Platelet-Rich Plasma Intrauterine Infusion as Assisted Reproduction Technology (ART) to Combat Repeated Implantation Failure (RIF): A Systematic Review and Meta-Analysis
Abstract
Background: Repeated implantation failure (RIF) is considered one of the major challenges facing clinician in assisted reproduction technologies (ART) despite the significant advances that have been made in this field. Platelet rich plasma (PRP), also known as autologous conditioned plasma, is a protein concentrate with anti-inflammatory and pro-regenerative characteristics. The use of PRP in women undergoing ART has been studied in the past, with varying degrees of success. The goal of this trial was to see if injecting PRP into the uterus improves pregnancy outcomes in women receiving ART.
Methods: PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Clinical Trials were among the databases searched (CENTRAL), from 2015 to 2021. The pooled estimates were calculated using a meta-analysis with a random-effects model. There were 14 studies with a total of 1081 individuals (549 cases and 532 controls).
Results: There was no difference in miscarriage rates between women who got PRP and those who received placebo (P≤0.90). Chemical pregnancy (P≤0.00), clinical pregnancy (P ≤0.001), and implantation rate (P≤ 0.001) were all significantly higher in women. Endometrial thickness increased in women who got PRP vs women who received placebo after the intervention (P ≤0.001).
Conclusion: PRP may be an alternate therapeutic approach for individuals with thin endometrium and RIF, according to the findings of this comprehensive study. To determine the subgroup that would benefit the most from PRP, more prospective, big, and high-quality randomized controlled trials (RCTs) are needed.
1. Simon A, Laufer N (2012). Assessment and treatment of repeated implantation fail-ure (RIF). J Assist Reprod Genet, 29(11):1227-39.
2. Rinehart J (2007). Recurrent implantation failure: definition. J Assist Reprod Genet, 24(7):284-7.
3. Hoozemans DA, Schats R, Lambalk CB, et al (2004). Human embryo implantation: current knowledge and clinical implications in assisted reproductive technology. Reprod Biomed Online, 9(6):692-715.
4. Diedrich K, Fauser BCJM, Devroey P, et al (2007). The role of the endometrium and embryo in human implantation. Hum Reprod Update, 13(4):365-377.
5. Kissin DM, Jamieson DJ, Barfield WD. (2014). Monitoring health outcomes of assisted reproductive technology. N Engl J Med, 371: 91–93.
6. Allen VM, Wilson RD, Cheung A (2006). Genetics Committee, Reproductive En-docrinology and Infertility Committee. Pregnancy outcomes after assisted re-productive technology. J Obstet Gynaecol Can, 28(3):220-233.
7. Lebovitz O, Orvieto R (2014). Treating patients with “thin” endometrium - an ongoing challenge. Gynecol Endocrinol, 30(6):409-414.
8. Paulson RJ (2011). Hormonal induction of endometrial receptivity. Fertil Steril, 96(3):530–535.
9. Bourgain C, Devroey P (2003). The endo-metrium in stimulated cycles for IVF. Hum Reprod Update, 9(6):515-22.
10. lujovsky D, Farquhar C, Quinteiro Retamar AM, et al (2016). Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev, 6: CD002118.
11. Sobek A, Tkadlec E, Klaskova E, et al (2020). Cytoplasmic Transfer Improves Human Egg Fertilization and Embryo Quality: an Evaluation of Sibling Oo-cytes in Women with Low Oocyte Qual-ity. Reprod Sci, 28(5):1362-1369.
12. Yoshioka S, Fujiwara H, Nakayama T, et al (2006). Intrauterine administration of au-tologous peripheral blood mononuclear cells promotes implantation rates in pa-tients with repeated failure of IVF-embryo transfer. Hum Reprod, 21(12):3290-4.
13. Yu N, Zhang B, Xu M, et al (2010). Intrau-terine administration of autologous pe-ripheral blood mononuclear cells (PBMCs) activated by HCG improves the implantation and pregnancy rates in patients with repeated implantation fail-ure: a prospective randomized study. Am J Reprod Immunol, 76(3):212-6.
14. Zadehmodarres S, Salehpour S, Saharkhiz N, et al (2017). Treatment of thin endo-metrium with autologous platelet-rich plasma: a pilot study. JBRA Assist Reprod, 21(1):54-56.
