Background/Objectives: Inflammation, infections, and oxidative stress (OS) all have an impact on male infertility, which is a complicated, multifaceted illness. OS affects motility and fertilization capability. It accomplishes this through damaging sperm DNA, oxidizing proteins, and triggering lipid peroxidation. These effects occur due to an imbalance between reactive oxygen species (ROS) and antioxidant defenses. Methods: This review aims to evaluate the impact of oxidative stress and inflammation on male infertility by assessing recent literature. Results: Pro-inflammatory cytokines, like TNF-α and IL-6, interfere with spermatogenesis and promote oxidative damage. Additionally, infections caused by pathogens like Escherichia coli and Chlamydia trachomatis alter the reproductive microenvironment, leading to sperm dysfunction and inflammation. Conclusions: Early detection and targeted treatment are essential due to the intricate interactions among these elements. Microbiota-modulating techniques, antimicrobial therapies, anti-inflammatory drugs, and antioxidants are therapeutic approaches that may help reduce oxidative damage and enhance male fertility.

Chronic inflammation is increasingly recognized as a critical factor in female reproductive health; influencing natural conception and the outcomes of assisted reproductive technologies such as in vitro fertilization (IVF). An essential component of innate immunity, the NLR family pyrin domain-containing 3 (NLRP3) inflammasome is one of the major mediators of inflammatory responses, and its activation is closely linked to oxidative stress. This interaction contributes to a decline in oocyte quality, reduced fertilization potential, and impaired embryo development. In the ovarian milieu, oxidative stress and NLRP3 inflammasome activation interact intricately, and their combined effects on oocyte competence and reproductive outcomes are significant. The aims of this review are to examine these molecular mechanisms and to explore therapeutic strategies targeting oxidative stress and NLRP3 inflammasome activity, with the goal of enhancing female fertility and improving clinical outcomes in reproductive health.

Male factors may be present in up to 50–70% of infertile couples and the prevalence of male infertility accounts for 20–30% of infertility cases. Understanding the mechanisms and causes behind male infertility remains a challenge, but new diagnostic tools such as DNA fragmentation might aid in cases where the routine semen analysis is insufficient. DNA fragmentation, which refers to damages or breaks of the genetic material of the spermatozoa, is considered one of the main causes of male infertility due to impaired functional capability of sperm. The aim of the present narrative review is to investigate and enlighten the potential correlation between DNA fragmentation and male infertility parameters such as the seminal profile and the reproductive outcomes. Comprehensive research in PubMed/Medline and Scopus databases was conducted and 28 studies were included in the present review. Fourteen studies provided data regarding the impact of DNA fragmentation and seminal parameters and showed a correlation of significantly lower sperm count, lower concentration, motility, and abnormal morphology with an increased DNA fragmentation index (DFI). Similarly, 15 studies provided data regarding the impact of DFI on reproductive outcomes. Two studies showed higher aneuploidy rates with higher DFI values, and seven studies showed significantly lower pregnancy rates and live birth rates with higher DFI values. Ultimately, the studies included in this review highlight, collectively, the importance of measuring sperm DFI in the assessment of male infertility. Further studies are needed to explore the effectiveness of interventions aiming to reduce DFI levels.

The human gut microbiome is integral to maintaining systemic physiological balance, with accumulating evidence emphasizing its critical role in reproductive health. This review investigates the bidirectional interactions between the gut microbiota and the female reproductive system, mediated by neuroendocrine, immune, and metabolic pathways, constituting the gut–reproductive axis. Dysbiosis, characterized by microbial imbalance, has been linked to reproductive disorders such as polycystic ovary syndrome (PCOS), endometriosis, infertility, impaired spermatogenesis, and pregnancy complications. These associations can be explained by immunological dysregulation, systemic inflammation, altered sex hormone metabolism, and hypothalamic–pituitary–gonadal (HPG) axis disturbances. This review aims to clarify the molecular and cellular mechanisms underpinning gut–reproductive interactions and to evaluate the feasibility of microbiome-targeted therapies as clinical interventions for improving reproductive outcomes.

Background: Mitochondria are essential for placental function as they regulate energy metabolism, oxidative balance, and apoptotic signaling. Increasing evidence suggests that placental mitochondrial dysfunction may play a role in the development of many poor perinatal outcomes, including preeclampsia, intrauterine growth restriction (IUGR), premature birth, and stillbirth. Nonetheless, no systematic review has thoroughly investigated this connection across human research. This study aims to consolidate evidence from human research concerning the link between placental mitochondrial dysfunction and negative birth outcomes. Methods: A systematic search of PubMed, Scopus, and Web of Science identified human research examining placental mitochondrial features (e.g., mtDNA copy number, ATP production, oxidative stress indicators) in connection with adverse pregnancy outcomes. Methodological variety resulted in narrative data extraction and synthesis. Results: Twenty-nine studies met the inclusion criteria. Mitochondrial dysfunction was consistently associated with PE, IUGR, FGR, and PTB. The most often observed outcomes included diminished mtDNA copy number, decreased ATP production, elevated reactive oxygen species (ROS), and disrupted mitochondrial dynamics, characterized by increased DRP1 and decreased MFN2. Early-onset preeclampsia and symmetric fetal growth restriction exhibited particularly severe mitochondrial abnormalities, indicating a primary placental origin of the condition. Conclusions: A significant factor contributing to adverse pregnancy outcomes is the dysfunction of placental mitochondria. The analogous molecular signatures across many disorders suggest promising avenues for developing targeted therapies aimed at improving maternal–fetal health and predictive biomarkers.

The prediction of in vitro fertilization (IVF) outcome is an imperative achievement in assisted reproduction, substantially aiding infertile couples, health systems and communities. To date, the assessment of infertile couples depends on medical/reproductive history, biochemical indications and investigations of the reproductive tract, along with data obtained from previous IVF cycles, if any. Our project aims to develop a novel tool, integrating omics and artificial intelligence, to propose optimal treatment options and enhance treatment success rates. For this purpose, we will proceed with the following: (1) recording subfertile couples’ lifestyle and demographic parameters and previous IVF cycle characteristics; (2) measurement and evaluation of metabolomics, transcriptomics and biomarkers, and deep machine learning assessment of the oocyte, sperm and embryo; (3) creation of artificial neural network models to increase objectivity and accuracy in comparison to traditional techniques for the improvement of the success rates of IVF cycles following an IVF failure. Therefore, “omics” data are a valuable parameter for embryo selection optimization and promoting personalized IVF treatment. “Omics” combined with predictive models will substantially promote health management individualization; contribute to the successful treatment of infertile couples, particularly those with unexplained infertility or repeated implantation failures; and reduce multiple gestation rates.