Is There any Role for Granulocyte Colony Stimulating Factor in Improvement of Implantation in Intrauterine Insemination? A Prospective Double-Blind Randomized Control Trial

Document Type : Original Article

Authors

1 Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

3 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Granulocyte colony stimulating factor (GCSF) has been introduced as an immunomodulatory agent by increasing implantation rate in vitro fertilization (IVF) patients but it has not been studied in intrauterine insemination (IUI) patients. The aim of this study is to answer the role of GCSF in implantation rate of IUI.
Materials and Methods: In this prospective double-blind randomized control trial, 320 eligible patients were enrolled, who were referred to the referral infertility clinic of Shiraz University of Medical Sciences from February 2018 till the end of 2019. They were divided into two groups randomly. After collecting the demographic data, all patients received clomiphene citrate from the 5th day of the menstruation cycle for 5 days. 50-150 units of recombinant purified follicle-stimulating factor (FSH) were started from the 8th day of the cycle. Follicle monitoring was done by transvaginal sonography till a mature follicle of 18 mm or more was developed. Human chorionic gonadotropin (HCG) injection was done in both groups with intrauterine administration of 300 μg GCSF in the case group and normal saline in the control group simultaneously. After 36 hours, IUI was performed. The clinical pregnancy, miscarriage, and ongoing pregnancy rates of both groups were calculated by SPSS software.
Results: The results showed improvement of clinical pregnancy rate [15.38% vs. 13.81% OR=1.17 (0.62-2.21)], miscarriage rate [3.84% vs. 5.26% OR=0.74 (0.25-2.20)] and ongoing pregnancy rate [11.53% vs. 8.55% OR=1.37 (0.65-2.92)] in the GCSF group compared to the control. However, the results revealed no statistically significance (P>0.05).
Conclusion: Although it was not statistically significant, 300 μg Intrauterine GCSF administration simultaneously with hCG injection in standard IUI procedure might increase the pregnancy outcomes. Further studies are warranted (registration number: IRCT201212079281N2).

