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

NCT04727671 | Completed Phase 4

• 1 other identifier: Ph-CT-4298
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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

• Maturation Rate%:

  Within two hours after oocyte retrieval

• Fertilization Rate%:

  16-18 hours after microinjection.

• Cleavage Rate%:

  Day 2 after microinjection.

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 (hCG) 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:

• PCOS women diagnosed according to the Rotterdam criteria 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 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)

• 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.

  PMID: 27510637 BACKGROUND

• 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.

  PMID: 25987810 BACKGROUND

• 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.

  PMID: 24040457 BACKGROUND

• 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.

  PMID: 25288473 BACKGROUND

• 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.

  PMID: 27126581 BACKGROUND

• 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.

  PMID: 27711226 BACKGROUND

• 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.

  PMID: 29095972 BACKGROUND

• 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.

  PMID: 25141961 BACKGROUND

• 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.

  PMID: 14711538 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; Polycystic Ovary Syndrome

Interventions

Triptorelin Pamoate; cetrorelix; Menotropins; Chorionic Gonadotropin

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Gonadal Disorders; Endocrine System 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 27, 2021
• Study Start: December 22, 2019
• Primary Completion: August 15, 2021
• Study Completion: December 30, 2021
• Last Updated: October 24, 2023

Record last verified: 2023-10

Locations

SY (1)