Does Letrozole Improve the Outcomes and/or Reduce the Cost of IVF-ET Cycles? (Cost-Less)

Controlled Ovarian Stimulation With Letrozole Supplementation

This research is being done to determine whether the success rate of in vitro fertilization treatment can be improved, while lowering the cost incurred from infertility medications using a pill called letrozole.

Study Overview

• Status: Withdrawn
• Conditions: Infertility
• Intervention / Treatment: Drug: Letrozole; Drug: Std IVF Protocol

Detailed Description

Specific Aim:

1. To determine whether addition of letrozole to gonadotropins would reduce the amount of gonadotropins used in an IVF-ET cycle, thereby reducing the cost.
2. To determine whether letrozole improves IVF-ET success compared to standard ovarian stimulation protocols.

Null Hypothesis: Use of Letrozole for ovulation induction in IVF is not less expensive than the standard therapy by a clinically relevant amount.

Alternative Hypothesis: Use of Letrozole for ovulation induction in IVF is better than the standard therapy by a clinically relevant amount.

Protocol:

Infertile women <40 years of age with age-appropriate ovarian reserve (as determined by day2/3 E2, FSH, and AMH) will be randomized between two protocols: one with letrozole and one with standard ovulation induction.

In both groups, serum FSH will be measured each time a sample is obtained for estradiol. Sera will be frozen for further batch assay.

Number of embryos to be transferred will be decided following the ASRM guidelines. The day of embryo transfer (D-3 vs D-5) will be based on the number and quality of embryos as per established clinical criteria.

Power Considerations

A review of 1473 cycles of patients less than 40 years old over the last 6 years (2002 - 2008) revealed average cost per cycle to be $3,152 +/- 1685(SD).

For the purpose of this power analysis we consider a 20% decrease in medication cost to be clinically significant. Thus a decrease from $ 3152.83 to $ 2522.26 will be considered clinically significant (20% decrease). For an alpha of 0.05 and a power of 80% for a two tailed test 113 patients will need to complete each arm.

Allowing for 10% drop-out we will attempt to randomize 125 patients to each arm of the study.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Center For Human Reproduction

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Normal Ovarian Function
2. Normal uterus

Exclusion Criteria:

1. Age 40 and above
2. Diminished ovarian reserve (based on markers and/or previous poor response)
3. Previous oophorectomy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Letrozole; 1) Letrozole/ Recombinant FSH	Drug: Letrozole; 1) Letrozole 5 mg starting on cycle day 2, which will be continued until the day of trigger. Recombinant FSH at doses 100-225 units, as determined by BMI, AFC, age, and ovarian reserve markers will be added on cycle day 4. The dose will be adjusted based on the response. An antagonist will be administered once the lead follicle reaches 14-mm in diameter or when estradiol level reaches 250 pg/mL. Oocyte maturation will be triggered by 20 iu of leuprolide acetate.; Other Names: Femara
Active Comparator: Standard IVF; luteal phase GnRHa suppression/gonadotropin	Drug: Std IVF Protocol; 2) Long protocol with luteal phase GnRHa suppression with gonadotropin dose at 200-450 IU. Oocyte maturation will be triggered by 250 micg of ovidrel.; Other Names: Ovulation induction with Human Menopausal gonoadotropins

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cost of Treatment	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pregnancy and implantation rates	4 weeks
Incidence of Ovarian Hyper stimulation Syndrome	4 weeks
Multiple Birth Rate	10 months

Collaborators and Investigators

• Sponsor: Center for Human Reproduction
• Investigators: Study Director: David Barad, MD. MS, CHR; Principal Investigator: Kutluk Oktay, MD, CHR/ New York Medical College

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Anticipated): December 1, 2009
• Study Completion (Anticipated): April 1, 2010

Study Registration Dates

• First Submitted: December 5, 2008
• First Submitted That Met QC Criteria: December 8, 2008
• First Posted (Estimate): December 9, 2008

Study Record Updates

• Last Update Posted (Estimate): June 25, 2015
• Last Update Submitted That Met QC Criteria: June 24, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: In Vitro Fertilization; Letrozole; Ovulation Induction; Cost of Infertility Treatment
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: CHR #5/17/08-2