Abstract

Research Article

Rejuvenation of Ovarian Function after Autologous Platelet Lysate Injection: Promising Evidence from Confirmed Cases

Athanasios Garavelas, Efstathios Michalopoulos*, Panagiotis Mallis and Eros Nikitos

Published: 13 December, 2023 | Volume 6 - Issue 4 | Pages: 225-232

Intraovarian injection of autologous Platelet Lysate (PL) can be considered a potential therapeutic strategy for ovarian function rejuvenation. Especially, in women diagnosed with Poor Ovarian Response (POR) or Primary Ovarian Insufficiency (POI), the exogenous administration of the autologous platelet-derived growth factors, influence positively the regulation of the serum Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), and Anti-Mullerian Hormone (AMH) and Estradiol (E2). Therefore, the evaluation of the serum levels of the aforementioned hormones was performed on 10 participants with a mean age of 43 ± 4 years diagnosed with POR or POI, who received intraovarian PL injection monotherapy. The monitoring of the serum hormone levels was performed for 3 months. The results of this study clearly showed that all participants were characterized by elevated levels of FSH and LH and reduced levels of E2 and AMH, prior to the PL injection. However, the levels of all hormones started to change after the 1st month of follow-up monitoring. Moreover, 40% of the participants conceived successfully either by natural way or after in vitro Fertilization (IVF). Considering these, the intraovarian injection of autologous PL exhibited promising evidence regarding the altering of hormone levels at physiological values. Moreover, the contained PL growth factors were implicated in angiogenesis promotion and also in toleration of the inflammatory microenvironment, regulating positively ovarian function. In conclusion, the intraovarian autologous PL injection is considered a safe, effective, and tolerable therapeutic strategy in women with POR or POI. Moreover, the results of this study were very encouraging, especially for the women with infertility issues, who want their genetic offspring.

Read Full Article HTML DOI: 10.29328/journal.cjog.1001153 Cite this Article Read Full Article PDF

Keywords:

Poor ovarian response; Premature ovarian insufficiency; Platelet iysate; Intraovarian infusion; Follicle stimulating hormone; Pregnancy; Rejuvenation

