Female fertility preservation: 25 years of progress, expanding indications and future prospects

Abstract BACKGROUND There has been an unprecedented progress in the field of fertility preservation (FP) beginning in the late 1990s. Specifically, technological innovations, refinements in the protocols, and a deeper understanding of reproductive physiology have collectively contributed the increased success and utilization of FP methods. OBJECTIVE AND RATIONALE The objectives of this review are: (i) to identify the most recent and significant advances in FP, and (ii) based on evidence, to provide a comprehensive and up-to-date source of contemporary FP management approaches to guide clinicians in critical decision-making. In addition to cancer treatments, the indications for FP have expanded to include various systemic conditions such as haematological, metabolic, genetic, and immunological disorders, as well as gonadal surgery and a wish to delay childbearing. Due to the introduction of random start ovarian stimulation protocols and use of anti-oestrogen agents along with ovarian stimulation drugs, coupled with increased success with oocyte cryopreservation, improvements in ovarian tissue cryopreservation and refinements of transplantation techniques, women can now benefit from various FP options through an individualized approach. SEARCH METHODS We searched for peer-reviewed articles in PubMed, Embase, and Cochrane Library databases containing the key words: FP, ovarian ageing, chemotherapy, radiotherapy, embryo cryopreservation, oocyte cryopreservation, ovarian tissue cryopreservation, and in vitro follicle growth, in the English-language literature from inception to May 2025. OUTCOMES Cryopreservation of embryos have long been performed successfully in the field of ART. With the advent and widespread of use vitrification, the experimental tag was removed and oocyte cryopreservation was defined as a standard technique of FP. The applicability, success, and safety of random start ovarian stimulation protocols have been demonstrated in many studies including meta-analyses. Improvements in ovarian tissue cryopreservation outcomes have been reported with robotic surgery, use of neovascularizing extracellular matrix, and adjuvant pharmacotherapy. The use of GnRH analogues along with chemotherapy has been trialled as a way of avoiding the need for FP. Although the rate of premature ovarian insufficiency was reported to be lower in some patient populations treated this way, no improvements in live birth rates have been demonstrated. Among the emerging and future options are the use of ovarian tissue freezing and pharmacological approaches to delay menopause and reproductive ageing, non-suppressive gonadoprotective pharmacotherapy, in vitro gametogenesis and in vitro purging of cancer cells from ovarian tissue for cryopreservation. Animal studies have reported success with in vitro follicle growth, and progress is being made with human ovarian tissue. WIDER IMPLICATIONS The evolution of FP techniques has profound implications for clinical practice, not only for individuals facing fertility-compromising treatments or conditions, but also for the potential deferral of reproductive ageing. The advent of in vitro primordial follicle growth and gametogenesis may further revolutionize the landscape of reproductive medicine and FP. REGISTRATION NUMBER N/A.