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      Defining Low Prognosis Patients Undergoing Assisted Reproductive Technology: POSEIDON Criteria—The Why

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          Abstract

          Women with impaired ovarian reserve or poor ovarian response (POR) to exogenous gonadotropin stimulation present a challenge for reproductive specialists. The primary reasons relate to the still limited knowledge about the POR pathophysiology and the lack of practical solutions for the management of these conditions. Indeed, clinical trials using the current standards to define POR failed to show evidence in favor of a particular treatment modality. Furthermore, critical factors for reproductive success, such as the age-dependent embryo aneuploidy rates and the intrinsic ovarian resistance to gonadotropin stimulation, are not taken into consideration by the current POR criteria. As a result, the accepted definitions for POR have been criticized for their inadequacy concerning the proper patient characterization and for not providing clinicians a guide for therapeutic management. A novel system to classify infertility patients with “expected” or “unexpected” inappropriate ovarian response to exogenous gonadotropins—the POSEIDON criteria—was developed to provide a more nuanced picture of POR and to guide physicians in the management of such patients. The new standards are provoking as they challenge the current terminology of POR in favor of the newly defined concept of “low prognosis.” This article provides readers a critical appraisal of the existing criteria that standardize the definition of POR and explains the primary reasons for the development of the POSEIDON criteria.

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          Most cited references78

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          The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening.

          To determine the relationship between the age of the female partner and the prevalence and nature of human embryonic aneuploidy. Retrospective. Academic. Trophectoderm biopsies. Comprehensive chromosomal screening performed on patients with blastocysts available for biopsy. Evaluation of the impact of maternal age on the prevalence of aneuploidy, the probability of having no euploid embryos within a cohort, the complexity of aneuploidy as gauged by the number of aneuploid chromosomes, and the trisomy/monosomy ratio. Aneuploidy increased predictably after 26 years of age. A slightly increased prevalence was noted at younger ages, with >40% aneuploidy in women 23 years and under. The no euploid embryo rate was lowest (2% to 6%) in women aged 26 to 37, was 33% at age 42, and was 53% at age 44. Among the biopsies with aneuploidy, 64% involved a single chromosome, 20% two chromosomes, and 16% three chromosomes, with the proportion of more complex aneuploidy increasing with age. Finally, the trisomy/monosomy ratio approximated 1 and increased minimally with age. The lowest risk for embryonic aneuploidy was between ages 26 and 30. Both younger and older age groups had higher rates of aneuploidy and an increased risk for more complex aneuploidies. The overall risk did not measurably change after age 43. Trisomies and monosomies are equally prevalent. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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            Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles.

            While live birth is the principal clinical outcome following in vitro fertilization (IVF) treatment, the number of eggs retrieved following ovarian stimulation is often used as a surrogate outcome in clinical practice and research. The aim of this study was to explore the association between egg number and live birth following IVF treatment and identify the number of eggs that would optimize the IVF outcome. Anonymized data on all IVF cycles performed in the UK from April 1991 to June 2008 were obtained from the Human Fertilization and Embryology Authority (HFEA). We analysed data from 400 135 IVF cycles. A logistic model was fitted to predict live birth using fractional polynomials to handle the number of eggs as a continuous independent variable. The prediction model, which was validated on a separate HFEA data set, allowed the estimation of the probability of live birth for a given number of eggs, stratified by age group. We produced a nomogram to predict the live birth rate (LBR) following IVF based on the number of eggs and the age of the female. The median number of eggs retrieved per cycle was 9 [inter-quartile range (IQR) 6-13]. The overall LBR was 21.3% per fresh IVF cycle. There was a strong association between the number of eggs and LBR; LBR rose with an increasing number of eggs up to ∼15, plateaued between 15 and 20 eggs and steadily declined beyond 20 eggs. During 2006-2007, the predicted LBR for women with 15 eggs retrieved in age groups 18-34, 35-37, 38-39 and 40 years and over was 40, 36, 27 and 16%, respectively. There was a steady increase in the LBR per egg retrieved over time since 1991. The relationship between the number of eggs and live birth, across all female age groups, suggests that the number of eggs in IVF is a robust surrogate outcome for clinical success. The results showed a non-linear relationship between the number of eggs and LBR following IVF treatment. The number of eggs to maximize the LBR is ∼15.
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              Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos?

              What is the impact of ovarian response on cumulative live birth rates (LBR) following utilization of all fresh and frozen embryos in women undergoing their first ovarian stimulation cycle, planned to undergo single embryo transfer (SET).
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                17 August 2018
                2018
                : 9
                : 461
                Affiliations
                [1] 1ANDROFERT, Andrology and Human Reproduction Clinic , Campinas, Brazil
                [2] 2Department of Surgery, University of Campinas (UNICAMP) , Campinas, Brazil
                [3] 3Faculty of Health, Aarhus University , Aarhus, Denmark
                [4] 4ORIGEN, Center for Reproductive Medicine , Rio de Janeiro, Brazil
                [5] 5Division of Reproductive Medicine, Department of Gynecology and Obstetrics, University of São Paulo , Ribeirão Preto, Brazil
                [6] 6Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II , Naples, Italy
                [7] 7Fertility Clinic Skive Regional Hospital , Skive, Denmark
                Author notes

                Edited by: John Lui Yovich, Pivet Medical Center, Australia

                Reviewed by: Nikolaos P. Polyzos, Dexeus University Hospital, Spain; Kevin Noel Keane, Curtin University, Australia

                *Correspondence: Sandro C. Esteves s.esteves@ 123456androfert.com.br

                This article was submitted to Reproduction, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2018.00461
                6107695
                30174650
                99e4539f-8a82-47cd-88bf-f5fd54722cf5
                Copyright © 2018 Esteves, Roque, Bedoschi, Conforti, Humaidan and Alviggi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 April 2018
                : 26 July 2018
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 86, Pages: 10, Words: 8200
                Categories
                Endocrinology
                Mini Review

                Endocrinology & Diabetes
                assisted reproductive technology,hypo-responder,low responder,ovarian stimulation,poor ovarian response,poor ovarian reserve,poseidon criteria

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