Assessment and Prevention of Pain During Ovarian Stimulation in Patients With Endometriosis

Study Overview
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Brief Summary
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Randomized double blinded placebo-controlled trial to evaluate the impact of ovarian hyperstimulation on endometriosis-related symptoms and to evaluate the impact of letrozole use during ovarian hyperstimulation with respect to endometriosis-related symptoms, embryo/egg quality and quantity, and pregnancy rates.

Detailed Description
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Randomized double blinded placebo-controlled trial to evaluate: (1) the impact of letrozole use during ovarian hyperstimulation with respect to endometriosis-related symptoms, embryo/egg quality and quantity, and pregnancy rates, (2) the impact of ovarian hyperstimulation on endometriosis-related symptoms. There will be a total of 60 participants, 20 participants with endometriosis randomized to the placebo group, 20 participants with endometriosis randomized to the letrozole group and 20 control patients with no history of endometriosis. Letrozole and placebo medication will be started on the first day of gonadotropin injections and continued until the day of trigger shot. Medication will be restarted the night of egg retrieval and continued for 2 weeks post retrieval. Endometriosis associated symptoms will be evaluated using a survey modeled after the clinical survey developed by the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project. Surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval.

Official Title
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Assessment and Prevention of Pain During Ovarian Stimulation in Patients With Endometriosis

Conditions
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Endometriosis, Ovarian Hyperstimulation

Intervention / Treatment
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* Drug: Placebo oral tablet
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-42 years Planning to undergo controlled ovarian hyperstimulation Prior diagnosis of endometriosis by one of the following: (1) surgical diagnosis (2) endometrioma on pelvic ultrasound Planning to freeze all retrieved oocytes/embryos prior to transfer Exclusion Criteria: Hypersensitivity to letrozole Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up, or interpretation of study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 42 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Endometriosis Letrozole<br>Participants will be asked to take 5mg letrozole daily throughout their ovarian stimulation and for 2 weeks following retrieval. Participants will be blinded to their randomization to letrozole. Participants will be asked to complete surveys during their stimulation and up to 12 weeks following retrieval to evaluate endometriosis associated symptoms. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm. | Drug: Letrozole<br>* 5mg oral daily<br>|
| Placebo Comparator: Endometriosis Placebo<br>Participants will be asked to take one tablet placebo daily throughout their ovarian stimulation and for 2 weeks following retrieval. Participants will be blinded to their randomization to placebo. Participants will be asked to complete surveys during their stimulation and up to 12 weeks following retrieval to evaluate endometriosis associated symptoms. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm. | Drug: Placebo oral tablet<br>* 1 tablet oral daily<br>|
| No Intervention: No Endometriosis Control<br>Participants will be asked to complete surveys during their ovarian stimulation and up to 12 weeks following retrieval to evaluate symptoms of pelvic pain. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Delta in Endometriosis Pain Score Pre and Post Stimulation With and Without Use Of Letrozole | To evaluate how letrozole impacts pain scores throughout controlled ovarian hyperstimulation in patients with endometriosis. Pain scores will be evaluated using a 0-10 visual acuity scale, where 0 is no pain and 10 is the worst imaginable pain. The average delta between pre-stimulation pain score and day of trigger shot pain score will be compared between patients with endometriosis receiving placebo and with endometriosis receiving letrozole. | Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Delta in Endometriosis Pain Score Pre and Post Stimulation Compared to No Endometriosis | To evaluate the impact of endometriosis on pain scores throughout controlled ovarian hyperstimulation. Pain scores will be evaluated using a 0-10 visual acuity scale, where 0 is no pain and 10 is the worst imaginable pain. The average delta between pre-stimulation pain score and day of trigger shot will be compared between patients with endometriosis receiving placebo and patients without endometriosis. | Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot). | 
| Trend in Endometriosis Pain Score Pre and Post Stimulation With Use Of Letrozole | To evaluate the impact of letrozole on endometriosis pain scores throughout controlled ovarian hyperstimulation. Pain scores will be evaluated using a 0-10 visual acuity scale, where 0 is no pain and 10 is the worst imaginable pain. The trend in pain scores from pre-stimulation through 12 weeks post retrieval will be compared between patients with endometriosis receiving placebo, patients with endometriosis receiving letrozole and patients without endometriosis. | Pre-stimulation through 12 weeks post retrieval | 
| Does Letrozole Impact Embryo and Egg Quantity in Endometriosis | To describe the impact of letrozole on egg/embryo quality in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation. The number of eggs retrieved per AFC and the number of eggs retrieved per total number of mature follicles will be compared between the two groups. | Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval). | 
| Follicular Fluid | To compare follicular fluid average estradiol levels between placebo, letrozole and control groups. | Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval). | 
| Pregnancy Outcomes | To compare pregnancy rates in the placebo, letrozole and control groups. Pregnancy will be defined as positive serum hCG after transfer of embryo. The rate will determined by positive hCG per transfer. | Up to 2 years. | 
| Egg Maturity | To describe the impact of letrozole on egg maturity. Measured by number of MII eggs per total number eggs retrieved in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation. | Baseline ultrasound to time of cryopreservation of eggs/embryos, which occurs within 7 days of retrieval.. | 
| Embryo Grade | To describe the impact of letrozole on embryo quality. Measured by fraction of freezable quality embryos (6c or greater, grades 1-2 for symmetry and fragmentation) in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endometriosis, Letrozole