References

  1. Panda SR, Sachan S, Hota S. A Systematic Review Evaluating the Efficacy of Intra-Ovarian Infusion of Autologous Platelet-Rich Plasma in Patients With Poor Ovarian Reserve or Ovarian Insufficiency. Cureus. 2020 Dec 12;12(12):e12037. doi: 10.7759/cureus.12037. PMID: 33457137; PMCID: PMC7797441.
  2. Goswami D, Conway GS. Premature ovarian failure. Hum Reprod Update. 2005 Jul-Aug;11(4):391-410. doi: 10.1093/humupd/dmi012. Epub 2005 May 26. PMID: 15919682.
  3. De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010 Sep 11;376(9744):911-21. doi: 10.1016/S0140-6736(10)60355-8. Epub 2010 Aug 11. PMID: 20708256.
  4. Cohen J, Chabbert-Buffet N, Darai E. Diminished ovarian reserve, premature ovarian failure, poor ovarian responder--a plea for universal definitions. J Assist Reprod Genet. 2015 Dec;32(12):1709-12. doi: 10.1007/s10815-015-0595-y. Epub 2015 Oct 13. PMID: 26463876; PMCID: PMC4681731.
  5. Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19. PMID: 21505041.
  6. Fragoulakis V, Maniadakis N. Estimating the long-term effects of in vitro fertilization in Greece: an analysis based on a lifetime-investment model. Clinicoecon Outcomes Res. 2013 Jun 20;5:247-55. doi: 10.2147/CEOR.S44784. PMID: 23818800; PMCID: PMC3694799.
  7. Chae-Kim JJ, Gavrilova-Jordan L. Premature Ovarian Insufficiency: Procreative Management and Preventive Strategies. Biomedicines. 2018 Dec 28;7(1):2. doi: 10.3390/biomedicines7010002. PMID: 30597834; PMCID: PMC6466184.
  8. Sfakianoudis K, Simopoulou M, Rapani A, Grigoriadis S, Maziotis E, Giannelou P, Pantou A, Vaxevanoglou T, Fakiridou M, Koutsilieris M, Pantos K. The Impact of the Economic Recession in Greece on Assisted Reproduction Demand: A Retrospective Longitudinal Study. Medicina (Kaunas). 2019 Sep 29;55(10):654. doi: 10.3390/medicina55100654. PMID: 31569483; PMCID: PMC6843187.
  9. Women are having their first child at an older age - Products Eurostat News – Eurostat. https://ec.europa.eu/eurostat/web/products-eurostat-news/-/ddn-20200515-2.
  10. Shelling AN, Ahmed Nasef N. The Role of Lifestyle and Dietary Factors in the Development of Premature Ovarian Insufficiency. Antioxidants (Basel). 2023 Aug 11;12(8):1601. doi: 10.3390/antiox12081601. PMID: 37627595; PMCID: PMC10451748.
  11. Ebrahimi M, Akbari Asbagh F. Pathogenesis and causes of premature ovarian failure: an update. Int J Fertil Steril. 2011 Jul;5(2):54-65. Epub 2011 Sep 23. PMID: 24963360; PMCID: PMC4059950.
  12. Matsuda F, Inoue N, Manabe N, Ohkura S. Follicular growth and atresia in mammalian ovaries: regulation by survival and death of granulosa cells. J Reprod Dev. 2012;58(1):44-50. doi: 10.1262/jrd.2011-012. PMID: 22450284.
  13. Rimon-Dahari N, Yerushalmi-Heinemann L, Alyagor L, Dekel N. Ovarian Folliculogenesis. Results Probl Cell Differ. 2016;58:167-90. doi: 10.1007/978-3-319-31973-5_7. PMID: 27300179.
  14. Yang DZ, Yang W, Li Y, He Z. Progress in understanding human ovarian folliculogenesis and its implications in assisted reproduction. J Assist Reprod Genet. 2013 Feb;30(2):213-9. doi: 10.1007/s10815-013-9944-x. PMID: 23388838; PMCID: PMC3585681.
  15. Vegetti W, Alagna F. FSH and folliculogenesis: from physiology to ovarian stimulation. Reprod Biomed Online. 2006 Jun;12(6):684-94. doi: 10.1016/s1472-6483(10)61080-2. PMID: 16792843.
  16. Fadini R, Coticchio G, Brambillasca F, Mignini Renzini M, Novara PV, Brigante C, De Ponti E, Dal Canto M. Clinical outcomes from mature oocytes derived from preovulatory and antral follicles: reflections on follicle physiology and oocyte competence. J Assist Reprod Genet. 2015 Feb;32(2):255-61. doi: 10.1007/s10815-014-0386-x. Epub 2014 Dec 2. PMID: 25449291; PMCID: PMC4354189.
  17. Erickson GF, Shimasaki S. The physiology of folliculogenesis: the role of novel growth factors. Fertil Steril. 2001 Nov;76(5):943-9. doi: 10.1016/s0015-0282(01)02859-x. PMID: 11704115.
  18. Trombly DJ, Woodruff TK, Mayo KE. Roles for transforming growth factor beta superfamily proteins in early folliculogenesis. Semin Reprod Med. 2009 Jan;27(1):14-23. doi: 10.1055/s-0028-1108006. Epub 2009 Feb 5. PMID: 19197801; PMCID: PMC2947191.
  19. Hussein MR. Apoptosis in the ovary: molecular mechanisms. Hum Reprod Update. 2005 Mar-Apr;11(2):162-77. doi: 10.1093/humupd/dmi001. Epub 2005 Feb 10. PMID: 15705959.
