Therapy for Infertile PCOS Patients Ovulating Under Clomiphene Citrate or Metformin

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 ]

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 35 Years (Adult)
Sexes 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

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Palomba S, Orio F Jr, Falbo A, Russo T, Tolino A, Zullo F. Clomiphene citrate versus metformin as first-line approach for the treatment of anovulation in infertile patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007 Sep;92(9):3498-503. Epub 2007 Jun 26.

Palomba S, Orio F Jr, Falbo A, Manguso F, Russo T, Cascella T, Tolino A, Carmina E, Colao A, Zullo F. Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005 Jul;90(7):4068-74. Epub 2005 Apr 19.

Palomba S, Falbo A, Orio F Jr, Manguso F, Russo T, Tolino A, Annamaria C, Dale B, Zullo F. A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination. Hum Reprod. 2005 Oct;20(10):2879-86. Epub 2005 Jun 15.

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

Keywords provided by Stefano Palomba, 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; Metformin; Citric Acid; Clomiphene; Enclomiphene

Zuclomiphene; Hypoglycemic Agents; Physiological Effects of Drugs; Anticoagulants; 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