Reply to ‘Defining poor ovarian response during IVF cycles, in women aged <40 years, and its relationship with treatment outcome’
Centre for Reproductive Medicine, University of Bristol, 4 Priory Road, Clifton, Bristol, BS9 4HU, UK
1 Email: chandra.kailasam{at}repromed-bristol.co.uk
Sir,
We are very grateful to Klinkert et al. for drawing attention to the potential confounding effect of the different starting doses of FSH dependent on age. In our initial paper (Kailasam et al., 2004
), we had chosen to present the statistics as simply as possible to illustrate our key message that in defining poor response one must consider both the response and the degree of stimulation. However, this letter provides us with the opportunity to present further analyses illustrating that this point remains true irrespective of age up to 40 years.
There is no doubt that ovarian responsiveness declines with age. Our point is that if there is a satisfactory response to the higher dose of gonadotrophin, couples retain a good chance of success despite being aged up to 40 years, whereas failure to respond to a high FSH dose is associated with a poor outcome whatever the woman's age.
Splitting the analysis of the effect of FSH dose and number of eggs recovered shown in Table III of our original paper (Kailasam et al. 2004) into women <35 years versus 
35 years yields Table I.
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This illustrates that the association between the clinical pregnancy rate and the number of eggs recovered related to total FSH dose required is remarkably similar in women above and below 35 years of age.
We used logistic regression to test further the effects of age, total dose of FSH and the number of oocytes recovered. The program (SPSS) was offered the following categorical variables: age <35 years (reference) versus 35 years; oocytes recovered >4 (reference) versus 
4; FSH dose 3000 IU (reference) versus >3000 IU plus all possible interaction terms. Models were derived by forward selection using the likelihood ratio statistic based on maximum likelihood estimates.
Forward selection derived a model where the only significant predictors were the dose of FSH and the number of eggs recovered (Table II).
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Although it has been suggested that the maximum dose for all patients should be 150 IU, many may feel otherwise and suggest benefit up to 300 IU of FSH daily.
In our study, patients whose cycles were cancelled for poor ovarian response on an initial gonadotrophin dose of <300 IU had a clinical pregnancy rate of 22% during a subsequent cycle when the dose of gonadotrophins was increased to 300 IU, thereby suggesting a beneficial effect.
In conclusion, poor response to ovarian stimulation is more common in women >35 years but is not confined to them. At least up to 40 years of age, definition of the response including the dose of gonadotrophin provides a more accurate prognosis for pregnancy than age.
References
Kailasam C, Keay SD, Wilson P, Ford WC and Jenkins JM (2004) Defining poor ovarian response during IVF cycles, in women aged <40 years, and its relationship with treatment outcome. Hum Reprod 19, 1544–1547.
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