Clinical trial NCT04727684: Effect of GnRH Agonist vs GnRH Antagonist on Oocyte Morphology in Polycystic Ovary Syndrome Patients During IVF/ICSI
Official title: Effect of GnRH Agonist (Long Protocol) vs GnRH Antagonist (Flexible Protocol) on Oocyte Morphology in Polycystic Ovary Syndrome Patients During IVF/ICSI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: In Vitro Fertilization
Infertility
Intracytoplasmic Sperm Injection
Polycystic Ovary Syndrome
Keywords: GnRH Agonist
GnRH Antagonist
Oocyte morphology
Assisted reproduction technique
In Vitro Fertilization
Intracytoplasmic sperm injection
Polycystic Ovary Syndrome
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: Selection of developmentally competent oocytes enhances IVF efficiency. Usually, oocyte quality is determined based on its nuclear maturation and the presence of specific cytoplasmic and extracytoplasmic morphologic features. Gonadotropin-releasing hormone agonists (GnRH Agonists) and gonadotropin-releasing hormone antagonists (GnRH Antagonists) are used during controlled ovarian stimulation (COS) protocols in order to prevent premature luteinizing hormone (LH) surge and premature ovulation. However, GnRH receptors are also expressed in extra-pituitary tissues such as ovary, but it is still unknown whether the type of GnRH analogues used during COS could affect the oocyte morphology in polycystic ovary syndrome (PCOS) patients. 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 oocyte morphology in PCOS patients during IVF/ICSI.


Eligibility criteria: Inclusion Criteria:

* PCOS 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 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: Prevalence of oocyte dysmorphisms among the studied groups:
timeFrame: Before oocytes microinjection
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: Number of Metaphase I Oocytes (MI):
timeFrame: Within two hours after oocyte retrieval
measure: Number of Germinal Vesicle Oocytes (GV):
timeFrame: Within two hours after oocyte retrieval
measure: Number of Atretic Oocytes:
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: Aguilar-Rojas A, Huerta-Reyes M. Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review). Oncol Rep. 2009 Nov;22(5):981-90. doi: 10.3892/or_00000525.
citation: Cheung LW, Wong AS. Gonadotropin-releasing hormone: GnRH receptor signaling in extrapituitary tissues. FEBS J. 2008 Nov;275(22):5479-95. doi: 10.1111/j.1742-4658.2008.06677.x.
citation: Setti AS, Figueira RC, de Almeida Ferreira Braga DP, Azevedo MC, Iaconelli A Jr, Borges E Jr. Oocytes with smooth endoplasmic reticulum clusters originate blastocysts with impaired implantation potential. Fertil Steril. 2016 Dec;106(7):1718-1724. doi: 10.1016/j.fertnstert.2016.09.006. Epub 2016 Oct 12.
citation: Sfontouris IA, Lainas GT, Lainas TG, Faros E, Banti M, Kardara K, Anagnostopoulou K, Kontos H, Petsas GK, Kolibianakis EM. Complex chromosomal aberrations in a fetus originating from oocytes with smooth endoplasmic reticulum (SER) aggregates. Syst Biol Reprod Med. 2018 Aug;64(4):283-290. doi: 10.1080/19396368.2018.1466375. Epub 2018 May 2.
citation: Stigliani S, Moretti S, Casciano I, Canepa P, Remorgida V, Anserini P, Scaruffi P. Presence of aggregates of smooth endoplasmic reticulum in MII oocytes affects oocyte competence: molecular-based evidence. Mol Hum Reprod. 2018 Jun 1;24(6):310-317. doi: 10.1093/molehr/gay018.
citation: Setti AS, Figueira RC, Braga DP, Colturato SS, Iaconelli A Jr, Borges E Jr. Relationship between oocyte abnormal morphology and intracytoplasmic sperm injection outcomes: a meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2011 Dec;159(2):364-70. doi: 10.1016/j.ejogrb.2011.07.031. Epub 2011 Aug 6.
citation: Lazzaroni-Tealdi E, Barad DH, Albertini DF, Yu Y, Kushnir VA, Russell H, Wu YG, Gleicher N. Oocyte Scoring Enhances Embryo-Scoring in Predicting Pregnancy Chances with IVF Where It Counts Most. PLoS One. 2015 Dec 2;10(12):e0143632. doi: 10.1371/journal.pone.0143632. eCollection 2015.
citation: Wissing ML, Bjerge MR, Olesen AI, Hoest T, Mikkelsen AL. Impact of PCOS on early embryo cleavage kinetics. Reprod Biomed Online. 2014 Apr;28(4):508-14. doi: 10.1016/j.rbmo.2013.11.017. Epub 2013 Dec 17.
citation: Cota AM, Oliveira JB, Petersen CG, Mauri AL, Massaro FC, Silva LF, Nicoletti A, Cavagna M, Baruffi RL, Franco JG Jr. GnRH agonist versus GnRH antagonist in assisted reproduction cycles: oocyte morphology. Reprod Biol Endocrinol. 2012 Apr 27;10:33. doi: 10.1186/1477-7827-10-33.
citation: Zanetti BF, Braga DPAF, Setti AS, Iaconelli A Jr, Borges E Jr. Effect of GnRH analogues for pituitary suppression on oocyte morphology in repeated ovarian stimulation cycles. JBRA Assist Reprod. 2020 Jan 30;24(1):24-29. doi: 10.5935/1518-0557.20190050.
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.