630 nm LED phototherapy enhances ovarian function and fertility potential in advanced reproductive age females

Ovarian aging, a major contributor to declining fertility in women of advanced reproductive age (ARA), is strongly associated with impaired mitochondrial function within oocytes. Although current mitochondrial‐targeted strategies can improve ovarian function, their clinical application remains limited by cost and side effects. In this study, 630 nm light‐emitting diode (LED) phototherapy is shown to ameliorate ovarian aging phenotypes in ARA mice by enhancing mitochondrial complex II activity via upregulation of succinate dehydrogenase subunit B (SDHB). This intervention restores oocyte adenosine triphosphate (ATP) production, improves meiotic progression, and significantly increases blastocyst formation. To assess translational feasibility, a wearable 630 nm LED phototherapy device is developed and evaluated in a pilot clinical study in women with diminished ovarian reserve (DOR). After treatment, the antral follicle count (AFC) significantly increases from a median of 2 (IQR 1–5) to 6 (IQR 2–7; p = 0.011), and the number of oocytes retrieved showed a non‐significant tendency to increase from 2 (IQR 1–5) to 5 (IQR 2–7; p = 0.083), indicating a potential improvement in ovarian reserve. These findings demonstrate that 630 nm LED phototherapy enhances mitochondrial function and oocyte competence, providing a promising non‐invasive strategy to improve fertility in women affected by ovarian aging.