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

Abstract

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.

Impaired fertility in men diagnosed with inflammatory arthritis: results of a large multicentre study (iFAME-Fertility)

“…This is even more striking if we consider that several frequently prescribed anti-rheumatic drugs have been associated with reversible or irreversible testicular toxicity. 7 The majority of people aspire to have children and it is known that men desire parenthood as much as women do. [8][9][10] Nonetheless, the impact of IA on one of the most important markers of fertility, the male fertility rate (total number of children per man), [11][12][13] has never been studied before.…”

“…This is even more striking if we consider that several frequently prescribed anti-rheumatic drugs have been associated with reversible or irreversible testicular toxicity. 7 …”

Treatment of Autoimmune Bullous Diseases During Pregnancy and Lactation: A Review Focusing on Pemphigus and Pemphigoid Gestationis

“…Women treated with mycophenolate mofetil, methotrexate or cyclophosphamide should be advised to discontinue therapy 6 weeks, 3 months and one ovulation cycle before conception, respectively ( Patsatsi et al, 2019 ). The authors of a very recent systematic review on the effect of paternal exposure to immunosuppressive drugs on fertility, pregnancy and offspring outcomes concluded that data regarding pregnancy and offspring outcomes were limited but no significant negative effects associated with paternal immunosuppressant exposure were reported ( Perez-Garcia et al, 2020 ).…”

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