High doses of follicle stimulating hormone (FSH) during assisted reproductive technologies (ART) are correlated with decreased live birth rates in women and decreased ovarian function in cattle. Thus, the overarching hypothesis for my thesis research is that high FSH doses during ovarian stimulation are detrimental to ovulatory follicle function and oocyte quality. The small ovarian reserve (number of morphologically healthy oocytes) heifer (SORH) model was chosen to test this hypothesis because it mimics traits in infertile women with a small ovarian reserve who require ART to achieve pregnancy. The excessive FSH (Ex-FSH) doses not further increasing number of ovulatory-size follicles during ovarian stimulation were detrimental to ovulatory follicle function because they decreased circulating concentrations of estradiol and ovulation rate and caused severe abnormalities in cell-signaling pathways in granulosa and cumulus cells and oocytes resulting in aberrant luteinization, cumulus expansion, and resumption of meiosis. The prematurely expanded cumulus-oocyte complexes (COCs) contained poor quality oocytes while capacity of COCs to respond to an ovulatory hCG stimulus and resume meiosis was impaired. Circulating concentrations of anti-Mullerian hormone (AMH) and antral follicle count (AFC) in the SORH model were correlated positively with number of functional and dysfunctional ovulatory-size follicles developing during ovarian stimulation with various FSH doses (including Ex-FSH). These results support the conclusions that: i) ovarian stimulation with Ex-FSH impairs ovulatory follicle function and oocyte quality, thereby increasing oocyte wastage and decreasing ART outcomes, and ii) AMH and AFC are not predictive of the impact of Ex-FSH doses during ovarian stimulation on number of high-quality oocytes available for ART.
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