Cover
Vol. 9 No. 2 (2019)

Published: December 31, 2019

Pages: 18-38

Research Article

Intrauterine Infusion of Autologous Platelet-Rich Plasma Affects the Endometrial Thickness, Epidermal Growth Factor and Pregnancy Outcome in Patients Undergoing IUI

Abstract

Despite developments in assisted reproductive technology, there is immaterial progress in the implantation and pregnancy rates. Intrauterine infusion (IUIF) of autologous platelet-rich plasma (PRP) might renew implantation rates through its paracrine properties by progression cytokines and growth factors which favor implantation. Here we determine whether the IUIF of autologous PRP had a role in pregnancy outcome through its outcome on epidermal growth factor and endometrial thickness. An overall of 43 patients where prospectively randomly dispersed into two groups subjected to a superovulation program using Letrozole® tablet orally 2.5 mg twice daily 12 hours apart from day 2 for 5 days for one cycle. 20 women were considered as control receiving the conventional intrauterine insemination (IUI) management while 23 of them were given PRP by IUIF on the day of human chorionic gonadotrophin injection. The IUI was done for both groups 36-48 hours after confirming ovulation. The blood samples were collected from both groups on the day of IUI for the valuation of epidermal growth factor and an ultrasound was done on the day of human chorionic gonadotrophin injection and day of IUI for assessment of endometrial thickness. The mean endometrial thickness in the PRP group at the day of IUI was significantly thicker than that of the control group and the difference in percentage change of endometrial thickness between PRP group and controls significantly higher in PRP group. The mean epidermal growth factor and the pregnancy rate were significantly superior in the PRP group than that of controls. In conclusion, autologous PRP IUIF was well-tolerated and resulted in a significant expansion in endometrial thickness, epidermal growth factor Level and, subsequent pregnancy rate in an infertile woman undergoing IUI.

