Department of OB/GYN, University of Vermont, C-211A Given, Burlington VT, 054050068, USA Baylor College of Medicine, 6550 Fannin, 801 Houston, Texas 77030, USA
Dear Sir,
We appreciate the comments made by van Weering et al. (2001) regarding our manuscript (Casson et al., 2000). We agree that our case series represents very preliminary data, which certainly requires more formal confirmation prior to dissemination into clinical practice. However, several of the points made in their Letter to the Editor deserve some clarification.
While it is true that the paracrine ovarian IGF-1 axis is not mandatory for successful folliculogenesis and conception, there is much data demonstrating the gonadotrophin-augmenting relevance of this effect (Yeh and Adashi, 1999). The correspondents' contention that the IGF-1 effect is not mandatory does not negate the possibility that DHEA augmentation may improve ovarian response in certain patients.
They also felt that speculation regarding the role of DHEA as a pro-hormone for follicular steroid production was not correct, despite Hanings' data to the contrary (Haning et al., 1993). It is also true, as van Weering and co-workers state, that follicles destined for atresia are androgenic, however mature or dominant follicles are oestrogen dominant. Finally, if as van Weering and co-workers state, the rate limiting step in ovarian steroidogenesis is side chain cleavage, what better way to circumvent this effect than administer DHEA, a 19-carbon steroid?
We fully appreciate the shortcomings of this study, particularly the use of rFSH in the study cycles. We have read with interest the study by Shats et al. (Schats et al., 2000) showing improved response with rFSH over highly purified urinary FSH in normal responders undergoing IVF with ovarian down regulation. Of course the very modest improvement they saw may not hold in our poor responder population, who were not down-regulated. Additionally, the one patient in our series with the most vigorous response to DHEA used highly purified urinary FSH in both the control and DHEA-augmented cycles.
Van Weering et al. made two other comments about our case series. They noted quite correctly that the patient with the most vigorous response to adjunctive DHEA administration had two cycles in the series. That this may skew the results is uncontested. However, assessment of the data using only her first cycle, or with her cycle averages, yielded the same pattern of statistical significance as our reported data. They also noted that baseline oestradiol concentrations were not reported. They were however, measured and did not differ between the groups. We did not measure concentrations and agree the results might have been interesting.
We understand fully the limitations of our case series, and the very preliminary nature of our conclusions. However, on the basis of our observations, we believe the possible beneficial effect of DHEA on ovarian stimulation in poor responder populations is certainly worthy of further investigation.
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, 21292132.
Haning, R.V. Jr., Hackett, R.J., Flood, C.A. et al. (1993) Plasma dehydroepiandrosterone sulfate serves as a prehormone for 48% of follicular fluid testosterone during treatment with menotropins. J. Clin. Endocrinol. Metab., 76, 13011307.[Abstract]
Schats, R., De Sutter, P., Bassil, S. et al. (2000) Ovarian stimulation during assisted reproduction treatment: a comparison of recombinant and highly purified urinary human FSH. Hum. Reprod., 15, 16911697.
Yeh, J. and Adashi, E.Y. (1999) The ovarian life cycle. In Yen. S.S.C., Jaffe, R.B. and Barbieri, R.L. (eds) Reproductive endocrinology: physiology, pathophysiology, and clinical management. W.B.Saunders Co., Philadelphia, p 172.