Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Antagonist/Letrozole in Poor Responders

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
homa oskouian, Yazd Research & Clinical Center for Infertility
ClinicalTrials.gov Identifier:
NCT00823004
First received: January 14, 2009
Last updated: December 20, 2013
Last verified: December 2013

January 14, 2009
December 20, 2013
June 2008
February 2009   (final data collection date for primary outcome measure)
pregnancy rate [ Time Frame: 5 weeks ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00823004 on ClinicalTrials.gov Archive Site
stimulation outcomes [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Antagonist/Letrozole in Poor Responders
GnRH Antagonist /Letrozole Versus Microdose GnRH Agonist Flare Protocol in Poor Responders Undergoing in Vitro Fertilization

Failure to respond to controlled ovarian hyperstimulation (COH) is still a major concern in assisted reproduction and there is no consensus on the ovarian stimulation choice regime for poor responders.

Aim: To evaluate and compare the efficacy of a microdose GnRH agonist flare (MF) and a GnRH antagonist/letrozole (A/L) protocols in poor responders undergoing in vitro fertilization (IVF).

Methods: One hundred eighty poor responder patients will be randomized to an ovarian stimulation protocol with either a MF or a letrozole and high dose FSH/hMG and flexible GnRH antagonist protocol.

All women receive 21 days of an oral contraceptive. A MF protocol will be used for ovarian stimulation in 90 patients. Three days after the last pill, a GnRH-agonist buserelin (Suprefact, Aventis Pharma, Frankfurt, Germany) 50 µg SC twice daily will be initiated and two days after that, recombinant FSH (Gonal-F, Serono, Aubonne, Switzerland) or hMG (Merional, IBSA, Lugano, Switzerland) 300-450 IU/day will be administered. Ninetyty patients will be assigned to an A/L protocol. After oral contraceptive withdrawal bleeding on day 3 of cycle, recombinant FSH or hMG 300-450 IU/day will be initiated and letrozole (Femara, Novartis, East Hanover, NJ) 5 mg/day will be administered for 5 days. When the dominant follicle reached 14 mm in mean diameter, ganirelix acetate (Antagon, Organon, West Orange, NJ) 0.25 mg SC daily will be started.

Patients weill be monitored by serial vaginal ultrasonography and measurement of serum E2 level. When at least two follicles with a mean diameter of 18 mm will be achieved hCG (Pregnyl, Organon, Oss, the Netherlands) 10000 IU will be administered. Cycle cancellation will be considered when fewer than two follicles with normal growth pattern weill be noted.

Oocyte retrieval will be performed 34-36 hours after hCG administration. Conventional IVF or intracytoplasmic sperm injection (ICSI) will be performed as appropriate. Embryos with 4-6 equally sized blastomers on day 2 with ≤ 20% fragmentation and no multinucleation will be considered top quality embryos. Embryos with 2-6 equally or unequally blastomers with ≤20% fragmentation and no multinucleation will be considered good quality embryos. Embryos will be transferred on day 2 or 3 under ultrasound guidance, with a C.C.D. embryo transfer catheter ( Laboratoire C.C.D., Paris, France). Luteal support with progesterone in oil (Progesterone, Aburaihan Co., Tehran, Iran) 100 mg daily IM will be started on the day of oocyte retrieval.

Serum β-hCG level will be measured 14 days after embryo transfer and a transvaginal ultrasonography will be performed 3 weeks after positive β-hCG for documentation of gestational sac and fetal heart activity. Clinical pregnancy will be considered as the presence of a gestational sac with fetal heart activity.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Ovarian Stimulation
  • Drug: letrozole
    letrozole 5mg/day from day 3 to day 7 of menstrual cycle
    Other Name: letrozole (Femara, Novartis, East Hanover, NJ)
  • Drug: oral contraceptive (Marvelone)
    oral contraceptive, first 21 days
    Other Name: Marvelon
  • Drug: GnRH agonist (buserelin)
    50 µg SC twice daily
    Other Name: suprefact
  • Drug: recombinant FSH or hMG
    recombinant FSH or hMG 300-450 IU/day
    Other Names:
    • Gonal F
    • Merional
  • Drug: ganirelix acetate
    GnRH antagonist (ganirelix acetate) when a leading follicle reaches a mean diameter of 14 mm, 0.25 mg per day (Antagon, Organon, West Orange, NJ)
    Other Name: Antagon
  • Active Comparator: 1
    A/L: Poor responders who will receive letrozole and GnRH antagonist for ovarian stimulation
    Interventions:
    • Drug: letrozole
    • Drug: oral contraceptive (Marvelone)
    • Drug: recombinant FSH or hMG
    • Drug: ganirelix acetate
  • Active Comparator: 2
    MF: In this arm poor responders are treated by microdose GnRH agonist flare protocol
    Interventions:
    • Drug: oral contraceptive (Marvelone)
    • Drug: GnRH agonist (buserelin)
    • Drug: recombinant FSH or hMG
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
120
October 2009
February 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • at least one previous failed IVF cycle in which three or fewer follicles with a mean diameter of 16 mm were achieved, and/or
  • serum E2 level measured on the day of hCG administration was ≤500 pg/ml

Exclusion Criteria:

  • day 3 serum FSH level ≥12 mIU/mL
  • there is no age limit
Female
Not Provided
Yes
Contact information is only displayed when the study is recruiting subjects
Iran, Islamic Republic of
 
NCT00823004
1969yazdRCCI
Yes
homa oskouian, Yazd Research & Clinical Center for Infertility
Yazd Research & Clinical Center for Infertility
Not Provided
Principal Investigator: homa oskouian, M.D. Research and clinical center for infertility
Principal Investigator: robab davar, MD Research and clinical center for infertility
Yazd Research & Clinical Center for Infertility
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP