ReviewState of the art: Reproduction and pregnancy in rheumatic diseases
Introduction
Throughout the last decade, increasing awareness has been raised on issues related to reproduction in chronic diseases. Rheumatic diseases can affect quality of life and reproduction in both genders. Hormones, fertility, pregnancy, and management of high-risk pregnancy are important topics for patients and their doctors alike. This article gives a concise overview of current basic and clinical research presented at the VIII International Conference on Reproduction and Pregnancy and the rheumatic diseases 25–27, 2014 September in Trondheim, Norway.
Section snippets
Sex hormones and autoimmune diseases
The preponderance of women affected by chronic immune/inflammatory diseases clearly indicates that female sex hormones play an important role in the etiology and pathophysiology of autoimmunity [1]. In human subjects estrogens are generally considered as at least enhancing the humoral immune response. They act on cells by their peripheral metabolites rather than through their serum levels that may exert opposite dose-related effects [2].
Estrogen receptors (ERα and ERβ) are necessary for the
Fertility
Fertility problems in women with rheumatic disease occur not only in diseases with extensive systemic inflammation and autoantibody production, but also in the predominantly inflammatory joint diseases (IJD) [8]. Women with IJD have a prolonged time to pregnancy compared to women in the general population, and seem also to require assisted reproduction more often [9]. Whether they also have a reduced ovarian reserve has not been clarified. In a prospective study of 245 women with rheumatoid
Pregnancy and rheumatic diseases
The response of rheumatic diseases to pregnancy varies in regard to disease activity. Likewise pregnancy outcome is different depending on disease extent and severity, presence of autoantibodies, comorbidities, therapy as well as non-disease related factors.
The obstetric antiphospholipid syndrome
The pathogenesis of obstetric antiphospholipid syndrome (OAPS) is rather heterogeneous, complex and not fully understood yet. Differently from the model of aPL-mediated thrombosis, no need for a second hit is required for the induction of placental damage and pregnancy loss [71], [72]. As shown ex vivo on human term placentae and, more recently, in vivo in a mouse model, β2GPI is abundant on the trophoblast surface and is available for binding to aPL, particularly anti-β2GPI [73].
Intraplacental
Complications of high risk pregnancies
In spite of the overall improved outcomes of pregnancy in women with rheumatic disease several serious complications are still increased. Abnormal placentation may result in miscarriage, preterm birth, preeclampsia and intra-uterine growth restriction (IUGR) depending on severity and maternal constitutional factors [96], [97]. They are therefore most correctly perceived as part of a continuum of pregnancy complications (Fig. 1). Immune dysregulation has over the last decade been accepted as the
Therapy before conception and during pregnancy
Questions regarding therapy before and during pregnancy and lactation are of great concern for patients and their treating physicians. Special interest has focused on inhibitors of tumor necrosis factor-alpha (TNF-alpha) because of their frequent use both in female and male patients with rheumatic disease [114].
Measurements of transplacental passage of four TNF inhibitors in an ex vivo human placental perfusion model, and in patients showed differences among adalimumab (ADA), etanercept (ETA),
Counseling and pregnancy planning
Planning is essential to increase the probability of success of pregnancies. Planned pregnancies have demonstrated reduced flare rates and better obstetric outcomes in women with SLE [121]. Thus, preconceptional risk assessment and counseling should be ideally performed in every woman with systemic autoimmune diseases before attempting pregnancy.
In the preconceptional visit, several issues should be assessed in order to estimate the risk for complications: the age of the patient; the outcome of
Conclusion
Reproduction issues including fertility and pregnancy are of great importance for women and men with rheumatic disease. Due to an increasing recognition of risk factors and an interdisciplinary approach women with rheumatic diseases can undergo successful infertility treatment and can have successful pregnancies. New therapeutic options are available both for the management of lupus complications and the APS during pregnancy. Increasing experience with the effect of TNF inhibitors on pregnancy
Take-home messages
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Reduced numbers of children in rheumatic diseases can be due to autoimmunity or disease related fertility problems.
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In women with rheumatic diseases and infertility advanced techniques in assisted reproduction make it possible to have children.
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Maternal and fetal problems are frequent in rheumatic diseases and relate to specific serology, disease severity and disease activity at conception.
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Abnormal placentation may result in miscarriage, preterm birth, preeclampsia and intra-uterine growth
Disclosure statement
The authors declare no conflict of interest.
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