The effect of intrauterine injection of granulocyte stimulating factor (G-CSF) on IUI success rate

Document Type : Original Article

Authors

1 Assistant Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

2 General Practitioner, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

3 Associate Professor of Health Policy, Social Determinants of Health Research Center, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

Abstract

Introduction: IUI or injection of washed sperm into the uterine cavity is one of the assisted reproductive techniques that has been widely used in the treatment of infertility. This study was performed with aim to evaluate the effect of intrauterine injection of granulocyte stimulating factor (G-CSF) on the success rate of IUI in patients referred to the infertility center of Ardabil University of Medical Sciences.
Methods: This clinical trial study was performed in 2019-2020 on 100 women with primary infertility referred to the Infertility Center of Ardabil University of Medical Sciences for IUI. The subjects were randomly divided into intervention and control groups each with 50 women. To stimulate ovulation for the women in two groups, clomiphene citrate was administered from the third to the fifth day of menstruation at a dose of 50-100 mg daily for five days and gonadotropin ampoules were administered with dose 150 mg at days 7 and 9 and after reaching to at least one follicle with 20 ml diameter, HCG was injected for the final maturation of the oocyte. In the intervention group, in addition to previous procedures on the day of HCG injection, 100 micrograms of G-CSF was injected intrauterine with IUI catheter, and then IUI was performed 36 hours later. Collected data were analyzed by SPSS (version 25). P<0.05 was considered significant.
Results: The success rate of IUI based on βHCG test was 20% in the case group and 4% in the control group, which showed a statistically significant difference in the success rate of pregnancy (p=0.028).
Conclusion: The results of the present study showed that G-CSF administration improves the chance of pregnancy compared to no treatment.

