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Therapy for Infertile PCOS Patients Ovulating Under Clomiphene Citrate or Metformin

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Stefano Palomba, University Magna Graecia
ClinicalTrials.gov Identifier:
NCT00502229
First received: July 12, 2007
Last updated: April 5, 2013
Last verified: April 2013
History of Changes
  Purpose

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 Intervention Phase
Polycystic Ovary Syndrome
Infertility
 Drug: Clomiphene citrate, metformin, highly purified urinary FSH
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Magna Graecia:

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

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

Enrollment: 0
Study Start Date: January 2010
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group A
Continuing treatment
 Drug: Clomiphene citrate, metformin, highly purified urinary FSH
Active Comparator: Group B
Gonadotrophins
 Drug: Clomiphene citrate, metformin, highly purified urinary FSH

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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00502229

Locations
Italy
Pugliese Hospital
Catanzaro, Catanzaro, CZ, Italy, 88100
Sponsors and Collaborators
University Magna Graecia
Investigators
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
  More Information

Publications:

Responsible Party: Stefano Palomba, Associate Professor, University Magna Graecia
ClinicalTrials.gov Identifier: NCT00502229     History of Changes
Other Study ID Numbers: 05/2006c
Study First Received: July 12, 2007
Last Updated: April 5, 2013
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University Magna Graecia:
Clomiphene citrate
Controlled overian stimulation
Infertility
 Metformin
Polycystic ovary syndrome
Treatment

Additional relevant MeSH terms:
Infertility
Polycystic Ovary Syndrome
Genital Diseases, Male
Genital Diseases, Female
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
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
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Selective Estrogen Receptor Modulators
Hypoglycemic Agents

ClinicalTrials.gov processed this record on June 18, 2013