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

Study Overview
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Brief Summary
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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.

Detailed Description
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Specific Aim: To determine whether addition of letrozole to gonadotropins would reduce the amount of gonadotropins used in an IVF-ET cycle, thereby reducing the cost. 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.

Official Title
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Controlled Ovarian Stimulation With Letrozole Supplementation

Conditions
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Infertility

Intervention / Treatment
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* Drug: Letrozole
* Drug: Std IVF Protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal Ovarian Function Normal uterus Exclusion Criteria: Age 40 and above Diminished ovarian reserve (based on markers and/or previous poor response) Previous oophorectomy

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letrozole<br>1) Letrozole/ Recombinant FSH | Drug: Letrozole<br>* 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.<br>* Other names: Femara;|
| Active Comparator: Standard IVF<br>luteal phase GnRHa suppression/gonadotropin | Drug: Std IVF Protocol<br>* 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.<br>* Other names: Ovulation induction with Human Menopausal gonoadotropins;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost of Treatment |  | 4 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cost of Infertility Treatment, Ovulation Induction, Letrozole, In Vitro Fertilization