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

This study has been completed.
Sponsor:
Information provided by:
Wilford Hall Medical Center
ClinicalTrials.gov Identifier:
NCT00413179
First received: December 18, 2006
Last updated: NA
Last verified: December 2006
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Polycystic Ovary Syndrome
Anovulation
Oligoovulation
Infertility
Hyperandrogenism
Drug: Metformin
Drug: Clomiphene citrate
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: The Effect of Metformin Added to Clomiphene Citrate on Pregnancy Rates in Hyperandrogenic, Chronic Oligoovulatory or Anovulatory Women: A Randomized Trial

Resource links provided by NLM:


Further study details as provided by Wilford Hall Medical Center:

Primary Outcome Measures:
  • Pregnancy Rates
  • Ovulation Rates

Secondary Outcome Measures:
  • Pregnancy Outcome

Estimated Enrollment: 56
Study Start Date: December 1997
Estimated Study Completion Date: April 2003
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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00413179

Locations
United States, Texas
Wiford Hall Medical Center
Lackland AFB, Texas, United States, 78236
Sponsors and Collaborators
Wilford Hall Medical Center
Investigators
Principal Investigator: Randal D Robinson, MD Wilford Hall Medical Center and Brooke Army Medical Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00413179     History of Changes
Other Study ID Numbers: FWH19970383H
Study First Received: December 18, 2006
Last Updated: December 18, 2006
Health Authority: United States: Institutional Review Board

Keywords provided by Wilford Hall Medical Center:
Polycystic Ovarian Syndrome
Chronic Anovulation
Chronic Oligoovulation
Infertility
Hyperandrogenism
Metformin
Ovulation induction

Additional relevant MeSH terms:
Anovulation
Infertility
Polycystic Ovary Syndrome
Hyperandrogenism
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Genital Diseases, Male
Ovarian Cysts
Cysts
Neoplasms
46, XX Disorders of Sex Development
Disorders of Sex Development
Urogenital Abnormalities
Adrenogenital Syndrome
Congenital Abnormalities
Citric Acid
Clomiphene
Metformin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists

ClinicalTrials.gov processed this record on July 26, 2014