Mannose Binding Lectin (MBL) gene polymorphism and in vitro fertilization outcome

Abstract

Objective: MBL is a serum protein and a component of the innate immune system. By binding to carbohydrate residues on microorganisms, MBL activates the complement system and marks microbes for opsonization. MBL binding to Chlamydia has been demonstrated. The gene coding for MBL is polymorphic and the variant alleles result in decreased MBL serum levels. The association between C. pneumoniae and cardiovascular disease was shown to depend on the presence of variant MBL alleles. Given the relationship between Chlamydia and infertility, we examined the relationship between MBL genotype, infertility etiology and IVF outcome.Design: Prospective analysis of the association between MBL genotype, etiology of infertility and IVF outcome.Materials and Methods: MBL genotypes at codon 54 were determined in 185 consecutive IVF patients by polymerase chain reaction, endonuclease digestion and gel electrophoresis, using DNA isolated from cervical swabs. IVF outcome and the etiology of infertility were obtained at the conclusion of MBL genotype testing. Implantation was defined as the presence of a fetal heart beat. Statistics utilized included Categorical Chi-square testing and Student’s t-test where appropriate. P value < 0.05 was considered significant. Data is presented as mean ± standard deviation.Results: The wild type MBL genotype (AA) was present in 138 (74.6%) of the patients; 47 (25.4%) had variant alleles (41 were AB and 6 were BB). There were no differences in the age, oocyte yield, fertilization percentage or number of embryos transferred based on the MBL genotype result. Patients with the variant alleles had a trend towards an increased rate of tubal infertility (25.6% vs. 16.8%, p = 0.2). Among all subjects, the rates of pregnancy, clinical pregnancy and implantation were not related to the MBL genotype. However, among patients carrying the AB genotype, those with tubal infertility were less likely to achieve a clinical pregnancy than patients with non-tubal infertility (20% vs. 57.7%; P < 0.05). Patients with tubal and non-tubal infertility who had the AA genotype did not differ in pregnancy outcome.Conclusion: Possession of the MBL AB genotype is associated with a decreased IVF success rate in women with tubal infertility. Possession of this genotype, which results in reduced serum MBL levels and lowered innate immune defense against infection, may render women less effective in eliminating microorganisms from the upper genital tract. Analysis of tubal infertility patients for MBL genotypes may have predictive value for IVF outcome and for selecting patients that may need antibiotic prophylaxis. Objective: MBL is a serum protein and a component of the innate immune system. By binding to carbohydrate residues on microorganisms, MBL activates the complement system and marks microbes for opsonization. MBL binding to Chlamydia has been demonstrated. The gene coding for MBL is polymorphic and the variant alleles result in decreased MBL serum levels. The association between C. pneumoniae and cardiovascular disease was shown to depend on the presence of variant MBL alleles. Given the relationship between Chlamydia and infertility, we examined the relationship between MBL genotype, infertility etiology and IVF outcome. Design: Prospective analysis of the association between MBL genotype, etiology of infertility and IVF outcome. Materials and Methods: MBL genotypes at codon 54 were determined in 185 consecutive IVF patients by polymerase chain reaction, endonuclease digestion and gel electrophoresis, using DNA isolated from cervical swabs. IVF outcome and the etiology of infertility were obtained at the conclusion of MBL genotype testing. Implantation was defined as the presence of a fetal heart beat. Statistics utilized included Categorical Chi-square testing and Student’s t-test where appropriate. P value < 0.05 was considered significant. Data is presented as mean ± standard deviation. Results: The wild type MBL genotype (AA) was present in 138 (74.6%) of the patients; 47 (25.4%) had variant alleles (41 were AB and 6 were BB). There were no differences in the age, oocyte yield, fertilization percentage or number of embryos transferred based on the MBL genotype result. Patients with the variant alleles had a trend towards an increased rate of tubal infertility (25.6% vs. 16.8%, p = 0.2). Among all subjects, the rates of pregnancy, clinical pregnancy and implantation were not related to the MBL genotype. However, among patients carrying the AB genotype, those with tubal infertility were less likely to achieve a clinical pregnancy than patients with non-tubal infertility (20% vs. 57.7%; P < 0.05). Patients with tubal and non-tubal infertility who had the AA genotype did not differ in pregnancy outcome. Conclusion: Possession of the MBL AB genotype is associated with a decreased IVF success rate in women with tubal infertility. Possession of this genotype, which results in reduced serum MBL levels and lowered innate immune defense against infection, may render women less effective in eliminating microorganisms from the upper genital tract. Analysis of tubal infertility patients for MBL genotypes may have predictive value for IVF outcome and for selecting patients that may need antibiotic prophylaxis.