Abstract: Cannabis consumption and legalization is increasing globally, raising concerns about its impact on fertility. In humans, we previously demonstrated that tetrahydrocannabinol (THC) and its metabolites reach the ovarian follicle. An extensive body of literature describes THC’s impact on sperm, however no such studies have determined its effects on the oocyte. Herein, we investigate the impact of THC on human female fertility through both a clinical and in vitro analysis. In a case-control study, we show that follicular fluid THC concentration is positively correlated with oocyte maturation and THC-positive patients exhibit significantly lower embryo euploid rates than their matched controls. In vitro, we observe a similar, but non-significant, increased oocyte maturation rate following THC exposure and altered expression of key genes implicated in extracellular matrix remodelling, inflammation, and chromosome segregation. Furthermore, THC induces oocyte chromosome segregation errors and increases abnormal spindle morphology. Finally, this study highlights potential risks associated with cannabis use for female fertility (Research: Cannabis impacts female fertility as evidenced by an in vitro investigation and a case-control study | Nature Communications