Patterns of Endometrial Immune Remodeling Following Intrauterine Platelet-Rich Plasma Administration Are Associated with Baseline Macrophage Abundance

Platelet-rich plasma (PRP) has emerged as a regenerative therapy for improving endometrial receptivity, although its effects on the endometrial immune microenvironment remain poorly understood. This prospective paired-sample study investigated changes in the endometrial immune microenvironment following intrauterine PRP administration during the window of implantation. Twenty-seven women undergoing assisted reproductive treatment provided paired endometrial biopsies before and after PRP administration. Stromal CD3+ T lymphocytes, CD4+ T-helper lymphocytes, CD56+ natural killer cells, and CD68+ macrophages were quantified by immunohistochemistry and digital image analysis. No significant overall changes in CD3+, CD4+, CD56+, or CD68+ cell abundance were observed after PRP administration (all p > 0.05). Nevertheless, exploratory analysis of individual paired trajectories showed that 77.8% of patients met the study-specific criterion for a coordinated immune remodeling pattern, defined as a concordant increase or decrease in at least three of the four analyzed immune cell populations. Patients with a coordinated-increase pattern had lower baseline CD68+ macrophage abundance than those with a coordinated-decrease pattern, with a large standardized effect size (Hedges’ g = 1.28) and nominal statistical significance (p = 0.04). However, this association did not remain significant after FDR correction (q = 0.165). These findings indicate heterogeneous, patient-specific patterns of endometrial immune-cell change following intrauterine PRP administration and suggest that baseline macrophage abundance may represent a candidate factor associated with subsequent immune remodeling patterns. The coordinated-remodeling classification and its association with baseline macrophage abundance should be considered exploratory and hypothesis-generating.