scholarly journals Association between HOX Transcript Antisense RNA Single-Nucleotide Variants and Recurrent Implantation Failure

2021 ◽  
Vol 22 (6) ◽  
pp. 3021
Author(s):  
Jeong Yong Lee ◽  
Eun Hee Ahn ◽  
Hyeon Woo Park ◽  
Ji Hyang Kim ◽  
Young Ran Kim ◽  
...  

Recurrent implantation failure (RIF) refers to the occurrence of more than two failed in vitro fertilization–embryo transfers (IVF-ETs) in the same individual. RIF can occur for many reasons, including embryo characteristics, immunological factors, and coagulation factors. Genetics can also contribute to RIF, with some single-nucleotide variants (SNVs) reported to be associated with RIF occurrence. We examined SNVs in a long non-coding RNA, homeobox (HOX) transcript antisense RNA (HOTAIR), which is known to affect cancer development. HOTAIR regulates epigenetic outcomes through histone modifications and chromatin remodeling. We recruited 155 female RIF patients and 330 healthy controls, and genotyped HOTAIR SNVs, including rs4759314, rs920778, rs7958904, and rs1899663, in all participants. Differences in these SNVs were compared between the patient and control groups. We identified significant differences in the occurrence of heterozygous genotypes and the dominant expression model for the rs1899663 and rs7958904 SNVs between RIF patients and control subjects. These HOTAIR variants were associated with serum hemoglobin (Hgb), luteinizing hormone (LH), total cholesterol (T. chol), and blood urea nitrogen (BUN) levels, as assessed by analysis of variance (ANOVA). We analyzed the four HOTAIR SNVs and found significant differences in haplotype patterns between RIF patients and healthy controls. The results of this study showed that HOTAIR is not only associated with the development of cancer but also with pregnancy-associated diseases. This study represents the first report showing that HOTAIR is correlated with RIF.

2010 ◽  
Vol 93 (2) ◽  
pp. 437-441 ◽  
Author(s):  
Erika B. Johnston-MacAnanny ◽  
Janice Hartnett ◽  
Lawrence L. Engmann ◽  
John C. Nulsen ◽  
M. Melinda Sanders ◽  
...  

Author(s):  
İrem Gülfem Albayrak ◽  
Fatemeh Azhari ◽  
Ezgi Nur Çolak ◽  
Burçin Karamustafaoğlu Balcı ◽  
Ege Ülgen ◽  
...  

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Chang Soo Ryu ◽  
Young Ran Kim ◽  
Jung Oh Kim ◽  
Hui Jeong An ◽  
Sung Hwan Cho ◽  
...  

Abstract Recurrent implantation failure (RIF) is a common reproductive clinical condition treated by fertility specialists at in vitro fertilization (IVF) clinics. Several factors affect embryo implantation including the age of the female, the quality of embryos and the sperm, genetics, immunologic factors. Here, we investigated the association of Argonaute 1 (AGO1) and Argonaute 2 (AGO2) polymorphisms and RIF. We collected blood samples from 167 patients with RIF and 211 controls. Genetic polymorphisms were detected by polymerase chain reaction (PCR) – restriction fragment length polymorphism analysis and real-time PCR. We found that the AGO2 rs4961280C>A polymorphism (adjusted odds ratio [AOR] = 1.984; P = 0.023) was significantly associated with RIF. Furthermore, in RIF patients with three or more consecutive implantation failure, the AGO2 rs4961280C>A CA genotype (AOR = 2.133; P = 0.013) and dominant model (AOR = 2.272; P = 0.006) were both significantly associated with prevalence of RIF. An analysis of variance revealed that patients with the AGO2 rs2292779C>G genotypes (CC: 6.52 ± 2.55; CG: 7.46 ± 3.02; GG: 8.42 ± 2.74; P = 0.044) and the dominant model (CC: 6.52 ± 2.55; CG+GG: 7.70 ± 2.97; P = 0.029) exhibited significantly increased white blood cell levels. Furthermore, patients with the AGO1 rs595961G>A dominant model (GG: 36.81 ± 8.69; GA+AA: 31.58 ± 9.17; P = 0.006) and the AGO2 rs4961280C>A recessive model (CC+CA: 35.42 ± 8.77; AA: 22.00 ± 4.24; P = 0.035) exhibited a significantly decreased number of CD4+ helper T cells. Our study showed that AGO1 and AGO2 polymorphisms are associated with the prevalence of RIF. Hence, the results suggest that variations in AGO1 and AGO2 genotypes may be useful clinical biomarkers for the development and prognosis of RIF.


