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

Infertility Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04724343
• Other study ID #: Ph-CT-4299
• Status: Completed
• Phase: Phase 4
• Start date: December 22, 2019
• Est. completion date: July 5, 2022

Study information

• Verified date: October 2023
• Source: Damascus University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 (PlGF); which is known for his pivotal role in the regulation of ovulation, embryo development, and implantation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: July 5, 2022
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 39 Years

Eligibility

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.

Related Conditions & MeSH terms

• In Vitro Fertilization
• Infertility
• Intracytoplasmic Sperm Injection

Intervention

Drug:
• Triptorelin acetate
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.
• Cetrorelix
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 Gonadotropin
Dosage adjustment according to the ovarian response.
• 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.

Locations

Country	Name	City	State
Syrian Arab Republic	Orient Hospital	Damascus

Sponsors (1)

Lead Sponsor	Collaborator
Damascus University

Country where clinical trial is conducted

Syrian Arab Republic, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Immediately after oocyte retrieval (35±2 hours after hCG administration)
Secondary	Number of oocytes retrieved:	The oocytes will be retrieved by transvaginal ultrasound-guided follicle aspiration 35±2 hours after hCG administration.	Immediately after oocyte retrieval (35±2 hours after hCG administration)
Secondary	Number of Metaphase II Oocytes (MII):	The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.	Within two hours after oocyte retrieval
Secondary	Maturation Rate%:	Maturation Rate is calculated by dividing the number of mature (MII) oocytes by the number of retrieved oocytes.	Within two hours after oocyte retrieval
Secondary	Fertilization Rate%:	Fertilization Rate is calculated by dividing the number of obtained zygote (2PN) by the number of injected oocytes.	16-18 hours after microinjection
Secondary	Cleavage Rate%:	Cleavage rate is calculated by dividing the number of cleavaged embryos by the number of zygotes (2PN).	Day 2 after microinjection
Secondary	Embryo Quality:	Embryos are assessed using Nikon SMZ1500 stereoscope based on ESHRE criteria (2011).	Day of transfer (2 or 3 days after microinjection)
Secondary	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.	Day of transfer (2 or 3 days after microinjection)
Secondary	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.	2 weeks after embryo transfer
Secondary	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.	3-4 weeks after embryo transfer