We will discuss the effect of rheumatoid and psoriatic mediations on fertility in men. The effect of those medications on the born baby will be dealt with in another video.

Now we start with two very important pieces of information about rheumatoid and psoriatic medications and their effect on pregnancy:

First: Much of the available data on the effects of medications in general on fertility in men are based upon maternal exposures. Less attention has been paid to the impact of these medications if men where the ones who were using them and how they affected their fertility.

Second: Effects of any medication on fertility in humans will never come from research studies where some subjects will use the mediation and others will not, and then we compare their fertility. This will never happen as this is not an ethical thing to do. Data come from reports of doctors who were seeing patients who used those medications and how those reports, over the years, from more and more doctors about more and more patients suggested or confirmed that a certain medication had some effect on fertility or not.

The effect of rheumatoid and psoriatic medications on fertility in men is mostly related to the possible effect of those medications on the production of sperms by the testis.

The only rheumatoid medication that might affect sperm production in men is salasopyrin. This is the brand name and its generic name is sulfasalazine.

It can cause reversible decrease in the number of sperms and can also adversely impact sperm quality meaning it can reduce sperm motility.

It is important to note here two important points:

One: this effect might happen in some men and will not happen in all men using this medication.

Two: this effect on sperm production and sperm quality does not affect the baby at all. There is no possibility for any abnormality that can happen to the baby.

Now how do we manage this problem?

We do not routinely discontinue salasopyrin in men who are planning a pregnancy with their wives. In men taking salasopyrin in whom attempts at pregnancy have not been successful, we obtain a semen analysis, and if it is abnormal, we suggest stopping the medication for three months to allow for recovery of the process of sperm production. Then we wait till their wife conceives. After that, we restart the medication once again.

Apart from salasopyrin, the limited data that we have about the rest of the antirheumatic medications do not indicate or do not provide any evidence or clue that any other medications from this family affect fertility.

We classify the arthritis medications with respect to their possible effect on fertility into three groups depending on how confident we are that they do not have an effect on fertility:

Group one: a group that is generally presumed safe and do not appear to have a negative impact on fertility

Medications in this group include the following names and you will find their generic names also on the screen:

Humira, enbrel, remicade. Also, imuran, all antiinflammmatory painkillers (we call them NSAIDs), neoral, plaquenil and finally methotrexate. Concerning methotrexate, there is no reduction in fertility in men taking methotrexate in doses used to treat rheumatic diseases which are up to 30 mg once per week.

Group two: this is a group where medications are probably safe but we are not as so confident about that as we are about medications in group one. Why? Because although the available data that we have does not suggest they have adverse effects on fertility yet, at the same time, we still consider those data too limited; not enough to tell with statistical confidence.

Medications in this group include cimzia, simponi, mabthera, orencia, actemra, kevzara, cosentyx, taltz and stelara. 

Group three: is a group where we have no data at all about its medications concerning the effect on fertility. Here the medications are too new to have any data or reports about them. This group includes xeljanz, olumiant, rinvoq, smyraf and otezla.

Remember: the data presented here in this Article are up to date as of now: 2022. For later dates, refer to later updates. 

Finally, because of the extreme importance of the data in this Article for couples who are planning a pregnancy, I will left the important references for this Article below on this page.

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1. Tiseo BC, Cocuzza M, Bonfa E, et al. Male fertility potential alteration in rheumatic diseases: a systematic review. Int Braz J Urol 2016; 42:11.
2. Birnie GG, McLeod TI, Watkinson G. Incidence of sulphasalazine-induced male infertility. Gut 1981; 22:452.
3. Toovey S, Hudson E, Hendry WF, Levi AJ. Sulphasalazine and male infertility: reversibility and possible mechanism. Gut 1981; 22:445.
4. O'Moráin C, Smethurst P, Doré CJ, Levi AJ. Reversible male infertility due to sulphasalazine: studies in man and rat. Gut 1984; 25:1078.
5. Micu MC, Ostensen M, Villiger PM, et al. Paternal exposure to antirheumatic drugs-What physicians should know: Review of the literature. Semin Arthritis Rheum 2018; 48:343.
6. Mouyis M, Flint JD, Giles IP. Safety of anti-rheumatic drugs in men trying to conceive: A systematic review and analysis of published evidence. Semin Arthritis Rheum 2019; 48:911.
7. Montagna GL, Malesci D, Buono R, Valentini G. Asthenoazoospermia in patients receiving anti-tumour necrosis factor {alpha} agents. Ann Rheum Dis 2005; 64:1667.
8. Mahadevan U, Terdiman JP, Aron J, et al. Infliximab and semen quality in men with inflammatory bowel disease. Inflamm Bowel Dis 2005; 11:395.
9. Villiger PM, Caliezi G, Cottin V, et al. Effects of TNF antagonists on sperm characteristics in patients with spondyloarthritis. Ann Rheum Dis 2010; 69:1842.
10. Paschou S, Voulgari PV, Vrabie IG, et al. Fertility and reproduction in male patients with ankylosing spondylitis treated with infliximab. J Rheumatol 2009; 36:351.
11. Said TM, Agarwal A, Falcone T, et al. Infliximab may reverse the toxic effects induced by tumor necrosis factor alpha in human spermatozoa: an in vitro model. Fertil Steril 2005; 83:1665.
12. Micu MC, Micu R, Surd S, et al. TNF-α inhibitors do not impair sperm quality in males with ankylosing spondylitis after short-term or long-term treatment. Rheumatology (Oxford) 2014; 53:1250.
13. Dejaco C, Mittermaier C, Reinisch W, et al. Azathioprine treatment and male fertility in inflammatory bowel disease. Gastroenterology 2001; 121:1048.
14. El-Beheiry A, El-Mansy E, Kamel N, Salama N. Methotrexate and fertility in men. Arch Androl 1979; 3:177.
15. Martini AC, Molina RI, Tissera AD, et al. Analysis of semen from patients chronically treated with low or moderate doses of aspirin-like drugs. Fertil Steril 2003; 80:221.
16. Porat-Soldin O, Soldin SJ. Preliminary studies on the in vitro and in vivo effect of salicylate on sperm motility. Ther Drug Monit 1992; 14:366.
17. Ingram MJ, Zeller E, Moss GP, Hall CE. A potential anti-implantation and spermicidal strategy: putative derivatives of nonoxynol-9 and anti-inflammatory agents and their spermicidal activity. Eur J Contracept Reprod Health Care 2006; 11:258.
18. Nukumizu LA, Gonçalves Saad C, Ostensen M, et al. Gonadal function in male patients with ankylosing spondylitis. Scand J Rheumatol 2012; 41:476.
19. Jones A, Clary MJ, McDermott E, et al. Outcomes of pregnancies fathered by solid-organ transplant recipients exposed to mycophenolic acid products. Prog Transplant 2013; 23:153.
20. Haberman J, Karwa G, Greenstein SM, et al. Male fertility in cyclosporine-treated renal transplant patients. J Urol 1991; 145:294.
21. Choy JT, Brannigan RE. The determination of reproductive safety in men during and after cancer treatment. Fertil Steril 2013; 100:1187.
22. Trasler JM, Hales BF, Robaire B. Chronic low dose cyclophosphamide treatment of adult male rats: effect on fertility, pregnancy outcome and progeny. Biol Reprod 1986; 34:275.
23. Codrington AM, Hales BF, Robaire B. Spermiogenic germ cell phase-specific DNA damage following cyclophosphamide exposure. J Androl 2004; 25:354.
24. Taylor JD, Baumgartner A, Schmid TE, Brinkworth MH. Responses to genotoxicity in mouse testicular germ cells and epididymal spermatozoa are affected by increased age. Toxicol Lett 2019; 310:1.
25. Flint J, Panchal S, Hurrell A, et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2016; 55:1693.
26. Kumar P, Das A, Lal NR, et al. Safety of important dermatological drugs (retinoids, immune suppressants, anti androgens and thalidomide) in reproductively active males with respect to pregnancy outcome: A brief review of literature. Indian J Dermatol Venereol Leprol 2018; 84:539.
27. Franks ME, Macpherson GR, Figg WD. Thalidomide. Lancet 2004; 363:1802.
28. Fairley JL, Oon S, Saracino AM, Nikpour M. Management of cutaneous manifestations of lupus erythematosus: A systematic review. Semin Arthritis Rheum 2020; 50:95.
29. Vargesson N. Thalidomide-induced teratogenesis: history and mechanisms. Birth Defects Res C Embryo Today 2015; 105:140.
30. Teo SK, Harden JL, Burke AB, et al. Thalidomide is distributed into human semen after oral dosing. Drug Metab Dispos 2001; 29:1355.
31. Zakhem GA, Motosko CC, Mu EW, Ho RS. Infertility and teratogenicity after paternal exposure to systemic dermatologic medications: A systematic review. J Am Acad Dermatol 2019; 80:957.

