Ovarian Stimulation (OS) Does Not Influence the Uterine Immune Environment in Healthy Infertile Women

Abstract Research question There is some controversy regarding the impact of ovarian stimulation (OS) on immune cells in women undergoing IVF. Our aim was to determine whether OS impacted immune uterine cells in healthy patients undergoing IVF. Design Prospective cohort study. 28 patients undergoing IVF and 47 healthy oocyte donors were included. Endometrial biopsies were taken in a natural cycle and after OS. All the patients had a normal karyotype, pelvic ultrasound, cervical cytology and TSH level, as well as normal glucose and insulin levels and inherited and acquired thrombophilia tests. They tested negative for HPV, Chlamydia, Ureaplasma and Mycoplasma. Immune cells were analyzed using three techniques flow cytometry, immunohistochemistry and gene expression. An HLA-C tetramer was used as an “artificial embryo”. The gene expression of TNF alpha and IL-10 was analyzed. Results We compared the % and gene expression of the CD56brightCD16− uterine NK (uNK), CD56dimCD16+ NK cells, CD56−CD16+ NK cells, TregCD25+CD4+FoxP3+ cells, the uNK binding to the HLA-C tetramer, and the TNFalpha and IL-10 expression. No between- or within-group differences were observed in natural vs OS cycles. Conclusion OS does not affect the uterine immune cell population or HLA-C binding in healthy women undergoing OS. Further studies are underway to find out if women with previous autoimmune disorders may provide different responses.