Back to resultsEffect of GnRH Agonist vs GnRH Antagonist on IVF/ICSI Outcomes in Polycystic Ovary Syndrome Patients.
Primary Purpose
In Vitro Fertilization, Intracytoplasmic Sperm Injection, Infertility
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
About this trial
This is an interventional treatment trial for In Vitro Fertilization focused on measuring GnRH Agonist, GnRH Antagonist, Assisted reproduction technique, In Vitro Fertilization, Intracytoplasmic sperm injection, Polycystic Ovary Syndrome, Placental growth factor
Eligibility Criteria
Inclusion Criteria:
- PCOS women diagnosed according to the Rotterdam criteria 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
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.
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.
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
1. Study Identification
Unique Protocol Identification Number
NCT04727671
Brief Title
Effect of GnRH Agonist vs GnRH Antagonist on IVF/ICSI Outcomes in Polycystic Ovary Syndrome Patients.
Official Title
Effect of GnRH Agonist (Long Protocol) vs GnRH Antagonist (Flexible Protocol) on IVF/ICSI Outcomes in Polycystic Ovary Syndrome Patients.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
December 22, 2019 (Actual)
Primary Completion Date
August 15, 2021 (Actual)
Study Completion Date
December 30, 2021 (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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
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 (hCG) when at least three follicles become more than 16-17 mm.
Primary Outcome Measure Information:
Title
Follicular fluid Placental Growth Factor (PlGF) Concentrations:
Description
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.
Time Frame
Immediately after oocyte retrieval (35±2 hours after hCG administration)
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
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 diagnosed according to the Rotterdam criteria 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
Citations:
PubMed Identifier
27510637
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.
Results Reference
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25987810
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.
Results Reference
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PubMed Identifier
24040457
Citation
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.
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Effect of GnRH Agonist vs GnRH Antagonist on IVF/ICSI Outcomes in Polycystic Ovary Syndrome Patients.
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