Does male hepatitis B virus (HBV) infection affect fertility?

Author: Zhu Yong Obstetrics and Gynecology Hospital, Fudan University

Reviewer: Liang Guoqing, deputy chief physician, Department of Obstetrics and Gynecology, Fudan University Hospital

Hepatitis B virus (HBV) infection is a serious public health problem worldwide. The "Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022)" states that approximately 86 million people in China are chronically infected with HBV[1]. HBV is usually transmitted through mother-to-child transmission, blood (including blood transfusion, minor skin and mucosal trauma), and sexual contact. In my country, HBV transmission is mainly through mother-to-child transmission, accounting for 40% to 50% of new infections[1].

Figure 1 Copyright image, no permission to reprint

——Then the question is, if the father is infected with HBV, does his semen carry HBV? Will it be transmitted to the baby? To answer the above questions, we need to analyze the different stages of HBV infection.

The four natural stages of chronic HBV infection are: immune tolerance, immune clearance, immune control, and immune reactivation[1,2].

1. Immune tolerance stage: The main characteristics are high concentration of hepatitis B virus DNA (HBV-DNA), positive hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) (commonly known as the "big three positive" state), basically normal alanine transferase (ALT) level, and no liver necrotizing inflammation. The above test results can be understood as follows: HBV at this stage causes very little damage to the liver of the infected person, but the virus is highly contagious.

2. Immune clearance period (or active period): The main characteristics are HBV-DNA positive, but the concentration has decreased, HBeAg and HBsAg are positive, which also belongs to the "big three positive" state, but the difference from the above "immune tolerance period" is that the ALT level is elevated, the systemic immune system is relatively active, and it constantly attacks the HBV-infected liver cells, causing severe inflammation and necrosis in the liver cells. If the continuous immune activity period is accompanied by repeated fluctuations in ALT, progressive liver fibrosis will eventually occur, leading to cirrhosis.

3. Immune control stage (inactive stage): The main features are opposite to the symptoms of the active stage, with HBV-DNA concentration lower than 2000 IU/mL or undetectable, HBeAg negative and HBsAg positive, the presence of hepatitis B e antibody (HBeAb), commonly known as the "small three positive" state, ALT within the normal range, and no obvious inflammation and necrosis in liver biopsy. The above test results can be understood as follows: HBV has been dormant or latent in the body and is in a quiet state.

4. Immune reactivation period: The main feature is that HBV gradually recovers from dormancy and begins to become active, HBV-DNA concentration begins to rise, HBeAg is negative, HBsAg and HBeAb are positive. It is still in the "small three positive" state at this time, but it is different from the immune control period in that ALT begins to rise, and hepatocyte inflammation and necrosis accelerates. At this time, the risk of progression to severe liver fibrosis is very high.

Combining the above different stages, it can be seen that the common feature of the immune tolerance period, control period and reactivation period is that HBV is relatively active, so these three stages are contagious. If during the period of active HBV-DNA replication, the father's semen or body fluids will transmit HBV to the mother through sexual transmission and other means. If the mother becomes pregnant naturally without vaccination (passive acquisition of HBV antibody protection), it may bring the risk of HBV infection to the offspring. The only exception is that during the immune control period, HBV-DNA replication is paused, HBV infectivity is controlled, and HBV is usually undetectable in the father's semen or body fluids. Therefore, even men who carry HBV in their bodies will not infect women and offspring through sexual transmission.

——Does that mean that men during the above-mentioned period of HBV activeness will definitely not be able to have babies?

The answer is not completely negative. In vitro fertilization using assisted reproductive technology may avoid HBV infection. First of all, we need to briefly understand what assisted reproductive technology is. Assisted reproductive technology generally refers to the use of reproductive medicine technology to perform in vitro operations on human gametes such as sperm, eggs, and embryos to achieve the purpose of conception. At present, related derivative technologies such as artificial insemination (AID), in vitro fertilization-embryo transfer (IVF) and intracytoplasmic sperm injection (ICSI) have been developed.

Figure 2 Copyright image, no permission to reprint

If a HBV-positive male undergoes assisted reproduction, he may transmit HBV to a female through horizontal transmission during artificial insemination or in vitro fertilization, or vertically transmit HBV to embryos and offspring through HBV-infected sperm [3,4]. Therefore, all major reproductive centers emphasize HBV screening before assisted reproduction, further testing whether the male has HBV infection and HBV load, and assessing the risk of transmission. In addition, some institutions have tried to use sperm washing to remove sperm with poor motility (including sperm damaged by HBV infection) during the treatment of male HBV-infected patients, thereby reducing the impact of HBV on in vitro fertilization results. A more complete strategy is to inject HBV vaccine into the female at the same time, and both parties conceive through assisted reproductive technology, which will also reduce the probability of HBV transmission to the offspring.

In summary, although male HBV infection may have an impact on the baby, through effective medical intervention measures, the vast majority can still have healthy offspring.

References:

[1] Chinese Society of Hepatology, Chinese Society of Infectious Diseases. Guidelines for the prevention and treatment of chronic hepatitis B (2022 edition)[J]. Chinese Journal of Hepatology, 2022, 30(12): 1309-1331.

[2] World Health Organization. Guidelines for the Prevention, Diagnosis, Care and Treatment for People with Chronic Hepatitis B Infection (Text Extract): Executive Summary[J]. Infect Dis Immun, 2024,4(3):103-105.

[3] WANG Z, LIU W, ZHANG M, et al. Effect of hepatitis B virus infection on sperm quality and outcomes of assisted reproductive techniques in infertile males[J]. Front Med (Lausanne), 2021,8:744350.

[4] XU Y, GAN K, HOU L, et al. The association between hepatitis B virus and semen quality: A systematic review and meta-analysis[J]. BMC Urol., 2024,24(1):47.