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The Effects of Diabetes Mellitus on Ovarian Injury and Reserve: An Experimental Study

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      Abstract

      Objective: The study aims to investigate the effects of diabetes mellitus (DM) on ovarian injury and reserve in a rat model. Study Design: In this prospective experimental study, 16 female Sprague-Dawley albino rats (12 weeks, 220-240 g) were randomly divided into 2 groups. Group 1 included 8 normal healthy rats as controls. No drug was administered to the controls. Group 2 included the other 8 rats in which diabetes was induced by intraperitoneal injections of streptozotocin (STZ). After overt DM occurred (blood glucose >250 mg/dl), all the animals were euthanized and blood samples were collected by cardiac puncture for biochemical analysis. Bilateral oophorectomy was performed for histopathological examination. Immunoexpressions of nuclear factor-kappa B (NF-kB) and caspase-3 as well as anti-Müllerian hormone (AMH) levels were assessed. Values were analyzed by t test. Results: Immunoexpressions of NF-kB and caspase-3 were significantly higher in non-treated diabetic rats than in the control group (p = 0.011 and p = 0.010, respectively). In healthy control group, AMH levels (3.22 ± 0.58 ng/ml) were significantly higher than in the non-treated diabetic group (1.41 ± 0.25 ng/dl; p = 0.024). Conclusion: Hyperglycemia causes severe ovarian injury via NF-kB pathway and caspase-3 apoptotic pathway, leading to the decrease in ovarian reserve in STZ-induced diabetic rats.

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      Most cited references 30

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      The pathobiology of diabetic complications: a unifying mechanism.

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        Oxidative stress and diabetic complications.

        Oxidative stress plays a pivotal role in the development of diabetes complications, both microvascular and cardiovascular. The metabolic abnormalities of diabetes cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. This increased superoxide production causes the activation of 5 major pathways involved in the pathogenesis of complications: polyol pathway flux, increased formation of AGEs (advanced glycation end products), increased expression of the receptor for AGEs and its activating ligands, activation of protein kinase C isoforms, and overactivity of the hexosamine pathway. It also directly inactivates 2 critical antiatherosclerotic enzymes, endothelial nitric oxide synthase and prostacyclin synthase. Through these pathways, increased intracellular reactive oxygen species (ROS) cause defective angiogenesis in response to ischemia, activate a number of proinflammatory pathways, and cause long-lasting epigenetic changes that drive persistent expression of proinflammatory genes after glycemia is normalized ("hyperglycemic memory"). Atherosclerosis and cardiomyopathy in type 2 diabetes are caused in part by pathway-selective insulin resistance, which increases mitochondrial ROS production from free fatty acids and by inactivation of antiatherosclerosis enzymes by ROS. Overexpression of superoxide dismutase in transgenic diabetic mice prevents diabetic retinopathy, nephropathy, and cardiomyopathy. The aim of this review is to highlight advances in understanding the role of metabolite-generated ROS in the development of diabetic complications.
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          A systematic review of tests predicting ovarian reserve and IVF outcome.

          The age-related decline of the success in IVF is largely attributable to a progressive decline of ovarian oocyte quality and quantity. Over the past two decades, a number of so-called ovarian reserve tests (ORTs) have been designed to determine oocyte reserve and quality and have been evaluated for their ability to predict the outcome of IVF in terms of oocyte yield and occurrence of pregnancy. Many of these tests have become part of the routine diagnostic procedure for infertility patients who undergo assisted reproductive techniques. The unifying goals are traditionally to find out how a patient will respond to stimulation and what are their chances of pregnancy. Evidence-based medicine has progressively developed as the standard approach for many diagnostic procedures and treatment options in the field of reproductive medicine. We here provide the first comprehensive systematic literature review, including an a priori protocolized information retrieval on all currently available and applied tests, namely early-follicular-phase blood values of FSH, estradiol, inhibin B and anti-Müllerian hormone (AMH), the antral follicle count (AFC), the ovarian volume (OVVOL) and the ovarian blood flow, and furthermore the Clomiphene Citrate Challenge Test (CCCT), the exogenous FSH ORT (EFORT) and the gonadotrophin agonist stimulation test (GAST), all as measures to predict ovarian response and chance of pregnancy. We provide, where possible, an integrated receiver operating characteristic (ROC) analysis and curve of all individual evaluated published papers of each test, as well as a formal judgement upon the clinical value. Our analysis shows that the ORTs known to date have only modest-to-poor predictive properties and are therefore far from suitable for relevant clinical use. Accuracy of testing for the occurrence of poor ovarian response to hyperstimulation appears to be modest. Whether the a priori identification of actual poor responders in the first IVF cycle has any prognostic value for their chances of conception in the course of a series of IVF cycles remains to be established. The accuracy of predicting the occurrence of pregnancy is very limited. If a high threshold is used, to prevent couples from wrongly being refused IVF, a very small minority of IVF-indicated cases (approximately 3%) are identified as having unfavourable prospects in an IVF treatment cycle. Although mostly inexpensive and not very demanding, the use of any ORT for outcome prediction cannot be supported. As poor ovarian response will provide some information on OR status, especially if the stimulation is maximal, entering the first cycle of IVF without any prior testing seems to be the preferable strategy.
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            Author and article information

            Affiliations
            Departments of aObstetrics and Gynecology, bAnesthesiology and Reanimation, cPathology, dCardiovascular Surgery, and eBiochemistry, Erzincan University, School of Medicine, Erzincan, Turkey
            Journal
            GOI
            Gynecol Obstet Invest
            10.1159/issn.0378-7346
            Gynecologic and Obstetric Investigation
            Gynecol Obstet Invest
            S. Karger AG (Basel, Switzerland karger@123456karger.com http://www.karger.com )
            0378-7346
            1423-002X
            September 2016
            19 December 2015
            : 81
            : 5
            : 424-429
            © 2015 S. Karger AG, Basel

            Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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            Figures: 2, Tables: 1, References: 37, Pages: 6
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