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.