The molecular puzzle of recurrent implantation failure: integrating genetic, epigenetic, and immune mechanisms for precision reproductive medicine

Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12(6):731–46.

Article  PubMed  Google Scholar 

Busnelli A, Reschini M, Cardellicchio L, Vegetti W, Somigliana E, Vercellini P. How common is real repeated implantation failure? An indirect estimate of the prevalence. Reprod Biomed Online. 2020;40(1):91–7.

Article  PubMed  Google Scholar 

Bashiri A, Halper KI, Orvieto R. Recurrent implantation failure-update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol. 2018;16:1–18.

Article  Google Scholar 

Dehghan Z, Salehi M. The expression of miR-31 and its target gene FOXP3 in recurrent implantation failure patients. Int J Womens Health Reprod Sci. 2020;8:389–95.

Article  Google Scholar 

Mrozikiewicz AE, Kurzawińska G, Ożarowski M, Walczak M, Ożegowska K, Jędrzejczak P. Polymorphic variants of genes encoding angiogenesis-related factors in infertile women with recurrent implantation failure. Int J Mol Sci. 2023;24(5):4267.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nowak I, Wilczyńska K, Wilczyński JR, Malinowski A, Radwan P, Radwan M, et al. KIR, LILRB and their ligands’ genes as potential biomarkers in recurrent implantation failure. Arch Immunol Ther Exp. 2017;65:391–9.

Article  CAS  Google Scholar 

Dong X, Zhou M, Li X, Huang H, Sun Y. Gene profiling reveals the role of inflammation, abnormal uterine muscle contraction and vascularity in recurrent implantation failure. Front Genet. 2023;14:1108805.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim JO, Ahn EH, Sakong JH, An HJ, Park HS, Kim YR, et al. Association of miR-27a A> G, miR-423 C> a, miR-449b A> G, and miR-604 A> G polymorphisms with risk of recurrent implantation failure. Reprod Sci. 2020;27:29–38.

Article  CAS  PubMed  Google Scholar 

Turienzo A, Lledó B, Ortiz JA, Morales R, Sanz J, Llácer J, et al. Prevalence of candidate single nucleotide polymorphisms on p53, IL-11, IL-10, VEGF and APOE in patients with repeated implantation failure (RIF) and pregnancy loss (RPL). Hum Fertil. 2018. https://doi.org/10.1080/14647273.2018.1524935.

Article  Google Scholar 

Lee Y, Ahn EH, Ryu CS, Kim JO, An HJ, Cho SH, et al. Association between microRNA machinery gene polymorphisms and recurrent implantation failure. Exp Ther Med. 2020;19(4):3113–23.

CAS  PubMed  PubMed Central  Google Scholar 

Fraire-Zamora JJ, Liperis G, Serdarogullari M, Ammar OF, Pirtea P, Viganò P, et al. Recurrent implantation failure: science or fiction? Hum Reprod. 2025;40(3):565–9.

Article  PubMed  Google Scholar 

Ma J, Gao W, Li D. Recurrent implantation failure: a comprehensive summary from etiology to treatment. Front Endocrinol (Lausanne). 2022;13:1061766.

Article  PubMed  Google Scholar 

Magdi Y, El-Damen A, Fathi AM, Abdelaziz AM, Abd-Elfatah Youssef M, Abd-Allah AA, et al. Revisiting the management of recurrent implantation failure through freeze-all policy. Fertil Steril. 2017;108(1):72–7.

Article  PubMed  Google Scholar 

Zhao Y, He D, Zeng H, Luo J, Yang S, Chen J, et al. Expression and significance of miR-30d-5p and SOCS1 in patients with recurrent implantation failure during implantation window. Reprod Biol Endocrinol. 2021;19:1–10.

Article  CAS  Google Scholar 

Sun Y, Cui L, Lu Y, Tan J, Dong X, Ni T, et al. Prednisone vs placebo and live birth in patients with recurrent implantation failure undergoing in vitro fertilization: a randomized clinical trial. JAMA. 2023;329(17):1460–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee HA, Ahn EH, Jang HG, Kim JO, Kim JH, Lee YB, et al. Association between miR-605 A> G, miR-608 G> C, miR-631 I> D, miR-938 C> T, and miR-1302-3 C> T polymorphisms and risk of recurrent implantation failure. Reprod Sci. 2019;26(4):469–75.

