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

Primary Purpose

Polycystic Ovary Syndrome, Anovulation, Oligoovulation

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Metformin
Clomiphene citrate
Placebo
Sponsored by
59th Medical Wing
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Ovary Syndrome focused on measuring Polycystic Ovarian Syndrome, Chronic Anovulation, Chronic Oligoovulation, Infertility, Hyperandrogenism, Metformin, Ovulation induction

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

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.

Sites / Locations

  • Wiford Hall Medical Center

Outcomes

Primary Outcome Measures

Pregnancy Rates
Ovulation Rates

Secondary Outcome Measures

Pregnancy Outcome

Full Information

First Posted
December 18, 2006
Last Updated
December 18, 2006
Sponsor
59th Medical Wing
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1. Study Identification

Unique Protocol Identification Number
NCT00413179
Brief Title
The Effect of Metformin Added to Clomiphene Citrate on Pregnancy Rates in Hyperandrogenic, Chronic Oligoovulatory or Anovulatory Women
Official Title
The Effect of Metformin Added to Clomiphene Citrate on Pregnancy Rates in Hyperandrogenic, Chronic Oligoovulatory or Anovulatory Women: A Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
December 2006
Overall Recruitment Status
Completed
Study Start Date
December 1997 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
April 2003 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
59th Medical Wing

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome, Anovulation, Oligoovulation, Infertility, Hyperandrogenism
Keywords
Polycystic Ovarian Syndrome, Chronic Anovulation, Chronic Oligoovulation, Infertility, Hyperandrogenism, Metformin, Ovulation induction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
56 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Type
Drug
Intervention Name(s)
Clomiphene citrate
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Pregnancy Rates
Title
Ovulation Rates
Secondary Outcome Measure Information:
Title
Pregnancy Outcome

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Randal D Robinson, MD
Organizational Affiliation
Wilford Hall Medical Center and Brooke Army Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wiford Hall Medical Center
City
Lackland AFB
State/Province
Texas
ZIP/Postal Code
78236
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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