Endometriosis, Ovarian Hyperstimulation
Conditions
Keywords
Endometriosis, Letrozole
Brief summary
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
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.
Interventions
DRUGPlacebo oral tablet
1 tablet oral daily
DRUGLetrozole
5mg oral daily
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Delta in Endometriosis Pain Score Pre and Post Stimulation With and Without Use Of Letrozole | Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Delta in Endometriosis Pain Score Pre and Post Stimulation of Patients Receiving Placebo Compared to No Endometriosis | Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot). | 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. |
| Comparative Trends in Endometriosis Pain Score Pre and Post Stimulation of Patients With Endometriosis Receiving Either Placebo or Letrozole and Patients Without Endometriosis | Pre-stimulation through 12 weeks post retrieval. This time span varies per each patient's course of treatment but is typically 14 weeks in tota | 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 calculated change 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. |
| Does Letrozole Impact Egg Quantity in Endometriosis Patients | Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval). | To describe the impact of letrozole on egg quantity in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole and those without endometriosis during controlled ovarian stimulation. The total arm aggregate number of MII eggs retrieved per baseline arm aggregate Antral Follicle Count will be compared between the three groups. |
| Follicular Fluid | Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval). | To compare follicular fluid average estradiol levels between placebo, letrozole and control groups. |
| Pregnancy Outcomes | Up to 2 years. | 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. |
| Egg Maturity | Baseline ultrasound to time of cryopreservation of eggs/embryos, which occurs within 7 days of retrieval.. | 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. |
| Embryo Grade | 2 weeks | To describe the impact of letrozole on embryo quality. Measured by the average total number 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 and those without endometriosis during controlled ovarian stimulation. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMarcelle I Cedars
University of California, San Francisco
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment United States | 60 participants |
| Sex: Female, Male Female | 60 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 1 / 20 | 0 / 20 | 0 / 20 |
Outcome results
None listed