Role of inflammatory factors in the etiology and treatment of recurrent implantation failure

Wang, Qian; Sun, Yong; Fan, Reiqi; Wang, Mengxue; Ren, Chune; Jiang, Aifang; Yang, Ting‐Ting

doi:10.1016/j.repbio.2022.100698

Cited by 15 publications

(7 citation statements)

References 65 publications

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“…Vaccination-induced elevations in serum levels of activated T cells, 47 production of autoantibodies (eg, antiphospholipid antibody), 48 and temporary immune-mediated disruptions to the hypothalamic-pituitary-ovarian axis 49 can lead to menstrual or ovarian dysfunction as well as impaired embryo implantation. 50 Our study reinforces COVID-19 vaccine safety by demonstrating similarities in key reproductive outcomes between vaccinated and unvaccinated patients undergoing IVF. As COVID-19 continues to be a part of modern life, with the potential formation of novel mutations of varying infectivity and virulence, vaccination remains a critical component of health maintenance.…”

Section: Discussionsupporting

confidence: 76%

Coronavirus Disease 2019 (COVID-19) Vaccination and Assisted Reproduction Outcomes

Chamani

Taylor

Dadoun

et al. 2023

Obstetrics &Amp; Gynecology

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OBJECTIVE: To assess the association between coronavirus disease 2019 (COVID-19) vaccination and female assisted reproduction outcomes through a systematic review and meta-analysis. DATA SOURCES: We searched Medline (OVID), EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov on January 11, 2023, for original articles on assisted reproduction outcomes after COVID-19 vaccination. The primary outcome was rates of clinical pregnancy; secondary outcomes included number of oocytes retrieved, number of mature oocytes retrieved, fertilization rate, implantation rate, ongoing pregnancy rate, and live-birth rate. METHODS OF STUDY SELECTION: Two reviewers independently screened citations for relevance, extracted pertinent data, and rated study quality. Only peer-reviewed published studies were included. TABULATION, INTEGRATION, AND RESULTS: Our query retrieved 216 citations, of which 25 were studies with original, relevant data. Nineteen studies reported embryo transfer outcomes, with a total of 4,899 vaccinated and 13,491 unvaccinated patients. Eighteen studies reported data on ovarian stimulation outcomes, with a total of 1,878 vaccinated and 3,174 unvaccinated patients. There were no statistically significant results among our pooled data for any of the primary or secondary outcomes: clinical pregnancy rate (odds ratio [OR] 0.94, 95% CI 0.88–1.01, P=.10), number of oocytes retrieved (mean difference −0.26, 95% CI −0.68 to 0.15, P=.21), number of mature oocytes retrieved (mean difference 0.31, 95% CI −0.14 to 0.75, P=.18), fertilization rate (OR 0.99, 95% CI 0.87–1.11, P=.83), implantation rate (OR 0.92, 95% CI 0.84–1.00, P=.06), ongoing pregnancy rate (OR 0.95, 95% CI 0.86–1.06, P=.40), or live-birth rate (OR 0.95, 95% CI 0.78–1.17, P=.63). A subanalysis based on country of origin and vaccine type was also performed for the primary and secondary outcomes and did not change the study results. CONCLUSION: Vaccination against COVID-19 is not associated with different fertility outcomes in patients undergoing assisted reproductive technologies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023400023.

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Section: Discussionsupporting

confidence: 76%

Coronavirus Disease 2019 (COVID-19) Vaccination and Assisted Reproduction Outcomes

Chamani

Taylor

Dadoun

et al. 2023

Obstetrics &Amp; Gynecology

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“…Abnormal inflammation is considered a cause of RIF [ 29 ], and elevated levels of inflammation negatively affect sperm and egg quality [ 30 ]. STAT3 acts as an anti-inflammatory factor through activating immune suppressor IL-10 [ 31 , 32 ] while IL-6 and TNF-α are key pro-inflammatory cytokines that mediate the inflammation cascade [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Association between Inflammatory-Related Polymorphism in STAT3, IL-1β, IL-6, TNF-α and Idiopathic Recurrent Implantation Failure

