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
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
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
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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