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      Effect of Growth Hormone on Uterine Receptivity in Women With Repeated Implantation Failure in an Oocyte Donation Program: A Randomized Controlled Trial

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          Abstract

          Background and Objective:

          Administration of growth hormone (GH) during ovarian stimulation has been shown to improve success rates of in vitro fertilization. GH beneficial effect on oocyte quality is shown in several studies, but GH effect on uterine receptivity is not clear. To assess it, we studied whether GH administration can improve the chance of pregnancy and birth in women who experienced repeated implantation failure (RIF) using donated oocyte programs.

          Design and Study Population:

          A total of 105 infertile women were enrolled in the randomized controlled trial: 70 women were with a history of RIF with donated oocytes, and 35 infertile women underwent the first oocyte donation attempt. Women receiving donated oocytes were treated with progressively increasing doses of oral estradiol, followed by intravaginal progesterone after previous pituitary desensitization with gonadotropin-releasing hormone agonist. Thirty-five RIF patients were treated with GH (GH patients), whereas the rest of the 35 RIF patients (non-GH patients) and 35 first-attempt patients (positive control group) were not.

          Results:

          RIF patients receiving GH showed significantly thicker endometrium and higher pregnancy and live birth rates as compared with RIF patients of non-GH study group, although these rates remained somewhat lower as compared with the non-RIF patients of the positive control group. No abnormality was detected in any of the babies born.

          Conclusion:

          Our data of improved implantation, pregnancy, and live birth rates among infertile RIF patients treated with GH indicate that GH improves uterine receptivity.

          Abstract

          Growth hormone administration improves pregnancy and birth rates among infertile women experiencing repeated implantation failure after receiving donated oocytes.

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          Most cited references39

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          An endometrial gene expression signature accurately predicts recurrent implantation failure after IVF

          The primary limiting factor for effective IVF treatment is successful embryo implantation. Recurrent implantation failure (RIF) is a condition whereby couples fail to achieve pregnancy despite consecutive embryo transfers. Here we describe the collection of gene expression profiles from mid-luteal phase endometrial biopsies (n = 115) from women experiencing RIF and healthy controls. Using a signature discovery set (n = 81) we identify a signature containing 303 genes predictive of RIF. Independent validation in 34 samples shows that the gene signature predicts RIF with 100% positive predictive value (PPV). The strength of the RIF associated expression signature also stratifies RIF patients into distinct groups with different subsequent implantation success rates. Exploration of the expression changes suggests that RIF is primarily associated with reduced cellular proliferation. The gene signature will be of value in counselling and guiding further treatment of women who fail to conceive upon IVF and suggests new avenues for developing intervention.
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            Addition of growth hormone to gonadotrophins in ovarian stimulation of poor responders treated by in-vitro fertilization: a systematic review and meta-analysis.

            Whether the addition of growth hormone (GH) can improve the probability of pregnancy in poor responders undergoing ovarian stimulation for in-vitro fertilization (IVF) has been examined to date by several underpowered studies, which have not provided solid conclusions. A computerized literature search in MEDLINE, EMBASE, CENTRAL and randomized controlled trial (RCT) registries was performed independently by two reviewers, aiming to identify RCTs that evaluated the following research question: does GH addition increase the probability of pregnancy in poor responders undergoing ovarian stimulation with gonadotrophin releasing hormone (GnRH) analogues and gonadotrophins for IVF? Six relevant RCTs were identified, including a total of 169 patients. GH addition significantly increased clinical pregnancy (rate difference: +16%, 95% CI: +4 to +28; fixed effects model) (number-needed-to-treat (NNT) = 6, 95% CI: 4-25) and live birth rates (rate difference: +17%, 95% CI: +5 to +30; fixed effects model) (NNT = 6; 95% CI: 3-20). Furthermore, GH addition was associated with a significantly higher proportion of patients reaching embryo transfer (rate difference: +22%, 95% CI: +7 to +36; fixed effects model). The present meta-analysis provides evidence that GH addition increases the probability of clinical pregnancy and live birth in poor responders undergoing ovarian stimulation with GnRH analogues and gonadotrophins for IVF. However, the total number of patients analyzed is small and thus further RCTs are warranted to prove or disprove this finding.
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              Growth Hormone and Reproduction: A Review of Endocrine and Autocrine/Paracrine Interactions

              The somatotropic axis, consisting of growth hormone (GH), hepatic insulin-like growth factor I (IGF-I), and assorted releasing factors, regulates growth and body composition. Axiomatically, since optimal body composition enhances reproductive function, general somatic actions of GH modulate reproductive function. A growing body of evidence supports the hypothesis that GH also modulates reproduction directly, exerting both gonadotropin-dependent and gonadotropin-independent actions in both males and females. Moreover, recent studies indicate GH produced within reproductive tissues differs from pituitary GH in terms of secretion and action. Accordingly, GH is increasingly used as a fertility adjunct in males and females, both humans and nonhumans. This review reconsiders reproductive actions of GH in vertebrates in respect to these new conceptual developments.
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                Author and article information

                Journal
                J Endocr Soc
                J Endocr Soc
                JS
                JS
                Journal of the Endocrine Society
                Endocrine Society (Washington, DC )
                2472-1972
                01 January 2018
                19 December 2017
                19 December 2017
                : 2
                : 1
                : 96-105
                Affiliations
                [1 ]Competence Centre on Health Technologies, University of Tartu, 50410 Tartu, Estonia
                [2 ]Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, 18016 Granada, Spain
                [3 ]MARGen Clinic, Molecular Assisted Reproduction and Genetics, 18006 Granada, Spain
                [4 ]Department of Obstetrics and Gynecology, University of Granada, 18016 Granada, Spain
                [5 ]Department of Maternal and Fetal Health, San Camillo Forlanini Hospital, 00152 Rome, Italy
                Author notes
                Correspondence:  Jan Tesarik, MD, PhD, MARGen Clinic, Camino de Ronda 2, 18006 Granada, Spain. E-mail: jtesarik@ 123456clinicamargen.com .
                Article
                JS_201700359
                10.1210/js.2017-00359
                5779111
                29379897
                f16a4b31-c5eb-4b6d-abb3-71e7711fdb18
                Copyright © 2018 Endocrine Society

                This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 06 September 2017
                : 14 December 2017
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 38, Pages: 10
                Categories
                Clinical Research Articles
                Reproductive Biology and Sex-Based Medicine

                endometrial receptivity,growth hormone,implantation failure,ivf,rif

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