The Role of Granulocyte Colony Stimulating Factor in Embryo Transfer Outcomes

Infertility Clinical Trial

Official title:

The Role of Granulocyte Colony Stimulating Factor in Embryo Transfer Outcomes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06174298
• Other study ID #: NFC-2023-001
• Status: Recruiting
• Phase: Phase 4
• Start date: March 20, 2024
• Est. completion date: January 10, 2025

Study information

• Verified date: March 2024
• Source: Newlife Fertility Centre
• Contact: Samuel Soliman, M.D.
• Phone: +1 905-896-7100
• Email: drsoliman[@]newlifefertility.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to test the effect of granulocyte colony-stimulating factor (G-CSF, A.K.A. Filgrastim) in infertility patients undergoing in vitro fertilization (IVF) treatment. The main question it aims to answer is: Can in vitro fertilization-embryo transfer (IVF-ET) outcomes be improved by supplementing the transfer media with Granulocyte colony-stimulating factor (GCSF)? Participants will undergo their embryo transfer as per the normal clinic protocol but will be randomized to either receive the standard embryo transfer media or the GCSG-supplemented transfer media. Researchers will compare the GCSF and standard transfer media groups to see if clinical outcomes are improved (i.e., implantation rate, pregnancy, clinical pregnancy rate, live birth rate).

Description:

Please see uploaded study protocol.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: January 10, 2025
• Est. primary completion date: January 10, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 38 Years

Eligibility

Inclusion Criteria:

• Recruited subjects will either be undergoing a fresh IVF-ET cycle in which the embryo(s) generated from the initial treatment cycle are transferred during that same cycle (i.e., on day 5 or 6 post-egg retrieval) or an FET cycle in which the embryo(s) transferred were generated in a previous IVF cycle and were cryopreserved for subsequent warming and transfer.

Exclusion Criteria:

• Patients with uterine factor or severe male factor infertility will be excluded.
• Patients who have had previous IVF failures will be excluded.

Related Conditions & MeSH terms

• Infertility
• Infertility of Uterine Origin
• Infertility Unexplained
• Infertility, Female
• Infertility,Female
• Infertility; Female, Nonimplantation

Intervention

Drug:
• Granulocyte Colony-Stimulating Factor (Filgrastim)
Intervention Group Fresh Embryo Transfers: On day 5 or 6 of culture, viable embryos will be transferred into a center-well dish containing 1 mL of embryo transfer media supplemented with GCSF. The embryos will be cultured in this medium for approximately 3 hours before the embryo transfer (ET) procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician. Intervention Group Frozen Embryo Transfers: Cryopreserved embryos will be thawed according to the Kitazato thawing protocol and will be subsequently transferred to a center-well dish containing 1 mL of embryo transfer media supplemented with GCSF. The embryos will be cultured in this medium for approximately 3 hours before the ET procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician.

Other:
• Standard Embryo Transfer Media
Control Group Fresh Embryo Transfers: On day 5 or 6 of culture, viable embryos will be transferred into a center-well dish containing 1 mL of embryo transfer media. The embryos will be cultured in this medium for approximately 3 hours before the embryo transfer (ET) procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician. Control Group Frozen Embryo Transfers: Cryopreserved embryos will be thawed according to the Kitazato thawing protocol and will be subsequently transferred to a center-well dish containing 1 mL of embryo transfer media. The embryos will be cultured in this medium for approximately 3 hours before the ET procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician.

Locations

Country	Name	City	State
Canada	Newlife Fertility Centre	Mississauga	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Newlife Fertility Centre

Country where clinical trial is conducted

Canada, 

References & Publications (23)

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Cai L, Jeon Y, Yoon JD, Hwang SU, Kim E, Park KM, Kim KJ, Jin MH, Lee E, Kim H, Jeung EB, Hyun SH. The effects of human recombinant granulocyte-colony stimulating factor treatment during in vitro maturation of porcine oocyte on subsequent embryonic development. Theriogenology. 2015 Oct 15;84(7):1075-87. doi: 10.1016/j.theriogenology.2015.06.008. Epub 2015 Jun 19. — View Citation

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Davidson LM, Coward K. Molecular mechanisms of membrane interaction at implantation. Birth Defects Res C Embryo Today. 2016 Mar;108(1):19-32. doi: 10.1002/bdrc.21122. Epub 2016 Mar 10. — View Citation

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Giacomini G, Tabibzadeh SS, Satyaswaroop PG, Bonsi L, Vitale L, Bagnara GP, Strippoli P, Jasonni VM. Epithelial cells are the major source of biologically active granulocyte macrophage colony-stimulating factor in human endometrium. Hum Reprod. 1995 Dec;10(12):3259-63. doi: 10.1093/oxfordjournals.humrep.a135899. — View Citation

Kolibianakis E, Bourgain C, Albano C, Osmanagaoglu K, Smitz J, Van Steirteghem A, Devroey P. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up. Fertil Steril. 2002 Nov;78(5):1025-9. doi: 10.1016/s0015-0282(02)03323-x. — View Citation

Nimbkar-Joshi S, Rosario G, Katkam RR, Manjramkar DD, Metkari SM, Puri CP, Sachdeva G. Embryo-induced alterations in the molecular phenotype of primate endometrium. J Reprod Immunol. 2009 Dec;83(1-2):65-71. doi: 10.1016/j.jri.2009.08.011. Epub 2009 Oct 31. — View Citation

Obidniak D, Gzgzyan A, Dzhemlikhanova L, Feoktistov A. Effect of colony-stimulating growth factor on outcome of frozen-thawed embryo transfer in patients with repeated implantation failure. Fertility and Sterility. 2016;106(3):e134-e135.

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 Oct 2;9(9):e102286. doi: 10.1371/journal.pone.0102286. eCollection 2014. — View Citation

Scarpellini F, Sbracia M. G-CSF treatment improves IVF outcome in women with recurrent implantation failure in IVF. Journal of Reproductive Immunology. 2012;1(94):103.

Seshadri S, Morris G, Serhal P, Saab W. Assisted conception in women of advanced maternal age. Best Pract Res Clin Obstet Gynaecol. 2021 Jan;70:10-20. doi: 10.1016/j.bpobgyn.2020.06.012. Epub 2020 Aug 7. — View Citation

Singh R, Singh M, Jindal A, Jindal P. A prospective randomized controlled study (RCT) of Intra-uterine administration of Granulocyte Colony-Stimulating Factor (G-CSF) before embryo-transfer on resistant thin endometrium in IVF cycles. OXFORD UNIV PRESS GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND; 2015:280-280.

Sjoblom C, Wikland M, Robertson SA. Granulocyte-macrophage colony-stimulating factor promotes human blastocyst development in vitro. Hum Reprod. 1999 Dec;14(12):3069-76. doi: 10.1093/humrep/14.12.3069. — View Citation

Tevkin S, Lokshin V, Shishimorova M, Polumiskov V. The frequency of clinical pregnancy and implantation rate after cultivation of embryos in a medium with granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with preceding failed attempts of ART. Gynecol Endocrinol. 2014 Oct;30 Suppl 1:9-12. doi: 10.3109/09513590.2014.945767. — View Citation

Thum MY, Abdalla HI, Taylor D. Relationship between women's age and basal follicle-stimulating hormone levels with aneuploidy risk in in vitro fertilization treatment. Fertil Steril. 2008 Aug;90(2):315-21. doi: 10.1016/j.fertnstert.2007.06.063. Epub 2007 Oct 22. — View Citation

Würfel W. Approaches to a better implantation. J Assist Reprod Genet. 2000;17(8):473.

Yan J, Wu K, Tang R, Ding L, Chen ZJ. Effect of maternal age on the outcomes of in vitro fertilization and embryo transfer (IVF-ET). Sci China Life Sci. 2012 Aug;55(8):694-8. doi: 10.1007/s11427-012-4357-0. Epub 2012 Aug 30. — View Citation

Zhang L, Xu WH, Fu XH, Huang QX, Guo XY, Zhang L, Li SS, Zhu J, Shu J. 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 Nov;298(5):861-871. doi: 10.1007/s00404-018-4892-4. Epub 2018 Sep 15. — View Citation

Zhao Y, Rong H, Chegini N. Expression and selective cellular localization of granulocyte-macrophage colony-stimulating factor (GM-CSF) and GM-CSF alpha and beta receptor messenger ribonucleic acid and protein in human ovarian tissue. Biol Reprod. 1995 Oct;53(4):923-30. doi: 10.1095/biolreprod53.4.923. — View Citation

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* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Implantation Rate	Number of embryos implanted (i.e. number of gestational sacs observed under ultrasound guidance) divided by total number of embryos transferred	From enrollment to the time of 6-week ultrasound.
Primary	Clinical Pregnancy Rate	Number of patients with fetal heartbeats detected at time of 6-week ultrasound divided by the total number of patients in that group.	From enrollment to the time of 6-week ultrasound.
Primary	Pregnancy Rate	Number of patients with a positive beta-human chorionic gonadotropin (bhCG) pregnancy blood test at 10 days post-ET divided by the total number of patients in that group.	From enrollment to the time of blood test at 10 days post-ET.
Primary	Live Birth Rate	Total Number of infants born divided by the total number of embryo transfers performed (i.e., patients) in that group.	From enrollment to the time of birth (up to 9-months post-ET).
Secondary	Spontaneous Abortion Rate	Number of patients with a confirmed clinical pregnancy who lost their pregnancy before 20 weeks of gestation divided by the total number of patients with confirmed clinical pregnancies.	From enrollment to the time of pregnancy loss (up to 20 weeks post-ET).
Secondary	Biochemical Pregnancy Rate	Number of patients who had a positive beta-human chorionic gonadotropin (bhCG) pregnancy blood test at 10 days post-ET but that did not display a gestational sac/fetal heartbeat at 6-week ultrasound, divided by the total number of patients in that group.	From enrollment to the time of 6-week ultrasound.