Sperm DNA Integrity is Unaffected by Thiopurine Treatment in Men With Inflammatory Bowel Disease

Grosen, Anne; Nersting, Jacob; Bungum, Mona; Christensen, Lisbet Ambrosius; Schmiegelow, Kjeld; Spanò, Marcello; Julsgaard, Mette; Cordelli, Eugenia; Leter, Giorgio; Larsen, Peter B.; Hvas, Christian Lodberg; Kelsen, Jens

doi:10.1093/ecco-jcc/jjy086

Cited by 17 publications

(12 citation statements)

References 36 publications

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“…Four studies that included a total of 75 cases and 40 controls exposed to azathioprine were included ( Baumgarten et al , 1977 ; Farthing and Dawson, 1983 ; Dejaco et al , 2001 ; Grosen et al , 2019c ). Sperm quality, sperm DNA fragmentation index (DFI) and the male endocrine reproductive axis appear not to be negatively affected by azathioprine exposure.…”

Section: Discussionmentioning

confidence: 99%

The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review

Perez-Garcia

Dolhain

Vorstenbosch

et al. 2020

Human Reproduction Update

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BACKGROUND Information regarding the possible influence of immunosuppressive drugs on male sexual function and reproductive outcomes is scarce. Men diagnosed with immune-mediated diseases and a wish to become a father represent an important neglected population since they lack vital information to make balanced decisions about their treatment. OBJECTIVE AND RATIONALE The aim of this research was to systematically review the literature for the influence of paternal immunosuppressive drug use on many aspects of male sexual health, such as sexual function, fertility, pregnancy outcomes and offspring health outcomes. SEARCH METHODS A systematic literature search was performed in the bibliographic databases: Embase (via Elsevier embase.com), MEDLINE ALL via Ovid, Cochrane Central Register of Trials (via Wiley) and Web of Science Core Collection. Additionally, Google Scholar and the Clinical trial registries of Europe and the USA were searched. The databases were searched from inception until 31 August 2019. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes and offspring health with a list of immunosuppressive drugs. Studies were included if they were published in English and if they included original data on male human exposure to immunosuppressive drugs. A meta-analysis was not possible to perform due to the heterogeneity of the data. OUTCOMES A total of 5867 references were identified, amongst which we identified 161 articles fulfilling the eligibility criteria. Amongst these articles, 50 included pregnancy and offspring outcomes and 130 included sexual health outcomes. Except for large Scandinavian cohorts, most of the identified articles included a small number of participants. While a clear negative effect on sperm quality was evident for sulfasalazine and cyclophosphamide, a dubious effect was identified for colchicine, methotrexate and sirolimus. In three articles, exposure to tumour necrosis factor-α inhibitors in patients diagnosed with ankylosing spondylitis resulted in improved sperm quality. The information regarding pregnancy and offspring outcomes was scant but no large negative effect associated with paternal immunosuppressive drug exposure was reported. WIDER IMPLICATIONS Evidence regarding the safety of immunosuppressive drugs in men with a wish to become a father is inconclusive. The lack of standardisation on how to evaluate and report male sexual function, fertility and reproduction as study outcomes in men exposed to immunosuppressive drugs is an important contributor to this result. Future research on this topic is needed and should be preferably done using standardised methods.

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Section: Discussionmentioning

confidence: 99%

The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review

Perez-Garcia

Dolhain

Vorstenbosch

et al. 2020

Human Reproduction Update

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“…The administration of AZA in IBD patients did not generally report negative effects on semen quality, 40,59,60 although Farthing et al observed an increased percentage of oligo‐ and asthenozoospermia in 5 patients treated with AZA 11 . This study, however, did not report results for each patient, and therefore, it is not possible to evaluate them within the current WHO guidelines 4 .…”

Section: Resultsmentioning

confidence: 73%

“…Grosen et al further reported lower total and progressive motility in patients treated with AZA/6‐MP compared with healthy controls, although this was still in the reference values provided by WHO 4,59 . In addition, AZA/6‐MP did not appear to negatively affect sperm DNA integrity evaluated by using sperm chromatin structure assay (SCSA) and COMET assays 59 . IBD patients treated with MTX were reported in one study, in which patients were concurrently treated with IFN inhibitors or 5‐ASA 61 .…”

