Research Topic

POSEIDON’s Stratification of ‘Low Prognosis Patients in ART”: The WHY, the WHAT, and the HOW.

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Management of patients with an impaired ovarian reserve or poor ovarian response (POR) to exogenous gonadotropin stimulation has challenged reproductive specialists for a long time. Apart from our limited understanding of its pathophysiology, there is wide heterogeneity in the definition of POR and overall disappointing outcomes in assisted reproductive technology (ART) cycles.

A critical shortcoming of the existing POR criteria, which is largely based on ovarian biomarkers and number of oocyte retrieved after controlled ovarian stimulation (COS), is that they group women with diverse baseline characteristics. This may explain the lack of scientific evidence to support any effective intervention for the POR patient category when the existing criteria were used for designing clinical trials. As a result, practitioners have utilized different strategies in clinical management –often not evidence-based– since none of the POR criteria provide a clear path for management.

In practical terms, counting the number of oocytes retrieved or estimating such numbers using ovarian biomarkers is not enough for clinical management. Equally important is to determine the ovarian sensitivity to gonadotropins, which is modulated by genetic factors involving both the gonadotropins and their receptors, and the age-related decrease in oocyte quality that largely depends on chromosomal abnormalities occurring prior to meiosis II.

The POSEIDON (Patient-Oriented Strategies Encompassing Individualized Oocyte Number) group -created in 2015- introduced a new stratification for classifying infertility patients with confirmed or expected inappropriate ovarian response to exogenous gonadotropins. Furthermore, the group introduced a new measure for successful ART treatment, namely, the ability to retrieve the number of oocytes necessary to obtain at least one euploid embryo for transfer in each patient. The aim of this new system was to provide a more nuanced picture of POR using clinically relevant criteria to guide the physician in the management of such patients. Essentially, the POSEIDON group proposed a change in the definition of POR from heterogeneous criteria to the concept of low prognosis, which is suggested to better reflect the fate of these patients in ART.

The POSEIDON system combines quality and quantity for the stratification of patients with confirmed or expected inappropriate ovarian response, and allow clinicians to estimate the number of oocytes needed to achieve a new marker of successful outcome. It is suggested that the new concept of low prognosis helps to improve the management of patients undergoing ART, promotes a tailored approach to patient handling, and identifies more homogeneous populations for clinical trials. Using the POSEIDON concept, clinicians would be able to set patient expectations and establish a workable plan to reduce the time-to-pregnancy. This can be achieved by pharmacological and/or laboratory approaches.

This Research Topic is intended to provide clinicians and scientists involved in the study and care of infertile couples a thoughtful and comprehensive review of the significance of the POSEIDON concept and its implications for practice. Our goals are to cover all important aspects related to the diagnosis and clinical management of low responders, from epidemiology to ART, contemplating pathophysiology, genetics, ovarian biomarkers, ovarian stimulation strategies and alternative treatment modalities.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Management of patients with an impaired ovarian reserve or poor ovarian response (POR) to exogenous gonadotropin stimulation has challenged reproductive specialists for a long time. Apart from our limited understanding of its pathophysiology, there is wide heterogeneity in the definition of POR and overall disappointing outcomes in assisted reproductive technology (ART) cycles.

A critical shortcoming of the existing POR criteria, which is largely based on ovarian biomarkers and number of oocyte retrieved after controlled ovarian stimulation (COS), is that they group women with diverse baseline characteristics. This may explain the lack of scientific evidence to support any effective intervention for the POR patient category when the existing criteria were used for designing clinical trials. As a result, practitioners have utilized different strategies in clinical management –often not evidence-based– since none of the POR criteria provide a clear path for management.

In practical terms, counting the number of oocytes retrieved or estimating such numbers using ovarian biomarkers is not enough for clinical management. Equally important is to determine the ovarian sensitivity to gonadotropins, which is modulated by genetic factors involving both the gonadotropins and their receptors, and the age-related decrease in oocyte quality that largely depends on chromosomal abnormalities occurring prior to meiosis II.

The POSEIDON (Patient-Oriented Strategies Encompassing Individualized Oocyte Number) group -created in 2015- introduced a new stratification for classifying infertility patients with confirmed or expected inappropriate ovarian response to exogenous gonadotropins. Furthermore, the group introduced a new measure for successful ART treatment, namely, the ability to retrieve the number of oocytes necessary to obtain at least one euploid embryo for transfer in each patient. The aim of this new system was to provide a more nuanced picture of POR using clinically relevant criteria to guide the physician in the management of such patients. Essentially, the POSEIDON group proposed a change in the definition of POR from heterogeneous criteria to the concept of low prognosis, which is suggested to better reflect the fate of these patients in ART.

The POSEIDON system combines quality and quantity for the stratification of patients with confirmed or expected inappropriate ovarian response, and allow clinicians to estimate the number of oocytes needed to achieve a new marker of successful outcome. It is suggested that the new concept of low prognosis helps to improve the management of patients undergoing ART, promotes a tailored approach to patient handling, and identifies more homogeneous populations for clinical trials. Using the POSEIDON concept, clinicians would be able to set patient expectations and establish a workable plan to reduce the time-to-pregnancy. This can be achieved by pharmacological and/or laboratory approaches.

This Research Topic is intended to provide clinicians and scientists involved in the study and care of infertile couples a thoughtful and comprehensive review of the significance of the POSEIDON concept and its implications for practice. Our goals are to cover all important aspects related to the diagnosis and clinical management of low responders, from epidemiology to ART, contemplating pathophysiology, genetics, ovarian biomarkers, ovarian stimulation strategies and alternative treatment modalities.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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