Successful pregnancy depends on precise molecular regulation of uterine physiology, especially during the menstrual cycle. Deregulated oxidative stress (OS), often influenced by inflammatory changes but also by environmental factors, represents a constant threat to this delicate balance. Oxidative stress induces a reciprocally regulated nuclear factor erythroid 2-related factor 2/peroxisome proliferator-activated receptor-gamma (Nrf2/PPARγ) pathway. However, increased PPARγ activity appears to be a double-edged sword in endometrial physiology. Activated PPARγ attenuates inflammation and attenuates OS to restore redox homeostasis. However, it also interferes with physiological processes during the menstrual cycle, such as hormonal signaling and angiogenesis. This review provides an elucidation of the molecular mechanisms that support the interplay between PPARγ and OS. Additionally, it offers fresh perspectives on the Nrf2/PPARγ pathway concerning endometrial receptivity and its potential implications for infertility.

The increased interest in assisted reproduction through in vitro fertilization (IVF) leads to an urgent need to identify biomarkers that reliably highly predict the success of pregnancy. Despite advances in diagnostics, treatment, and IVF approaches, the 30% success rate of IVF seems insurmountable. Idiopathic infertility does not have any explanation for IVF failure especially when a patient is treated with a healthy competitive embryo capable of implantation and development. Since appropriate intercellular communication is essential after embryo implantation, the emergence of the investigation of embryonic secretome including short non-coding RNA (sncRNA) molecules is crucial. That’s why biomarker identification, sncRNAs secreted during the IVF process into the blastocyst’s cultivation medium, by the implementation of artificial intelligence opens the door to a better understanding of the bidirectional communication between embryonic cells and the endometrium and so the success of the IVF. This study presents a set of promising new sncRNAs which are revealed to predictively distinguish a high-quality embryo, suitable for an embryo transfer in the IVF process, from a low-quality embryo with 86% accuracy. The identified exact combination of miRNAs/piRNAs as a non-invasively obtained biomarker for quality embryo determination, increasing the likelihood of implantation and the success of pregnancy after an embryo transfer.

Purpose: In vitro fertilization occurs in a controlled laboratory setting, where oocytes are fertilized by sperm, and the resulting embryos are cultured to the blastocyst stage before transfer to the uterus. The secreted/consumed substances by the embryo in the extracellular environment (secretome) contain a variety of molecules that may provide insights into embryo quality. This study presents new perspectives on the non-invasive and cost-effective assessment and evaluation of embryos during the IVF process, utilizing a spent embryo culture medium (SECM). Methods: The SECM was used from blastocysts prepared for a single blastocyst transfer and was analyzed in two groups—the SECM with successful (F) (n = 30) and unsuccessful (N) (n = 36) embryo implantation in the woman's uterus. Building on our previous next-generation sequencing results, we decided to validate the expression levels of specific miRNAs, particularly hsa-miR-16-5p and hsa-miR-92a-3p, to assess their potential to predict embryo implantation success. Results: Our results demonstrate different expression levels of miRNA molecules in the monitored groups, which could lead to their use in non-invasive analysis of the implantation potential of embryos in the IVF process. In this study, we employed a metabolomics approach using 3D fluorescence analysis of SECM to identify differences between the studied groups, F and N. Our preliminary results indicate a slightly increased metabolic activity in the group with unsuccessful embryo implantation group. Conclusions: This is our pilot study where we demonstrated the use of two approaches in analyzing the SECM to predict the implantation potential of embryos in the IVF process which promises further development.

Infertility affects approximately one in six couples worldwide and can be caused by a variety of male and female factors, requiring a comprehensive diagnostic evaluation. In vitro fertilization (IVF) is a widely used assisted reproductive technology; however, despite advances in embryo culture systems, implantation and transfer success rates remain below 30%. Current IVF practice strongly relies on embryologists’ ability to select high-quality, euploid embryos for transfer. Nevertheless, embryo quality alone does not determine successful pregnancy outcomes. Implantation depends on complex biochemical and molecular interactions between the embryo and the receptive uterine endometrium. This review summarizes current knowledge on the molecular mechanisms underlying preimplantation embryo development and implantation. Particular attention is given to embryo metabolism, embryo–endometrium communication, and decidualization processes. Understanding these molecular pathways may facilitate the identification of novel biomarkers associated with embryo viability, implantation potential, and uterine receptivity, ultimately contributing to improved diagnostics and therapeutic strategies in female infertility research and assisted reproduction.