Pre-IVF Treatment With a GnRH Antagonist in Women With Endometriosis

• Status: Recruiting
• Trial end date: 2024-10-01
• Target enrollment: 0
• Participant gender: Female

Summary

A Phase 3 randomized clinical trial of oral GnRH antagonist pre-treatment for women with endometriosis who are undergoing IVF, with a primary outcome of live birth rate. The investigators' central hypothesis is that in infertile woman with endometriosis undergoing in vitro fertilization-embryo transfer (IVF-ET), live birth rates will improve in those pretreated with GnRH antagonist compared to placebo.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Northwestern University; University of Colorado, Denver; University of North Carolina

Criteria

Inclusion Criteria:

1. Women who plan to undergo IVF for treatment of infertility.

2. Age ≥18 and <38 years at time of 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 > 0.8 ng/ml, resulted within 6 months of planned IVF cycle start.

6. Uterine cavity assessment by sonohysterogram or hysteroscopy within 6 months indicating absence of focal intracavitary pathology and hence adequacy for embryo transfer. Ultrasound 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 subjects 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 GnRH agonists or antagonists within 6 months of study start, unless the antagonist was a part of a regular IVF cycle.

2. Use of depot medroxyprogesterone acetate (MPA) or birth control implants (e.g. Implanon® or Nexplanon®) within 10 months of study start.

3. Continuous use of oral progestins (MPA, NETA) within 3 months 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) 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

7. Presence of hydrosalpinx measuring >2cm on ultrasound, untreated endometrial polyps or intrauterine adhesions.

8. Abnormal cytology on a pap smear within last year. (CIN1 or HPV okay, 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 suicide attempts in last 1 year.

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. -