15. Russell SJ, Kwok YSS, Nguyen TTTN, et al (2022). Autologous platelet-rich plasma improves the endometrial thickness and live birth rate in patients with recurrent implantation failure and thin endome-trium. J Assist Reprod Genet 39: 1305–1312.
16. Allahveisi A, Seyedoshohadaei F, Rezaei M, et al (2020). The effect of platelet-rich plasma on the achievement of pregnancy during frozen embryo transfer in women with a history of failed implantation. Heliyon, 6(3): e03577.
17. Bos-Mikich A, de Oliveira R, Frantz N (2018). Platelet-rich plasma therapy and reproductive medicine. J Assist Reprod Genet, 35(5): 753–756.
18. Chang Y, Li J, Chen Y, et al (2015). Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med, 8(1):1286–1290.
19. Eftekhar M, Neghab N, Naghshineh E, et al (2018). Can autologous platelet rich plasma expand endometrial thickness and improve pregnancy rate during frozen-thawed embryo transfer cycle? A randomized clinical trial. Taiwan J Obstet Gynecol, 57(6):810–813.
20. Chang Y, Li J, Wei L N, et al (2019). Autologous platelet-rich plasma infusion improves clinical pregnancy rate in frozen embryo transfer cycles for women with thin endometrium. Medicine, 98(3):e14062.
21. GKim H, Shin JE, Koo HS, et al (2019). Effect of Autologous Platelet-Rich Plasma Treatment on Refractory Thin Endometrium During the Frozen Embryo Transfer Cycle. A Pilot Study. Front Endocrinol (Lausanne), 10: 61.
22. Mehrafza M, Kabodmehri R, Nikpouri Z, et al (2019). Comparing the Impact of Autologous Platelet-rich Plasma and Granulocyte Colony Stimulating Factor on Pregnancy Outcome in Patients with Repeated Implantation Failure. J Reprod Infert, 20(1):35–41.
23. Nazari L, Salehpour S, Hosseini M S, et al (2020). The effects of autologous platelet-rich plasma in repeated implantation failure: a randomized controlled trial. Hum Fertil, 23(3):209–213.
24. Maleki-Hajiagha A, Razavi M, Rezaeinejad M, et al (2019). Intrauterine administration of autologous peripheral blood mononuclear cells in patients with recurrent implantation failure: A systematic review and meta-analysis. J Reprod Immunol, 131: 50–56.
25. Tehraninejad E S, Kashani N G, Hosseini A, et al (2021). Autologous platelet-rich plasma infusion does not improve pregnancy outcomes in frozen embryo transfer cycles in women with history of repeated implantation failure without thin endometrium. J Obstet Gynaecol Res, 47(1):147–151.
26. Frantz N, Ferreira M, Kulmann M I, et al (2020). Platelet-Rich plasma as an effective alternative approach for improving endometrial receptivity - a clinical retrospective study. JBRA Assist Reprod, 24(4):442–446.
27. Aghajanzadeh F, Esmaeilzadeh S, Basirat Z, et al (2020). Using autologous intrauterine platelet-rich plasma to improve the reproductive outcomes of women with recurrent implantation failure. JBRA Assist Reprod, 24(1):30–33.
28. Zamaniyan M, Peyvandi S, Heidaryan Gorji, et al (2021). Effect of platelet-rich plasma on pregnancy outcomes in infertile women with recurrent implantation failure: a randomized controlled trial. Gynecol Endocrinol, 37(2):141–145.
29. Zargar M, Pazhouhanfar P, Najafian M, et al (2021). Effects of intrauterine autologous platelet-rich plasma infusions on outcomes in women with repetitive in vitro fertilization failures: a prospective randomized study. Clin Exp Obstet Gynecol, 48(1):179–184).
30. Obidniak D, Gzgzyan A, Feoktistov, et al (2017). Randomized controlled trial evaluating efficacy of autologous plate-let-rich plasma therapy for patients with recurrent implantation failure. Fertil Steril, 108 (3): E370.
31. Madhavan A, Naidu P, Rani K Kaur, et al (2018). Intrauterine autologous platelet-rich plasma therapy to improve implantation rates in patients undergoing frozen embryo transfer: A pilot study. The Onco Fertility Journal, 1(2):81–85.
