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      An ever-challenging relationship: lupus and pregnancy

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          Abstract

          Systemic lupus erythematous (SLE) is a chronic inflammatory disease with an unknown etiology and an autoimmune pathogenesis, and its clinical manifestations can involve multiple organs through polymorphic biological changes. Nowadays, pregnancy is possible for most patients with SLE, and good outcomes can be expected for both mother and child. This became possible as a consequence of increasingly better monitoring and treatment of pregnant women with SLE. The following article outlines the problems associated with fertility, course of pregnancy, and breastfeeding in women with SLE.

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          EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome

          L Andreoli, G Bertsias, N Agmon-Levin … (2017)
          Objectives Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Methods Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. Results Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. Conclusions Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.
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            Disordered IL-33/ST2 Activation in Decidualizing Stromal Cells Prolongs Uterine Receptivity in Women with Recurrent Pregnancy Loss

            Madhuri Salker, Jaya Nautiyal, Jennifer Steel … (2012)
            Decidualization renders the endometrium transiently receptive to an implanting blastocyst although the underlying mechanisms remain incompletely understood. Here we show that human endometrial stromal cells (HESCs) rapidly release IL-33, a key regulator of innate immune responses, upon decidualization. In parallel, differentiating HESCs upregulate the IL-33 transmembrane receptor ST2L and other pro-inflammatory mediators before mounting a profound anti-inflammatory response that includes downregulation of ST2L and increased expression of the soluble decoy receptor sST2. We demonstrate that HESCs secrete factors permissive of embryo implantation in mice only during the pro-inflammatory phase of the decidual process. IL-33 knockdown in undifferentiated HESCs was sufficient to abrogate this pro-inflammatory decidual response. Further, sequential activation of the IL-33/ST2L/sST2 axis was disordered in decidualizing HESCs from women with recurrent pregnancy loss. Signals from these cultures prolonged the implantation window but also caused subsequent pregnancy failure in mice. Thus, Il-33/ST2 activation in HESCS drives an autoinflammatory response that controls the temporal expression of receptivity genes. Failure to constrain this response predisposes to miscarriage by allowing out-of-phase implantation in an unsupportive uterine environment.
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              State of the art: Reproduction and pregnancy in rheumatic diseases.

              Monika Østensen, Laura Andreoli, Antonio Brucato … (2015)
              Throughout the last decade, increasing awareness has been raised on issues related to reproduction in rheumatic diseases including basic research to clarify the important role of estrogens in the etiology and pathophysiology of immune/inflammatory diseases. Sub- or infertility is a heterogeneous condition that can be related to immunological mechanisms, to pregnancy loss, to disease burden, to therapy, and to choices in regard to family size. Progress in reproductive medicine has made it possible for more patients with rheumatic disease to have children. Active disease in women with rheumatoid arthritis (RA) affects their children's birth weight and may have long-term effects on their future health status. Pregnancy complications as preeclampsia and intrauterine growth restriction are still increased in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), however, biomarkers can monitor adverse events, and several new therapies may improve outcomes. Pregnancies in women with APS remain a challenge, and better therapies for the obstetric APS are needed. New prospective studies indicate improved outcomes for pregnancies in women with rare diseases like systemic sclerosis and vasculitis. TNF inhibitors hold promise for maintaining remission in rheumatological patients and may be continued at least in the first half of pregnancy. Pre-conceptional counseling and interdisciplinary management of pregnancies are essential for ensuring optimal pregnancy outcomes.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Reumatologia
                Journal ID (iso-abbrev): Reumatologia
                Journal ID (publisher-id): RU
                Title: Reumatologia
                Publisher: Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie
                ISSN (Print): 0034-6233
                ISSN (Electronic): 2084-9834
                Publication date (Electronic): 22 March 2017
                Publication date (Print): 2017
                Volume: 55
                Issue: 1
                Pages: 29-37
                Affiliations
                University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
                Author notes
                Address for correspondence: Teodora Donisan, Sf. Maria Hospital, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania. tel. +40740135024, fax +40752087037. e-mail: teodora.donisan@gmail.com
                Article
                Publisher ID: 29675
                DOI: 10.5114/reum.2017.66685
                PMC ID: 5380770
                PubMed ID: 28386140
                SO-VID: 8ce89bdb-dd05-4422-a3d2-5236849e8f02
                Copyright © Copyright: © 2017 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                History
                Date received : 21 January 2017
                Date accepted : 11 February 2017
                Categories
                Subject: Review Paper

                Keywords: systemic lupus erythematosus,pregnancy
                Data availability:
                Keywords: systemic lupus erythematosus, pregnancy

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