Iranian Society of Gynecology Oncology

Document Type : Original Research Article


1 Department of Clinical infertility and Reproduction, High Institute for Infertility Diagnosis and Assisted Reproductive Technologies, AL Nahrain University, Baghdad, Iraq

2 High Institute for Infertility Diagnosis and Assisted Reproductive Technologies, AL Nahrain University, Baghdad, Iraq


Background & Objective: Granulosa cells, the endometrium, and the placenta all play a role in the secretion of G-CSF in the reproductive tract. G-CSF affects immunological regulation, which is crucial for enhancing pregnancy viability and maintenance. To evaluate the effects of granulocyte-colony stimulating factor subcutaneous injection on the miscarriage rate, ongoing pregnancy rate, and livebirth rate after single and multiple doses of G-CSF factor.
Materials & Methods: At the High Institute for Infertility Diagnosis and Assisted Reproductive Technologies at Al-Nahrain University, a prospective comparison study with a random sample selection was conducted from December 2021 to December 2022. It included 121 infertile women who had previously unsuccessful intracytoplasmic sperm injection (ICSI) procedures and who had finished ICSI protocols and reached the embryo transfer day. Patients were divided into three groups on the day of the embryo transfer: The non-G-CSF group (49 patients) received no additional treatment; the single-G-CSF group (31 patients) received a single subcutaneous injection of granulocyte-colony stimulating factor one hour after embryo transfer; and the multiple-G-CSF group (41 patients) received weekly injections of G-CSF until a fetal heartbeat could be detected, starting one hour after the embryo transfer.
Results: The multiple G-CSF group had better results in the miscarriage rate, ongoing pregnancy rate, and livebirth rate (23.5%, 34.1%, and 31.7%, respectively) when compared to the single G-CSF group (42.9%, 16.1, and 12.9%, respectively) and the non-G-CSF group (37.5%, 12.2%, and 10.2%, respectively).
Conclusion: Multiple subcutaneous G-CSF doses can improve the miscarriage rate, ongoing pregnancy rate, and live birth rate. A single dose of G-CSF for infertile women has no appreciable benefits.


