Rabbit Anti-Human UNK (a.a. 640-810) Polyclonal antibody

PurposeUsing 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?MethodsSix-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.ResultsDistinct 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.ConclusionsFlow 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.

Problem To what extent do endocrine, immunological, gene expression and histological markers of endometrial receptivity correlate? Method of study Between November 2017 and September 2019, 121 women referred to a University Hospitals Fertility Clinic consented to inclusion in this cohort study. The women underwent timed endometrial biopsy followed by blood samples in a hormone-substituted cycle. Of these, 37 women had just started IVF treatment, and the remaining 84 had experienced recurrent implantation failure following IVF/ICSI. The hormone-substituted cycle consisted of initiation with oral oestradiol followed by addition of vaginal progesterone treatment for five full days. Endometrial biopsies were subject to histological examination, immune cell markers by immunohistochemistry (CD56(+), CD16(+), CD163(+), FoxP3) and gene expression microarray analyses with the endometrial receptivity array (ERA(R)) test (Igenomix). Plasma progesterone and oestradiol were measured on the day of biopsy. Results CD56(+)uterine natural killer (uNK) cell counts correlate with transcriptional markers of endometrial receptivity assessed by the ERA test. Endometrial maturation, receptivity and immunological markers were not correlated with mid-luteal blood plasma progesterone level. Mid-luteal serum oestradiol level correlated with markers of endometrial maturation and receptivity. The tests were carried out during a standard hormone substitution cycle, and the findings may not apply in the natural cycle. Conclusion CD56(+)uNK cell counts and endometrial receptivity assessed by the ERA test appear to be linked. Mid-luteal progesterone levels were not correlated to the tested markers of endometrial receptivity. In contrast, mid-luteal oestradiol level was inversely related to markers of endometrial receptivity and maturation.