Can a focus on intracellular signaling assist us with ovarian stimulation in poor-prognosis patients?

Poor ovarian response remains one of the most challenging phenotypes in reproductive medicine. Research suggests that diminished ovarian reserve, advanced maternal age, and unexpected poor response may be due to different pathophysiologies, requiring distinct clinical management. This review focuses on the biological mechanisms that may provide an avenue for improved clinical outcomes by enhancing oocyte quality through more targeted therapy: differing follicle-stimulating hormone isoforms; follicle-stimulating hormone dose effects; distinct signaling pathways of luteinizing hormone and human chorionic gonadotropin (hCG); androgen priming; growth hormone; letrozole cotreatment; coenzyme Q10; platelet-rich plasma; and mTOR inhibitors. Basic and clinical evidence is presented, and the therapeutic implications for treatment of the primary defect are explained. Although the clinical evidence is not yet strong for many of these factors, all are biologically plausible. This constitutes a "call to action" to correctly evaluate their possible role in improving assisted reproductive technology outcomes.