- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04724343
Effect of GnRH Agonist vs GnRH Antagonist on IVF/ICSI Outcomes.
October 22, 2023 updated by: Damascus University
Effect of GnRH Agonist (Long Protocol) vs GnRH Antagonist (Flexible Protocol) on IVF/ICSI Outcomes.
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 (PlGF); which is known for his pivotal role in the regulation of ovulation, embryo development, and implantation.
Study Overview
Status
Completed
Study Type
Interventional
Enrollment (Actual)
50
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Damascus, Syrian Arab Republic
- Orient Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 39 years (Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Women undergoing IVF/ICSI.
- Age: 18-39 years.
- Both ovaries present.
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Agonist Group (Long protocol):
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).
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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.
Dosage adjustment 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.
|
Experimental: Antagonist Group (Flexible protocol):
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).
|
Dosage adjustment 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.
0.25 mg subcutaneously (SC) once daily starting from the day detecting a leading follicle diameter ≥ 14 mm until the day of ovulation triggering.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Follicular fluid Placental Growth Factor (PlGF) Concentrations:
Time Frame: Immediately after oocyte retrieval (35±2 hours after hCG administration)
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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.
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Immediately after oocyte retrieval (35±2 hours after hCG administration)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Metaphase II Oocytes (MII):
Time Frame: Within two hours after oocyte retrieval
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The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.
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Within two hours after oocyte retrieval
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Maturation Rate%:
Time Frame: Within two hours after oocyte retrieval
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Maturation Rate is calculated by dividing the number of mature (MII) oocytes by the number of retrieved oocytes.
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Within two hours after oocyte retrieval
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Biochemical Pregnancy Rate% (Per Embryo Transfer):
Time Frame: 2 weeks after embryo transfer
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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.
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2 weeks after embryo transfer
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Clinical Pregnancy Rate% (Per Embryo Transfer):
Time Frame: 3-4 weeks after embryo transfer
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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.
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3-4 weeks after embryo transfer
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Number of oocytes retrieved:
Time Frame: Immediately after oocyte retrieval (35±2 hours after hCG administration)
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The oocytes will be retrieved by transvaginal ultrasound-guided follicle aspiration 35±2 hours after hCG administration.
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Immediately after oocyte retrieval (35±2 hours after hCG administration)
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Fertilization Rate%:
Time Frame: 16-18 hours after microinjection
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Fertilization Rate is calculated by dividing the number of obtained zygote (2PN) by the number of injected oocytes.
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16-18 hours after microinjection
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Cleavage Rate%:
Time Frame: Day 2 after microinjection
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Cleavage rate is calculated by dividing the number of cleavaged embryos by the number of zygotes (2PN).
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Day 2 after microinjection
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Embryo Quality:
Time Frame: Day of transfer (2 or 3 days after microinjection)
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Embryos are assessed using Nikon SMZ1500 stereoscope based on ESHRE criteria (2011).
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Day of transfer (2 or 3 days after microinjection)
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High Quality Embryos rate%:
Time Frame: Day of transfer (2 or 3 days after microinjection)
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High Quality Embryos rate is calculated by dividing the number of high quality embryos (Grade I) by the total number of cleavaged embryos.
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Day of transfer (2 or 3 days after microinjection)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Sally Kadoura, B Pharm, MD, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria
- Study Director: Abdul Hakim Nattouf, MD, PhD, Professor at Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria
- Study Director: Marwan Alhalabi, MD, PhD, Professor at Department of Embryology and Reproductive Medicine, Faculty of Medicine, Damascus University, Damascus, Syria.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 22, 2019
Primary Completion (Actual)
January 1, 2022
Study Completion (Actual)
July 5, 2022
Study Registration Dates
First Submitted
January 18, 2021
First Submitted That Met QC Criteria
January 22, 2021
First Posted (Actual)
January 26, 2021
Study Record Updates
Last Update Posted (Actual)
October 24, 2023
Last Update Submitted That Met QC Criteria
October 22, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Urogenital Diseases
- Genital Diseases
- Infertility
- Physiological Effects of Drugs
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Hormone Antagonists
- Contraceptive Agents, Hormonal
- Contraceptive Agents
- Reproductive Control Agents
- Contraceptive Agents, Female
- Fertility Agents, Female
- Fertility Agents
- Luteolytic Agents
- Triptorelin Pamoate
- Chorionic Gonadotropin
- Cetrorelix
- Menotropins
Other Study ID Numbers
- Ph-CT-4299
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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