Effect of GnRH Agonist vs GnRH Antagonist on IVF/ICSI Outcomes in Polycystic Ovary Syndrome Patients.

Infertility Clinical Trial

Official title:

Effect of GnRH Agonist (Long Protocol) vs GnRH Antagonist (Flexible Protocol) on IVF/ICSI Outcomes in Polycystic Ovary Syndrome Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04727671
• Other study ID #: Ph-CT-4298
• Status: Completed
• Phase: Phase 4
• Start date: December 22, 2019
• Est. completion date: December 30, 2021

Study information

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

Clinical Trial Summary

This prospective, non-randomised, open-label, clinical trial is conducting on polycystic ovary syndrome (PCOS) subjects 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: December 30, 2021
• Est. primary completion date: August 15, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 39 Years

Eligibility

Inclusion Criteria:

• PCOS women diagnosed according to the Rotterdam criteria 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 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
• Polycystic Ovary Syndrome
• Syndrome

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 (10)

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

Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, Lizneva D, Natterson-Horowtiz B, Teede HJ, Yildiz BO. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016 Aug 11;2:16057. doi: 10.1038/nrdp.2016.57. — 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

Dennett CC, Simon J. The role of polycystic ovary syndrome in reproductive and metabolic health: overview and approaches for treatment. Diabetes Spectr. 2015 May;28(2):116-20. doi: 10.2337/diaspect.28.2.116. No abstract available. — 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

Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004 Jan;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004. — View Citation

Tal R, Seifer DB, Grazi RV, Malter HE. Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation. Reprod Biol Endocrinol. 2014 Aug 20;12:82. doi: 10.1186/1477-7827-12-82. — 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 Elisa 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