title: Resistance of uterine radial artery blood flow was correlated with peripheral blood NK cell fraction and improved with low molecular weight heparin therapy in women with unexplained recurrent pregnancy loss.
abstract: OBJECTIVE
  To investigate whether peripheral blood natural killer (pbNK) cell levels are associated with uterine blood flow, and low molecular weight heparin (LMWH) treatment is effective to improve uterine blood flow in women with decreased uterine blood flow and unexplained recurrent pregnancy loss (RPL).
  
  
  METHODS
  This was a prospective controlled study. Study population included 33 pregnant women (between 5 and 7 weeks gestation) with ≥ 2 RPL and controls were 47 healthy pregnant women. pbNK cell fractions (CD3(-)/56(+)/16(+)) of peripheral blood mononuclear cells were measured by flow cytometry. Uterine color-pulsed Doppler ultrasound was performed to evaluate uterine radial artery resistance index (URa-RI). In RPL women with elevated URa-RI (≥ 0.5), LMWH (ranges 40-60 mg/day) was administered subcutaneously daily and URa-RI was reassessed 1 week later. Pregnancy outcome was analyzed at 12 weeks gestation.
  
  
  RESULTS
  URa-RI was significantly higher in pregnant women with RPL than controls (0.60 ± 0.14 versus 0.54 ± 0.12, P = 0.039). In pregnant women with RPL, pbNK cell fractions displayed a positive correlation with URa-RI (Pearson's r = 0.429, P = 0.013). URa-RI was significantly decreased 1 week after LMWH treatment as compared to that of pretreatment (pretreatment RI: 0.65 ± 0.11 versus post-treatment RI: 0.56 ± 0.13, P = 0.011). Pregnancy outcome of RPL women with LMWH treatment was not different from that of pregnant controls (73.3% versus 85.0%, P = NS).
  
  
  CONCLUSIONS
  Increased pbNK cells are associated with decreased uterine radial artery blood flow. LMWH treatment effectively decreases URa-RI with improved pregnancy outcome in women with RPLs and elevated URa-RI. A larger scale study is needed to verify these findings.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
authors.forename: Hwa Seon
authors.initials: HS
authors.lastname: Koo
authors.forename: Joanne
authors.initials: J
authors.lastname: Kwak-Kim
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Yi
authors.forename: Hyun Kyong
authors.initials: HK
authors.lastname: Ahn
authors.forename: Chan Woo
authors.initials: CW
authors.lastname: Park
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Cha
authors.forename: Inn Soo
authors.initials: IS
authors.lastname: Kang
authors.forename: Kwang Moon
authors.initials: KM
authors.lastname: Yang
mesh_terms: D000026:Abortion, Habitual / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D000328:Adult; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D017534:Radial Artery / Q000502:physiology*; D012039:Regional Blood Flow; D014599:Uterus / Q000098:blood supply*
chemical_list: D006495:Heparin, Low-Molecular-Weight
keywords: Low molecular weight heparin; NK cell; recurrent pregnancy loss; resistance index; uterine blood flow