Reply of the Author:

Abstract

Thank you for the opportunity to respond to the comments made by Jansen regarding our review article about recombinant and urinary hCG in assisted reproduction (1Ludwig M. Doody K.J. Doody K.M. Use of recombinant human chorionic gonadotropin in ovulation induction.Fertil Steril. 2003; 79: 1051-1059Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar). The three main points raised in the letter are the relevance of the comparison criteria between the two drugs, the cost difference issue, and the difference in safety. In addressing the first point, it should be emphasized that although reducing the incidence of ovarian hyperstimulation syndrome (OHSS) is an important aspect of the management of ovarian stimulation in general, it is not the primary endpoint of comparisons of urinary and recombinant hCG. The hCG injection is a critical stage of the treatment cycle, and it is important to ensure that patients receive the optimum treatment. Jansen points out that no significant differences have been observed in head-to-head clinical trials and suggests that the efficacy of the two drugs is similar. It should be stressed that this does not mean that the two products are “equivalent.” It only means that until now, head-to-head clinical trials have not been powered enough to show a significant difference. A valid approach to increase the power is to pool clinical trials in a meta-analysis. Since the preparation and submission of our review, the results of such a meta-analysis comparing urinary and recombinant hCG, based on the three head-to-head studies cited in our review, have become available and show a clear trend toward an improved singleton pregnancy rate and live birth rate with recombinant hCG compared with urinary hCG (2Daya S. Gunby J. Singleton pregnancy resulting from recombinant versus urinary human chorionic gonadotrophin—a meta-analysis.Fertil Steril. 2002; 78: S147-148Abstract Full Text Full Text PDF Google Scholar). The second point raised is the cost difference between recombinant and urinary products. The view of Jansen that urinary hCG would be more “cost-effective” than recombinant hCG because the latter is more expensive is too reductionist, because drug prices are not the only component of medical costs. A cost-effectiveness analysis should involve a comparison of both costs and outcomes. Finally, the third issue questions the difference in safety; recombinant hCG injections deliver the hormone at high purity and in a consistent dose. Subcutaneous injections are certainly a benefit over the IM route that is required for urinary hCG in many countries. Local site reaction is a valid clinical parameter because uncomfortable injection site reactions could potentially compromise compliance, particularly in those patients who choose to self-administer. Regarding the theoretical risk of prion infection, clearly the safety of patients is paramount—whether they receive urinary or recombinant products. In conclusion, the combined results from valid randomized trials confirm the trend toward a clinical superiority of recombinant hCG in treatment with assisted reproductive techniques, and its greater cost-effectiveness confers benefits that will be appreciated by policy makers, health care providers, insurance companies, and patients.