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The growing prevalence of in vitro fertilization-embryo transfer procedures has resulted in an increased incidence of recurrent implantation failure (RIF), necessitating focused research in this area. STAT3, a key factor in maternal endometrial remodeling and stromal proliferation, is crucial for successful embryo implantation. While the relationship between STAT3 and RIF has been studied, the impact of single nucleotide polymorphisms (SNPs) in miRNAs, well-characterized gene expression modulators, on STAT3 in RIF cases remains uncharacterized. Here, we investigated 161 RIF patients and 268 healthy control subjects in the Korean population, analyzing the statistical association between miRNA genetic variants and RIF risk. We aimed to determine whether SNPs in specific miRNAs, namely miR-218-2 rs11134527 G>A, miR-34a rs2666433 G>A, miR-34a rs6577555 C>A, and miR-130a rs731384 G>A, were significantly associated with RIF risk. We identified a significant association between miR-34a rs6577555 C>A and RIF prevalence (implantation failure [IF] ≥ 2: adjusted odds ratio [AOR] = 2.264, 95% CI = 1.007–5.092, p = 0.048). These findings suggest that miR-34a rs6577555 C>A may contribute to an increased susceptibility to RIF. However, further investigations are necessary to elucidate the precise mechanisms underlying the role of miR-34a rs6577555 C>A in RIF. This study sheds light on the genetic and molecular factors underlying RIF, offering new avenues for research and potential advancements in the diagnosis and treatment of this complex condition. [ABSTRACT FROM AUTHOR]

Recurrent implantation failure (RIF) refers to two or more unsuccessful in vitro fertilization embryo transfers in the same individual. Embryonic characteristics, immunological factors, and coagulation factors are known to be the causes of RIF. Genetic factors have also been reported to be involved in the occurrence of RIF, and some single nucleotide polymorphisms (SNPs) may contribute to RIF. We examined SNPs in FSHR, INHA, ESR1, and BMP15, which have been associated with primary ovarian failure. A cohort of 133 RIF patients and 317 healthy controls consisting of all Korean women was included. Genotyping was performed by Taq-Man genotyping assays to determine the frequency of the following polymorphisms: FSHR rs6165, INHA rs11893842 and rs35118453, ESR1 rs9340799 and rs2234693, and BMP15 rs17003221 and rs3810682. The differences in these SNPs were compared between the patient and control groups. Our results demonstrate a decreased prevalence of RIF in subjects with the FSHR rs6165 A>G polymorphism [AA vs. AG adjusted odds ratio (AOR) = 0.432; confidence interval (CI) = 0.206–0.908; p = 0.027, AA+AG vs. GG AOR = 0.434; CI = 0.213–0.885; p = 0.022]. Based on a genotype combination analysis, the GG/AA (FSHR rs6165/ESR1 rs9340799: OR = 0.250; CI = 0.072–0.874; p = 0.030) and GG-CC (FSHR rs6165/BMP15 rs3810682: OR = 0.466; CI = 0.220–0.987; p = 0.046) alleles were also associated with a decreased RIF risk. Additionally, the FSHR rs6165GG and BMP15 rs17003221TT+TC genotype combination was associated with a decreased RIF risk (OR = 0.430; CI = 0.210–0.877; p = 0.020) and increased FSH levels, as assessed by an analysis of variance. The FSHR rs6165 polymorphism and genotype combinations are significantly associated with RIF development in Korean women. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the potential association of five miRNA machinery gene polymorphisms (DICER1 rs3742330A>G, DROSHA rs10719T>C, RAN rs14035C>T, XPO5 rs11077A>C and DGCR8 rs417309G>A) with recurrent implantation failure (RIF), a clinical condition in which good-quality embryos repeatedly fail to implant following two or more in vitro fertilization cycles, and its associated risk factors in Korean women. Therefore, the present study performed genotype analysis and assessed the frequency of these miRNA gene polymorphisms in patients diagnosed with RIF (n=119) and randomly selected controls (n=210) with at least one live birth and no history of pregnancy loss. The DROSHA rs10719T>C and RAN rs14035C>T polymorphisms were identified to be significantly associated with decreased prevalence of RIF. Additionally, the DROSHA rs10719 TC and the RAN rs14035 CT genotypes were present at significantly lower frequencies in the RIF group than in the control group (adjusted odds ratio=0.550; 95% CI, 0.339-0.893; P=0.016; and adjusted odds ratio=0.590; 95% CI, 0.363-0.958; P=0.033, respectively). Furthermore, the combined RAN rs14035 CT+TT genotype was observed to be associated with decreased RIF prevalence (adjusted odds ratio=0.616; 95% CI, 0.386-0.982; P=0.042). Genotype combination analysis for the various miRNA polymorphisms revealed that the DROSHA TC genotype exhibited a highly significant negative association with RIF prevalence when combined with the RAN CT genotype (adjusted odds ratio=0.314; 95% CI, 0.147-0.673; P=0.003; false discovery rate-adjusted P=0.023). The present study revealed an association between the DROSHA rs10719 and RAN rs14035 3'UTR polymorphisms and decreased risk of RIF in Korean women, which suggests that these gene polymorphisms could represent potential markers for predicting RIF risk. [ABSTRACT FROM AUTHOR]

