Therapy for Infertile PCOS Patients Ovulating Under Clomiphene Citrate or Metformin

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: NCT00502229
Recruitment Status : Withdrawn
First Posted : July 17, 2007
Last Update Posted : April 9, 2013
Information provided by (Responsible Party):
Stefano Palomba, University Magna Graecia

Brief Summary:

Several data demonstrated that both clomiphene citrate (CC) and metformin are two safe and valid first-step options to induce ovulation in infertile anovulatory PCOS patients. Notwithstanding a high percentage of patients ovulate under treatment, only ~40% and 60% of subjects obtain a pregnancy after CC and metformin, respectively.

For these patients, controlled ovarian stimulation (COS) followed by intrauterine insemination (IUI) could be the next therapeutic step before assisted reproductive techniques since IUI improves significantly the fertility in couples with unexplained infertility. Furthermore, to date it is not defined if COS should be obtained using the same ovulatory agent (CC or metformin) or switching the treatment to gonadotropins.

In this view, the aim of the present study will be to evaluate the best management of infertile PCOS patients ovulating after CC or metformin.

Condition or disease Intervention/treatment Phase
Polycystic Ovary Syndrome Infertility Drug: Clomiphene citrate, metformin, highly purified urinary FSH Phase 4

Detailed Description:

Infertile PCOS patients who ovulated under CC or metformin without pregnancy achievement will be enrolled and treated with three trials of COS plus IUI. All patients will be randomly allocated into two different groups (groups A and B). In group A, COS will be obtained using the same ovulatory agent (CC or metformin) employed in the previous ovulatory cycles, whereas in group B using gonadotropins in a low-dose step-up regimen.

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 and the will be analyzed also categorizing the patients according to ovulatory agent used for COS (CC or metformin).

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. Cumulative pregnancy rate, our primary end-point, will be calculated by the Kaplan-Maier method, and the differences between the two groups will be assessed with the log-rank test. Cox proportional-hazards model will be used to calculate the hazard ratio for new pregnancy in both groups.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: What is the Following Step to Improve Fertility in Infertile PCOS Patients Ovulating Under Clomiphene Citrate or Metformin? A Randomized Controlled Clinical Study.
Study Start Date : January 2010
Actual Primary Completion Date : January 2011

Arm Intervention/treatment
Active Comparator: Group A
Continuing treatment
Drug: Clomiphene citrate, metformin, highly purified urinary FSH
Active Comparator: Group B
Drug: Clomiphene citrate, metformin, highly purified urinary FSH

Primary Outcome Measures :
  1. Pregnancy rate [ Time Frame: one year ]

Secondary Outcome Measures :
  1. Ovulation rate Abortion rate Live-birth rate Adverse events [ Time Frame: one year ]

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00502229

Pugliese Hospital
Catanzaro, Catanzaro, CZ, Italy, 88100
Sponsors and Collaborators
University Magna Graecia
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

Responsible Party: Stefano Palomba, Associate Professor, University Magna Graecia Identifier: NCT00502229     History of Changes
Other Study ID Numbers: 05/2006c
First Posted: July 17, 2007    Key Record Dates
Last Update Posted: April 9, 2013
Last Verified: April 2013

Keywords provided by Stefano Palomba, University Magna Graecia:
Clomiphene citrate
Controlled overian stimulation
Polycystic ovary syndrome

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Genital Diseases, Male
Genital Diseases, Female
Ovarian Cysts
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Citric Acid
Hypoglycemic Agents
Physiological Effects of Drugs
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Selective Estrogen Receptor Modulators