32. Coksuer H, Akdemir Y, Ulas Barut M (2019). 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, 35(9):815-818.
33. Melo P, Navarro C, Jones C, et al (2020). 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, 37(4):855–863.
34. Eldredge JD (2000). Evidence-based librarianship: an overview. Bull Med Libr Assoc, 88(4):289–302.
35. Glujovsky D, Farquhar C (2016). Cleavage-stage or blastocyst transfer: what are the benefits and harms? Fertil Steril, 106(2):244–250.
36. Maheshwari A, Hamilton M, Bhattacharya S (2016). Should we be promoting embryo transfer at blastocyst stage? Reprod Biomed Online, 32(2):142–146.
37. Alves R, Grimalt R (2018). A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and Classification. Skin Appendage Disord, 4(1):18–24.
38. Fadadu PP, Mazzola AJ, Hunter CW, et al (2019). Review of concentration yields in commercially available platelet-rich plasma (PRP) systems: a call for PRP standardization. Reg Anesth Pain Med, 2018-100356.
39. Sánchez AR, Sheridan PJ, Kupp LI, et al (2003). Is platelet-rich plasma the perfect enhancement factor? A current review. Int J Oral Maxillofac Implants,18(1):93-103.
40. Bendinelli P, Matteucci E, Dogliotti G, et al (2010). Molecular basis of anti-inflammatory action of platelet-rich plasma on human chondrocytes: mechanisms of NF-κB inhibition via HGF. J Cell Physiol, 225(3):757–766.
41. Filardo G, Kon E, Roffi A, et al (2015). Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration. Knee Surg Sports Traumatol Arthrosc, 23(9):2459–2474.
42. Li H, Hicks J J, Wang L, et al (2016). Customized platelet-rich plasma with transforming growth factor β1 neutralization antibody to reduce fibrosis in skeletal muscle. Biomaterials, 87: 147–156.
43. Meheux CJ, McCulloch PC, Lintner DM, et al (2016). Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review. Arthroscopy, 32(3):495–505.
44. Dai WL, Zhou A G, Zhang H, et al (2017). Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials. Arthroscopy, 33(3):659-670.e1.
45. Gibreel A, El-Adawi N, Elgindy E, et al (2015). Endometrial scratching for women with previous IVF failure undergoing IVF treatment. Gynecol Endocrinol, 31(4):313–316.
46. Maleki-Hajiagha A, Razavi M, Rouholamin S, et al (2020). Intrauterine infusion of autologous platelet-rich plasma in wom-en undergoing assisted reproduction: A systematic review and meta-analysis. J Reprod Immunol, 137:103078.
2. Rinehart J (2007). Recurrent implantation failure: definition. J Assist Reprod Genet, 24(7):284-7.
3. Hoozemans DA, Schats R, Lambalk CB, et al (2004). Human embryo implantation: current knowledge and clinical implications in assisted reproductive technology. Reprod Biomed Online, 9(6):692-715.
4. Diedrich K, Fauser BCJM, Devroey P, et al (2007). The role of the endometrium and embryo in human implantation. Hum Reprod Update, 13(4):365-377.
5. Kissin DM, Jamieson DJ, Barfield WD. (2014). Monitoring health outcomes of assisted reproductive technology. N Engl J Med, 371: 91–93.
6. Allen VM, Wilson RD, Cheung A (2006). Genetics Committee, Reproductive En-docrinology and Infertility Committee. Pregnancy outcomes after assisted re-productive technology. J Obstet Gynaecol Can, 28(3):220-233.
7. Lebovitz O, Orvieto R (2014). Treating patients with “thin” endometrium - an ongoing challenge. Gynecol Endocrinol, 30(6):409-414.
8. Paulson RJ (2011). Hormonal induction of endometrial receptivity. Fertil Steril, 96(3):530–535.
9. Bourgain C, Devroey P (2003). The endo-metrium in stimulated cycles for IVF. Hum Reprod Update, 9(6):515-22.
10. lujovsky D, Farquhar C, Quinteiro Retamar AM, et al (2016). Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev, 6: CD002118.