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  1. Sun Y, Parsanezhad M. The effect of group therapy on depression and anxiety in infertile women. Journal of Jondi Shapour University of Medical Sciences 2003; 38:7.
  2. Bakhtiari A. Assessment of infertility reasons & some effective factors on infertile couple, Babol, 1999. Journal of Babol University of Medical Sciences 2000; 2(2):50-6.
  3. Mansour R, Tawab N, Kamal O, El-Faissal Y, Serour A, Aboulghar M, et al. Intrauterine injection of human chorionic gonadotropin before embryo transfer significantly improves the implantation and pregnancy rates in in vitro fertilization/intracytoplasmic sperm injection: a prospective randomized study. Fertility and sterility 2011; 96(6):1370-4.
  4. Vahidi S, Ardalan A, Mohammad K. Prevalence of primary infertility in the Islamic Republic of Iran in 2004-2005. Asia Pacific Journal of Public Health 2009; 21(3):287-93.
  5. Yavuz A, Demirci O, Sözen H, Uludoğan M. Predictive factors influencing pregnancy rates after intrauterine insemination. Iranian journal of reproductive medicine 2013; 11(3):227.
  6. 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. Journal of Reproductive Immunology 2011; 88(2):118-23.
  7. Scarpellini F, Sbracia M. Use of granulocyte colony-stimulating factor for the treatment of unexplained recurrent miscarriage: a randomised controlled trial. Human Reproduction 2009; 24(11):2703-8.
  8. 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. Fertility and sterility 2014; 101(3):710-5.
  9. 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. Human Reproduction 2013; 28(1):172-7.
  10. Shams-Eldeen NM, Shalan HM, Hemida RA, Elmetwally AG. Clomiphene citrate in LH surge suppression for women undergoing ICSI. Middle East Fertility Society Journal 2018; 23(4):281-5.
  11. Homan G, Brown S, Moran J, Homan S, Kerin J. Human chorionic gonadotropin as a predictor of outcome in assisted reproductive technology pregnancies. Fertility and sterility 2000; 73(2):270-4.
  12. Claman P, Wilkie V, Collins D. Timing intrauterine insemination either 33 or 39 hours after administration of human chorionic gonadotropin yields the same pregnancy rates as after superovulation therapy. Fertility and sterility 2004; 82(1):13-6.
  13. Requena A, Cruz M, Pacheco A, García-Velasco JA. Ongoing pregnancy rates in intrauterine insemination are affected by late follicular-phase progesterone levels. Fertility and Sterility 2015; 104(4):879-83.
  14. Hansen KR, Eisenberg E, Baker V, Hill MJ, Chen S, Talken S, et al. Midluteal progesterone: a marker of treatment outcomes in couples with unexplained infertility. The Journal of Clinical Endocrinology & Metabolism 2018; 103(7):2743-51.
  15. Giles J, Cruz M, González-Ravina C, Caligara C, Prados N, Martínez JC, et al. Small-sized follicles could contribute to high-order multiple pregnancies: outcomes of 6552 intrauterine insemination cycles. Reproductive BioMedicine Online 2018; 37(5):549-54.
  16. Santjohanser C, Knieper C, Franz C, Hirv K, Meri O, Schleyer M, et al. Granulocyte-colony stimulating factor as treatment option in patients with recurrent miscarriage. Archivum immunologiae et therapiae experimentalis 2013; 61:159-64.
  17. Gleicher N, Vidali A, Barad DH. Successful treatment of unresponsive thin endometrium. Fertility and sterility 2011; 95(6):2123-e13.
  18. Jalilvand F, Gasemzadeh A, Hamdi K, Navali N, Pia H, Farzadi L. Efficacy of uteral injection of G-CSF in repeated implantation failure: a clinical trial study. Medical Journal of Tabriz University of Medical Sciences 2018; 40(1):16-21.
  19. Zeyneloglu HB, Onalan G, Durak T, Alyazici I, Unal E. Granulocyte macrophage colony stimulating factor (G-CSF) administration for art patients with repeated implantation failure (RIF): which route is best?. Fertility and Sterility 2013; 100(3):S291-2.
  20. Yanagi K, Makinoda S, Fujii R, Miyazaki S, Fujita S, Tomizawa H, et al. Cyclic changes of granulocyte colony-stimulating factor (G-CSF) mRNA in the human follicle during the normal menstrual cycle and immunolocalization of G-CSF protein. Human Reproduction 2002; 17(12):3046-52.
  21. Ghomian N, Mousavifar N, Rostami Nezhad V, Ghanaei N. Frequency of pregnancy and its predicting factors in IUI cycles at Milad Infertility Center during 2011-2013. The Iranian Journal of Obstetrics, Gynecology and Infertility 2017; 20(10):13-20.
