Effect of hepatitis B virus infection in males on pregnancy outcomes of intrauterine insemination – Nature

Report on the Association Between Male Hepatitis B Virus Infection and Intrauterine Insemination Outcomes

Executive Summary

This report details a retrospective analysis investigating the impact of male Hepatitis B Virus (HBV) infection on the outcomes of Intrauterine Insemination (IUI). The study aligns with key United Nations Sustainable Development Goals (SDGs), particularly SDG 3 (Good Health and Well-being), by addressing reproductive health and infectious disease management. The primary finding indicates a significant association between male HBV infection and an increased rate of early pregnancy loss. This highlights a critical area for clinical intervention and counseling to improve health outcomes and support SDG 5 (Gender Equality) by promoting shared responsibility in reproductive health. The findings underscore the need for integrated healthcare strategies to mitigate the reproductive consequences of HBV, contributing to SDG 10 (Reduced Inequalities) in health access and outcomes.

1.0 Introduction

The global health agenda, as outlined in the Sustainable Development Goals, emphasizes the importance of combating infectious diseases and ensuring universal access to reproductive healthcare services (SDG 3, Targets 3.3 and 3.7). Hepatitis B Virus (HBV) infection remains a significant public health challenge, particularly in regions like China with high prevalence. While HBV is primarily known for its effects on the liver, its capacity to infect extrahepatic tissues, including the male reproductive system, poses a direct threat to reproductive well-being. This study was initiated to address a gap in understanding the specific impact of male HBV infection on the outcomes of Assisted Reproductive Technologies (ART), specifically IUI. By clarifying this relationship, this research aims to provide evidence-based guidance for clinical practice, thereby supporting the achievement of good health and well-being for all.

1.1 Study Objective

The primary objective was to assess the impact of male HBV infection on IUI pregnancy outcomes, with a specific focus on rates of pregnancy, live birth, and pregnancy loss. The study employed a refined patient categorization methodology and robust statistical analysis to ensure the reliability of its findings and their contribution to global health knowledge (SDG 17).

2.0 Methodology

A retrospective cohort study was conducted using data from 1,686 IUI cycles performed at the Assisted Reproductive Center of Zhongshan City People’s Hospital between January 2015 and September 2023.

2.1 Patient Cohort and Grouping

• Study Group: Comprised couples where the male partner was HBV-infected and the female partner was uninfected.
• Control Group: Comprised couples where both partners were HBV-uninfected.
• Couples with HBV-convalescent status were excluded to ensure a clear distinction between infected and uninfected states, enhancing the study’s precision.
• Propensity score matching (1:4 ratio) was used to control for confounding variables such as female age and infertility duration, ensuring comparability between the groups.

2.2 Procedures and Outcome Measures

1. Clinical Procedures: Standard protocols were followed for ovulation stimulation, semen processing (density gradient centrifugation), IUI, and luteal phase support.
2. Primary Outcome Measures:
   • hCG Positivity Rate
   • Clinical Pregnancy Rate
   • Early Pregnancy Loss Rate (defined as biochemical pregnancies and early abortions)
   • Preterm Birth Rate
   • Low Birth Weight Rate

2.3 Statistical Analysis

Data were analyzed using t-tests, chi-square tests, and multivariate Generalized Estimating Equation (GEE) analysis to adjust for potential confounding factors. A P-value of

3.0 Results

After propensity score matching, the final analysis included 88 cycles in the HBV-infective group and 311 cycles in the HBV-uninfective control group.

3.1 Pregnancy and Birth Outcomes

The analysis revealed no statistically significant differences between the HBV-infective and HBV-uninfective groups in the following outcomes (P > 0.05):

• hCG Positivity Rate
• Clinical Pregnancy Rate
• Preterm Birth Rate
• Low Birth Weight Rate
• Mean Birth Weight
• Infant Gender Ratio

3.2 Key Finding: Early Pregnancy Loss

A statistically significant difference was observed in the rate of early pregnancy loss. The rate was substantially higher in the HBV-infective group compared to the control group.

