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      Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions

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          Abstract

          Recurrent implantation failure (RIF) refers to cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos. The definition should also take advanced maternal age and embryo stage into consideration. The failure of embryo implantation can be a consequence of uterine, male, or embryo factors, or the specific type of IVF protocol. These cases should be investigated to determine the most likely etiologies of the condition, as this is a complex problem with several variables. There are multiple risk factors for recurrent implantation failure including advanced maternal age, smoking status of both parents, elevated body mass index, and stress levels. Immunological factors such as cytokine levels and presence of specific autoantibodies should be examined, as well as any infectious organisms in the uterus leading to chronic endometritis. Uterine pathologies such as polyps and myomas as well as congenital anatomical anomalies should be ruled out. Sperm analysis, pre-implantation genetic screening and endometrial receptivity should be considered and evaluated, and IVF protocols should be tailored to specific patients or patient populations. Treatment approaches should be directed toward individual patient cases. In addition, we suggest considering a new initial step in approach to patients with RIF, individualized planned activities to activate the brain's reward system in attempt to improve immunological balance in the body.

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          Evidence that the endometrial microbiota has an effect on implantation success or failure.

          Bacterial cells in the human body account for 1-3% of total body weight and are at least equal in number to human cells. Recent research has focused on understanding how the different bacterial communities in the body (eg, gut, respiratory, skin, and vaginal microbiomes) predispose to health and disease. The microbiota of the reproductive tract has been inferred from the vaginal bacterial communities, and the uterus has been classically considered a sterile cavity. However, while the vaginal microbiota has been investigated in depth, there is a paucity of consistent data regarding the existence of an endometrial microbiota and its possible impact in reproductive function.
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            The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure.

            To demonstrate the clinical value of the endometrial receptivity array (ERA) in patients with repeated implantation failure (RIF), for guiding their personalized embryo transfer (pET) as a novel therapeutic strategy.
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              GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type.

              Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist was not the only variable between the compared study arms.
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                Author and article information

                Contributors
                abashiri@bgu.ac.il
                khalps1@gmail.com
                Raoul.Orvieto@sheba.health.gov.il
                Journal
                Reprod Biol Endocrinol
                Reprod. Biol. Endocrinol
                Reproductive Biology and Endocrinology : RB&E
                BioMed Central (London )
                1477-7827
                5 December 2018
                5 December 2018
                2018
                : 16
                : 121
                Affiliations
                [1 ]ISNI 0000 0004 0470 8989, GRID grid.412686.f, Recurrent Pregnancy Loss Clinic, Maternal-Fetal Medicine, and Ultrasound, , Soroka University Medical Center, ; P.O.B. 151, 84101 Beer Sheva, Israel
                [2 ]ISNI 0000 0004 1937 0511, GRID grid.7489.2, Faculty of Health Sciences, , Ben-Gurion University of the Negev, ; P.O.B. 151, 84101 Beer Sheva, Israel
                [3 ]ISNI 0000 0001 2107 2845, GRID grid.413795.d, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, ; Tel-Hashomer, 52621 Ramat Gan, Israel
                [4 ]ISNI 0000 0004 1937 0546, GRID grid.12136.37, Sackler Faculty of Medicine, , Tel-Aviv University, ; Tel Aviv, Israel
                Author information
                http://orcid.org/0000-0001-9766-8370
                Article
                414
                10.1186/s12958-018-0414-2
                6282265
                30518389
                86cd45f0-a1bd-4314-b53a-66cbd3399176
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 June 2018
                : 3 October 2018
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Human biology
                recurrent implantation failure-rif,low molecular weight heparin,endometrial scratching,chronic endometritis,preimplantation genetic screening- pgs,ivig,progesterone,reward system

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