The Role of LH in Controlled Ovarian Stimulation

Abstract

Although exogenous FSH is the main regulator of follicular growth in stimulated cycles, LH plays a key role in promoting steroidogenesis and follicle development. Stimulation protocols with LH supplementation are mandatory in patients with hypogonadotropic hypogonadism who do not achieve adequate steroidogenesis by stimulation with FSH alone, but resume adequate estrogen production by LH supplementation. In normogonadotropic women undergoing controlled ovarian stimulation (COS), the hypogonadotropic state after GnRH analogues is short in duration, and the resting levels of LH are usually sufficient for promoting optimal follicular development. An increased body of evidence otherwise indicates that at least three subgroups of normogonadotropic patients indeed seem to benefit from the addition of LH activity to the stimulation protocol: (1) patients >35 years, (2) patients with a decreased ovarian reserve/poor response to COS (poor responders), and (3) patients with an initial poor response to rec-hFSH (hyporesponders). Possible reasons for a beneficial effect of LH activity supplementation include the biological aging of the ovary and pharmacogenetics involving the LH molecule and its receptor.

The three gonadotropins containing LH activity are human menopausal gonadotropin (hMG), with 1:1 ratio of FSH/LH in which LH activity is driven by hCG; recombinant human LH (rec-LH), with only LH activity driven by pure LH; and a combination of recombinant FSH and recombinant LH, with 2:1 ratio of pure FSH/LH activity. In addition to the higher purity and specific activity of rec-hLH compared with hMG, LH activity is markedly different at the molecular and functional levels between these gonadotropins. The choice of the type of gonadotropin preparations containing LH activity should be considered when tailoring COS with LH supplementation because they may influence cycle outcome.