In Vitro FertilizationPhase 4NCT04724343

Effect of GnRH Agonist vs GnRH Antagonist on IVF/ICSI Outcomes.

A Phase 4 study testing Triptorelin acetate, Cetrorelix and recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin in people with In Vitro Fertilization and Intracytoplasmic Sperm Injection, run by Damascus University at 1 site in Syria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The aim of this prospective, non-randomised, open-label, clinical trial is to compare the effects of two pituitary suppression regimens; GnRH Agonist-Long Protocol and GnRH Antagonist-Flexible Protocol on clinical and embryological IVF/ICSI outcomes, and on the follicular fluid levels of Placental Growth Factor… Read more about this study

Who is it for?: Ages 18 to 39 years, women only
Conditions the study is for: In Vitro Fertilization, Intracytoplasmic Sperm Injection, Infertility
What is being tested?: Triptorelin acetate, Cetrorelix and recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: 1 siteSyria
Study dates: 22 Dec 2019to 5 Jul 2022
Phase: Phase 4
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 39 years
Women only
No healthy volunteers
Adult

Who may be able to join

Women undergoing IVF/ICSI.
Age: 18-39 years.
Both ovaries present.

Who cannot join

Age ≥ 40 years.
History of three or more previous IVF failures.
Patients with hormonal disorders like hyperprolactinemia, thyroid disorders.
Patients with Polycystic ovary syndrome.
Patients who previously undergo Unilateral Oophorectomy.
Patients with chronic diseases: diabetes mellitus, cardiovascular diseases, liver diseases, kidney diseases.
Patients with diseases may affect IVF outcomes: Endometriosis, uterine fibroids, Hydrosalpinx, Adenomyosis, autoimmune diseases,
Cancer.

Trial locations and contacts

1 site in 1 country.

Syria1 site

Orient Hospital
Damascus

Other trials in Syria

About this study

Official title: Effect of GnRH Agonist (Long Protocol) vs GnRH Antagonist (Flexible Protocol) on IVF/ICSI Outcomes.

Conditions: In Vitro Fertilization, Intracytoplasmic Sperm Injection, Infertility
Being tested: Triptorelin acetate, Cetrorelix, recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin, Human Chorionic Gonadotropin (hCG)
Keywords: GnRH Agonist, GnRH Antagonist, Assisted reproduction technique, In Vitro Fertilization, Intracytoplasmic sperm injection, Placental growth factor
Medical subject headings: Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Triptorelin acetateDrug
0.05-0.1 mg subcutaneously (SC) once daily from the mid-luteal phase (day 21) of the cycle until the day of ovulation triggering.
CetrorelixDrug
0.25 mg subcutaneously (SC) once daily starting from the day detecting a leading follicle diameter ≥ 14 mm until the day of ovulation triggering.
recombinant-FSH or recombinant-FSH + human Menopausal GonadotropinDrug
Dosage adjustment according to the ovarian response.
Human Chorionic Gonadotropin (hCG)Drug
Ovulation will be triggered by the administration of 10,000 IU of Human Chorionic Gonadotropin (hCG) when at least three follicles become more than 16-17 mm.

Study groups in NCT04724343
Study group	Role	What they receive
Agonist Group (Long protocol):	Active comparator	The pituitary down-regulation in this group will be carried out using 0.05-0.1 mg of Triptorelin acetate subcutaneously (SC) once daily from the mid-luteal phase (day 21) of the menstrual cycle until the ovulation triggering day. When the suppressive effect is obtained, ovarian stimulation will commence with recombinant Follicle-Stimulating Hormone (r-FSH) or r-FSH + human Menopausal Gonadotropin (hMG) and the dose will be adjusted according to the ovarian response. Ovulation will be triggered by the administration of 10,000 IU of human Chorionic Gonadotropin (hCG) when at least three follicles become more than 16-17 mm. After 35±2 hours of ovulation triggering, the oocytes will be retrieved by transvaginal ultrasound-guided follicle aspiration. Then they will be prepared to undergo an Intracytoplasmic Sperm Injection (ICSI). Receives: Drug: Triptorelin acetate; Drug: recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin; Drug: Human Chorionic Gonadotropin (hCG)
Antagonist Group (Flexible protocol):	Experimental	The ovarian stimulation in this group will be started with recombinant Follicle-Stimulating Hormone (r-FSH) or r-FSH + human Menopausal Gonadotropin (hMG) on the third day of the menstrual cycle and the dose will be adjusted according to the ovarian response. Initiation of 0.25 mg of GnRH antagonist; Cetrorelix; will take place after detecting a leading follicle diameter ≥ 14 mm. GnRH antagonist administration will be continued till the day of ovulation triggering, which will be accomplished by given 10,000 IU of human Chorionic Gonadotropin (hCG) when at least three follicles become more than 16-17 mm. After 35±2 hours of ovulation triggering, the oocytes will be retrieved by transvaginal ultrasound-guided follicle aspiration. Then they will be prepared to undergo an Intracytoplasmic Sperm Injection (ICSI). Receives: Drug: Cetrorelix; Drug: recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin; Drug: Human Chorionic Gonadotropin (hCG)

What is being measured

The primary outcome is the main question the study is designed to answer.

