Cover
Vol. 11 No. 2 (2021)

Published: October 31, 2021

Pages: 73-89

Research Article

Improving Endometrial Parameters and Enhancing Implantation in ICSI Patients with Intra-Uterine Infusion of Autologous Platelet-Rich Plasma

Abstract

The crosstalk between a receptive endometrium and a functional blastocyst during human embryo implantation is crucial for conception. Because platelets rich plasma (PRP) with concentrated platelets 4-5 times higher than normal, when release of granules containing growth factors including VEGF, TGF, PDGF, IGF, and EGF, these factors involved for sub endometrial angiogenesis and endometrial receptivity. 44 women under the age of 40 were given antagonist ovarian stimulation treatments, the oocytes were harvested utilizing 2-D power doppler ultrasound guidance, then ICSI done for them. On the hCG day all had an intrauterine autologous PRP infusion. Power Doppler is utilized to measure endometrial thickness (EnT), pulsatility index (PI), and resistance index (RI) of sub endometrial arteries, as well as serum levels of VEGF and EGF were measured on the hCG day and ovum pickup (OPU). The ultrasound findings, on the hCG day compared to those of OPU in all women with intrauterine infused autologous PRP were highly significant (HS). The mean EnT, RI, PI, VEGF and EGF at OPU day was lower than that on hCG day in a HS manner, with (p < 0.001), (p < 0.001), (p=0.047), (p < 0.001), and (p<0.001) respectively. These characteristics were shown to be significantly and independently associated to intrauterine PRP infusion. After PRP injection, both growth factors serum levels (VEGF and EGF) increased, and ultrasonography sub-endometrial metrics such as EnT, RI, and PI changed as the thickness grew while vascular resistance decreased, and all considered as predictors of endometrial receptivity.

