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      Management of Women With an Unexpected Low Ovarian Response to Gonadotropin

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          Abstract

          POSEIDON groups 1 and 2 patients respond poorly (<4 oocytes retrieved) or sub-optimally (4–9 oocytes retrieved) to gonadotropin stimulation despite the presence of adequate ovarian parameters, which negatively affect their cumulative chances of delivering a baby using Assisted Reproductive Technology. A polygenic trait involving gonadotropins and/or their receptors seems to be the primary pathophysiology mechanism explaining this phenomenon. The clinical management is mainly focused on maximizing oocyte yield as to increase the likelihood of having at least one euploid embryo for transfer. Indices such as FORT (follicle output rate) and FOI (follicle-to-oocyte index) may be used to determine if the ovarian reserve was properly explored during a previous ovarian stimulation. Testing for the presence of common polymorphisms affecting gonadotropins and/or their receptors can also be considered to identify patients at risk of hypo-response. An individualized estimation of the minimum number of oocytes needed to obtain at least one euploid embryo can assist counseling and treatment planning. Among currently existing pharmacological interventions, use of recombinant FSH in preference over urinary gonadotropin preparations, FSH dosage increase, and use of rLH supplementation may be considered -alone or combined- for optimally managing POSEIDON's groups 1 and 2 patients. However, given the recent introduction of the POSEIDON criteria, there is still a lack of studies examining the role of interventions specifically to patients classified as groups 1 and 2, thus making it an area for open research.

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          Most cited references72

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          Pharmacogenomics in the clinic.

          After decades of discovery, inherited variations have been identified in approximately 20 genes that affect about 80 medications and are actionable in the clinic. And some somatically acquired genetic variants direct the choice of 'targeted' anticancer drugs for individual patients. Current efforts that focus on the processes required to appropriately act on pharmacogenomic variability in the clinic are moving away from discovery and towards implementation of an evidenced-based strategy for improving the use of medications, thereby providing a cornerstone for precision medicine.
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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
                27 June 2019
                2019
                : 10
                : 387
                Affiliations
                [1] 1Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II , Naples, Italy
                [2] 2ANDROFERT, Andrology and Human Reproduction Clinic , Campinas, Brazil
                [3] 3Department of Surgery, University of Campinas , Campinas, Brazil
                [4] 4Faculty of Health, Aarhus University , Aarhus, Denmark
                [5] 5GENERA, Centre for Reproductive Medicine, Clinica Valle Giulia , Rome, Italy
                [6] 6Medical Oncology, Department of Senology, National Cancer Institute, IRCCS Fondazione G. Pascale , Naples, Italy
                Author notes

                Edited by: Robert Fischer, Fertility Center Hamburg (FCH), Germany

                Reviewed by: Thomas Strowitzki, Universität Heidelberg, Germany; Giuliano Marchetti Bedoschi, University of São Paulo, Brazil

                *Correspondence: Alessandro Conforti confale@ 123456hotmail.it

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

                Article
                10.3389/fendo.2019.00387
                6610322
                31316461
                abd8eb84-17f0-45b4-b5be-eb8f300ea1b0
                Copyright © 2019 Conforti, Esteves, Cimadomo, Vaiarelli, Di Rella, Ubaldi, Zullo, De Placido 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
                : 23 January 2019
                : 29 May 2019
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 77, Pages: 10, Words: 8105
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                hypo-response,ovarian stimulation,assisted reproductive technology,ovarian reserve,follicle-to-oocyte index,poseidon criteria,suboptimal response,art calculator

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