The morphological substrate and molecular mechanisms of impaired pregnancy outcomes in women with hereditary thrombophilias and undifferentiated connective tissue dysplasia
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01.01.2018 |
Demura T.
Kogan E.
Zanozin A.
Kolosovsky D.
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Arkhiv Patologii |
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© 2018, Media Sphera Publishing Group. All rights reserved. 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). The investigators examined obstetric/gynecological history data, determined the levels of PAI-1 and homocysteine in the blood samples of patients in the subgroups with HT (1A and 1B); assessed the results of the methionine test, and identified the polymorphism or mutations of the following genes: FII, FV (Leiden), FVII, FXII, FXIII, GpIa, GpIb (-5), GpIb (T145M), GpIIIa, PAI-1, FBGb, MTHFR, MTRR, MTR, SLC19A1, angiotensin gene (M235T and T145M), angiotensin-converting enzyme, and their homo-or heterozygosity. Endometrial morphological and immunohistochemical examinations were carried out using primary antibodies to sex hormone receptors, LIF, PAI-1, and osteopontin. Results. The number of pregnancies in the study group was comparable to the number of patients in each subgroup. Childbirth was considered to be a favorable pregnancy outcome; missed miscarriage was an unfavorable one. There were the most favorable outcomes in Subgroup 1C with uCTD and the least one in Subgroup 1B. Comparison of hemostatic system indicators revealed statistically significant differences only in the incidence of disaggregated thrombopathy (88% in Group 1B and 55% in Group 1A). In the endometrium of the study group, there was delayed maturation; sclerotic foci and dyscirculatory disorders were more frequent in the stroma. Conclusion. In HT, uCTD, and, to a greater extent, its concurrence, a genetically determined predisposition to impaired implantation develops due to genetically determined endometrial remodeling that leads to infertility and impaired pregnancy outcomes.
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