Possible therapeutic options for enhancing the number of oocytes in poor ovarian responders

Poor ovarian response (POR) is associated with low ovarian reserve, which is seen commonly as a result of ovarian aging although it can be associated with genetic conditions, diseases, previous ovarian surgery, chemotherapy, or toxic-related injury to the ovary. Despite pharmacologic advances, innovation in laboratory equipment and advances in embryo culture and selection, success rates in assisted reproductive technology are hampered by age-related infertility, because of sociocultural trends favoring delayed childbearing attitudes. Poor ovarian response represents a challenging subgroup of patients, characterized by a low ovarian reserve and/or a suboptimal response to ovarian stimulation. Different classification systems have been proposed to define POR, but none has proven useful to improve the clinical management of these patients. Assisted reproductive technology in these patients is associated with poor outcomes, significant psychologic burden, and high dropout rates after the first in vitro fertilization attempt. To our knowledge, no specific protocol has been proven better than the other in POR, and no drug to date has proven to increase the antral follicle pool. Advances in ovarian physiology have identified multiple follicular waves within a cycle, with continuous follicular recruitment. This opens the possibility of a multicycle approach, in which two or more consecutive stimulation cycles can be performed irrespective of the menstrual dates, with the aim of obtaining the desired number of oocytes necessary to obtain at least one euploid blastocyst. The multicycle approach increases the number of eggs and embryos available for transfer or vitrification, reduces time to pregnancy, and decreases dropout rates. Nonpharmacological interventions to increase ovarian response, such as intraovarian platelet-rich plasma, remain controversial and have not been proven effective in recent prospective randomized trials. Future directions and research on POR is discussed.