Intraovarian PRP therapy as a method for preparing women with low ovarian reserve for assisted reproductive technology programs: A literature review
DOI:
https://doi.org/10.37800/RM.1.2026.683Keywords:
intraovarian PRP , assisted reproductive technologies, low ovarian reserve, premature ovarian insufficiencyAbstract
Relevance: Ovarian senescence is a physiological process associated with a progressive decline in both the quantity and quality of oocytes stored within follicular cohorts. The main causes of diminished ovarian reserve (DOR) include age-related changes, endocrine disorders, genetic and autoimmune factors, prior ovarian surgery, exposure to chemotherapy and radiotherapy, as well as adverse environmental influences. DOR has major clinical and scientific significance in assisted reproductive technology (ART) programs, as it substantially worsens reproductive outcomes and prognosis. The growing number of women with premature ovarian failure, advanced reproductive age, and late motherhood is driving the search for new approaches aimed at restoring ovarian function. One such approach is intraovarian autologous platelet-rich plasma (PRP) therapy.
This study aimed to review the current evidence regarding the mechanisms of action, clinical efficacy, and safety of intraovarian autologous platelet-rich plasma therapy in women with diminished ovarian reserve.
Materials and Methods: A literature search was conducted using the study’s keywords across international databases (PubMed, Scopus, Web of Science, and Google Scholar) and available domestic scientific sources for 2015-2025.
Results: Intraovarian PRP therapy improves microcirculation and transient restoration of the follicular reserve, increases the number of antral follicles, follicle-stimulating hormone, and the quality of eggs, which positively affects the success of VRT. However, the generalizability of the results is limited by the high heterogeneity of the available studies in design, sample size, inclusion criteria, and intraovarian PRP plasma therapy protocols. Obtained data evidence the need for further multi-center randomized controlled studies.
Conclusion: Intraovarian PRP therapy is a promising method of restoring ovarian function and improving ovarian reserve in women with DOR. Early clinical results indicate potential effects of PRP, such as improving oocyte quality and supporting fertility. However, further studies are needed to fully assess the long-term effects and safety.
References
1. European Society of Human Reproduction and Embryology (ESHRE). (2016). ESHRE Guideline: Management of women with premature ovarian insufficiency. Human Reproduction, 31(5), 926–937. https://doi.org/10.1093/humrep/dew027
2. Hansen, K. R., Craig, L. B., Zavy, M. T., Klein, N. A., & Soules, M. R. (2012). Ovarian primordial and nongrowing follicle counts according to the STRAW staging system. Menopause, 19(2), 164–171. https://doi.org/10.1097/gme.0b013e31823b0b2e
3. Shi, Y., Ren, Y., Zhao, W., et al. (2020). Mitochondrial dysfunction in ovarian aging. Aging and Disease, 11(5), 1210–1228. https://doi.org/10.14336/AD.2020.1113
4. Reynolds, A. C., Nichols, H. B., Rosen, M. P., et al. (2023). Cancer treatment–related ovarian dysfunction in women. Journal of Clinical Oncology, 41(6), 1341–1356. https://doi.org/10.1200/JCO.22.01885
5. Шишиморова, М. С., Тевкин, С. И., & Джусубалиева, Т. М. (2022). «Женщины 40+ в "свежих" недонорских программах ВРТ: шанс на успех?» Ремедиум, 3, 24–33. https://doi.org/10.37800/RM.3.2022.24-33
6. Cohen, J., et al. (2016). Outcomes of first IVF/ICSI in young women with diminished ovarian reserve. Minerva Ginecologica, 69(4), 315–321. https://doi.org/10.23736/S0026-4784.16.04003-X
7. Marx R.E. (2004).Platelet-rich plasma: evidence to support its use.Journal of Oral and Maxillofacial Surgery, 62(4), 489–496.https://doi.org/10.1016/j.joms.2003.12.003
8. Moustakli E., et al. Platelet-Rich Plasma (PRP) in Reproductive Medicine: a critical review of PRP therapy in low-reserve and premature ovarian insufficiency. Biomedicines. 2025;13(5):1257. PMCID: PMC12109040. https://doi.org/10.3390/biomedicines13051257
9. Elias M., et al. Platelet-rich plasma treatment of the ovaries significantly improves fertility parameters and reproductive outcomes in diminished ovarian reserve patients: a systematic review and meta-analysis. Journal of Ovarian Research. 2024;17:23. https://doi.org/10.1186/s13048-024-01423-2
10. Kawamura K., Cheng Y., Suzuki N., et al. Hippo signaling disruption and Akt stimulation of ovarian follicle growth. Proc Natl Acad Sci U S A. 2013;110(43):17474–17479. https://doi.org/10.1073/pnas.1312830110
11. 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. Preprints. 2023. https://doi.org/10.20944/preprints202306.1357.v1
