Abstract
Diabetes-associated infertility results from interconnected immunometabolic, oxidative, inflammatory, and endocrine disturbances that impair reproductive function in both sexes. Conventional therapies address individual symptoms but often fail to target this systemic, immune-mediated complexity. This narrative review summarizes preclinical and clinical evidence on the role of Traditional Chinese Medicine (TCM) in managing diabetic infertility, with a focus on immune-endocrine interactions, cytokine modulation, and inflammatory signaling. TCM interventions - including single-herb extracts, multi-herb formulations, and non-pharmacological approaches such as acupuncture and mind-body interventions-enhance insulin sensitivity, suppress pro-inflammatory cascades (NF-κB, TNF-α, IL-6), and regulate key immunometabolic pathways such as PI3K/Akt and AMPK. Mechanistic studies have also demonstrated improved nitric oxide bioavailability, endothelial function, and mitochondrial protection in gametogenic cells. They further show stabilization of hypothalamic-pituitary-gonadal and immune signaling, along with modulation of the gut-microbiota-immune axis. These immunomodulatory effects contribute to better spermatogenesis, semen quality, ovulation, endometrial receptivity, implantation, and pregnancy outcomes, particularly in individuals with insulin resistance or polycystic ovary syndrome. Overall, TCM shows promise as an adjunctive immunomodulatory strategy for diabetic infertility, supported by preliminary evidence of reproductive benefits. However, current evidence remains limited, and well-designed multicenter, immunology-informed clinical trials are required to confirm its efficacy.