Immunomorphological Features of the Placenta in Allogeneic Pregnancy as the Background for the Development of Obstetric Complications.

OBJECTIVE: To study the structural and immunohistochemical features of placentas in women after assisted reproductive technology (ART) with allogeneic eggs (oocyte donation and surrogate motherhood). STUDY DESIGN: The study involved 89 women whose pregnancy occurred as a result of in vitro fertilization (IVF) with a donor egg in a surrogate motherhood program (IVF-SM, n = 47 patients) or oocyte donation (IVF-DO, n = 42). The comparison group consisted of 21 patients in whom pregnancy occurred as a result of IVF with their own egg (IVF-OE). A clinical and anamnestic analysis of the pregnant women was carried out. Morphological and immunohistochemical studies were performed on placental material. Immunohistochemical analysis of CD8, CD56, CD138, and CD25/CD4 markers indicating the processes of impaired tolerance in placenta was carried out. -Results: We observed a predominance of women aged >40 (range 42.7-3.91) years with a burdened somatic and obstetric-gynecological history and a high incidence of hypertensive pregnancy complications, such as gestational arterial hypertension (27.4%) and preeclampsia (28.5%), in the IVF-DO group. The IVF-SM group included mainly somatically healthy women aged <30 (29.4-3.19) years with a high risk of termination of pregnancy in the third trimester (49.6%) and premature birth (21.6%). Placentas taken from women after allogeneic pregnancy had pronounced signs of immune alteration, such as chronic histiocytic intervillositis, lymphoplasmacytic deciduitis, chronic chorioamnionitis, chronic villitis, and perivillous fibrinoid with lymphocytes (p [F] < 0.05). Immunohistochemical study of the placentas showed accumulation of CD138+ plasma cells, CD8+ T lymphocytes, and uterine natural killer cells, and a decrease in the number of CD25/CD4+ regulatory T cells (Tregs) in the structures of the uteroplacental region (Kruskal-Wallis test, p < 0.05). CONCLUSION: Placentas after IVF with oocyte donation and surrogate motherhood programs are characterized by similar changes, associated with the development of chronic inflammation in the structures of the placenta and immunohistochemical signs of impaired immunological tolerance at the maternal-fetal interface. The data we obtained allow us to classify pregnancies under surrogate motherhood programs as a risk factor for the development of pregnancy complications with immune pathogenesis.

Structural, immunohistochemical and molecular features of placentas and placental sites after in vitro fertilization with donor eggs (surrogate motherhood).

OBJECTIVE: to identify structural, immunohistochemical and molecular features of placentas and placental sites afterin vitro fertilization (IVF) with donor eggs (surrogate motherhood). STUDY DESIGN: morphological and immunohistochemical studies were performed on placental material obtained after delivery by caesarean section. The study included 26 women patients whose pregnancy resulted from IVF with a donor egg (IVF-SM group). The comparison group included 13 women patients whose pregnancy occurred after IVF with their own eggs (IVF-OE). Immunohistochemistry of biopsy material was performed using mouse antibodies to total cytokeratin (clone AE1/AE3) and murine antibodies to HLA-DR (clone TAL.1B5). Molecular studies were performed on DNA samples isolated from venous blood. HLA-DNA-TEH reagent kits and polymerase chain reaction were used for genotyping the main human histocompatibility complex class II (DQA1, DQB1 and DRB1). RESULTS: Histological examination of placenta in IVF-SM group showed a high incidence of central ischemic infarctions (69% of cases), dissociated cotyledon development (61%), pathological villus immaturity (46%) and massive perivillous fibrin deposition (73%). This group also had a pronounced lymphoplasmacytic deciduitis, which was 2 times higher than in the control group, and an expressed inflammatory process in the placental sites. Remodeling of the spiral arteries was incomplete in more than 40% of cases, and 30% of spiral arteries had no gestational changes. In comparison group, a complete gestational adjustment was found in more than 90% of spiral arteries. A focal lymphohistiocytic infiltration in perivascular regions, and a decrease in the number of multinucleated cells as compared with the control were also observed. For seven female surrogate mothers and their children, allelic polymorphisms of genes of HLA II class were studied. CONCLUSION: Placental material of women from IVF-SM group is characterized by complex immune response in sites of tight contact between maternal and fetal tissues. The immune pathogenesis is associated with an increase in the number of HLA-DR positive cells, defects in remodeling of the spiral arteries, development of areas of chronic inflammation in perivascular regions, and a decrease in the number of multinucleated cells. Genetic incompatibility between alleles of HLA II genes can be a molecular predictor of impaired immune tolerance.