11. Sobek A, Tkadlec E, Klaskova E, et al (2020). Cytoplasmic Transfer Improves Human Egg Fertilization and Embryo Quality: an Evaluation of Sibling Oo-cytes in Women with Low Oocyte Qual-ity. Reprod Sci, 28(5):1362-1369.
12. Yoshioka S, Fujiwara H, Nakayama T, et al (2006). Intrauterine administration of au-tologous peripheral blood mononuclear cells promotes implantation rates in pa-tients with repeated failure of IVF-embryo transfer. Hum Reprod, 21(12):3290-4.
13. Yu N, Zhang B, Xu M, et al (2010). Intrau-terine administration of autologous pe-ripheral blood mononuclear cells (PBMCs) activated by HCG improves the implantation and pregnancy rates in patients with repeated implantation fail-ure: a prospective randomized study. Am J Reprod Immunol, 76(3):212-6.
14. Zadehmodarres S, Salehpour S, Saharkhiz N, et al (2017). Treatment of thin endo-metrium with autologous platelet-rich plasma: a pilot study. JBRA Assist Reprod, 21(1):54-56.
15. Russell SJ, Kwok YSS, Nguyen TTTN, et al (2022). Autologous platelet-rich plasma improves the endometrial thickness and live birth rate in patients with recurrent implantation failure and thin endome-trium. J Assist Reprod Genet 39: 1305–1312.
16. Allahveisi A, Seyedoshohadaei F, Rezaei M, et al (2020). The effect of platelet-rich plasma on the achievement of pregnancy during frozen embryo transfer in women with a history of failed implantation. Heliyon, 6(3): e03577.
17. Bos-Mikich A, de Oliveira R, Frantz N (2018). Platelet-rich plasma therapy and reproductive medicine. J Assist Reprod Genet, 35(5): 753–756.
18. Chang Y, Li J, Chen Y, et al (2015). Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med, 8(1):1286–1290.
19. Eftekhar M, Neghab N, Naghshineh E, et al (2018). Can autologous platelet rich plasma expand endometrial thickness and improve pregnancy rate during frozen-thawed embryo transfer cycle? A randomized clinical trial. Taiwan J Obstet Gynecol, 57(6):810–813.
20. Chang Y, Li J, Wei L N, et al (2019). Autologous platelet-rich plasma infusion improves clinical pregnancy rate in frozen embryo transfer cycles for women with thin endometrium. Medicine, 98(3):e14062.
21. GKim H, Shin JE, Koo HS, et al (2019). Effect of Autologous Platelet-Rich Plasma Treatment on Refractory Thin Endometrium During the Frozen Embryo Transfer Cycle. A Pilot Study. Front Endocrinol (Lausanne), 10: 61.
22. Mehrafza M, Kabodmehri R, Nikpouri Z, et al (2019). Comparing the Impact of Autologous Platelet-rich Plasma and Granulocyte Colony Stimulating Factor on Pregnancy Outcome in Patients with Repeated Implantation Failure. J Reprod Infert, 20(1):35–41.
23. Nazari L, Salehpour S, Hosseini M S, et al (2020). The effects of autologous platelet-rich plasma in repeated implantation failure: a randomized controlled trial. Hum Fertil, 23(3):209–213.
24. Maleki-Hajiagha A, Razavi M, Rezaeinejad M, et al (2019). Intrauterine administration of autologous peripheral blood mononuclear cells in patients with recurrent implantation failure: A systematic review and meta-analysis. J Reprod Immunol, 131: 50–56.
25. Tehraninejad E S, Kashani N G, Hosseini A, et al (2021). Autologous platelet-rich plasma infusion does not improve pregnancy outcomes in frozen embryo transfer cycles in women with history of repeated implantation failure without thin endometrium. J Obstet Gynaecol Res, 47(1):147–151.
26. Frantz N, Ferreira M, Kulmann M I, et al (2020). Platelet-Rich plasma as an effective alternative approach for improving endometrial receptivity - a clinical retrospective study. JBRA Assist Reprod, 24(4):442–446.
27. Aghajanzadeh F, Esmaeilzadeh S, Basirat Z, et al (2020). Using autologous intrauterine platelet-rich plasma to improve the reproductive outcomes of women with recurrent implantation failure. JBRA Assist Reprod, 24(1):30–33.
