Browsing by Author "Todorovic, Jelena (56641105000)"

Reproductive failure (recurrent foetal loss, unexplained infertility and IVF implantation failure) may be, in a number of cases, explained by thrombophilia, either acquired or inherited. Several genes contribute to thrombophilia, some with major effect (Factor V, Factor II), and some with minor effect (MTHFR, PAI-1, ATIII, etc.). The aim of this study was to estimate frequency of thrombophilia-associated genotypes (FII20210G > A, FV1691G > A, MTHFR677C > T and PAI-1 -675 4G/5G) in a group of 1631 Serbian women experiencing reproductive failure, and compare it with a healthy, female control group. Our results showed marginally significant (p = 0.050) differences in allele frequencies between patients and controls for the FV1691 mutations. For the FII20210G > A, although the statistical significance was not achieved (p = 0.076), we found higher frequency of variant allele in patients compared to controls (1.87% vs. 0.38%, respectively) which may point to a possible role of this polymorphism in thrombotic events. For the MTHFR677C > T and PAI-1 -675 4G/5G, we found no difference in distributions of genotype or allele frequencies between these two groups (p > 0.05). For three subjects with very rare genotypes (two patients homozygous for FV1691G > A and one patient homozygous for FII20210G > A) we performed additional biochemical analyses for haemostasis, as well as genotyping of two polymorphisms (MTHFR1298A > C and ATIII786G > A). © 2016 The British Fertility Society.

A numerous factor can cause infertility, but around one of four reproductive failure cases remain unexplained and diagnosed as idiopathic infertility. In the past few decades, analysis of gene polymorphisms takes a significant place in pathogenesis of infertility. The aim of this study was to evaluate the possible role of hemostasis-related gene polymorphisms in unexplained infertility. The study includes 117 female patients with idiopathic infertility and 130 fertile women with at least one born child. Eight polymorphisms important for hemostasis (ITGB3 1565T>C, FV 1691G>A, FII 20210G>A, MTHFR 677C>T and 1298A>C, ATIII 786G>A, PAI-14G/5G and ACE I/D) were genotyped by real-time PCR system. The frequencies of alleles and genotypes of examined polymorphisms were analyzed in SPSS statistical program, whereas gene interactions were identified using the GMDR software. Examination of etiological factors has shown that family history is a significant factor in assessing individual risk for infertility. The alleles and genotypes frequency of FV 1691G>A and FII 20210G>A polymorphisms were statistically different between control and patient group leading to a greater risk for infertility. The analysis of epistatic relationship between examined hemostasis-related gene polymorphisms identified more complex high-risk genotypes associated with infertility. Our results suggest that positive family history could be important predictive factor for fertility problems, pointing to the potential hereditary basis of this condition. Polymorphisms FVL and FII prothrombin are independent risk factors for idiopathic infertility, whereas multilocus interactions approach should be taken into consideration for the future research. © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Unexplained infertility refers to the absence of a definable cause of reproductive failure. Vitamin D receptor (VDR) acts as a transcription factor and regulates a number of vitamin D-responsive genes, including those involved in the immune system. Recent finding that VDR is expressed in reproductive tissues suggests a possible importance of vitamin D in pregnancy. We conducted a case-control study to examine the association of polymorphisms in VDR gene with reproductive success. DNA from 117 female patients with unexplained infertility and 130 fertile controls was isolated from peripheral blood and VDR genotypes (FokI, BsmI, ApaI and TaqI) were detected by PCR-RFLP. Haplotypes were determined using Haploview software. Our results show significant association of FokI and BsmI polymorphisms with infertility (p < 0.05). The haplotype analysis confirmed strong linkage disequilibrium between closely positioned BsmI, ApaI and TaqI polymorphisms. Two haplotypes were associated with infertility: (i) haplotype bAT was increasing the risk for secondary infertility; while (ii) haplotype BAT had a protective role against primary infertility (p < 0.05). By changing the expression and the activity of VDR gene, which leads to the change in expression of vitamin D-responsive genes, these polymorphisms and haplotypes could possibly have an effect on immune system in the female reproductive tract. © 2018, © 2018 The British Fertility Society.