12. Habara O., Logan C.Y., Kanai-Azuma M., Nusse R., Takase H.M.
WNT signaling in pre-granulosa cells is required for ovarian folliculogenesis and female fertility. Development. 2021;148(9):dev198846. https://doi.org/10.1242/dev.198846
13. Cedars, M. I. (2022). Evaluation of Female Fertility-AMH and Ovarian Reserve Testing. The Journal of Clinical Endocrinology & Metabolism, 107(2), e165–e172. https://doi.org/10.1210/clinem/dgac039
14. Abedini A., Zamberlam G., Lapointe E., Tourigny C., Boyer A., Paquet M., Hayashi K., Honda H., Kikuchi A., Price C.A., Boerboom D. (2016).WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling. The FASEB Journal, 30(4), 1534–1547.
https://doi.org/10.1096/fj.15-280313
15. Clark K.L., George J.W., Przygrodzka E., Plewes M.R., Hua G., Wang C., Davis J.S. Hippo signaling in the ovary: emerging roles in ovarian physiology and pathology. Endocrine Rev. 2022;43(6):1074–1096. https://doi.org/10.1210/endrev/bnac013
16. Zhu M., Xu M., Zhang J., Zheng C. The role of Hippo pathway in ovarian development. Front Physiol. 2023;14:1198873. https://doi.org/10.3389/fphys.2023.1198873
17. 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(2):94. https://doi.org/10.5653/cerm.2019.03405
18. Sills E.S., Rickers N.S., Svid C.S., Rickers J.M., Wood S.H.
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(1):84–90. https://doi.org/10.22088/IJMCM.BUMS.8.1.84
19. Cakıroğlu Y., Yücetürk A., Karaosmanoğlu O., Kopuk S.Y., Korun Z.E., Herlihy N., Scott R.T. Jr., Tıraş B., Seli E. Ovarian reserve parameters and IVF outcomes in 510 women with poor ovarian response treated with intraovarian injection of autologous platelet-rich plasma. Aging (Albany NY). 2022;14(6):2513–2523. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004561/
20. Sfakianoudis K., Simopoulou M., Grigoriadis S., Pantou A., Tsioulou P., Maziotis E., Rapani A., Giannelou P., Nitsos N., Kokkali G., Koutsilieris M., Vlahos N., Mastorakos G. 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(6):1809. https://doi.org/10.3390/jcm9061809
21. Devenutto L.M., Valzacchi G.R., Ercolano M., Etchegoyen O. Intraovarian platelet-rich plasma injection in poor responders. JBRA Assist Reprod. 2024;28(3):450–456. https://doi.org/10.5935/1518-0557.20240031
22. Potiris A., Stavros S., Voros C., Christopoulos P., Pouliakis A., Savvidis M., Papapanagiotou A., Karampitsakos T., Topis S., Vrantza T., Salvara M., Gerede A., Anysiadou S., Daskalakis G., Drakakis P., Domali E. Intraovarian platelet-rich plasma administration for anovulatory infertility: preliminary findings of a prospective cohort study. J Clin Med. 2024;13(17):5292. https://doi.org/10.3390/jcm13175292
23. Barrenetxea G., Celis R., Barrenetxea J., Martínez E., De Las Heras M., Gómez O., Aguirre O.Intraovarian platelet-rich plasma injection and IVF outcomes in patients with poor ovarian response: a double-blind randomized controlled trial. Hum Reprod. 2024;39(4):760–769. https://doi.org/10.1093/humrep/deae038
24. Barad D.H., Albertini D.F., Molinari E., Gleicher N. Preliminary report of intraovarian injections of autologous platelet-rich plasma (PRP) in extremely poor prognosis patients with only oocyte donation as alternative: a prospective cohort study. Hum Reprod Open. 2022;2022(3):hoac027. https://doi.org/10.1093/hropen/hoac027
25. Farimani M., Heshmati S., Poorolajal J., Bahmanzadeh M. A report on three live births in women with poor ovarian response following intra-ovarian injection of platelet-rich plasma (PRP). Mol Biol Rep. 2019;46(3):1611–1616. https://doi.org/10.1007/s11033-019-04609-w
26. Agarwal R., Shruthi R., Radhakrishnan G., Singh A. Evaluation of dehydroepiandrosterone (DHEA) supplementation on diminished ovarian reserve: a randomized, double-blinded, placebo-controlled study. J Obstet Gynaecol India. 2017;67(2):137–142. https://doi.org/10.1007/s13224-016-0941-8