32. Thalidomide highlights of prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020785s055lbl.pdf (Accessed on October 05, 2019).

33. Flint J, Panchal S, Hurrell A, et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part II: analgesics and other drugs used in rheumatology practice. Rheumatology (Oxford) 2016; 55:1698.
34. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol 2020; 72:529.
35. Weber-Schoendorfer C, Hoeltzenbein M, Wacker E, et al. No evidence for an increased risk of adverse pregnancy outcome after paternal low-dose methotrexate: an observational cohort study. Rheumatology (Oxford) 2014; 53:757.
36. Lee CY, Jin C, Mata AM, et al. A pilot study of paternal drug exposure: the Motherisk experience. Reprod Toxicol 2010; 29:353.
37. Beghin D, Cournot MP, Vauzelle C, Elefant E. Paternal exposure to methotrexate and pregnancy outcomes. J Rheumatol 2011; 38:628.
38. Viktil KK, Engeland A, Furu K. Outcomes after anti-rheumatic drug use before and during pregnancy: a cohort study among 150,000 pregnant women and expectant fathers. Scand J Rheumatol 2012; 41:196.
39. Wallenius M, Lie E, Daltveit AK, et al. No excess risks in offspring with paternal preconception exposure to disease-modifying antirheumatic drugs. Arthritis Rheumatol 2015; 67:296.
40. Morken NH, Diaz-Garcia C, Reisaeter AV, et al. Obstetric and neonatal outcome of pregnancies fathered by males on immunosuppression after solid organ transplantation. Am J Transplant 2015; 15:1666.
41. Midtvedt K, Bergan S, Reisæter AV, et al. Exposure to Mycophenolate and Fatherhood. Transplantation 2017; 101:e214.
42. Chakravarty EF, Sanchez-Yamamoto D, Bush TM. The use of disease modifying antirheumatic drugs in women with rheumatoid arthritis of childbearing age: a survey of practice patterns and pregnancy outcomes. J Rheumatol 2003; 30:241.
43. Brent RL. Teratogen update: reproductive risks of leflunomide (Arava); a pyrimidine synthesis inhibitor: counseling women taking leflunomide before or during pregnancy and men taking leflunomide who are contemplating fathering a child. Teratology 2001; 63:106.
44. De Santis M, Straface G, Cavaliere A, et al. Paternal and maternal exposure to leflunomide: pregnancy and neonatal outcome. Ann Rheum Dis 2005; 64:1096.
45. Chambers CD, Johnson DL, Robinson LK, et al. Birth outcomes in women who have taken leflunomide during pregnancy. Arthritis Rheum 2010; 62:1494.
46. Weber-Schoendorfer C, Beck E, Tissen-Diabaté T, Schaefer C. Leflunomide - A human teratogen? A still not answered question. An evaluation of the German Embryotox pharmacovigilance database. Reprod Toxicol 2017; 71:101.
47. Bérard A, Zhao JP, Shui I, Colilla S. Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes. Ann Rheum Dis 2018; 77:500.
48. Larsen MD, Friedman S, Magnussen B, Nørgård BM. Birth Outcome of Children Fathered by Men Treated with Systemic Corticosteroids during the Conception Period - A Cohort Study based on Nationwide Data. Basic Clin Pharmacol Toxicol 2018; 122:133.
49. Pendse S, Ginsburg E, Singh AK. Strategies for preservation of ovarian and testicular function after immunosuppression. Am J Kidney Dis 2004; 43:772.

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This post was prepared and published by  Dr. Hatem Eleishi. Dr. Hatem Eleishi is a professor of rheumatology at Cairo university (Egypt) and is especially dedicated to supporting arthritis patients with online educational videos and articles about arthritis causes and treatment. He also runs a rheumatology clinic in Cairo and a center for www.tabibakom.com/en that, in addition to providing online rheumatology consultations, also provides online medical consultations in several different medical specialties by expert consultants from Egypt, Canada and the United States.

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