Does Subcutaneous Administration of Granulocyte Colony Stimulating Factor Improve Pregnancy Outcome in Patients Undergoing Intracytoplasmic Sperm Injection?

Document Type: Original Article

Authors

1 Assistant Professor of Obstetrics & Gynecology, Reproductive Health Research Center, Department of Obstetrics & Gynecology, Alzahra Hospital, Guilan University of Medical Sciences, Rasht, Iran

2 Obstetrician and Gynecologist, Mehr Fertility Research Center, Guilan University of Medical Sciences, Rasht, Iran

3 Nutritionist, Mehr Fertility Research Center, Guilan University of Medical Sciences, Rasht, Iran

4 Embryologist, Mehr Fertility Research Center, Guilan University of Medical Sciences, Rasht, Iran

5 Developmental Biologist, Mehr Fertility Research Center, Guilan University of Medical Sciences, Rasht, Iran

6 Statistician, Mehr Fertility Research Center, Guilan University of Medical Sciences, Rasht, Iran

Abstract

Background:Expression of granulocyte colony stimulating factor (G-CSF) and its receptors in embryo and endometrium implicates the involvement of this glycoprotein on implantation process. In the present study, we aimed to evaluate the impact of routine use of subcutaneous administration of G-CSF on pregnancy outcomes in intracytoplasmic sperm injection (ICSI) patients.
Methods: In this retrospective study, ICSI outcomes were compared between two groups of patients: the first group (n=108) who received subcutaneous G-CSF (300 mcg) two hours before the embryo transfer and the second group (n=110) who did not receive it. Pregnancy outcome was compared between the two groups. P-value<0.05 was considered statistically significant.
Results:There was no significant difference between G-CSF and control groups with respect to the rate of implantation (respectively, 23%vs. 23%, p=0.49), chemical (respectively, 43.5%vs. 50%, p=0.34) and clinical (respectively, 40.7% vs. 46.4%, p=0.23) pregnancy. In logistic regression analyses, subcutaneous G-CSF administration was not associated with clinical pregnancy in both crude and adjusted odds ratios (OR) with 95% confidence interval (CI) (crude OR: 0.8, CI: 0.47-1.36, p=0.4, and adjusted OR: 0.99, CI: 0.48-2.07, p=0.99).
Conclusion:In the present study, subcutaneous G-CSF did not improve pregnancy outcomes in patients undergoing ICSI; therefore, the routine use of this cytokine is not suggested for all patients.

