Use of Autologous Exosomes to Enhance Oocyte Maturation in Patients with Diminished Ovarian Reserve: A Prospective, Randomized Clinical Trial (Pilot Study).

Oocyte development begins during embryonic life and remains arrested in prophase I until meiotic resumption during ovulation. A substantial proportion of oocytes retrieved during assisted reproductive procedures remain immature at the metaphase I (MI) stage and fail to achieve the maturation required for fertilization. In women with diminished ovarian reserve, alterations in the ovarian microenvironment may impair the biochemical signaling necessary for normal oocyte development. Autologous exosomes have emerged as a potential strategy to enhance meiotic progression through the transfer of bioactive molecules. This study aimed to evaluate the in vitro efficacy of autologous exosomes in improving the maturation potential of immature oocytes in women with diminished ovarian reserve. A prospective, randomized, controlled pilot study was conducted in 32 women aged 38-46 years. A total of 111 oocytes were retrieved (52 metaphase II [MII] and 59 MI oocytes), and only MI oocytes were included in the experimental analysis. MI oocytes were cultured either in conventional medium or in medium supplemented with autologous exosomes. The exosome-supplemented group demonstrated significantly higher in vitro maturation rates compared with the conventional culture group (63.63% vs. 11.53%; p < 0.001). Fertilization rates among matured oocytes were 76.19% and 33.33% in Groups II and I, respectively. In addition, favorable embryo development outcomes were observed in the exosome-treated group. Autologous exosome supplementation may enhance in vitro maturation and fertilization outcomes in women with diminished ovarian reserve. After accounting for clustering of oocytes within patients using generalized estimating equations, exosome supplementation remained significantly associated with successful oocyte maturation (OR 15.46, 95% CI 5.16-46.39; p < 0.001).