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      Male fertility potential alteration in rheumatic diseases: a systematic review

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          ABSTRACT

          Background

          Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility.

          Materials and Methods

          A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases.

          Results

          A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies.

          Conclusions

          Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy.

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          Most cited references124

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          Oxidative stress, DNA damage and apoptosis in male infertility: a clinical approach.

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            Significance of sperm characteristics in the evaluation of male infertility.

            To compare sperm characteristics among: patients undergoing infertility evaluation, patients with male factor infertility (MFI), healthy sperm donors, and men with proven fertility; to examine the overlap of sperm characteristics in all four of these groups; and to identify good discriminators of fertility versus infertility among sperm characteristics. Retrospective study. Male infertility clinic at a tertiary care hospital. Proven fertile men (n = 56), normal donors (n = 91), men presenting for infertility evaluation (n = 406), and MFI patients (n = 166). None. Routine semen analysis. Using current World Health Organization (WHO) reference values, a large group of MFI patients presented with higher sperm concentration (27.5 x 10(6) to 99.2 x 10(6)), resulting in broader overlap with fertile men and poor sensitivity (0.48). Similarly, percentage normal morphology (%) using Tygerberg's strict criteria was low in most of the MFI patients (sensitivity 0.83), almost half of the fertile men also presented with abnormal morphology (specificity 0.51). Of all the variables examined, sperm motility (%) was superior, having minimum overlap range (lower and upper cut-off values 46% and 75%) and high sensitivity (0.74) and specificity (0.90). Areas under curve were higher for motility (0.90) and concentration (0.84) compared with morphology (WHO 0.65 and Tygerberg's strict criteria 0.74). Sperm motility and concentration provide more accurate information than morphology (WHO and Tygerberg's criteria) during infertility evaluation. Redefining the reference values for concentration and morphology may significantly increase the importance of routine semen analysis.
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              Clinical relevance of oxidative stress and sperm chromatin damage in male infertility: an evidence based analysis

              Oxidative stress (OS) in the reproductive tract is now a real entity and concern due to the potential harmful effects of high levels of reactive oxygen species (ROS) on sperm number, motility, quality, and function including damage to sperm nuclear DNA. Evaluation of OS related damage to non-functional sperm is highly relevant as intracytoplasmic sperm injection (ICSI) technique, an effective therapy for severe male factor infertility, bypasses the majority of reproductive tract deficiencies. Despite the controversial findings in the existing literature, there is now enough evidence to show that sperm DNA damage is detrimental to reproductive outcomes. In addition, spermatozoa of infertile men are suggested to carry more DNA damage than do the spermatozoa from fertile men. Besides impairment of fertility such damage is likely to increase the transmission of genetic diseases during the assisted reproductive procedures. Standardization of protocols to assess reactive oxygen species and DNA damage is very important in introducing these tests in such clinical practice. Thus evaluation of seminal ROS levels and extent of sperm DNA damage especially in an infertile male may help develop new therapeutic strategies and improve success of assisted reproductive techniques (ART).
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                Author and article information

                Journal
                Int Braz J Urol
                Int Braz J Urol
                ibju
                International Brazilian Journal of Urology : official journal of the Brazilian Society of Urology
                Sociedade Brasileira de Urologia
                1677-5538
                1677-6119
                Jan-Feb 2016
                Jan-Feb 2016
                : 42
                : 1
                : 11-21
                Affiliations
                [1 ]Departamento de Urologia da Faculdade de Medicina da Universidade de São Paulo, Brasil;
                [2 ] Divisão de Reumatologia da Faculdade de Medicina da Universidade de São Paulo, Brasil;
                [3 ] Unidade de Reumatologia Pediátrica do Departamento de Pediatria da Faculdade de Medicina da Universidade de São Paulo, Brasil
                Author notes
                Correspondence address: Marcello Cocuzza, MD. Departamento de Urologia da Universidade de São Paulo (USP). Av. Dr. Enéas de Carvalho Aguiar, 255/7º andar - Sala 710F. Cerqueira César, São Paulo, SP, 05403-000, Brasil. Telephone: +55 11 3069-8080. E-mail: mcocuzza@ 123456uol.com.br

                CONFLICT OF INTEREST

                None declared.

                Article
                S1677-5538.IBJU.2014.0595
                10.1590/S1677-5538.IBJU.2014.0595
                4811221
                27120778
                345e3146-1f94-428a-9879-43dfa9fdb384

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 November 2014
                : 17 September 2015
                Page count
                Figures: 1, Tables: 5, Equations: 0, References: 55, Pages: 11
                Categories
                Review Article

                rheumatic diseases,fertility,infertility, male
                rheumatic diseases, fertility, infertility, male

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