Preconception Immunoglobulins and Complements as Potential Biomarkers in Unexplained Female Infertility in Saudi Arabia

Background: Immunological abnormalities are currently under investigation to potentially unravel the etiology of frustrating cases of unexplained female infertility (UFI).Objectives: To explore the prevalence of immunological abnormalities in the levels of total immunoglobulins and complements in the cases of UFI.Methods: Females with a history of UFI were included in this cross-sectional study. They were consulted at the clinical immunology clinic at the King Abdulaziz University Hospital (KAUH). Their demographics, clinical features, total immunoglobulins, and complement test results were collected and analyzed for any relationship with UFI.Results: One hundred and twenty-one cases of UFI with an average age of 34 +/- 5.6 (range from 23 to 49 years old) were studied. Secondary infertility was predominant in 99 cases (81.8%). An overall prevalence of at least one abnormal level of total immunoglobulins or complements was found in 65 cases (55.1%). The predominant immunological abnormalities were elevated levels of immunoglobulins (hypergammaglobulinemia) in 51 cases (43.2%), high IgG in 26 cases (22%), high IgA in 14 cases (11.9%), and high IgM in 11 cases (9.3%). This was followed by elevated levels of complements (hypercomplementemia) in C4 in nine cases (8.5%). A significant association was found between the high C4 group and some parameters of infertility, including primary infertility (p = 0.005), no pregnancy (p = 0.001), and no abortion (p = 0.047), in comparison to that of the normal C4 group. Moreover, a statistically significant association was found between the high IgA group and abortion in comparison to the normal IgA group (p = 0.054).Conclusion: At least one abnormal level of total immunoglobulins or complements was detected in more than half of the UFI cases. The commonest abnormalities were hypergammaglobulinemia (IgG, IgM, IgA) and hypocomplementenemia (C4), which showed a potential association with some infertility parameters. These findings may encourage the screening of general immunological tests to explore promising new immunopathology in UFI.