Gonadotropin in assisted reproduction: An evolution perspective

Abstract

The introduction of gonadotropin therapy in medical practice represented an essential upgrade in infertility treatment. Follicle stimulation hormone (FSH) has a major role in follicular recruitment and growth. Improvements in purification techniques and recombinant technology have led to the two main FSH currently available: highly purified human menopausal gonadotropin (HP-hMG), with 1:1 ratio of FSH/luteinizing hormone (LH) activity; and recombinant human FSH (rec-hFSH), with only FSH activity. Both of them are safe to use and have overall similar clinical efficacy. However, rec-hFSH is purer than HP-HMG. Moreover, the introduction of filled-by-mass technology virtually eliminated batch-to-batch variation, enabled FSH accurate dosing and the development of novel prefilled pen devices that made treatment more patient-friendly. LH supplementation has also been introduced in controlled ovarian stimulation (COH), initally in hypogonadotropic hypogonadism women and then, in older patients (≥ 35 years), poor and slow/hypo responders and those with deeply suppressed endogenous LH. At present, three formulations with LH activity are available (i) hMG in which LH activity is given by hCG, (ii) recombinant human LH (rec-hLH), and (iii) fixed combination of rec-hFSH and rec-hLH at 2:1 ratio. Recent advances in the therapeutical options for COH include the introduction of the long acting FSH and the new family of pen injectors. Research now focuses on the development of small orally bioactive agonists of FSH and LH receptors that may in the future replace gonadotropin injections.