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      Thyroid autoimmunity and obstetric outcomes in women with recurrent miscarriage: a case–control study

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          Abstract

          Objectives

          Thyroid antibody positivity during pregnancy has been associated with adverse outcomes including miscarriage and preterm delivery. The aim of the study is to evaluate the obstetric outcome in pregnant women with recurrent miscarriage and their response to levothyroxine ( l-T 4) therapy.

          Study design and methods

          All pregnant and non-pregnant women between 21 and 35 years of age with a history of two or more consecutive miscarriages were included in the study. A third group comprising 100 pregnant women without a history of miscarriage were taken as healthy controls. Thyroid autoimmunity, prevalence of subclinical hypothyroidism and maternal and foetal complications were analysed in all the groups with appropriate statistical methods.

          Results

          The mean age of the patients included in the study was 27.0±3.1 years. Of 100 pregnant patients with previous recurrent miscarriage, thyroid autoimmunity (thyroid peroxidase antibody (TPOAb +) >34 U/ml) was found in 31% of the cases. The incidence of subclinical hypothyroidism was higher in TPOAb + group than in TPOAb group (52 vs 16%; P=0.0002). There was no difference in the prevalence of miscarriage or obstetric outcomes between recurrent miscarriage and healthy pregnant women group irrespective of TPO status.

          Conclusions

          The prevalence of thyroid autoimmunity was higher in pregnant women with a history of recurrent abortion compared with healthy pregnant control population. Following l-T 4 treatment, there was no difference in prevalence of miscarriage between hypothyroid and euthyroid individuals in TPOAb + women.

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          Most cited references24

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          Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications.

          Euthyroid women with autoimmune thyroid disease show impairment of thyroid function during gestation and seem to suffer from a higher rate of obstetrical complications. We sought to determine whether these women suffer from a higher rate of obstetrical complications and whether levothyroxine (LT(4)) treatment exerts beneficial effects. This was a prospective study. The study was conducted in the Department of Obstetrics and Gynecology. A total of 984 pregnant women were studied from November 2002 to October 2004; 11.7% were thyroid peroxidase antibody positive (TPOAb(+)). TPOAb(+) patients were divided into two groups: group A (n = 57) was treated with LT(4), and group B (n = 58) was not treated. The 869 TPOAb(-) patients (group C) served as a normal population control group. Rates of obstetrical complications in treated and untreated groups were measured. At baseline, TPOAb(+) had higher TSH compared with TPOAb(-); TSH remained higher in group B compared with groups A and C throughout gestation. Free T(4) values were lower in group B than groups A and C after 30 wk and after parturition. Groups A and C showed a similar miscarriage rate (3.5 and 2.4%, respectively), which was lower than group B (13.8%) [P < 0.05; relative risk (RR), 1.72; 95% confidence interval (CI), 1.13-2.25; and P < 0.01; RR = 4.95; 95% CI = 2.59-9.48, respectively]. Group B displayed a 22.4% rate of premature deliveries, which was higher than group A (7%) (P < 0.05; RR = 1.66; 95% CI = 1.18-2.34) and group C (8.2%) (P < 0.01; RR = 12.18; 95% CI = 7.93-18.7). Euthyroid pregnant women who are positive for TPOAb develop impaired thyroid function, which is associated with an increased risk of miscarriage and premature deliveries. Substitutive treatment with LT(4) is able to lower the chance of miscarriage and premature delivery.
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            Recurrent miscarriage: aetiology, management and prognosis.

            Recurrent miscarriage (RM) is a heterogeneous condition. A large number of studies has recently been published, yet many of them have conflicting conclusions. The various aetiological factors, management, prognostic features and outcomes of a subsequent pregnancy in women with RM are reviewed.
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              Pathogenesis of infertility and recurrent pregnancy loss in thyroid autoimmunity.

              Thyroid autoimmunity is the most prevalent autoimmune state that affects up to 4% of women during the age of fertility. A growing body of clinical studies links thyroid autoimmunity as a cause of infertility and adverse pregnancy outcomes that includes miscarriage or preterm deliveries. Importantly, these adverse effects are persistent in euthyroid women. In the current review we elaborate on the pathogenesis that underlies infertility and increased pregnancy loss among women with autoimmune thyroid disease. Such mechanisms include thyroid autoantibodies that exert their effect in a TSH-dependent but also in a TSH-independent manner. The later includes quantitative and qualitative changes in the profile of endometrial T cells with reduced secretion of IL-4 and IL-10 along with hypersecretion of interferon-γ. Polyclonal B cells activation is 2-3 time more frequent in thyroid autoimmunity and is associated with increased titers of non-organ specific autoantibodies. Hyperactivity and Increased migration of cytotoxic natural killer cells that alter the immune and hormonal response of the uterus is up to 40% more common in women with thyroid autoimmunity. Lack of vitamin D was suggested as a predisposing factor to autoimmune diseases, and was shown to be reduced in patients with thyroid autoimmunity. In turn, its deficiency is also linked to infertility and pregnancy loss, suggesting a potential interplay with thyroid autoimmunity in the context of infertility. In addition, thyroid autoantibodies were also suggested to alter fertility by targeting zona pellucida, human chorionic gonadotropin receptors and other placental antigens. Copyright © 2011 Elsevier Ltd. All rights reserved.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                BioScientifica (Bristol )
                2049-3614
                22 June 2013
                1 June 2013
                : 2
                : 2
                : 118-124
                Affiliations
                [1 ]Departments of Obstetrics and Gynecology Post Graduate Institute of Medical Education and Research (PGIMER) ChandigarhIndia
                [2 ]Department of Endocrinology Post Graduate Institute of Medical Education and Research (PGIMER) ChandigarhIndia
                [3 ]Department of Pharmacology Post Graduate Institute of Medical Education and Research (PGIMER) ChandigarhIndia
                Author notes
                Correspondence should be addressed to A Bhansali Email: anilbhansaliendocrine@ 123456rediffmail.com
                Article
                EC130012
                10.1530/EC-13-0012
                3691574
                23802061
                cecadd25-d645-4346-a629-5c3d1d21e22f
                © 2013 The Authors

                This work is licensed under a Creative Commons Attribution 3.0 Unported License.

                History
                : 1 March 2013
                : 2 April 2013
                Categories
                Research

                recurrent miscarriage,thyroid peroxidase,hypothyroidism,preterm birth

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