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

Disclosures

J Viral Hepat. 2021;28(9):1234-1245. 

In This Article

Results

Characteristics of the Included Studies

From 1461 articles identified during the literature search, 385 articles were selected and underwent abstract screening. Of 149 articles that underwent full-text screening, a total of 42 articles met our inclusion criteria. Studies with minimal importance or insufficient data were excluded from the study in the last screening. The articles that met our inclusion criteria were divided into two different groups:

  • A group of 33 articles that studied the effect of HBV infection on different pregnancy complications in natural pregnancy.

  • A group of 9 articles that were focused on the effect of HBV on IVF outcome.

We assessed different parameters in each group. Preterm birth, stillbirth, pre-eclampsia, placenta previa, GDM, PROM, LBW and placental abruption as well as the number of good quality follicles, number of oocytes retrieved, number of fertilized oocytes, number of viable embryos, PR, implantation rate and livebirth rate were assessed. The data extracted from the studies are presented in Table 1 and Table 2. All the study subjects involved were treated in hospital-based settings.

Meta-analysis

a. The effect of HBV infection on pregnancy complications.

1. GDM

The analysis of the results of 27 articles[14–17,19–39] showed a significant association between GMD and HBV infection among pregnant women with a OR (95% CI) = 1.32 (1.17–1.48) and p < 0.01 for the overall effect, and p < 0.01 and I 2 = 87.3% for heterogeneity (Figure 2).

Figure 2.

Forest plots of the effect of HBV infection on GDM

2. Preterm birth

Thirty eligible articles concerning the effect of HBV infection on pregnancy complications were included to assess the effects of HBV on preterm birth.[14–17,19–25,27,28,30–38,40–47] The results revealed significantly higher rates of preterm birth among HBV+ women compared to HBV− women (p < 0.01) [OR (95% CI) = 1.26 (1.14–1.40)]. For heterogeneity, p < 0.01 and I 2 = 72.2% (Figure 3).

Figure 3.

Forest plots of the effect of HBV infection on preterm birth

3. Pre-eclampsia

Nineteen articles[14–17,19,21–28,30,32,33,35,37,39,41,46] reported the effects of HBV infection on pre-eclampsia and the results indicated statistically significant difference between HBV+ and HBV− pregnant females regarding the rates of pre-eclampsia occurrence (p = 0.001). The HBV negatives seemed to have higher rates of pre-eclampsia [OR (95% CI) = 0.83 (0.75–0.93)]. For heterogeneity, p = 0.22 and I 2 = 19.9% (Figure 4).

Figure 4.

Forest plots of the effect of HBV infection on pre-eclampsia (A) and placenta previa (B)

4. Placenta previa

Placenta previa was investigated in 10 studies,[14–16,19–21,23,32,33,35–37] and there was no significant association between HBV infection and placenta previa (p = 0.43); however, HBV+ patients seemed to have higher rates of placenta previa. The obtained OR was 1.15 (0.81–1.63). For heterogeneity, p = 0.06 and I 2 = 44.1% (Figure 4).

5. PROM

Twelve investigations[15,16,19,20,24,31,32,35–37,44–46] assessed the effects of HBV infection on PROM. However, PROM rate was higher among HBV infected women, it was insignificant (p = 0.53) [OR (95% CI) = 1.11 (0.79–1.55)]. For heterogeneity, p < 0.01 and I 2 = 91.2% (Figure 5).

Figure 5.

Forest plots of the effect of HBV infection on PROM (A) and stillbirth (B)

6. STILLBIRTH

A group of 13 studies[17,19,22,25,31,33,35,36,38,40,42–44,47] evaluated the effects of HBV infection on stillbirth. Our results showed no significant difference in the prevalence of stillbirth among HBV+ pregnant women compared to HBV negatives (p = 0.37) [OR (95% CI) = 1.14 (0.86–1.51)]. For heterogeneity, p < 0.01 and I 2 = 70.7% (Figure 5).

