Polyendocrine metabolic ovarian syndrome (PMOS) remains a leading cause of anovulatory infertility worldwide, traditionally managed through systemic hormonal and metabolic stabilization. However, recent evidence has increasingly identified ovarian fibrosis, which is characterized by excessive extracellular matrix deposition and structural remodeling, as a critical hallmark of reproductive decline in affected individuals. This review provides a comprehensive synthesis of the evolving PMOS landscape, bridging the gap between classic endocrine dysfunction and the newly recognized fibrotic microenvironment. We systematically evaluate the pathogenesis of PMOS, ranging from hyperandrogenemia and insulin resistance to chronic low-grade inflammation, while detailing the molecular drivers of fibrosis such as the TGF-β/CTGF axis and mitochondrial exhaustion. Furthermore, we analyze current therapeutic modalities, including pharmacological agents, regenerative medicine, and traditional Chinese medicine, which highlight a paradigm shift toward precision interventions. Despite these advancements, the precise causal mechanisms linking PMOS to fibrotic pathology remain underexplored, and targeted curative strategies are scarce. We conclude by proposing that alleviating ovarian fibrosis through drug, metabolic, and immunomodulatory pathways represents a high-potential frontier. Future research should prioritize these anti-fibrotic strategies to not only alleviate symptoms but also fundamentally restore ovarian function and extend reproductive longevity.

Male infertility (MI) represents a complex clinical issue affecting millions of couples worldwide. Its diverse etiologies and incompletely elucidated mechanisms limit the development of effective therapeutic strategies. Animal models, serving as a bridge between basic research and clinical practice, play an indispensable role in simulating the pathophysiological processes of human MI, deciphering key underlying mechanisms, and screening and evaluating potential therapeutic agents. This review systematically summarizes the various animal models employed in MI research, including chemically induced models (e.g., using tripterygium glycosides or cyclophosphamide), endocrine-disrupting agent-induced models (e.g., using Bisphenol A (BPA) or finasteride), and physically induced models (e.g., via heat stress or experimental varicocele). We focus on elucidating the core pathological mechanisms these models recapitulate, encompassing oxidative stress, inflammatory responses, novel cell death pathways such as apoptosis, pyroptosis, and ferroptosis, as well as endocrine disruption of the hypothalamic-pituitary-gonadal (HPG) axis. Through an in-depth analysis of the characteristics of each model, associated signaling pathways-including the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, and the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome, and identified pharmacological targets, this article aims to provide insights into the complex etiology of human MI and offer a crucial theoretical foundation and experimental framework for the development and translation of novel mechanism-based therapeutics.

This report explores the case of a young, normal-responder nulligravida with peritoneal endometriosis and recurrent implantation failure, with poor embryo quality during multiple failed attempts at IVF treatment. The patient underwent Dienogest (Visabelle®) pretreatment followed by a combination protocol of Stop GnRH-agonist/GnRH-antagonist for controlled ovarian stimulation, culminating in a natural cycle frozen-thawed embryo transfer with modified luteal phase support. This combined approach produced several high-quality embryos leading to a successful singleton pregnancy. These findings provide new insights into addressing endometriosis-associated infertility and repeated IVF failure.

Artificial intelligence (AI) is generating genuine excitement in reproductive medicine for good reason. The promise of more consistent embryo assessment, reduced inter-observer variability, better outcome prediction and meaningful support for the embryologist's judgment represents a real opportunity to improve care for patients who have already invested enormously in the pursuit of a family. Realizing that promise, however, depends on something the field has not always done well which is insisting on rigorous validation before widespread adoption. This editorial is written in that spirit, as advocates for AI who believe the technology's long-term acceptance by patients, clinicians and embryologists will be determined by how carefully we deploy it now and how we proceed going forward. How will we know when AI is ready to fully deploy in the IVF lab? The answer requires distinguishing between being safe and being safe and effective and the medical community has not yet reached consensus on either standard for most applications. Professional societies will need to lead that process. However, in the meantime, with commercial adoption accelerating and stakeholder incentives not always aligned with patient welfare, we propose criteria as a starting framework for that discussion.

Ovarian aging is characterized by the progressive depletion of the follicular reserve and deterioration of reproductive endocrine function, yet its cellular basis has been disproportionately attributed to oocyte and granulosa cell decline. Theca cells - the principal androgen-producing cell type of the ovarian follicle - have remained critically underappreciated in this context. Operating through the classical two-cell, two-gonadotropin model, theca cells supply androgen precursors that granulosa cells aromatize into estradiol, and their dysfunction therefore impairs estrogen biosynthesis irrespective of granulosa cell competence. During ovarian aging, theca cells undergo quantitative decline, transcriptional reprogramming, and progressive steroidogenic impairment. Single-cell transcriptomic analyses reveal age-dependent upregulation of senescence pathways - including CDKN1A, NF-κB, and SASP-associated factors - alongside downregulation of FOXP1, a transcription factor that normally suppresses cellular senescence through direct repression of CDKN1A. Senescent theca-interstitial cells elaborate pro-inflammatory mediators, most notably CCL5, TNF-α, IL-1β, and IL-6, which suppress steroidogenic gene expression, induce granulosa cell apoptosis, and promote ovarian fibrosis, collectively accelerating follicular atresia. At the molecular level, mitochondrial dysfunction driven by aberrant GSK3β activation impairs oxidative phosphorylation and steroidogenic capacity, while dysregulation of the PTEN/PI3K/Akt/FOXO1 axis uncouples theca cells from LH-dependent gonadotropin signaling. Theca cell dysfunction further underlies distinct clinical entities, including premature ovarian insufficiency, diminished ovarian reserve, and polycystic ovary syndrome. Emerging therapeutic strategies - encompassing mesenchymal stem cell-derived exosomes, senolytics, mitochondria-targeted interventions, and Wnt/β-catenin pathway modulation - have demonstrated efficacy in restoring theca cell function in preclinical models. This review repositions theca cells as active, bidirectionally regulated participants in ovarian aging-integral to, rather than upstream of, the oocyte-granulosa-theca unit-and proposes theca-specific biomarkers and targeted interventions as priorities for future translational research.