Clinical trial NCT04727671: Effect of GnRH Agonist vs GnRH Antagonist on IVF/ICSI Outcomes in Polycystic Ovary Syndrome Patients.
Official title: Effect of GnRH Agonist (Long Protocol) vs GnRH Antagonist (Flexible Protocol) on IVF/ICSI Outcomes in Polycystic Ovary Syndrome Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: In Vitro Fertilization
Intracytoplasmic Sperm Injection
Infertility
Polycystic Ovary Syndrome
Keywords: GnRH Agonist
GnRH Antagonist
Assisted reproduction technique
In Vitro Fertilization
Intracytoplasmic sperm injection
Polycystic Ovary Syndrome
Placental growth factor
Lead sponsor: Damascus University
Sponsor class: OTHER
First posted: 2021-01-27
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: Follicular fluid Placental Growth Factor (PlGF) Concentrations:
timeFrame: Immediately after oocyte retrieval (35±2 hours after hCG administration)
Secondary outcomes:
measure: Number of oocytes retrieved
timeFrame: Immediately after oocyte retrieval (35±2 hours after hCG administration)
measure: Number of Metaphase II Oocytes (MII):
timeFrame: Within two hours after oocyte retrieval
measure: Maturation Rate%:
timeFrame: Within two hours after oocyte retrieval
measure: Fertilization Rate%:
timeFrame: 16-18 hours after microinjection.
measure: Cleavage Rate%:
timeFrame: Day 2 after microinjection.
measure: Embryo Quality:
timeFrame: Day of transfer (2 or 3 days after microinjection).
measure: High Quality Embryos rate%:
timeFrame: Day of transfer (2 or 3 days after microinjection).
measure: Biochemical Pregnancy Rate% (Per Embryo Transfer):
timeFrame: 2 weeks after embryo transfer
measure: Clinical Pregnancy Rate% (Per Embryo Transfer):
timeFrame: 3-4 weeks after embryo transfer
Other outcomes:
Locations:
city: Damascus
country: Syrian Arab Republic
facility: Orient Hospital
Study officials:
affiliation: Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria
name: Sally Kadoura, B Pharm, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Professor at Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria
name: Abdul Hakim Nattouf, MD, PhD
role: STUDY_DIRECTOR
affiliation: Professor at Department of Embryology and Reproductive Medicine, Faculty of Medicine, Damascus University, Damascus, Syria.
name: Marwan Alhalabi, MD, PhD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
citation: 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.
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.
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.
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.
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.
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.