Metformin Administration in Infertile Anovulatory PCOS Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00501787
Recruitment Status : Withdrawn
First Posted : July 16, 2007
Last Update Posted : April 9, 2013
Information provided by (Responsible Party):
Stefano Palomba, University Magna Graecia

July 12, 2007
July 16, 2007
April 9, 2013
January 2008
October 2012   (Final data collection date for primary outcome measure)
Ovulation rate
Same as current
Complete list of historical versions of study NCT00501787 on Archive Site
  • Adverse events
  • Adherence rate
  • Pregnancy rate
  • Abortion rate
  • Live-birth rate
Same as current
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Metformin Administration in Infertile Anovulatory PCOS Patients
Tailored Versus Non-tailored Metformin Protocol for Ovulation Induction in Infertile Anovulatory PCOS Patients. A Randomized Controlled Clinical Study

In a recent prospective study evaluating the efficacy of 1700 mg/day metformin as first-line approach for infertile anovulatory patients with PCOS, we identified predictors for metformin efficacy. Our analysis demonstrated that body mass index (BMI) and insulin resistance were the strongest predictors for both ovulation and pregnancy. In particular, adjusting the data for insulin resistance, a trend in reduced effectiveness was observed with increasing BMI. On the other hand, adjusting the data for BMI, a trend in improved efficacy was detected for higher insulin resistance degrees.

To date, no dose-finding study is currently available in literature evaluating the best dose of metformin to administer. In addition, very few data regarding the best protocol for metformin treatment also are available. However, in order to reduce drug-related side effects incidence due to start-up syndrome, metformin is generally administrated with meals at incremental weekly doses until the maximum dosage ranging from 500 to 2550 mg daily; the doses are reduced if side effects appear. This commonly accepted protocol has not been supported by scientific evidences.

The aim of the present study will be to evaluate in a clinical setting the compliance, the safety and the effectiveness of two schedules for metformin administration in infertile anovulatory PCOS patients.

Infertile anovulatory PCOS eligible patients will be enrolled and randomly allocated to receive tailored (tailored group) or non-tailored metformin treatment (non-tailored group).

Tailored metformin treatment will consist of incremental doses regimen starting from a dosage of 850 mg daily (one tablet daily) with a weekly increase up to 2550 mg daily (three tablets daily). The dosage of metformin will be reduced according to the appearance of serous or affecting compliance drug-related side effects. Conversely, non-tailored metformin treatment consisted of fixed doses regimen of 850 mg twice daily. For both groups, the treatment will be of six months.

All patients eligible will undergo baseline assessment consisting of anthropometric, hormonal, and ultrasonographic evaluations. During the study, the clinical and reproductive outcomes, and the adverse experience will be evaluated in each patient.

Data will be analyzed using the intention-to-treat principle and a P value of 0.05 or less will be considered significant. Continuous variables will be analyzed with the unpaired t test and general linear model for repeated measures analysis with Bonferroni test for the post-hoc analysis as required. For categorical variables, the Pearson chi-square and Fisher's exact tests will be used.

Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Polycystic Ovary Syndrome
Drug: Metformin
  • Active Comparator: Group B
    Intervention: Drug: Metformin
  • Active Comparator: Group A
    Intervention: Drug: Metformin
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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October 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Polycystic ovary syndrome (using NIH criteria)
  • Anovulatory infertility (using WHO criteria)

Exclusion Criteria:

  • Age <18 or >35 years
  • Severe obesity (BMI >35)
  • Neoplastic, metabolic, hepatic, and cardiovascular disorders or other concurrent medical illnesses
  • Hypothyroidism, hyperprolactinemia, Cushing's syndrome, and non-classical congenital adrenal hyperplasia Current or previous (within the last six months) use of oral contraceptives, glucocorticoids, antiandrogens, antidiabetic and anti-obesity drugs or other hormonal drugs
  • Previous use of ovulation induction agents
  • Intention to start a diet or a specific program of physical activity
  • Organic pelvic diseases
  • Previous pelvic surgery
  • Suspected peritoneal factor infertility
  • Tubal or male factor infertility or sub-fertility
Sexes Eligible for Study: Female
18 Years to 35 Years   (Adult)
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Contact information is only displayed when the study is recruiting subjects
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Stefano Palomba, University Magna Graecia
University Magna Graecia
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Principal Investigator: Stefano Palomba, MD Department of Obstetrics & Gynecology, University "Magna Graecia" of Catanzaro
Principal Investigator: Francesco Orio, MD Department of Endocrinology, University "Federico II" of Naples
Principal Investigator: Achille Tolino, MD Department of Obstetrics & Gynecology, University "Federico II" of Naples
University Magna Graecia
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP