Treatment of Infertility in Women With Polycystic Ovary Syndrome

Condition(s) targeted: Polycystic Ovary Syndrome; Infertility; Pregnancy

Intervention: metformin XR (Drug); clomiphene citrate (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: National Institute of Child Health and Human Development (NICHD)

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting up to 10% of women. The primary symptoms of PCOS are menstrual irregularities, increased body and facial hair, acne, and infertility. This study will test a combination of medications in women with PCOS to determine which works best to overcome infertility.

Official title: Pregnancy in Polycystic Ovary Syndrome: A 30 Week Double-Blind Randomized Trial of Clomiphene Citrate, Metformin XR, and Combined Clomiphene Citrate/Metformin XR For the Treatment of Infertility in Women With Polycystic Ovary Syndrome

Study design: Treatment, Randomized, Double-Blind, Active Control, Factorial Assignment, Safety/Efficacy Study

Primary outcome: Live birth rate

Secondary outcome:

singleton live birth rate

ovulation rate

cycles to first ovulation

cycles to conception

abortion rate

cycles to pregnancy

weeks from pregnancy to live birth

Detailed description: PCOS is characterized by excess circulating androgen levels and chronic anovulation. The fundamental pathophysiologic defect is unknown, but PCOS is characterized by insulin resistance and compensatory hyperinsulinemia. Improvements in insulin sensitivity in PCOS women, either through lifestyle changes or through pharmaceutical intervention, have consistently resulted in a marked improvement in the reproductive and metabolic abnormalities in PCOS. Resumption of ovulation occurs in up to 70% of women treated for PCOS. This study will evaluate the safety and effectiveness of clomiphene citrate and metformin XR in achieving a successful pregnancy in infertile PCOS women.

Women with PCOS who are seeking pregnancy will be enrolled in this study. Women will be randomized to one of three different treatment arms: A) metformin XR 1000 mg twice/day; B) clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle); or C) metformin XR 1000 mg twice/day with clomiphene citrate 50 mg/day for 5 days (day 3-7 of cycle). Women will continue on study medications for 30 weeks, 6 treatment cycles, or until they become pregnant. Progesterone levels will be drawn weekly to monitor ovulation.

Minimum age: 18 Years. Maximum age: 39 Years. Gender(s): Female.

Criteria:

Inclusion Criteria

- Eight or fewer menstrual cycles in the past year or intermenstrual periods of 45 days

or longer

- Elevated testosterone level

- Good general health

- Sperm concentration in partner of 20 million/ml or greater

- Ability to have intercourse 2-3 times per week

- One functional fallopian tube and normal uterine cavity

University of Alabama at Birmingham, Birmingham, Alabama 35249, United States

Stanford University, Stanford, California 94305, United States

University of California at San Diego, La Jolla, California 92037, United States

University of Colorado, Aurora, Colorado 80045, United States

Wayne State, Detroit, Michigan 48201, United States

University of Medicine and Dentistry New Jersey, Newark, New Jersey 07103, United States

University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Penn State, Hershey, Pennsylvania 17033, United States

Baylor College of Medicine, Houston, Texas 77030, United States

University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States

Virginia Commonwealth University, Richmond, Virginia 23298, United States

Related publications:

Myers ER, Silva SG, Hafley G, Kunselman AR, Nestler JE, Legro RS; National Institute of Child Health and Human Development Reproductive Medicine Network. Estimating live birth rates after ovulation induction in polycystic ovary syndrome: sample size calculations for the pregnancy in polycystic ovary syndrome trial. Contemp Clin Trials. 2005 Jun;26(3):271-80.

Starting date: November 2002
Ending date: February 2006
Last updated: September 28, 2007