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

• Sponsor: Cairo University (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT03263299
• Collaborator: (none)
• Enrollment: 120
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 13
• Patients Per Site Per Month: 9.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Invitro Fertilization	Drug: cabergoline; Drug: Aspirin; Drug: GnRH agonist	Phase 4

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Value of Cabergoline and Low Dose Aspirin in Poor Responders Undergoing ICSI-ET Using Microdose GnRH Agonist Flare-Up-Protocol
• Anticipated Study Start Date: Aug 1, 2017
• Anticipated Primary Completion Date: Aug 1, 2018
• Anticipated Study Completion Date: Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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	Drug: cabergoline; Cabergoline was administered in a dose of 1 mg/week in two divided doses which was terminated after embryo transfer; Drug: Aspirin; Aspirin was administered in daily dose of 80 mg initiated at the start of down-regulation with luteal leuprolide; 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.
Active Comparator: Aspirin group Aspirin was administered in daily dose of 80 mg initiated at the start of down-regulation with luteal leuprolide	Drug: Aspirin; Aspirin was administered in daily dose of 80 mg initiated at the start of down-regulation with luteal leuprolide; 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.
Active Comparator: 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.	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.

Outcome Measures

Primary Outcome Measures

1. clinical pregnancy [4 weeks after embryo transfer]

   Intrauterine gestational sac detection by transvaginal ultrasound

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 39 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kasr Alainy medical school	Cairo		Egypt	12151

Sponsors and Collaborators

• Cairo University

Investigators

• Principal Investigator: Ahmed Maged, MD, kasr Alainy medical school

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ahmed Maged, Professor, Cairo University
• ClinicalTrials.gov Identifier: NCT03263299
• Other Study ID Numbers: 8
• First Posted: Aug 28, 2017
• Last Update Posted: Aug 28, 2017
• Last Verified: Aug 1, 2017

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Aspirin; Cabergoline

Study Results

No Results Posted as of Aug 28, 2017