• HBV-Infective Group: 43.75%
• HBV-Uninfective Group: 14.00% (P

The GEE analysis confirmed this finding, demonstrating that male HBV infection significantly increased the risk of early pregnancy loss (adjusted OR = 7.022; 95% CI 1.889–26.100; P

4.0 Discussion and Analysis in the Context of SDGs

4.1 Implications for SDG 3 (Good Health and Well-being)

The study’s central finding—that male HBV infection is a significant risk factor for early pregnancy loss—directly impacts SDG 3. It highlights a critical challenge to ensuring healthy lives and promoting well-being. The potential mechanisms, including HBV-induced sperm DNA damage and paternal-fetal vertical transmission, suggest that the virus compromises embryonic viability. This knowledge is crucial for developing targeted health interventions. Addressing this issue requires integrating HBV screening and management into reproductive health services, thereby helping to end the epidemic of viral hepatitis (Target 3.3) and improve maternal and infant health outcomes.

4.2 Relevance to SDG 5 (Gender Equality) and SDG 10 (Reduced Inequalities)

This research contributes to SDG 5 by focusing on a male-factor contribution to pregnancy loss, promoting a more equitable and comprehensive understanding of reproductive health that involves both partners. It empowers couples with crucial information, enabling them to make informed decisions about family planning and fertility treatments (Target 5.6). Furthermore, by identifying a specific health disparity affecting individuals with HBV, the study calls for equitable access to specialized care. This aligns with SDG 10 by highlighting the need to reduce health inequalities and ensure that vulnerable populations receive the support necessary to achieve their reproductive goals.

4.3 Potential Mechanisms and Future Research

The elevated rate of early pregnancy loss may serve as a natural selection mechanism to eliminate embryos compromised by paternal HBV transmission. Several factors could contribute to this outcome:

1. Sperm DNA Damage: HBV integration into sperm chromosomes can lead to DNA fragmentation, impairing embryonic development.
2. Female Immune Response: Introduction of HBV antigens via semen may alter the immune environment of the female reproductive tract, making it less conducive to maintaining a pregnancy.
3. Vertical Transmission: Direct infection of the embryo from sperm could lead to developmental failure.

Further prospective, multicenter research is essential to validate these findings and elucidate the underlying mechanisms, embodying the spirit of SDG 17 (Partnerships for the Goals) to advance scientific knowledge for sustainable development.

5.0 Conclusion and Recommendations

This report concludes that while male HBV infection does not appear to affect the rates of conception or live birth in IUI cycles, it is strongly associated with a significantly increased risk of early pregnancy loss. This finding has profound implications for clinical practice and public health policy aimed at achieving the Sustainable Development Goals.

Recommendations

• Enhanced Clinical Counseling (SDG 3 & 5): Couples where the male partner is HBV-infected should be counseled about the increased risk of early pregnancy loss. This allows for informed decision-making and provides crucial psychosocial support.
• Integrated Health Services (SDG 3 & 10): Reproductive health clinics should integrate HBV management into their services, including viral load monitoring and consideration of antiviral therapy for male partners prior to initiating ART.
• Prioritize Further Research (SDG 3 & 17): Future large-scale, prospective studies are needed to confirm these findings and investigate the roles of sperm DNA integrity, female immune response, and the uterine microbiome in this process.

Analysis of Sustainable Development Goals in the Article

1. Which SDGs are addressed or connected to the issues highlighted in the article?

1. SDG 3: Good Health and Well-being

   • Explanation: The entire article is fundamentally centered on health. It investigates a specific communicable disease, the Hepatitis B Virus (HBV), and its impact on reproductive health outcomes. The study’s focus on disease prevalence, infertility treatments (assisted reproductive technologies), and pregnancy outcomes like early pregnancy loss, preterm birth, and low birth weight directly aligns with the goal of ensuring healthy lives and promoting well-being for all at all ages. The article mentions that “China is recognized as a high-prevalence region for HBV,” highlighting a significant public health challenge, and explores how this disease affects the “heightened risk of infertility” and the outcomes of intrauterine insemination (IUI), a key reproductive health service.