References

  1. Diagnostic evaluation of the infertile female: a committee opinion. Fertility and Sterility. Elsevier BV; 2015;103(6):e44–e50. Doi: http://dx.doi.org/10.1016/j.fertnstert.2 015.03.019 . [PubMed][Elsevier]
  2. Eftekhar M, Hosseinisadat R, Baradaran R, Naghshineh E. Effect of granulocyte colony stimulating factor (G-CSF) on IVF outcomes in infertile women: an RCT. International journal of reproductive biomed. (Yazd), 2016;14(5):341-346. [PubMed] [PMC]
  3. Zhang S, Lin H, Kong S, Wang S, Wang H, Wang H, Armant DR. Physiological and molecular determinants of embryo implantation. Molecular Aspects of Medicine. Elsevier BV; 2013;34(5):939–80. Doi: http://dx.doi.org/10.1016/j.mam.2012. 12.011 [PubMed][Elsevier][PMC]
  4. Fauque P, Lehert P, Lamotte M, Bettahar-Lebugle K, Bailly A, Diligent C, Clédat M, Pierrot P, Guénédal ML, Sagot P. Clinical success of intrauterine insemination cycles is affected by the sperm preparation time. Fertility and Sterility. Elsevier BV; 2014;101(6):1618–1623.e3. Doi: http://dx.doi.org/10.1016/j.fertnstert.2 014.03.015 [PubMed][Elsevier]
  5. Koli P, Anil M, Ramya NR, Patil K, Swamy MK. Intrauterine insemination: A retrospective review on determinants of success. International Journal of Reproduction, contraception, Obstetrics and gynecology, 2013;2(3):311-314. [ResearchGate][IJRCOG]
  6. Requena A, Herrero J, Landeras J, Navarro E, Neyro JL, Salvador C, Tur R, Callejo J, Reynolds LP, Caton JS, Redmer DA, Grazul-Bilska AT, Vonnahme KA, Borowicz PP, Luther JS, Wallace JM, Wu G, Spencer TE. Evidence for altered placental blood flow and vascularity in compromised pregnancies. The Journal of Physiology. Wiley; 2006;572(1):51–8. Doi: http://dx.doi.org/10.1113/jphysiol.200 5.104430 [PubMed][Wiley][PMC]
  7. Lee JW, Kwon OH, Kim TK, Cho YK, Choi KY, Chung HY, Cho BC, Yang JD, Shin JH. Platelet-Rich Plasma: Quantitative Assessment of Growth Factor Levels and Comparative Analysis of Activated and Inactivated Groups. Archives of Plastic Surgery. Korean Society of Plastic and Reconstructive Surgeons; 2013;40(5):530. Doi: http://dx.doi.org/10.5999/aps.2013.40. 5.530 [PubMed][APS][PMC]
  8. Tandulwadkar SR, Naralkar MV, Surana AD, Selvakarthick M, Kharat AH. Autologous intrauterine platelet- rich plasma instillation for suboptimal endometrium in frozen embryo transfer cycles: A pilot study. Journal of Human Reproductive Sciences. Medknow; 2017;10(3):208. Doi: http://dx.doi.org/10.4103/jhrs.jhrs_28 _17 [PubMed][PMC][Wolters Kluwer]
  9. Cole BJ, Seroyer ST, Filardo G, Bajaj S, Fortier LA. Platelet-Rich Plasma: Where Are We Now and Where Are We Going? Sports Health: A Multidisciplinary Approach. SAGE Publications; 2010;2(3):203–10. Doi: http://dx.doi.org/10.1177/1941738110 366385 [PubMed][PMC] [SAGE]
  10. Litvinov RI, Weisel JW, Andrianova IA, Peshkova AD, Minh GL. Differential Sensitivity of Various Markers of Platelet Activation with Adenosine Diphosphate. BioNanoScience. 2018;9(1):53–58. [PubMed][PMC]
  11. Chang Y, Li J, Chen Y, Wei L, Yang X, Shi Y, Liang X1. Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. International journal of clinical and experimental medicine, 2015;8(1):1286–1290. [PubMed] [PMC]
  12. Yuan T, Zhang T, Li C, Han Z. A New Perspective to Evaluate Doppler Vascular Impedance in Hypertensive Disorders Complicating Pregnancy: Multilevel Modeling Established in a Case Control Study. Open Journal of Obstetrics and Gynecology, 2015;5(6):350-359. [Scirp] [ResearchGate]
  13. Paulson RJ. Hormonal induction of endometrial receptivity. Fertility and Sterility. Elsevier BV; 2011;96(3):530–5. Doi: http://dx.doi.org/10.1016/j.fertnstert.2 011.07.1097 [PubMed][Elsevier]
  14. Senturk LM, Erel CT. Thin endometrium in assisted reproductive technology. Current Opinion in Obstetrics and Gynecology. Ovid Technologies (Wolters Kluwer Health); 2008;20(3):221–8. Doi: http://dx.doi.org/10.1097/gco.0b013e3 28302143c [PubMed] [Wolters Kluwer]
  15. Dreux AC, Lamb DJ, Modjtahedi H, Ferns GAA. The epidermal growth factor receptors and their family of ligands: Their putative role in atherogenesis. Atherosclerosis. Elsevier BV; 2006;186(1):38–53. Doi: http://dx.doi.org/10.1016/j.atheroscler osis.2005.06.038 [PubMed][Elsevier]
  16. Simón C, Martı́n JC, Pellicer A. Paracrine regulators of implantation. Best Practice & Research Clinical Obstetrics & Gynaecology. Elsevier BV; 2000;14(5):815–26. Doi: http://dx.doi.org/10.1053/beog.2000.0 121 [PubMed]
