Effect of Addition of Aromatase Inhibitor to Ovarian Stimulation Therapy in IVF Treatment

Study Overview
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Brief Summary
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This project seeks to determine whether estradiol suppression achieved with adjuvant treatment with an aromatase inhibitor improves end-follicular and midluteal phase parameters during IVF. 128 patients will be randomized to either placebo or active treatment.

Detailed Description
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The aim of the study is to investigate whether the detrimental effects of ovarian stimulation on outcomes in fresh embryo transfer cycles be ameliorated by co-treatment with aromatase inhibitors? The research questions are: Can the impact of ovarian stimulation on late follicular phase sex steroid levels (and hence endometrial receptivity) be mitigated by co-treatment with aromatase inhibitors during ovarian stimulation? Does co-treatment with aromatase inhibitors 'normalize' the endocrinology of the midluteal phase

Official Title
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Reducing the Impact of Ovarian Stimulation - The RIOT Project. Study RIOT-A: The Role of Aromatase Inhibitor in Reducing the Detrimental Effects of Ovarian Stimulation to Optimize Outcomes in Fresh Embryo Transfer Cycles

Conditions
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Infertility

Intervention / Treatment
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* Drug: Letrozole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Indication for IVF/ICSI treatment Eligible for IVF/ICSI treatment according to local criteria Regular cycles 21-35 days (both included) Age < 40 AMH 8- 32 (both included) Written consent EXCLUSION CRITERIA Any contraindication for IVF/ICSI treatment according to local criteria Previous stimulation for IVF/ICSI with < 4 oocytes obtained PCOS Undergoing IVF/ICSI for the purpose of fertility preservation Allergy towards study drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Lactose Monohydrate<br>2 tablets of placebo are administered daily from stimulation start to day before hCG as adjunctive therapy to 150 IU of recFSH | Drug: Placebo<br>* Adjuvant therapy to recFSH during ovarian stimulation<br>* Other names: Lactose Monohydrate;|
| Active Comparator: Letrozole 5mg<br>2 tablets of 2,5mg Letrozole are administered daily from stimulation start to day before hCG as adjunctive therapy to 150 IU of recFSH | Drug: Letrozole<br>* Adjuvant therapy to recFSH during ovarian stimulation<br>* Other names: Aromatase Inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum progesterone level |  | Assessed during stimulation treatment on day before hCG injection (throughout the study completion, up to 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum estradiol, testosterone and androstenedione levels |  | Assessed on stimulation day 5, day of hCG administration (or the day before), day 7 and 10 after hCG administration. Assessed throughout study completion, up to 3 years. | 
| P and 17-hydroxyprogesterone (17-HP) Area Under the Curve. |  | Assessed during stimulation treatment throughout the study completion, up to 3 years. | 
| Follicular fluid concentration of estradiol, testosterone, inhibin B and AMH levels |  | Assessed during stimulation treatment (throughout the study completion, up to 3 years | 
| Total IU of Follicle Stimulating Hormone used per cycle. |  | Assessed throughout study completion, up to 3 years | 
| Number of follicles > 12 mm |  | Assessed in stimulated cycle on day of hCG administration or the day before (throughout the study completion), up to 3 years. Cycle length is between 21 and 35 days | 
| Number of oocytes obtained oocytes obtained. |  | Assessed in stimulated cycle at time of oocyte pick up after follicle aspiration (throughout the study completion, up to 3 years).Cycle length is between 21 and 35 days | 
| Proportion of oocytes resulting in top quality day 2, day 3 embryos or day 5/6 embryos according to validated morphological criteria. |  | Assessed at day 2-3 after oocyte pick up following stimulation (throughout study completion, up to 3 years) | 
| Oocyte fertilization rate |  | Assessed during stimulation treatment (throughout the study completion, up to 3 years | 
| Number and quality of embryos obtained, including rate of blastocyst formation. |  | Assessed during stimulation treatment (throughout the study completion, up to 3 years | 
| Endometrial thickness in millimeters |  | Assessed throughout the study completion, up to 3 years | 
| Implantation rate |  | Assessed during stimulation treatment (throughout the study completion, up to 3 years | 
| Biochemical pregnancy rate |  | Assessed 2 weeks after embryo transfer following stimulation (throughout study completion, up to 3 years) | 
| Clinical pregnancy rate |  | Pregnancy scan at gestational age week 7-8 (3-4 weeks after the positive hCG in serum). Assessed throughout study completion, up to 3 years. | 
| Morphokinetic parameters of embryo quality as measured using a Time Lapse analysis in centers employing this technology. |  | Assessed from time of oocyte pick-up to embryo transfer following stimulation (throughout study completion, up to 3 years) | 
| Reported side effects |  | From start of stimulation and administration of study medication to pregnancy scan week gestational age 7-8. Assessed throughout study completion, up to 3 years. |