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mTOR Inhibition via Low-dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve
Sills, E.S.; Harrity, C.; Wood, S.H.; Tan, S.L. MTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve? Journal of Personalized Medicine 2023, 13, 1147, doi:10.3390/jpm13071147.
Sills, E.S.; Harrity, C.; Wood, S.H.; Tan, S.L. MTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve? Journal of Personalized Medicine 2023, 13, 1147, doi:10.3390/jpm13071147.
Sills, E.S.; Harrity, C.; Wood, S.H.; Tan, S.L. MTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve? Journal of Personalized Medicine 2023, 13, 1147, doi:10.3390/jpm13071147.
Sills, E.S.; Harrity, C.; Wood, S.H.; Tan, S.L. MTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve? Journal of Personalized Medicine 2023, 13, 1147, doi:10.3390/jpm13071147.
Abstract
No major breakthroughs have entered mainstream clinical fertility practice since egg donation and intracytoplasmic sperm injection decades ago, and oocyte deficits secondary to advanced age continue as the main manifestation of diminished ovarian reserve. In the meantime, several unproven IVF ‘accessories’ have emerged including so-called ovarian rejuvenation which entails placing fresh autologous platelet-rich plasma (PRP) directly into ovarian tissue. Among cellular responses attributed to this intervention are reduced oxidative stress, slowed apoptosis, and improved metabolism. Besides impacting the existing follicle pool, platelet growth factors might also facilitate de novo oocyte recruitment by specified gene upregulation targeting uncommitted ovarian stem cells. Because disordered activity at mechanistic target of rapamycin (mTOR) has been shown to exacerbate or accelerate ovarian aging, PRP-discharged plasma cytokines combined with mTOR suppression by pulsed/cyclic rapamycin represents a novel fusion technique to enhance ovarian function. While beneficial effects have already been observed experimentally in oocytes and embryos with mTOR inhibition alone, this is the first discussion of intraovarian platelet cytokines followed by low-dose, phased rapamycin. For refractory cases, this investigational, tailored approach could amplify or sustain ovarian capacity sufficient to permit retrieval of competent oocytes via distinct but complementary pathways—thus reducing dependency on oocyte donation.
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