Search Results (31)

Background: Primary dysmenorrhea (PD) is a prevalent gynecological condition that significantly compromises the quality of life in adolescents and women of reproductive age. Within traditional Chinese medicine (TCM), Cold Coagulation and Blood Stasis Primary Dysmenorrhea (CCBS-PD) represents the most frequently observed syndrome pattern of PD. Wenjing Decoction (WJD), a classical TCM formulation, has been extensively employed for the treatment of CCBS-PD. However, given the multi-component and complex nature of WJD, the potential mechanisms underpinning its therapeutic effect have yet to be elucidated. Methods: A rat model of CCBS-PD was induced through ice-water bath stimulation in conjunction with estradiol benzoate and oxytocin. The pharmacological effects of WJD were evaluated by writhing response, hemorheological parameters, uterine index, histopathological examination, and biochemical assays. Serum-exposed constituents of WJD were characterized using UPLC-Orbitrap Exploris 120 MS. To study the mechanisms of WJD, methods from network pharmacology, molecular docking, and off-target metabolomics were used. Western blot analysis examined representative proteins in the signaling pathways predicted by network pharmacology. Network pharmacology and metabolomics were integrated to construct a pathway–metabolite–target–compound network, and representative targets were analyzed by RT-qPCR. Results: WJD treatment reduced writhing responses, improved hemorheological abnormalities, and alleviated uterine pathological changes in CCBS-PD rats. Serum pharmacochemistry identified 62 WJD-derived constituents. Metabolomics analysis indicated that WJD was associated with alterations in nitrogen metabolism, valine/leucine/isoleucine biosynthesis and arginine biosynthesis. Network pharmacology and molecular docking suggested several candidate compounds and targets, including Robinetin, Levistolide A, Pratol, 7,4′-dihydroxyflavone, EGFR, AKT1, ESR1, MMP9, MAPK3, and TNF. RT-qPCR showed that selected genes, including AKT1, EGFR, MAPK3, TNF, ESR1, MMP9 and CASP3, were changed in the model group and partially restored following WJD improvement. Western blot analysis demonstrated that WJD treatment decreased the phosphorylation levels of AKT, ERK1/2, and NF-κB, and down-regulated the protein expression of COX-2. Conclusions: WJD showed beneficial effects in a CCBS-PD rat model. Synthesized assessments indicate a potential link to the actions of serum-exposed constituents, alterations in amino acid metabolism, and modulation of inflammation-related signaling pathways. This research offers initial indications suggesting the multi-component and multi-target pharmacological actions of WJD, although the underlying mechanisms remain to be validated through targeted metabolomics and functional studies. Full article

Polyendocrine metabolic ovarian syndrome (PMOS), renamed from polycystic ovary syndrome (PCOS) by global consensus in May 2026, is one of the most common endocrine diseases in women of reproductive age, affecting physical and mental health. Growing evidence suggests that medicine–food homology (MFH) plants and their bioactive compounds may help regulate PMOS-related metabolism and reproductive abnormalities through dietary intervention. This review summarizes their reported roles and potential mechanisms. Based on the existing literature, this review presents nine edible plant resources identified under the MFH/dietary-use framework and 21 bioactive constituents or constituent classes, all selected for detailed synthesis from a broader eligible evidence base and with reported PMOS-related bioactivity. Across preclinical studies, these constituents appear to act through convergent, multi-target mechanisms, including anti-inflammatory and antioxidant activities to reduce systemic inflammation, as well as restoring hormone balance, correcting abnormal lipid metabolism, relieving insulin resistance and protecting ovarian function. Importantly, the evidence base remains predominantly preclinical, with few human randomized trials. Key translational barriers include insufficient standardization of preparations and doses, limited oral bioavailability of several constituents, safety and herb–drug interaction concerns, and uncertain formulation feasibility for functional-food applications. By integrating evidence at the plant and compound levels, this review provides a mechanistic rationale—rather than clinical proof—for further investigation of dietary strategies relevant to PMOS and proposes a framework for the development and evaluation of MFH-based functional foods. Full article

