Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 2, pp 199–210 | Cite as

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

  • Kevin MarronEmail author
  • David Walsh
  • Conor Harrity
Reproductive Physiology and Disease



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.


Endometrium ART Natural killer cells Lymphocytes Immunophenotype 



preimplantation genetic analysis-aneuploidy


recurrent pregnancy loss


recurrent miscarriage


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

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

Conflict of interest

The authors declare no conflict of interest is present.

Supplementary material

10815_2018_1300_MOESM1_ESM.docx (636 kb)
ESM 1 (DOCX 635 kb)
10815_2018_1300_MOESM2_ESM.jpg (461 kb)
ESM 2 Co-localisation of CD45 lymphocytes with 7-AAD illustrating only live endometrial derived cells are analysed in the lymphocytes gate. (JPG 460 kb)
10815_2018_1300_MOESM3_ESM.docx (13 kb)
ESM 3 (DOCX 13 kb)
10815_2018_1300_MOESM4_ESM.docx (33 kb)
ESM 4 (DOCX 33 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Sims IVF ClinicDublinIreland
  2. 2.RCSIBeaumont HospitalDublinIreland

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