The Effects of Hepatitis B Virus Infection on Natural and IVF Pregnancy

A Meta-Analysis Study

Marziye Farsimadan; Seyed Mohammad Riahi; Huda Muhaddien Muhammad; Alireza Emamvirdizadeh; Mohsen Tabasi; Mohammad Motamedifar; Giandomenico Roviello


J Viral Hepat. 2021;28(9):1234-1245. 

In This Article


Search Strategy

We searched Embase, Web of Science, PubMed and Google Scholar databases to find potentially relevant papers concerning the effects of HBV infection on pregnancy outcomes and complications in natural and IVF pregnancy published up to January 2021. No restrictions on date, language or geographical location were applied to the search. The search was restricted to human studies. We searched these databases using keywords that were a combination of virus name and words such as female infertility, fertilization, abortion, miscarriage, failed pregnancy, pregnancy complications, low birth weight (LBW), premature rupture of membranes (PROM), gestational diabetes mellitus (GMD), pre-eclampsia, stillbirth, livebirth, placental abruption, placenta previa, preterm birth, reproductive disorder, reproductive failure, foetal death, decreased pregnancy outcome, reduced pregnancy rates (PR), implantation rate, recurrent spontaneous abortion (RSA), recurrent miscarriage (RM), in vitro fertilization (IVF) and assisted reproductive technology (ART). LBW is defined by the as a birth weight of an infant of 2499 g or less, regardless of gestational age.

Four authors screened titles and abstracts to identify potentially relevant articles that met our inclusion criteria. Full text of these articles was then screened independently to assess whether they answered any of the following questions about the effect of HBV infection on natural and IVF pregnancies: (1) has HBV infection affected the frequency of natural pregnancy in women? (2) has HBV infection led to increased rates of pregnancy complications and infertility among women with natural pregnancy? (3) has HBV infection affected the outcome of IVF treatment and rates of successful pregnancy in women undergoing IVF treatment? (4) has HBV infection led to increased rates of infertility and higher rates of pregnancy complications included in this study among women undergoing IVF treatment?

In the present study, all review and screening processes were done according to the PRISMA guidelines for reporting systematic reviews ( We reached consensus on which reports to include by discussion or by asking a third reviewer to adjudicate.

Types of Studies

Eligible studies that were included in this meta-analysis were the studies investigating the associations of HBV with female infertility and pregnancy outcomes. Full articles (cohort or case-controlled study) relevant to the topic were enrolled in this study. Abstracts, comments, reviews and editorials were not included. Duplicated hits and studies with low-quality or insufficient data were excluded. The lists of the published articles were searched for possible relative papers too. If applicable, the corresponding authors of relevant ongoing studies were contacted for information regarding unpublished data.

Data Collection

Predesigned data extraction forms were used to collect data. The following data were collected from each included study: first author, year of publication, country of origin, design, the total number of subjects, number of infected cases, number of infected controls, the effect on fertility potential, the effect on pregnancy outcome and the detection methods. Women of all ages were included. For each parameter, the number of individuals (HBV+/HBV−) or the mean difference along with the relevant standard deviation (SD) were imported. In case the mean differences or SDs were not available, connections were made with the authors to receive the required data. Finally, after assessing the information of 149 studies that were related to the area of this study, a total of 42 studies were included in the analysis. The data were extracted by three authors independently. Disagreements between reviewers were discussed to obtain consensus. Figure 1 represents a flow chart showing the study selection process.

Figure 1.

The flow chart for the search methodology

Assessment of Study Quality

The quality of the included studies was assessed using the Newcastle-Ottawa scale.[18] The scale consists of nine items covering three dimensions: (i) selection, scoring a maximum of 4; (ii) comparability, maximum score 2; and (iii) exposure (case-control)/outcome (cohort), maximum score 3, with a maximum total of nine representing high quality.

Statistical Analysis

All data were analysed using Stata® 13.0 (StataCorp LP., College Station, TX, USA). When p > 0.1 and I 2 < 50%, the fixed-effects model was used; otherwise, the random-effects model was used. In addition, publication bias was detected by Begg's and Egger's test. For all of the statistical analyses, a value of p < 0.05 was regarded as statistically significant and all of the tests were two-sided.