In the antiviral treatment of chronic hepatitis B, can the wife get pregnant while the male patient is taking the medication? Some doctors even have the same question. Because of the fear of genotoxicity of antiviral drugs for male patients, some male patients stop or change their medication during treatment in order for their wives to have children, resulting in virological rebound and abnormal liver function. Whether the currently listed anti-hepatitis B virus has any effect on male fertility or not, and whether it causes changes in semen and sperm, it is clear from the known literature that interferon has an anti-reproductive effect in both human trials and animal tests, which means that it leads to a lower probability of conception. Whether there is a mutagenic potential, there is only one literature in which doctors examined the semen of male patients with long-acting interferon + ribavirin and found that the sperm count of these patients decreased and the round cell/sperm ratio (reflecting sperm abnormalities) increased and returned to normal only after 4 months of drug withdrawal; in addition, the DNA fragmentation index (reflecting the chromosomal structure of semen) of the semen of these patients increased significantly and did not return to normal after 8 months of drug withdrawal normalization. This indicates that long-acting interferon + ribavirin significantly affects the quality of fertility in male patients, and therefore it is recommended that male patients should still use contraception for more than 6-8 months after stopping interferon. No articles on the effects of lamivudine, telbivudine, adefovir and entecavir on male sperm were retrieved so far. A careful reading of the instructions for these drugs revealed that the results of animal tests done before clinical trials on these drugs showed no effect on the fertility of males. The lamivudine instruction manual states in the paragraph for use in pregnant and lactating women, “There is also no effect on the reproductive capacity of females and males (animals).” The genotoxicity paragraph states, “No significant genotoxicity was observed.” The genotoxicity paragraph of the tebivudine instruction states, “In in vivo and in vitro tests, tebivudine did not show genotoxicity.” The reproductive toxicity paragraph states, “No evidence of impaired fertility was observed when male or female rats given 2000 mg/kg/day of telbivudine (exposure levels at the fractionation up to 14 times the human therapeutic dose exposure level) were mated with unadministered rats.” “Another study showed reduced fertility when male and female rats were given either 500 or 1000 mg/kg/day of telbivudine. …… but found no abnormalities in sperm morphology or function and no histological abnormalities in the testes or ovaries.” In the Adefovir (Hovalix) instructions for use in pregnant and lactating women, it states, “Adefovir has no effect on fertility in males and females.” In the reproductive toxicity paragraph it states, “Adefovir had no effect on fertility or reproduction in both male and female rats when given orally.” (However, some domestic adefovir instructions contain no such content) In the genotoxicity paragraph of the instructions for entecavir (Boludin), it states, “Entecavir was found not to be a mutation inducer.” In the reproductive toxicity paragraph it states, “At doses up to 30 mg/kg, no effects on fertility were found in male and female rats at doses administered at more than 90 times the maximum recommended human dose of 1.0 mg/day. …… when dosed to 35 times or more the human dose, degenerative changes in the vas deferens were found in rodents and dogs. No testicular alterations were found in monkey experiments.” (However, there is no such content in some domestic entecavir instructions.) Please note that the doses used in animal tests are often dozens of times the doses used in human treatment. For the treatment of hepatitis B, the daily dose of lamivudine for adults is 100 mg, tebivudine is 600 mg, and adefovir is 10 mg, while entecavir is only 0.5 mg or 1 mg; and the doses used in animal tests are calculated for dosing per kilogram of body weight per day. In this case there is no significant reproductive toxicity and it is very safe for men. Therefore, it can be said that all male patients taking all currently marketed anti-hepatitis B virus nuclear (acid) analogues for treatment do not affect their wives’ pregnancy. Theoretically, as long as the drugs do not have mutagenic effects on male sperm, men taking the drugs after their wives become pregnant are not affected at all. The U.S. Food and Drug Administration (FDA) classifies drugs into five classes according to their safety during pregnancy. Class A: Animal experiments and clinical observations have not revealed any damage to the fetus. Class B: No harm to the embryo confirmed in animal studies, but not confirmed in clinical studies or no clinically verified information. Grade C: Teratogenic or embryonic killing effect on embryo was confirmed only in animal experiments, but lack of research data to confirm in human. Grade D: clinical data confirming the harm to fetus, but the efficacy of treating pregnant women’s diseases is certain, and there is no substitute drug, so weigh the pros and cons before using it. Grade X: Confirmed to be harmful to the fetus and prohibited during pregnancy. This classification is limited to the safety of the fetus during a woman’s pregnancy after maternal exposure to drugs taken by the mother, and does not include the effect of drugs taken by men on their wives’ fertility. To date, no national pharmacovigilance authority has made specific classifications for the use of medications for male fertility. This is because the effects of medications on male fertility are minimal. If some effects do occur, they generally only affect the quality and quantity of sperm, making it less likely that his wife will conceive a child, and generally do not affect the development of the fetus in the mother’s body. Therefore, there is no global safety classification for fertility in wives while men are taking the drug. The effectiveness of antiviral therapy is related to the patient’s adherence to treatment. Random discontinuation of medication often leads to treatment failure, abandonment of previous efforts, and even exacerbation of liver disease, which can result in the life of the patient. The incidence of drug resistance is higher after discontinuation or random drug changes, and the discontinuation affects the health of male patients, thus indirectly affecting their fertility and sperm health. Therefore, male patients taking nucleoside drugs antiviral, their wives can get pregnant, do not stop the drug, adhere to treatment; patients receiving interferon therapy is recommended to contraception.