The success of in vitro fertilization (IVF) and female reproductive capacity are significantly determined by oocyte quality. Increasing data highlights the significance of oxidative stress—a state of imbalance between reactive oxygen species (ROS) and antioxidant defenses—in regulating oocyte competence. Normal folliculogenesis and ovulation rely on optimal ROS levels; excessive oxidative stress (OS) can lead to DNA fragmentation, undermine meiotic spindle integrity, and trigger apoptosis in cumulus and granulosa cells. Molecular insults impair nuclear and cytoplasmic maturation, thereby impacting fertilization potential and embryonic development. Individuals with polycystic ovarian syndrome (PCOS), endometriosis, advanced maternal age, and metabolic disorders—conditions associated with suboptimal IVF outcomes—frequently exhibit redox imbalance. This narrative review examines significant oxidative markers in the follicular environment, exploring the molecular processes linking OS to diminished oocyte quality and discussing therapy techniques aimed at mitigating oxidative damage. Maintaining redox homeostasis in the ovarian milieu appears to be an effective strategy for enhancing oocyte competence and optimizing outcomes in assisted reproduction.

The functional deterioration of granulosa cells (GCs), essential for follicular growth, steroidogenesis, and oocyte competence, indicates ovarian aging and reduced fertility. An expanding corpus of research indicates that oxidative stress is a primary molecular contributor to granulosa cell dysfunction, culminating in mitochondrial impairment, reduced metabolic support for oocytes, and the activation of regulated apoptotic pathways that end in follicular atresia. Ferroptosis, an emergent type of iron-dependent lipid peroxidation, has been identified as a crucial mechanism contributing to chemotherapy-induced ovarian insufficiency, polycystic ovary syndrome (PCOS), and granulosa cell death in aging ovaries, in addition to conventional apoptosis. The SIRT1-Nrf2 axis acts as a crucial anti-oxidative and anti-ferroptotic system that protects GC viability, maintains mitochondrial homeostasis, and upholds redox equilibrium. SIRT1 promotes mitochondrial biogenesis and metabolic resilience by deacetylating downstream proteins, including FOXO3 and PGC-1α. Nrf2 simultaneously controls the transcriptional activation of detoxifying and antioxidant enzymes, including HO-1, SOD2, NQO1, and GPX4, which are critical inhibitors of ferroptosis. Disruption of SIRT1-Nrf2 signalling accelerates GC senescence, follicular depletion, and reproductive aging. In contrast, pharmaceutical and nutraceutical therapies, including metformin, melatonin, resveratrol, and agents that increase NAD⁺ levels, may reverse ovarian deterioration and reactivate SIRT1-Nrf2 activity. This narrative review highlights innovative treatment prospects for ovarian aging, fertility preservation, and assisted reproduction by synthesising current evidence on ferroptotic pathways, SIRT1-Nrf2 interactions, and oxidative stress in granulosa cells. An understanding of these interrelated biological networks enables the development of tailored therapies that postpone ovarian ageing and enhance reproductive outcomes for women receiving fertility therapy.

Exosomal microRNAs (ex-miRs), encapsulated in extracellular vesicles (EVs), play a vital role in facilitating paracrine communication among granulosa cells (GCs), cumulus cells (CCs), and the oocyte inside follicular fluid (FF). These small non-coding RNAs are crucial for regulating folliculogenesis, oocyte maturation, and early embryonic development via modulating intracellular signaling networks. Dysregulation o has been associated with reproductive disorders such as polycystic ovarian syndrome (PCOS), diminished ovarian reserve (DOR), and inadequate ovarian response (POR), impacting oocyte quality and fertility outcomes. This narrative review consolidates molecular data from current human and animal studies regarding ex-miR expression patterns, functional targets, and pathway involvement within the context of assisted reproductive technologies (ARTs). A literature-based analysis was undertaken, focusing on signaling pathways, pathogenic processes, and clinical implications. Specifically, ex-miRs—such as miR-21, miR-34c, miR-143-3p, miR-155-5p, miR-339-5p, and miR-424-5p—were identified as regulators of critical pathways including phosphoinositide 3-kinase (PI3K)–AKT, ERK1/2, TGF-β/SMAD, and Rb–E2F1. These ex-miRs regulate apoptosis, glycolysis, mitochondrial function, and cell cycle expansion to influence oocyte competence. Pathological patterns in PCOS and POR are associated with altered ex-miR expression that disrupts metabolic and developmental signaling. Research utilizing animal models confirmed that modifications in EV-associated miRNA influence in vitro maturation (IVM) efficiency and blastocyst quality. Ex-miRs serve as intriguing non-invasive biomarkers and potential therapeutic targets for ARTs. Their mechanical involvement in oocyte and follicular physiology positions them for integration into forthcoming precision-based infertility therapies. For its implementation in reproductive medicine, EV profiling requires standardization and further functional validation in clinical environments.