28. Zamaniyan M, Peyvandi S, Heidaryan Gorji, et al (2021). Effect of platelet-rich plasma on pregnancy outcomes in infertile women with recurrent implantation failure: a randomized controlled trial. Gynecol Endocrinol, 37(2):141–145.
29. Zargar M, Pazhouhanfar P, Najafian M, et al (2021). Effects of intrauterine autologous platelet-rich plasma infusions on outcomes in women with repetitive in vitro fertilization failures: a prospective randomized study. Clin Exp Obstet Gynecol, 48(1):179–184).
30. Obidniak D, Gzgzyan A, Feoktistov, et al (2017). Randomized controlled trial evaluating efficacy of autologous plate-let-rich plasma therapy for patients with recurrent implantation failure. Fertil Steril, 108 (3): E370.
31. Madhavan A, Naidu P, Rani K Kaur, et al (2018). Intrauterine autologous platelet-rich plasma therapy to improve implantation rates in patients undergoing frozen embryo transfer: A pilot study. The Onco Fertility Journal, 1(2):81–85.
32. Coksuer H, Akdemir Y, Ulas Barut M (2019). 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, 35(9):815-818.
33. Melo P, Navarro C, Jones C, et al (2020). 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, 37(4):855–863.
34. Eldredge JD (2000). Evidence-based librarianship: an overview. Bull Med Libr Assoc, 88(4):289–302.
35. Glujovsky D, Farquhar C (2016). Cleavage-stage or blastocyst transfer: what are the benefits and harms? Fertil Steril, 106(2):244–250.
36. Maheshwari A, Hamilton M, Bhattacharya S (2016). Should we be promoting embryo transfer at blastocyst stage? Reprod Biomed Online, 32(2):142–146.
37. Alves R, Grimalt R (2018). A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and Classification. Skin Appendage Disord, 4(1):18–24.
38. Fadadu PP, Mazzola AJ, Hunter CW, et al (2019). Review of concentration yields in commercially available platelet-rich plasma (PRP) systems: a call for PRP standardization. Reg Anesth Pain Med, 2018-100356.
39. Sánchez AR, Sheridan PJ, Kupp LI, et al (2003). Is platelet-rich plasma the perfect enhancement factor? A current review. Int J Oral Maxillofac Implants,18(1):93-103.
40. Bendinelli P, Matteucci E, Dogliotti G, et al (2010). Molecular basis of anti-inflammatory action of platelet-rich plasma on human chondrocytes: mechanisms of NF-κB inhibition via HGF. J Cell Physiol, 225(3):757–766.
41. Filardo G, Kon E, Roffi A, et al (2015). Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration. Knee Surg Sports Traumatol Arthrosc, 23(9):2459–2474.
42. Li H, Hicks J J, Wang L, et al (2016). Customized platelet-rich plasma with transforming growth factor β1 neutralization antibody to reduce fibrosis in skeletal muscle. Biomaterials, 87: 147–156.
43. Meheux CJ, McCulloch PC, Lintner DM, et al (2016). Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review. Arthroscopy, 32(3):495–505.
44. Dai WL, Zhou A G, Zhang H, et al (2017). Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials. Arthroscopy, 33(3):659-670.e1.
45. Gibreel A, El-Adawi N, Elgindy E, et al (2015). Endometrial scratching for women with previous IVF failure undergoing IVF treatment. Gynecol Endocrinol, 31(4):313–316.
46. Maleki-Hajiagha A, Razavi M, Rouholamin S, et al (2020). Intrauterine infusion of autologous platelet-rich plasma in wom-en undergoing assisted reproduction: A systematic review and meta-analysis. J Reprod Immunol, 137:103078.
| Files | ||
| Issue | Vol 52 No 8 (2023) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v52i8.13394 | |
| Keywords | ||
| Clinical pregnancy Implantation rate Platelet rich plasma Randomized controlled trials | ||
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How to Cite
1.
Huang C, Ye X, Ye L, lu L, Liu F. Platelet-Rich Plasma Intrauterine Infusion as Assisted Reproduction Technology (ART) to Combat Repeated Implantation Failure (RIF): A Systematic Review and Meta-Analysis. Iran J Public Health. 2023;52(8):1542-1554.
