Human Reproduction, Vol. 16, No. 7, 1537-1538,
July 2001
© 2001 European Society of Human Reproduction and Embryology
Letters to the editor |
Augmentation of ovarian response by dehydroepiandrosterone
IVF centre, Department of Reproductive Medicine, Vrije Universiteit Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
Dear Sir,
In a recent article, Casson and co-workers (Casson et al., 2000
) report a case series in which the augmentation of ovarian response by dehydroepiandrosterone (DHEA) is described. In this study micronized DHEA is administered orally 2 months prior to ovarian stimulation in patients with unexplained infertility and with a previous poor response to ovarian stimulation. The authors make the assumption that DHEA administration raises follicular insulin-like growth factor-1 (IGF-1) concentrations, which by a paracrine effect could enhance the gonadotrophin effect. IGF-1 may modulate ovarian follicular development but it is not mandatory. Women with Laron-type dwarfism lacking IGF factors are capable of conceiving spontaneously (Menashe et al., 1991). However, their second assumption, namely that exogenous administered DHEA will affect ovarian response in its role as a steroid pro-hormone, is very unlikely because the endogenous androgen precursors are already present in surplus amounts compared to oestradiol. The rate-limiting step in steroid hormone synthesis thus appears to be the conversion of cholesterol into pregnenolone and not precursor availability (Strauss and Penning, 1999).
Another point of criticism is that the study is based on several methodological misconceptions. First, the control cycle consists of a vigorous gonadotrophin stimulation, while the study stimulation cycle consisted of two ampoules rFSH 75 IU twice a day. It is not explained in detail what a `vigorous' stimulation is. The dosage in the control cycle and the study cycle should have been identical. Secondly, as indicated by the authors, a major confounder is introduced by using two different FSH preparations: urinary FSH in the control cycles and recombinant FSH in the study cycle. There may be a different ovarian response to stimulation with rFSH, as is the case in normal responders (Schats et al., 2000). Taken together, the authors cannot conclude that DHEA administration is responsible for the observed augmentation of ovarian response because it is just as likely to be the result of using a different FSH preparation and dosage in the experimental cycles.
Thirdly, the statistical analysis is confounded by the fact that one out of five patients is enrolled twice in this study. This particular patient accounts for the two extreme peak oestradiol values and therefore contributes unproportionally to the data presented.
Finally the reason why the authors measure and report the subjects' baseline serum dehydroepiandrosterone-sulphate (DHEA-S) and testosterone concentrations before and after treatment with DHEA is not given. Baseline serum oestradiol and serum IGF-1 concentrations would have been more logical.
In conclusion, an interesting theory is not tested in a proper methodological way and the results therefore have little scientific value.
Notes
To whom correspondence should be addressed. E-mail: h.vanweering{at}azvu.nl
References
Casson, P.R., Lindsay, M.S., Pisarska,M.D. et al (2000) Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum. Reprod., 15, 2129–2132.
Menashe, Y., Sack, J., and Mashiach, S. (1991) Spontaneous pregnancies in two women with Laron-type dwarfism: are growth hormone and circulating insulin-like growth factor mandatory for induction of ovulation? Hum. Reprod., 6, 670–671.
Schats, R., Sutter, P.D., Bassil, S. et al. (2000) Ovarian stimulation during assisted reproduction treatment: a comparison of recombinant and highly purified urinary human FSH [In Process Citation]. Hum. Reprod., 15, 1691–1697.
Strauss, J.F. and Penning, T.M. (1999) Synthesis of the sex steroid hormones: molecular and structural biology with applications to clinical practice. In Fauser, B.C.J.M., Rutherford, A.J., Strauss, J.F. et al. (eds), Molecular Biology in Reproductive Medicine. The Parthenon Publishing Group, New York, pp. 201–233.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||