Skip to main content
SpringerLink
Log in

The Effects of Autologous Platelet-Rich Plasma on Pregnancy Outcomes in Repeated Implantation Failure Patients Undergoing Frozen Embryo Transfer: A Randomized Controlled Trial

  • Reproductive Biology: Clinical Trials
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Repeated implantation failure (RIF) is a disorder in which good-quality embryos fail to implant in the endometrium following several in vitro fertilization (IVF) cycles. This study aimed to evaluate the efficiency and safety of intrauterine infusion of platelet-rich plasma (PRP) in improvement of pregnancy outcomes in RIF patients undergoing frozen embryo transfer (FET). A total of 438 women with a history of RIF undergoing FET were assessed for eligibility to enter the study. Patients were randomly assigned to the intervention (PRP) and control groups. The intervention group received an intrauterine infusion of 0.5 ml PRP 48 h before embryo transfer while the control group received standard treatment. The rates of chemical and clinical pregnancy were defined as the primary outcome values. All women were followed up until the study endpoints that included the number of neonates born and pregnancy-related complications. Three hundred and ninety-three participants accomplished the study and their data were analyzed. The chemical pregnancy, clinical pregnancy, and live birth rates were higher in the PRP group than control group (p value: <0.0001; p value: <0.0001; p value: <0.0001 respectively). However, there were no significant differences between the two groups in terms of multiple pregnancies and pregnancy complications except for spontaneous abortion. The spontaneous abortion rate was significantly higher in the control group compared to the PRP group (p value = 0.0262). These results suggest that intrauterine infusion of PRP is an effective and safe route to improve pregnancy outcomes in RIF patients undergoing FET.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available from IVF center.

Code Availability

Not applicable.

References

  1. Coughlan C, Ledger W, Wang Q, Liu F, Demirol A, Gurgan T, et al. Recurrent implantation failure: definition and management. Reprod BioMed Online. 2014;28(1):14–38. https://doi.org/10.1016/j.rbmo.2013.08.011.

    Article  CAS  PubMed  Google Scholar 

  2. Magdi Y, El-Damen A, Fathi AM, Abdelaziz AM, Youssef MA-E, Abd-Allah AA-E, et al. Revisiting the management of recurrent implantation failure through freeze-all policy. Fertil Steril. 2017;108(1):72–7.

    Article  Google Scholar 

  3. Timeva T, Shterev A, Kyurkchiev S. Recurrent implantation failure: the role of the endometrium. J Reprod Infertil. 2014;15(4):173–83.

    PubMed  PubMed Central  Google Scholar 

  4. Hosseinirad H, Novin MG, Hosseini S, Nazarian H, Amidi F, Paktinat S, et al. Effect of 1, 25 (OH) 2-vitamin D3 on expression and phosphorylation of progesterone receptor in cultured endometrial stromal cells of patients with repeated implantation failure. Acta Histochem. 2020;122(2):151489.

    Article  CAS  Google Scholar 

  5. Bashiri A, Halper KI, Orvieto R. Recurrent Implantation failure-update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol. 2018;16(1):121. https://doi.org/10.1186/s12958-018-0414-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Semsarzadeh N, Khetarpal S. Platelet-rich plasma and stem cells for hair growth: a review of the literature. Aesthet Surg J. 2020;40(4):NP177–NP88.

    PubMed  Google Scholar 

  7. Alves R, Grimalt R. A review of platelet-rich plasma: history, biology, mechanism of action, and classification. Skin Appendage Disord. 2018;4(1):18–24. https://doi.org/10.1159/000477353.

    Article  PubMed  Google Scholar 

  8. Cavalcante MB, Cavalcante CTMB, Sarno M, Barini R. Intrauterine perfusion immunotherapies in recurrent implantation failures: systematic review. Am J Reprod Immunol. 2020;83(6):e13242.

    Article  Google Scholar 

  9. Amable PR, Carias RBV, Teixeira MVT, da Cruz Pacheco I, Corrêa do Amaral RJF, Granjeiro JM, et al. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther. 2013;4(3):67. https://doi.org/10.1186/scrt218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chang Y, Li J, Chen Y, Wei L, Yang X, Shi Y, et al. Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med. 2015;8(1):1286–90.

    PubMed  PubMed Central  Google Scholar 

  11. Maleki-Hajiagha A, Razavi M, Rouholamin S, Rezaeinejad M, Maroufizadeh S, Sepidarkish M. Intrauterine infusion of autologous platelet-rich plasma in women undergoing assisted reproduction: a systematic review and meta-analysis. J Reprod Immunol. 2020;137:103078.

