Molecular Biology Reports

, Volume 46, Issue 2, pp 1611–1616 | Cite as

A report on three live births in women with poor ovarian response following intra-ovarian injection of platelet-rich plasma (PRP)

  • Marzie Farimani
  • Safoura Heshmati
  • Jalal Poorolajal
  • Maryam BahmanzadehEmail author
Original Article


The prevalence of poor response to gonadotropin stimulation is approximately 9–24% in women undergoing in vitro fertilization. Interestingly, due to containing a variety of growth factors, platelet-rich plasma (PRP) can play an important role in tissue regeneration and healing. Thus, in this research, we aimed to investigate the intra-ovarian injection of PRP in women with poor ovarian response. To this goal, 23 poor responders constituted the study population, from among whom 19 women were enrolled. These patients underwent ovarian stimulation according to the Shanghai protocol. Immediately after the first follicular puncture, 2 mL of PRP was injected into each ovary. 1 day after the first puncture and PRP injection, the second stimulation was initiated. Then, oocyte retrieval was followed. About 2–3 months after the first cycle, the patients underwent another treatment with ovarian stimulation according to the Shanghai protocol and then, follicular puncture was performed. The mean numbers of oocytes before and after PRP injection were 0.64 and 2.1, respectively. Two patients experienced spontaneous conceptions. The third case achieved clinical pregnancy and delivered a healthy baby in June 2018. The results of this study appeared to be the first report on the effects of intra-ovarian PRP injection on the increase of ovarian responses, even on the spontaneous conceptions of women with poor ovarian response.


