Detailed endometrial immune assessment of both normal and adverse reproductive outcome populations
Using a comprehensive flow cytometric panel, do endometrial immune profiles in adverse reproductive outcomes such as repeat implantation failure (RIF) and repeat pregnancy loss (RPL) differ from each other and male-factor controls?
Six-hundred and twelve patients had an endometrial biopsy to assess the immunophenotype. History on presentation was used to subdivide the population into recurrent implantation failure (RIF) [n = 178], recurrent pregnancy loss (RPL) [n = 155], primary infertility [n = 130] and secondary infertility [n = 114]. A control group was utilised for comparative purposes [n = 35] and lymphocyte subpopulations were described.
Distinct lymphocyte percentage differences were noted across the populations. Relative to controls and RPL, patients with a history of RIF had significantly raised uterine NKs (53.2 vs 45.2 & 42.9%, p < 0.0001). All sub-fertile populations had increased percentage peripheral type NKs (p = 0.001), and exhibited increased CD69+ activation (p = 0.005), higher levels of B cells (p < 0.001), elevated CD4:CD8 ratio (p < 0.0001), lower T-regs (p = 0.034) and a higher proportion of Th1+ CD4s (p = 0.001). Patient aetiology confers some distinct findings, RPL; pNK, Bcells and CD4 elevated; RIF; uNK and CD56 raised while CD-8 and NK-T lowered.
Flow cytometric endometrial evaluation has the ability to provide a rapid and objective analysis of lymphocyte subpopulations. The findings show significant variations in cellular proportions of immune cells across the patient categories relative to control tissue. The cell types involved suggest that a potential differential pro-inflammatory bias may exist in patients with a history of adverse reproductive outcomes. Immunological assessment in appropriate populations may provide insight into the underlying aetiology of some cases of reproductive failure.
KeywordsEndometrium ART Natural killer cells Lymphocytes Immunophenotype
preimplantation genetic analysis-aneuploidy
recurrent pregnancy loss
repeat implantation failure
assisted reproductive technologies
hormone replacement therapy
uterine type natural killer cells
peripheral blood type natural killer cells
cluster of differentiation
T helper type 1 (pro-inflammatory)
T helper type 2 (anti-inflammatory)
Thanks to the Sims IVF patients who contributed tissue samples to facilitate the analysis and the Staff of the Clinic for their support. Thanks also to Dr. Renate Van der Molen, UMC Radboud, for critical appraisal of the manuscript.
Compliance with ethical standards
Informed consent was obtained from all individual participants included in the study.
Conflict of interest
The authors declare no conflict of interest is present.
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