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Human Reproduction, Vol. 18, No. 8, 1603-1612, August 2003
© 2003 European Society of Human Reproduction and Embryology

Ovarian modulators of type 1 11{beta}-hydroxysteroid dehydrogenase (11{beta}HSD) activity and intra-follicular cortisol:cortisone ratios correlate with the clinical outcome of IVF

L.M. Thurston1, D.P. Norgate1, K.C. Jonas1, L. Gregory2, P.J. Wood3, B.A. Cooke1 and A.E. Michael1,4

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

Key words: 11{beta}HSD/cortisol/cortisone/hydroxysteroid dehydrogenase/IVF


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