2. What specific targets under those SDGs can be identified based on the article’s content?

1. Target 3.3: By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases.

   • Explanation: This target is directly relevant as the article’s primary subject is the Hepatitis B Virus (HBV), a communicable disease explicitly named in the target. The study provides data on the high prevalence of HBV in China, stating that “approximately 5–7% of the population testing positive for HBsAg,” and notes that at their reproductive center, the “prevalence rate of HBsAg in male patients undergoing IUI treatment is 11.3%.” By investigating the health consequences of HBV, the research contributes to the body of knowledge needed to effectively combat the disease and manage its impacts.

2. Target 3.7: By 2030, ensure universal access to sexual and reproductive health-care services, including for family planning, information and education, and the integration of reproductive health into national strategies and programmes.

   • Explanation: The study is set within the context of assisted reproductive technologies (ART), specifically intrauterine insemination (IUI), which are critical components of sexual and reproductive health-care services. The article addresses couples “diagnosed with infertility and eligible for IUI” and analyzes the outcomes of these treatments. By examining how a prevalent disease like HBV affects the success of IUI, the research provides crucial information for improving the effectiveness and counseling related to these reproductive health services.

3. Target 3.2: By 2030, end preventable deaths of newborns and children under 5 years of age, with all countries aiming to reduce neonatal mortality to at least as low as 12 per 1,000 live births and under-5 mortality to at least as low as 25 per 1,000 live births.

   • Explanation: While the article does not measure neonatal mortality directly, it investigates key contributing factors. The study’s primary finding is that male HBV infection is associated with a significantly higher “early pregnancy loss rate” (43.75% vs. 14.00%). Early pregnancy loss is the first step in preventing live births. Furthermore, the study measures other critical newborn health outcomes such as “preterm birth rate” and “low birth weight rate.” Understanding and mitigating the factors that lead to these adverse outcomes are essential for achieving the goal of reducing newborn deaths.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

1. Indicator 3.3.4: Hepatitis B incidence per 100,000 population.

   • Explanation: The article does not provide incidence data (new cases) but offers crucial prevalence data (existing cases), which is directly related to understanding the scale of the hepatitis epidemic. It states, “China is recognized as a high-prevalence region for HBV, with approximately 5–7% of the population testing positive for HBsAg.” This prevalence data serves as a baseline measure against which the progress of combating hepatitis can be assessed.

2. Implied Indicators for Reproductive and Newborn Health (Targets 3.7 and 3.2)

   • Explanation: The article defines and measures several specific “Outcome measures” that serve as direct indicators for the quality and success of reproductive health services and factors affecting newborn health. These are:
     • Early pregnancy loss rate: Measured as “(Number of early pregnancy loss cases/Number of hCG positive cases) ×100%.” The study found this rate was significantly higher in the HBV-infective group (43.75%), directly measuring a negative reproductive outcome relevant to both Target 3.7 and 3.2.
     • Clinical pregnancy rate: Measured as “(Number of clinical pregnancy cases/Number of IUI treatment cycles) ×100%.” This is a key performance indicator for the effectiveness of IUI services under Target 3.7.
     • Preterm birth rate: Defined as delivery between 28 and 36 weeks and measured as a percentage of singleton deliveries. This is a direct indicator related to newborn health under Target 3.2.
     • Low birth weight rate: Defined as a birth weight less than 2,500g and measured as a percentage of singleton deliveries. This is another direct indicator for newborn health and survival prospects under Target 3.2.

4. Summary Table of Findings

Source: nature.com