Platelet rich plasma Ovary Infertility Poor ovarian response Pregnancy 



The study was funded by vice-chancellor for Research and Technology, Hamadan University of Medical Sciences, Iran (Grant No. 960115299).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Jirge PR (2016) Poor ovarian reserve. J Hum Reprod Sci 9:62CrossRefGoogle Scholar
  2. 2.
    Giovanale V, Pulcinelli F, Ralli E, Primiero F, Caserta D (2015) Poor responders in IVF: an update in therapy. Gynecol Endocrinol 31(4):253–257CrossRefGoogle Scholar
  3. 3.
    Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, Shoham Z (2014) Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod BioMed Online 29(6):684–691. CrossRefGoogle Scholar
  4. 4.
    Moffat R, Pirtea P, Gayet V, Wolf JP, Chapron C, de Ziegler D (2014) Dual ovarian stimulation is a new viable option for enhancing the oocyte yield when the time for assisted reproductive technnology is limited. Reprodu BioMed Online 29(6):659–661. CrossRefGoogle Scholar
  5. 5.
    Sighinolfi G, Sunkara SK, La Marca A (2018) New strategies of ovarian stimulation based on the concept of ovarian follicular waves: from conventional to random and double stimulation. Reprod Biomed Online 37:489–497CrossRefPubMedGoogle Scholar
  6. 6.
    Murase T, Iwase A, Komatsu K, Bayasula, Nakamura T, Osuka S, Takikawa S, Goto M, Kotani T, Kikkawa F (2017) Follicle dynamics: visualization and analysis of follicle growth and maturation using murine ovarian tissue culture. J Assist Reprod Genet. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Siess W (1989) Molecular mechanisms of platelet activation. Physiol Rev 69(1):58–178CrossRefPubMedGoogle Scholar
  8. 8.
    Das D, Arur S (2017) Conserved insulin signaling in the regulation of oocyte growth, development, and maturation. Mol Reprod Dev 84:444–459CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Emori C, Sugiura K (2014) Role of oocyte-derived paracrine factors in follicular development. Anim Sci J 85(6):627–633CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Marini MG, Perrini C, Esposti P, Corradetti B, Bizzaro D, Riccaboni P, Fantinato E, Urbani G, Gelati G, Cremonesi F (2016) Effects of platelet-rich plasma in a model of bovine endometrial inflammation in vitro. Reprod Biol Endocrinol 14(1):58CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Xie X, Zhang C, Tuan RS (2014) Biology of platelet-rich plasma and its clinical application in cartilage repair. Arthritis Res Ther 16(1):204CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Sekerci C, Tanidir Y, Sener T, Sener G, Cevik O, Yarat A, Alev-Tuzuner B, Cetinel S, Kervancioglu E, Sahan A (2017) Effects of platelet-rich plasma against experimental ischemia/reperfusion injury in rat testis. J Pediatr Urol 13(3):e311–317CrossRefGoogle Scholar
  13. 13.
    Jang H-Y, Myoung SM, Choe JM, Kim T, Cheon Y-P, Kim YM, Park H (2017) Effects of autologous platelet-rich plasma on regeneration of damaged endometrium in female rats. Yonsei Med J 58(6):1195–1203CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Molina A, Sanchez J, Sanchez W, Vielma V (2018) Platelet-rich plasma as an adjuvant in the endometrial preparation of patients with refractory endometrium. JBRA Assist Reprod. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Farimani M, Bahmanzadeh M, Poorolajal J (2016) A new approach using autologous platelet-rich plasma (PRP) to treat infertility and to improve population replacement rate. J Res Health Sci 16(3):172–173PubMedGoogle Scholar
  16. 16.
    Farimani M, Poorolajal J, Rabiee S, Bahmanzadeh M (2017) Successful pregnancy and live birth after intrauterine administration of autologous platelet-rich plasma in a woman with recurrent implantation failure: a case report. Int J Reprod Biomed 15(12):803CrossRefGoogle Scholar
  17. 17.
    Scarpellini F, Sbracia M (2012) G-CSF treatment improves IVF outcome in women with recurrent implantation failure in IVF. J Reprod Immunol 94(1):103CrossRefGoogle Scholar
  18. 18.
    Fung M, Grossman B, Hillyer C, Westhoff C (2014) American assocation of blood banks. Technical manual, 18th edn. American Association of Blood Banks, Bethesda, pp 645–661Google Scholar
  19. 19.
    Bassiouny YA, Dakhly DMR, Bayoumi YA, Hashish NM (2016) Does the addition of growth hormone to the in vitro fertilization/intracytoplasmic sperm injection antagonist protocol improve outcomes in poor responders? a randomized, controlled trial. Fertil Steril 105(3):697–702CrossRefPubMedGoogle Scholar
  20. 20.
    Chang Y, Li J, Chen Y, Wei L, Yang X, Shi Y, Liang X (2015) Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med 8(1):1286–1290PubMedPubMedCentralGoogle Scholar
  21. 21.
    Sleer LS, Taylor CC (2007) Cell-type localization of platelet-derived growth factors and receptors in the postnatal rat ovary and follicle. Biol Reprod 76(3):379–390CrossRefPubMedGoogle Scholar
  22. 22.
    Abir R, Nitke S, Ben-Haroush A, Fisch B (2006) In vitro maturation of human primordial ovarian follicles. Clinical significance, progress in mammals, and methods for growth evaluation. Histol Histopathol 21:887–898PubMedGoogle Scholar