Follicular fluid Placental Growth Factor (PlGF) Concentrations:
Follicular fluid samples will be obtained on the day of oocyte retrieval, then they will be centrifuged to eliminate cellular elements and debris. After that, the supernatants will be frozen at -80 until assayed using an Eliza kit.
Measured: Immediately after oocyte retrieval (35±2 hours after hCG administration)

Secondary outcomes (9)

Number of oocytes retrieved:
The oocytes will be retrieved by transvaginal ultrasound-guided follicle aspiration 35±2 hours after hCG administration.
Measured: Immediately after oocyte retrieval (35±2 hours after hCG administration)
Number of Metaphase II Oocytes (MII):
The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.
Measured: Within two hours after oocyte retrieval
Maturation Rate%:
Maturation Rate is calculated by dividing the number of mature (MII) oocytes by the number of retrieved oocytes.
Measured: Within two hours after oocyte retrieval
Fertilization Rate%:
Fertilization Rate is calculated by dividing the number of obtained zygote (2PN) by the number of injected oocytes.
Measured: 16-18 hours after microinjection
Cleavage Rate%:
Cleavage rate is calculated by dividing the number of cleavaged embryos by the number of zygotes (2PN).
Measured: Day 2 after microinjection
Embryo Quality:
Embryos are assessed using Nikon SMZ1500 stereoscope based on ESHRE criteria (2011).
Measured: Day of transfer (2 or 3 days after microinjection)
High Quality Embryos rate%:
High Quality Embryos rate is calculated by dividing the number of high quality embryos (Grade I) by the total number of cleavaged embryos.
Measured: Day of transfer (2 or 3 days after microinjection)
Biochemical Pregnancy Rate% (Per Embryo Transfer):
Biochemical pregnancy is defined as a positive serum beta-hCG pregnancy test after 2 weeks of embryo transfer. The biochemical pregnancy rate is calculated by dividing the number of women who are biochemically pregnant by the number of women who have at least 1 embryo transferred.
Measured: 2 weeks after embryo transfer
Clinical Pregnancy Rate% (Per Embryo Transfer):
Clinical pregnancy is defined as the presence of a gestational sac on ultrasound after 3-4 weeks of embryo transfer. The clinical pregnancy rate is calculated as by dividing the number of women who are clinically pregnant divided by the number of women who have at least 1 embryo transferred.
Measured: 3-4 weeks after embryo transfer

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Dec 20195 Jul 2022

First posted26 Jan 2021
Study start22 Dec 2019
Primary completion1 Jan 2022
Study completion5 Jul 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (6)Papers the sponsor has linked to this study.
Other trials for In Vitro FertilizationStudies 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 4
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04724343
Sponsor's protocol ID: Ph-CT-4299
Status last verified: Oct 2023
First submitted: 18 Jan 2021
Last updated: 24 Oct 2023
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Lai Q, Zhang H, Zhu G, Li Y, Jin L, He L, Zhang Z, Yang P, Yu Q, Zhang S, Xu JF, Wang CY. Comparison of the GnRH agonist and antagonist protocol on the same patients in assisted reproduction during controlled ovarian stimulation cycles. Int J Clin Exp Pathol. 2013 Aug 15;6(9):1903-10. eCollection 2013.
PubMed 24040457
Hoseini FS, Noori Mugahi SM, Akbari-Asbagh F, Eftekhari-Yazdi P, Aflatoonian B, Aghaee-Bakhtiari SH, Aflatoonian R, Salsabili N. A randomized controlled trial of gonadotropin-releasing hormone agonist versus gonadotropin-releasing hormone antagonist in Iranian infertile couples: oocyte gene expression. Daru. 2014 Oct 7;22(1):67. doi: 10.1186/s40199-014-0067-4.
PubMed 25288473
Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016 Apr 29;4(4):CD001750. doi: 10.1002/14651858.CD001750.pub4.
PubMed 27126581
Binder NK, Evans J, Salamonsen LA, Gardner DK, Kaitu'u-Lino TJ, Hannan NJ. Placental Growth Factor Is Secreted by the Human Endometrium and Has Potential Important Functions during Embryo Development and Implantation. PLoS One. 2016 Oct 6;11(10):e0163096. doi: 10.1371/journal.pone.0163096. eCollection 2016.
PubMed 27711226
Bender HR, Trau HA, Duffy DM. Placental Growth Factor Is Required for Ovulation, Luteinization, and Angiogenesis in Primate Ovulatory Follicles. Endocrinology. 2018 Feb 1;159(2):710-722. doi: 10.1210/en.2017-00739.
PubMed 29095972
Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011 Jun;26(6):1270-83. doi: 10.1093/humrep/der037. Epub 2011 Apr 18.
PubMed 21502182

