Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (PCOS) Women (OWL-PCOS)

Couples Inclusion Criteria:

• Partner with sperm concentration of >=14 million/mL in at least one ejaculate with motile sperm.
• Ability to have regular intercourse 2-3 times per week during the ovulation induction phase of study.
• At least one patent tube and normal uterine cavity as determined by sonohysterogram, hysterosalpingogram, or hysteroscopy/laparoscopy within the last 3 years, or confirmation of a intrauterine pregnancy within the past 2 years.
• No previous sterilization procedures(vasectomy, tubal ligation) that have been reversed.
• Wanting to seek pregnancy.

Inclusion Criteria:

• Chronic anovulation or oligomenorrhea defined as intermenstrual periods of >= 45 days or a total of <=8 periods per year.
• Hyperandrogenism will be an elevated total testosterone >=50 ng/dL.
• Hirsutism determined by a modified Ferriman-Gallwey Score >8.
• PCO on ultrasound (12 or more follicles measuring 2-9 mm in diameter).
• BMI >=27 to <=42.
• Normal EKG to rule out any abnormalities with the heart.

Exclusion Criteria:

• Current pregnancy.
• Patients on oral contraceptives, depo progestins, or hormonal implants.
• Patients with hyperprolactinemia defined as two prolactin levels at least one week apart >30 ng/mL.
• Patients with known 21-hydroxylase deficiency by a fasting 17-hydroxyprogesterone (17-OHP) level <2 ng/mL and ACTH stimulation test as needed, or other enzyme deficiency.
• Patients with menopausal FSH levels >20 mIU/mL.
• Patients with uncorrected thyroid disease (TSH <0.45 mIU/ML or >4.5 mIU/ML).
• Patients diagnosed with Type1 or Type II diabetes.
• Patients with liver disease defined as AST or ALT >2 times normal or total bilirubin >2.5 mg/dL.
• Patients with renal disease defined as BUN >30 mg/dL or serum creatinine >1.4 mg/dL.
• Patients with significant anemia (Hemoglobin <10 mg/dL).
• Patients with a history of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident.
• Patients with known heart disease that is likely to be exacerbated by pregnancy.
• Patients with a history of , or suspected cervical carcinoma, endometrial carcinoma, or breast carcinoma. A normal PAP smear or reassuring colposcopy based on current ACOG guidelines will be required.
• Patient with current history of alcohol abuse.
• Patients enrolled simultaneously into other investigative studies.
• Patients taking other medications know to affect reproductive function or metabolism.
• Patients with a suspected adrenal or ovarian tumor secreting androgens.
• Patients with suspected Cushing's syndrome.
• Patients who have undergone a bariatric surgery procedure in the recent past (<12 months).
• Patients with untreated poorly controlled hypertension defined as systolic blood pressure >=150 mm Hg or average diastolic >=100 mm Hg on three measurements obtained 5 minutes apart. If treated, average systolic blood pressure >= 140 mm Hg or average diastolic >= 90 mm Hg.
• Patients with medical conditions that represent contraindications to orlistat, OCP, clomiphene, and/or pregnancy.
• Patients currently participating in lifestyle intervention program (Weight Watchers, Atkins Diet, Curves) or lost more than 5% body weight within the last 6 months.