DOI QR코드

DOI QR Code

Intraovarian platelet-rich plasma administration could improve blastocyst euploidy rates in women undergoing in vitro fertilization

  • Merhi, Zaher (Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, SUNY Downstate Health Sciences University) ;
  • Seckin, Serin (Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, SUNY Downstate Health Sciences University) ;
  • Mouanness, Marco (Rejuvenating Fertility Center)
  • Received : 2021.10.27
  • Accepted : 2022.05.19
  • Published : 2022.09.30

Abstract

Objective: Platelet-rich plasma (PRP) therapy has received a considerable attention as an adjunct to fertility treatments, especially in women with very low ovarian reserve and premature ovarian insufficiency. Although recent studies have demonstrated that PRP led to improvements in folliculogenesis and biomarkers of ovarian reserve, the effect of intraovarian PRP administration on embryo genetics has not been studied. Methods: We report a pilot study of patients who had preimplantation genetic testing for aneuploidy (PGT-A) before and then within 3 months following PRP administration. Twelve infertile women with at least one prior failed in vitro fertilization (IVF) cycle underwent ovarian stimulation (cycle 1) with a gentle stimulation protocol and PGT-A performed at the blastocyst stage. Following cycle 1, autologous intraovarian PRP administration was performed. Within 3 months following PRP administration, the patients underwent cycle 2 and produced blastocysts for PGT-A. The percentage of euploid embryos between both cycles was compared. Results: The mean age of all participants was 40.08±1.46 years, and their mean body mass index was 26.18±1.18 kg/m2. The number of good-quality embryos formed at the blastocyst stage was similar between cycle 1 and cycle 2 (3.08±0.88 vs. 2.17±0.49, respectively; p=0.11). Among all patients in cycle 1, 3 of 37 embryos were euploid (8.11%) while in cycle 2, 11 out of 28 embryos were euploid (39.28%, p=0.002). Three clinical pregnancies were noted among this patient group. Conclusion: This novel study is the first to present an improvement in the embryo euploidy rate following intraovarian PRP application in infertile women with prior failed IVF cycles. The growth factors present in PRP may exhibit a local paracrine effect that could improve meiotic aberrations in human oocytes and thus improve euploidy rates. Whether PRP improves live birth rates and lowers miscarriage rates remains to be determined in large trials.

