Is methotrexate safe for men with an immune-mediated inflammatory disease and an active desire to become a father? Results of a prospective cohort study (iFAME-MTX)

Introduction Current scientific evidence guiding the decision whether men with an active desire to become a father should be treated with methotrexate (MTX) remains controversial. We aimed to prospectively evaluate the testicular toxicity profile of MTX focusing on several markers of male fertility, including semen parameters and sperm DNA fragmentation index (sDFI). As a secondary outcome, we aimed to evaluate whether MTX-polyglutamates can be detected in spermatozoa and seminal plasma and to evaluate the enzymatic activity in spermatozoa of folylpolyglutamate synthetase (FPGS). Methods In a prospective cohort study, men ≥18 years who started therapy with MTX were invited to participate (MTX-starters). Participants were instructed to produce two semen samples (a pre-exposure and a post-exposure sample after 13 weeks). Healthy men ≥18 years were invited to participate as controls. Conventional semen analyses, male reproductive endocrine axis and sDFI were compared between groups. FPGS enzymatic activity and MTX-PG1-5 concentrations were determined by mass spectrometry analytical methods. Results In total, 20 MTX-starters and 25 controls were included. The pre-exposure and postexposure semen parameters of MTX-starters were not statistically significant different. Compared with healthy controls, the conventional semen parameters and the sDFI of MTX-starters were not statistically significant different. These data were corroborated by the marginal accumulation of MTX-PGs in spermatozoa, consistent with the very low FPGS enzymatic activity associated with the expression of an alternative FPGS splice-variant. Discussion Treatment with MTX is not associated with testicular toxicity, consistent with the very low concentration of intracellular MTX-PG. Therefore, therapy with MTX can be safely started or continued in men and with a wish to become a father.</p

Global Application of the Assessment of Communication Skills of Paediatric Endocrinology Fellows in the Management of Differences in Sex Development Using the ESPE E-Learning.Org Portal

Background: Information sharing in chronic conditions such as disorders of/differences in sex development (DSD) is essential for a comprehensive understanding by parents and patients. We report on a qualitative analysis of communication skills of fellows undergoing training in paediatric endocrinology. Guidelines are created for the assessment of communication between health professionals and individuals with DSD and their parents. Methods: Paediatric endocrinology fellows worldwide were invited to study two interactive online cases (www.espe-elearning.org) and to describe a best practice communication with (i) the parents of a newborn with congenital adrenal hyperplasia and (ii) a young woman with 46,XY gonadal dysgenesis. The replies were analysed regarding completeness, quality, and evidence of empathy. Guidelines for structured assessment of responses were developed by 22 senior paediatric endocrinologists worldwide who assessed 10 selected replies. Consensus of assessors was established and the evaluation guidelines were created. Results: The replies of the fellows showed considerable variation in completeness, quality of wording, and evidence of empathy. Many relevant aspects of competent clinical communication were not mentioned; 15% (case 1) and 17% (case 2) of the replies were considered poor/insufficient. There was also marked variation between 17 senior experts in the application of the guidelines to assess communication skills. The guidelines were then adjusted to a 3-level assessment with empathy as a separate key item to better reflect the qualitative differences in the replies and for simplicity of use by evaluators. Conclusions: E-learning can play an important role in assessing communication skills. A practical tool is provided to assess how information is shared with patients with DSD and their families and should be refined by all stakeholders, notably interdisciplinary health professionals and patient representatives.Fil: Kranenburg, Laura J.C.. Erasmus University Medical Center; Países BajosFil: Reerds, Sam T.H.. Erasmus University Medical Center; Países BajosFil: Cools, Martine. University of Ghent; BélgicaFil: Alderson, Julie. NHS Foundation Trust. University Hospitals Bristol; Reino UnidoFil: Muscarella, Miriam. University of California; Estados UnidosFil: Magrite, Ellie. Ffounder And Trustee;Fil: Kuiper, Martijn. Erasmus University Medical Center;Fil: Abdelgaffar, Shereen. Cairo University; EgiptoFil: Balsamo, Antonio. Universidad de Bologna; ItaliaFil: Brauner, Raja. Universite de Paris V; FranciaFil: Chanoine, Jean Pierre. British Columbia Children’s Hospital. Department of Paediatrics; CanadáFil: Deeb, Asma. Mafraq Hospital; Emiratos Arabes UnidosFil: Fechner, Patricia. University of Washington; Estados UnidosFil: German, Alina. Technion - Israel Institute of Technology; IsraelFil: Holterhus, Paul Martin. Universitätsklinikum Schleswig-Holstein; Alemania. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Juul, Anders. Universidad de Copenhagen; DinamarcaFil: Mendonca, Berenice B.. Universidade de Sao Paulo; BrasilFil: Neville, Kristen. Sydney Children's Hospital; AustraliaFil: Nordenstrom, Anna. Karolinka Institutet; SuizaFil: Oostdijk, Wilma. Leiden University; Países BajosFil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Rutter, Meilan M.. University of Cincinnati; Estados UnidosFil: Shah, Nalini. Seth GS Medical College & KEM Hospital; IndiaFil: Luo, Xiaoping. Tongji Hospital; ChinaFil: Grijpink, Kalinka. Delft University of Technology; Países BajosFil: Drop, Stenvert L.S.. Erasmus University Medical Center; Países Bajo