Human Reproduction, Vol. 18, No. 8, 1603-1612,
August 2003
© 2003 European Society of Human Reproduction and Embryology
Ovarian modulators of type 1 11
-hydroxysteroid dehydrogenase (11
HSD) activity and intra-follicular cortisol:cortisone ratios correlate with the clinical outcome of IVF
1 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; 2 Cardiff Assisted Reproduction Unit, University Hospital of Wales, Heath Park, Cardiff CF4 4XN; 3 Regional Endocrine Unit, Southampton General Hospital, Southampton SO16 6YD, UK
4 To whom correspondence should be addressed. e-mail: t.michael{at}rfc.ucl.ac.uk
BACKGROUND: Follicular fluid (FF) contains compounds that can modulate NADP+-dependent oxidation of cortisol by type 1 11
-hydroxysteroid dehydrogenase (11
HSD). The objective of this study was to investigate the relationships between levels of the ovarian modulators of type 1 11
HSD, 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 11
HSD stimuli were significantly lower (P < 0.0001) and levels of the hydrophobic ovarian 11
HSD 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 11
HSD 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). CONLCUSIONS: 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 11
HSD.
Key words: 11
HSD/cortisol/cortisone/hydroxysteroid dehydrogenase/IVF
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