Pregnancy in Polycystic Ovary Syndrome II

Summary

The primary research hypothesis is that ovulation induction with an aromatase inhibitor (letrozole) is more likely to result in live birth than ovulation induction with a selective estrogen receptor modulator (clomiphene citrate) in infertile women with PCOS. A safety hypothesis will also be incorporated into the primary research hypothesis in which we hypothesize both treatments are equally safe for mother and child.

Secondary research hypotheses include:

1. Treatment with letrozole is more likely to result in singleton pregnancy compared to treatment with clomiphene citrate. Singleton pregnancy is defined as presence of a single intrauterine gestational sac with a single fetal pole and observable heart motion.
2. Treatment with letrozole will less likely result in a first trimester intrauterine fetal demise than treatment with clomiphene citrate. A first trimester IUFD is defined as a pregnancy that ends before 13 weeks gestation.
3. Treatment with letrozole is more likely to result in ovulation (increased ovulation rate) compared to treatment with clomiphene citrate. Ovulation is defined as a midluteal progesterone level ≥ 3 ng/mL.
4. The shortest time to pregnancy will be with letrozole.
5. Age, body mass index, SHBG, testosterone, LH, Anti-Mullerian Hormone (AMH), and degree of hirsutism and acne will be significant predictors of ovulation and conception regardless of treatment.
6. Improvement in SHBG, testosterone, AMH, and LH levels will be significant predictors of ovulation and conception regardless of treatment.
7. DNA polymorphisms in estrogen action genes will predict response to study drug.
8. Quality of Life will be better on letrozole than clomiphene.
9. Letrozole will be more cost effective at achieving singleton pregnancies than clomiphene.

Conditions

• Pregnancy
• Polycystic Ovary Syndrome

Interventions

DRUG

Clomiphene citrate

Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

DRUG

Letrozole

Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• Penn State University

  collaborator OTHER

• University of Colorado, Denver

  collaborator OTHER

• University of Michigan

  collaborator OTHER

• University of Pennsylvania

  collaborator OTHER

• The University of Texas Health Science Center at San Antonio

  collaborator OTHER

• University of Vermont

  collaborator OTHER

• Wayne State University

  collaborator OTHER

• Yale University

  lead OTHER

Principal Investigators

• Esther Eisenberg, MD, MPH · Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

• Nanette Santoro, MD · Albert Einstein College of Medicine

• Richard Legro, MD · Pennsylvania State University College of Medicine

• Robert Brzyski, MD, PhD · The University of Texas Health Science Center at San Antonio

• Peter Casson, MD · University of Vermont

• Michael Diamond, MD · Wayne State University

• Heping Zhang, PhD · Yale University

• Gregory M Christman, MD · University of Michigan

• Christos Coutifaris, MD · University of Pennsylvania

• William D Schlaff, MD · University of Colorado Denver Health Science Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-02-28

Primary Completion

2013-05-31

Completion

2013-05-31

Countries

• United States

Study Locations