AUTHOR=Alviggi Carlo , Conforti Alessandro , Esteves Sandro C. , Vallone Roberta , Venturella Roberta , Staiano Sonia , Castaldo Emanuele , Andersen Claus Yding , De Placido Giuseppe 

TITLE=Understanding Ovarian Hypo-Response to Exogenous Gonadotropin in Ovarian Stimulation and Its New Proposed Marker—The Follicle-To-Oocyte (FOI) Index

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00589

DOI=10.3389/fendo.2018.00589

ISSN=1664-2392

ABSTRACT=Hypo-responsiveness to controlled ovarian stimulation is an undervalued topic in reproductive medicine. This phenomenon manifests either as an “initial slow response” to FSH stimulation concerning estradiol levels rise and follicular growth or can be retrospectively diagnosed in women who require higher-than-expected doses of gonadotropins considering the patient’s  age, body mass index, and ovarian reserve. The pathophysiology mechanisms explaining the ovarian resistance to gonadotropin stimulation are not fully understood, but the fact that both hypo-responders and normal responders share similar phenotypic characteristics suggests a genotype-based mechanism. Indeed, existing evidence supports the association between specific gonadotropin and their receptor polymorphisms and ovarian hypo-response. Apart from genotypic trait, environmental contaminants and oxidative stress might also be involved in the hypo-response pathogenesis. The ratio between the number of oocytes collected at the ovum pick up and the number of antral follicles at the beginning of OS [Follicle to oocyte index (FOI)] is proposed as a novel parameter to assess the hypo-response. Compared with traditional ovarian reserve markers, the FOI might reflect most optimally the dynamic nature of follicular growth in response to exogenous gonadotropin. In this review, we contextualize the role of FOI as a parameter to identify this condition, discuss the underlying mechanisms potentially implicated in the pathogenesis of hypo-response, and appraise possible the treatment strategies to overcome hyper-responsiveness to gonadotropin stimulation.