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
  Purpose

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.


Condition Intervention Phase
Ovarian Stimulation
Drug: letrozole
Drug: oral contraceptive (Marvelone)
Drug: GnRH agonist (buserelin)
Drug: recombinant FSH or hMG
Drug: ganirelix acetate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: GnRH Antagonist /Letrozole Versus Microdose GnRH Agonist Flare Protocol in Poor Responders Undergoing in Vitro Fertilization

Resource links provided by NLM:


Further study details as provided by Yazd Research & Clinical Center for Infertility:

Primary Outcome Measures:
  • pregnancy rate [ Time Frame: 5 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • stimulation outcomes [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 120
Study Start Date: June 2008
Study Completion Date: October 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
A/L: Poor responders who will receive letrozole and GnRH antagonist for 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: 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: 2
MF: In this arm poor responders are treated by microdose GnRH agonist flare protocol
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

Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00823004

Locations
Iran, Islamic Republic of
Research and clinical center for infertility
Yazd, Iran, Islamic Republic of, 8916877391
Sponsors and Collaborators
Yazd Research & Clinical Center for Infertility
Investigators
Principal Investigator: homa oskouian, M.D. Research and clinical center for infertility
Principal Investigator: robab davar, MD Research and clinical center for infertility
  More Information

No publications provided

Responsible Party: homa oskouian, fellowship, Yazd Research & Clinical Center for Infertility
ClinicalTrials.gov Identifier: NCT00823004     History of Changes
Other Study ID Numbers: 1969yazdRCCI
Study First Received: January 14, 2009
Last Updated: December 20, 2013
Health Authority: Iran: Ministry of Health

Keywords provided by Yazd Research & Clinical Center for Infertility:
controlled ovarian hyperstimulation
pregnancy rate
Poor responders
GnRH antagonist
GnRH agonist
letrozole
in vitro fertilization
controlled ovarian hyperstimulation

Additional relevant MeSH terms:
Buserelin
Triptorelin
Contraceptive Agents
Contraceptives, Oral
Ganirelix
Deslorelin
Letrozole
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Female
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Luteolytic Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Aromatase Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014