Ovarian stimulation does not influence the uterine immune environment in healthy infertile women

Reprod Biomed Online. 2020 Jan;40(1):113-123. doi: 10.1016/j.rbmo.2019.08.004. Epub 2019 Aug 22.


Research question: There is some controversy regarding the impact of ovarian stimulation on immune cells in women undergoing IVF. The study's aim was to determine whether ovarian stimulation affected immune uterine cells in healthy women undergoing IVF.

Design: This prospective cohort study included 28 patients undergoing IVF and 47 healthy oocyte donors. Endometrial biopsies were taken in a natural cycle and after ovarian stimulation. All participants had a normal karyotype, pelvic ultrasound and cervical cytology results and thyroid-stimulating hormone concentration, as well as normal glucose and insulin concentrations and inherited and acquired thrombophilia test results. Screening tests including human papillomavirus were normal. Immune cells were analysed using three techniques: fluorescence-activated cell sorting, immunohistochemistry and gene expression. A human leukocyte antigen (HLA)-C tetramer was used as an 'artificial embryo'. The expression of genes including those for tumour necrosis factor (TNF)-α and interleukin-10 (IL-10) was analysed.

Results: A comparison was made of the percentage and gene expression of CD56brightCD16- uterine natural killer (uNK), CD56dimCD16+ natural killer cells, CD56-CD16+ natural killer cells and TregCD25+CD4+FoxP3+ cells, uNK binding to the HLA-C tetramer, and TNF-α and IL-10 expression. No between- or within-group differences were observed in natural versus ovarian stimulation cycles.

Conclusions: Ovarian stimulation does not affect the uterine immune cell population or HLA-C binding in healthy women undergoing ovarian stimulation. Further studies are underway to find out if different responses might be seen in women with previous autoimmune disorders.

Keywords: Endometrial biopsies; Immune cell populations; Natural cycles; Ovarian stimulation; Peripheral blood natural killer cells; Uterine natural killer cells.

MeSH terms

  • Adult
  • Embryo Implantation / immunology
  • Female
  • Humans
  • Infertility, Female / immunology*
  • Killer Cells, Natural / immunology*
  • Menstrual Cycle / immunology
  • Ovulation Induction*
  • Prospective Studies
  • Uterus / immunology*