Effect of GnRH Agonist vs GnRH Antagonist on Oocyte Morphology During IVF/ICSI

NCT04724486 | Completed Phase 4

• 1 other identifier: Ph-CT-4301
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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, especially with the limited and conflicted currently available data. Thus, we are conducting this prospective, non-randomised, open-label, clinical trial to compare the effects of two pituitary suppression regimens; GnRH Agonist-Long Protocol and GnRH Antagonist-Flexible Protocol on oocyte morphology during IVF/ICSI.

Conditions

In Vitro Fertilization; Intracytoplasmic Sperm Injection; Infertility

Keywords

GnRH Agonist; GnRH Antagonist; Oocyte morphology; Assisted reproduction technique; In Vitro Fertilization; Intracytoplasmic sperm injection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Number of oocytes retrieved:

  Immediately after oocyte retrieval (35±2 hours after hCG administration)

• Number of Metaphase II Oocytes (MII):

  Within two hours after oocyte retrieval

• Number of Metaphase I Oocytes (MI):

  Within two hours after oocyte retrieval

• Number of Germinal Vesicle Oocytes (GV):

  Within two hours after oocyte retrieval

• Number of Atretic Oocytes:

  Within two hours after oocyte retrieval

Study Arms (2)

Agonist Group (Long protocol):

ACTIVE COMPARATOR

The pituitary down-regulation in this group will be carried out using 0.05-0.1 mg of Triptorelin acetate subcutaneously (SC) once daily from the mid-luteal phase (day 21) of the menstrual cycle until the ovulation triggering day. When the suppressive effect is obtained, ovarian stimulation will commence with recombinant Follicle-Stimulating Hormone (r-FSH) or r-FSH + human Menopausal Gonadotropin (hMG) and the dose will be adjusted according to the ovarian response. 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. After 35±2 hours of ovulation triggering, the oocytes will be retrieved by transvaginal ultrasound-guided follicle aspiration. Then they will be prepared to undergo an Intracytoplasmic Sperm Injection (ICSI).

Drug: Triptorelin acetate; Drug: recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin; Drug: Human Chorionic Gonadotropin (hCG)

Antagonist Group (Flexible protocol):

EXPERIMENTAL

The ovarian stimulation in this group will be started with recombinant Follicle-Stimulating Hormone (r-FSH) or r-FSH + human Menopausal Gonadotropin (hMG) on the third day of the menstrual cycle and the dose will be adjusted according to the ovarian response. Initiation of 0.25 mg of GnRH antagonist; Cetrorelix; will take place after detecting a leading follicle diameter ≥ 14 mm. GnRH antagonist administration will be continued till the day of ovulation triggering, which will be accomplished by given 10,000 IU of human Chorionic Gonadotropin (hCG) when at least three follicles become more than 16-17 mm. After 35±2 hours of ovulation triggering, the oocytes will be retrieved by transvaginal ultrasound-guided follicle aspiration. Then they will be prepared to undergo an Intracytoplasmic Sperm Injection (ICSI).

Drug: Cetrorelix; Drug: recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin; Drug: Human Chorionic Gonadotropin (hCG)

Interventions

Triptorelin acetate DRUG

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.

Agonist Group (Long protocol):

Cetrorelix DRUG

0.25 mg subcutaneously (SC) once daily starting from the day detecting a leading follicle diameter ≥ 14 mm until the day of ovulation triggering.

Antagonist Group (Flexible protocol):

recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin DRUG

Dosage adjustment according to the ovarian response.

Agonist Group (Long protocol):; Antagonist Group (Flexible protocol):

Human Chorionic Gonadotropin (hCG) DRUG

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.

Agonist Group (Long protocol):; Antagonist Group (Flexible protocol):

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women undergoing IVF/ICSI.
• Age: 18-39 years.
• Both ovaries present.

You may not qualify if:

• Age ≥ 40 years
• History of three or more previous IVF failures.
• Patients with hormonal disorders like hyperprolactinemia, thyroid disorders.
• Patients with Polycystic Ovarian 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.

Sponsors & Collaborators

• Damascus University: lead

Study Sites (1)

Orient Hospital

Damascus, Syria

Location

Related Publications (10)

• 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.

  PMID: 19787210 BACKGROUND

• 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.

  PMID: 18959738 BACKGROUND

• 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.

  PMID: 27743693 BACKGROUND

• 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.

  PMID: 29718716 BACKGROUND

• 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.

  PMID: 29635518 BACKGROUND

• 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.

  PMID: 21824710 BACKGROUND

• 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.

  PMID: 26630267 BACKGROUND

• 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.

  PMID: 22540993 BACKGROUND

• 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.

  PMID: 31436072 BACKGROUND

• 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.

  PMID: 21502182 BACKGROUND

MeSH Terms

Conditions

Infertility

Interventions

Triptorelin Pamoate; cetrorelix; Menotropins; Chorionic Gonadotropin

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Gonadotropins, Pituitary; Gonadotropins; Pituitary Hormones, Anterior; Pituitary Hormones; Biological Products; Complex Mixtures; Placental Hormones; Pregnancy Proteins

Study Officials

• Sally Kadoura, B Pharm, MD

  Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria

  PRINCIPAL INVESTIGATOR

• Abdul Hakim Nattouf, MD, PhD

  Professor at Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria

  STUDY DIRECTOR

• Marwan Alhalabi, MD, PhD

  Professor at Department of Embryology and Reproductive Medicine, Faculty of Medicine, Damascus University, Damascus, Syria.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2021
• First Posted: January 26, 2021
• Study Start: August 22, 2020
• Primary Completion: March 15, 2022
• Study Completion: July 15, 2022
• Last Updated: October 24, 2023

Record last verified: 2023-10

Locations

SY (1)