A new role for natural killer cells, interleukin (IL)-12, and IL-18 in repeated implantation failure after in vitro fertilization

Fertil Steril. 2004 Jan;81(1):59-65. doi: 10.1016/j.fertnstert.2003.06.007.


Objective: To investigate the endometrial immunohistochemical staining of interleukin (IL)-12 and IL-18 and to quantify the CD56 bright natural killer (NK) cells in relation to Doppler vascular disorders.

Design: Controlled clinical study.

Setting: Research unit of a university hospital. PATIENT(S)": Thirty-five women with repeated implantation failure after ET in IVF and 12 fertile control patients.Ultrasound evaluation and endometrial biopsy on day 20.

Main outcome measure(s): The balance between IL-12 and IL-18, the number of NK cells, and the vascular status among fertile and implantation failure patients.

Result(s): The control patients displayed normal vascular parameters, a weak anti-IL-12 staining, a consistent moderate stromal anti-IL-18 staining, and fewer than 15 NK cells/field. This pattern was observed among only 17% (6/35) of the implantation failure group. The remaining patients fit into one of two patterns: [1] 37% (13/35) had more than 40 NK cells/field with a strong anti-IL-12 and/or anti-IL-18 staining, and [2] the remaining 46% (16/35) had a marked local depletion of IL-18 and IL-12. Respectively, 85% and 31% of two groups displayed abnormal vascular parameters.

Conclusion(s): Distinctions between the different local dysregulations of the cytokine network may provide clues for further exploration and treatment.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD56 Antigen / metabolism
  • Embryo Implantation*
  • Embryo Transfer
  • Endometrium / immunology
  • Female
  • Fertilization in Vitro / methods*
  • Humans
  • Infertility, Female / therapy*
  • Interleukin-12 / physiology*
  • Interleukin-18 / physiology*
  • Killer Cells, Natural / physiology*
  • Luteal Phase
  • Male
  • Neovascularization, Pathologic / immunology
  • Predictive Value of Tests
  • Pregnancy
  • Reference Values
  • Treatment Failure
  • Ultrasonography
  • Uterus / blood supply
  • Uterus / diagnostic imaging
  • Uterus / physiology


  • CD56 Antigen
  • Interleukin-18
  • Interleukin-12