Extended High Dose Letrozole Regimen Versus Short Low Dose Letrozole Regimen as an Adjuvant to GnRH Antagonist Protocol in the Management of Poor Responders Undergoing IVF-ET

NCT01219153 | Completed Phase 2 DMC

• 1 other identifier: Ext letro/GnRHant
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this randomized controlled trial is to compare the efficacy of extended high dose letrozole regimen (5 mg /day for the first 5 days of cycle and 2.5 mg/day for the subsequent 3 days ) with short low dose letrozole regimen (2,5 mg/day from cycle day 3 to 7 ) as an adjuvant to GnRH antagonist protocol in the management of patients with poor ovarian response undergoing IVF-ET.

Conditions

Infertility

Keywords

Letrozole ,IVF, poor responders , GnRH antagonist

Outcome Measures

Primary Outcomes (1)

• Clinical pregnancy rate per started cycle

  Presence of intrauterine gestational sac detected by transvaginal ultrasound

  5 weeks after embryo transfer

Secondary Outcomes (1)

• Ongoing Pregnancy Rate per started cycle

  18 weeks after embryo transfer

Study Arms (2)

Extended high dose letrozole regimen /GnRH antagonist

EXPERIMENTAL

Drug: Extended high dose letrozole regimen /GnRH antagonist protocol

Short low dose letrozole regimen /GnRH antagonist

ACTIVE COMPARATOR

Drug: Short low dose letrozole regimen /GnRH antagonist protocol

Interventions

Extended high dose letrozole regimen /GnRH antagonist protocol DRUG

Letrozole (Femara; Novertis pharma AG, Basle, Switzerland) is administered starting on cycle day one for 8 consecutive days . The dose of letrozole is 5mg /day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days . Highly purified urinary FSH (HP-uFSH) (Fostimon, IBSA) 300 IU/day is started on cycle day 5 and is continued until and including the day of HCG administration. Starting from cycle day 8 , the dose of HP-uFSH is adjusted individually according to ovarian response which is monitored using transvaginal ultrasound and serum estradiol. GnRH antagonist (cetrorelix acetate)(Cetrotide®) 0.25 mg S.C once daily is started when the leading follicle is 14 mm in mean diameter and is continued until and including the day of HCG administration .

Also known as: Extended letrozole/GnRHant

Extended high dose letrozole regimen /GnRH antagonist

Short low dose letrozole regimen /GnRH antagonist protocol DRUG

Letrozole (Femara; Novertis pharma AG, Basle, Switzerland)2.5 mg /daily is administered for 5 consecutive days starting on cycle day 3. Highly purified urinary FSH (HP-uFSH) (Fostimon, IBSA) 300 IU/day is started on cycle day 3 and is continued until and including the day of HCG administration. Starting from cycle day 8 , the dose of HP-uFSH is adjusted individually according to ovarian response which is monitored using transvaginal ultrasound and serum estradiol. GnRH antagonist (cetrorelix acetate)(Cetrotide®) 0.25 mg S.C once daily is started when the leading follicle is 14 mm in mean diameter and is continued until and including the day of HCG administration .

Also known as: Short Letrozole/GnRHant

Short low dose letrozole regimen /GnRH antagonist

Eligibility Criteria

• Age: 30 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients who produced less than three mature follicles in response to standard GnRH agonist long protocol in their first IVF cycle

You may not qualify if:

• Age \> 42 years
• FSH\> 12 IU/L
• Irregular menstrual cycles
• Unilateral ovary
• Polycystic ovary syndrome
• Endometriosis
• Male factor of infertility requiring ICSI
• History of recurrent miscarriage
• Endocrinologic disorders
• Systemic disease contraindicating pregnancy

Sponsors & Collaborators

• Cairo University: lead
• Ahmed Elgazzar Hospital: collaborator

Study Sites (1)

Ahmed Elgazzar hospital , Assisted conception unit

Giza, Egypt

Location

Related Publications (3)

• Badawy A, Mosbah A, Tharwat A, Eid M. Extended letrozole therapy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a novel protocol. Fertil Steril. 2009 Jul;92(1):236-9. doi: 10.1016/j.fertnstert.2008.04.065. Epub 2008 Aug 15.

  PMID: 18706549 BACKGROUND

• Yarali H, Esinler I, Polat M, Bozdag G, Tiras B. Antagonist/letrozole protocol in poor ovarian responders for intracytoplasmic sperm injection: a comparative study with the microdose flare-up protocol. Fertil Steril. 2009 Jul;92(1):231-5. doi: 10.1016/j.fertnstert.2008.04.057. Epub 2008 Aug 3.

  PMID: 18678368 RESULT

• Fouda UM, Sayed AM. Extended high dose letrozole regimen versus short low dose letrozole regimen as an adjuvant to gonadotropin releasing hormone antagonist protocol in poor responders undergoing IVF-ET. Gynecol Endocrinol. 2011 Dec;27(12):1018-22. doi: 10.3109/09513590.2011.579661. Epub 2011 Jun 30.

  PMID: 21714697 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Study Officials

• Usama M Fouda, M.D, PhD

  Cairo University

  STUDY CHAIR

• Ahmed M Sayed, M.D, PhD

  Cairo University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 12, 2010
• First Posted: October 13, 2010
• Study Start: September 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: December 1, 2010
• Last Updated: July 12, 2011

Record last verified: 2011-07

Locations

EG (1)