  20. Garavelas A, Mallis P, Michalopoulos E, Nikitos E. Clinical Benefit of Autologous Platelet-Rich Plasma Infusion in Ovarian Function Rejuvenation: Evidence from a Before-After Prospective Pilot Study. Medicines (Basel). 2023 Feb 27;10(3):19. doi: 10.3390/medicines10030019. PMID: 36976308; PMCID: PMC10056078.
  21. Rickers NS, Sills ES. Is autologous platelet activation the key step in ovarian therapy for fertility recovery and menopause reversal? Biomedicine (Taipei). 2022 Dec 1;12(4):1-8. doi: 10.37796/2211-8039.1380. PMID: 36816178; PMCID: PMC9910228.
  22. Sharara FI, Lelea LL, Rahman S, Klebanoff JS, Moawad GN. A narrative review of platelet-rich plasma (PRP) in reproductive medicine. J Assist Reprod Genet. 2021 May;38(5):1003-1012. doi: 10.1007/s10815-021-02146-9. Epub 2021 Mar 15. PMID: 33723748; PMCID: PMC8190208.
  23. Ahmadian S, Sheshpari S, Pazhang M, Bedate AM, Beheshti R, Abbasi MM, Nouri M, Rahbarghazi R, Mahdipour M. Intra-ovarian injection of platelet-rich plasma into ovarian tissue promoted rejuvenation in the rat model of premature ovarian insufficiency and restored ovulation rate via angiogenesis modulation. Reprod Biol Endocrinol. 2020 Aug 5;18(1):78. doi: 10.1186/s12958-020-00638-4. PMID: 32758249; PMCID: PMC7405361.
  24. Cakiroglu Y, Saltik A, Yuceturk A, Karaosmanoglu O, Kopuk SY, Scott RT, Tiras B, Seli E. Effects of intraovarian injection of autologous platelet rich plasma on ovarian reserve and IVF outcome parameters in women with primary ovarian insufficiency. Aging (Albany NY). 2020 Jun 5;12(11):10211-10222. doi: 10.18632/aging.103403. Epub 2020 Jun 5. PMID: 32507764; PMCID: PMC7346073.
  25. Park HS, Ulin M, Cetin E. Ovarian Rejuvenation Using Platelet-Rich Plasma: a Promising Option for Women in Early Menopause to Have a Baby. Reprod Sci. 2020 Nov;27(11):1983-1984. doi: 10.1007/s43032-020-00315-2. Epub 2020 Sep 15. PMID: 32935255.
  26. Aflatoonian A, Lotfi M, Saeed L, Tabibnejad N. Effects of Intraovarian Injection of Autologous Platelet-Rich Plasma on Ovarian Rejuvenation in Poor Responders and Women with Primary Ovarian Insufficiency. Reprod Sci. 2021 Jul;28(7):2050-2059. doi: 10.1007/s43032-021-00483-9. Epub 2021 Mar 8. PMID: 33683669.
  27. Petryk N, Petryk M. Ovarian Rejuvenation Through Platelet-Rich Autologous Plasma (PRP)-a Chance to Have a Baby Without Donor Eggs, Improving the Life Quality of Women Suffering from Early Menopause Without Synthetic Hormonal Treatment. Reprod Sci. 2020 Nov;27(11):1975-1982. doi: 10.1007/s43032-020-00266-8. Epub 2020 Jul 22. PMID: 32700285.
  28. Mallis P, Michalopoulos E, Balampanis K, Sarri EF, Papadopoulou E, Theodoropoulou V, Georgiou E, Kountouri A, Lambadiari V, Stavropoulos-Giokas C. Investigating the production of platelet lysate obtained from low volume Cord Blood Units: Focus on growth factor content and regenerative potential. Transfus Apher Sci. 2022 Dec;61(6):103465. doi: 10.1016/j.transci.2022.103465. Epub 2022 May 20. PMID: 35623959.
  29. Pavlovic V, Ciric M, Jovanovic V, Stojanovic P. Platelet Rich Plasma: a short overview of certain bioactive components. Open Med (Wars). 2016 Aug 12;11(1):242-247. doi: 10.1515/med-2016-0048. PMID: 28352802; PMCID: PMC5329835.
  30. Klatte-Schulz F, Schmidt T, Uckert M, Scheffler S, Kalus U, Rojewski M, Schrezenmeier H, Pruss A, Wildemann B. Comparative Analysis of Different Platelet Lysates and Platelet Rich Preparations to Stimulate Tendon Cell Biology: An In Vitro Study. Int J Mol Sci. 2018 Jan 10;19(1):212. doi: 10.3390/ijms19010212. PMID: 29320421; PMCID: PMC5796161.
  31. Protogerou V, Beshari SE, Michalopoulos E, Mallis P, Chrysikos D, Samolis AA, Stavropoulos-Giokas C, Troupis T. The Combined Use of Stem Cells and Platelet Lysate Plasma for the Treatment of Erectile Dysfunction: A Pilot Study-6 Months Results. Medicines (Basel). 2020 Mar 18;7(3):14. doi: 10.3390/medicines7030014. PMID: 32197323; PMCID: PMC7151592.
  32. Protogerou V, Michalopoulos E, Mallis P, Gontika I, Dimou Z, Liakouras C, Stavropoulos-Giokas C, Kostakopoulos N, Chrisofos M, Deliveliotis C. Administration of Adipose Derived Mesenchymal Stem Cells and Platelet Lysate in Erectile Dysfunction: A Single Center Pilot Study. Bioengineering (Basel). 2019 Mar 5;6(1):21. doi: 10.3390/bioengineering6010021. PMID: 30841525; PMCID: PMC6466012.
