FSH isoform composition of commercial gonadotrophin preparations: a neglected aspect?

The clinical efficacy of commercial gonadotrophin preparations has been the subject of an intense debate during recent years. Arguments have primarily focused on the origin of FSH activity (urine versus recombinant derived) and whether the preparation included LH-like activity. FSH isoform composition has received little or no attention, and is usually considered to have negligible effect on clinical effectiveness. By presenting the available data on the FSH isoform composition of commercial gonadotrophin preparations, the present paper challenges this assumption. To evaluate whether the FSH isoform composition affected the efficacy of a product, a meta-analysis was performed that compared a preparation expressing an acidic isoform profile (urinary-derived Metrodin-HP) with a preparation rich in less acidic isoforms (recombinant derived Gonal F). A total of five randomized clinical trials that specifically compared these two preparations was identified and included in the analysis. All parameters relating to the direct effect of FSH on the follicle differed significantly in favour of the product rich in less acidic isoforms, while data on pregnancy outcome did not reach significance. The importance of the FSH isoform profile and whether the FSH is derived from urine or by recombinant technique is discussed in relation to clinical efficacy. It is suggested that the FSH isoform profile of commercial gonadotrophin preparations is of clinical importance and should be taken into account when evaluating efficacy.