Oocyte quality is the primary determinant of success in assisted reproductive technologies (ART), and mitochondrial dysfunction is increasingly recognized as a central mediator of poor oocyte competence across advanced maternal age, recurrent implantation failure, polycystic ovary syndrome, endometriosis, and obesity. Chemical interventions improve the mitochondrial microenvironment but cannot restore depleted mitochondrial mass, while heterologous mitochondrial replacement remains constrained by ethical, legal, and biological limitations. This review examines the biological basis for mitochondrial intervention in oocytes, evaluates chemical and cellular therapeutic approaches, and assesses the evidence for autologous Adipose Stem Cell-derived Mitochondria ENergy Transfer (ASCENT). Mitochondria govern oocyte ATP production, calcium-mediated meiotic integrity, and redox homeostasis, and their disruption contributes to aneuploidy, fertilization failure, and embryonic arrest. Among cellular interventions, autologous adipose-derived stem cell mitochondrial transplantation offers minimally invasive tissue accessibility, morphological compatibility with oocyte mitochondria, robust membrane potential, and a preclinically validated Mito-ICSI delivery platform. Notably, ASCENT is currently the only autologous approach for which safety across three consecutive offspring generations has been reported in a mammalian model, with primary maternal origin of offspring mtDNA confirmed. Together, preclinical efficacy, transgenerational safety, and human proof-of-concept support progression toward a rigorously designed clinical trial, while ASC-derived mitochondria hold broader relevance in regenerative medicine. Full article

Haptic technology restores the sense of touch to robotic systems and has become increasingly important for safe and intuitive human–robot interaction in healthcare. Despite substantial advances over the past two decades, widespread clinical adoption remains limited, highlighting a persistent gap between laboratory research and real-world medical deployment. This review synthesizes research from robotics, human–computer interaction, neuroscience, and clinical medicine based on a systematic literature search conducted in IEEE Xplore, PubMed, and Scopus (2000–2025). The review adopts an information-centric perspective, focusing on the clinically relevant information conveyed through haptic feedback rather than force reproduction alone. The review examines tactile, kinesthetic, and hybrid feedback modalities; summarizes key principles of haptic rendering, stability, and control; and evaluates applications in surgical robotics, teleoperation, rehabilitation, prosthetics, and medical training. Evidence indicates that haptic feedback can improve performance, reduce excessive forces, and enhance situational awareness, although benefits remain task-dependent. Clinical translation continues to be constrained by sensing limitations, miniaturization challenges, stability requirements, human factors, and regulatory considerations. Current research is increasingly directed toward sensorless force estimation, artificial intelligence-assisted haptic rendering, wearable and soft haptic interfaces, and neurohaptic technologies, reflecting a shift toward task-oriented and information-centric feedback. Future progress will depend less on maximizing physical realism and more on delivering clinically meaningful information through stable, interpretable, and user-centered haptic systems. This review provides a roadmap for advancing clinically deployable haptic technologies in healthcare. Full article