Article  CAS  PubMed  Google Scholar 

Li H, Su N, Zhu Y, Wang W, Cai M, Luo X, Xia W, Quan S. Growth hormone inhibits the JAK/STAT3 pathway by regulating SOCS1 in endometrial cells in vitro: a clue to enhance endometrial receptivity in recurrent implantation failure. European Journal of Histochemistry: EJH. 2022;67(1):3580.

Article  Google Scholar 

Lai Z-Z, Wang Y, Zhou W-J, Liang Z, Shi J-W, Yang H-L, et al. Single-cell transcriptome profiling of the human endometrium of patients with recurrent implantation failure. Theranostics. 2022;12(15):6527.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Guo F, Si C, Zhou M, Wang J, Zhang D, Leung PC, et al. Decreased PECAM1-mediated TGF-β1 expression in the mid-secretory endometrium in women with recurrent implantation failure. Hum Reprod. 2018;33(5):832–43.

Article  CAS  PubMed  Google Scholar 

Liu C, Yao W, Yao J, Li L, Yang L, Zhang H, et al. Endometrial extracellular vesicles from women with recurrent implantation failure attenuate the growth and invasion of embryos. Fertil Steril. 2020;114(2):416–25.

Article  CAS  PubMed  Google Scholar 

Paul AB, Sadek ST, Mahesan AM. The role of microRNAs in human embryo implantation: a review. J Assist Reprod Genet. 2019;36:179–87.

Article  PubMed  Google Scholar 

Zhang M, Cai X, Liu J, Zhou J, Shi Q, Jiang Y, et al. A novel lncRNA lncSAMD11-1: 1 interacts with PIP4K2A to promote endometrial decidualization by stabilizing FoxO1 nuclear localization. Int J Biochem Cell Biol. 2022;151:106280.

Article  CAS  PubMed  Google Scholar 

Piekarska K, Radwan P, Tarnowska A, Radwan M, Wilczyński JR, Malinowski A, et al. ERAP/HLA-C and KIR genetic profile in couples with recurrent implantation failure. Int J Mol Sci. 2022;23(20):12518.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen W, Yang Q, Hu L, Wang M, Yang Z, Zeng X, et al. Shared diagnostic genes and potential mechanism between PCOS and recurrent implantation failure revealed by integrated transcriptomic analysis and machine learning. Front Immunol. 2023;14:1175384.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao X, Zhao Y, Jiang Y, Zhang Q. Deciphering the endometrial immune landscape of RIF during the window of implantation from cellular senescence by integrated bioinformatics analysis and machine learning. Front Immunol. 2022;13:952708.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bastu E, Mutlu MF, Yasa C, Dural O, Aytan AN, Celik C, Buyru F, Yeh J. Role of Mucin 1 and Glycodelin A in recurrent implantation failure. Fertility and sterility. 2015;103(4):1059–64.

Article  CAS  PubMed  Google Scholar 

Lozano FM, Lledó B, Morales R, Cascales A, Hortal M, Bernabeu A, et al. Characterization of the endometrial microbiome in patients with recurrent implantation failure. Microorganisms. 2023;11(3):741.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pirtea P, Cedars MI, Devine K, Ata B, Franasiak J, Racowsky C, et al. Recurrent implantation failure: reality or a statistical mirage?: Consensus statement from the July 1, 2022 Lugano Workshop on recurrent implantation failure. Obstetrical & Gynecological Survey. 2023. https://doi.org/10.1097/ogx.0000000000001189.

Article  Google Scholar 

Saifitdinova AF, Glotov OS, Poliakova IV, Bichevaya NK, Loginova JA, Kuznetsova RA, et al. Mosaicism in preimplantation human embryos. Integrative Physiology. 2020;1(3):225–30.

Article  Google Scholar 

Pei Z, Deng K, Lei C, Du D, Yu G, Sun X, et al. Identifying balanced chromosomal translocations in human embryos by Oxford nanopore sequencing and breakpoints region analysis. Front Genet. 2021;12:810900.

Article  CAS  PubMed  Google Scholar 

Canovas S, Ross PJ, Kelsey G, Coy P. DNA methylation in embryo development: epigenetic impact of ART (assisted reproductive technologies). Bioessays. 2017;39(11):1700106.

Article  Google Scholar 

Sciorio R, Manna C, Fauque P, Rinaudo P. Can cryopreservation in assisted reproductive technology (art) induce epigenetic changes to gametes and embryos? J Clin Med. 2023;12(13):4444.

Article  CAS 

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