Oral GnRH antagonist treatment for women with endometriosis undergoing IVF

Pre-IVF Treatment With a GnRH Antagonist in Women With Endometriosis - A Prospective Clinical Trial

This study is testing if a new oral medication can help women with endometriosis have more successful pregnancies through IVF compared to those who don’t take the medication.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 297 (estimated)
• Ages: 18 Years to 40 Years
• Sex: Female
• Sponsor: Yale University (Academic / other)
• Locations: 5 sites (Aurora, Colorado and 4 other locations)
• Trial ID: NCT06375811 on ClinicalTrials.gov

What this trial studies

This Phase 3 clinical trial investigates the effects of an oral GnRH antagonist on live birth rates in women with endometriosis who are preparing for in vitro fertilization (IVF). The study aims to determine if pre-treatment with this medication can improve outcomes compared to those who do not receive the pre-treatment. Participants will be randomized to receive either the GnRH antagonist or a placebo, with the primary outcome being the rate of live births. The trial seeks to address the challenges of infertility associated with endometriosis and provide a new treatment option that avoids the limitations of previous therapies.

Who should consider this trial

Good fit: Ideal candidates include women aged 18 to 39 with a documented diagnosis of endometriosis who are planning to undergo IVF.

Not a fit: Patients who are outside the age range or do not have a confirmed diagnosis of endometriosis may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve live birth rates for women with endometriosis undergoing IVF.

How similar studies have performed: While previous studies have explored GnRH agonists, this is one of the first to evaluate the efficacy of GnRH antagonists specifically for endometriosis-related infertility.

Eligibility criteria

Inclusion Criteria:

1. Women who plan to undergo IVF for treatment of infertility.
2. Age ≥18 and \<40 years at time of egg retrieval or signing informed consent.
3. Documentation of diagnosis of endometriosis by surgical visualization of endometriosis (laparoscopy or laparotomy) or diagnosis by pathology within the last 10 years before the initial trial entry visit or documentation of ovarian endometrioma \>2 cm or two or more smaller endometriomas that total \>2 cm in diameter. If entry is based on the presence of an endometrioma, transvaginal ultrasound evaluation must document the same unambiguous endometrioma on two separate occasions in more than one menstrual cycle. Images will be printed or transmitted electronically and read centrally by investigators at Yale to assure uniform diagnostic criteria (classic ground glass appearance) are applied.
4. Body mass index (BMI) of 18-40 kg/m2 (both inclusive) at screening.
5. AMH \> 0.5ng/ml, within 12 months of a fresh IVF cycle start. For frozen embryo transfers (FET) , AMH level eligibility criteria may not be met as long as the patient has at least one good quality blastocyst stored for the FET.
6. No known uterine cavity abnormalities at time of screening. Uterine cavity assessment by sonohysterogram or hysteroscopy within 12 months of embryo transfer indicating absence of focal intracavitary pathology and hence establishing adequate cavity at the time of embryo transfer. Ultrasound or MRI features suggestive of adenomyosis will be acceptable for inclusion. Type 3 fibroids are allowed up to 4cm size.
7. Presence of at least one ovary with no clinically significant abnormalities other than endometrioma. For eligible women with evidence of a hemorrhagic ovarian cyst, a repeat US will be needed in a subsequent menstrual cycle to ensure persistent cyst for patient to be deemed eligible.
8. Negative urine or cervical swab for gonorrhea and chlamydia within 12 months of screening.
9. Willing and able to comply with trial procedures, including reporting of obstetrical outcomes after delivery.

Exclusion Criteria:

1. Use of depot GnRH agonists within 6 months of study start. Use of subcutaneous antagonists or nasal agonist within 2 months of study start unless part of regular IVF or previous IUI cycle°.
2. Use of depot medroxyprogesterone acetate (MPA) (injectable) or birth control implants (e.g., Implanon® or Nexplanon®) within 6 months of study start°.
3. Continuous use of oral progestins (MPA, NETA) within 1 month of study start°.
4. Use of aromatase inhibitors, danazol or hormonal contraceptives (Including combined oral contraceptive pill, progestin-only pill, transdermal patch or contraceptive ring, or double barrier contraception) within 1 month of study start.
5. Pregnancy greater than 8 weeks in length within the last 6 months.
6. Number of previous IVF/ICSI attempts ≥3 unsuccessful (negative pregnancy test).
7. Presence of hydrosalpinx measuring \>2cm on ultrasound, untreated endometrial polyps or intrauterine adhesions.
8. Abnormal cytology on a cervical screening based on the American College of Obstetricians and Gynecologists (ACOG) guidelines and patient age. (CIN1 or HPV allowed to participate in the study, CIN2 excluded unless treated and cleared, CIN3 excluded).
9. History of malignancy within 5 years of the start of screening, except for treated basal cell carcinoma and squamous cell carcinoma of the skin.
10. Any thoughts of suicide in the last 12 months per self-report, or documented in the electronic medical record (EMR).
11. Hypersensitivity to the study drugs.
12. Planned surgical treatment of endometriosis or planned surgery in the abdominal-pelvic area within the duration of the trial.
13. Untreated abnormal prolactin or TSH
14. Any conditions that preclude pregnancy.
15. Patients with a known history of a low-trauma fracture or other risk factors for osteoporosis or bone loss.
16. Patients with cirrhosis or abnormal LFTs per self report or documented in the electronic medical record (EMR).

    * Exclusion criteria number 1,2, and 3 are not required to be met by individuals in the standard of care arm of the study. The study team will collect the information regarding whether the subject has used these drugs in the aforementioned time frame using the concomitant medication log and the individual will be allowed to participate in the study under the standard of care arm only.

Where this trial is running

Aurora, Colorado and 4 other locations

• University of Colorado Department of Obstetrics & Gynecology — Aurora, Colorado, United States (Recruiting)
• Yale School of Medicine Dept.of Ob/Gyn & Reproductive Sciences — New Haven, Connecticut, United States (Recruiting)
• Northwestern University Department of Obstetrics and Gynecology — Chicago, Illinois, United States (Recruiting)
• Johns Hopkins, Division of Reproductive Science and Women's Health Research — Baltimore, Maryland, United States (Recruiting)
• Duke Fertility — Morrisville, North Carolina, United States (Recruiting)

Study contacts

• Principal investigator: Hugh Taylor, MD — Yale University
• Study coordinator: Heping Zhang, PhD

Conditions Infertility; Endometriosis