ICSINCT04547699
Cytokines Supplementation to Culture Media and ICSI Outcome
A study testing A single step culture medium in people with ICSI, run by Mansoura Integrated Fertility Center at 2 sites in Egypt.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 38 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- ICSI
- What is being tested?
- A single step culture medium
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 700 participants
- Where
- 2 sitesEgypt
- Study dates
- 1 Feb 2020to 1 Jul 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 38 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Patients who fitted the medical definition of infertility "One year of unprotected intercourse but not pregnant".
Who cannot join
- 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)
Trial locations and contacts
2 sites in 1 country.
Egypt2 sites
Mansoura Integrated fertility Center
Al Mansurah, Dekahlia
Mansoura Integrated Fertility Center
Al Mansurah, 3311
About this study
Official title: 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).
Read the 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
- Conditions
- ICSI
- Being tested
- A single step culture medium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A single step culture mediumCombination product
A single step culture medium (SSCM; Global, Life Global)+5mg/ml life global protein, without supplementation of CYK
| Study group | Role | What they receive |
|---|---|---|
| HSA | Placebo comparator | A single step culture medium (SSCM; Global, Life Global)+5mg/ml (10% Vol/Vol) life global protein, Receives: Combination Product: A single step culture medium |
| CYK+ high HSA | Experimental | 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). Receives: Combination Product: A single step culture medium |
| CYK+low HSA | Active comparator | 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). Receives: Combination Product: A single step culture medium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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,
Measured: 9 months
Secondary outcomes (10)
Fertilization rate
Fertilization rate (fertilized oocytes with two pronuclei/ number of MII oocytes) ×100 %
Measured: 4 weeks
Top quality day 3 embryos
embryos with seven or eight blastomeres of stage-proper sizes, and <10% fragmentation by volume
Measured: 4 weeks
Blastocyst formation rate
(number of blastocysts/number of cultured embryos for blastocyst formation) ×100%
Measured: 4 weeks
Top blastocyst rate
(number of high quality blastocysts/number of formed blastocysts) ×100%
Measured: 4 weeks
Available embryo rate
number of transferred and frozen embryos/number of zygotes (2 pronuclei) ×100%
Measured: 4 weeks
clinical pregnancy rate
number of cycles with clinical pregnancy/number of transferred cycles) ×100%
Measured: 8 weeks
Biochemical pregnancy rate
number of cycles with biochemical pregnancy/number of Cycles with positive HCG) ×100%.
Measured: 6 weeks
Implantation rate
number of implanted embryos/number of transferred embryos) ×100%
Measured: 8 weeks
Early embryo loss rat
number of early spontaneously aborted embryos/number of transferred embryos) × 100%.
Measured: 16 weeks
ongoing pregnancy rate
number of clinical pregnancies after 12 weeks divided by number of embryo transfers multiplied by 100
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2020
- Study start1 Feb 2020
- Primary completion1 Jul 2021
- Study completion1 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ICSIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter, randomized, double-blinded and prospective study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 700 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mansoura Integrated Fertility Center
- Sponsor type
- University, hospital or other
- Collaborators
- Rahem Fertility Center
- Responsible party
- Principal investigator, Emad Mohamad Sedeek, Mansoura Integrated Fertility Center
- Investigators
- Emad M Sedeek, MS, Principal investigator, MIFC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04547699
- Sponsor's protocol ID
- Cytokine plus Global Protein
- Status last verified
- Jun 2023
- First submitted
- 30 Aug 2020
- Last updated
- 18 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPD will be shared
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.
PubMed 31312101Guzeloglu-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.
PubMed 19197806Fawzy 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.
PubMed 31551154
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Cytokine Supplementation With Various Protein Concentrations Into Human in Vitro Culture Medium on ICSI Cycle Outcome
- ClinicalTrials.gov ID
- NCT04547699
- Acronym / sponsor ID
- Cytokine plus Global Protein
- Conditions
- ICSI
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 700 participants (actual)
- Lead sponsor
- Mansoura Integrated Fertility CenterUniversity, hospital or other
- Collaborators
- Rahem Fertility Center
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 1 Jul 2021 (actual)
- Study completion
- 1 Jul 2022 (actual)
- First posted
- 14 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Multicenter, randomized, double-blinded and prospective study
| Arm | Type | Receives |
|---|---|---|
| HSA | Placebo comparator | Combination Product: A single step culture mediumA single step culture medium (SSCM; Global, Life Global)+5mg/ml (10% Vol/Vol) life global protein, |
| CYK+ high HSA | Experimental | Combination Product: A single step culture mediumA 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). |
| CYK+low HSA | Active comparator | Combination Product: A single step culture mediumA 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). |
Who may qualify
- Ages
- 18 to 38 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Patients who fitted the medical definition of infertility "One year of unprotected intercourse but not pregnant".
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| A single step culture mediumA single step culture medium (SSCM; Global, Life Global)+5mg/ml life global protein, without supplementation of CYK | Combination product | CYK+ high HSA, CYK+low HSA, HSA |
Primary outcome
live birth rate
Time frame: 9 months
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,
10 secondary outcomes
Fertilization rate
Time frame: 4 weeks
Top quality day 3 embryos
Time frame: 4 weeks
Blastocyst formation rate
Time frame: 4 weeks
Top blastocyst rate
Time frame: 4 weeks
Available embryo rate
Time frame: 4 weeks
clinical pregnancy rate
Time frame: 8 weeks
Biochemical pregnancy rate
Time frame: 6 weeks
Implantation rate
Time frame: 8 weeks
Early embryo loss rat
Time frame: 16 weeks
ongoing pregnancy rate
Time frame: 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2023.
- Background: PubMed 31312101Fukui 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.
- Background: PubMed 19197806Guzeloglu-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.
- Background: PubMed 31551154Fawzy 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.
- Individual participant dataSharing planned: Yes. all IPD will be shared
Related trials for ICSI
Active, not recruitingObservational study
Fresh Versus Vitrified-Warmed Donor Oocytes: Embryological and Clinical Outcomes
Infertility, Donor Oocyte Assisted Reproduction
Active, not recruitingPhase 4
GnRH for Luteal Support in IVF/ICSI/FET Cycles
Infertility
Recruiting
Dual Trigger VS HCG Trigger for Final Oocyte Maturation in Normal Responders
ICSI, IVF
Not yet recruiting
Intra-ovarian CAPA-IVM vs Standard IVM
Infertility (IVF Patients), Infertility
Active, not recruitingObservational study
Detection of Microplastics in Human Granulosa Cells and in the Follicular Fluid of Women Undergoing ICSI Treatment
Female Infertility, Environmental Exposure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emad M Sedeek, MS principal investigator
MIFC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing A single step culture medium in people with ICSI, run by Mansoura Integrated Fertility Center at 2 sites in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
live birth rate (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04547699, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2023.