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mTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve?

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 ‘acces...

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Autores principales: Sills, E. Scott, Harrity, Conor, Wood, Samuel H., Tan, Seang Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381109/
https://www.ncbi.nlm.nih.gov/pubmed/37511761
http://dx.doi.org/10.3390/jpm13071147
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author Sills, E. Scott
Harrity, Conor
Wood, Samuel H.
Tan, Seang Lin
author_facet Sills, E. Scott
Harrity, Conor
Wood, Samuel H.
Tan, Seang Lin
author_sort Sills, E. Scott
collection PubMed
description 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 having an impact on the existing follicle pool, platelet growth factors might also facilitate de novo oocyte recruitment by specified gene upregulation targeting uncommitted ovarian stem cells. Given that disordered activity at the 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 proposal is the first to discuss 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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spelling pubmed-103811092023-07-29 mTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve? Sills, E. Scott Harrity, Conor Wood, Samuel H. Tan, Seang Lin J Pers Med Brief Report 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 having an impact on the existing follicle pool, platelet growth factors might also facilitate de novo oocyte recruitment by specified gene upregulation targeting uncommitted ovarian stem cells. Given that disordered activity at the 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 proposal is the first to discuss 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. MDPI 2023-07-17 /pmc/articles/PMC10381109/ /pubmed/37511761 http://dx.doi.org/10.3390/jpm13071147 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Sills, E. Scott
Harrity, Conor
Wood, Samuel H.
Tan, Seang Lin
mTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve?
title mTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve?
title_full mTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve?
title_fullStr mTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve?
title_full_unstemmed mTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve?
title_short mTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve?
title_sort mtor inhibition via low-dose, pulsed rapamycin with intraovarian condensed platelet cytokines: an individualized protocol to recover diminished reserve?
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381109/
https://www.ncbi.nlm.nih.gov/pubmed/37511761
http://dx.doi.org/10.3390/jpm13071147
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