Effect of GnRH Agonist vs GnRH Antagonist on Oocyte Morphology in Polycystic Ovary Syndrome Patients During IVF/ICSI

Infertility Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04727684
• Other study ID #: Ph-CT-4300
• Status: Completed
• Phase: Phase 4
• Start date: August 22, 2020
• Est. completion date: May 12, 2022

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: May 12, 2022
• Est. primary completion date: February 15, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 39 Years

Eligibility

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.

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 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 (14)

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. — 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

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. — View 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. — 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

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. — 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

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of oocyte dysmorphisms among the studied groups:	Before being subjected to ICSI, the oocytes from both groups will be morphologically analyzed under an inverted microscope; Nikon Eclipse Ti2; in order to detect cytoplasmic and extra-cytoplasmic dysmorphisms.	Before oocytes microinjection
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	Number of Metaphase I Oocytes (MI):	The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.	Within two hours after oocyte retrieval
Secondary	Number of Germinal Vesicle Oocytes (GV):	The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.	Within two hours after oocyte retrieval
Secondary	Number of Atretic Oocytes:	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