Section: Resultsmentioning

confidence: 87%

“…This study, however, did not report results for each patient, and therefore, it is not possible to evaluate them within the current WHO guidelines 4 . Grosen et al further reported lower total and progressive motility in patients treated with AZA/6‐MP compared with healthy controls, although this was still in the reference values provided by WHO 4,59 . In addition, AZA/6‐MP did not appear to negatively affect sperm DNA integrity evaluated by using sperm chromatin structure assay (SCSA) and COMET assays 59 .…”

Section: Resultsmentioning

confidence: 95%

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The impact of autoimmune systemic inflammation and associated medications on male reproductive health in patients with chronic rheumatological, dermatological, and gastroenterological diseases: A systematic review

Finelli

Leisegang

Finocchi

et al. 2021

American J Rep Immunol

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Autoimmune disorders currently affect 5%‐8% of the global population, characterized by an aberrant chronic inflammatory response to self‐antigens. The aim of this study was to systematically review the current available evidence investigating the impact of systemic autoimmune diseases and associated immunosuppressive treatment on fertility parameters of adult men. Clinical trials, observational studies, and case reports written in English and reporting semen analysis, evaluation of seminal oxidative stress, and/or sperm DNA fragmentation in patients affected by psoriasis and psoriatic arthritis, celiac disease, inflammatory bowel diseases, systemic lupus erythematosus, ankylosing spondylitis, hidradenitis suppurativa, uveitis, dermatomyositis, and rheumatoid arthritis were collected by searching on PubMed, EMBASE, OVID, Scopus, and Cochrane Library databases, with no limit of time. The study quality and the extent of bias in design, methods, and outcome assessment were evaluated by applying the Joanna Briggs Institute Critical Appraisal tools. Evidence suggested that various autoimmune diseases or relevant medications can adversely affect male fertility parameters and that patients may benefit of counseling and sperm cryopreservation. Clinical trials further investigating any adverse effect of autoimmunity and related thereby on male infertility are warranted, to develop appropriate guidelines for males diagnosed and treated for autoimmune disorders.

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“…Dejaco et al[58] showed that the sperm quality of 18 IBD patients was not altered after 3 months of using azathioprine. In a cohort of 40 IBD men[59], thiopurines did not decrease sperm quality but was sometimes associated with the impairment of sperm motility. Methotrexate (MTX) can be responsible for oligospermia and is reversible after stopping usage; this drug is contraindicated for both women and men because it is embryotoxic[60].…”

Section: Fertilitymentioning

confidence: 99%

Sexual health and fertility for individuals with inflammatory bowel disease

Leenhardt¹,

Rivière²,

Papazian³

et al. 2019

WJG

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The impact of a chronic disease such as inflammatory bowel disease (IBD) on sexual functioning and body image can significantly impair the quality of life of patients. This review considers the sexual and fertility aspects of IBD patients and their daily management. Modern IBD healthcare management should include appropriate communication on sexuality and consider psychological, physiological, and biological issues. Patients with IBD have less children than the general population, and voluntary childlessness is frequent. The most influential factors reported by IBD patients who experience fertility alteration are psychological and surgery-related problems. Pregnancy is a major concern for patients, and any pregnancy for IBD patients should be closely followed-up to keep the chronic disease in a quiescent state. Preconceptional consultation is of great help.

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Sperm DNA Integrity is Unaffected by Thiopurine Treatment in Men With Inflammatory Bowel Disease

Abstract: Thiopurines do not increase sperm DNA fragmentation but may impair sperm motility in this IBD cohort. Our findings support existing epidemiological data that thiopurine therapy is safe during preconception and should not be abandoned.

Cited by 17 publications

References 36 publications

The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review

The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review

The impact of autoimmune systemic inflammation and associated medications on male reproductive health in patients with chronic rheumatological, dermatological, and gastroenterological diseases: A systematic review

Sexual health and fertility for individuals with inflammatory bowel disease

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