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
International Pilot Study for Dual Non-invasive Assesment of Embryo Development
Infertility
RecruitingPhase 2
Ubiquinone vs. Ubiquinol Supplementation
IVF
Recruiting
Trigger Timing in Ovarian Stimulations
IVF Outcome
Active, not recruiting
Automation of the In Vitro Fertilization Laboratory
Infertility, ART
RecruitingPhase 4
Study of G-CSF for DOR in Patients Undergoing IVF
Diminished Ovarian Reserve, IVF

All In Vitro Fertilization trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of GnRH Agonist (Long Protocol) vs GnRH Antagonist (Flexible Protocol) on IVF/ICSI Outcomes.
ClinicalTrials.gov ID: NCT04724343
Acronym / sponsor ID: Ph-CT-4299
Conditions: In Vitro Fertilization, Intracytoplasmic Sperm Injection, Infertility
Keywords: GnRH Agonist, GnRH Antagonist, Assisted reproduction technique, In Vitro Fertilization, Intracytoplasmic sperm injection, Placental growth factor
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: Damascus UniversityUniversity, hospital or other
Study start: 22 Dec 2019 (actual)
Primary completion: 1 Jan 2022 (actual)
Study completion: 5 Jul 2022 (actual)
First posted: 26 Jan 2021 (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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Agonist Group (Long protocol):	Active comparator	Drug: Triptorelin acetate, Drug: recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin, Drug: Human Chorionic Gonadotropin (hCG)The pituitary down-regulation in this group will be carried out using 0.05-0.1 mg of Triptorelin acetate subcutaneously (SC) once daily from the mid-luteal phase (day 21) of the menstrual cycle until the ovulation triggering day. When the suppressive effect is obtained, ovarian stimulation will commence with recombinant Follicle-Stimulating Hormone (r-FSH) or r-FSH + human Menopausal Gonadotropin (hMG) and the dose will be adjusted according to the ovarian response. Ovulation will be triggered by the administration of 10,000 IU of human Chorionic Gonadotropin (hCG) when at least three follicles become more than 16-17 mm. After 35±2 hours of ovulation triggering, the oocytes will be retrieved by transvaginal ultrasound-guided follicle aspiration. Then they will be prepared to undergo an Intracytoplasmic Sperm Injection (ICSI).
Antagonist Group (Flexible protocol):	Experimental	Drug: Cetrorelix, Drug: recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin, Drug: Human Chorionic Gonadotropin (hCG)The ovarian stimulation in this group will be started with recombinant Follicle-Stimulating Hormone (r-FSH) or r-FSH + human Menopausal Gonadotropin (hMG) on the third day of the menstrual cycle and the dose will be adjusted according to the ovarian response. Initiation of 0.25 mg of GnRH antagonist; Cetrorelix; will take place after detecting a leading follicle diameter ≥ 14 mm. GnRH antagonist administration will be continued till the day of ovulation triggering, which will be accomplished by given 10,000 IU of human Chorionic Gonadotropin (hCG) when at least three follicles become more than 16-17 mm. After 35±2 hours of ovulation triggering, the oocytes will be retrieved by transvaginal ultrasound-guided follicle aspiration. Then they will be prepared to undergo an Intracytoplasmic Sperm Injection (ICSI).

Who may qualify

Ages: 18 to 39 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (3 listed)

Women undergoing IVF/ICSI.
Age: 18-39 years.
Both ovaries present.

Key exclusion criteria (8 listed)

Age ≥ 40 years.
History of three or more previous IVF failures.
Patients with hormonal disorders like hyperprolactinemia, thyroid disorders.
Patients with Polycystic ovary syndrome.
Patients who previously undergo Unilateral Oophorectomy.

