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

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

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.

Study Overview

• Status: Unknown
• Conditions: Invitro Fertilization
• Intervention / Treatment: Drug: cabergoline; Drug: Aspirin; Drug: GnRH agonist

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 Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ayman Hany, MD; Email: aymanobgyn@gmail.com

Study Locations

• Egypt
  • Cairo, Egypt, 12151
    • Kasr Alainy medical school

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 39 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical pregnancy	Intrauterine gestational sac detection by transvaginal ultrasound	4 weeks after embryo transfer

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 1, 2017
• Primary Completion (ANTICIPATED): August 1, 2018
• Study Completion (ANTICIPATED): September 1, 2018

Study Registration Dates

• First Submitted: August 24, 2017
• First Submitted That Met QC Criteria: August 24, 2017
• First Posted (ACTUAL): August 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 28, 2017
• Last Update Submitted That Met QC Criteria: August 24, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Dopamine Agonists; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Aspirin; Cabergoline
• Other Study ID Numbers: 8

Drug and device information, study documents

• 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