References

  1. World Health Organization. WHO laboratory manual for the examination and processing of human semen, 5th ed. 2010 World Health Organization. [Online article link]
  2. Szamatowicz M, Szamatowicz J. Proven and unproven methods for diagnosis and treatment of infertility. Advances in Medical Sciences. Elsevier BV; 2020 Mar;65(1):93– 6. [Online article link]
  3. Dieamant F, Vagnini LD, Petersen CG, Mauri AL, Renzi A, Petersen B, et al. New therapeutic protocol for improvement of endometrial receptivity (PRIMER) for patients with recurrent implantation failure (RIF) - A pilot study. JBRA Assisted Reproduction. GN1 Genesis Network; 2019. [Online article link]
  4. Elsokkary M, Eldin AB, Abdelhafez M, Rateb A, Samy M, Eldorf A, et al. The reproducibility of the novel utilization of five-dimensional ultrasound and power Doppler in the prediction of endometrial receptivity in intracytoplasmic sperm- injected women: a pilot prospective clinical study. Archives of Gynecology and Obstetrics. Springer Science and Business Media LLC; 2018 Dec 19;299(2):551–8. [Online article link]
  5. Liu H, Chen Y, Yan F, Han X, Wu J, Liu X, et al. Ultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 Expression for Endometrial Receptivity Evaluation. Theranostics. Ivyspring International Publisher; 2015;5(2):206–17. [Online article link]
  6. Bos-Mikich A, Ferreira MO, de Oliveira R, Frantz N. Platelet-rich plasma or blood- derived products to improve endometrial receptivity? Journal of Assisted Reproduction and Genetics. Springer Rahmatullah, et al. http://doi.org/10.28969/IJEIR.v11.i2.r6 85 Science and Business Media LLC; 2019 Jan 4;36(4):613–20. [Online article link]
  7. Fioravanti C, Frustaci I, Armellin E, Condò R, Arcuri C, Cerroni L. Autologous blood preparations rich in platelets, fibrin and growth factors. ORAL & implantology (Rome). 2016 Jul 23;8(4):96-113. [Online article link]
  8. Hou Z, Zhang Q, Zhao J, Xu A, He A, Huang X, et al. Value of endometrial echo pattern transformation after hCG trigger in predicting IVF pregnancy outcome: a prospective cohort study. Reproductive Biology and Endocrinology. Springer Science and Business Media LLC; 2019 Sep 5;17(1). [Online article link]
  9. Rahmatullah WS, Al-Obaidi MT, AL-Saadi WI, Selman MO, Faisal GG. Role of Vascular Endothelial Growth Factor (VEGF) and Doppler Sub-endometrial Parameters as Predictors of Successful Implantation in Intracytoplasmic Sperm Injection (ICSI) Patients. Siriraj Medical Journal. Faculty of Medicine Siriraj Hospital, Mahidol University; 2020 Jan 1;72(1):33–40. [Online article link]
  10. Khan MS, Shaikh A, Ratnani R. Ultrasonography and Doppler Study to Predict Uterine Receptivity in Infertile Patients Undergoing Embryo Transfer. The Journal of Obstetrics and Gynecology of India. Springer Science and Business Media LLC; 2015 Sep 8;66(S1):377–82. [Online article link]
  11. Maged AM, Kamel AM, Abu-Hamila F, Elkomy RO, Ohida OA, Hassan SM, et al. The measurement of endometrial volume and sub-endometrial vascularity to replace the traditional endometrial thickness as predictors of in-vitro fertilization success. Gynecological Endocrinology. Informa UK Limited; 2019 Apr 21;35(11):949–54. [Online article link]
  12. Hershko Klement A, Berkovitz A, Wiser A, Gonen O, Amichay K, Cohen I, et al. GnRH-antagonist programming versus GnRH agonist protocol: a randomized trial. European Journal of Obstetrics & Gynecology and Reproductive Biology. Elsevier BV; 2015 Feb;185:170–3. [Online article link] Rahmatullah, et al. http://doi.org/10.28969/IJEIR.v11.i2.r6 86
  13. Zhang D, Xia L, Xu H, Chen Q, Jin B, Zhang A, et al. Flexible Low-Dose GnRH Antagonist Protocol Is Effective in Patients With Sufficient Ovarian Reserve in IVF. Frontiers in Endocrinology. Frontiers Media SA; 2018 Dec 19;9. [Online article link]
  14. Huang J, Lin J, Cai R, Lu X, Song N, Gao H, et al. Significance of endometrial thickness change after human chorionic gonadotrophin triggering in modified natural cycles for frozen-thawed embryo transfer. Annals of Translational Medicine. AME Publishing Company; 2020 Dec;8(23):1590–1590. [Online article link]
  15. Larson RC, Ignotz GG, Currie WB. Platelet derived growth factor (PDGF) stimulates development of bovine embryos during the fourth cell cycle. Development. 1992 Jul;115(3):821-6. [Online article link]
  16. 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. International Journal of Reproductive BioMedicine. Knowledge E; 2019 Jul 29; 443-448. [Online article link]
  17. Aghajanova L, Houshdaran S, Balayan S, Irwin J, Huddleston H, Giudice L. Platelets for endometrial regeneration: a novel approach. Fertility and Sterility. Elsevier BV; 2016 Sep;106(3):e82. [Online article link]
  18. 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. International Journal of Reproductive BioMedicine. 2016 Oct;14(10):625-628. [Online article link]
  19. Garcia-Velasco JA, Acevedo B, Alvarez C, Alvarez M, Bellver J, Fontes J, et al. Strategies to manage refractory endometrium: state of the art in 2016. Reproductive BioMedicine Online. Elsevier BV; 2016 May;32(5):474–89. [Online article link]
  20. Motwani Y, Sharma R. To study the effect of autologous platelet-rich plasma instillation on suboptimal endometrium and Rahmatullah, et al. http://doi.org/10.28969/IJEIR.v11.i2.r6 87 pregnancy outcomes in infertile women undergoing frozen embryo transfer cycle. Fertility Science and Research. Medknow; 2020;7(2):141. [Online article link]
  21. Singh N, Bahadur A, Mittal S, Malhotra N, Bhatt A. Comparative analysis of endometrial blood flow on the day of hCG by 2D Doppler in two groups of women with or without genital tuberculosis undergoing IVF-ET in a developing country. Archives of Gynecology and Obstetrics. Springer Science and Business Media LLC; 2010 Aug 6;283(1):115–20. [Online article link]
  22. Alfer J, Happel L, Dittrich R, Beckmann M, Hartmann A, Gaumann A, et al. Insufficient Angiogenesis: Cause of Abnormally Thin Endometrium in Subfertile Patients? Geburtshilfe und Frauenheilkunde. Georg Thieme Verlag KG; 2017 Jul;77(07):756–64. [Online article link]
  23. Zhu Y, Lu H, Huo Z, Ma Z, Dang J, Dang W, et al. MicroRNA-16 inhibits feto- maternal angiogenesis and causes recurrent spontaneous abortion by targeting vascular endothelial growth factor. Scientific Reports. Springer Science and Business Dr. Wafaa Salih Rahmatullah Media LLC; 2016 Oct 17;6(1). [Online article link]