Keywords


  1. PrabhuDas M, Bonney E, Caron K, Dey S, Erlebacher A, Fazleabas A, et al. Immune mechanisms at the maternal-fetal interface: perspectives and challenges. Nat Immunol 2015; 16(4):328-34.
  2. Yoshinaga K. Review of factors essential for blastocyst implantation for their modulating effects on the maternal immune system. Semin Cell Dev Biol 2008; 19(2):161-9.
  3. Gumperz JE, Parham P. The enigma of the natural killer cell. Nature 1995; 378(6554):245-8.
  4. Loke YW, King A. Immunology of human placental implantation: clinical implications of our current understanding. Mol Med Today 1997; 3(4):153-9.
  5. Hiby S, Regan L, Lo W, Farrell L, Carrington M, Moffett A. Association of maternal killer-cell immunoglobulin-like receptors and parental HLA-C genotypes with recurrent miscarriage. Hum Reprod 2008; 23(4):972-6.
  6. Duan JS. Production of granulocyte colony stimulating factor in decidual tissue and its significance in pregnancy. Osaka City Med J 1990; 36(2):81-97.
  7. Shorter SC, Vince GS, Starkey PM. Production of granulocyte colony-stimulating factor at the materno-foetal interface in human pregnancy. Immunology 1992; 75(3):468-74.
  8. Sharma R, Das A. Organ-specific phenotypic and functional features of NK cells in humans. Immunol Res 2014; 58(1):125-31.
  9. Uzumaki H, Okabe T, Sasaki N, Hagiwara K, Takaku F, Itoh S. Characterization of receptor for granulocyte colony-stimulating factor on human circulating neutrophils. Biochem Biophys Res Commun 1988; 156(2):1026-32.
  10. Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood 1991; 78(11):2791-808.
  11. Würfel W, Santjohanser C, Hirv K, Bühl M, Meri O, Laubert I, et al. High pregnancy rates with administration of granulocyte colony-stimulating factor in ART-patients with repetitive implantation failure and lacking killer-cell immunglobulin-like receptors. Hum Reprod 2010; 25(8):2151-2.
  12. Lédée N, Gridelet V, Ravet S, Jouan C, Gaspard O, Wenders F, et al. Impact of follicular G-CSF quantification on subsequent embryo transfer decisions: a proof of concept study. Hum Reprod 2012; 28(2):406-13.
  13. Gleicher N, Kim A, Michaeli T, Lee HJ, Shohat-Tal A, Lazzaroni E, et al. A pilot cohort study of granulocyte colony-stimulating factor in the treatment of unresponsive thin endometrium resistant to standard therapies. Hum Reprod 2013; 28(1):172-7.
  14. Tehraninejad E, Davari Tanha F, Asadi E, Kamali K, Aziminikoo E, Rezayof E. G-CSF intrauterine for thin endometrium, and pregnancy outcome. J Family Reprod Health 2015; 9(3):107-12.
  15. Aleyasin A, Abediasl Z, Nazari A, Sheikh M. Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial. Reproduction 2016; 151(6):637-42.
  16. Eftekhar M, Miraj S, Farid Mojtahedi M, Neghab N. Efficacy of Intrauterine infusion of granulocyte colony stimulating factor on patients with history of implantation failure: a randomized control trial. Int J Reprod Biomed (Yazd) 2016; 14(11):687-90.
  17. 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. Reprod Biol Endocrinol 2016; 14(1):62.
  18. Arefi S, Fazeli E, Esfahani M, Borhani N, Yamini N, Hosseini A, et al. Granulocyte-colony stimulating factor may improve pregnancy outcome in patients with history of unexplained recurrent implantation failure: an RCT. Int J Reprod Biomed (Yazd) 2018; 16(5):299-304.
  19. Li Y, Pan P, Chen X, Li L, Li Y, Yang D. Granulocyte colony-stimulating factor administration for infertile women with thin endometrium in frozen embryo transfer program. Reprod Sci 2014; 21(3):381-5.
  20. Barad DH, Yu Y, Kushnir VA, Shohat-Tal A, Lazzaroni E, Lee HJ, et al. A randomized clinical trial of endometrial perfusion with granulocyte colony-stimulating factor in in vitro fertilization cycles: impact on endometrial thickness and clinical pregnancy rates. Fertil Steril 2014; 101(3):710-5.
  21. Eftekhar M, Naghshineh E, Khani P. Role of granulocyte colony-stimulating factor in human reproduction. J Res Med Sci 2018; 29:23-7.
  22. Salmassi A, Schmutzler AG, Schaefer S, Koch K, Hedderich J, Jonat W, et al. Is granulocyte colony-stimulating factor level predictive for human IVF outcome? Hum Reprod 2005; 20(9):2434-40.
  23. Lédée N, Petitbarat M, Rahmati M, Dubanchet S, Chaouat G, Sandra O, et al. New pre-conception immune biomarkers for clinical practice: interleukin-18, interleukin-15 and TWEAK on the endometrial side, G-CSF on the follicular side. J Reprod Immunol 2011; 88(2):118-23.
  24. Basu S, Dunn A, Ward A. G-CSF: function and modes of action. Int J Mol Med 2002; 10(1):3-10.
  25. Uzumaki H, Okabe T, Sasaki N, Hagiwara K, Takaku F, Tobita M, et al. Identification and characterization of receptors for granulocyte colony-stimulating factor on human placenta and trophoblastic cells. Proc Natl Acad Sci U S A 1989; 86(23):9323-6.
  26. Rahmati M, Petitbarat M, Dubanchet S, Bensussan A, Chaouat G, Ledee N. Granulocyte-Colony Stimulating Factor related pathways tested on an endometrial ex-vivo model. PLoS One 2014; 9(10):e102286.
  27. Kunicki M, Łukaszuk K, Liss J, Skowrońska P, Szczyptańska J. Granulocyte colony stimulating factor treatment of resistant thin endometrium in women with frozen-thawed blastocyst transfer. Syst Biol Reprod Med 2017; 63(1):49-57.
  28. Eftekhar M, Hosseinisadat R, Baradaran R, Naghshineh E. Effect of granulocyte colony stimulating factor (G-CSF) on IVF outcomes in infertile women: An RCT. Int J Reprod Biomed (Yazd) 2016; 14(5):341-6.
  29. Xu B, Zhang Q, Hao J, Xu D, Li Y. Two protocols to treat thin endometrium with granulocyte colony-stimulating factor during frozen embryo transfer cycles. Reprod Biomed Online 2015; 30(4):349-58.