  22. Lédée N, Frydman R, Osipova A, Taieb J, Gallot V, Lombardelli L, et al. Levels of follicular G-CSF and interleukin-15 appear as noninvasive biomarkers of subsequent successful birth in modified natural in vitro fertilization/intracytoplasmic sperm injection cycles. Fertility and sterility 2011; 95(1):94-8.
  23. Makinoda S, Mikuni M, Sogame M, Kobamatsu Y, Furuta I, Yamada H, et al. Erythropoietin, granulocyte‐colony stimulating factor, interleukin‐1β and interleukin‐6 during the normal menstrual cycle. International Journal of Gynecology & Obstetrics 1996; 55(3):265-71.
  24. Salmassi A, Schmutzler AG, Huang L, Hedderich J, Jonat W, Mettler L. Detection of granulocyte colony-stimulating factor and its receptor in human follicular luteinized granulosa cells. Fertility and sterility 2004; 81:786-91.
  25. Basirat Z, Shamsoddin M. Association of Follicular Response with Outcome of Intrauterine Insemination in Infertile Women. Journal of Babol University of Medical Sciences 2009; 11(1):19-24.
  26. Soria M, Pradillo G, García J, Ramón P, Castillo A, Jordana C, et al. Pregnancy predictors after intrauterine insemination: analysis of 3012 cycles in 1201 couples. Journal of reproduction & infertility 2012; 13(3):158-66.
  27. Iberico G, Vioque J, Ariza N, Lozano JM, Roca M, Llácer J, et al. Analysis of factors influencing pregnancy rates in homologous intrauterine insemination. Fertility and sterility 2004; 81(5):1308-13.
  28. Dinelli L, Courbiere B, Achard V, Jouve E, Deveze C, Gnisci A, et al. Prognosis factors of pregnancy after intrauterine insemination with the husband's sperm: conclusions of an analysis of 2,019 cycles. Fertility and sterility; 101(4):994-1000.
  29. Speroff L, Fritz MA, editors. Clinical gynecologic endocrinology and infertility. lippincott Williams & wilkins; 2005.
  30. Basirat Z, Shamsoddin M. Association of Follicular Response with Outcome of Intrauterine Insemination in Infertile Women. Journal of Babol University of Medical Sciences 2009; 11(1):19-24.
  31. Gerli S, Gholami H, Manna A, Di Frega AS, Vitiello C, Unfer V. Use of ethinyl estradiol to reverse the antiestrogenic effects of clomiphene citrate in patients undergoing intrauterine insemination: a comparative, randomized study. Fertility and sterility 2000; 73(1):85-9.
  32. Deng CY, Clark S. Superovulation and intrauterine insemination in treatment of idiopathic infertility in 202 cycles. Zhongguo yi xue ke xue Yuan xue bao. Acta Academiae Medicinae Sinicae 2004; 26(2):178-81.
  33. Houmard BS, Juang MP, Soules MR, Fujimoto VY. Factors influencing pregnancy rates with a combined clomiphene citrate/gonadotropin protocol for non-assisted reproductive technology fertility treatment. Fertility and sterility 2002; 77(2):384-6.
  34. Tay PY, Raj VM, Kulenthran A, Sitizawiah O. Prognostic factors influencing pregnancy rate after stimulated intrauterine insemination. Medical Journal of Malaysia 2007; 62(4):286.
  35. Dickey RP, Olar TT, Taylor SN, Curole DN, Rye PH, Matulich EM. Relationship of follicle number, serum estradiol, and other factors to birth rate and multiparity in human menopausal gonadotropin-induced intrauterine insemination cycles. Fertility and sterility 1991; 56(1):89-92.
  36. van Rumste MM, den Hartog JE, Dumoulin JC, Evers JL, Land JA. Is controlled ovarian stimulation in intrauterine insemination an acceptable therapy in couples with unexplained non‐conception in the perspective of multiple pregnancies?. Human reproduction 2006; 21(3):701-4.
  37. Souter I, Baltagi LM, Kuleta D, Meeker JD, Petrozza JC. Women, weight, and fertility: the effect of body mass index on the outcome of superovulation/intrauterine insemination cycles. Fertility and sterility 2011; 95(3):1042-7.
  38. Sermondade N, Huberlant S, Bourhis-Lefebvre V, Arbo E, Gallot V, Colombani M, et al. Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis. Human reproduction update 2019; 25(4):439-51.
  39. Bafrani HH, Abedzadeh M, Fruzanfard F, Tabasi Z. Effects of patient age, duration and cause of infertility and number of pre-ovulatory follicles on intrauterine insemination outcomes. Koomesh 2010; 12(1).
  40. Fukutomi T, Kohno M, Izumi Y, Watanabe M, Hayashi Y, Nomori H. Pulmonary pleomorphic carcinoma producing granulocyte–macrophage colony-stimulating factor: report of a case. Surgery today 2012; 42:288-91.
  41. Salimi S, Sargolzaei N, Robati ZS, Ajdary M, Farzaneh F. Pregnancy rate in two methods of fallopian tube perfusion (FSP) with standard intrauterine insemination (IUI) in infertile patients. The Iranian Journal of Obstetrics, Gynecology and Infertility 2023; 26(4):1-7.