7. Miscarriage rate

Eleven out of 42 studies included in this meta-analysis[11,14,20,22,33,35,41,43,48–50] investigated the rate of miscarriage in the HBV+ females compared with controls and our meta-analysis revealed no significant effect of HBV infection on miscarriage rates among pregnant women [OR (95% CI) = 1.04 (0.88–0.124)] with a p = 0.63 for the overall effect (p = 0.60 for natural pregnancy and p = 0.85 for IVF), and p = 0.007 and I 2 = 58.9% for heterogeneity (Figure 6).

Figure 6.

Forest plots of the effect of HBV infection on miscarriage rate

8. Placental abruption

The evaluation of six studies[15,16,19,35,36,46] concerning the impact of HBV infection on placental abruption did not show a significant correlation between the higher rates of HBV infection and the incidence of placental abruption among females (p = 0.16) [OR (95% CI) = 1.13 (0.95–1.35)]. For heterogeneity, p = 0.39 and I 2 = 3.8% (Figure S1).

9. Low birth weight

Evaluation of 18 studies[14,16,17,21,23,24,26,28,32–34,36,37,39,40,42,44,46,47] that investigated the effect of HBV infection on LBW indicated no statistically significant relationship was found between HBV infection and LBW (p = 0.26) [OR (95% CI) = 1.06 (0.96–1.17)]. For heterogeneity, p < 0.01 and I 2 = 61.4% (Figure S2).

b. The effect of HBV infection on IVF

1. Number of oocytes retrieved

Among the nine selected IVF studies, six articles reported the number of oocytes retrieved[20,51–55] and according to our results, no relationship was observed between the number of oocytes retrieved and rates of HBV infection in females. [SMD (95% CI) = 0.04 (−0.05 to 0.13)]. For overall effect p = 0.35, and for heterogeneity, p = 0.50 and I 2 = 0.0% (Figure S3).

2. Number of fertilized oocytes

Five IVF articles[20,52–55] assessed the numbers of fertilized oocytes. The results of the related articles revealed no significant difference in the numbers of fertilized oocytes in HBV-infected women compared to non–HBV-infected individuals (p = 0.62) [SMD (95% CI) = 0.03 (−0.10 to 0.17)]. For heterogeneity, p = 0.10 and I 2 = 47.3% (Figure S3).

3. Number of viable embryos

Number of viable embryos was studied in five investigations.[51–55] The number of viable embryos seemed to be higher among controls; however, it was not significant (p = 0.62) [SMD (95% CI) = −0.04 (−0.23 to 0.14)]. For heterogeneity, p = 0.07 and I 2 = 52.9% (Figure S3).

4. Number of good quality follicles

Only three studies[51,53,54] reported the number of good quality follicles and there was no difference between the number of good quality follicles in HBV- women in comparison with HBV+ ones (p = 0.87) [SMD (95% CI) = −0.01 (−0.17 to 0.14)]. For heterogeneity, p = 0.83 and I 2 = 0.0% (Figure S3).

5. Pregnancy rate

Analysing the results of all nine IVF investigations included in our study[20,49–55] indicated no significant association between the rate of PR and HBV infection [OR (95% CI) = 1.12 (0.88–1.41)]. For overall effect p = 0.36, and p = 0.15 and I 2 = 32.5% for heterogenicity (Figure S4).

6. Implantation rate

The analysis of the four relevant studies[20] showed no significant effect of HBV infection on implantation rate (p = 0.67) [OR (95% CI) = 1.03 (0.89–1.21)]. For heterogeneity, p = 0.87 and I 2 = 0.0% (Figure S4).

7. Livebirth rate

The results from five studies[20,51–54] evaluating the influence of HBV infection on the livebirth rates showed not significant association between the rates of livebirth and HBV infection among women undergoing IVF treatment (p = 0.29) [OR (95% CI) = 1.25 (0.82–1.90)]. For heterogeneity, p = 0.01 and I 2 = 66.1% (Figure S5).

Sensitivity Analysis

We conducted a sensitivity analysis to assess whether any one of these studies affected the results of the meta-analysis. No single study significantly changed the results, which indicated that the results were statistically stable and reliable.

Publication Bias

For publication bias, Egger's regression test was performed. The results showed no publication bias (p > 0.05); however, a little evidence of publication bias was found for GDM p = 0.06 and Live birth p = 0.06.

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