The Effect of Metformin Added to Clomiphene Citrate on Pregnancy Rates in Hyperandrogenic, Chronic Oligoovulatory or Anovulatory Women

December 18, 2006 updated by: 59th Medical Wing

The Effect of Metformin Added to Clomiphene Citrate on Pregnancy Rates in Hyperandrogenic, Chronic Oligoovulatory or Anovulatory Women: A Randomized Trial

The purpose of our study was to conduct a placebo controlled, double-blind randomized trial in chronic oligoovulatory or anovulatory , hyperandrogenic, infertility patients comparing the effects of adjuvant metformin plus clomiphene citrate to clomiphene citrate plus placebo on pregnancy rates and ovulation rates. We hypothesized that combining metformin with clomiphene citrate would result in higher ovulation and pregnancy rates in hyperandrogenic women who have chronic oligoovulation or anovulation as the sole etiology for their infertility and who have unknown responsiveness to clomiphene citrate.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Women with polycystic ovary syndrome (PCOS), defined as chronic oligoovulation or anovulation and hyperandrogenism, are primarily treated with clomiphene citrate as first line therapy if they desire pregnancy. However, women with PCOS have lower than expected pregnancy rates in response to clomiphene citrate. Approximately 20% of women with PCOS are resistant to clomiphene citrate. Subjects with chronic oligoovulation or anovulation and hyperandrogenism will ovulate 80% of the time, but pregnancy occurs in only 40%. The ideal initial treatment regimen for women with PCOS who desire pregnancy has not been determined.

Metformin (Glucophage; Bristol-Myers Squibb, Princeton, NJ) is an insulin sensitizer and lowers serum insulin and androgen levels. Numerous case studies, case series, retrospective studies, and non-placebo controlled prospective studies, have suggested an improvement in insulin sensitivity, spontaneous menses, ovulatory response and pregnancies when metformin was given alone or prior to initiation of ovulation inducing agents in women with chronic anovulation and hyperandrogenism.

However, there has been conflicting evidence in the literature regarding the effect of metformin alone or in combination with ovulation inducing agents regarding ovulation and pregnancy rates in prospective, randomized trials. Therefore, it remains unknown if the use of metformin plus clomiphene citrate in non-selected, infertility patients with PCOS improves ovulation and pregnancy rates compared to the use of clomiphene citrate alone.

Women with a history of infertility and diagnosed with hyperandrogenic, oligoovulatory or anovulatory cycles as the sole etiology for their infertility were randomized to receive clomiphene citrate 50 mg days 5-9, plus metformin 500 mg three times daily versus clomiphene plus placebo. The dose of clomiphene was increased up to a maximum dose of 250 mg in a step-wise fashion until ovulation was confirmed with an ovulation predictor kit. Once ovulation was confirmed the subjects continued the ovulatory dose of clomiphene for 6 ovulatory cycles or until conception. Metformin or placebo was started on cycle day one and discontinued 8 days after the LH surge and/or by cycle day 21. A positive HCG, ovulation rates and pregnancy outcome were the outcome measures.

Study Type

Interventional

Enrollment

56

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Lackland AFB, Texas, United States, 78236
        • Wiford Hall Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Married
  • Hyperandrogenic women 18-40 years old who desired fertility and who demonstrated chronic anovulation or oligoovulation
  • Had patent fallopian tubes and whose partners had normal semen analyses were eligible for enrollment in the study.

Exclusion Criteria:

  • Androgen secreting tumours
  • Diabetes mellitus
  • Thyroid abnormalities
  • Hyperprolactinemia
  • Adult onset congenital adrenal hyperplasia
  • Diminished ovarian reserve
  • Subjects who used hormonal medications two months prior to the start of the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Pregnancy Rates
Ovulation Rates

Secondary Outcome Measures

Outcome Measure
Pregnancy Outcome

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

59th Medical Wing

Investigators

  • Principal Investigator: Randal D Robinson, MD, Wilford Hall Medical Center and Brooke Army Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 1997

Primary Completion

December 7, 2022

Study Completion

April 1, 2003

Study Registration Dates

First Submitted

December 18, 2006

First Submitted That Met QC Criteria

December 18, 2006

First Posted (Estimate)

December 19, 2006

Study Record Updates

Last Update Posted (Estimate)

December 19, 2006

Last Update Submitted That Met QC Criteria

December 18, 2006

Last Verified

December 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FWH19970383H

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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