Endometrial Effects of Metformin Action in Women With Polycystic Ovarian Syndrome (PCOS)
Condition: Polycystic Ovarian Syndrome
MeSH terms: Polycystic Ovary Syndrome; Syndrome
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Endometrin (progesterone 100mg vaginal inserts); Metformin
Intervention type(s): Drug; Drug
Intervention description(s): once a day, 6-8 days as specified (prior to each EMBx); per clinical care guidelines
Intervention MeSH terms: Metformin; Progesterone
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        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.
      
Biospecimen description: 
      blood, endometrium tissue biopsy
    
Keywords: Polycystic Ovarian Syndrome (PCOS); Metformin; Endometrin