Comparative Study Between Minidose Long Protocol and Microdose Flare Protocol in Controlled Ovarian Hyperstimulation

• Sponsor: Kasr El Aini Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02342197
• Collaborator: (none)
• Enrollment: 60
• Arms: 2
• Duration (Months): 11

Study Details

Study Description

Brief Summary

Objective: To compare two stimulation protocols, the minidose long protocol and the microdose flare protocol designed for low responders undergoing ICSI.

Design: Randomized prospective study. Setting: University hospital IVF unit. Patients: 60 poor responder patients coming for IVF center for ICSI. Interventions: Minidose long protocol in which half the dose of agonist was administered from the mid luteal phase until the day of HCG administration was compared with microdose flare protocol in which half the dose of GnRH was administered from the second day of the cycle until the day of HCG administration. Both groups received Gn stimulation from the second day of the cycle (300-450 IU).

Main outcome measures: Number of oocytes retrieved.

Condition or Disease	Intervention/Treatment	Phase
Infertility	Drug: Decapeptyl	Phase 3

Detailed Description

Patients and methods:

60 patients expected to have poor response for ovarian stimulation attending kasr EL-Aini hospital IVF center planning for ICSI during the year 2011 were randomized to receive ovulation induction for controlled ovarian hyperstimulation by either one of two protocols: Minidose long protocol and microdose flare protocol.

Inclusion criteria:

All patients included were classified as poor responders when one of the following criteria was present:

• Age > 35 years.

• Day 3 serum FSH level > 10m IU/ml.

• Number of antral follicles measuring 4-8mm during the early phase < 6.

• Small ovarian volume.

• AMH < 1.

• Prior poor ovarian response to COH (oocytes < 5).

Exclusion criteria:

• Polycystic ovarian syndrome patients.

• Patients with Endometriosis.

• Normal responders to ovulation induction.

• Patients having ovarian cyst.

• Patients receiving ovulation induction in the preceding cycle. The study was approved by Kasr El-Aini IVF center research committee. Each patient had given informed consent after full explanation of the procedure. Randomization was performed according to a computer generated list. The patients were randomized to two groups.

The Minidose long protocol:

Decapeptyl 50µg/ day was administered SC from cycle day 21 until menstruation. On the second day of the cycle, patients were assessed for downregulation; E2 level < 50 pg/ml, endometrial thickness less than 5 mm, no follicles > 15mm. Once patient downregulation was confirmed, Gn dose was commenced at an initial dose of 300-450 IU/day for the first 5 days followed by individual adjustment in Gn dose according to ovarian response and the dose of Decapeptyl 50µg/day was continued until day of HCG administration.

The microdose flare protocol:

Administration of OCP's at the prior menses followed by Decapeptyl 50µg/day SC started on the second day of the cycle and continued until the day of HCG administration. Gn was started concomitantly on the second day of the cycle as described above.

Cycle monitoring:

Monitoring consisted of several ultrasound examination and serum E2 level in both protocols. The starting Gn dosage was determined by a combination of factors including patient age, ovarian reserve testing, prior stimulation response and was adjusted according to individual response. Serum LH levels were measured from day 6 of stimulation to exclude premature luteinization (LH > 15 IU/L).

10,000 IU HCG was administered intramuscular when at least two leading follicles were 18mm in diameter. Oocyte retrieval was performed 35 hours after HCG administration by ultrasound guided transvaginal aspiration.

Laboratory procedures:

The ICSI procedure was performed 4 hours after oocyte aspiration for all the mature oocytes. Fertilization was assessed 16-18 hours after ICSI and was considered normal only when two distinct pronuclei were present. The embryos obtained were categorized on day 2-3 into 3 grades depending on their morphological appearance, zonal thickness, cytoplasmic fragmentation and blastomere size.

Transfer procedure and luteal support:

Depending on patient age, embryo quality and the number of embryos available, 1-4 embryos were transferred 2-3 days after oocyte collection under transabdominal ultrasound guidance using a cook catheter.

The luteal phase was supported with micronized progesterone 400 mg twice daily administered vaginally until a pregnancy test was performed.

Outcome measures:

To assess a difference in pregnancy rates between the two protocols, a sample size of 100's of patients should be considered but considering the size of our work, it would be many years before such large samples could be recruited. We therefore chose to focus on oocyte number as a main outcome measure.

The data recorded for analysis included: age, infertility history and etiology, day 3 FSH, duration of stimulation, number of gonadotrophin ampoules required, E2 level on the day of HCG administration, number of oocytes retrieved and fertilized and number of embryos transferred.

