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

January 23, 2026 updated by: University of California, San Francisco
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94158
        • UCSF Center for Reproductive Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 38 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Letrozole
5mg oral daily
Placebo Comparator: 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.
Drug: Placebo oral tablet
1 tablet oral daily
No Intervention: 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.

What is the study measuring?

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
Time Frame: 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.
Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Follicular Fluid
Time Frame: 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.
Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval).
Pregnancy Outcomes
Time Frame: 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.
Up to 2 years.
Egg Maturity
Time Frame: 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.
Baseline ultrasound to time of cryopreservation of eggs/embryos, which occurs within 7 days of retrieval..
Average Delta in Endometriosis Pain Score Pre and Post Stimulation of Patients Receiving Placebo Compared to No Endometriosis
Time Frame: 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.
Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot).
Comparative Trends in Endometriosis Pain Score Pre and Post Stimulation of Patients With Endometriosis Receiving Either Placebo or Letrozole and Patients Without Endometriosis
Time Frame: 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.
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
Does Letrozole Impact Egg Quantity in Endometriosis Patients
Time Frame: 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.
Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval).
Embryo Grade
Time Frame: 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.
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Investigators

  • Principal Investigator: Marcelle I Cedars, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 17, 2019

Primary Completion (Actual)

October 1, 2023

Study Completion (Actual)

January 1, 2025

Study Registration Dates

First Submitted

May 28, 2019

First Submitted That Met QC Criteria

June 26, 2019

First Posted (Actual)

June 28, 2019

Study Record Updates

Last Update Posted (Actual)

January 28, 2026

Last Update Submitted That Met QC Criteria

January 23, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18-26544

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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