Relict yew plants (Taxus L.) are not only ornamental plants with valuable wood but also have the ability to synthesize the unique compound taxol, which is successfully used in the treatment of cancer due to its powerful cytotoxic effect. Due to the presence of taxol, all parts of yew plants are extremely poisonous, but there have been cases where animals have eaten yew cones without fatal consequences. The biosynthesis of taxol is carried out due to the interaction of the isoprenoid and phenolic pathways of the secondary metabolism of plants. Despite the close attention of researchers to the peculiarities of taxol metabolism, there is very little data on the tissue and intracellular localization of both taxols and phenolic compounds in yew plants. Polyphenols are known to be physiologically active mediators involved in respiration, photosynthesis, plant growth and development, as well as in the process of in vitro dedifferentiation. Since Taxus is a relict species and has a limited and hard-to-reach range in nature, technologies that allow yew plants to be restored without removing plant material from the natural environment are of great practical importance: overcoming deep physiological dormancy of seeds, microclonal reproduction and initiation of plant growth. In vitro cultures are possible sources of biologically active and medicinal products. The aims and objectives of this study are to determine the characteristics of the formation and localization of phenolic compounds with high biological activity in various organs of plants of the genus Taxus and to determine the biological activity of ethanolic extracts from this plant. The objects of this study were the generative organs of Taxus canadensis, collected during the entire growing season (April–October) from plants growing in the Moscow region. The localization of various classes of polyphenols was determined by histochemical methods using light microscopy. Histochemical studies have shown the abundant presence of polyphenols in yew megastrobiles, microstrobiles, cones, seeds and aril. Ethanolic plant extracts were used to determine the biological activity. Flavans were dominant in the aril at various stages of vegetation, which was confirmed by our biochemical and histochemical studies. Extractive substances of T. canadensis show high antibacterial activity, especially in its shoot extracts. Ethanolic extracts from plant shoots showed greater biological activity than seed extracts. Aril extracts had the lowest cytotoxicity. Full article

Polycystic ovarian syndrome (PCOS) is a complex endocrine and metabolic disorder that affects reproductive health, metabolic function, and long-term cardiovascular health in women of reproductive age. The syndrome is characterized by hyperandrogenism, chronic anovulation, insulin resistance, oxidative stress, and ovarian microenvironment remodeling. While current treatments focus on symptom relief through hormone regulation, insulin sensitizers, or ovulation induction, there is a need to target the underlying molecular and cellular processes that drive disease progression and infertility. Breakthroughs in reproductive and metabolic medicine have led to the development of next-generation therapeutics for PCOS that aim to restore ovarian function at the molecular level. Nanoparticle- and nanofiber-based drug delivery systems offer targeted delivery to the ovaries, improved bioavailability, and controlled release of insulin sensitizers, antioxidants, and anti-androgens. Metabolic reprogramming strategies that target insulin resistance, mitochondrial dysfunction, and autophagy have emerged as potential disease-modifying interventions. In addition, AI-enabled precision medicine approaches are reshaping PCOS management through phenotype-based classification, predictive modeling, and personalized fertility optimization. In this review, we highlight recent advancements in understanding the molecular pathophysiology of PCOS and introduce novel therapeutics that harness intelligent drug delivery, ovarian microenvironment restoration, and AI-based interventions. We discuss the potential of these innovative strategies to update PCOS management options for long-term ovarian restoration and fertility. Full article

Endometriosis is a chronic hormone-responsive disorder linked to infertility, usually characterized by the presence of ectopic endometrium in the pelvis that disrupts local homeostasis. Advances in single-cell “omic” methods have revealed the remarkable cellular diversity within the eutopic endometrium and endometriosis lesions, uncovering distinct populations with unique transcriptional and functional profiles. These studies have highlighted alterations in immune cell subsets, stromal and epithelial cell signaling, and intercellular communication networks that collectively impair oocyte quality, embryo development, and endometrial receptivity in women with endometriosis. By dissecting the molecular signatures of individual cells, single-cell approaches provide insights into the mechanisms driving persistent inflammation, impaired angiogenesis, hormonal dysregulation, and immune dysfunction in endometriosis. Importantly, emerging evidence indicates that infertility and reduced assisted reproductive technology (ART) success in endometriosis reflect coordinated cellular and molecular dysfunction rather than solely anatomical abnormalities. Single-cell analyses of oocytes, granulosa cells, and endometrial cell populations demonstrate transcriptomic and epigenetic alterations affecting mitochondrial function, steroid metabolism, immune regulation, and implantation-related signaling pathways, offering a biological explanation for impaired implantation and variable ART outcomes. Integration of these findings with clinical observations supports the concept that endometriosis-associated reproductive failure arises from combined ovarian and endometrial defects detectable at the cellular level. Current single-cell studies highlight candidate biomarker signatures with the potential to improve patient stratification, predict ART outcomes, and guide individualized therapeutic strategies. As these discoveries are refined into clinically applicable biomarker panels, single-cell technologies are poised to bridge mechanistic understanding and precision reproductive medicine, enabling more personalized management approaches aimed at restoring reproductive competence in patients with endometriosis. Full article

