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

• ClinicalTrials.gov Identifier: NCT03945812
• Recruitment Status: Recruiting
• First Posted: May 10, 2019
• Last Update Posted: February 16, 2021
• Sponsor: ClinAmygate
• Collaborators: Wael Elbanna Clinic; National Research Centre, Egypt
• Information provided by (Responsible Party): Emad Roushdy, ClinAmygate

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Infertility	Drug: Granulocyte Colony Stimulating Factor; Other: Platelet Rich Plasma Arm; Other: Saline	Phase 4

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.
• 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 390 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Impact of Using Granulocyte Colony Stimulating Factor (G-CSF) Versus Platelet Rich Plasma (PRP) on the Outcomes of Frozen Embryo Transfer; Double-blinded Randomized Placebo-controlled Trial (Endotrial)
• Actual Study Start Date: June 15, 2019
• Estimated Primary Completion Date: June 15, 2021
• Estimated Study Completion Date: December 15, 2021

Arms and Interventions

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 cycle will be performed.	Drug: Granulocyte Colony Stimulating Factor; Filgrastim, Amgen, California, USA 300 mg/1.0 mL; Other Name: 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 cycle 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 cycle will be performed.	Other: Saline; Saline 9%; Other Name: Saline 9%

Outcome Measures

Primary Outcome Measures :

1. The clinical pregnancy rate [ Time Frame: Up to 2 weeks ]
   The clinical pregnancy rate

Secondary Outcome Measures :

1. Chemical pregnancy rate [ Time Frame: Up to 2 weeks ]
   Chemical pregnancy rate
2. endometrial thickness [ Time Frame: Up to 2 weeks ]
   endometrial thickness in all groups (histopathology & TVUS)
3. Implantation rate [ Time Frame: Up to 2 weeks ]
   Implantation rate
4. Miscarriage rate [ Time Frame: With second trimester ]
   Miscarriage rate
5. Live-birth rate [ Time Frame: 1 year ]
   Live-birth rate

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 40 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• All women aged 20-40 years
• non-smoker
• BMI < 30
• Normal endometrial cavity confirmed by hysteroscopy

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

Contacts and Locations

Contacts

Contact: Emad RH Issak, Dip; 00201272228989; dr.emad.r.h.issak@gmail.com

Contact: Wael SS Elbanna, MD; 00201227760402

Locations

Egypt

Wael El-Banna Clinic; Recruiting

Maadi, Cairo, Egypt

Contact: Wael SS El-Banna, MD

Sponsors and Collaborators

ClinAmygate

Wael Elbanna Clinic

National Research Centre, Egypt

Investigators

• Study Director: Emad RH Issak, Dip; ClinAmygate

More Information

Publications:

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. Review.

Rinehart J. Recurrent implantation failure: definition. J Assist Reprod Genet. 2007 Jul;24(7):284-7. Epub 2007 Aug 3. Review.

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.

• Responsible Party: Emad Roushdy, Director, ClinAmygate
• ClinicalTrials.gov Identifier: NCT03945812
• Other Study ID Numbers: INDV-0909012
• First Posted: May 10, 2019
• Last Update Posted: February 16, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Emad Roushdy, ClinAmygate:

GCSF; PRP; Pregnancy

Additional relevant MeSH terms:

Infertility; Lenograstim; Sargramostim; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs