Are uterine natural killer and plasma cells in infertility patients associated with endometriosis, repeated implantation failure, or recurrent pregnancy loss?

Abstract

Purpose Infertility is a debilitating situation that millions of women around the world suffer from, but the causal relationship between infertility and endometriosis is still unclear. We hypothesize that the immune cell populations of uterine natural killer cells (uNK) and plasma cells (PC) which define chronic endometritis could differ in patients with or without endometriosis and therefore be the link to endometriosis-associated infertility. Methods Our retrospective study includes 173 patients that underwent an endometrial scratching in the secretory phase of the menstrual cycle and subsequently immunohistochemical examination for uNK cells and PC. Sixty-seven patients were diagnosed with endometriosis, 106 served as the control cohort. Results The risk for an elevated number of uNK cells in women with endometriosis is not increased as compared to the control group. Our findings suggest that patients with endometriosis are 1.3 times more likely to have chronic endometritis (CE) as compared to those without and that the treatment with doxycycline might increase pregnancy rates. Endometriosis and an increased number of uNK cells seem to be unrelated. Conclusions In contrast to the lately published connection between endometriosis, infertility and increased uNK cells, we could not find any evidence that patients with endometriosis are more prone to elevated uterine uNK cells. Counting of PC in endometrial biopsies might be a new approach in the search of biomarkers for the nonsurgical diagnosis of endometriosis since our findings suggest a connection.

Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis

“…Hypoxia-induced factor-1a is stabilized by activation of signal transducer and activator of transcription-3 recently shown to be overexpressed in women with endometriosis and infertility. Cycylo-oyxgenase 2 and signal transducer and activator of transcription-3 expression have been linked to inflammatory cytokines such as interleukin (IL)-17 and IL-6 (63)(64)(65), which also are elevated in women with endometriosis (66) Conversely, despite reports of increased uterine natural killer (uNK) cells in infertility, Freitag et al (67) could not find any evidence that patients with endometriosis are more prone to elevated uterine uNK cell.…”

Immunological Risk Factors in Recurrent Pregnancy Loss: Guidelines Versus Current State of the Art

“…However, a benefit of longer antibiotic courses was demonstrated [ 87 ]. First-line therapy with doxycycline for 14–21 days is a promising approach with cure-rates of up to 95% [ 96 , 97 , 98 ]. Still, a test of cure by performing a re-biopsy should be performed after completion.…”

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

“…Several reports on the importance of KIR receptors in endometriosis [51,52] and the expression of NKG2D [53]. However, more analysis is required because of the contradictory reports on uNK cells in endometriosis and inflammatory events related to pregnancy loss [54,55].…”