Recurrent implantation failure (RIF) is diagnosed when pregnancy failure occurs after 2 consecutive in vitro fertilization–embryo transfers (IVF-ET) to the endometrium using at least 4 high-quality embryos. MicroRNAs (miRNAs) are a class of small noncoding RNA and reported to play an important role in cell proliferation as well as implantation process. Recently, it has been reported that miRNA can regulate RIF occurrence. So, we were to examine the association between the specific miRNA polymorphisms and RIF in Korean women. Genotyping was performed by polymerase chain reaction—restriction fragment length polymorphism (PCR-RFLP) assay to determine the frequency of the following polymorphisms: miR-605A>G, miR-608G>C, miR-631I>D, miR-938C>T, and miR-1302-3C>T. Our results demonstrate a decreased incidence of RIF in patients with the miR-1302-3C>T polymorphism (adjusted odds ratio [AOR], 0.234; 95% confidence interval [CI], 0.089-0.618; P = .003). Based on our allele combination analysis, the C-T (miR-938/miR-1302-3: OR = 0.259; 95% CI, 0.100-0.674; P = .003) allele was also associated with decreased RIF risk. From our interaction analysis with miR-1302-3, the miR-1302-3CC genotype (AOR = 43.332; 95% CI, 5.576-336.745) showed an association with RIF prevalence in participants with an activated partial thromboplastin time (aPTT) ≤22.6. We found that the miR-1302-3C>T polymorphism is significantly associated with RIF development in Korean women. Specifically, our study suggests that the T allele of miR-1302-3 may decrease the risk of RIF in Korean women. [ABSTRACT FROM AUTHOR]

The objective of the present study was to investigate the association between recurrent implantation failure (RIF) and vascular endothelial growth factor (VEGF) gene polymorphisms that are associated with various female infertility disorders. A total of 116 women diagnosed with RIF and 218 control subjects were genotyped for the VEGF -2578C>A, -1154G>A, -634C>G and 936C>T polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism assay. The VEGF -2578AA genotype was associated with an increased prevalence (≥4) of RIF [adjusted odds ratio (AOR)=2.77; 95% confidence interval (CI)=1.10-7.02; P=0.031], whereas the VEGF -634CG+GG genotype was associated with an increased incidence of total RIF (AOR=2.03; 95% CI=1.02-4.05; P=0.044) and ≥4 RIF (AOR=3.16; 95% CI=1.19-8.37; P=0.021). The results of the haplotype analysis indicated that -2578A/-1154A/-634G/936C (AOR=1.76; 95% CI=1.03-3.00; P=0.040 for total RIF and AOR=2.11; 95% CI=1.12-3.97; P=0.021 for ≥4 RIF) was associated with the occurrence of RIF. In addition, it was revealed that there was a significant difference in serum prolactin level associated with the VEGF -634C>G polymorphism (P=0.013). Therefore the findings of the present study indicate that the VEGF -2578AA genotype, -634G allele and -2578A/-1154A/-634G/936C haplotype may be genetic markers for susceptibility to RIF. However, further studies on VEGF promoter polymorphisms that include an independent randomized-controlled population are required to confirm these results. [ABSTRACT FROM AUTHOR]