I-24: Individualized Controlled Ovarian Stimulation (iCOS)

Background: With the recent development of recombinant gonadotropins (FSH and LH), it has become possible to further adjust the stimulation protocol according to the expected needs of the patient. In this respect, the possible beneficial role of exogenous LH activity supplementation for stimulated ART cycles has received increasing attention. According to the two-cell, two- gonadotropin theory, both FSH and LH are required for normal folliculogenesis in humans. LH stimulates the production of androgens in the theca cells, which in turn are aromatised to estradiol by the granulosa cells under the action of FSH. However, at a follicle size of 8-10 mm in normogonadotropic women, the granulosa cell also acquires LH receptors in addition to the FSH receptors, already present. Once LH receptors are expressed in the granulosa cell, LH is able to regulate both steroidogenesis and growth of the follicle; thus, from this moment on FSH function can to a large extent be replaced by LH activity. Materials and Methods: During recent years an increasing body of scientific evidence has raised the question whether the endogenous LH level achieved after down-regulation with either GnRHa or GnRH antagonist is really optimal for all patients, or whether sub-groups of patients exist who might benefit from exogenous LH supplementation. Several studies have until now addressed the effect of LH activity supplementation. The results of these studies indicate that two subgroups of normogonadotropic patients: patients > 35 years of age and patients with an initial sub-optimal response to FSH only preparations seem to benefit from modifications of the stimulation protocol in terms of exogenous LH activity supplementation. Possible biological reasons for a beneficial effect of LH activity supplementation in these sub-groups will be discussed as well as molecular, structural and functional differences between LH and hCG. Finally, the importance - or not of late follicular progesterone rise during COS will be debated. Conclusions: Age and LH gene polymorphisms and are some of the factors known until now to influence the ovarian response after COS. LH supplementation in sub-groups seems to improve the ovarian response and the reproductive outcome. Ovarian response to stimulation with FSH is a polygenic trait and the future scenario of ART will include pharmacogenetics in order to define the specific needs of gonadotropins to secure the most optimal ovarian response.