  17. Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nature Medicine. Springer Science and Business Media LLC; 2012;18(12):1754–67. Doi: http://dx.doi.org/10.1038/nm.3012 [PubMed][PMC][ResearchGate][Natu re]
  18. Stavreus-Evers A, Aghajanova L, Brismar H, Eriksson H, Landgren BM, Hovatta O. Co-existence of heparin- binding epidermal growth factor-like growth factor and pinopodes in human endometrium at the time of implantation. Molecular Human Reproduction, Oxford University Press (OUP); 2002;8(8):765–9. Doi: http://dx.doi.org/10.1093/molehr/8.8.7 65 [PubMed][OxFord]
  19. Ejskjær K, Sørensen BS, Poulsen SS, Mogensen O, Forman A, Nexø E. Expression of the epidermal growth factor system in human endometrium during the menstrual cycle. MHR: Basic science of reproductive medicine. Oxford University Press (OUP); 2005;11(8):543–51. Doi: http://dx.doi.org/10.1093/molehr/gah2 07 [PubMed][OxFord]
  20. Chia CM, Winston RM, Handyside AH. EGF, TGF-alpha and EGFR expression in human preimplantation embryos. Development. 1995;121(2):299-307. [PubMed] [DevBio]
  21. Chobotova K, Spyropoulou I, Carver J, Manek S, Heath JK, Gullick WJ, Barlow DH, Sargent IL, Mardon HJ. Heparin-binding epidermal growth factor and its receptor ErbB4 mediate implantation of the human blastocyst. Mechanisms of Development. Elsevier BV; 2002;119(2):137–44. Doi: http://dx.doi.org/10.1016/s0925- 4773(02)00342-8 [PubMed][Elsevier]
  22. Amable PR, Carias RB, Teixeira MV, da Cruz Pacheco I, Correa do Amaral RJ, Granjeiro JM, Borojevic R. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Research & Therapy. Springer Science and Business Media LLC; 2013;4(3):67. Doi: http://dx.doi.org/10.1186/scrt218 [PubMed][PMC][BMC]
  23. Mikhael NW, El-Esawy FM. Skin rejuvenation with autologous concentrated platelet-rich plasma. The Egyptian Journal of Dermatology and Venereology, 2014;34(1):5-9. [ESDV]
  24. Fatemi HM, Popovic-Todorovic B. Implantation in assisted reproduction: a look at endometrial receptivity. Reproductive BioMedicine Online. Elsevier BV; 2013;27(5):530–8. Doi: http://dx.doi.org/10.1016/j.rbmo.2013. 05.018 [PubMed][Elsevier]
  25. Berner A, Boerckel JD, Saifzadeh S, Steck R, Ren J, Vaquette C, Qiyi Zhang J, Nerlich M, Guldberg RE, Hutmacher DW, Woodruff MA. Biomimetic tubular nanofiber mesh and platelet rich plasma-mediated delivery of BMP-7 for large bone defect regeneration. Cell and Tissue Research. Springer Science and Business Media LLC; 2012;347(3):603–12. Doi: http://dx.doi.org/10.1007/s00441-011- 1298-z [PubMed][Springer]
  26. Andia I, Abate M. Platelet-rich plasma: underlying biology and clinical correlates. Regenerative Medicine. Future Medicine Ltd; 2013;8(5):645–58. Doi: http://dx.doi.org/10.2217/rme.13.59 [PubMed][FutureMed]
  27. Makrigiannakis A, Minas V, Kalantaridou SN, Nikas G, Chrousos GP. Hormonal and cytokine regulation of early implantation. Trends in Endocrinology & Metabolism. Elsevier BV; 2006;17(5):178–85. Doi: http://dx.doi.org/10.1016/j.tem.2006.0 5.001 [PubMed][Cell]
  28. Garcia-Velasco JA, Acevedo B, Alvarez C, Alvarez M, Bellver J, Fontes J, Landeras J, Manau D, Martinez F, Muñoz E, Robles A, Rodriguez-Tabernero L. Strategies to manage refractory endometrium: state of the art in 2016. Reproductive BioMedicine Online. Elsevier BV; 2016;32(5):474–89. Doi: http://dx.doi.org/10.1016/j.rbmo.2016. 02.001 [PubMed][Elsevier]
  29. Zadehmodarres S, Salehpour S, Saharkhiz N, Nazari L. Treatment of thin endometrium with autologous platelet-rich plasma: a pilot study. JBRA Assisted Reproduction. GN1 Genesis Network; 2017;21(1). Doi: http://dx.doi.org/10.5935/1518- 0557.20170013 [PubMed][JBRA] [PMC]
  30. Jang HY, Myoung SM, Choe JM, Kim T, Cheon YP, Kim YM, Park H. Effects of autologous plateletrich plasma on regeneration of damaged endometrium in female rats. Yonsei Medical Journal, Yonsei University College of Medicine (KAMJE); 2017;58(6):1195. Doi: http://dx.doi.org/10.3349/ymj.2017.58 .6.1195 [PubMed][YMJ][PMC]
  31. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic‐Canic M. Growth factors and cytokines in wound healing. Wound Repair and Regeneration. Wiley; 2008;16(5):585– 601. Doi: http://dx.doi.org/10.1111/j.1524- 475x.2008.00410.x [PubMed][Wiley]
  32. Karimipour DJ, Rittié L, Hammerberg C, Min VK, Voorhees JJ, Orringer JS, Sachs DL, Hamilton T, Fisher GJ. Molecular Analysis of Aggressive Microdermabrasion in Photoaged Skin. Archives of Dermatology. American Medical Association (AMA); 2009;145(10). Doi: http://dx.doi.org/10.1001/archdermato l.2009.231 [PubMed][JAMA]
