Menstrual Effluent Derived Immune Cell Composition Is Distinct in Women Using Contraceptives: A Pilot Study

Menstrual effluent (ME) is widely used to study immune-related reproductive disorders. However, women using contraceptives are often excluded from such studies due to limited knowledge of their impact on the endometrial immune cell composition. This gap in knowledge restricts our ability to include women using contraceptives in the scientific investigations and account for potential immunological variations associated with contraceptive use. Therefore, we aim to investigate whether contraceptive use is associated with differences in the uterine immune system.

ME was collected from women using combined oral contraceptives (COC, n = 5), a copper intrauterine device (IUD, n = 3), or no contraceptives (n = 5). Immune cells were isolated from ME and analyzed using flow-cytometry. Data were analyzed using an unpaired t-test, followed by multiple testing correction using the false discovery rate (FDR) method.

Women using COCs exhibited a marked reduction in the frequency of the immunoregulatory CD56^brightCD16^- endometrial Natural Killer (eNK) cells compared to women using no contraceptives (30.1% ± 5.99 and 66.0% ± 10.6; p = 0.001). Additionally, women using copper IUD showed elevated frequencies of proliferating Ki-67⁺CD8⁺ T cells compared to COC users and controls (19.8% ± 4.3, 2.69% ± 1.23, and 3.77% ± 4.4).

This pilot study highlights the importance of considering contraceptive use when studying immune-related reproductive problems.