The investigators aim is to conduct a prospective un-blinded pilot study of premenopausal women diagnosed with Polycystic Ovarian Syndrome (PCOS), defined using criteria developed at the 1990 NICHD conference on PCOS, undergoing treatment for ovulation induction with Metformin. We propose that improving insulin sensitivity with use of Metformin in women diagnosed with PCOS has facilitatory influences on the uterine endometrium.

Endometrial assessments are proposed following three month and then nine month treatment with metformin; expression of specified markers at respective time points will be compared to baseline.

Visit 1: Screening

• Signed informed consent
• Comprehensive history intake
• Physical exam: Vital signs, height, weight, waist circumferences, waist : hip ratio
• Urine pregnancy test
• Subjects provided with a 10 day supply of vaginal progesterone and EMBx will be scheduled between days 6-8 of progesterone use.

Visit 2: Baseline

• Urine pregnancy test
• Endometrium thickness will be measured via transvaginal ultrasound
• EMBx: sample of endometrial tissue will be sent for histopathology to rule out endometrial hyperplasia or cancer
• 20cc blood
• Metformin prescription and dispensing will be as per clinical care.
• Women will be advised to use barrier method of contraception (ie; condoms, contraceptive jellies or foam, sponge, diaphragm, or cervical cap) for the duration of the study.

Visits 3 and 5 (Weeks 8-10 and 30-34, respectively)

• Urine pregnancy test
• A 10 day course of vaginal progesterone to allow scheduling of EMBx's time points specified under visit 1

Visits 4 and 6 (Weeks 12 ± 1 week and 36 ± 1 week respectively)

- The procedure specified for baseline (Visit 2) will be repeated.

Inclusion Criteria:

• Premenopausal between 18-42 years of age
• Diagnosed with PCOS as defined by chronic oligo- or amenorrhea (8 menstrual periods annually); biochemical hyperandrogenemia (elevated total or free testosterone) and /or clinical hyperandrogenism (excessive facial hair &/or acne); exclusion of common medical disorders (normal thyroid function tests and serum prolactin and exclusion of 21-hydroxylase deficiency by a fasting 17-hydroxyprogesterone <200 ng/dl).
• Acceptable health on the basis of interview, medical history, physical examination, and laboratory tests (CBC, SMA20, urinalysis) performed within the past 6 months
• Able to provide signed informed consent
• Able to comply with study requirements
• Willing to delay the start of clinically prescribed metformin treatment

Exclusion Criteria:

• Known diabetics or those with clinically significant and known pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, neoplastic and malignant disease (other than non-melanoma skin cancer)
• Current use of hormonal contraceptives
• Seeking pregnancy; use of fertility drugs within 6 months of study
• Current or recent (within 3 months) use of metformin
• Ingestion of any investigational drug within two months prior to study onset
• Evidence of endometrial hyperplasia or cancer upon baseline EMBx

Women will be recruited from the multi-physician Yale Reproductive Endocrinology clinical practice and Yale Fertility Center. Metformin is a routinely employed therapeutic strategy utilized for managing PCOS by practitioners at YFC. Almost 1/3 of the patients with PCOS are not interested in pursuing fertility in the immediate future and it is these patients who will be offered participation in the trial.