The Influence of Methotrexate Treatment on Male Fertility and Pregnancy Outcome After Paternal Exposure

Grosen, Anne; Kelsen, Jens; Hvas, Christian Lodberg; Bellaguarda, Emanuelle; Hanauer, Stephen B.

doi:10.1097/mib.0000000000001064

Cited by 41 publications

(29 citation statements)

References 77 publications

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“…In this review, no animal studies were included. Animal studies show effects on reproductive outcomes for drugs such as methotrexate and thiopurines ( Grosen et al , 2017 ; Simsek et al , 2018 ). Outcomes of animal studies are not always predictive for humans.…”

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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“…Furthermore, in a recent study, the administration of folic and folinic acid together with methotrexate therapy improved germ cell toxicity in mice. 7,13 The most important alkylating agent used in male patients with rheumatic diseases is cyclophosphamide (CYC). This drug may induce depletion of germinal epithelium and cause damage in Sertoli and Leydig cells.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9] To our knowledge, there is neither human nor animal data on the effect of abatacept on the gonads. [9][10][11][12][13] In this study, we aimed to demonstrate the effect of subcutaneous (SC) injections of abatacept on the histology of testes in mice.…”

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confidence: 99%

Does Abatacept Induce Testicular Toxicity?

Al-Mogairen

2020

Arch Rheumatol

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Objectives: This study aims to demonstrate the effect of subcutaneous injections of abatacept on the histology of testes in mice. Materials and methods: The study included 20 male BALB/c mice (average weight, 25 g; aged 12-14 weeks). Ten mice received subcutaneous (SC) injections of abatacept (0.25 mg per 25 g body weight per 0.03 mL normal saline [NS]) at zero, two, four and eight weeks. As the control group, 10 mice received SC injections of NS (0.03 mL). At the post-injection 10 th week, the mice were sacrificed, and histopathological studies were conducted. Results: The results showed that 3/10 mice died of the abatacept-treated group. Testicular histology for the abatacept-treated group showed that 7/7 displayed no histopathological changes. Conclusion: To our knowledge, this is the first control-blinded study of BALB/c mice suggesting that abatacept may not have testicular toxicity. Further fertility and testicular toxicology evaluations including semen analysis and gonadal hormones should be performed to clarify our findings.

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“…Leflunomide and mycophenolate should be avoided in men and women who do not use adequate contraception, and methotrexate should also be avoided in pregnancy 155. Whether methotrexate use in men poses risks for fertility or fetal birth defects is unclear 156…”

Section: Treatment Optionsmentioning

confidence: 99%

New advances in the management of pulmonary sarcoidosis

Culver

Judson

2019

BMJ

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Sarcoidosis is a highly variable granulomatous multisystem syndrome. It affects individuals in the prime years of life; both the frequency and severity of sarcoidosis are greater in economically disadvantaged populations. The diagnosis, assessment, and management of pulmonary sarcoidosis have evolved as new technologies and therapies have been adopted. Transbronchial needle aspiration guided by endobronchial ultrasound has replaced mediastinoscopy in many centers. Advanced imaging modalities, such as fluorodeoxyglucose positron emission tomography scanning, and the widespread availability of magnetic resonance imaging have led to more sensitive assessment of organ involvement and disease activity. Although several new insights about the pathogenesis of sarcoidosis exist, no new therapies have been specifically developed for use in the disease. The current or proposed use of immunosuppressive medications for sarcoidosis has been extrapolated from other disease states; various novel pathways are currently under investigation as therapeutic targets. Coupled with the growing recognition of corticosteroid toxicities for managing sarcoidosis, the use of corticosteroid sparing anti-sarcoidosis medications is likely to increase. Besides treatment of granulomatous inflammation, recognition and management of the non-granulomatous complications of pulmonary sarcoidosis are needed for optimal outcomes in patients with advanced disease.

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The Influence of Methotrexate Treatment on Male Fertility and Pregnancy Outcome After Paternal Exposure

Cited by 41 publications

References 77 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

Does Abatacept Induce Testicular Toxicity?

New advances in the management of pulmonary sarcoidosis

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