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
Triptorelin acetate0.05-0.1 mg subcutaneously (SC) once daily from the mid-luteal phase (day 21) of the cycle until the day of ovulation triggering.	Drug	Agonist Group (Long protocol):
Cetrorelix0.25 mg subcutaneously (SC) once daily starting from the day detecting a leading follicle diameter ≥ 14 mm until the day of ovulation triggering.	Drug	Antagonist Group (Flexible protocol):
recombinant-FSH or recombinant-FSH + human Menopausal GonadotropinDosage adjustment according to the ovarian response.	Drug	Agonist Group (Long protocol):, Antagonist Group (Flexible protocol):
Human Chorionic Gonadotropin (hCG)Ovulation will be triggered by the administration of 10,000 IU of Human Chorionic Gonadotropin (hCG) when at least three follicles become more than 16-17 mm.	Drug	Agonist Group (Long protocol):, Antagonist Group (Flexible protocol):

Primary outcome

Follicular fluid Placental Growth Factor (PlGF) Concentrations:
Time frame: Immediately after oocyte retrieval (35±2 hours after hCG administration)
Follicular fluid samples will be obtained on the day of oocyte retrieval, then they will be centrifuged to eliminate cellular elements and debris. After that, the supernatants will be frozen at -80 until assayed using an Eliza kit.

9 secondary outcomes

Number of oocytes retrieved:
Time frame: Immediately after oocyte retrieval (35±2 hours after hCG administration)
Number of Metaphase II Oocytes (MII):
Time frame: Within two hours after oocyte retrieval
Maturation Rate%:
Time frame: Within two hours after oocyte retrieval
Fertilization Rate%:
Time frame: 16-18 hours after microinjection
Cleavage Rate%:
Time frame: Day 2 after microinjection
Embryo Quality:
Time frame: Day of transfer (2 or 3 days after microinjection)
High Quality Embryos rate%:
Time frame: Day of transfer (2 or 3 days after microinjection)
Biochemical Pregnancy Rate% (Per Embryo Transfer):
Time frame: 2 weeks after embryo transfer
Clinical Pregnancy Rate% (Per Embryo Transfer):
Time frame: 3-4 weeks after embryo transfer

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 24 Oct 2023.
Background: PubMed 24040457Lai Q, Zhang H, Zhu G, Li Y, Jin L, He L, Zhang Z, Yang P, Yu Q, Zhang S, Xu JF, Wang CY. Comparison of the GnRH agonist and antagonist protocol on the same patients in assisted reproduction during controlled ovarian stimulation cycles. Int J Clin Exp Pathol. 2013 Aug 15;6(9):1903-10. eCollection 2013.
Background: PubMed 25288473Hoseini FS, Noori Mugahi SM, Akbari-Asbagh F, Eftekhari-Yazdi P, Aflatoonian B, Aghaee-Bakhtiari SH, Aflatoonian R, Salsabili N. A randomized controlled trial of gonadotropin-releasing hormone agonist versus gonadotropin-releasing hormone antagonist in Iranian infertile couples: oocyte gene expression. Daru. 2014 Oct 7;22(1):67. doi: 10.1186/s40199-014-0067-4.
Background: PubMed 27126581Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016 Apr 29;4(4):CD001750. doi: 10.1002/14651858.CD001750.pub4.
Background: PubMed 27711226Binder NK, Evans J, Salamonsen LA, Gardner DK, Kaitu'u-Lino TJ, Hannan NJ. Placental Growth Factor Is Secreted by the Human Endometrium and Has Potential Important Functions during Embryo Development and Implantation. PLoS One. 2016 Oct 6;11(10):e0163096. doi: 10.1371/journal.pone.0163096. eCollection 2016.
Background: PubMed 29095972Bender HR, Trau HA, Duffy DM. Placental Growth Factor Is Required for Ovulation, Luteinization, and Angiogenesis in Primate Ovulatory Follicles. Endocrinology. 2018 Feb 1;159(2):710-722. doi: 10.1210/en.2017-00739.
Background: PubMed 21502182Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011 Jun;26(6):1270-83. doi: 10.1093/humrep/der037. Epub 2011 Apr 18.

Related trials for In Vitro Fertilization

RecruitingObservational study
International Pilot Study for Dual Non-invasive Assesment of Embryo Development
Infertility
RecruitingPhase 2
Ubiquinone vs. Ubiquinol Supplementation
IVF
Recruiting
Trigger Timing in Ovarian Stimulations
IVF Outcome
Active, not recruiting
Automation of the In Vitro Fertilization Laboratory
Infertility, ART
RecruitingPhase 4
Study of G-CSF for DOR in Patients Undergoing IVF
Diminished Ovarian Reserve, IVF

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.

Sally Kadoura, B Pharm, MD principal investigator

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria

Abdul Hakim Nattouf, MD, PhD study director

Professor at Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria

Marwan Alhalabi, MD, PhD study director

Professor at Department of Embryology and Reproductive Medicine, Faculty of Medicine, Damascus University, Damascus, Syria.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 3 inclusion and 8 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 24 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Syria. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Follicular fluid Placental Growth Factor (PlGF) Concentrations: (time frame: Immediately after oocyte retrieval (35±2 hours after hCG administration)). 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 NCT04724343, which also lists 6 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 24 Oct 2023.