Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
권호 표지
DOI QR코드

DOI QR Code

The efficacy of intrauterine instillation of granulocyte colony-stimulating factor in infertile women with a thin endometrium: A pilot study

  • Lee, Dayong (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Jo, Jae Dong (Ellemedi Women Clinic) ;
  • Kim, Seul Ki (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Jee, Byung Chul (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Kim, Seok Hyun (Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine)
  • Received : 2016.09.18
  • Accepted : 2016.11.21
  • Published : 2016.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: The study aimed to investigate the efficacy of intrauterine instillation of granulocyte colony-stimulating factor (G-CSF) on the day of ovulation triggering or oocyte retrieval in infertile women with a thin endometrium. Methods: Fifty women whose endometrial thickness (EMT) was ${\leq}8mm$ at the time of triggering during at least one previous in vitro fertilization (IVF) cycle and an index IVF cycle were selected. On the day of triggering (n = 12) or oocyte retrieval (n = 38), $300{\mu}g$ of G-CSF was instilled into the uterine cavity. Results: In the 50 index IVF cycles, the mean EMT was $7.2{\pm}0.6mm$ on the triggering day and increased to $8.5{\pm}1.5mm$ on the embryo transfer day (p< 0.001). The overall clinical pregnancy rate was 22.0%, the implantation rate was 15.9%, and the ongoing pregnancy rate was 20%. The clinical pregnancy rate (41.7% vs. 15.8%), the implantation rate (26.7% vs. 11.7%), and the ongoing pregnancy rate (41.7% vs. 13.2%) were higher when G-CSF was instilled on the triggering day than when it was instilled on the retrieval day, although this tendency was likewise not statistically significant. Aspects of the stimulation process and mean changes in EMT were similar in women who became pregnant and women who did not. Conclusion: Intrauterine instillation of G-CSF enhanced endometrial development and resulted in an acceptable pregnancy rate. Instillation of G-CSF on the triggering day showed better outcomes. G-CSF instillation should be considered as a strategy for inducing endometrial growth and good pregnancy results in infertile women with a thin endometrium.

