Ovarian modulators of type 1 11β-hydroxysteroid dehydrogenase (11βHSD) 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 11β-hydroxysteroid dehydrogenase (11βHSD). The objective of this study was to investigate the relationships between levels of the ovarian modulators of type 1 11βHSD, 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 11βHSD stimuli were significantly lower (P < 0.0001) and levels of the hydrophobic ovarian 11βHSD 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 11βHSD 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 11βHSD.