Intrauterine Platelet Rich Plasma (PRP) Infusion Could Change The Leukemia Inhibitory Factor (LIF) Pattern In The Endometrial Secretion Of Women With Recurrent Implantation Failure: A Randomized Clinical Trial

Abstract

Background:

RIF is an extremely devastating condition for patients with infertility that has no universally accepted definition. Among therapeutic method used, intrauterine infusion of PRP improves chances of clinical pregnancy and live birth. This satisfactory evidence emphasizes on the investigation of the underlying mechanisms of PRP on cytokines and growth factor involving in embryo implantation. The aim of current study is to find the effect of intrauterine infusion of PRP on LIF level in the endometrial secretion of patients with RIF.

Material and Method:

In order to determine the effect of intrauterine infusion of PRP on LIF level in women with RIF, 20 RIF women undergoing ET cycle were recruited and divided into PRP group(n=11) and non-PRP group(n=9). All of these women underwent endometrial secretion aspiration two times. In PRP group endometrial secretion aspiration performed immediately before PRP infusion and immediately before ET, in non-PRP group 48 hrs Before ET and immediately before ET. The concentration of LIF was measured using LEGENplex ™ MultiAnalyteFlowAssay kit.

Results:

The concentration of LIF was significantly higher in PRP group compared to non-PRP group. Also, significant difference in the terms of clinical pregnancy rate has been found between PRP group and non-PRP group.

Conclusion:

The findings of current trial suggest that intrauterine infusion of PRP might be a potential method to improve clinical pregnancy rates in women with RIF.

 In fact PRP have the potential to elevate the level of vital cytokine such as LIF involving in the embryo implantation pathway.

Keywords: Recurrent Implantation Failure (RIF) Platelet Rich Plasma (PRP) Leukemia Inhibitory Factor (LIF) References