Keywords

References

  1. Labarta E, de Los Santos MJ, Escriba MJ, Pellicer A, Herraiz S. Mitochondria as a tool for oocyte rejuvenation. Fertil Steril 2019;111:219-26. https://doi.org/10.1016/j.fertnstert.2018.10.036
  2. Sills ES, Wood SH. Autologous activated platelet-rich plasma injection into adult human ovary tissue: molecular mechanism, analysis, and discussion of reproductive response. Biosci Rep 2019;39:BSR20190805. https://doi.org/10.1042/BSR20190805
  3. Pavlovic V, Ciric M, Jovanovic V, Stojanovic P. Platelet rich plasma: a short overview of certain bioactive components. Open Med (Wars) 2016;11:242-7. https://doi.org/10.1515/med-2016-0048
  4. Middleton KK, Barro V, Muller B, Terada S, Fu FH. Evaluation of the effects of platelet-rich plasma (PRP) therapy involved in the healing of sports-related soft tissue injuries. Iowa Orthop J 2012;32:150-63.
  5. Lee KY, Baker HP, Hanaoka CM, Tjong VK, Terry MA. Treatment of patellar and hamstring tendinopathy with platelet-rich plasma in varsity collegiate athletes: a case series. J Orthop 2019;18:91-4.
  6. Lin CP, Chang KV, Huang YK, Wu WT, Ozcakar L. Regenerative injections including 5% dextrose and platelet-rich plasma for the treatment of carpal tunnel syndrome: a systematic review and network meta-analysis. Pharmaceuticals (Basel) 2020;13:49. https://doi.org/10.3390/ph13030049
  7. Badsha H, Harifi G, Murrell WD. Platelet rich plasma for treatment of rheumatoid arthritis: case series and review of literature. Case Rep Rheumatol 2020;2020:8761485.
  8. Kassir M, Kroumpouzos G, Puja P, Katsambas A, Galadari H, Lotti T, et al. Update in minimally invasive periorbital rejuvenation with a focus on platelet-rich plasma: a narrative review. J Cosmet Dermatol 2020;19:1057-62. https://doi.org/10.1111/jocd.13376
  9. Zarin M, Karbalaei N, Keshtgar S, Nemati M. Platelet-rich plasma improves impaired glucose hemostasis, disrupted insulin secretion, and pancreatic oxidative stress in streptozotocin-induced diabetic rat. Growth Factors 2019;37:226-37. https://doi.org/10.1080/08977194.2020.1735382
  10. Xu J, Gou L, Zhang P, Li H, Qiu S. Platelet-rich plasma and regenerative dentistry. Aust Dent J 2020;65:131-42. https://doi.org/10.1111/adj.12754
  11. Yin S, Yang X, Bi H, Zhao Z. Combined use of autologous stromal vascular fraction cells and platelet-rich plasma for chronic ulceration of the diabetic lower limb improves wound healing. Int J Low Extrem Wounds 2021;20:135-42. https://doi.org/10.1177/1534734620907978
  12. Graf Guimaraes C, Mulinari-Brenner F, Werner B, Kusma S. Platelet-rich plasma associated with hair transplants for the treatment of androgenetic alopecia showed no benefits. J Eur Acad Dermatol Venereol 2020;34:e340-2.
  13. Colombo GV, Fanton V, Sosa D, Criado Scholz E, Lotti J, Aragona SE, et al. Use of platelet rich plasma in human infertility. J Biol Regul Homeost Agents 2017;31(2 Suppl. 2):179-82.
  14. Pantos K, Simopoulou M, Pantou A, Rapani A, Tsioulou P, Nitsos N, et al. A case series on natural conceptions resulting in ongoing pregnancies in menopausal and prematurely menopausal women following platelet-rich plasma treatment. Cell Transplant 2019; 28:1333-40. https://doi.org/10.1177/0963689719859539
  15. Sfakianoudis K, Simopoulou M, Grigoriadis S, Pantou A, Tsioulou P, Maziotis E, et al. 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;9:1809. https://doi.org/10.3390/jcm9061809
  16. Sills ES, Rickers NS, Li X, Palermo GD. First data on in vitro fertilization and blastocyst formation after intraovarian injection of calcium gluconate-activated autologous platelet rich plasma. Gynecol Endocrinol 2018;34:756-60. https://doi.org/10.1080/09513590.2018.1445219
  17. 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;27:1975-82. https://doi.org/10.1007/s43032-020-00266-8
  18. Melo P, Navarro C, Jones C, Coward K, Coleman L. The use of autologous platelet-rich plasma (PRP) versus no intervention in women with low ovarian reserve undergoing fertility treatment: a non-randomized interventional study. J Assist Reprod Genet 2020;37:855-63. https://doi.org/10.1007/s10815-020-01710-z
  19. Wood SH, Sills ES. Intraovarian vascular enhancement via stromal injection of platelet-derived growth factors: exploring subsequent oocyte chromosomal status and in vitro fertilization outcomes. Clin Exp Reprod Med 2020;47:94-100. https://doi.org/10.5653/cerm.2019.03405
  20. Sills ES, Rickers NS, Svid CS, Rickers JM, Wood SH. Normalized ploidy following 20 consecutive blastocysts with chromosomal error: healthy 46, XY pregnancy with IVF after intraovarian injection of autologous enriched platelet-derived growth factors. Int J Mol Cell Med 2019;8:84-90.
  21. Merhi Z, Seckin S, Mouanness M. Intraovarian PRP injection improved hot flashes in a woman with very low ovarian reserve. Reprod Sci 2022;29:614-9. https://doi.org/10.1007/s43032-021-00655-7
  22. Mouanness M, Ali-Bynom S, Jackman J, Seckin S, Merhi Z. Use of intra-uterine injection of platelet-rich plasma (PRP) for endometrial receptivity and thickness: a literature review of the mechanisms of action. Reprod Sci 2021;28:1659-70. https://doi.org/10.1007/s43032-021-00579-2
  23. Finch CE. The menopause and aging, a comparative perspective. J Steroid Biochem Mol Biol 2014;142:132-41. https://doi.org/10.1016/j.jsbmb.2013.03.010
  24. Lopatina T, Bruno S, Tetta C, Kalinina N, Porta M, Camussi G. Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential. Cell Commun Signal 2014;12:26. https://doi.org/10.1186/1478-811X-12-26
  25. Hosseini L, Shirazi A, Naderi MM, Shams-Esfandabadi N, Borjian Boroujeni S, Sarvari A, et al. Platelet-rich plasma promotes the development of isolated human primordial and primary follicles to the preantral stage. Reprod Biomed Online 2017;35:343-50. https://doi.org/10.1016/j.rbmo.2017.04.007
  26. Sills ES, Takeuchi T, Tucker MJ, Palermo GD. Genetic and epigenetic modifications associated with human ooplasm donation and mitochondrial heteroplasmy: considerations for interpreting studies of heritability and reproductive outcome. Med Hypotheses 2004;62:612-7. https://doi.org/10.1016/j.mehy.2003.10.008
  27. Jing Y, Li L, Li YY, Ouyang YC, Sun QY, Zhang CL, et al. Embryo quality, and not chromosome nondiploidy, affects mitochondrial DNA content in mouse blastocysts. J Cell Physiol 2019;234:10481-8. https://doi.org/10.1002/jcp.27713
  28. Liu Y, Xu J, Zhu F, Ye H, Hu C, Huang J, et al. Research advances in the regulation of the putative ovarian germline stem cell niche on female germline stem cells. Syst Biol Reprod Med 2019;65:121-8. https://doi.org/10.1080/19396368.2018.1515272
  29. Wu M, Xiong J, Ma L, Lu Z, Qin X, Luo A, et al. Enrichment of female germline stem cells from mouse ovaries using the differential adhesion method. Cell Physiol Biochem 2018;46:2114-26. https://doi.org/10.1159/000489452