Birth defect rates in women using Adalimumab (Humira(®) ) to treat immunologic-based infertility in IVF patients

Am J Reprod Immunol. 2011 Sep;66(3):237-41. doi: 10.1111/j.1600-0897.2011.00994.x. Epub 2011 Apr 19.


Problem: This study compares the birth defect rate in women using preconception TNF-α inhibitor (Adalimumab) during an in vitro fertilization (IVF) cycle to a similar population of women not using these immunologic therapies.

Method of study: One hundred subfertile women aged ≤38years experienced ongoing pregnancies of which 36 resulted in twin pregnancies (136 babies). These successful cycles were divided into two different treatment groups: group I comprised 31 cycles (23 ICSI) using preconception Adalimumab (Humira) with or without pre- or post-conception intravenous immunoglobulin (IVIG) (last dose of Humira given 65.3±41.5days before embryo transfer). Group II comprised 69 cycles (58 ICSI) with no exposure to Humira or IVIG. Group I included all eligible fresh cycles containing at least five 5-celled embryos on day 3. Group II had similar entry criteria, but eligible cycles were randomly selected owing to a larger population size. Patients were later contacted by the clinic for neonatal health information.

Results: Delivery outcomes were as follows: group I experienced one case of DiGeorge syndrome (chromosome 22 deletion) that was electively terminated out of 41 babies (10 sets of twins) delivered. Group II experienced one case of neonatal heart defect and another case of Edward's syndrome (Trisomy 18) out of 95 babies (26 sets of twins) delivered. The anomaly rate was 2.44% (1/41) and 2.11% (2/95) for groups I and II, respectively, comparable to the expected birth defect rate for the normal IVF population.

Conclusion: Preconception TNF-α inhibitor does not appear to increase the birth defect rate in women undergoing IVF. A larger, clinical trial with blinded delivery assessment is needed to confirm these safety conclusions.

MeSH terms

  • Adalimumab
  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Congenital Abnormalities / epidemiology*
  • Enoxaparin / administration & dosage
  • Female
  • Fertilization in Vitro
  • Humans
  • Infertility, Female
  • Interleukin-10 / blood
  • Pregnancy
  • Th1-Th2 Balance
  • Tumor Necrosis Factor-alpha / blood


  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Enoxaparin
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Adalimumab