Elevated preconception CD56+ 16+ and/or Th1:Th2 levels predict benefit from IVIG therapy in subfertile women undergoing IVF

Am J Reprod Immunol. 2011 Nov;66(5):394-403. doi: 10.1111/j.1600-0897.2011.01018.x. Epub 2011 May 30.


Problem: 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?

Method of study: 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.

Results: 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).

Conclusion: 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.

MeSH terms

  • Adult
  • CD56 Antigen / metabolism*
  • Cytokines / metabolism*
  • Embryo Implantation
  • Embryo Transfer
  • Female
  • Fertilization in Vitro / methods*
  • Humans
  • Immunoglobulins, Intravenous / immunology
  • Immunoglobulins, Intravenous / therapeutic use*
  • Infertility / immunology
  • Infertility / therapy*
  • Live Birth
  • Preconception Care
  • Predictive Value of Tests
  • Pregnancy
  • Pregnancy Rate
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Treatment Outcome


  • CD56 Antigen
  • Cytokines
  • Immunoglobulins, Intravenous
  • NCAM1 protein, human