Granulocyte Colony Stimulating Factor Versus Platelet Rich Plasma and Outcomes of Frozen Embryo Transfer

The Impact of Using Granulocyte Colony Stimulating Factor (G-CSF) Versus Platelet Rich Plasma (PRP) on the Outcomes of Frozen Embryo Transfer; Randomized Controlled Study

The rationale behind this current study is to assess the impact of using PRP versus GCSF on the outcomes of frozen embryo transfer in term of clinical pregnancy rates.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Granulocyte Colony Stimulating Factor; Other: Platelet Rich Plasma Arm; Other: Saline

Detailed Description

INTRODUCTION AND STUDY RATIONALE Despite the advancements in the treatment of infertility, repeated failure of implantation continues as a challenging difficulty.

Embryo implantation is affected by many factors. Many efforts were made to improve the implantation rate by different methods blastocyst transfer, assisted hatching, preimplantation genetic screening, hysteroscopy, removal of hydrosalpinges and endometrial scratch. Furthermore, infertility specialists suggested some empirical methods like the infusion in the uterine cavity of platelet-rich plasma (PRP) in patients with thin endometrium which has been shown to be effective in improving the pregnancy rate.

Another factor is granulocyte colony stimulating factor (G-CSF) which has receptors in endometrial cells and may have a role in implantation. The use of G-CSF in assisted reproductive technology (ART) has been tried by many research studies either via intrauterine or systemic administration.

There is only one study compared the impact of PRP and GCSF administration on the pregnancy rate and on the endometrial thickness with a small sample size.

The rationale behind this current study is to assess the impact of using PRP versus GCSF on the outcomes of frozen embryo transfer in term of clinical pregnancy rates.

STUDY OBJECTIVES

Primary:

The primary objective of the study is to compare the clinical pregnancy rate determined by presence of fetal heart beat in transvaginal ultrasound after embryo transfer in all groups.

Secondary:

To compare the following in the three study arms:

• Chemical pregnancy determined by positive serum β-HCG, 2 weeks after embryo transfer.
• Clinical pregnancy rate adjusted by the endometrial thickness (thin versus normal) in all groups.
• Clinical pregnancy rate adjusted by PGS in all groups
• The midluteal endometrial thickness in all groups (histopathology & TVUS).
• The number of women who had thin endometrium and reaches endometrial thickness ≥ 7 mm after using G-CSF or PRP.
• Implantation rate
• Miscarriage rate
• Live-birth rate

• Study Type: Interventional
• Enrollment (Actual): 390
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo
    • Maadi, Cairo, Egypt
      • Hayat center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No

Study Population

Women visiting the center for IVF by frozen embryo transfer

Description

Inclusion Criteria:

• All women aged 20-40 years
• non-smoker
• BMI < 30
• Normal endometrial cavity confirmed by hysteroscopy
• Visiting the center for IVF by frozen embryo transfer during the period of the study

Exclusion Criteria:

• History of anti-phospholipid syndrome confirmed by serological tests.
• History of any hematological and immunological disorders
• History of chromosomal or genetic abnormalities in the patient or in the family
• Any uterine abnormalities (congenital or acquired)
• Previous uterine surgeries except caesarean section
• Hypersensitivity to G-CSF
• Uncontrolled systemic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Granulocyte Colony Stimulating Factor Arm; Women in this group will receive G-CSF with conventional hormonal therapy: Estradiol valerate 6mg/day from day 2 of menstrual cycle Vaginal sildenafil citrate 25mg / 6 hours Then frozen embryo transfer will be performed.	Drug: Granulocyte Colony Stimulating Factor; Filgrastim, Amgen, California, USA 300 mg/1.0 mL; Other Names: Filgrastim
Active Comparator: Platelet Rich Plasma Arm; Women in this group will receive PRP with conventional hormonal therapy: Estradiol valerate 6mg/day from day 2 of menstrual cycle Vaginal sildenafil citrate 25mg / 6 hours Then frozen embryo transfer will be performed.	Other: Platelet Rich Plasma Arm; Platelet Rich Plasma Arm
Placebo Comparator: Saline; Women in this group will receive saline with conventional hormonal therapy: Estradiol valerate 6mg/day from day 2 of menstrual cycle Vaginal sildenafil citrate 25mg / 6 hours Then frozen embryo transfer will be performed.	Other: Saline; Saline 9%; Other Names: Saline 9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The clinical pregnancy rate	The clinical pregnancy rate	Up to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemical pregnancy rate	Chemical pregnancy rate	Up to 2 weeks
endometrial thickness	endometrial thickness in all groups (histopathology & TVUS)	Up to 2 weeks
Implantation rate	Implantation rate	Up to 2 weeks
Miscarriage rate	Miscarriage rate	With second trimester
Live-birth rate	Live-birth rate	1 year

Collaborators and Investigators

• Sponsor: Wael Elbanna Clinic
• Collaborators: National Research Centre, Egypt
• Investigators: Principal Investigator: Wael SS Elbanna, Consultant, Wael Elbanna Clinic

Publications and helpful links

General Publications

• Chang Y, Li J, Chen Y, Wei L, Yang X, Shi Y, Liang X. Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med. 2015 Jan 15;8(1):1286-90. eCollection 2015.
• Mehrafza M, Kabodmehri R, Nikpouri Z, Pourseify G, Raoufi A, Eftekhari A, Samadnia S, Hosseini A. 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 Jan-Mar;20(1):35-41.
• Coughlan C, Ledger W, Wang Q, Liu F, Demirol A, Gurgan T, Cutting R, Ong K, Sallam H, Li TC. Recurrent implantation failure: definition and management. Reprod Biomed Online. 2014 Jan;28(1):14-38. doi: 10.1016/j.rbmo.2013.08.011. Epub 2013 Sep 14.
• Rinehart J. Recurrent implantation failure: definition. J Assist Reprod Genet. 2007 Jul;24(7):284-7. doi: 10.1007/s10815-007-9147-4. Epub 2007 Aug 3.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): April 15, 2021
• Study Completion (Actual): March 8, 2023

Study Registration Dates

• First Submitted: May 8, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 10, 2019

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Pregnancy; PRP; GCSF
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: INDV-0909012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No