Polycystic Ovary Syndrome (PCOS) is characterized by a self-perpetuating vicious cycle between insulin resistance (IR) and hyperandrogenism (HA). While lifestyle management remains the internationally recommended first-line treatment, current clinical management, primarily relying on combined oral contraceptives and metformin, offers symptomatic relief or “masking” of the phenotype but fails to adequately disrupt this core pathophysiological loop, while also carrying potential intergenerational safety concerns. This review systematically evaluates the paradigm shift toward mechanism-based precision medicine. First, we analyze emerging precision-targeted therapies that intervene in specific pathological nodes: (1) metabolic regulators (e.g., GLP-1RAs, SGLT2i, and brown adipose tissue (BAT) activators) that target systemic glucotoxicity and the novel “BAT-Ovarian axis”; (2) neuroendocrine modulators (e.g., NK3R antagonists) that act as negative modulators of the hyperactive GnRH pulse generator; and (3) innovative androgen synthesis inhibitors (e.g., Artemisinins) that utilize a degradation-at-source mechanism. Complementing these, we explore the strategic value of Natural Products through the lens of “Network Pharmacology”, highlighting their ability to restore systemic homeostasis via multi-target modulation. Finally, we address critical translational challenges, specifically the need to establish long-term reproductive and offspring safety, providing a roadmap for developing true disease-modifying treatments for PCOS. Distinct from reviews limited to isolated therapeutic modalities, this article uniquely bridges current clinical management with emerging organ-specific precision targets and natural product networks. Full article

Exosomes are nanoscale extracellular vesicles that mediate intercellular communication by transporting microRNAs, proteins, and lipids. Generated through Endosomal Sorting Complex Required for Transport (ESCRT)-dependent mechanisms or ESCRT-independent pathways, exosomes are released when multivesicular bodies fuse with the plasma membrane. The ESCRT-dependent pathway involves sequential protein complexes (ESCRT-0, I, II, III) that recognize and sort ubiquitinated cargo, induce membrane budding, and facilitate vesicle scission. In contrast, the ESCRT-independent pathway relies on membrane lipids such as ceramide and proteins like tetraspanins (CD9, CD63, CD81) to promote vesicle formation without ESCRT machinery. Furthermore, post-translational modifications, including ubiquitination, sumoylation, and phosphorylation, further serve as molecular switches, modulating the affinity of ESCRT complexes or cargo proteins for membrane domains and affecting ILV formation rates. In reproductive medicine, exosomes regulate oocyte maturation, embryo–endometrial crosstalk, placental development, and maternal–fetal communication. Altered exosomal signaling contributes to obstetric complications, including preeclampsia, gestational diabetes mellitus, and preterm birth, whereas distinct exosomal miRNA signatures serve as potential diagnostic biomarkers. In gynecology, dysregulated exosomes are implicated in endometriosis, polycystic ovary syndrome, premature ovarian insufficiency, and gynecological malignancies. In contrast, mesenchymal stem cell-derived exosomes show therapeutic promise in restoring ovarian function and enhancing fertility outcomes. The distinctive molecular profiles of circulating exosomes enable minimally invasive diagnosis, while their biocompatibility and ability to cross biological barriers position them as vehicles for targeted drug delivery. Characterization of accessible data provides non-invasive opportunities for disease monitoring. However, clinical translation faces challenges, including standardization of isolation protocols, establishment of reference ranges for biomarkers, and optimization of therapeutic dosing. This review summarizes exosome biogenesis, characterization methods, physiological functions, and clinical applications in obstetrics and gynecology, with an emphasis on their diagnostic and therapeutic potential. Future directions include large-scale biomarker validation studies, engineering approaches to enhance exosome targeting, and integration with precision medicine platforms to advance personalized reproductive healthcare. Full article

