In particular, FSHR polymorphisms (e.g., Ser680Asn and Thr307Ala) have been associated with reduced sensitivity to gonadotropins ( 18) and may be the most reasonable explanation for the inadequate response following ovarian stimulation ( 19). Ovarian sensitivity in relation to gonadotropin treatment has been the dominating theory, with evidence deriving from the investigation of the genetic variations of gonadotropins and their receptors ( 17). Several pathophysiological explanations have been proposed in order to clarify the nature of unexpected poor/suboptimal response. If we further consider that suboptimal response to stimulation significantly impairs cumulative live birth rates ( 11– 13) and that women with unexpected poor/suboptimal responders may have better prognosis compared to patients with predicted low response ( 14– 16), it could be stated that POSEIDON group 1 patients may represent the most interesting group, on which clinical research should focus in the future. Therefore, although prognosis is very bad in old poor responders, irrespective of the treatment modality used ( 9, 10), substantial benefit could be anticipated in younger women if an adequate number of oocytes is harvested. The age-related decline in fertility, owing to a significant decrease in both oocyte quantity (as reflected by lower oocyte yield) and quality (as reflected by higher aneuploidy and spontaneous abortion rates), is directly associated with the very low LBR observed in older women ( 8). Management of women belonging to the POSEIDON group 1 requires a distinct diagnostic and therapeutic approach in relation to patients' characteristics, which should be specifically tailored to their young age and the adequate ovarian reserve of these women ( 6).Īge is undeniably the strongest determinant of treatment success in women seeking fertility advice ( 7). POSEIDON Group 1 apparently includes the best prognosis patients, compared to other POSEIDON groups, referring to young infertile women (<35 years old), with adequate ovarian reserve markers (AFC ≥ 5 AMH ≥ 1.2 ng/ml), and unexpected poor (<3 oocytes retrieved) or suboptimal (4–9 oocytes retrieved) response following conventional ovarian stimulation ( 5). In this regard, four different patients' categories have been identified through the POSEIDON criteria, taking into account patients' age, ovarian reserve markers and response to stimulation in order to define patients' actual prognosis. In this context, patient classification is not only based on the number of oocytes retrieved, but also on various other features that may affect treatment success and should be carefully taken into consideration in the era of tailored-approach treatment, such as age and ovarian “sensitivity” to exogenous gonadotropins. Recently, the POSEIDON group proposed a more detailed stratification of low responders, taking into account essential baseline characteristics of infertile women, which could have a significant impact on their reproductive outcome ( 5). oocyte quality, grouping together women with different biologic characteristics and therefore altered clinical prognosis. Still, a major limitation of the available published research is the striking diversity in the definitions used to define poor ovarian response, which could hamper the validity of the results ( 1, 2).ĭespite the recent attempt by the European Society of Human Reproduction and Embryology (ESHRE) to apply a uniform definition for women who respond poorly to ovarian stimulation, the so called “Bologna” criteria ( 3), it seems that clinicians are still reluctant to use them in clinical studies ( 4), mainly due to the inability of these criteria to distinguish alterations in oocyte quantity vs. Poor ovarian responders represent one of the most difficult group of patients in every day clinical fertility practice.
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