+) cell elevation, IVF success rates are low without IVIG therapy but significantly improve with IVIG therapy. In patients with normal Th1:Th2 and normal CD56(+) cell levels, IVF success rates were not further improved with IVIG therapy. IVIG may be a useful treatment option for patients with previous IVF failure and preconception Th1:Th2 and/or NK elevation. Preconception immune testing may be a critical tool for determining which patients will benefit from IVIG therapy. Prospective controlled studies (preferably double-blind, stratified, and randomized) are needed for confirmation.