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      Metformin therapy before conception versus throughout the pregnancy and risk of gestational diabetes mellitus in women with polycystic ovary syndrome: a systemic review, meta-analysis and meta-regression

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          Abstract

          The results of studies that assessed the impact of metformin treatments on gestational diabetes mellitus (GDM) in patients with polycystic ovary syndrome (PCOS) are inconclusive. In addition, the impact of time and duration of metformin therapy for an optimum reduction of GDM has not been reported in these studies. This study aimed to summarize current knowledge regarding the effect of metformin-therapy before conception versus throughout pregnancy on the risk of GDM in women with PCOS. PubMed, Scopus, Google Scholar and ScienceDirect databases were searched to identify relevant studies. Both fixed and random effect models were used. Subgroup analyses were performed based on the on the study methodology. The association between the PCOS status and GDM was assessed using the univariate and multiple meta-regression analysis adjusted by the BMI and metformin therapy. Forty-eight of 1397 identified studies were included involving 5711 PCOS patients and 20,296 controls. Regardless of metformin therapy, the prevalence of GDM diagnosed in the second trimester among women with PCOS was significantly higher than healthy controls that was independent of obesity. Including all studies, the increased risk of GDM among women with PCOS, compared to healthy controls, disappeared after the adjustment of metformin-therapy (β = 0.08, 95% CI 0.04, 0.2; p = 0.624). By excluding observational studies as a source of bias, the prevalence of GDM among women with PCOS treated using metformin before conception till the end of pregnancy did not differ from treated just before conception (β = − 0.09, 95% CI − 0.2, 0.02; p = 0.092) or those without metformin therapy (β = − 0.05, 95% CI − 0.07, 0.04; p = 0.301). The results remained unchanged after the subgroup analysis based on the methodology of RCTs and non-RCTs studies. The main body of literature in the current meta-analysis was observational, which may be mixed with some sources of bias. Also, a lack of well-designed and high quality interventional studies means that the findings should be interpreted with cautious. In this respect, decisions regarding the continuation or discontinuation of metformin therapy in women with PCOS are somewhat arbitrary and can be made individually based on the patient’s condition given the presence or absence of other GDM risk factors. Additional well-designed RCTs still need for precise recommendation.

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          A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome.

          Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with many characteristic features, including hyperandrogenaemia, insulin resistance and obesity which may have significant implications for pregnancy outcomes and long-term health of the woman. This meta-analysis was conducted to evaluate the risk of pregnancy and neonatal complications in women with PCOS. Electronic databases were searched for the following MeSH headings: PCOS, hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus, type II. A handsearch of human reproduction and fertility and sterility was also conducted. Studies in which pregnancy outcomes in women with PCOS were compared with controls were considered for inclusion in this meta-analysis. Fifteen of 525 identified studies were included, involving 720 women presenting with PCOS and 4505 controls. Women with PCOS demonstrated a significantly higher risk of developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70-5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98-6.81), pre-eclampsia (OR 3.47; 95% CI: 1.95-6.17) and preterm birth (OR 1.75; 95% CI: 1.16-2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31; 95% CI: 1.25-4.26) and a higher perinatal mortality (OR 3.07; 95% CI: 1.03-9.21), unrelated to multiple births. In conclusion, women with PCOS are at increased risk of pregnancy and neonatal complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at reducing these risks.
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            Placental hormones and the control of maternal metabolism and fetal growth.

            To examine the roles of the placental and pituitary hormones in the control of maternal metabolism and fetal growth. In addition to promoting growth of maternal tissues, placental growth hormone (GH-V) induces maternal insulin resistance and thereby facilitates the mobilization of maternal nutrients for fetal growth. Human placental lactogen (hPL) and prolactin increase maternal food intake by induction of central leptin resistance and promote maternal beta-cell expansion and insulin production to defend against the development of gestational diabetes mellitus. The effects of the lactogens are mediated by diverse signaling pathways and are potentiated by glucose. Pathologic conditions of pregnancy are associated with dysregulation of GH-V and hPL gene expression. The somatogenic and lactogenic hormones of the placenta and maternal pituitary gland integrate the metabolic adaptations of pregnancy with the demands of fetal and neonatal development. Dysregulation of placental growth hormone and/or placental lactogen in pathologic conditions of pregnancy may adversely impact fetal growth and postnatal metabolic function.
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              Normal pregnancy- a state of insulin resistance.

              Purpose of insulin resistance (IR) adapted by mother is to deliver enough quantity of nutrients to the growing fetus. Many maternal hormones and factors play role in causation of IR during pregnancy.
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                Author and article information

                Contributors
                +98-021-22432500 , behboudi@endocrine.ac.ir , s.behboudi@hotmail.com
                Journal
                Diabetol Metab Syndr
                Diabetol Metab Syndr
                Diabetology & Metabolic Syndrome
                BioMed Central (London )
                1758-5996
                23 July 2019
                23 July 2019
                2019
                : 11
                : 58
                Affiliations
                [1 ]GRID grid.411600.2, Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, , Shahid Beheshti University of Medical Sciences, ; No 24, Parvane Street, Yaman Street, Velenjak, P.O.Box: 19395-4763, Tehran, Iran
                [2 ]ISNI 0000 0001 0166 0922, GRID grid.411705.6, Department of Epidemiology and Biostatistics, School of Public Health, , Tehran University of Medical Sciences, ; Tehran, Iran
                Article
                453
                10.1186/s13098-019-0453-7
                6651943
                1696eae3-5e45-408b-bd63-659bce8099b0
                © The Author(s) 2019

                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
                : 9 April 2019
                : 8 July 2019
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Nutrition & Dietetics
                gestational diabetes mellitus,meta-analysis,meta-regression,metformin therapy,polycystic ovary syndrome

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