  23. 23.
    Yoon S-J, Kim K-H, Chung H-M, Choi D-H, Lee W-S, Cha K-Y, Lee K-A (2006) Gene expression profiling of early follicular development in primordial, primary, and secondary follicles. Fertil Steril 85(1):193–203CrossRefPubMedGoogle Scholar
  24. 24.
    Pinkas H, Fisch B, Rozansky G, Felz C, Kessler-Icekson G, Krissi H, Nitke S, Ao A, Abir R (2008) Platelet-derived growth factors (PDGF-A and-B) and their receptors in human fetal and adult ovaries. Mol Hum Reprod 14(4):199–206CrossRefPubMedGoogle Scholar
  25. 25.
    Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM (1996) Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383(6600):531CrossRefGoogle Scholar
  26. 26.
    Vitt UA, Hsueh AJ (2002) Stage-dependent role of growth differentiation factor-9 in ovarian follicle development. Mol Cell Endocrinol 186(2):211–217CrossRefGoogle Scholar
  27. 27.
    Vitt U, Hayashi M, Klein C, Hsueh A (2000) Growth differentiation factor-9 stimulates proliferation but suppresses the follicle-stimulating hormone-induced differentiation of cultured granulosa cells from small antral and preovulatory rat follicles. Biol Reprod 62(2):370–377CrossRefPubMedGoogle Scholar
  28. 28.
    Pantos K, Nitsos N, Kokkali G, Vaxevanoglou T, Markomichali C, Pantou A, Grammatis M, Lazaros L, Sfakianoudis K Ovarian rejuvenation and folliculogenesis reactivation in peri-menopausal women after autologous platelet-rich plasma treatment. In: Abstracts, ESHRE 32nd Annual Meeting (2016) pp 3–6Google Scholar
  29. 29.
    Sills ES, Rickers NS, Li X, Palermo GD (2018) First data on in vitro fertilization and blastocyst formation after intraovarian injection of calcium gluconate-activated autologous platelet rich plasma. Gynecol Endocrinol 34:1–5CrossRefGoogle Scholar
  30. 30.
    Sfakianoudis K, Simopoulou M, Nitsos N, Rapani A, Pantou A, Vaxevanoglou T, Kokkali G, Koutsilieris M, Pantos K (2018) A case series on platelet-rich plasma revolutionary management of poor responder patients. Gynecol Obstet Investig 84:1–8Google Scholar
  31. 31.
    Van Blerkom J, Antczak M, Schrader R (1997) The developmental potential of the human oocyte is related to the dissolved oxygen content of follicular fluid: association with vascular endothelial growth factor levels and perifollicular blood flow characteristics. Hum Reprod (Oxford England) 12(5):1047–1055CrossRefGoogle Scholar
  32. 32.
    Li Q, Geng X, Zheng W, Tang J, Xu B, Shi Q (2012) Current understanding of ovarian aging. Sci Chin Life Sci 55(8):659–669. CrossRefGoogle Scholar
  33. 33.
    Modlich U, Kaup F-J, Augustin HG (1996) Cyclic angiogenesis and blood vessel regression in the ovary: blood vessel regression during luteolysis involves endothelial cell detachment and vessel occlusion. Lab Investig; J Tech Methods Pathol 74(4):771–780Google Scholar
  34. 34.
    Redmer DA, Reynolds LP (1996) Angiogenesis in the ovary. Rev Reprod 1(3):182–192CrossRefPubMedGoogle Scholar
  35. 35.
    Huey S, Abuhamad A, Barroso G, Hsu M-I, Kolm P, Mayer J, Oehninger S (1999) Perifollicular blood flow Doppler indices, but not follicular pO2, pCO2, or pH, predict oocyte developmental competence in in vitro fertilization. Fertil Steril 72(4):707–712CrossRefPubMedGoogle Scholar
  36. 36.
    Robinson RS, Woad KJ, Hammond AJ, Laird M, Hunter MG, Mann GE (2009) Angiogenesis and vascular function in the ovary. Reproduction 138(6):869–881CrossRefPubMedGoogle Scholar
  37. 37.
    Wulff C, Dickson SE, Duncan WC, Fraser HM (2001) Angiogenesis in the human corpus luteum: simulated early pregnancy by HCG treatment is associated with both angiogenesis and vessel stabilization. Hum Reprod 16(12):2515–2524CrossRefPubMedGoogle Scholar
  38. 38.
    Kang B-J, Wang Y, Zhang L, Xiao Z, Li S-W (2016) bFGF and VEGF improve the quality of vitrified-thawed human ovarian tissues after xenotransplantation to SCID mice. J Assist Reprod Genet 33(2):281–289CrossRefPubMedGoogle Scholar
  39. 39.
    Fraser HM, Lunn SF (2000) Angiogenesis and its control in the female reproductive system. Br Med Bull 56(3):787–797CrossRefPubMedGoogle Scholar
  40. 40.
    Truman AM, Tilly JL, Woods DC (2017) Ovarian regeneration: the potential for stem cell contribution in the postnatal ovary to sustained endocrine function. Mol Cell Endocrinol 445:74–84CrossRefPubMedGoogle Scholar
  41. 41.
    Edessy M, Hosni HN, Shady Y, Waf Y, Bakr S, Kamel M (2016) Autologous stem cells therapy, the first baby of idiopathic premature ovarian failure. Acta Med Int 3(1):19CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Endometrium and Endometriosis Research CenterHamadan University of Medical SciencesHamadanIran
  2. 2.Department of Genecology, School of MedicineHamadan University of Medical SciencesHamadanIran
  3. 3.Research Center for Health SciencesHamadan University of Medical sciencesHamadanIran
  4. 4.Department of Epidemiology, School of Public HealthHamadan University of Medical SciencesHamadanIran
  5. 5.Department of Anatomical Sciences, School of MedicineHamadan University of Medical SciencesHamadanIran

Personalised recommendations