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

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 ofendometriosis (laparoscopy or laparotomy) or diagnosis by pathology within the last 10 years before the initial trial entry visit or documentation of ovarianendometrioma >2 cm or two or more smaller endometriomas that total >2 cm indiameter. If entry is based on the presence of an endometrioma, transvaginalultrasound evaluation must document the same unambiguous endometrioma on twoseparate occasions in more than one menstrual cycle. Images will be printed ortransmitted electronically and read centrally by investigators at Yale to assureuniform 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 embryotransfers (FET) , AMH level eligibility criteria may not be met as long as thepatient has at least one good quality blastocyst stored for the FET.

6. No known uterine cavity abnormalities at time of screening. Uterine cavityassessment by sonohysterogram or hysteroscopy within 12 months of embryo transferindicating absence of focal intracavitary pathology and hence establishing adequatecavity at the time of embryo transfer. Ultrasound or MRI features suggestive ofadenomyosis will be acceptable for inclusion. Type 3 fibroids are allowed up to 4cmsize.

7. Presence of at least one ovary with no clinically significant abnormalities otherthan endometrioma. For eligible women with evidence of a hemorrhagic ovarian cyst, arepeat US will be needed in a subsequent menstrual cycle to ensure persistent cystfor patient to be deemed eligible.

8. Negative urine or cervical swab for gonorrhea and chlamydia within 12 months ofscreening.

9. Willing and able to comply with trial procedures, including reporting of obstetricaloutcomes after delivery.

Exclusion Criteria:

1. Use of depot GnRH agonists within 6 months of study start. Use of subcutaneousantagonists or nasal agonist within 2 months of study start unless part of regularIVF or previous IUI cycle°.

2. Use of depot medroxyprogesterone acetate (MPA) (injectable) or birth controlimplants (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 combinedoral contraceptive pill, progestin-only pill, transdermal patch or contraceptivering, 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 polypsor intrauterine adhesions.

8. Abnormal cytology on a cervical screening based on the American College ofObstetricians and Gynecologists (ACOG) guidelines and patient age. (CIN1 or HPVallowed to participate in the study, CIN2 excluded unless treated and cleared, CIN3excluded).

9. History of malignancy within 5 years of the start of screening, except for treatedbasal 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 theelectronic medical record (EMR).

11. Hypersensitivity to the study drugs.

12. Planned surgical treatment of endometriosis or planned surgery in theabdominal-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 forosteoporosis or bone loss.

16. Patients with cirrhosis or abnormal LFTs per self report or documented in theelectronic medical record (EMR).

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