A large multicenter retrospective cohort study found that female patients with chronic hepatitis B virus infections may exhibit lower ovarian reserve compared with those without the infections when undergoing their first in vitro fertilization treatment.
In the study, published in BMC Medicine, investigators analyzed data from more than 38,000 infertile female patients treated between 2016 and 2022, including 1,574 patients who tested positive for hepatitis B surface antigen (HBsAg).
The investigators matched these patients by age and body mass index (BMI) with a control group of HBsAg-negative patients to evaluate ovarian reserve indicators. They assessed key ovarian function markers such as antral follicle count (AFC), anti-Müllerian hormone (AMH) levels, follicle-stimulating hormone (FSH) levels, and the number of retrieved and mature metaphase II (MII) oocytes.
The investigators showed that HBsAg-positive patients had significantly lower ovarian reserve markers compared with their hepatitis B virus (HBV)-negative counterparts. The median AFC was 11 in the HBsAg-positive group compared with 18 in the control group (P < .001), and median AMH levels were 2.25 ng/ml vs 6.81 ng/ml (P < .001). HBsAg-positive patients also demonstrated higher FSH levels and required greater total doses of gonadotropins for ovulation induction, resulting in fewer retrieved and mature oocytes. The prevalence of diminished ovarian reserve (DOR), defined as AMH < 1.1 ng/ml, was significantly higher among HBV-positive patients (23.08%) compared with HBV-negative patients (0.38%). Multivariate logistic regression analysis indicated that HBV infections were associated with a 103.9-fold increased risk of DOR (95% confidence interval = 45.7–236.3, P < .001).
Notably, no statistically significant difference in ovarian reserve was observed between HBeAg-positive and HBeAg-negative subgroups, suggesting that antigen status does not impact ovarian reserve among HBV-positive patients.
"This information is of guidance significance for HBsAg-positive [patients] with fertility needs, as regular monitoring of [HBV] levels should be accompanied by attention to ovarian reserve function. Our study also provides important insights into understanding the potential effects of chronic HBV infections on female fertility and ovarian reserve," said lead study author Yutao Li, of the Department of Assisted Reproduction Center at the Sichuan Provincial People’s Hospital at the University of Electronic Science and Technology of China, and colleagues.
Despite the findings, the investigators found no clear evidence linking HBV infections to poorer in vitro fertilization (IVF) outcomes in terms of pregnancy rates. They attributed this lack of association to factors such as pre-IVF antiviral treatments and comprehensive patient evaluations, which may mitigate the infection's impact on reproductive success. The retrospective design of the study and lack of data on HBV DNA levels and infection duration were noted as limitations.
Meanwhile, the investigators emphasized that future prospective, randomized studies are necessary to validate these findings and determine whether HBV-related reductions in ovarian reserve translate into clinically significant fertility impairments.
The study concluded that HBsAg positivity should be considered a significant factor during infertility evaluations as a result of its association with decreased ovarian reserve.
The authors declared no competing interests, with all analyses conducted under ethical research standards and appropriate institutional approvals obtained for the use of hospital discharge data.