1. Sadecki E, Weaver A, Zhao Y, Stewart EA, Ainsworth AJ. Fertility trends and comparisons in a historical cohort of US women with primary infertility. Reproductive health. 2022 Jan 18;19(1):13. PubMed PMID: 35042514. Pubmed Central PMCID: PMC8764822 and age-matched control women. The cohort included 1001 women with primary infertility diagnosed between 1980 and 1999 and 1001 age-matched controls from the same community and era. This cohort demonstrated baseline differences between the primary infertility and control groups, including differences in marital status, education, use of barrier contraception and smoking status. Additionally, the cohort showed an increased incidence in diagnosis of primary infertility from 1980 to 1999. Creation of this cohort will enable future research focused on long-term outcomes following primary infertility diagnosis and treatment. Epub 2022/01/20. eng.
2. Coughlan C, Ledger W, Wang Q, Liu F, Demirol A, Gurgan T, et al. Recurrent implantation failure: definition and management. Reproductive biomedicine online. 2014 Jan;28(1):14-38. PubMed PMID: 24269084. Epub 2013/11/26. eng.
3. Bashiri A, Halper KI, Orvieto R. Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions. Reproductive biology and endocrinology : RB&E. 2018 Dec 5;16(1):121. PubMed PMID: 30518389. Pubmed Central PMCID: PMC6282265. Epub 2018/12/07. eng.
4. Fukui Y, Hirota Y, Matsuo M, Gebril M, Akaeda S, Hiraoka T, et al. Uterine receptivity, embryo attachment, and embryo invasion: Multistep processes in embryo implantation. Reproductive medicine and biology. 2019 Jul;18(3):234-40. PubMed PMID: 31312101. Pubmed Central PMCID: PMC6613011. Epub 2019/07/18. eng.
5. Kim SM, Kim JS. A Review of Mechanisms of Implantation. Development & reproduction. 2017 Dec;21(4):351-9. PubMed PMID: 29359200. Pubmed Central PMCID: PMC5769129. Epub 2018/01/24. eng.
6. Pantos K, Grigoriadis S, Maziotis E, Pistola K, Xystra P, Pantou A, et al. The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature. International journal of molecular sciences. 2022 Feb 16;23(4). PubMed PMID: 35216313. Pubmed Central PMCID: PMC8875813. Epub 2022/02/27. eng.
7. Yoshinaga K. A historical review of blastocyst implantation research. Biology of reproduction. 2018 Jul 1;99(1):175-95. PubMed PMID: 30010858. Pubmed Central PMCID: PMC6279068. Epub 2018/07/17. eng.
8. Kelleher AM, Milano-Foster J, Behura SK, Spencer TE. Uterine glands coordinate on-time embryo implantation and impact endometrial decidualization for pregnancy success. Nature communications. 2018 Jun 22;9(1):2435. PubMed PMID: 29934619. Pubmed Central PMCID: PMC6015089. Epub 2018/06/24. eng.
9. Aghajanova L. Update on the role of leukemia inhibitory factor in assisted reproduction. Current opinion in obstetrics & gynecology. 2010 Jun;22(3):213-9. PubMed PMID: 20216416. Epub 2010/03/11. eng.
10. Hambartsoumian E. Endometrial leukemia inhibitory factor (LIF) as a possible cause of unexplained infertility and multiple failures of implantation. American journal of reproductive immunology (New York, NY : 1989). 1998 Feb;39(2):137-43. PubMed PMID: 9506211. Epub 1998/03/20. eng.
11. Wu M, Yin Y, Zhao M, Hu L, Chen Q. The low expression of leukemia inhibitory factor in endometrium: possible relevant to unexplained infertility with multiple implantation failures. Cytokine. 2013 May;62(2):334-9. PubMed PMID: 23541977. Epub 2013/04/02. eng.
12. Bahrami-Asl Z, Farzadi L, Fattahi A, Yousefi M, Quinonero A, Hakimi P, et al. Tacrolimus Improves the Implantation Rate in Patients with Elevated Th1/2 Helper Cell Ratio and Repeated Implantation Failure (RIF). Geburtshilfe und Frauenheilkunde. 2020 Aug;80(8):851-62. PubMed PMID: 32817992. Pubmed Central PMCID: PMC7428373. Epub 2020/08/21. eng.
13. Ersahin SS, Ersahin A. Endometrial injury concurrent with hysteroscopy increases the expression of Leukaemia inhibitory factor: a preliminary study. Reproductive biology and endocrinology : RB&E. 2022 Jan 10;20(1):11. PubMed PMID: 35012573. Pubmed Central PMCID: PMC8744211. Epub 2022/01/12. eng.
14. Lu Y, Yan J, Liu J, Tan J, Hong Y, Wei D, et al. Prednisone for patients with recurrent implantation failure: study protocol for a double-blind, multicenter, randomized, placebo-controlled trial. Trials. 2020 Aug 17;21(1):719. PubMed PMID: 32807234. Pubmed Central PMCID: PMC7430107. Epub 2020/08/19. eng.