Kwon,

Kim,

Kim

et al. 2023

Genes

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Recurrent implantation failure (RIF) is defined as a failure to achieve pregnancy after multiple embryo transfers. Implantation is closely related to inflammatory gradients, and interleukin-1beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) play a key role in maternal and trophoblast inflammation during implantation. Signal transducer and activator of transcription 3 (STAT3) interacts with cytokines and plays a critical role in implantation through involvement in the inflammation of the embryo and placenta. Therefore, we investigated 151 RIF patients and 321 healthy controls in Korea and analyzed the association between the polymorphisms (STAT3 rs1053004, IL-1β rs16944, IL-6 rs1800796, and TNF-α rs1800629, 1800630) and RIF prevalence. In this paper, we identified that STAT3 rs1053004 (AG, adjusted odds rate [AOR] = 0.623; p = 0.027; GG, AOR = 0.513; p = 0.043; Dominant, AOR = 0.601, p = 0.011), IL-6 rs1800796 (GG, AOR = 2.472; p = 0.032; Recessive, AOR = 2.374, p = 0.037), and TNF-α rs1800629 (GA, AOR = 2.127, p = 0.010, Dominant, AOR = 2.198, p = 0.007) have a significant association with RIF prevalence. This study is the first to investigate the association of each polymorphism with RIF prevalence in Korea and to compare their effect based on their function on inflammation.

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“…The decreased thickness of the endometrium is not conducive to embryo implantation and growth ( Vartanyan, Tsaturova & Devyatova, 2020 ). Endometrial infection and inflammation can lead to aberrant local immune responses in the endometrium and consequently prevent embryo implantation ( Wang et al, 2022 ). Furthermore, the dysregulation of endometrial microbiota has been associated with implantation failure ( Lozano et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting PART1 transcription in the endometrial epithelial cells

Zhang,

Yin,

et al. 2023

PeerJ

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Background In vitro fertilization-embryo transfer (IVF-ET) is a crucial assisted reproductive technology for treating infertility. However, recurrent implantation failure (RIF), a significant challenge in IVF-ET success, remains unresolved. This study aimed to explore the role and mechanism of FLI1 in endometrial receptivity and RIF. Methods Differential endometrial cell proportions between patients with RIF and control subjects were assessed using single-cell RNA sequencing (scRNA-seq) analysis. The chromatin accessibility of FLI1 in the luteal endometrial tissue of patients with RIF and control subjects was examined using the single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq). FLI1 mRNA and protein levels were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Cell viability and migration were examined via cell counting kit (CCK)-8 and scratch healing assays. Epithelial-mesenchymal transition markers were analyzed using western blotting. Mechanisms underlying FLI1’s regulation of PART1 transcription and expression in endometrial epithelial cells were explored using chromatin immunoprecipitation and dual-luciferase reporter assays. Adeno-associated virus (AAV) carrying epithelial cell-specific FLI1/PART1 overexpression sequences was uterinely injected in mice to assess FLI1/PART1 effects. Results scRNA-seq revealed diminished endometrial epithelial cell proportions in RIF patients. Meanwhile, scATAC-seq indicated enhanced chromatin accessibility of FLI1 in these cells. FLI1 exhibited specific expression in RIF patients’ endometrial epithelial cells. Specific FLI1 overexpression inhibited embryo implantation, while knockdown enhanced it. Pregnant mice injected with AAV encoding FLI1 overexpression had significantly lower implantation than AAV-negative controls. FLI1 binding to PART1 promoter heightened PART1 transcription and expression in endometrial epithelial cells. Rescue experiments illustrated FLI1’s role in embryo implantation by boosting PART1 expression. PART1 was notably elevated in RIF patients’ luteal endometrial tissue and non-receptive endometrial epithelial cells (HEC-1-A). Specific PART1 overexpression dampened embryo implantation, whereas knockdown promoted it. Pregnant mice injected with AAV encoding PART1 had lower implantation than negative controls. PART1 knockdown mitigated FLI1’s inhibitory impact on HEC-1-A cell viability and migration. Conclusions FLI1 overexpression in the endometrial epithelial cells of patients with RIF inhibited embryo implantation by binding to the PART1 promoter region to promote PART1 expression. These findings can aid in the development of novel therapeutic targets for RIF.

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Role of inflammatory factors in the etiology and treatment of recurrent implantation failure

Cited by 15 publications

References 65 publications

Coronavirus Disease 2019 (COVID-19) Vaccination and Assisted Reproduction Outcomes

Coronavirus Disease 2019 (COVID-19) Vaccination and Assisted Reproduction Outcomes

Genetic Association between Inflammatory-Related Polymorphism in STAT3, IL-1β, IL-6, TNF-α and Idiopathic Recurrent Implantation Failure

Friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting PART1 transcription in the endometrial epithelial cells

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