Value of Cabergoline and Low Dose Aspirin in Poor Responders Undergoing ICSI-ET With GnRH Agonist Flare-Up-Protocol

NCT ID: NCT03263299

Last Updated: 2017-08-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-31
• Study Completion Date: 2018-09-30

Brief Summary

Ovarian stimulation will be done using the Microdose flare-up regimen. The patient will receive diluted doses of the GnRH agonist leuprolide acetate 40 µg, given subcutaneously twice daily. Two days later, stimulation will be initiated by intramuscular (IM) injections of HMG (Merional, IBSA, Germany) in a dose of 300 IU/day.

Follicular monitoring began from the ninth day of the cycle by serial vaginal ultrasonography and measurement of serum E2 levels. IM injections of 10000 IU HCG (Choriomon; IBSA, Germany) will be injected when at least 2 follicles 18 mm were observed on ultrasonography.

Oocytes willbe retrieved 36 hours after hCG injection using a 17-gauge aspiration needle under transvaginal ultrasound guidance. The pelvis is evaluated with ultrasound to ensure that there is no internal bleeding.

After fertilization was confirmed when two polar bodies and two pronuclear were observed 18-20 hours after insemination, one to three grade A embryos were transferred at day 3 fertilization.

The luteal phase support will be initiated from the day of oocyte retrieval for all patients with (Cyclogest 400 mg, Actavis pharmaceutical, UK) vaginal suppositories per day till the day of serum pregnancy test was done.

Detailed Description

Ovarian stimulation was done using the Microdose flare-up regimen. The patient received diluted doses of the GnRH agonist leuprolide acetate 40 µg, given subcutaneously twice daily. Two days later, stimulation is initiated by intramuscular (IM) injections of HMG (Merional, IBSA, Germany) in a dose of 300 IU/day.

Follicular monitoring began from the ninth day of the cycle by serial vaginal ultrasonography and measurement of serum E2 levels. IM injections of 10000 IU HCG (Choriomon; IBSA, Germany) were injected when at least 2 follicles 18 mm were observed on ultrasonography.

Oocytes were retrieved 36 hours after hCG injection using a 17-gauge aspiration needle under transvaginal ultrasound guidance. The pelvis is evaluated with ultrasound to ensure that there is no internal bleeding.

After fertilization was confirmed when two polar bodies and two pronuclear were observed 18-20 hours after insemination, one to three grade A embryos were transferred at day 3 fertilization.

The luteal phase support was initiated from the day of oocyte retrieval for all patients with (Cyclogest 400 mg, Actavis pharmaceutical, UK) vaginal suppositories per day till the day of serum pregnancy test was done.

Serum β-hCG was performed 14 days after the embryo transfer to confirm chemical pregnancy. Clinical pregnancy was confirmed when there was an evidence of gestational sac, embryo and fetal heart activity at time of transvaginal ultrasound evaluation by the 6th week.

Conditions

Invitro Fertilization

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

cabergoline group

received cabergoline in addition to aspirin. Cabergoline was administered in a dose of 1 mg/week in two divided doses which was terminated after embryo transfer. Aspirin was administered in daily dose of 80 mg initiated at the start of down-regulation with luteal leuprolide

Group Type: ACTIVE_COMPARATOR

cabergoline

Intervention Type: DRUG

Cabergoline was administered in a dose of 1 mg/week in two divided doses which was terminated after embryo transfer

Aspirin

Intervention Type: DRUG

Aspirin was administered in daily dose of 80 mg initiated at the start of down-regulation with luteal leuprolide

GnRH agonist

Intervention Type: DRUG

Microdose flare-up regimen. The patient received diluted doses of the GnRH agonist leuprolide acetate 40 µg, given subcutaneously twice daily. Two days later, stimulation is initiated by intramuscular (IM) injections of HMG (Merional, IBSA, Germany) in a dose of 300 IU/day.

Aspirin group

Aspirin was administered in daily dose of 80 mg initiated at the start of down-regulation with luteal leuprolide

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

Aspirin was administered in daily dose of 80 mg initiated at the start of down-regulation with luteal leuprolide

GnRH agonist

Intervention Type: DRUG

Microdose flare-up regimen. The patient received diluted doses of the GnRH agonist leuprolide acetate 40 µg, given subcutaneously twice daily. Two days later, stimulation is initiated by intramuscular (IM) injections of HMG (Merional, IBSA, Germany) in a dose of 300 IU/day.

GnRH Group

Microdose flare-up regimen. The patient received diluted doses of the GnRH agonist leuprolide acetate 40 µg, given subcutaneously twice daily. Two days later, stimulation is initiated by intramuscular (IM) injections of HMG (Merional, IBSA, Germany) in a dose of 300 IU/day.

Group Type: ACTIVE_COMPARATOR

GnRH agonist

Intervention Type: DRUG

Microdose flare-up regimen. The patient received diluted doses of the GnRH agonist leuprolide acetate 40 µg, given subcutaneously twice daily. Two days later, stimulation is initiated by intramuscular (IM) injections of HMG (Merional, IBSA, Germany) in a dose of 300 IU/day.

Interventions

cabergoline

Cabergoline was administered in a dose of 1 mg/week in two divided doses which was terminated after embryo transfer

Intervention Type: DRUG

Aspirin

Aspirin was administered in daily dose of 80 mg initiated at the start of down-regulation with luteal leuprolide

Intervention Type: DRUG

GnRH agonist

Microdose flare-up regimen. The patient received diluted doses of the GnRH agonist leuprolide acetate 40 µg, given subcutaneously twice daily. Two days later, stimulation is initiated by intramuscular (IM) injections of HMG (Merional, IBSA, Germany) in a dose of 300 IU/day.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with a history of one or more failed IVF cycles with three or less retrieved oocytes

2. No age limitation

3. Patients with an inadequate ovarian response in previous cycle

4. Low estradiol (E2) levels in response to ovarian stimulation in previous cycle

5. Lower number of retrieved oocytes in previous trials.

Exclusion Criteria

1. Severe male factor (azospermia)

2. Hydrosalpinx

3. History of endometriosis

4. Endocrine or metabolic disorders

5. Follicle stimulating hormone (FSH) level > 15 mIU.

6. Antimullerian hormone (AMH)< 0.5 ng/ml

7. Any uterine causes of infertility e.g. septate uterus

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Ahmed Maged

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ahmed Maged, MD

Role: PRINCIPAL_INVESTIGATOR

kasr Alainy medical school

Locations

Kasr Alainy medical school

Cairo, , Egypt

Countries

Egypt

Central Contacts

Ahmed Maged, MD

Role: CONTACT

prof.ahmedmaged@gmail.com

01005227404

Ayman Hany, MD

Role: CONTACT

aymanobgyn@gmail.com

Other Identifiers

8

Identifier Type: -

Identifier Source: org_study_id