Effect of GnRH Agonist (Long Protocol) vs GnRH Antagonist (Flexible Protocol) on Oocyte Morphology in Polycystic Ovary Syndrome Patients During IVF/ICSI
Overview
- Phase
- Phase 4
- Intervention
- Triptorelin acetate
- Conditions
- In Vitro Fertilization
- Sponsor
- Damascus University
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Prevalence of oocyte dysmorphisms among the studied groups:
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
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,
Arms & Interventions
Agonist Group (long protocol):
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).
Intervention: Triptorelin acetate
Agonist Group (long protocol):
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).
Intervention: recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin
Agonist Group (long protocol):
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).
Intervention: Human Chorionic Gonadotropin (hCG)
Antagonist Group (Flexible protocol):
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: Cetrorelix
Antagonist Group (Flexible protocol):
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: recombinant-FSH or recombinant-FSH + human Menopausal Gonadotropin
Antagonist Group (Flexible protocol):
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: Human Chorionic Gonadotropin (hCG)
Outcomes
Primary Outcomes
Prevalence of oocyte dysmorphisms among the studied groups:
Time Frame: Before oocytes microinjection
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 Outcomes
- Number of oocytes retrieved:(Immediately after oocyte retrieval (35±2 hours after hCG administration))
- Embryo Quality:(Day of transfer (2 or 3 days after microinjection))
- High Quality Embryos rate%:(Day of transfer (2 or 3 days after microinjection))
- Clinical Pregnancy Rate% (Per Embryo Transfer):(3-4 weeks after embryo transfer)
- Number of Metaphase I Oocytes (MI):(Within two hours after oocyte retrieval)
- Cleavage Rate%:(Day 2 after microinjection)
- Number of Metaphase II Oocytes (MII):(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)
- Maturation Rate%:(Within two hours after oocyte retrieval)
- Fertilization Rate%:(16-18 hours after microinjection)
- Biochemical Pregnancy Rate% (Per Embryo Transfer):(2 weeks after embryo transfer)