Pre-IVF Treatment With a GnRH Antagonist in Women With Endometriosis (PREGnant)
- Study HIC#:2000027121
- Last Updated:01/28/2022
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.
- Age18 years - 38 years
- GenderFemale only
- Start Date12/01/2021
- End Date10/31/2023
Trial Purpose and Description
Infertility is a common complication of endometriosis; while IVF successfully treats endometriosis-associated infertility, pregnancy rates are diminished compared to other etiologies of infertility. The study's long- term objectives are to better identify and treat endometriosis related infertility. 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. The use of gonadotropin releasing hormone (GnRH) agonist prior to IVF has been suggested to improve success, however studies have been small and rarely reported live birth rates. Further, use of this approach is limited by the long treatment time required. Recent approval of an oral GnRH antagonist for endometriosis provides a novel option for women with endometriosis who are undergoing IVF. This agent avoids parenteral administration and the prolonged delay in initiation of action as was seen with GnRH agonists. There have been no studies on the efficacy of GnRH antagonists for the treatment of endometriosis-related infertility. The investigators propose a 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 have also recently demonstrated aberrant microRNAs in the circulation of women with endometriosis, a panel of which investigators have subsequently validated as a biomarker with high sensitivity and specificity for the detection of active disease. It is secondarily proposed that disease biomarkers will identify women who will benefit from GnRH antagonist pre-treatment, allowing a precision medicine approach to endometriosis-related infertility. The proposed study is significant due to the common occurrence of both infertility and endometrioses as well as the lack of precision in both diagnosis and therapy. The investigators use an innovative approach to identify endometriosis as well as a novel intervention designed to improve the prognosis of women with endometriosis undergoing IVF.
- Women who plan to undergo IVF for treatment of infertility.
- Age ≥18 and <38 years at time of signing informed consent.
- 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.
- Body mass index (BMI) of 18-40 kg/m2 (both inclusive) at screening.
- AMH > 0.8 ng/ml, resulted within 6 months of planned IVF cycle start.
- 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
- 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.
- Negative urine or cervical swab for gonorrhea and chlamydia within 12 months of screening.
- Willing and able to comply with trial procedures, including reporting of obstetrical outcomes after delivery.
- Use of GnRH agonists or antagonists within 6 months of study start, unless the antagonist was a part of a regular IVF cycle.
- Use of depot medroxyprogesterone acetate (MPA) or birth control implants (e.g. Implanon® or Nexplanon®) within 10 months of study start.
- Continuous use of oral progestins (MPA, NETA) within 3 months of study start.
- 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.
- Pregnancy greater than 8 weeks in length within the last 6 months.
- Number of previous IVF/ICSI attempts ≥3
- Presence of hydrosalpinx measuring >2cm on ultrasound, untreated endometrial polyps or intrauterine adhesions.
- Abnormal cytology on a pap smear within last year. (CIN1 or HPV okay, CIN2 excluded unless treated and cleared, CIN3 excluded).
- History of malignancy within 5 years of the start of screening, except for treated basal cell carcinoma and squamous cell carcinoma of the skin.
- Any suicide attempts in last 1 year.
- Hypersensitivity to the study drugs.
- Planned surgical treatment of endometriosis or planned surgery in the abdominal-pelvic area within the duration of the trial.
- Untreated abnormal prolactin or TSH
- Any conditions that preclude pregnancy. -