  33. Rebulla P, Pupella S, Santodirocco M, Greppi N, Villanova I, Buzzi M, De Fazio N, Grazzini G; Italian Cord Blood Platelet Gel Study Group (see Appendix 1). Multicentre standardisation of a clinical grade procedure for the preparation of allogeneic platelet concentrates from umbilical cord blood. Blood Transfus. 2016 Jan;14(1):73-9. doi: 10.2450/2015.0122-15. Epub 2015 Jul 29. PMID: 26509822; PMCID: PMC4731342.
  34. Mallis P, Michalopoulos E, Sarri EF, Papadopoulou E, Theodoropoulou V, Katsimpoulas M, Stavropoulos-Giokas C. Evaluation of the Regenerative Potential of Platelet-Lysate and Platelet-Poor Plasma Derived from the Cord Blood Units in Corneal Wound Healing Applications: An In Vitro Comparative Study on Corneal Epithelial Cells. Curr Issues Mol Biol. 2022 Sep 22;44(10):4415-4438. doi: 10.3390/cimb44100303. PMID: 36286018; PMCID: PMC9600746.
  35. Azmi AF, Yahya MAAM, Azhar NA, Ibrahim N, Ghafar NA, Ghani NAA, Nizar MAM, Yunus SSM, Singh TKL, Law JX, Ng SL. In Vitro Cell Proliferation and Migration Properties of Oral Mucosal Fibroblasts: A Comparative Study on the Effects of Cord Blood- and Peripheral Blood-Platelet Lysate. Int J Mol Sci. 2023 Mar 17;24(6):5775. doi: 10.3390/ijms24065775. PMID: 36982842; PMCID: PMC10058190.
  36. Ng SL, Azhar NA, Budin SB, Ibrahim N, Abdul Ghani NA, Abd Ghafar N, Law JX. Effects of Platelet Lysate Gels Derived from Different Blood Sources on Oral Mucosal Wound Healing: An In Vitro Study. Gels. 2023 Apr 17;9(4):343. doi: 10.3390/gels9040343. PMID: 37102955; PMCID: PMC10137921.
  37. Suresh A, Balouch B, Martha VV, Sataloff RT. Laryngeal Applications of Platelet Rich Plasma and Platelet Poor Plasma: A Systematic Review. J Voice. 2021 Aug 9:S0892-1997(21)00232-0. doi: 10.1016/j.jvoice.2021.07.007. Epub ahead of print. PMID: 34384663.
  38. Mallis P, Michalopoulos E, Balampanis K, Sarri EF, Papadopoulou E, Theodoropoulou V, Georgiou E, Kountouri A, Lambadiari V, Stavropoulos-Giokas C. Investigating the production of platelet lysate obtained from low volume Cord Blood Units: Focus on growth factor content and regenerative potential. Transfus Apher Sci. 2022 Dec;61(6):103465. doi: 10.1016/j.transci.2022.103465. Epub 2022 May 20. PMID: 35623959.
  39. Sfakianoudis K, Simopoulou M, Nitsos N, Rapani A, Pappas A, Pantou A, Chronopoulou M, Deligeoroglou E, Koutsilieris M, Pantos K. Autologous Platelet-Rich Plasma Treatment Enables Pregnancy for a Woman in Premature Menopause. J Clin Med. 2018 Dec 20;8(1):1. doi: 10.3390/jcm8010001. PMID: 30577435; PMCID: PMC6352170.
  40. Sfakianoudis K, Simopoulou M, Grigoriadis S, Pantou A, Tsioulou P, Maziotis E, Rapani A, Giannelou P, Nitsos N, Kokkali G, Koutsilieris M, Pantos K. Reactivating Ovarian Function through Autologous Platelet-Rich Plasma Intraovarian Infusion: Pilot Data on Premature Ovarian Insufficiency, Perimenopausal, Menopausal, and Poor Responder Women. J Clin Med. 2020 Jun 10;9(6):1809. doi: 10.3390/jcm9061809. PMID: 32532000; PMCID: PMC7355907.
  41. Fraser HM. Regulation of the ovarian follicular vasculature. Reprod Biol Endocrinol. 2006 Apr 12;4:18. doi: 10.1186/1477-7827-4-18. PMID: 16611363; PMCID: PMC1459163.
  42. Ishizuka B. Current Understanding of the Etiology, Symptomatology, and Treatment Options in Premature Ovarian Insufficiency (POI). Front Endocrinol (Lausanne). 2021 Feb 25;12:626924. doi: 10.3389/fendo.2021.626924. PMID: 33716979; PMCID: PMC7949002.
  43. Ferrari AR, Cortrezzi S, Borges E Junior, Braga D, Souza MDCB, Antunes RA. Evaluation of the Effects of Platelet-Rich Plasma on Follicular and Endometrial Growth: A Literature Review. JBRA Assist Reprod. 2021 Oct 4;25(4):601-607. doi: 10.5935/1518-0557.20210036. PMID: 34415119; PMCID: PMC8489815.
  44. McFee RM, Rozell TG, Cupp AS. The balance of proangiogenic and antiangiogenic VEGFA isoforms regulate follicle development. Cell Tissue Res. 2012 Sep;349(3):635-47. doi: 10.1007/s00441-012-1330-y. Epub 2012 Feb 10. PMID: 22322423; PMCID: PMC3429770.
  45. Mikhael S, Punjala-Patel A, Gavrilova-Jordan L. Hypothalamic-Pituitary-Ovarian Axis Disorders Impacting Female Fertility. Biomedicines. 2019 Jan 4;7(1):5. doi: 10.3390/biomedicines7010005. PMID: 30621143; PMCID: PMC6466056.

Figures:

Figure 1

Figure 1

Figure 1

Figure 2

Similar Articles

Recently Viewed

Read More

Most Viewed

Read More

Help ?