The goal of this three-armed randomized controlled trial is to establish the relative roles of treatment of hyperandrogenism versus obesity (as the largest modifiable factor contributing to insulin resistance) in treating infertility and improving pregnancy outcomes among obese PCOS women. The investigators hypothesize that the key to restoring ovulation leading to live birth is to correct hyperandrogenism with oral contraceptive pills, but the key to avoiding later pregnancy complications is to improve insulin sensitivity with weight loss.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility among women, and women with PCOS are at increased risk for pregnancy complications such as gestational diabetes and pre-eclampsia. Both hyperandrogenism (HA) and obesity exacerbated insulin resistance (IR) are characteristics of the syndrome, and are targets for treatment, but which should be the predominant focus is still unknown. Phase 1 of this study will be a randomized trial of three preconception interventions in infertile women with PCOS. The first arm will be a combined intervention of medication, meal replacements, and lifestyle modification to improve IR. Orlistat is a gastric lipase inhibitor that reduces the absorption of fat contained in a meal by about 30%. The second arm will be the use of a continuous OCP for 4 months to improve HA. Lo-Estrin 1/20 will be used in a continuous method for 4 months to suppress the ovary. The third arm is the combination of both to improve HA an IR. Phase II of this study will involve ovulation induction with clomiphene citrate with hopeful outcome of pregnancy. Finally, Phase III involve following the pregnancies for outcomes and complications.

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.