Keywords

References

1. Buckett W, Sierra S. The management of unexplained infertility: an evidence-based guideline from the Canadian Fertility and Andrology Society. Reprod Biomed Online. 2019; 39(4): 633-640.
2. Kandavel V, Cheong Y. Does intra-uterine insemination have a place in modern ART practice? Best Pract Res Clin Obstet Gynaecol. 2018; 53: 3-10.
3. Wang R, van Eekelen R, Mochtar MH, Mol F, van Wely M. Treatment strategies for unexplained infertility. Semin Reprod Med. 2020; 38(1): 48-54.
4. Ayeleke RO, Asseler JD, Cohlen BJ, Veltman-Verhulst SM. Intra-uterine insemination for unexplained subfertility. Cochrane Database Syst Rev. 2020; 3(3): CD001838.
5. Wang R, Danhof NA, Tjon-Kon-Fat RI, Eijkemans MJ, Bossuyt PM, Mochtar MH, et al. Interventions for unexplained infertility: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2019; 9(9): CD012692.
6. Bahadur G, Homburg R, Bosmans JE, Huirne JAF, Hinstridge P, Jayaprakasan K, et al. Observational retrospective study of UK national success, risks and costs for 319,105 IVF/ICSI and 30,669 IUI treatment cycles. BMJ Open. 2020; 10(3): e034566.
7. Wadhwa L, Mishra M. Therapeutic efficacy of endometrial scratching in repeated controlled ovarian stimulation (COS) failure cycles. J Hum Reprod Sci. 2018; 11(1): 59-71.
8. Jiang Y, Zhao Q, Zhang Y, Zhou L, Lin J, Chen Y, et al. Treatment of G-CSF in unexplained, repeated implantation failure: A systematic review and meta-analysis. J Gynecol Obstet Hum. 2020; 49(10):101866.
9. Bashiri A, Halper KI, Orvieto R. Recurrent implantation failure-update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol. 2018; 16(1): 121.
10. Cavalcante MB, Cavalcante C, Sarno M, Barini R. Intrauterine perfusion immunotherapies in recurrent implantation failures: Systematic review. Am J Reprod Immunol. 2020; 83(6): e13242.
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): 2151-2152.
12. Eftekhar M, Naghshineh E, Khani P. Role of granulocyte colony-stimulating factor in human reproduction. J Res Med Sci. 2018; 23: 7.
13. 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 Assist Reprod. 2019; 23(3): 250-254.
14. Zeyneloglu HB, Tohma YA, Onalan G, Moran U. Granulocyte colony-stimulating factor for intracytoplasmic sperm injection patients with repeated implantation failure: which route is best? J Obstet Gynaecol. 2020; 40(4): 526-530.
15. Zhang L, Xu WH, Fu XH, Huang QX, Guo XY, Zhang L, et al. Therapeutic role of granulocyte colony-stimulating factor (G-CSF) for infertile women under in vitro fertilization and embryo transfer (IVF-ET) treatment: a meta-analysis. Arch Gynecol Obstet. 2018; 298(5): 861-871.
16. Kamath MS, Chittawar PB, Kirubakaran R, Mascarenhas M. Use of granulocyte-colony stimulating factor in assisted reproductive technology: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2017; 214: 16-24.
17. Rocha MNC, Florêncio RS, Alves RRF. The role played by granulocyte colony stimulating factor (G-CSF) on women submitted to in vitro fertilization associated with thin endometrium: systematic review. JBRA Assist Reprod. 2020; 24(3): 278-282.
18. Lédée N, Lombroso R, Lombardelli L, Selva J, Dubanchet S, Chaouat G, et al. Cytokines and chemokines in follicular fluids and potential of the corresponding embryo: the role of granulocyte colony-stimulating factor. Hum Reprod. 2008; 23(9): 2001-2009.
19. Cruz M, Alecsandru D, García-Velasco JA, Requena A. Use of granulocyte colony-stimulating factor in ART treatment does not increase the risk of adverse perinatal outcomes. Reprod Biomed Online. 2019; 39(6): 976-980.
20. Moustafa S, Young SL. Diagnostic and therapeutic options in recurrent implantation failure. F1000Res. 2020; 9: F1000 Faculty Rev-208.
21. Aleyasin A, Abediasl Z, Nazari A, Sheikh M. Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial. Reproduction. 2016; 151(6): 637-642.
22. Zhong B. How to calculate sample size in randomized controlled trial? J Thorac Dis. 2009; 1(1): 51-54.
23. Kalem Z, Namli Kalem M, Bakirarar B, Kent E, Makrigiannakis A, Gurgan T. Intrauterine G-CSF administration in recurrent implantation failure (RIF): an Rct. Sci Rep. 2020; 10(1): 5139.
24. Boomsma CM, Cohlen BJ, Farquhar C. Semen preparation techniques for intrauterine insemination. Cochrane Database Syst Rev. 2019; 10(10): CD004507.
25. 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. J Reprod Infertil. 2019; 20(1): 35-41.
26. Ranisavljevic N, Raad J, Anahory T, Grynberg M, Sonigo C. Embryo transfer strategy and therapeutic options in infertile patients with thin endometrium: a systematic review. J Assist Reprod Genet. 2019; 36(11): 2217-2231.
27. Kamath MS, Kirubakaran R, Sunkara SK. Granulocyte-colony stimulating factor administration for subfertile women undergoing assisted reproduction. Cochrane Database Syst Rev. 2020; 1(1): CD013226.
28. Davari-Tanha F, Shahrokh Tehraninejad E, Ghazi M, Shahraki Z. The role of G-CSF in recurrent implantation failure: A randomized double blind placebo control trial. Int J Reprod Biomed. 2016; 14(12): 737-342.
29. Practice Committee of the American Society for Reproductive Medicine. Electronic address: ASRM@asrm.org; Practice Committee of the American Society for Reproductive Medicine. The role of immunotherapy in in vitro fertilization: a guideline. Fertil Steril. 2018; 110(3): 387-400.
30. 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.
31. Zhang T, Chen X, Wang CC, Li TC, Kwak-Kim J. Intrauterine infusion of human chorionic gonadotropin before embryo transfer in IVF/ET cycle: The critical review. Am J Reprod Immunol. 2019; 81(2): e13077.
32. Xie Y, Zhang T, Tian Z, Zhang J, Wang W, Zhang H, et al. Efficacy of intrauterine perfusion of granulocyte colony-stimulating factor (g-CSF) for Infertile women with thin endometrium: a systematic review and meta-analysis. Am J Reprod Immunol. 2017; 78(2): e12701.
International Journal of Fertility and Sterility
Volume 16, Issue 4
October 2022
Pages 281-285

Files

Cited by

Share

How to cite

Statistics