The primary outcome measure was the number of oocytes retrieved. The secondary outcome measures were implantation and clinical pregnancy rates. A clinical pregnancy was defined as a normal gestational sac measured with transvaginal ultrasound after 5 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparative Study Between Minidose Long Protocol and Microdose Flare Protocol in Controlled Ovarian Hyperstimulation for Poor Responders in ICSI Cycles
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Minidose long protocol Half dose of GnRH agonist (Decapeptyl 0.05) was started in the midluteal phase and Gn's was started from the second day of the cycle.	Drug: Decapeptyl; half the dose of Gn agonist; Other Names: GnRH agonist
Active Comparator: Microdose flare protocol Half the dose of GnRH agonist (Decapeptyl 0.05) was started on the second day of the cycle together with Gn's	Drug: Decapeptyl; half the dose of Gn agonist; Other Names: GnRH agonist

Outcome Measures

Primary Outcome Measures

1. Number of Oocytes Retrieved [12 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 42 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age > 35 years

• Day 3 serum FSH level > 10m IU/ml

• Number of antral follicles measuring 4-8mm during the early phase < 6

• Small ovarian volume

• AMH < 1

• Prior poor ovarian response to COH (oocytes < 5)

Exclusion Criteria:

• Polycystic ovarian syndrome patients

• Patients with Endometriosis

• Normal responders to ovulation induction

• Patients having ovarian cyst

• Patients receiving ovulation induction in the preceding cycle

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Kasr El Aini Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nawara Mohamed Hashish, Nawara Hashish, Kasr El Aini Hospital
• ClinicalTrials.gov Identifier: NCT02342197
• Other Study ID Numbers: 610012011
• First Posted: Jan 19, 2015
• Last Update Posted: Jan 28, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by Nawara Mohamed Hashish, Nawara Hashish, Kasr El Aini Hospital: Low responders; Minidose long protocol; Microdose flare protocol; Oocyte yield
• Additional relevant MeSH terms: Infertility; Triptorelin Pamoate

Study Results

Participant Flow

Arm/Group Title	Minidose Long Protocol	Microdose Flare Protocol
Arm/Group Description	Half dose of GnRH agonist (Decapeptyl 0.05) was started in the midluteal phase and Gn's was started from the second day of the cycle. Decapeptyl: half the dose of Gn agonist	Half the dose of GnRH agonist (Decapeptyl 0.05) was started on the second day of the cycle together with Gn's Decapeptyl: half the dose of Gn agonist
Period Title: Overall Study
STARTED	30	30
COMPLETED	27	28
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Minidose Long Protocol	Microdose Flare Protocol	Total
Arm/Group Description	Half dose of GnRH agonist (Decapeptyl 0.05) was started in the midluteal phase and Gn's was started from the second day of the cycle. Decapeptyl: half the dose of Gn agonist	Half the dose of GnRH agonist (Decapeptyl 0.05) was started on the second day of the cycle together with Gn's Decapeptyl: half the dose of Gn agonist	Total of all reporting groups
Overall Participants	30	30	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.4 (1.5)	37.1 (1.5)	37.2 (0.1)
Sex: Female, Male (Count of Participants)
Female	30 100%	30 100%	60 100%
Male	0 0%	0 0%	0 0%
BMI (kg/m2) (kg / m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg / m2]	30 (2.5)	31 (1.8)	30.5 (0.2)
Day 3 FSH (IU/L) (IU/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [IU/L]	8 (1.1)	7.6 (1.1)	7.8 (0.1)
Duration of infertility (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.1 (1.5)	5.7 (1.5)	5.4 (0.1)

Outcome Measures

1. Primary Outcome

Title	Number of Oocytes Retrieved
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Minidose Long Protocol	Microdose Flare Protocol
Arm/Group Description	Half dose of GnRH agonist (Decapeptyl 0.05) was started in the midluteal phase and Gn's was started from the second day of the cycle. Decapeptyl: half the dose of Gn agonist	Half the dose of GnRH agonist (Decapeptyl 0.05) was started on the second day of the cycle together with Gn's Decapeptyl: half the dose of Gn agonist
Measure Participants	27	28
Mean (Standard Deviation) [oocytes]	4 (1)	3.4 (0.7)

Adverse Events

Arm/Group Title	Minidose Long Protocol		Microdose Flare Protocol
Arm/Group Description	Half dose of GnRH agonist (Decapeptyl 0.05) was started in the midluteal phase and Gn's was started from the second day of the cycle. Decapeptyl: half the dose of Gn agonist		Half the dose of GnRH agonist (Decapeptyl 0.05) was started on the second day of the cycle together with Gn's Decapeptyl: half the dose of Gn agonist
All Cause Mortality
	Minidose Long Protocol		Microdose Flare Protocol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Minidose Long Protocol		Microdose Flare Protocol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Endocrine disorders
ovarian hyperstimulation	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Minidose Long Protocol		Microdose Flare Protocol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.