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. 2025 Mar;42(3):809-815.
doi: 10.1007/s10815-024-03359-4. Epub 2024 Dec 27.

Hepatitis B virus impacts embryonic development and methylation of maternal genes in assisted reproductive technology patients

Xia Liu  1 , Shixiang Dong  2 , Yu Ding  3 , Jinjin Li  4 , Jingyuan Wang  5
Affiliations

Hepatitis B virus impacts embryonic development and methylation of maternal genes in assisted reproductive technology patients

Xia Liu et al. J Assist Reprod Genet. 2025 Mar.

Abstract

Purpose: In China, the prevalence of hepatitis B virus (HBV) infection among infertile couples is a significant clinical problem. It is necessary to determine the effect of HBV infection on embryo development.

Methods: The 4301 fresh cycles and 5763 frozen embryo transfer (FET) cycles were grouped according to the couple with or without HBV infection. The embryo fertilization rate, cleavage rate, transplantable embryo rate, and rate of high-quality embryos were analysed. The methylation status of maternal antigen that embryos require (MATER), zygote arrest 1 (ZAR1) and growth differentiation factor 9 (GDF9) genes in the peripheral blood of assisted reproductive technology (ART) women was detected by methylation-specific polymerase chain reaction (MSP).

Results: The pregnancy rate of the female HBV-positive group was significantly lower than that of the HBV-negative group. The fertilization rate of intracytoplasmic sperm injection (ICSI) cycles in the male HBV-positive group was significantly lower than that of the male HBV-negative group. There were no differences in biochemistry or clinical pregnancy rates among the FET groups. The promoter methylation of GDF9 in HBV-positive ART women was higher than that in HBV-negative ART women, and that of ZAR1 in HBV-positive ART women was lower than that in HBV-negative ART women.

Conclusion: It was a detrimental effect of HBV infection on in vitro fertilization (IVF) and ICSI treatment outcomes in women. The HBV infection was associated with the maternal genes promoting methylation.

Keywords: Embryonic development; Hepatitis B virus; Assisted reproductive technology; Intracytoplasmic sperm injection.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interest.

Figures

Fig. 1
Fig. 1
GDF9, ZAR1, and MATER promoter methylation in HBV-positive and HBV-negative women. A Representative GDF9, ZAR1 and MATER promoter methylation by MSP. U, PCR product from the MSP assay using primers specific for the unmethylated allele; M, PCR product from the MSP assay using primers specific for the methylated allele; M, DL2000 DNA Marker; B The GDF9, ZAR1, and MATER MSP assay results for HBV-positive and HBV-negative women. *p < 0.05 vs. HBV-negative women
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