Antagonist/Letrozole in Poor Responders

December 20, 2013 updated by: homa oskouian, Yazd Research & Clinical Center for Infertility

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
A/L: Poor responders who will receive letrozole and GnRH antagonist for ovarian stimulation
letrozole 5mg/day from day 3 to day 7 of menstrual cycle
Other Names:
  • letrozole (Femara, Novartis, East Hanover, NJ)
oral contraceptive, first 21 days
Other Names:
  • Marvelon
recombinant FSH or hMG 300-450 IU/day
Other Names:
  • Gonal F
  • Merional
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 Names:
  • Antagon
Active Comparator: 2
MF: In this arm poor responders are treated by microdose GnRH agonist flare protocol
oral contraceptive, first 21 days
Other Names:
  • Marvelon
recombinant FSH or hMG 300-450 IU/day
Other Names:
  • Gonal F
  • Merional
50 µg SC twice daily
Other Names:
  • suprefact

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
pregnancy rate
Time Frame: 5 weeks
5 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
stimulation outcomes
Time Frame: 2 weeks
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: homa oskouian, M.D., Research and clinical center for infertility
  • Principal Investigator: robab davar, MD, Research and clinical center for infertility

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)

October 1, 2009

Study Registration Dates

First Submitted

January 14, 2009

First Submitted That Met QC Criteria

January 14, 2009

First Posted (Estimate)

January 15, 2009

Study Record Updates

Last Update Posted (Estimate)

December 23, 2013

Last Update Submitted That Met QC Criteria

December 20, 2013

Last Verified

December 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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