Review
State of the art: Reproduction and pregnancy in rheumatic diseases

https://doi.org/10.1016/j.autrev.2014.12.011Get rights and content

Abstract

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.

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

  • Reduced numbers of children in rheumatic diseases can be due to autoimmunity or disease related fertility problems.

  • In women with rheumatic diseases and infertility advanced techniques in assisted reproduction make it possible to have children.

  • Maternal and fetal problems are frequent in rheumatic diseases and relate to specific serology, disease severity and disease activity at conception.

  • 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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