title: [Impaired endometrial receptivity in primary infertility in women with undifferentiated connective tissue dysplasia and hereditary thrombophilia].
abstract: 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.
  
  
  OBJECTIVE
  to investigate endometrial morphological and immunophenotypic features in patients with primary infertility in the presence of uCTD and HT.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia.
authors.forename: A S
authors.initials: AS
authors.lastname: Zanozin
authors.affiliation: I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia.
authors.forename: T A
authors.initials: TA
authors.lastname: Demura
authors.affiliation: OOO 'Doctor Dimitry Kolosovsky Hematology Office', Moscow, Russia.
authors.forename: D Yu
authors.initials: DY
authors.lastname: Kolosovsky
authors.affiliation: V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Moscow, Russia.
authors.forename: N M
authors.initials: NM
authors.lastname: Faizullina
authors.affiliation: I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia.
authors.forename: E A
authors.initials: EA
authors.lastname: Kogan
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism; D003240:Connective Tissue Diseases / Q000150:complications / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007246:Infertility / Q000150:complications / Q000209:etiology / Q000473:pathology*; D007797:Laminin / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D019851:Thrombophilia / Q000150:complications / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005353:Fibronectins; C507837:LIF protein, human; D007797:Laminin; D053605:Leukemia Inhibitory Factor; D017395:Plasminogen Activator Inhibitor 1; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9