Keywords

References

  1. Senturk LM, Erel CT. Thin endometrium in assisted reproductive technology. Curr Opin Obstet Gynecol 2008;20:221-8. https://doi.org/10.1097/GCO.0b013e328302143c
  2. Kasius A, Smit JG, Torrance HL, Eijkemans MJ, Mol BW, Opmeer BC, et al. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis. Hum Reprod Update 2014;20:530-41. https://doi.org/10.1093/humupd/dmu011
  3. Gleicher N, Vidali A, Barad DH. Successful treatment of unresponsive thin endometrium. Fertil Steril 2011;95:2123.
  4. 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;28:172-7. https://doi.org/10.1093/humrep/des370
  5. Kunicki M, Lukaszuk K, Woclawek-Potocka I, Liss J, Kulwikowska P, Szczyptanska J. Evaluation of granulocyte colony-stimulating factor effects on treatment-resistant thin endometrium in women undergoing in vitro fertilization. Biomed Res Int 2014;2014:913235.
  6. Glujovsky D, Farquhar C, Quinteiro Retamar AM, Alvarez Sedo CR, Blake D. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev 2016;(6):CD002118.
  7. Shufaro Y, Simon A, Laufer N, Fatum M. Thin unresponsive endometrium: a possible complication of surgical curettage compromising ART outcome. J Assist Reprod Genet 2008;25:421-5. https://doi.org/10.1007/s10815-008-9245-y
  8. Rossman I, Bartelmez GW. The injection of the blood vascular system of the uterus. Anat Rec 1957;128:223-31. https://doi.org/10.1002/ar.1091280207
  9. Catt JW, Henman M. Toxic effects of oxygen on human embryo development. Hum Reprod 2000;15 Suppl 2:199-206. https://doi.org/10.1093/humrep/15.suppl_2.199
  10. Yang HW, Hwang KJ, Kwon HC, Kim HS, Choi KW, Oh KS. Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos. Hum Reprod 1998;13:998-1002. https://doi.org/10.1093/humrep/13.4.998
  11. Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, et al. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 1986;319:415-8. https://doi.org/10.1038/319415a0
  12. Fahey JV, Schaefer TM, Channon JY, Wira CR. Secretion of cytokines and chemokines by polarized human epithelial cells from the female reproductive tract. Hum Reprod 2005;20:1439-46. https://doi.org/10.1093/humrep/deh806
  13. Thomas J, Liu F, Link DC. Mechanisms of mobilization of hematopoietic progenitors with granulocyte colony-stimulating factor. Curr Opin Hematol 2002;9:183-9. https://doi.org/10.1097/00062752-200205000-00002
  14. Brouard N, Driessen R, Short B, Simmons PJ. G-CSF increases mesenchymal precursor cell numbers in the bone marrow via an indirect mechanism involving osteoclast-mediated bone resorption. Stem Cell Res 2010;5:65-75. https://doi.org/10.1016/j.scr.2010.04.002
  15. Chan RW, Schwab KE, Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod 2004;70:1738-50. https://doi.org/10.1095/biolreprod.103.024109
  16. Singh P, Hu P, Hoggatt J, Moh A, Pelus LM. Expansion of bone marrow neutrophils following G-CSF administration in mice results in osteolineage cell apoptosis and mobilization of hematopoietic stem and progenitor cells. Leukemia 2012;26:2375-83. https://doi.org/10.1038/leu.2012.117
  17. Schwab KE, Gargett CE. Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. Hum Reprod 2007;22:2903-11. https://doi.org/10.1093/humrep/dem265
  18. 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;86:9323-6. https://doi.org/10.1073/pnas.86.23.9323
  19. 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. Fertil Steril 2004;81 Suppl 1:786-91. https://doi.org/10.1016/j.fertnstert.2003.09.039
  20. 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;20:2434-40. https://doi.org/10.1093/humrep/dei071
  21. Ledee N, Munaut C, Aubert J, Serazin V, Rahmati M, Chaouat G, et al. Specific and extensive endometrial deregulation is present before conception in IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages. J Pathol 2011;225:554-64. https://doi.org/10.1002/path.2948
  22. Tanaka T, Miyama M, Masuda M, Mizuno K, Sakamoto T, Umesaki N, et al. Production and physiological function of granulocyte colony-stimulating factor in non-pregnant human endometrial stromal cells. Gynecol Endocrinol 2000;14:399-404. https://doi.org/10.3109/09513590009167710
  23. Scarpellini F, Sbracia M. Use of granulocyte colony-stimulating factor for the treatment of unexplained recurrent miscarriage: a randomised controlled trial. Hum Reprod 2009;24:2703-8. https://doi.org/10.1093/humrep/dep240
  24. 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. Arch Immunol Ther Exp (Warsz) 2013;61:159-64. https://doi.org/10.1007/s00005-012-0212-z
  25. 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:e102286. https://doi.org/10.1371/journal.pone.0102286
  26. Zhao J, Tian T, Zhang Q, Wang Y, Li Y. Use of granulocyte colonystimulating factor for the treatment of thin endometrium in experimental rats. PLoS One 2013;8:e82375. https://doi.org/10.1371/journal.pone.0082375

Cited by

  1. G-CSF and stem cell therapy for the treatment of refractory thin lining in assisted reproductive technology vol.34, pp.7, 2016, https://doi.org/10.1007/s10815-017-0922-6
  2. High granulocytic myeloid-derived suppressor cell levels in the peripheral blood predict a better IVF treatment outcome vol.32, pp.7, 2019, https://doi.org/10.1080/14767058.2017.1400002
  3. Embryo transfer strategy and therapeutic options in infertile patients with thin endometrium: a systematic review vol.36, pp.11, 2016, https://doi.org/10.1007/s10815-019-01576-w
  4. IM-12 activates the Wnt-β-catenin signaling pathway and attenuates rtPA-induced hemorrhagic transformation in rats after acute ischemic stroke vol.97, pp.6, 2016, https://doi.org/10.1139/bcb-2018-0384
  5. The incidence rate of unresponsive thin endometrium in frozen embryo transfer cycles: A case-series of therapy with granulocyte colony stimulating factor vol.17, pp.12, 2016, https://doi.org/10.18502/ijrm.v17i12.5797
  6. Stereological and histopathological evaluation of doxorubicin-induced toxicity in female rats’ ovary and uterus and palliative effects of quercetin and vitamin E vol.39, pp.12, 2016, https://doi.org/10.1177/0960327120937329