    Article  Google Scholar 

  12. Zamaniyan M, Peyvandi S, Heidaryan Gorji H, Moradi S, Jamal J, Yahya Poor Aghmashhadi F, Hossein Mohammadi M. Effect of platelet-rich plasma on pregnancy outcomes in infertile women with recurrent implantation failure: a randomized controlled trial. Gynaecol Endocrinol. 2021;37(2):141–5.

  13. Nazari L, Salehpour S, Hoseini S, Zadehmodarres S, Ajori L. Effects of autologous platelet-rich plasma on implantation and pregnancy in repeated implantation failure: a pilot study. Int J Reprod BioMed. 2016;14(10):625–8.

    PubMed  PubMed Central  Google Scholar 

  14. Nazari L, Salehpour S, Hosseini MS, Hashemi Moghanjoughi P. The effects of autologous platelet-rich plasma in repeated implantation failure: a randomized controlled trial. Hum Fertil. 2020;23(3):209–13.

  15. Wirleitner B, Schuff M, Stecher A, Murtinger M, Vanderzwalmen P. Pregnancy and birth outcomes following fresh or vitrified embryo transfer according to blastocyst morphology and expansion stage, and culturing strategy for delayed development. Hum Reprod. 2016;31(8):1685–95.

    Article  CAS  Google Scholar 

  16. Jansen R, Mortimer D. Towards reproductive certainty: fertility and genetics beyond 1999: the plenary Proceedings of the 11th World Congress. CRC Press; 1999.

  17. Zeadna A, Son WY, Moon JH, Dahan MH. A comparison of biochemical pregnancy rates between women who underwent IVF and fertile controls who conceived spontaneously†. Hum Reprod. 2015;30(4):783–8. https://doi.org/10.1093/humrep/dev024.

    Article  CAS  PubMed  Google Scholar 

  18. Singh M, Chaudhry P, Asselin E. Bridging endometrial receptivity and implantation: network of hormones, cytokines, and growth factors. J Endocrinol. 2011;210(1):5–14. https://doi.org/10.1530/JOE-10-0461.

    Article  CAS  PubMed  Google Scholar 

  19. Allahveisi A, Seyedoshohadaei F, Rezaei M, Bazrafshan N, Rahimi K. The effect of platelet-rich plasma on the achievement of pregnancy during frozen embryo transfer in women with a history of failed implantation. Heliyon. 2020;6(3):e03577.

    Article  Google Scholar 

  20. Rageh K, Barakat AA-A, Ahmed KG, Ahmed AM. PRP in recurrent implantation failure, hope or hype? A prospective randomized controlled study. Evid Based Women's Health J. 2020;10(1):46–53.

    Article  CAS  Google Scholar 

  21. Rajaei S, Zamani AH, Jeddi-Tehrani M, Tavakoli M, Mohammadzadeh A, Dabbagh A, et al. Cytokine profile in the endometrium of normal fertile and women with repeated implantation failure. Iran J Immunol. 2011;8(4):201–8.

    CAS  PubMed  Google Scholar 

  22. Griffith OW, Chavan AR, Protopapas S, Maziarz J, Romero R, Wagner GP. Embryo implantation evolved from an ancestral inflammatory attachment reaction. Proc Natl Acad Sci. 2017;114(32):E6566–E75.

    Article  CAS  Google Scholar 

  23. Mor G, Cardenas I, Abrahams V, Guller S. Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci. 2011;1221(1):80–7.

    Article  CAS  Google Scholar 

  24. Marini MG, Perrini C, Esposti P, Corradetti B, Bizzaro D, Riccaboni P, et al. Effects of platelet-rich plasma in a model of bovine endometrial inflammation in vitro. Reprod Biol Endocrinol. 2016;14(1):1–17.

    Article  Google Scholar 

  25. Hosseinirad H, Novin MG, Hosseini S, Nazarian H, Safaei Z, Hashemi T, et al. Evaluation of expression and phosphorylation of progesterone receptor in endometrial stromal cells of patients with recurrent implantation failure compared to healthy fertile women. Reprod Sci. 2021;28(5):1457–65.

  26. Coksuer H, Akdemir Y, Ulas BM. Improved in vitro fertilization success and pregnancy outcome with autologous platelet-rich plasma treatment in unexplained infertility patients that had repeated implantation failure history. Gynecol Endocrinol. 2019;35(9):815–8.

    Article  Google Scholar 

  27. Samy A, Abbas AM, Elmoursi A, Elsayed M, Hussein RS. Effect of autologous platelet-rich plasma transfusion in the treatment of infertile women with thin endometrium and its implications in IVF cycles: a literature review. Middle East Fertil Soc J. 2020;25(1):5.