27. Yeung T.W.Y., Chai J., Li R.H.W., Lee V.C.Y., Ho P.C., Ng E.H.Y. A randomized, controlled, pilot trial on the effect of dehydroepiandrosterone (DHEA) supplementation on ovarian response markers, ovarian response, and in vitro fertilization outcomes in poor responders. Fertil Steril. 2014;102(1):108–115.e1. https://doi.org/10.1016/j.fertnstert.2014.03.044
28. Keane K.N., Yovich J.L., Hamidi A., Hinchliffe P.M., Dhaliwal S.S. (2017). Single-centre retrospective analysis of growth hormone supplementation in IVF patients classified as poor-prognosis. BMJ Open, 7(5), e018107. https://doi.org/10.1136/bmjopen-2017-018107
29. Tang Y., Li X., Hu C., Guan R., Wang Z., Zhang S., Tao G., Qu J., Gong F. (2025). Exploring the potential benefits of growth hormone co-treatment on embryo quality in IVF: a randomized controlled open-label trial. Reproductive Biology and Endocrinology, 23(1), 42. https://doi.org/10.1186/s12958-025-01374-3
30. Vaiarelli A., Cimadomo D., Argento C., Ubaldi N., Trabucco E., Drakopoulos P., et al. (2018). Double stimulation in the same ovarian cycle (DuoStim) to maximize the number of oocytes retrieved from poor prognosis patients: a multicenter experience and systematic review. Frontiers in Endocrinology, 9, 317. https://doi.org/10.3389/fendo.2018.00317
31. Polat M., Mumusoglu S., Kahyaoglu I., et al. (2021). Double or dual stimulation in poor ovarian responders. Therapeutic Advances in Reproductive Health, 15, 1–10. https://doi.org/10.1177/26334941211024172
32. Sharara F.I., Leong M., Mejia R.B. (2021).A narrative review of platelet-rich plasma (PRP) in reproductive medicine.Journal of Assisted Reproduction and Genetics, 38(12), 3273–3286. https://doi.org/10.1007/s10815-021-02146-9
33. Dohan Ehrenfest D.M., Rasmusson L., Albrektsson T. (2009).Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF).Trends in Biotechnology, 27(3), 158–167. https://doi.org/10.1016/j.tibtech.2008.11.009
34. Cavallo C., Roffi A., Grigolo B., Mariani E., Pratelli L., Merli G., Kon E., Marcacci M., Filardo G. (2016).Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules.BioMed Research International, 2016, 6591717.
https://doi.org/10.1155/2016/6591717
35. Fraidakis M., Giannakakis G., Anifantaki A., Skouradaki M., Tsakoumi P., Bitzopoulou P., Kourpa S., Zervakis A., Kakouri P. (2023). Intraovarian Platelet-Rich Plasma Injections: Safety and Thoughts on Efficacy Based on a Single Centre Experience With 469 Women.Cureus, 15 (5), e38674. https://doi.org/10.7759/cureus.38674
36. 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.Journal of Assisted Reproduction and Genetics. 2020;37:855–863. https://doi.org/10.1007/s10815-020-01710-z
37. Tickoo S., Kalra J., Mahajan N., Gupta S.Role on intraovarian platelet-rich plasma in the poor ovarian responder: effects and safety of monthly injections.Journal of South Asian Federation of Obstetrics and Gynaecology. 2023;15(5):601–604. https://doi.org/10.5005/jp-journals-10006-2055
38. Moustakli E., Potiris A., Zikopoulos A.Platelet-rich plasma (PRP) in reproductive medicine: a critical review of PRP therapy in low-reserve and premature ovarian insufficiency.Biomedicines. 2025;13(5):1257. https://doi.org/10.3390/biomedicines13051257
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 А.А. Бутабекова , С.С. Искаков , В.Н. Локшин
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The articles published in this Journal are licensed under the CC BY-NC-ND 4.0 (Creative Commons Attribution – Non-Commercial – No Derivatives 4.0 International) license, which provides for their non-commercial use only. Under this license, users have the right to copy and distribute the material in copyright but are not permitted to modify or use it for commercial purposes. Full details on the licensing are available at https://creativecommons.org/licenses/by-nc-nd/4.0/.
