Preface: The current view is that male Crohn’s patients experience reduced fertility. Currently, most studies focus on the effects of therapeutic drugs on male sperm. Therefore, this article will outline the effects of drugs commonly used to treat Crohn’s disease on male fertility. It is a product of the combination of sulfasalazine and 5-aminosalicylic acid with an azoic bond. After oral administration, most of it passes through the small intestine in its original form, and when it reaches the colon, the azoic bond is cleaved into sulfasalazine and 5-aminosalicylic acid by the action of bacterial reductase. The former acts only as a carrier, while 5-aminosalicylic acid remains mostly in the colon in direct contact with the colonic mucosa and exerts its therapeutic effect until it is completely excreted in the feces. Studies have found that more than 80% of patients using sulfasalazine have abnormal sperm count and quality, and that the metabolite sulfasalazine is the cause of this side effect. However, this effect is reversible. Sperm count, motility and morphology can return to normal after discontinuation of the drug. Mesalazine is a sulfonamide-free salicylic acid preparation, and there are two main types: one contains an enteric coating that allows for delayed release of the drug, such as Addisha; the other is an extended-release dosage form, such as Poldesan. Since it does not contain sulfasalazine, the adverse effects on sperm are avoided. One study found that patients using salazosulfapyridine who were switched to mesalazine similarly improved sperm abnormalities significantly. However, a systematic review further noted that the risk of congenital defects, stillbirth, preterm birth, and low birth weight was not increased in offspring born after the use of salazosulfapyridine. II. Methotrexate Methotrexate is an inhibitor of dihydrofolate reductase and is used to treat a variety of autoimmune diseases that are teratogenic and mutagenic. Animal studies have found that methotrexate can degenerate spermatocytes, supporting cells and testicular mesenchymal cells and affect sperm formation. However, this side effect can be reversed after discontinuation of the drug. In humans, a paper studying the use of methotrexate in psoriasis patients noted that methotrexate can damage the germinal epithelium and affect sperm formation, while having no effect on mesenchymal cells or testosterone production. Another systematic review did not find an effect of methotrexate on testicular and spermatogenic function, but the authors of that article noted that this may be due to the short follow-up period. We have mentioned in Crohn’s disease and fertility (women) that pregnancy outcomes are significantly worse in women with methotrexate. However, in male patients, the use of this drug is not associated with poor pregnancy outcome in the spouse. The use of azathioprine or mercaptopurine is not associated with abnormalities in sperm density, motility, or ejaculate volume in male patients. However, animal studies have found that although mercaptopurine does not affect sperm production or morphology, the risk of embryo uptake and spontaneous abortion becomes greater. This suggests that there may be recessive sperm damage and genetic abnormalities. In humans, a retrospective study from 2010 analyzed the outcome of 130 female pregnancies in which male partners were using mercaptopurines at the time of parental preparation, and the final study did not find significant adverse pregnancy outcomes. Another analysis of 154 pregnancies involving 76 men taking oral mercaptopurine also found no adverse prognosis. In contrast, another study found an increased risk of miscarriage or congenital anomalies with the use of mercaptopurine drugs during the 3 months of parental preparation. A meta-analysis of these studies found no increased risk of congenital anomalies in the fetus with the use of mercaptopurine medication during parental preparation. Given the current lack of evidence, this opinion is not conclusive. IV. Cyclosporine Cyclosporine is a fungal metabolite that inhibits T cells. In fact, cyclosporine is not recommended in the current guidelines for the treatment of Crohn’s disease. And there is a lack of anthropological data regarding its effect on sperm function in male patients. In contrast, the results of animal studies found that cyclosporine can cause a reduction in sperm count, reduced motility, testicular weight and testosterone levels, but the animal studies took much higher doses than normal human doses, so the conclusions are yet to be verified. Interestingly, one animal experiment found that cyclosporine helped to reduce the autoimmune orchitis caused by testicular damage. V. Hormones Hormones can cause a decrease in sperm concentration and motility, but this side effect is reversible. The use of hormones does not make men less fertile. Moreover, the addition of hormones to patients using azathioprine will not further affect fertility compared to patients without hormones. Sixth, TNF monoclonal antibodies (classical grams) There are no specific studies to explore the effect of classical grams on sperm in Crohn’s men. However, some studies have noted that the effect of the classical gene can reduce sperm motility and affect sperm morphology, and this effect is further increased with the number of injections of the classical gene. However, two other studies based on male patients with spondyloarthritis found that the use of taxanes did not affect testicular function or sperm quality compared to normal subjects. A systematic review analyzed 60 male patients who used TNF monoclonal antibodies prior to fertility preparation and ultimately did not find an association between TNF monoclonal antibodies and congenital anomalies and miscarriages, and instead, male patients using TNF monoclonal antibodies showed improved sperm activity and motility, which the authors speculate may be due to disease remission. VII. Ciprofloxacin and metronidazole Ciprofloxacin and metronidazole are used in the treatment of fistulotic Crohn’s disease and perianal Crohn’s disease. Metronidazole is not toxic to male sperm. In contrast, ciprofloxacin has been shown to reduce fertility in rats in animal studies by causing changes in the germinal epithelium and decreasing blood levels of various hormones, including testosterone, which affect sperm formation; sperm count, sperm motility and viability were also significantly reduced in rats. However, anthropological data in this area are lacking, so the effects of the drug on male patients remain unknown. Conclusion: For male Crohn’s patients who develop sperm dysfunction while preparing for childbirth, the first step should be to control disease remission and improve nutritional status. If zinc deficiency is present, zinc supplementation can improve testicular function and thus increase sperm count; and smoking and alcohol cessation should be avoided. If there is still a fertility disorder after nutritional improvement and medication adjustment, further consultation with a male or urologist is warranted.