15. Davar R, Pourmasumi S, Mohammadi B, Lahijani MM. The effect of low-dose aspirin on the pregnancy rate in frozen-thawed embryo transfer cycles: A randomized clinical trial. International journal of reproductive biomedicine. 2020 Sep;18(9):693-700. PubMed PMID: 33062915. Pubmed Central PMCID: PMC7521165. Epub 2020/10/17. eng.
16. Brinsden PR, Alam V, de Moustier B, Engrand P. Recombinant human leukemia inhibitory factor does not improve implantation and pregnancy outcomes after assisted reproductive techniques in women with recurrent unexplained implantation failure. Fertility and sterility. 2009 Apr;91(4 Suppl):1445-7. PubMed PMID: 18710712. Epub 2008/08/20. eng.
17. Lin Y, Qi J, Sun Y. Platelet-Rich Plasma as a Potential New Strategy in the Endometrium Treatment in Assisted Reproductive Technology. Frontiers in Endocrinology. 2021 2021-October-18;12. English.
18. Boomsma CM, Kavelaars A, Eijkemans MJ, Lentjes EG, Fauser BC, Heijnen CJ, et al. Endometrial secretion analysis identifies a cytokine profile predictive of pregnancy in IVF. Human reproduction (Oxford, England). 2009 Jun;24(6):1427-35. PubMed PMID: 19228761. Epub 2009/02/21. eng.
19. van Mourik MS, Macklon NS, Heijnen CJ. Embryonic implantation: cytokines, adhesion molecules, and immune cells in establishing an implantation environment. Journal of leukocyte biology. 2009 Jan;85(1):4-19. PubMed PMID: 18784344. Epub 2008/09/12. eng.
20. Pantos K, Grigoriadis S, Maziotis E, Pistola K, Xystra P, Pantou A, et al. The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature. International Journal of Molecular Sciences. 2022;23(4):2198.
21. Kimber SJ. Leukaemia inhibitory factor in implantation and uterine biology. Reproduction. 2005;130(2):131-45.
22. Dimitriadis E, White CA, Jones RL, Salamonsen LA. Cytokines, chemokines and growth factors in endometrium related to implantation. Human Reproduction Update. 2005;11(6):613-30.
23. Huang C, Sun H, Wang Z, Liu Y, Cheng X, Liu J, et al. Increased Krüppel-like factor 12 impairs embryo attachment via downregulation of leukemia inhibitory factor in women with recurrent implantation failure. Cell Death Discovery. 2018;4(1):1-13.
24. Yue X, Wu L, Hu W. The regulation of leukemia inhibitory factor. Cancer cell & microenvironment. 2015;2(3).
25. Hambartsoumian E. Endometrial leukemia inhibitory factor (LIF) as a possible cause of unexplained infertility and multiple failures of implantation. American Journal of Reproductive Immunology. 1998;39(2):137-43.
26. Mariee N, Li T, Laird S. Expression of leukaemia inhibitory factor and interleukin 15 in endometrium of women with recurrent implantation failure after IVF; correlation with the number of endometrial natural killer cells. Human reproduction. 2012;27(7):1946-54.
27. Steck T, Giess R, Suetterlin MW, Bolland M, Wiest S, Poehls UG, et al. Leukaemia inhibitory factor (LIF) gene mutations in women with unexplained infertility and recurrent failure of implantation after IVF and embryo transfer. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2004;112(1):69-73.
28. Lédée-Bataille N, Laprée-Delage G, Taupin JL, Dubanchet S, Frydman R, Chaouat G. Concentration of leukaemia inhibitory factor (LIF) in uterine flushing fluid is highly predictive of embryo implantation. Human reproduction. 2002 Jan;17(1):213-8. PubMed PMID: 11756390. Epub 2002/01/05. eng.
29. Steck T, Giess R, Suetterlin MW, Bolland M, Wiest S, Poehls UG, et al. Leukaemia inhibitory factor (LIF) gene mutations in women with unexplained infertility and recurrent failure of implantation after IVF and embryo transfer. European journal of obstetrics, gynecology, and reproductive biology. 2004 Jan 15;112(1):69-73. PubMed PMID: 14687743. Epub 2003/12/23. eng.
30. Krüger JP, Freymann U, Vetterlein S, Neumann K, Endres M, Kaps C. Bioactive Factors in Platelet-Rich Plasma Obtained by Apheresis. Transfusion Medicine and Hemotherapy. 2013;40(6):432-40.
31. Zhang S, Li P, Yuan Z, Tan J. Effects of platelet-rich plasma on the activity of human menstrual blood-derived stromal cells in vitro. Stem Cell Research & Therapy. 2018 2018/02/26;9(1):48.
32. Ida Bagus Putra Adnyana AANA, Anom Suardika, Kadek Agus Wijaya, Made Angga Diningrat. The Effect of Autologous Platelet Rich Plasma (PRP) Administration on Leukemia Inhibitory Factor (LIF) Level, Integrin β3, ER , and HOXA10 Expression on Endometrial Damage in Wistar Rats. International Journal of Science and Research (IJSR). 2021;10(8):841-8.
33. Kimber SJ. Leukaemia inhibitory factor in implantation and uterine biology. Reproduction. 2005 Aug;130(2):131-45. PubMed PMID: 16049151. Epub 2005/07/29. eng.
34. Markert UR, Morales-Prieto DM, Fitzgerald JS. Understanding the link between the IL-6 cytokine family and pregnancy: implications for future therapeutics. Expert review of clinical immunology. 2011 Sep;7(5):603-9. PubMed PMID: 21895473. Epub 2011/09/08. eng.
35. Mussano F, Genova T, Munaron L, Petrillo S, Erovigni F, Carossa S. Cytokine, chemokine, and growth factor profile of platelet-rich plasma. Platelets. 2016 Jul;27(5):467-71. PubMed PMID: 26950533. Epub 2016/03/08. eng.
36. Sarah Robertson DE. 7 September 2016.
37. Gur C, Diav-Citrin O, Shechtman S, Arnon J, Ornoy A. Pregnancy outcome after first trimester exposure to corticosteroids: a prospective controlled study. Reproductive Toxicology. 2004 2004/01/01/;18(1):93-101.
38. Perez-Garcia LF, Dolhain RJEM, Vorstenbosch S, Bramer W, van Puijenbroek E, Hazes JMW, et al. The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review. Human Reproduction Update. 2020;26(6):961-1001.
39. Schisterman EF, Gaskins AJ, Whitcomb BW. Effects of low-dose aspirin in in-vitro fertilization. Current opinion in obstetrics & gynecology. 2009 Jun;21(3):275-8. PubMed PMID: 19300253. Pubmed Central PMCID: PMC2736057. Epub 2009/03/21. eng.
40. Fishman P, Falach-Vaknin E, Sredni B, Meroni P, Rudniki C, Shoenfeld Y. Aspirin modulates interleukin-3 production: additional explanation for the preventive effects of aspirin in antiphospholipid antibody syndrome. The Journal of Rheumatology. 1995;22(6):1086-90.
41. Bates SM. Anticoagulation and in vitro fertilization and ovarian stimulation. Hematology American Society of Hematology Education Program. 2014 Dec 5;2014(1):379-86. PubMed PMID: 25696882. Epub 2015/02/20. eng.
42. Jutel M, Solarewicz-Madejek K, Smolinska S. Recombinant allergens: the present and the future. Human vaccines & immunotherapeutics. 2012 Oct;8(10):1534-43. PubMed PMID: 23095874. Pubmed Central PMCID: PMC3660775. Epub 2012/10/26. eng.
43. Zhao J, Xu B, Xie S, Zhang Q, Li YP. Whether G-CSF administration has beneficial effect on the outcome after assisted reproductive technology? A systematic review and meta-analysis. Reproductive biology and endocrinology : RB&E. 2016 Sep 22;14(1):62. PubMed PMID: 27659067. Pubmed Central PMCID: PMC5034435. Epub 2016/09/24. eng.
44. Eftekhar M, Sayadi M, Arabjahvani F. Transvaginal perfusion of G-CSF for infertile women with thin endometrium in frozen ET program: A non-randomized clinical trial. Iranian journal of reproductive medicine. 2014 Oct;12(10):661-6. PubMed PMID: 25469123. Pubmed Central PMCID: PMC4248151. Epub 2014/12/04. eng.
45. Mehrafza M, Kabodmehri R, Nikpouri Z, Pourseify G, Raoufi A, Eftekhari A, et al. Comparing the Impact of Autologous Platelet-rich Plasma and Granulocyte Colony Stimulating Factor on Pregnancy Outcome in Patients with Repeated Implantation Failure. Journal of reproduction & infertility. 2019 Jan-Mar;20(1):35-41. PubMed PMID: 30859080. Pubmed Central PMCID: PMC6386791. Epub 2019/03/13. eng.
46. Carp H, Toder V, Mashiach S. Graft versus host or host versus graft reaction after paternal immunization. Fertility and sterility. 1992;58(5):1085-7.
47. Pearlman S, Meek R, Cowchock F, Smith J, McFarland J, Aster R. Neonatal alloimmune thrombocytopenia after maternal immunization with paternal mononuclear cells: successful treatment with intravenous gamma globulin. American journal of perinatology. 1992;9(05/06):448-51.
48. Tanaka T, Umesaki N, Nishio J, Maeda K, Kawamura T, Araki N, et al. Neonatal thrombocytopenia induced by maternal anti-HLA antibodies: a potential side effect of allogenic leukocyte immunization for unexplained recurrent aborters. Journal of reproductive immunology. 2000;46(1):51-7.
49. Salamonsen LA, Dimitriadis E, Robb L. Cytokines in implantation. Seminars in reproductive medicine. 2000;18(3):299-310. PubMed PMID: 11299968. Epub 2001/04/13. eng.

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