    Article  Google Scholar 

  28. Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, et al. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med. 2014;42(1):35–41.

    Article  Google Scholar 

  29. Nazari L, Salehpour S, Hoseini S, Zadehmodarres S, Azargashb E. Effects of autologous platelet-rich plasma on endometrial expansion in patients undergoing frozen-thawed embryo transfer: a double-blind RCT. Int J Reprod Biomed. 2019;17(6):443–8. https://doi.org/10.18502/ijrm.v17i6.4816.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost. 2004;91(01):4–15.

    Article  CAS  Google Scholar 

  31. Elnehrawy NY, Ibrahim ZA, Eltoukhy AM, Nagy HM. Assessment of the efficacy and safety of single platelet-rich plasma injection on different types and grades of facial wrinkles. J Cosmet Dermatol. 2017;16(1):103–11.

    Article  Google Scholar 

  32. Fukawa T, Yamaguchi S, Akatsu Y, Yamamoto Y, Akagi R, Sasho T. Safety and efficacy of intra-articular injection of platelet-rich plasma in patients with ankle osteoarthritis. Foot Ankle Int. 2017;38(6):596–604.

    Article  Google Scholar 

  33. Raeissadat SA, Karimzadeh A, Hashemi M, Bagherzadeh L. Safety and efficacy of platelet-rich plasma in treatment of carpal tunnel syndrome; a randomized controlled trial. BMC Musculoskelet Disord. 2018;19(1):1–6.

    Article  Google Scholar 

  34. Monteleone PA, Peregrino PF, Baracat EC, Serafini PC. Transfer of 2 embryos using a double-embryo transfer protocol versus 2 sequential single-embryo transfers: the impact on multiple pregnancy. Reprod Sci. 2018;25(10):1501–8.

    Article  Google Scholar 

  35. Fadadu PP, Mazzola AJ, Hunter CW, Davis TT. Review of concentration yields in commercially available platelet-rich plasma (PRP) systems: a call for PRP standardization. Reg Anesth Pain Med. 2019;44(6):652–9.

    Article  Google Scholar 

  36. Amable PR, Carias RBV, Teixeira MVT, da Cruz PÍ. do Amaral RJFC, Granjeiro JM, et al. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther. 2013;4(3):1–13.

    Article  Google Scholar 

  37. Van Hoogenhuijze N, Kasius J, Broekmans F, Bosteels J, Torrance H. Endometrial scratching prior to IVF; does it help and for whom? A systematic review and meta-analysis. Hum Reprod Open. 2019;2019(1):hoy025.

    PubMed  PubMed Central  Google Scholar 

  38. Lensen S, Venetis C, Ng EH, Young SL, Vitagliano A, Macklon NS, et al. Should we stop offering endometrial scratching prior to in vitro fertilization? Fertil Steril. 2019;111(6):1094–101.

    Article  Google Scholar 

  39. Wadhwa L, Mishra M. Therapeutic efficacy of endometrial scratching in repeated controlled ovarian stimulation (COS) failure cycles. J Hum Reprod Sci. 2018;11(1):59–71.

    Article  Google Scholar 

  40. Madhavan A, Naidu P, Rani KK, Kaur J, Mahajan N. Intrauterine autologous platelet-rich plasma therapy to improve implantation rates in patients undergoing frozen embryo transfer: a pilot study. Onco Fertil J. 2018;1(2):81.

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledge all staffs who worked in IVF center at Gandi Hospital, Tehran, Iran, with especial thanks to Ms. Nahid Zadehnajaf, Ms. Mahnam Malakouti, and Ms. Marjan Nasirzadeh for their great help in this study.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Preventative Gynecology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Leila Nazari, Saghar Salehpour, Sedighe Hosseini & Samaneh Sheibani

  2. Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hossein Hosseinirad

Authors
  1. Leila Nazari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saghar Salehpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sedighe Hosseini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Samaneh Sheibani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hossein Hosseinirad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samaneh Sheibani.

Ethics declarations

Ethics Approval

The present study was approved by the ethical committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran. The trial was registered at the Iranian Registry of Clinical Trials (IRCT2016072229027N1).

Consent to Participate

Written informed consent was obtained from all the participants.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nazari, L., Salehpour, S., Hosseini, S. et al. The Effects of Autologous Platelet-Rich Plasma on Pregnancy Outcomes in Repeated Implantation Failure Patients Undergoing Frozen Embryo Transfer: A Randomized Controlled Trial. Reprod. Sci. 29, 993–1000 (2022). https://doi.org/10.1007/s43032-021-00669-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-021-00669-1

Keywords

Search

Navigation