Uncomplicated oocyte donation pregnancies display an elevated CD163‐positive type 2 macrophage load in the decidua, which is associated with fetal‐maternal HLA mismatches

PROBLEM: The embryo of an oocyte donation (OD) pregnancy is completely allogeneic to the mother, which may challenge the maternal immune system to tolerize the fetus. Decidual macrophages are essential in maintaining a healthy pregnancy, and type 2 macrophages may exhibit immune suppressive activity. We hypothesized that the composition of decidual macrophages is different between uncomplicated OD pregnancies and non‐OD in vitro fertilization (IVF) pregnancies, and is related to fetal‐maternal incompatibility. METHOD OF STUDY: Women with uncomplicated pregnancy were enrolled: 25 singleton OD pregnancies and 17 non‐OD IVF pregnancies. The extent of immunohistochemical staining of CD14 (pan‐macrophage marker) and CD163 (type 2 macrophage marker) in both decidua basalis and parietalis was quantitated by digital image analysis. Maternal and fetal DNA was typed for human leukocyte antigen (HLA)‐A, ‐B, C, ‐DRB1, and ‐DQB1, and fetal‐maternal HLA mismatches were calculated. RESULTS: OD pregnancies showed a higher percentage of CD163+ staining (P = .040) and higher CD163/CD14 ratio (P = .032) in the parietalis than non‐OD IVF. The OD group was separated into a semi‐allogeneic group (≤5 fetal maternal HLA mismatches) and a fully allogeneic group (> 5 mismatches). The HLA‐fully‐allogeneic OD group, but not the HLA‐semi‐allogeneic OD group, showed significantly elevated CD163/CD14 ratio in the parietalis compared with the non‐OD IVF group (P < .05). CONCLUSIONS: Uncomplicated OD pregnancies display a higher CD163‐positive cell fraction in the total decidual macrophage population compared to autologous pregnancies, which may suggest that a local type 2 macrophage‐related mechanism is needed to compensate for the higher fetal‐maternal HLA mismatch load.