title: Ovarian modulators of type 1 11beta-hydroxysteroid dehydrogenase (11betaHSD) activity and intra-follicular cortisol:cortisone ratios correlate with the clinical outcome of IVF.
abstract: BACKGROUND
  Follicular fluid (FF) contains compounds that can modulate NADP(+)-dependent oxidation of cortisol by type 1 11beta-hydroxysteroid dehydrogenase (11betaHSD). The objective of this study was to investigate the relationships between levels of the ovarian modulators of type 1 11betaHSD, intra-follicular cortisol:cortisone ratios and the clinical outcome of IVF cycles.
  
  
  METHODS
  A single random sample of FF was aspirated from each of 132 patients undergoing gonadotrophin-stimulated IVF. Components of FF, resolved using C18 column chromatography, were evaluated for effects on NADP(+)-dependent cortisol oxidation in rat kidney homogenates. Intra- follicular steroid concentrations were measured by radioimmunoassays. Clinical pregnancies were confirmed by ultrasonography at 6 weeks post-embryo transfer.
  
  
  RESULTS
  Levels of the hydrophilic ovarian 11betaHSD stimuli were significantly lower (P<0.0001) and levels of the hydrophobic ovarian 11betaHSD inhibitors were significantly higher (P<0.002) in conception versus non-conception cycles. Intra-follicular cortisol:cortisone ratios increased with the degree of inhibition of 11betaHSD by the hydrophobic FF fractions. FF obtained from conception cycles had significantly higher cortisol:cortisone ratios than samples from non-conception cycles (12.9+/-0.3 versus 8.5+/-0.2, respectively; P<0.0001).
  
  
  CONCLUSIONS
  Conception by IVF is associated with elevated intra-follicular cortisol:cortisone ratios, which reflect low levels of ovarian stimuli and/or high levels of ovarian inhibitors of type 1 11betaHSD.
authors.affiliation: Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School (Royal Free Campus), University College London, Rowland Hill Street, London NW3 2PF, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Thurston
authors.forename: D P
authors.initials: DP
authors.lastname: Norgate
authors.forename: K C
authors.initials: KC
authors.lastname: Jonas
authors.forename: L
authors.initials: L
authors.lastname: Gregory
authors.forename: P J
authors.initials: PJ
authors.lastname: Wood
authors.forename: B A
authors.initials: BA
authors.lastname: Cooke
authors.forename: A E
authors.initials: AE
authors.lastname: Michael
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000328:Adult; D000818:Animals; D001681:Biological Assay; D003348:Cortisone / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro; D015571:Follicular Fluid / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010053:Ovary / Q000378:metabolism*; D010084:Oxidation-Reduction; D011247:Pregnancy; D011256:Pregnancy Outcome; D051381:Rats
chemical_list: D009249:NADP; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D006854:Hydrocortisone