Regenerative approaches in ovarian rejuvenation: hope for fertility restoration

Ovarian aging is a progressive biological process marked by a decrease in the amount and quality of oocytes, resulting in decreased fertility, diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), and menopause. Multiple molecular processes, including as oxidative stress, mitochondrial dysfunction, telomere shortening, DNA damage, apoptosis, and hormone imbalance, all contribute to poor ovarian function and follicular depletion. Conventional fertility therapies and assisted reproductive technologies focus on the effects of ovarian malfunction rather than improving ovarian activity itself, with little success in women with low ovarian reserve. Recently, ovarian rejuvenation has emerged as a viable regenerative method for enhancing the ovarian microenvironment, awakening dormant follicles, and restoring endocrine and reproductive function. This study looks at the biology of ovarian aging, the pathophysiology of ovarian dysfunction, and recent breakthroughs in ovarian rejuvenation treatments such as platelet-rich plasma (PRP) treatment, stem cell-based therapy, in vitro activation (IVA), and ovarian tissue transplantation (OTT). PRP therapy has the potential to improve ovarian reserve markers such as AMH, FSH, and AFC, whereas mesenchymal stem cell therapy may promote angiogenesis, reduce inflammation, and support follicular survival via paracrine mechanisms. IVA and OTT are also novel fertility preservation and restoration procedures for women with DOR and POI. Although first results are intriguing, existing evidence is limited due to small sample sizes, a lack of standardized techniques, and insufficient long-term safety data. More large-scale randomized clinical trials are needed to determine the efficacy, safety, and therapeutic application of ovarian rejuvenation therapy in reproductive medicine.