Lipid accumulation disrupts mitochondrial dynamics, leading to dysfunctional energy metabolism and increased oxidative stress. However, the relationship between mitochondrial dynamics and ovarian function in therapeutic contexts is still not fully elucidated. Therefore, the objective of this study was to demonstrate whether increased carnitine palmitoyltransferase 1A (CPT1A) expression induced by placenta-derived mesenchymal stem cells (PD-MSCs) improves ovarian function in ovaries of a lipid toxicity-induced rat model by regulating lipid metabolism and mitochondrial dynamics. A rat model of injury was induced through intraperitoneal administration of thioacetamide (TAA) for 12 weeks. During the 8th week of induction, PD-MSCs (2 × 10⁶ cells) were transplanted via the tail vein. Initially, we examined the engraftment of PD-MSCs. The inflammatory response (e.g., IL-6, TNFα) and apoptosis (e.g., LDH levels, TUNEL assay) were significantly increased in the non-transplanted (NTx) group compared to the normal group; however, they were significantly decreased in the transplanted (Tx) group compared to the NTx group (* p < 0.05). Additionally, oxidative stress was attenuated through the regulation of mitochondrial dynamics, including the expression of DRP1, ATP5B, and PGC1α, in the Tx group compared to the NTx group (* p < 0.05). In the NTx group, abnormally accumulated lipid droplets were observed due to dysfunctional mitochondria, whereas in the Tx group, the accumulation of lipid droplets and the expression of CPT1A were significantly comparable to those in the normal group (* p < 0.05). The levels of the steroidogenesis markers (e.g., CYP11A1 and HSD3β1) were decreased in the NTx group compared to the normal group and increased in the Tx group compared to the NTx group (* p < 0.05). The levels of sex hormone and follicular development were protected in the Tx group compared to the NTx group. Furthermore, cocultivation of PD-MSCs with etomoxir (CPT1A inhibitor)-treated primary theca cells increased the expression of steroidogenesis. In conclusion, PD-MSCs improve ovarian function in TAA-induced injury by reducing lipid accumulation and oxidative stress through the regulation of lipid metabolism and mitochondrial dynamics. The upregulation of CPT1A and related mitochondrial proteins contributes to enhanced steroidogenesis and restoration of ovarian homeostasis. These findings offer new insights into the application of stem cell therapies for reproductive medicine. Full article

Crateva tapia L. is a native tree species of the Caatinga biome, with medicinal and allelopathic properties. This study aimed to characterize the biometric and morphological traits of fruits, seeds, seedlings, and young plants of C. tapia, as well as to evaluate the germination pattern of its seeds under different temperatures, in order to understand the reproductive strategies and optimal conditions for its propagation. The results are intended to support conservation efforts, ecological restoration, and the sustainable use of the species within the Caatinga biome. The research was carried out at the Seed Analysis Laboratory of the Federal University of Paraíba, Campus II, Areia–PB, Brazil. The biometric data were obtained from 100 fruits and 100 seeds obtained from eight mother plants. The imbibition curve was determined from the weight of the seeds during 216 h at different temperatures, and the germination test was performed concomitantly. The fruits were morphologically described regarding the external and internal aspects of the pericarp. The seeds were described according to their consistency, color, texture, shape, hilum, and embryo. The fruits of C. tapia vary in size, fresh mass, and number of seeds, characterized as amphisarcidium, indehiscent, and polyspermic. The seeds are small, brown, reniform, and biting, with a cotyledonary embryo with a poorly differentiated hypocotyl–radicle axis, with a well-developed hilum and surrounded by a fleshy mesocarp. The germination of C. tapia seeds is epigeal-phanerocotyledonous; the seedlings have white axial roots containing absorbent hairs. Full article

