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

Primary Purpose

In Vitro Fertilization, Infertility, Intracytoplasmic Sperm Injection

Status
Completed
Phase
Phase 4
Locations
Syrian Arab Republic
Study Type
Interventional
Intervention
Triptorelin acetate
Cetrorelix
recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin
Human Chorionic Gonadotropin (hCG)
Sponsored by
Damascus University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for In Vitro Fertilization focused on measuring GnRH Agonist, GnRH Antagonist, Oocyte morphology, Assisted reproduction technique, In Vitro Fertilization, Intracytoplasmic sperm injection, Polycystic Ovary Syndrome

Eligibility Criteria

18 Years - 39 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Orient Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Agonist Group (long protocol):

Antagonist Group (Flexible protocol):

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of oocytes retrieved:
The oocytes will be retrieved by transvaginal ultrasound-guided follicle aspiration 35±2 hours after hCG administration.
Number of Metaphase II Oocytes (MII):
The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.
Number of Metaphase I Oocytes (MI):
The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.
Number of Germinal Vesicle Oocytes (GV):
The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.
Number of Atretic Oocytes:
The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.
Maturation Rate%:
Maturation Rate is calculated by dividing the number of mature (MII) oocytes by the number of retrieved oocytes.
Fertilization Rate%:
Fertilization Rate is calculated by dividing the number of obtained zygote (2PN) by the number of injected oocytes.
Cleavage Rate%:
Cleavage rate is calculated by dividing the number of cleavaged embryos by the number of zygotes (2PN).
Embryo Quality:
Embryos are assessed using Nikon SMZ1500 stereoscope based on ESHRE criteria (2011).
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.
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.
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.

Full Information

First Posted
January 18, 2021
Last Updated
October 22, 2023
Sponsor
Damascus University
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1. Study Identification

Unique Protocol Identification Number
NCT04727684
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
August 22, 2020 (Actual)
Primary Completion Date
February 15, 2022 (Actual)
Study Completion Date
May 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Damascus University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Agonist Group (long protocol):
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Antagonist Group (Flexible protocol):
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Triptorelin acetate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cetrorelix
Intervention Description
0.25 mg subcutaneously (SC) once daily starting from the day detecting a leading follicle diameter ≥ 14 mm until the day of ovulation triggering.
Intervention Type
Drug
Intervention Name(s)
recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin
Intervention Description
Dosage adjustment according to the ovarian response.
Intervention Type
Drug
Intervention Name(s)
Human Chorionic Gonadotropin (hCG)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Prevalence of oocyte dysmorphisms among the studied groups:
Description
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.
Time Frame
Before oocytes microinjection
Secondary Outcome Measure Information:
Title
Number of oocytes retrieved:
Description
The oocytes will be retrieved by transvaginal ultrasound-guided follicle aspiration 35±2 hours after hCG administration.
Time Frame
Immediately after oocyte retrieval (35±2 hours after hCG administration)
Title
Number of Metaphase II Oocytes (MII):
Description
The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.
Time Frame
Within two hours after oocyte retrieval
Title
Number of Metaphase I Oocytes (MI):
Description
The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.
Time Frame
Within two hours after oocyte retrieval
Title
Number of Germinal Vesicle Oocytes (GV):
Description
The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.
Time Frame
Within two hours after oocyte retrieval
Title
Number of Atretic Oocytes:
Description
The oocyte maturity will be assessed using Nikon SMZ1500 stereoscope.
Time Frame
Within two hours after oocyte retrieval
Title
Maturation Rate%:
Description
Maturation Rate is calculated by dividing the number of mature (MII) oocytes by the number of retrieved oocytes.
Time Frame
Within two hours after oocyte retrieval
Title
Fertilization Rate%:
Description
Fertilization Rate is calculated by dividing the number of obtained zygote (2PN) by the number of injected oocytes.
Time Frame
16-18 hours after microinjection
Title
Cleavage Rate%:
Description
Cleavage rate is calculated by dividing the number of cleavaged embryos by the number of zygotes (2PN).
Time Frame
Day 2 after microinjection
Title
Embryo Quality:
Description
Embryos are assessed using Nikon SMZ1500 stereoscope based on ESHRE criteria (2011).
Time Frame
Day of transfer (2 or 3 days after microinjection)
Title
High Quality Embryos rate%:
Description
High Quality Embryos rate is calculated by dividing the number of high quality embryos (Grade I) by the total number of cleavaged embryos.
Time Frame
Day of transfer (2 or 3 days after microinjection)
Title
Biochemical Pregnancy Rate% (Per Embryo Transfer):
Description
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.
Time Frame
2 weeks after embryo transfer
Title
Clinical Pregnancy Rate% (Per Embryo Transfer):
Description
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.
Time Frame
3-4 weeks after embryo transfer

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sally Kadoura, B Pharm, MD
Organizational Affiliation
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Abdul Hakim Nattouf, MD, PhD
Organizational Affiliation
Professor at Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Marwan Alhalabi, MD, PhD
Organizational Affiliation
Professor at Department of Embryology and Reproductive Medicine, Faculty of Medicine, Damascus University, Damascus, Syria.
Official's Role
Study Director
Facility Information:
Facility Name
Orient Hospital
City
Damascus
Country
Syrian Arab Republic

12. IPD Sharing Statement

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

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