Treatment with tumor necrosis factor inhibitors and intravenous immunoglobulin improves live birth rates in women with recurrent spontaneous abortion

Am J Reprod Immunol. 2008 Jul;60(1):8-16. doi: 10.1111/j.1600-0897.2008.00585.x. Epub 2008 Apr 1.


Problem: The purpose of this study was to investigate whether treatment with tumor necrosis factor (TNF) inhibitors combined with intravenous immunoglobulin (IVIG) increases live birth rates among women with recurrent spontaneous abortion (RSA) concurrently treated with anticoagulants (AC).

Method of study: Seventy-five pregnancies in patients with a history of RSA were retrospectively evaluated. The population was divided into three groups: group I: 21 patients treated with AC (anticoagulants), group II: 37 patients treated with AC and IVIG, and group III: 17 patients treated with AC, IVIG and the TNF inhibitor Etanercept (Enbrel) or Adalimumab (Humira). In groups II and III, IVIG was administered at least once during the cycle of conception and/or at least once after a positive pregnancy test. In group III, either Adalimumab or Etanercept was administered by subcutaneous injection according to standard protocols. Statistical analysis of pregnancy outcome was performed using Fisher's exact test.

Results: Patient populations in the three treatment groups were similar in terms of age, past miscarriages, inherited thrombophilia and autoimmunity. The live birth rate was 19% (4/21) in group I, 54% (20/37) in group II, and 71% (12/17) in group III. There was significant improvement in pregnancy outcome in group II versus group I (P = 0.0127) and in group III versus group I (P = 0.0026). The live birth rate in group III compared to group II was not significantly different (P = 0.3723). Side effects of AC, IVIG and TNF inhibitor treatment were minimal in these patients, and no birth defects were identified in their offspring.

Conclusion: In women with RSA, addition of either IVIG or a TNF inhibitor + IVIG to the AC regimen appears to improve live birth rates compared to the treatment with AC alone. The positive effect of IVIG and TNF inhibitor therapy on pregnancy outcome merits further study in prospective clinical trials.

MeSH terms

  • Abortion, Habitual / prevention & control*
  • Adult
  • Anticoagulants / administration & dosage*
  • Drug Therapy, Combination
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulins, Intravenous / administration & dosage*
  • Immunosuppressive Agents / administration & dosage*
  • Middle Aged
  • Pregnancy
  • Pregnancy Rate*
  • Receptors, Tumor Necrosis Factor / administration & dosage*
  • Retrospective Studies
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Anticoagulants
  • Immunoglobulin G
  • Immunoglobulins, Intravenous
  • Immunosuppressive Agents
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept