Cytokines Supplementation to Culture Media and ICSI Outcome

Impact of Cytokine Supplementation With Various Protein Concentrations Into Human in Vitro Culture Medium on ICSI Cycle Outcome

A randomized clinical trial to evaluate the effect of cytokine supplementation in embryo culture medium with various protein concentrations aiming to evaluate the effects of cytokines (CYK) integration into the human in vitro culture medium with high and low human serum albumin (HSA) concentrations on live birth rates after intracytoplasmic sperm injection (ICSI).

Study Overview

• Status: Completed
• Conditions: ICSI
• Intervention / Treatment: Combination product: A single step culture medium

Detailed Description

Oocytes were injected, and embryos cultured and transferred in three supplemented culture media.

A- A single step culture medium (SSCM; Global, Life Global)+5mg/ml (10% Vol/Vol), life global protein, without supplementation of CYK (control n=200), B- A single step culture medium (SSCM; Global, Life Global)+5mg/ml (10% Vol/Vol), life global protein, with 2ng/mL GM-CSF (granulocyte macrophage colony stimulating factor) (G5035 Sigma), 5ng/mL HB-EGF (Heparine Binding Epidermal Growth Factor )(E4643 Sigma),and 5ng/mL LIF (Lukemia Inhbitory Factor) (SRP9001 Sigma)(n=200).

C- A single step culture medium (SSCM; Global, Life Global) +2mg/ml (5% Vol/Vol) life global protein, with 2ng/mL GM-CSF (G5035 Sigma), 5ng/mL HB-EGF (E4643 Sigma), and 5ng/mL LIF (SRP9001 Sigma).(n=200) Setting :- - Mansoura Integrated Fertility

• Study Type: Interventional
• Enrollment (Actual): 700
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Mansoura, Egypt, 3311
    • Mansoura Integrated Fertility Center
  • Dekahlia
    • Mansoura, Dekahlia, Egypt
      • Mansoura Integrated Fertility Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients who fitted the medical definition of infertility "One year of unprotected intercourse but not pregnant".

Exclusion Criteria:

• History of ovarian or adnexal surgery.
• Suspicious findings of ovarian malignancy.
• Presence of endocrine disorders such as diabetes mellitus, hyper-prolactinemia, thyroid dysfunction, congenital adrenal hyperplasia, Cushing's syndrome, and adrenal insufficiency.
• Presence of Globozoospermia (100% round-headed spermatozoa)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: HSA; A single step culture medium (SSCM; Global, Life Global)+5mg/ml (10% Vol/Vol) life global protein,	Combination product: A single step culture medium; A single step culture medium (SSCM; Global, Life Global)+5mg/ml life global protein, without supplementation of CYK
Experimental: CYK+ high HSA; A single step culture medium (SSCM; Global, Life Global)+5mg/ml (10% Vol/Vol) life global protein, supplemented with 2ng/mL GM-CSF (G5035 Sigma), 5ng/mL HB-EGF (E4643 Sigma),and 5ng/mL LIF (SRP9001 Sigma).	Combination product: A single step culture medium; A single step culture medium (SSCM; Global, Life Global)+5mg/ml life global protein, without supplementation of CYK
Active Comparator: CYK+low HSA; A single step culture medium (SSCM; Global, Life Global) +2mg/ml (5% Vol/Vol) life global protein, supplemented with 2ng/mL GM-CSF (G5035 Sigma), 5ng/mL HB-EGF (E4643 Sigma), and 5ng/mL LIF (SRP9001 Sigma).	Combination product: A single step culture medium; A single step culture medium (SSCM; Global, Life Global)+5mg/ml life global protein, without supplementation of CYK

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
live birth rate	the number of deliveries that resulted in at least one live born baby (>20 weeks gestational age or 500 gm birth weight ) expressed per 100 embryo transfer,	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fertilization rate	Fertilization rate (fertilized oocytes with two pronuclei/ number of MII oocytes) ×100 %	4 weeks
Top quality day 3 embryos	embryos with seven or eight blastomeres of stage-proper sizes, and <10% fragmentation by volume	4 weeks
Blastocyst formation rate	(number of blastocysts/number of cultured embryos for blastocyst formation) ×100%	4 weeks
Top blastocyst rate	(number of high quality blastocysts/number of formed blastocysts) ×100%	4 weeks
Available embryo rate	number of transferred and frozen embryos/number of zygotes (2 pronuclei) ×100%	4 weeks
clinical pregnancy rate	number of cycles with clinical pregnancy/number of transferred cycles) ×100%	8 weeks
Biochemical pregnancy rate	number of cycles with biochemical pregnancy/number of Cycles with positive HCG) ×100%.	6 weeks
Implantation rate	number of implanted embryos/number of transferred embryos) ×100%	8 weeks
Early embryo loss rat	number of early spontaneously aborted embryos/number of transferred embryos) × 100%.	16 weeks
ongoing pregnancy rate	number of clinical pregnancies after 12 weeks divided by number of embryo transfers multiplied by 100	16 weeks

Collaborators and Investigators

• Sponsor: Mansoura Integrated Fertility Center
• Collaborators: Rahem Fertility Center
• Investigators: Principal Investigator: Emad M Sedeek, MS, MIFC

Publications and helpful links

General Publications

• Fukui Y, Hirota Y, Matsuo M, Gebril M, Akaeda S, Hiraoka T, Osuga Y. Uterine receptivity, embryo attachment, and embryo invasion: Multistep processes in embryo implantation. Reprod Med Biol. 2019 May 24;18(3):234-240. doi: 10.1002/rmb2.12280. eCollection 2019 Jul.
• Guzeloglu-Kayisli O, Kayisli UA, Taylor HS. The role of growth factors and cytokines during implantation: endocrine and paracrine interactions. Semin Reprod Med. 2009 Jan;27(1):62-79. doi: 10.1055/s-0028-1108011. Epub 2009 Feb 5.
• Fawzy M, Emad M, Elsuity MA, Mahran A, Abdelrahman MY, Fetih AN, Abdelghafar H, Sabry M, Nour M, Rasheed SM. Cytokines hold promise for human embryo culture in vitro: results of a randomized clinical trial. Fertil Steril. 2019 Nov;112(5):849-857.e1. doi: 10.1016/j.fertnstert.2019.07.012. Epub 2019 Sep 21.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: August 30, 2020
• First Submitted That Met QC Criteria: September 10, 2020
• First Posted (Actual): September 14, 2020

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: Cytokine plus Global Protein

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD will be shared
• IPD Sharing Time Frame: 6 months after completion and for 3 months
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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