  33. Anitua E, de la Fuente M, Ferrando M, Quintana F, Larreategui Z, Matorras R, Orive G. Biological effects of plasma rich in growth factors (PRGF) on human endometrial fibroblasts. European Journal of Obstetrics & Gynecology and Reproductive Biology. Elsevier BV; 2016;206:125–30. Doi: http://dx.doi.org/10.1016/j.ejogrb.201 6.09.024 [PubMed][Elsevier]
  34. Song M, Xu X, Li Y, Hu R, Zhao J, Ha L, Ma X, Ma L, Chen Y. Expression of heparin-binding epidermal growth factor in the endometrium is positively correlated with IVF-ET pregnancy outcome. International Journal of Clinical and Experimental Pathology, 2016;9(8):8280-8285. [IJCEP]
  35. Ponsuksili S, Tesfaye D, Schellander K, Hoelker M, Hadlich F, Schwerin M, Wimmers K. Differential Expression of miRNAs and Their Target mRNAs in Endometria Prior to Maternal Recognition of Pregnancy Associates with Endometrial Receptivity for In Vivo-and In Vitro- Produced Bovine Embryos. Biology of Reproduction. Oxford University Press (OUP); 2014;91(6). Doi: http://dx.doi.org/10.1095/biolreprod.1 14.121392 [OxFord]
  36. Farimani M, Poorolajal J, Rabiee S, Bahmanzadeh M. Successful pregnancy and live birth after intrauterine administration of autologous platelet-rich plasma in a woman with recurrent implantation failure: A case report. International Journal of Reproductive Biomedicine, 2017;15:803-806. [PubMed][PMC]
  37. Molina A, Sánchez J, Sánchez W, Vielma V. Platelet-rich plasma as an adjuvant in the endometrial preparation of patients with refractory endometrium. JBRA assisted reproduction, GN1 Genesis Network; 2018;22(1):42-48. Doi: http://dx.doi.org/10.5935/1518- 0557.20180009 [PubMed][JBRA] [PMC]
  38. Fujiwara H. Immune cells contribute to systemic cross-talk between the embryo and mother during early pregnancy in cooperation with the endocrine system. Reproductive Medicine and Biology. Wiley; 2006;5(1):19–29. Doi: http://dx.doi.org/10.1111/j.1447- 0578.2006.00119.x [PMC][Wiley]
  39. Staun-Ram E, Goldman S, Gabarin D, Shalev E. Expression and importance of matrix metalloproteinases 2 and 9 (MMP2 and -9) in human trophoblast invasion. Reproductive Biology and Endocrinology. Springer Science and Business Media LLC; 2004;2(1):59. Doi: http://dx.doi.org/10.1186/1477- 7827-2-59 [BMC]
  40. Aflalo ED, Sod-Moriah UA, Potashnik G, Har-Vardi I. EGF increases expression and activity of PAs in preimplantation rat embryos and their implantation rate. Reproductive Biology and Endocrinology. Springer Science and Business Media LLC; 2007;5(1). Doi: http://dx.doi.org/10.1186/1477-7827- 5-4 [BMC] Biography Wafaa Abdul-Kareem Abaid She received the M.B.CH.B from the University of Baghdad College of Medicine, in 1996. After two years of rotation, she traveled to Yemen for work exposure. After taking permanency in obstetrics and gynecology in Al-Hakeem Hospital in 2011-2012, She received the High Diploma in obstetrics and gynecology in 2014 and occupied the position of senior in the Al-Hakeem Hospital from 2014 to 2017. Then she graduated from the High Institute for Fertility Diagnosis and ART’ in 2019. Now she is in Al-Kadhimya Hospital Om Al-Baneen Center. Dr. Manal Taha Meteab Al-Obaidi She received the M.B.CH.B. from Al- Mustansirya University, the High diploma (equivalent to MSc.) in Assisted Reproductive Technology, Ph.D. in reproductive physiology in 1997, 2003, and 2013 respectively. She occupied several academic positions including the head of the clinical reproductive physiology department and currently, she is the dean of the High Institute of Infertility Diagnosis and Assisted Reproductive Technologies, Al Nahrain University. She published more than 20 articles both local and international. Dr. Muayad S. Abood He received the M.B.CH.B. from Al-Kufa University, the M.Sc., and the Ph.D. in Pharmacology from Al Nahrain University, in 1998, 2008, and 2014, respectively. He occupied several academic positions including the dean assistant for scientific affairs in Al Nahrain University. He has more than 10 published papers both local and international. How to cite: Abaid WA, Al-Obiadi MT, Abood MS. Intrauterine Infusion of Autologous Platelet-Rich Plasma Affects the Endometrial Thickness, Epidermal Growth Factor and Pregnancy Outcome in Patients Undergoing IUI; Iraqi Journal of Embryos and Infertility Researches (IJEIR), (2019); 9(2): 18-38. Doi: http://doi.org/10.28969/IJEIR.v9.i2.r2 © 2019 Author(s)