Main Subjects

1. Homer HA. Modern management of recurrent miscarriage. Aust N Z J Obstet Gynaecol. 2019;59(1):36-44. [DOI:10.1111/ajo.12920] [PMID]
2. Mascarenhas M, Jeve Y, Polanski L, Sharpe A, Yasmin E, Bhandari HM. Management of recurrent implantation failure: British Fertility Society policy and practice guideline. Hum Fertil. 2022;25(5):813-37. [DOI:10.1080/14647273.2021.1905886] [PMID]
3. Recchia K, Jorge AS, Pessôa LV, Botigelli RC, Zugaib VC, de Souza AF, et al. Actions and Roles of FSH in Germinative Cells. Int J Mol Sci [Internet]. 2021; 22(18):[10110 p.]. [DOI:10.3390/ijms221810110] [PMID] [PMCID]
4. Ashary N, Tiwari A, Modi D. Embryo Implantation: War in Times of Love. Endocrinology. 2018;159(2):1188-98. [DOI:10.1210/en.2017-03082] [PMID]
5. Robert CA, Abbas MK, Suyeewin T, Haider MB. Mediator in the Embryo-endometrium Cross-talk: Granulocyte Colony-stimulating Factor in Infertility. Cureus. 2019;11(8):1-11. [DOI:10.7759/cureus.5390] [PMID] [PMCID]
6. 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. [DOI:10.1038/s41598-020-61955-7] [PMID] [PMCID]
7. Hou Z, Jiang F, Yang J, Liu Y, Zha H, Yang X, et al. What is the impact of granulocyte colony-stimulating factor (G-CSF) in subcutaneous injection or intrauterine infusion and during both the fresh and frozen embryo transfer cycles on recurrent implantation failure: a systematic review and meta-analysis? Reprod Biol Endocrinol. 2021;19(1):1-10. [DOI:10.1186/s12958-021-00810-4] [PMID] [PMCID]
8. Aramesh S, Azizi Kutenaee M, Najafi F, Ghaffari P, Taghavi SA. Granulocyte colony stimulating factor (GCSF) did not affect the fertility outcomes in women with unexplained infertility after intrauterine insemination: a randomised clinical trial. J Obstet Gynaecol. 2022;42(6):2480-5. [DOI:10.1080/01443615.2022.2080534] [PMID]
9. Hoff HS, Yuan L, Lessey BA, Young SL. Complex differential expression of colony stimulating factor (CSF) ligands and receptors in the human endometrium. Fertil Steril. 2016;106(3):e11. [DOI:10.1016/j.fertnstert.2016.07.039]
10. Papapanou M, Siristatidis C. Repeated implantation failure. in Management of Infertility: Elsevier; 2023. p. 345-55. [DOI:10.1016/B978-0-323-89907-9.00015-6]
11. Kong X, Tang G, Liu Y, Zheng Z, Li Y, Yan F. Efficacy of intrauterine infusion therapy before embryo transfer in recurrent implantation failure: A systematic review and network meta-analysis. J Reprod Immunol. 2023;156:103819. [DOI:10.1016/j.jri.2023.103819] [PMID]
12. Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, Kolibianakis E, et al. Erratum: ESHRE guideline: ovarian stimulation for IVF/ICSI. Hum Reprod Open. 2020;2020(4):hoaa067. [DOI:10.1093/hropen/hoaa067] [PMID] [PMCID]
13. Busnelli A, Somigliana E, Cirillo F, Levi-Setti PE. Is diminished ovarian reserve a risk factor for miscarriage? Results of a systematic review and meta-analysis. Hum Reprod Update. 2021;27(6):973-88. [DOI:10.1093/humupd/dmab018] [PMID]
14. Carvalho F, Coonen E, Goossens V, Kokkali G, Rubio C, Meijer-Hoogeveen M, et al. ESHRE PGT Consortium good practice recommendations for the organisation of PGT. Hum Reprod Open. 2020;2020(3):hoaa021. [DOI:10.1093/hropen/hoaa021] [PMID] [PMCID]
15. Landa-Solís C, Olivos-Meza A, Ortega-Sánchez O-DB, Velasquillo-Martínez C, Ibarra C. Mobilized Mesenchymal Stem Cells for Tissue Engineering in Preclinical Models. Int J Vaccin Res. 2016;1(1):1-5. [DOI:10.15226/2473-2176/1/1/00104]
16. Al-Jubouri WM, Al-Obaidi MT, Hussaini HA. Endometrial perfusion with granulocyte colony stimulating factor in infertile women. Pharmacologyonline. 2021;2:417-25.
17. Scarpellini F, Sbracia M. G-CSF treatment improves IVF outcome in women with recurrent implantation failure in IVF. J Reprod Immunol. 2012;1(94):103. [DOI:10.1016/j.jri.2012.03.435]
18. 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):526-30. [DOI:10.1080/01443615.2019.1631772] [PMID]
19. Sen U, Khastgir G. Comparative Study of The Role of Single Versus Double Dose of GCSF in Poor Endometrial Thickness Before Frozen Embryo Transfe. Bangladesh J Fertil Steril. 2021;1(1): 23-9.
20. Scarpellini F, Sbracia M. The use of G-CSF for implantation failure in IVF: a clinical trial. Fertil Steril. 2011;96(3):S93. [DOI:10.1016/j.fertnstert.2011.07.359]
21. Scarpellini F, Sbracia M. G-CSF treatment increases Treg cells in the decidua of women with recurrent pregnancy loss. Fertil Steril. 2013;100(3):S139. [DOI:10.1016/j.fertnstert.2013.07.1585]
22. 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. [DOI:10.1530/REP-16-0046] [PMID]
23. Torky H, El-Desouky ES, El-Baz A, Aly R, El-Taher O, Shata A, et al. Effect of Intra Uterine Granulocyte Colony Stimulating Factor vs. Human Chorionic Gonadotropin at Ovum Pick Up Day on Pregnancy Rate in IVF/ICSI Cases With Recurrent Implantation Failure. JBRA Assist Reprod. 2022;26(2):274-9. [DOI:10.5935/1518-0557.20210056]