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Changes in the number and cytotoxic potential of uterine Natural Killer (uNK) cells have been associated with reduced fertility. To provide a better characterization of immunophenotypes in the endometrium of women with uRPL (unexplained recurrent pregnancy loss), we examined the applicability of a set of five immune cell markers. The concentration (cells/mm 2 ) of CD45 + leukocytes, CD56 + uNK cells, and CD138 + plasma cells as well as of CD16 + and CD57 + cells, which indicate high cytotoxic uNK cells, were assessed by immunohistochemistry in endometrial biopsies from 61 uRPL patients and 10 controls. Control fertile endometria presented 90-300 CD56 + uNK cells/mm 2 . uRPL cases were classified in subgroups of low (uRPL-CD56 low &lt; 90 cells/mm 2 ), normal (uRPL-CD56 normal 90-300 cells/mm 2 ), and high uNK cell counts (uRPL-CD56 high &gt; 300 cells/mm 2 ). Some cases from the uRPL-CD56 low and uRPL-CD56 normal subgroups showed elevated proportions of cytotoxic CD16 + and CD57 + cells in relation to CD56 + cells. In the uRPL-CD56 high subgroup, the CD57/CD56 ratio was reduced in most samples and the CD16/CD56 ratio was unaltered. Analysis of CD138 excluded the influence of chronic endometritis on these observations. Our results reinforce a link between uRPL and a dysfunctional endometrial environment associated with distinct immune cell profiles.

Beyond Uterine Natural Killer Cell Numbers in Unexplained Recurrent Pregnancy Loss: Combined Analysis of CD45, CD56, CD16, CD57, and CD138