Altered Endometrial Memory T-Cell Profiles During the Window of Implantation in Women with Previous Miscarriage.

Aim: This study aimed to characterize and compare the composition of central (TCM), effector (TEM), tissue-resident (TRM), and terminally differentiated (TEMRA) memory T cells in mid-luteal endometrium during the window of implantation (WOI) in women with and without a previous miscarriage.

Methods

Stromal lymphocytes from endometrial samples (P + 5) were analyzed by multicolor flow cytometry to quantify total, CD4+ and CD8+ TCM (CD45RA-CCR7+), TEM (CD45RA-CCR7-), TRM (CD69+), and TEMRA (CD45RA+CCR7-) subsets. Participants were grouped as having no previous miscarriage (n = 38) or ≥1 previous miscarriage (n = 33), and the relative distribution of these memory subsets was compared between groups. Correlations, PCA and logistic regression were used to assess global memory network organization.

Results

Women with prior miscarriage exhibited higher TCM proportions among total and CD8+ lymphocytes (p < 0.01), alongside lower CD8+ TEM (p = 0.02) and higher CD4+ TEM (p = 0.01). TRM showed a mild, non-significant increase (p = 0.18), while TEMRA remained stable. TRM correlated positively with both TCM (r = 0.51) and CD4+ TEM (r = 0.40), indicating coordinated organization among memory subsets. Multivariate analyses (PCA and logistic regression) confirmed these trends and identified the TCM/TEM ratio as the most discriminative parameter.

Conclusions

Endometrial memory T-cell composition during the WOI differs in women with miscarriage history, characterized by central memory expansion and reduced effector memory proportions, with parallel increases in tissue-resident cells. These changes suggest persistent remodeling of the local immune memory network toward a long-lived, less differentiated phenotype that may influence implantation readiness in subsequent cycles.