Ovarian stimulation

Zeev Shoham

Department of Obstetrics and Gynecology, Kaplan Medical Center, Rehovot 76100, Israel

Dear Sir,

This is with reference to the article by Devroey et al. (1998) on the use of 100 IU of recombinant follicle stimulating hormone (FSH) as a starting dose for ovarian stimulation for in-vitro fertilization (IVF) and embryo transfer. The authors stated that `The possibility of lowering starting doses might therefore contribute to decreased exposure of medication, lower incidence of unwanted over-stimulation and therefore lower treatment costs'. This statement is based on the response of an unselected group of 43 patients who were treated with 100 IU of recombinant FSH and the results were compared with those of a different study (Out et al., 1995Go) in which patients were treated with either 150 or 225 IU of recombinant FSH or urinary FSH.

In my opinion this statement might be premature, since the study does not contain a control group and the comparison is not adequate. In fact, the rate of ovarian hyperstimulation syndrome (OHSS) in this study was 4.6%, compared with 3.2% in the study of Out et al. (1995). If we continue with the same line of comparison, another prospective study which used the same protocol but where the starting dosage was 150 IU of recombinant FSH (Bergh et al., 1997Go), we would find that the ovarian performance was better and the rate of OHSS was lower (Table I). With the recent interest in evidence-based medicine, it seems to me that such an important recommendation, i.e. changing protocols of ovarian stimulation, trying to cut down the drug used, decreasing rate of OHSS and yet achieving at least the same success rate, should be based on a prospective randomized study comparing the two different dosages in a large group of patients.


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Table I. Results obtained in three different studies. The studies of Devroey et al. (1998) and Bergh et al. (1997) used the same protocol with different starting doses. No direct comparison was performed but it seems that the study of Bergh et al. shows a tendency towards better ovarian performance, shorter duration of treatment, lower amount of drug used, increase number of oocytes collected, and lower rates of ovarian hyperstimulation syndrome (OHSS)
 
References

Bergh, C., Howles, C.M., Borg, K. et al. (1997) Recombinant human follicle stimulating hormone (r-FSH; Gonal-F) versus highly purified urinary FSH (Metrodin HP): results of a randomized comparative study in women undergoing assisted reproductive techniques. Hum. Reprod., 12, 2133–2139.[Abstract]

Devroey, P., Tournaye, H., Van Steirteghem, A. et al. (1998) The use of 100 IU starting dose of recombinant follicle stimulating hormone (Puregon) in in-vitro fertilization. Hum. Reprod., 13, 565–566.[Free Full Text]

Out, H.J., Mannaerts B.M.J.L., Driessen, S.G.A.J. and Coelingh Bennink, H.J.T. (1995) A prospective, randomised, assessor-blind, multicentre study comparing recombinant and urinary follicle stimulating hormone (Puregon versus Metrodin) in in-vitro fertilization. Hum. Reprod., 10, 2534–2540.[Abstract]


 
P. Devroey, H. Tournaye and A. Van Steirteghem

Centre for Reproductive Medicine, Academic Hospital, Dutch Speaking Free University, Laarbeeklaan 101, Brussels, Belgium

P. Hendrix and H.J. Out1

NV Organon, PO Box 20, 5340 BH Oss, The Netherlands

Dear Sir,

In our paper we stated in the discussion: `The possibility of lower starting doses might therefore contribute to decreased exposure of medication, lower incidence of unwanted overstimulation and therefore lower treatment costs' (Devroey et al., 1998Go). This is very much in the line of a recent editorial by Edwards et al. (1997) entitled: Why delay the obvious need for milder forms of ovarian stimulation?' Professor Shoham raises some questions on our statement.

Even without showing data, the statement seems rather obvious to us. A relationship between the gonadotrophin dose, the development of multiple follicles and the ovarian hyperstimulation syndrome (OHSS) has been fairly well established (Balen, 1995Go). A lower amount of drug given automatically means lower exposure and lower total costs for drugs.

The data we presented (from which we say in the first sentence of the discussion that they are not randomized and limited) show that a 100 IU starting dose can be given without jeopardizing ovarian response in an unselected series of 43 patients. This is of immediate clinical relevance since no published data yet exist on the use of these dosages. The paper does not say that a 100 IU starting dose is the best thing to do in assisted reproduction. The two women with OHSS had risk factors for the development of this syndrome, suggesting that dosing should even be further diminished.

The table provided by Shoham does not provide any useful contribution to this discussion. Studies comparing two different recombinant and two different urinary follicle stimulating hormone preparations with different starting doses defined in different protocols obviously do not provide any evidence against the possibility of lowering starting dosages. Edwards et al. (1997) state: `Would it not be wiser to start off the stimulation with low doses and then raise the amount later if necessary?' We have provided some limited data that it might be possible. However, we repeat the conclusion of our paper: `Prospective randomized clinical trials comparing different dosing schedules are urgently needed to determine the optimal scheme...'. These studies are currently being conducted.

Notes

1 To whom correspondence should be addressed Back

References

Balen, A. (1995) The effects of ovulation induction with gonadotrophins on the ovary and uterus and implications for assisted reproduction. Hum. Reprod., 10, 2233–2237.[ISI][Medline]

Devroey, P., Tournaye, H., Van Steirteghem, A. et al. (1998) The use of a 100 IU starting dose of recombinant follicle stimulating hormone (Puregon) in in-vitro fertilization. Hum. Reprod., 13, 565–566[Free Full Text]

Edwards, R.G., Lobo, R.A. and Bouchard, P. (1997) Why delay the obvious need for milder forms of ovarian stimulation? Hum. Reprod., 12, 399–401.[ISI][Medline]





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