ObjectiveTo investigate whether Helicobacter pylori (H.pylori) infection correlated with primary infertility, whether H. pylori infection caused the abnormal elevation of pro-inflammatory cytokines in primary infertility women, and whether cytotoxin associated gene A (CagA) protein played a key role in it.
MethodsFrom September 2015 to August 2016, 213 patients with primary infertility (infertility group) and 97 healthy individuals (control group) were selected. According to the common etiologies, patients with primary infertility were divided into groups with single-factor infertility, multifactorial infertility and unexplained reason groups. Serum H. pylori IgG antibody and CagA antibody were examined by H. pylori antibody type test kits. The levels of interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-18, IL-1β, granulocyte-macrophage-colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and IL-12p70 were tested by ProcartaPlex Immunoassays. Chi square test and independent sample t test were performed for statistical analysis and risk was assessed.
ResultsThe positive rate of serum H. pylori IgG antibody of patients with primary infertility was higher than that of healthy control group (74.0%, 37/50 vs 56.7%, 55/97), and the difference was statistically significant (odds ratio (OR)=2.173, 95% confidence interval (CI) 1.028 to 4.595, χ2=4.216, P=0.040). There was no statistically significant difference in the positive rate of CagA antibody between primary infertility group and healthy control group (71.7%, 91/127 vs 74.5%, 41/55, OR=0.863, 95%CI 0.421 to 1.772, P>0.05). The serum levels of IL-8, IL-18 and IFN-γ of H. pylori positive primary infertility patients were (35.14±12.16), (11.83±4.01) and (11.05±3.17) ng/L, respectively, which were all higher than those of H. pylori positive healthy control group ((21.44±12.35), (9.89±2.23) and (8.90±1.45) ng/L, respectively) and H. pylori negative primary infertility group ((11.45±8.63), (7.90±0.99) and (8.18±1.10) ng/L, respectively), and the differences were statistically significant (t=6.947, 3.366 and 4.811; 15.596, 8.900 and 8.068; all P<0.05). The levels of IL-8, IL-18 and IFN-γ of H. pylori positive unexplained reason primary infertility group were (39.97±11.52), (13.12±4.61) and (13.06±3.70) ng/L, respectively, which were all significantly higher than those of single-factor infertility group ((31.65±11.20), (11.12±3.46) and (10.14±2.41) ng/L, respectively) and multifactorial infertility group ((30.47±8.49), (11.13±3.79) and (10.07±2.50) ng/L, respectively); and the differences were statistically significant (t=4.217, 2.942 and 5.738; 5.138, 2.562 and 5.218; all P<0.05). In H. pylori positive primary infertility group, the levels of IL-8, IL-18 and IFN-γ of CagA positive patients were (40.42±13.80), (13.04±4.19) and (11.51±3.41) ng/L, respectively, which were all significantly higher than those of CagA negative patients ((23.49±11.57), (9.08±1.43) and (10.04±2.29) ng/L, respectively) and CagA positive individuals in healthy control group ((21.85±12.14), (10.20±2.29) and (9.31±2.38) ng/L, respectively); and the differences were statistically significant (t=6.507, 5.533 and 2.380; 7.417, 4.069 and 3.738; all P<0.05).
ConclusionCagA positive H. pylori infection can increase the level of serum pro-inflammatory cytokines, which may be a risk factor of primary infertility. To patients with unexplained primary infertility, this may be the cause of infertility.
