Age-related Variability of the Efficacy and Tolerability of Alternative Pituitary Suppression Regimens in Follicular Stimulation for Assisted Reproduction Purposes. A Randomised, Prospective, Multi-centre Clinical Trial

Pituitary suppression is strongly advised to be included within the follicular stimulation protocols to avoid the occurrence of a premature LH surge, which leads to cycle cancellation.

However, whatever the drug and the schedule selected to achieve it, it is clear that pituitary suppression constitute a major perturbation of the endocrine milieu and that it has an impact on the outcome of the stimulation.

Indeed, the data in the literature support the idea that pituitary down-regulation by GnRH agonists according to the so-called long protocol, resulting in a deeper suppression, result in better clinical outcomes as compared to the short protocol, at least in women of younger reproductive age. Conversely, it has been proposed that a less profound suppression (e.g. short protocol), that allows better background regulation from the pituitary, should be preferred in women of advanced reproductive age.

However, the majority of the data currently supporting the decision makers in selecting their pituitary suppression strategies is based on studies focussed on standard, good prognosis patients whereas just a few studies have specifically addressed the special issue of the advanced reproductive age. Inasmuch, very few data are available in pure (non resistant) advanced age patients and, however, no studies have compared in the same setting younger vs aged subjects with an adequate sample size.

Another intriguing aspect of the question is that the chronological age does not necessarily overlap with the reproductive age which, besides complicating the decisional process in the clinical practise, may also play as a confounding factor in the evaluation of the results from clinical trials. Several studies have validated the role of the so-called follicle antral count (AFC) and the anti-Mullerian hormone (AMH) circulating levels as having a predictive role in the evaluation of the actual reproductive age. In particular the latter, the AMH, appears to be easier to standardise and to be used as the best reference in multicentre clinical studies focussed on the reproductive age.