Trial Outcomes & Findings for Assessment and Prevention of Pain During Ovarian Stimulation in Patients With Endometriosis (NCT NCT04002141)
NCT ID: NCT04002141
Last Updated: 2026-01-28
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
60 participants
Primary outcome timeframe
Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot).
Results posted on
2026-01-28
Participant Flow
Participant milestones
| Measure |
Endometriosis Letrozole
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.
Letrozole: 5mg oral daily
|
Endometriosis Placebo
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.
Placebo oral tablet: 1 tablet oral daily
|
No Endometriosis Control
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.
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|---|---|---|---|
|
Overall Study
STARTED
|
20
|
20
|
20
|
|
Overall Study
COMPLETED
|
20
|
20
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Endometriosis Letrozole
n=20 Participants
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.
Letrozole: 5mg oral daily
|
Endometriosis Placebo
n=20 Participants
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.
Placebo oral tablet: 1 tablet oral daily
|
No Endometriosis Control
n=20 Participants
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.
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=60 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
20 Participants
n=20 Participants
|
20 Participants
n=20 Participants
|
20 Participants
n=20 Participants
|
60 Participants
n=60 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=60 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=20 Participants
|
20 Participants
n=20 Participants
|
20 Participants
n=20 Participants
|
60 Participants
n=60 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=60 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
20 participants
n=20 Participants
|
20 participants
n=20 Participants
|
20 participants
n=20 Participants
|
60 participants
n=60 Participants
|
PRIMARY outcome
Timeframe: Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot).Population: only includes those who completed stimulation and filled out survey for baseline and trigger pain
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.
Outcome measures
| Measure |
Endometriosis Letrozole
n=17 Participants
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.
Letrozole: 5mg oral daily
|
Endometriosis Placebo
n=16 Participants
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.
Placebo oral tablet: 1 tablet oral daily
|
No Endometriosis Control
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.
|
|---|---|---|---|
|
Average Delta in Endometriosis Pain Score Pre and Post Stimulation With and Without Use Of Letrozole
|
-2.5 Change in score on a scale
Standard Deviation 3.9
|
-2.7 Change in score on a scale
Standard Deviation 3.9
|
—
|
SECONDARY outcome
Timeframe: Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot).Population: only includes those who completed stimulation and filled out surveys for baseline and trigger
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.
Outcome measures
| Measure |
Endometriosis Letrozole
n=16 Participants
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.
Letrozole: 5mg oral daily
|
Endometriosis Placebo
n=16 Participants
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.
Placebo oral tablet: 1 tablet oral daily
|
No Endometriosis Control
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.
|
|---|---|---|---|
|
Average Delta in Endometriosis Pain Score Pre and Post Stimulation of Patients Receiving Placebo Compared to No Endometriosis
|
-2.7 Change in score on a scale
Standard Deviation 3.9
|
-0.6 Change in score on a scale
Standard Deviation 4.1
|
—
|
SECONDARY outcome
Timeframe: Pre-stimulation through 12 weeks post retrieval. This time span varies per each patient's course of treatment but is typically 14 weeks in totaPopulation: only includes those who filled out baseline and 12 week surveys and completed stimulation
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.
Outcome measures
| Measure |
Endometriosis Letrozole
n=12 Participants
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.
Letrozole: 5mg oral daily
|
Endometriosis Placebo
n=15 Participants
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.
Placebo oral tablet: 1 tablet oral daily
|
No Endometriosis Control
n=15 Participants
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.
|
|---|---|---|---|
|
Comparative Trends in Endometriosis Pain Score Pre and Post Stimulation of Patients With Endometriosis Receiving Either Placebo or Letrozole and Patients Without Endometriosis
|
-0.7 Change in score on a scale
Standard Deviation 2.0
|
-1.0 Change in score on a scale
Standard Deviation 2.3
|
-0.6 Change in score on a scale
Standard Deviation 2.9
|
SECONDARY outcome
Timeframe: Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval).Population: Only includes those who either froze eggs or used ICSI for fertilization as MII rates are not available for those who used conventional insemination
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.
Outcome measures
| Measure |
Endometriosis Letrozole
n=16 Participants
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.
Letrozole: 5mg oral daily
|
Endometriosis Placebo
n=16 Participants
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.
Placebo oral tablet: 1 tablet oral daily
|
No Endometriosis Control
n=18 Participants
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.
|
|---|---|---|---|
|
Does Letrozole Impact Egg Quantity in Endometriosis Patients
|
0.84 percentage of MII grade eggs per AFC
Standard Deviation 0.43
|
0.88 percentage of MII grade eggs per AFC
Standard Deviation 0.44
|
0.73 percentage of MII grade eggs per AFC
Standard Deviation 0.27
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 2 weeksPopulation: only those who completed cycles and froze embryos (does not include egg freezers)
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.
Outcome measures
| Measure |
Endometriosis Letrozole
n=13 Participants
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.
Letrozole: 5mg oral daily
|
Endometriosis Placebo
n=15 Participants
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.
Placebo oral tablet: 1 tablet oral daily
|
No Endometriosis Control
n=9 Participants
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.
|
|---|---|---|---|
|
Embryo Grade
|
2.9 count of freezable embryos
Standard Deviation 2.4
|
2.9 count of freezable embryos
Standard Deviation 2.4
|
3.3 count of freezable embryos
Standard Deviation 2.5
|
Adverse Events
Endometriosis Letrozole
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Endometriosis Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
No Endometriosis Control
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Endometriosis Letrozole
n=20 participants at risk
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.
Letrozole: 5mg oral daily
|
Endometriosis Placebo
n=20 participants at risk
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.
Placebo oral tablet: 1 tablet oral daily
|
No Endometriosis Control
n=20 participants at risk
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.
|
|---|---|---|---|
|
Reproductive system and breast disorders
Heavy Vaginal Bleeding
|
5.0%
1/20 • Number of events 1 • Ovarian stimulation baseline through 12 weeks post retrieval. This time span varies per each patient's course of treatment but is typically 14 weeks in tota
|
0.00%
0/20 • Ovarian stimulation baseline through 12 weeks post retrieval. This time span varies per each patient's course of treatment but is typically 14 weeks in tota
|
0.00%
0/20 • Ovarian stimulation baseline through 12 weeks post retrieval. This time span varies per each patient's course of treatment but is typically 14 weeks in tota
|
Other adverse events
Adverse event data not reported
Additional Information
Marcelle Cedars, MD, Director, Division of Reproductive Endocrinology
University of California, San Francisco
Phone: (415) 353-7475
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place