Infertility remains a major global health concern, with diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), polycystic ovary syndrome (PCOS), and impaired endometrial receptivity representing key contributors to poor assisted reproductive technology (ART) outcomes. Platelet-rich plasma (PRP), an autologous blood-derived concentrate enriched with growth factors and cytokines, has emerged as a promising regenerative therapy with angiogenic, anti-apoptotic, and proliferative properties. In reproductive medicine, intraovarian PRP has been evaluated for its potential to restore ovarian function in women with DOR and POI, improve oocyte competence and embryo euploidy, and promote ovulation in PCOS. Similarly, intrauterine PRP infusion or subendometrial zone injections has shown encouraging results in women with recurrent implantation failure and thin endometrium, enhancing endometrial thickness, receptivity, and implantation potential. Evidence from preclinical animal models and early clinical studies suggests multi-level mechanisms of action, including modulation of endocrine pathways, reduction in oxidative stress, activation of dormant follicles, and improvement of endometrial angiogenesis and receptivity. Despite these promising findings, results remain inconsistent due to heterogeneity in PRP preparation protocols, administration routes, timing, and study designs. Even though robust randomized controlled trials with standardized methodologies are needed to determine the efficacy and long-term reproductive outcomes of PRP in infertility treatment and anovulation in PCOS, PRP represents a novel and potentially transformative adjunct in reproductive endocrinology. Full article

Male infertility, as a globally significant reproductive health issue, remains idiopathic in over 40% of cases. Reproductive disorders in males induced by environmental pollutants, such as di(2-ethylhexyl) phthalate (DEHP), have garnered considerable attention in recent years. DEHP induces testicular oxidative stress and ferroptosis via its active metabolite MEHP, thereby leading to spermatogenic dysfunction. Lycium barbarum polysaccharide (LBP), a traditional food and medicine homologous substance, exhibits potential antioxidant and reproductive protective properties. However, the underlying mechanism by which LBP intervenes in the toxicity induced by DEHP remains to be elucidated. This study explored the protective effect and molecular mechanism of LBP on DEHP-induced testicular injury through in vivo and in vitro experiments. The result showed that DEHP exposure (150 mg/L in free drinking water for 6 weeks) significantly decreased testicular weight, sperm concentration, and sperm motility in mice, while DEHP exposure induced pathological damage to testicular tissue, as evidenced by cavitation of seminiferous tubules, reduced numbers of spermatocytes, and vacuolar degeneration of Sertoli cells. However, LBP (450 mg/L) treatment significantly reversed testicular damage and sperm parameters. In vitro, MEHP reduced the viability of GC2 cells (spermatocyte cell line) and TM4 cells (Sertoli cell line), and LBP significantly restored cell activity. Mechanistically, exposure to DEHP/MEHP results in iron overload (elevated levels of free Fe²⁺), lipid peroxidation (increased MDA and reduced GSH), and dysregulated expression of key proteins involved in ferroptosis and iron homeostasis within the testis and cells. Furthermore, it was demonstrated that when NRF2 was specifically inhibited by ML385 or silenced via siRNA, the protective effects of LBP were abrogated, thereby validating the critical role of NRF2 in the regulation of iron homeostasis by LBP. In conclusion, LBP mitigates DEHP-induced testicular injury by activating NRF2 to regulate iron homeostasis in Sertoli cells and spermatocytes cells. This study not only offers a potential strategy for the prevention and treatment of male reproductive disorders caused by DEHP exposure, but also underscores the reproductive protective effects and application prospects of LBP in this context. Full article

Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, driven by advances in two complementary strategies: organotypic in vitro spermatogenesis (IVS), which aims to complete spermatogenesis ex vivo using native testicular tissue, and in vitro gametogenesis (IVG), which seeks to generate male gametes de novo from pluripotent or reprogrammed somatic stem cells. To evaluate the current landscape and future potential of these approaches, a narrative, semi-systematic literature search was conducted in PubMed and Scopus for the period January 2010 to February 2025. Additionally, landmark studies published prior to 2010 that contributed foundational knowledge in spermatogenesis and testicular tissue modeling were reviewed to provide historical context. This narrative review synthesizes multidisciplinary evidence from cell biology, tissue engineering, and translational medicine to benchmark IVS and IVG technologies against species-specific developmental milestones, ranging from rodent models to non-human primates and emerging human systems. Key challenges—such as the reconstitution of the blood–testis barrier, stage-specific endocrine signaling, and epigenetic reprogramming—are discussed alongside critical performance metrics of various platforms, including air–liquid interface slice cultures, three-dimensional organoids, microfluidic “testis-on-chip” devices, and stem cell-derived gametogenic protocols. Particular attention is given to clinical applicability in contexts such as NOA, oncofertility preservation in prepubertal patients, genetic syndromes, and reprocutive scenarios involving same-sex or unpartnered individuals. Safety, regulatory, and ethical considerations are critically appraised, and a translational framework is outlined that emphasizes biomimetic scaffold design, multi-omics-guided media optimization, and rigorous genomic and epigenomic quality control. While the generation of functionally mature sperm in vitro remains unachieved, converging progress in animal models and early human systems suggests that clinically revelant IVS and IVG applications are approaching feasibility, offering a paradigm shift in reproductive medicine. Full article

Nitric oxide (NO) predominantly regulates endometrial receptivity, angiogenesis, immunological tolerance, and trophoblast invasion throughout the implantation period. Both insufficient and excessive nitric oxide production have been linked to suboptimal embryo implantation and infertility. The primary enzymatic source of uterine nitric oxide, along with hormonal, metabolic, and immunological variables and genetic variations in the endothelial nitric oxide synthase gene (NOS3), affects endothelial nitric oxide synthase (eNOS). Despite its considerable importance, there is limited knowledge regarding the practical implementation of nitric oxide-related diagnoses and therapies in reproductive medicine. A comprehensive assessment was performed in accordance with the PRISMA principles. Electronic searches were carried out in PubMed, Scopus, and Embase, and we analyzed the literature published from 2000 to 2024 regarding the association between NO, its metabolites (NO₂⁻ and NO₃⁻), eNOS expression, NOS3 gene variants, and reproductive outcomes. Relevant studies encompassed clinical trials, observational studies, and experimental research using either human or animal subjects. We collected data about therapeutic interventions, hormonal and immunological associations, nitric oxide measurement techniques, and in vitro fertilization success rates. A total of thirty-four studies were included. Dysregulated nitric oxide signaling, characterized by modified eNOS expression, oxidative stress, or NOS3 polymorphisms (e.g., Glu298Asp and intron 4 VNTR), was linked to diminished endometrial receptivity and an elevated risk of implantation failure and miscarriage. The dynamics of local uterine NO are essential as elevated and diminished systemic levels of NO₂⁻/NO₃⁻ corresponded with enhanced and decreased implantation rates, respectively. Among many therapeutic approaches, targeted hormone treatments, antioxidant therapy, and dietary nitrate supplements have demonstrated potential in restoring nitric oxide balance and enhancing reproductive outcomes. In animal models, the modification of nitric oxide significantly impacted decidualization, angiogenesis, and embryo viability. Nitric oxide is a multifaceted molecular mediator with considerable ramifications for successful implantation. Its therapeutic and diagnostic efficacy increases with its sensitivity to environmental, hormonal, and genetic alterations. Integrating targeted nitric oxide modulation, oxidative stress assessment, and NOS3 genotyping with personalized reproductive therapy will enhance endometrial receptivity and improve IVF outcomes. Future translational research should incorporate nitric oxide signaling into personalized treatment protocols for patients with unexplained infertility or recurrent implantation failure. Full article