Human Reproduction, Vol. 18, No. 1, 219,
January 2003
© 2003 European Society of Human Reproduction and Embryology
Any effect of adjuvant low dose prednisolone on follicular development and embryo implantation may be masked by the concomitant use of aspirin
Reproductive Medicine, European Hospital, Rome, Italy e-mail: ubaldi.fm{at}tin.it
Dear Sir,
The comments by Keay and colleagues on our recently published paper (Ubaldi et al., 2002
) can be summarized in three points concerning, respectively, the randomization protocol, the possible effects of low dose prednisolone on follicular development and the question of superimposition of the effects of prednisolone and aspirin.
The statement in the Materials and methods section, saying that randomization was carried out on the day of oocyte retrieval is incorrect and is due to an error in the manuscript preparation. In fact, randomization was done before the beginning of ovarian stimulation. The fact that placebo was not used within the trial is unlikely to have influenced the study results because outcome measures were objective and not subjective. It is difficult to imagine how the awareness of participating in a clinical study could influence processes such as follicular development, fertilization or implantation.
We agree that the use of low dose prednisolone, according to the protocol of our study, may have influenced both follicular development and processes related to embryo implantation in the uterus. The effect on follicular development might be more evident if low responders were included in this study. This, however, was not the case. This study was not designed so as to address problems of low response to ovarian stimulation. Prednisolone was used for at least 4 weeks since the beginning of ovarian stimulation. In case of pregnancy this treatment was prolonged until week 8–9 of gestation.
After the publication of the beneficial effect of low dose aspirin on ovarian response to gonadotrophins (Rubenstein et al., 1999) we have included this treatment in our routine protocol, with the exception of patients with specific contraindications. We do not know whether low dose prednisolone treatment would be beneficial if aspirin were omitted.
In conclusion, we show the absence of detectable effects of low dose prednisolone on pregnancy and implantation rates in a group of patients with normal response to ovarian stimulation and with the use of a routine ovarian stimulation protocol. The failure to detect any improvement in these outcome measures strongly suggests that there are no beneficial effects of low dose prednisolone on either ovarian stimulation or uterine receptivity in this group of patients.
References
Rubenstein, M., Marrazi, A. and Polak de Fried, E. (1999) Low-dose aspirin treatment improves ovarian responsiveness, uterine and ovarian blood flow velocity, implantation and pregnancy rates in patients undergoing in vitro fertilization: a prospective, randomized, double-blind placebo controlled assay. Fertil. Steril., 71, 825–829.[CrossRef][Web of Science][Medline]
Ubaldi, F., Rienzi, L., Ferrero, S., Anniballo, R., Iacobelli, M., Cobellis, L. and Greco, E. (2002) Low dose prednisolone administration in routine ICSI patients does not improve pregnancy and implantation rates. Hum. Reprod., 17, 1544–1547.
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