Author(s):  
Xavier Santamaria ◽  
Carlos Simón

AbstractUnexplained infertility (UI) and recurrent implantation failure (RIF) are diagnoses based on failed pregnancy attempts within current infertility treatment models. Both diagnoses are made when fertility is unexplained based on current diagnostic methods and has no clear cause; UI is diagnosed when testing is inconclusive, and RIF is diagnosed after three failed in vitro fertilization cycles. In both cases, interventions are often introduced without an understanding of the cause of the infertility, frequently leading to frustration for patients and caregivers. Here, we review evidence to support an influence of endometrial factor in patients given these poorly defined diagnoses and possible treatments targeting the endometrium to improve outcomes in these patients.


2019 ◽  
Author(s):  
Min Fu ◽  
Xiaowei Zhang ◽  
Weiping Qian ◽  
Yiheng Liang ◽  
Shouren Lin ◽  
...  

Abstract In vitro fertilization-embryo transfer (IVF-ET) is now widely applied in treating infertility. As the number of IVF cycles continues to increase, recurrent implantation failure (RIF) has become a big challenge. The cause of RIF is very complex and remains largely unrevealed, especially for those without any pathological features. It has been proved that vaginal microbiota is associated with many female reproductive diseases, such as pregnancy-related diseases, sexually transmitted diseases, tubal factor infertility, and first trimester miscarriage after in vitro fertilization (IVF) and so on. Hence, vaginal microbiota and its metabolome may also relate to RIF. In this study, we characterized the vaginal microbiota and metabolome of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first IVF cycle were used as controls. Results Based on 16S rDNA sequencing of the vaginal microbiota, the RIF group presented higher microbial α-diversity than the control group (0.80±0.50 vs 0.50±0.39, P-value=0.016) and harbored more non-Lactobacillus microorganisms, including 25 significantly increased genera of both aerobic and anaerobic bacteria. The metabolomic profile showed that the relative abundances of 37 metabolites among 2,507 metabolites were significantly different between the two groups. Among them, 2',3-cyclic UMP and phosphoinositide were the top two metabolites significantly upregulated in the RIF group, while glycerophospholipids and benzopyran were important metabolites that were significantly downregulated. Lysobisphosphatidic acid (LPA) and prostaglandin (PG) metabolized from glycerophospholipids are key factors affecting implantation and decidualization. Benzopyran, as a selective estrogen receptor modulator (SERM), may affect the outcome of pregnancy. All of the metabolome outcomes may result in or from the differential microbiota composition in the RIF patients. Conclusions In conclusion, significant differences were presented in the vaginal microbiota and metabolome between RIF patients and women who became pregnant in the first IVF cycle, which are related to embryo implantation. This study not only deeply investigates the relationship between RIF and the vaginal microbial community and its metabolites but also provides a profound understanding of the pathogenesis of RIF.


2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Jeong Yong Lee ◽  
Eun Hee Ahn ◽  
Jung Oh Kim ◽  
Han Sung Park ◽  
Chang Soo Ryu ◽  
...  

Abstract Background Recurrent implantation failure (RIF) is the failure of embryos to implant more than two times in a given individual. There is debate about a precise definition for RIF, but we consider more than two implantation failures for individuals who undergo in vitro fertilization-embryo transfer (IVF-ET) to constitute RIF. There are many potential reasons for RIF, including embryonic factors, immunological factors, uterine factors, coagulate factors, and genetic factors. Genetic variation has been suggested as one of the contributing factors leading to RIF, and a number of single-nucleotide polymorphisms (SNPs) have been reported to be associated with RIF. The recent elucidation of miRNA functions has provided new insight into the regulation of gene expression. Methods We investigated associations between polymorphisms in four miRNAs and RIF in 346 Korean women: 118 patients with RIF and 228 controls. We determined the genotypes of the miRNAs in the study participants by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis. We analyzed the effects of genotypes, allele combinations, and environmental and clinical factors on the risk of RIF. Results The miR-25 T/miR-125aT/miR-222G (odds ratio (OR), 0.528; 95% confidence interval (CI), 0.282–0.990; P = 0.044) and miR-25 T/miR-125aT allele combinations were associated with a reduced risk of RIF. The miR-25 T/miR-32C/miR-125aC/miR-222 T allele combination was associated with an increased risk of RIF. The miR-222GT+TT genotypes interacted with high prothrombin time (≥ 12 s) to increase the risk of RIF. Conclusions MicroRNA polymorphisms are significantly different between patients that experience RIF and healthy controls. Combinations of microRNA polymorphisms were associated with the risk of RIF. Interactions between environmental factors and genotypes increased the risk of RIF in Korean women.


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