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<p>Unexplained infertility (UI) and recurrent pregnancy loss (RPL) pose substantial challenges in reproductive medicine, often arising from impaired endometrial receptivity during the critical implantation window. This narrative review synthesizes current evidence on the role of genetic polymorphisms in key regulatory genes interleukin-2 (IL-2), thrombin-activatable fibrinolysis inhibitor (TAFI), progestagen-associated endometrial protein (PAEP), and vascular endothelial growth factor (VEGF) in modulating immune responses, fibrinolytic balance, uterine remodeling, and angiogenesis. We explore how single nucleotide polymorphisms (SNPs) in these genes influence molecular and cellular mechanisms essential for successful embryo implantation and pregnancy maintenance. The review highlights associations of specific SNPs such as IL-2 -330 T/G, TAFI Thr325Ile, VEGF − 1154 G/A, and VEGF − 2578&#xa0;C/A with altered gene expression and protein function, contributing to implantation failure, pregnancy loss, and infertility. Understanding these genetic factors enhances insights into the pathogenic pathways of UI and RPL and may guide the development of diagnostic markers and personalized therapeutic strategies to improve reproductive outcomes.</p>

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The genetic landscape of implantation: how IL-2, TAFI, PAEP, and VEGF variants impact fertility outcomes

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月20日

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  • Bita Moudi,
  • Zahra Heidari,
  • Marzieh Ghasemi

摘要

Unexplained infertility (UI) and recurrent pregnancy loss (RPL) pose substantial challenges in reproductive medicine, often arising from impaired endometrial receptivity during the critical implantation window. This narrative review synthesizes current evidence on the role of genetic polymorphisms in key regulatory genes interleukin-2 (IL-2), thrombin-activatable fibrinolysis inhibitor (TAFI), progestagen-associated endometrial protein (PAEP), and vascular endothelial growth factor (VEGF) in modulating immune responses, fibrinolytic balance, uterine remodeling, and angiogenesis. We explore how single nucleotide polymorphisms (SNPs) in these genes influence molecular and cellular mechanisms essential for successful embryo implantation and pregnancy maintenance. The review highlights associations of specific SNPs such as IL-2 -330 T/G, TAFI Thr325Ile, VEGF − 1154 G/A, and VEGF − 2578 C/A with altered gene expression and protein function, contributing to implantation failure, pregnancy loss, and infertility. Understanding these genetic factors enhances insights into the pathogenic pathways of UI and RPL and may guide the development of diagnostic markers and personalized therapeutic strategies to improve reproductive outcomes.