[Evaluation of morphological activity of primary Sjogren's syndrome on bioptates of minor salivary glands]. / Otsenka morfologicheskoi aktivnosti bolezni Shegrena po bioptatam malykh slyunnykh zhelez.

BACKGROUND: The results of the morphological study of the minor salivary glands can be used to assess the activity of the primary Sjogren's syndrome and to decide on adequate therapy.The existing protocol of The Sjögren's International Clinical Collaborative Alliance (SICCA) prescribes the methodology for examining biopsy specimens for suspected Sjögren's disease, however, experts interpret data from the analysis of histological preparations differently. OBJECTIVE: To identify morphological forms of sialadenitis, as well as to determine the focus score in Russian patients based on the retrospective analysis of minor salivary glands biopsies of patients with primary Sjogren's syndrome. MATERIAL AND METHODS: Biopsies of minor salivary glands were studied in 92 patients with primary Sjogren's syndrome and 42 patients without rheumatic disease. RESULTS: Focal lymphocytic sialadenitis was detected in 69 patients with primary Sjogren's syndrome. The focus score in patients with primary Sjogren's syndrome was 7.32 (2.8-14.17). In patients without rheumatic diseases, this index was 0.48 (p<0.05). Patients with confluent lymphocytic foci need immunohistochemical examination and dynamic monitoring to exclude lymphoproliferative diseases. CONCLUSION: The index of morphological activity of sialadenitis in primary Sjogren's syndrome ranges from 2.8 to 14.17 and reflects the activity of the underlying disease.It should be taken into account in the diagnosis and prescription of adequate therapy. Further study of the correlations of morphological and clinical and laboratory parameters will lead to clarification of the criterion signs of the disease.

[The morphological substrate and molecular mechanisms of impaired pregnancy outcomes in women with hereditary thrombophilias and undifferentiated connective tissue dysplasia]. / Morfologicheskii substrat i molekuliarnye mekhanizmy narushenii iskhodov beremennosti u zhenshchin s nasledstvennymi trombofiliiami i nedifferentsirovannoi displaziei soedinitel'noi tkani.

Hereditary thrombophilias (HT) and undifferentiated connective tissue dysplasia (uCTD) are important causes of female infertility. Moreover, there are signs of their common pathogenesis: a number of proteins, such as PAI-1, play an important role in the pathogenesis of both conditions, as well as in the development of infertility in patients with HT and uCTD OBJECTIVE: To determine the morphological substrate and molecular mechanisms of impaired pregnancy outcomes in women with uCTD and HT. SUBJECT AND METHODS: A study group included 130 reproductive-aged female patients with primary infertility and a control group consisted of 11 patients (surrogate mothers). An endometrial pipelle biopsy sample was taken from each patient on days 6-8 after ovulation according to the ultrasound findings. The study group patients were divided into subgroups: 1A) infertility and HT (n=91); 1B) infertility, NT, and uCTD (n=19); 1C) infertility and uCTD (n=20).

[Impaired endometrial receptivity in primary infertility in women with undifferentiated connective tissue dysplasia and hereditary thrombophilia]. / Narushenie retseptivnosti endometriya pri pervichnom besplodii zhenshchin s sindromom nedifferentsirovannoi displazii soedinitel'noi tkani i nasledstvennymi trombofiliyami.

The concurrence of undifferentiated connective tissue dysplasia (uCTD) and hereditary thrombophilia (HT) often accompanies female infertility, in the pathogenesis of which impaired endometrial receptivity plays an important role. AIM: to investigate endometrial morphological and immunophenotypic features in patients with primary infertility in the presence of uCTD and HT. MATERIAL AND METHODS: The pipelle endometrial biopsy specimens taken in the implantation window were examined in 81 patients, including 13 women with a clinical diagnosis of uCTD, 40 with HT, 19 with uCTD concurrent with HT, and in a control group of 9 heathy surrogate mothers. Morphological, immunohistochemical, and morphometric examinations were done to study the paraffin-embedded endometrial biopsy sections stained with hematoxylin and eosin, pikrofuksin by van Gieson, and with toluidine blue. Immunohistochemical tests were carried out using primary antibodies against ER, PgR, LIF, PAI-1, VEGF, Collagen I, Collagen III, fibronectin, laminin, MMP-2, and MMP-9. RESULTS: The uCTD, HT, and uCTD + HT groups were found to have signs of decreased endometrial receptivity as dramatically lower counts of mature pinopodes, slower endometrial maturation, reduced expression of the receptivity marker LIF, and deviations of the stromal progesterone-estrogen index from the normal value. Sclerotic foci with type III collagen accumulation were detected in the endometrial stroma. CONCLUSION: uCTD and HT and especially their concurrence are commonly a concomitant disease and risk factors for infertility in women due to impaired endometrial receptivity. In uCTD, connective tissue remodeling processes are substantially retarded, which ultimately leads to increased processes of endometrial stromal sclerosis, reduced endometrial receptivity, and infertility. The most pronounced morphological and immunophenotypical changes have been ascertained to develop in the uCTD + NT group. The findings may be used to predict and devise new infertility treatments in patients with uCTD + NT.

[The role of inherited thrombophilia and undifferentiated connective tissue dysplasia syndrome in the pathogenesis of female infertility: A clinical and morphological study].

UNLABELLED: Impaired endometrial receptivity is a major cause of reproductive losses in in vitro fertilization (IVF) cycles given a normal embryo. Its causes may be associated with many diseases, including inherited thrombophilia (IT) and undifferentiated connective tissue dysplasia syndrome (uCTDS). However, endometrial receptivity remains little studied. OBJECTIVE: to investigate the morphological and immunohistochemical substrates of impaired endometrial receptivity in women with uCTDS, IT, and their concurrence. SUBJECTS AND METHODS: Antibodies against ER, PgR, LIF, VEGF, and PAI-1 were used to morphologically and immunohistochemically examine pipelle endometrial biopsy specimens taken from 141 women in the implantation window (on days 6-7 after ovulation). In accordance with their clinical diagnoses, the patients were divided into 4 groups: 1) 13 patients with uCTDS; 2) 100 with IT; 3) 19 with uCTDS and IT; 4) 9 healthy surrogate mothers (a control group). In the examined groups, a total of 145 (90.1%) out of all the IVF protocols were unsuccessful. In the remaining 16 (9.9%) patients without exception, miscarriage started at less than 10 weeks' gestation. RESULTS: In the implantation window, the endometrium was immature in 101 (83.1%) women and corresponded to late proliferation or early secretion phases; 102 (84.3%) women were also found to have no mature pinopodes, pointing to the fact that the endometrial receptivity was very low. Immunohistochemical examination revealed the lower expression of the receptivity marker LIF in the endometrial surface epithelium and its higher expression in the stroma in the study groups (p < 0.05 for the uCTDS and uCTDS+IT groups) and the higher expression of PAI-1 and VEGF in the epithelium, stroma, and endothelium in the study groups than in the control group (p < 0.05), suggesting the intensity of neoangiogenetic processes and impaired fibrinolysis in these patients. CONCLUSION: uCTDS and IT are risk factors of impaired endometrial receptivity in the pathogenesis of infertility. The manifestations of impaired endometrial receptivity in this case are a decrease in mature pinopodes in the surface epithelium; focal stromal sclerosis; and redistribution of the receptivity marker LIF from the surface epithelium to the stroma, which may be used for diagnosis, prediction, and the development of targeted therapy.