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Detailed endometrial immune assessment of both normal and adverse reproductive outcome populations

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

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?

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

PGT-A:

preimplantation genetic analysis-aneuploidy

RPL:

recurrent pregnancy loss

RM:

recurrent miscarriage

RIF:

repeat implantation failure

ART:

assisted reproductive technologies

HRT:

hormone replacement therapy

uNK:

uterine type natural killer cells

pNK:

peripheral blood type natural killer cells

CD:

cluster of differentiation

Th1:

T helper type 1 (pro-inflammatory)

Th2:

T helper type 2 (anti-inflammatory)

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Acknowledgements

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.

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Authors and Affiliations

  1. Sims IVF Clinic, Clonskeagh Road, Clonskeagh, Dublin, 14, Ireland

    Kevin Marron & David Walsh

  2. RCSI, Beaumont Hospital, Dublin, Ireland

    Conor Harrity

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  1. Kevin Marron
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  2. David Walsh
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Correspondence to Kevin Marron.

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Informed consent was obtained from all individual participants included in the study.

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Co-localisation of CD45 lymphocytes with 7-AAD illustrating only live endometrial derived cells are analysed in the lymphocytes gate. (JPG 460 kb)

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Marron, K., Walsh, D. & Harrity, C. Detailed endometrial immune assessment of both normal and adverse reproductive outcome populations. J Assist Reprod Genet 36, 199–210 (2019). https://doi.org/10.1007/s10815-018-1300-8

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  • DOI: https://doi.org/10.1007/s10815-018-1300-8

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