Background: Endometrial receptivity is crucial for successful embryo implantation in assisted reproductive technologies (ARTs). MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) have emerged as important post-transcriptional regulators of endometrial function, although their diagnostic and molecular functions are poorly understood. Methods: A systematic review was conducted following PRISMA 2020 principles and registered in PROSPERO (CRD420251001811). We looked at 28 peer-reviewed publications published between 2010 and 2025 that used endometrial tissue, blood, uterine fluid, saliva, and embryo culture medium to study miRNAs and other non-coding RNAs in endometrial receptivity, recurrent implantation failure (RIF), and infertility. Results: MiRNAs like miR-145, miR-30d, miR-223-3p, and miR-125b influence implantation-related pathways such as HOXA10, LIF-STAT3, PI3K-Akt, and Wnt/β-catenin. Dysregulated expression profiles were linked to inadequate decidualization, immunological imbalance, and poor angiogenesis. CeRNA networks that include lncRNAs (e.g., H19 and NEAT1) and circRNAs (e.g., circ_0038383) further regulate miRNA activity. Non-invasive biomarkers derived from plasma, uterine fluid, and embryo media showed high prediction accuracy for implantation outcomes. Conclusions: MiRNA signatures offer a functional and diagnostic blueprint for endometrial receptivity. This systematic review provides a timely and thorough synthesis of the existing literature, with the goal of bridging the gap between molecular discoveries and therapeutic applications. By emphasizing both the mechanistic importance and diagnostic value of certain miRNA signatures, it paves the way for future precision-based techniques in embryo transfer and endometrial assessment in ART.

Background: Epigenetic modifications have an important role in controlling ovarian function, modulating ovarian response and implantation success in Assisted Reproductive Technologies (ART). The alterations, such as DNA methylation and non-coding RNA control, have been identified as key variables regulating ovarian physiology and reproductive outcomes. This systematic review investigates the significance of epigenetic pathways in ovarian function, with an emphasis on their effect on ART success rates. Methods: A thorough search of the PubMed, Scopus, and EMBASE databases was performed to find articles published between 2015 and 2024 that investigated the connection between epigenetic changes and ovarian function in ART patients. Studies that examined miRNA expression, DNA methylation, and histone changes in follicular fluid, granulosa cells, and embryos were included. The study followed the PRISMA recommendations to guarantee scientific rigor and repeatability. The data were combined into a thorough study of epigenetic markers linked to ovarian aging, ovarian reserve, and implantation success. Results: A total of 15 studies satisfied the inclusion criteria, with substantial relationships found between distinct epigenetic markers and ovarian function. Changes in miRNA expression patterns in follicular fluid and granulosa cells were associated with oocyte maturation, ovarian reserve, and implantation potential. Women with low ovarian reserve and polycystic ovary syndrome (PCOS) have different DNA methylation patterns. MiR-27a-3p and miR-15a-5p were shown to be involved with granulosa cell malfunction and poor ovarian response, whereas global DNA hypomethylation was linked to ovarian aging and ART results. Conclusions: Epigenetic alterations affect ovarian function via pathways that control hormone signaling, follicular development, and implantation success. Further study is needed to determine the practical applicability of epigenetic biomarkers in predicting ART effectiveness and enhancing patient treatment procedures.

Women of reproductive age, especially those with polycystic ovarian syndrome (PCOS), often use glucagon-like peptide-1 receptor agonists (GLP-1RAs) to improve their metabolic functions. A growing body of evidence suggests that GLP-1R signaling may directly affect ovarian physiology, influencing granulosa cell proliferation, survival pathways, and steroidogenic production, in addition to its systemic metabolic effects. Nonetheless, there is a limited comprehension of the molecular mechanisms that regulate these activities and their correlation with menstrual function, reproductive potential, and assisted reproduction. This comprehensive review focuses on ovarian biology, granulosa cell signaling networks, steroidogenesis, and translational fertility outcomes, integrating clinical, in vivo, and in vitro information to elucidate the effects of GLP-1 receptor agonists on reproductive health. We conducted a thorough search of PubMed, Scopus, and Web of Science for randomized trials, prospective studies, animal models, and cellular experiments evaluating the effects of GLP-1RA on reproductive or ovarian outcomes, in accordance with PRISMA criteria. The retrieved data included metabolic changes, androgen levels, monthly regularity, ovarian structure, granulosa cell growth and death, FOXO1 signaling, FSH-cAMP-BMP pathway activity, and fertility or IVF results. Clinical trials shown that GLP-1 receptor agonists improve menstrual regularity, decrease body weight and central adiposity, increase sex hormone-binding globulin levels, and lower free testosterone in overweight and obese women with PCOS. Liraglutide, when combined with metformin, significantly improved IVF pregnancy rates, whereas exenatide increased natural conception rates. Mechanistic studies demonstrate that GLP-1R activation affects FOXO1 phosphorylation, hence promoting granulosa cell proliferation and anti-apoptotic processes. Incretin signaling altered steroidogenesis by reducing the levels of StAR, P450scc, and 3β-HSD, so inhibiting FSH-induced progesterone synthesis, while simultaneously enhancing BMP-Smad signaling. Animal studies demonstrated both beneficial (enhanced follicular growth, anti-apoptotic effects) and detrimental results (oxidative stress, granulosa cell death, uterine inflammation), indicating a context- and dose-dependent response. GLP-1 receptor agonists influence female reproductive biology by altering overall physiological processes and specifically impacting the ovaries via FOXO1 regulation, steroidogenic enzyme expression, and BMP-mediated FSH signaling. Preliminary clinical data indicate improved reproductive function in PCOS, as seen by increased pregnancy rates in both natural and IVF cycles; nevertheless, animal studies reveal a potential risk of ovarian and endometrial damage. These results highlight the need for controlled human research to clarify reproductive safety, molecular pathways, and optimum therapy timing, particularly in non-PCOS patients and IVF settings.