Therapy for Infertile PCOS Patients Ovulating Under Clomiphene Citrate or Metformin - Full Text View

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:

MedlinePlus related topics: Infertility Polycystic Ovary Syndrome

Drug Information available for: Clomiphene citrate Metformin Clomiphene Sodium citrate Metformin hydrochloride Citric acid monohydrate

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:

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
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:


Polycystic Ovary Syndrome Adnexal Diseases Cysts Endocrine System Diseases Genital Diseases, Female Gonadal Disorders Neoplasms Ovarian Cysts Ovarian Diseases Clomiphene Enclomiphene Metformin Zuclomiphene	Estrogen Antagonists Estrogen Receptor Modulators Fertility Agents Fertility Agents, Female Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Hypoglycemic Agents Pharmacologic Actions Physiological Effects of Drugs Reproductive Control Agents Selective Estrogen Receptor Modulators Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015