title: Endometrial beta3 integrin profile reflects endometrial receptivity defects in women with unexplained recurrent pregnancy loss.
abstract: BACKGROUND
  The pathophysiology of recurrent pregnancy loss (RPL) is still unknown in 50% of the cases. Herein we measure the expression of beta3 integrin subunit, a well-known implantation marker, in women with or without RPL and correlate it with the histological dating of the endometrial tissue.
  
  
  METHODS
  LH-timed endometrial biopsies were obtained from cases (RPL; n = 21, age 33.9+/-4.7) and healthy controls (n = 29; age 29.8+/-4.1) during the mid-secretory phase (post ovulatory day: 8 to 10). Endometrial samples were timed histologically according to Noyes' criteria and underwent immunohistochemical staining for beta3 integrin expression. For statistical analysis the semi-quantitative HSCORE was assessed. Type I (beta3 negative in an out-of-phase endometrium) and Type II defect (beta3 negative in an in-phase endometrium) were also analysed. Statistical analysis was done with Student t-test, Mann Whitney U test, ANCOVA and chi square for trend. Significance was set as P < 0.05.
  
  
  RESULTS
  The mean (SD) age in controls was lower compared to cases [(29.8 (4.1) vs. 33.9 (4.7) - P = 0.001; Student t-test)]. The median (range) expression of beta3 integrin in controls and cases was 1.94 (0 to 3.5) vs. 0.82 (0 to 3.6), respectively (P = 0.001; Mann Whitney U test). Significance was still significant after adjusting for age (P = 0.03;ANCOVA). The normal positive staining > =0.7 of beta3 integrin subunit and in-phase endometrium was seen in 24 out of 29 (82.8%) controls, but in only 6 out of 21 (28.6%) of cases with RPL; Type I and II defects were seen in 10.3 and 6.9% of controls, while present in 52.4 and 19.1% of cases, respectively (P = 0.0005; chi-square).
  
  
  CONCLUSIONS
  Women with unexplained RPL had significantly reduced integrin expression compared to controls. Our findings underline the need for further molecular analysis of endometrial tissue in affected women.
authors.affiliation: Department of Gynecological Endocrinology and Reproductive Medicine, University Hospital Heidelberg, Heidelberg, Germany. ariane.germeyer@med.uni-heidelberg.de.
authors.forename: Ariane
authors.initials: A
authors.lastname: Germeyer
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Savaris
authors.forename: Julia
authors.initials: J
authors.lastname: Jauckus
authors.forename: Bruce
authors.initials: B
authors.lastname: Lessey
mesh_terms: D000026:Abortion, Habitual / Q000209:etiology*; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D015536:Down-Regulation; D010064:Embryo Implantation; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005298:Fertility; D005858:Germany; D006801:Humans; D007150:Immunohistochemistry; D039661:Integrin beta3 / Q000378:metabolism*; D008183:Luteal Phase; D007986:Luteinizing Hormone / Q000652:urine; D009657:North Carolina; D012189:Retrospective Studies; D014591:Uterine Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000652:urine
chemical_list: D015415:Biomarkers; C061248:ITGB3 protein, human; D039661:Integrin beta3; D007986:Luteinizing Hormone