Therapy for Infertile PCOS Patients Ovulating Under Clomiphene Citrate or Metformin

Sponsor

University Magna Graecia (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00502229

Collaborator

(none)

Enrollment

Location

Arms

Study Details

Study Description

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 Design

Study Type:

Interventional

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 :

Jan 1, 2010

Actual Primary Completion Date :

Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Pregnancy rate [one year]

Secondary Outcome Measures

Ovulation rate Abortion rate Live-birth rate Adverse events [one year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	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