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.”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Drug: Clomiphene citrate, metformin, highly purified urinary FSH

Primary Measures

• Pregnancy rate
  • Time Frame: one year
    

Secondary Measures

• Ovulation rate Abortion rate Live-birth rate Adverse events
  • Time Frame: one year
    

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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 35 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University Magna Graecia

Overall Clinical Trial Officials and Contacts

Stefano Palomba, MD Principal Investigator Department of Obstetrics & Gynecology, University “Magna Graecia” of Catanzaro  

Overall Contact: Stefano Palomba, MD +39-0961-883234 stefanopalomba@tin.it

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00502229

Study ID Number: 05/2006c

ClinicalTrials.gov Identifier: NCT00502229

Health Authority: Italy: The Italian Medicines Agency