title: Regulation of vascular endothelial growth factor-A and its soluble receptor sFlt-1 by luteinizing hormone in vivo: implication for ovarian follicle angiogenesis.
abstract: OBJECTIVE
  To determine in vivo whether LH supplementation during the late follicular phase induces ovarian follicle angiogenesis in humans, as reflected by vascular endothelial growth factor (VEGF)-A, its soluble receptor sFlt-1, and placental growth factor (PlGF) expression.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled study.
  
  
  METHODS
  Academic tertiary care medical center.
  
  
  METHODS
  Twenty infertile, healthy women (aged 18-39 years) undergoing IVF.
  
  
  METHODS
  Administration of recombinant FSH after down-regulation and equal randomization of subjects to receive recombinant LH 75 IU/day or placebo when two or more follicles reached a mean diameter of 14 mm.
  
  
  METHODS
  Serum and follicular fluid (FF) VEGF-A, sFlt-1, and PlGF protein levels were measured.
  
  
  RESULTS
  Recombinant LH increased both the FF VEGF-A/sFlt-1 ratio statistically significantly and PlGF/sFlt-1 insignificantly. Recombinant LH did not affect the serum VEGF/sFlt-1 ratio. Plasma levels of PlGF were undetectable.
  
  
  CONCLUSIONS
  This in vivo study demonstrates for the first time in humans that LH induces ovarian follicular angiogenesis via modulation of VEGF-A and its soluble receptor sFlt-1 expression. A constant VEGF-A/sFlt-serum ratio may prevent adverse effects of VEGF-A. Because angiogenesis is essential during the periovulatory period, recombinant LH supplementation during the late follicular phase may improve ovulation induction outcome.
authors.affiliation: Sara Racine IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Gutman
authors.forename: Vivian
authors.initials: V
authors.lastname: Barak
authors.forename: Sharon
authors.initials: S
authors.lastname: Maslovitz
authors.forename: Ami
authors.initials: A
authors.lastname: Amit
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Lessing
authors.forename: Eli
authors.initials: E
authors.lastname: Geva
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004624:Embryo Transfer; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage*; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage; D015571:Follicular Fluid / Q000378:metabolism*; D005498:Follicular Phase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007247:Infertility, Female / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007986:Luteinizing Hormone / Q000008:administration & dosage*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D054315:Oocyte Retrieval; D006080:Ovarian Follicle / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D010062:Ovulation Induction / Q000379:methods*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000378:metabolism*
chemical_list: D005300:Fertility Agents, Female; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1