Metformin in Infertile PCOS Patients

Polycystic Ovary Syndrome Clinical Trial

Official title:

Efficacy of Long- Versus Short-term Metformin Protocol in Infertile Anovulatory PCOS Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00501904
• Other study ID #: 05/2006b
• Status: Recruiting
• Phase: Phase 4
• First received: July 12, 2007
• Last updated: December 1, 2015
• Start date: April 2012
• Est. completion date: December 2016

Study information

• Verified date: December 2015
• Source: University Magna Graecia
• Contact: Stefano Palomba, MD
• Phone: +39-0961-883234
• Email: stefanopalomba[@]tin.it
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

Metformin, an oral biguanide administrated for treating type-2 diabetes mellitus, is a safe and effective drug recently experimented also in patients with polycystic ovary syndrome (PCOS). The administration of metformin induces ovulatory cycles in CC-resistant or -nonresistant patients with PCOS, and improves the ovulation rate as an additional treatment in women who received CC.

To date, it is unknown the best protocol for metformin administration. In particular, it is not known how long patients who ovulate under metformin should continue treatment before switching to second-line ovulation induction therapy. In this regard, in a recent study by the Kaplan-Meier survival analysis we demonstrated that the first pregnancy occurred late after metformin with an estimated median of seven months.

Based on these considerations, the aim of the present study will be to evaluate the clinical efficacy of metformin according to its duration of administration in infertile PCOS patients ovulating under treatment.

Description:

Infertile PCOS patients having three ovulatory cycles under metformin, administered using tailored protocol, will be enrolled and randomized in two groups (groups A and B). Patients of group A will continue metformin administration for further three cycles followed by six months of progestogens cyclically administered, whereas patients of group B will continue metformin therapy for further nine cycles.

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 in each patient.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Polycystic ovary syndrome (using NIH criteria)

• Anovulatory infertility (using WHO criteria)

• Ovulatory cycles under metformin (three cycles)

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 drugsPrevious use of ovulation induction agents

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome

Intervention

Drug:
• Metformin

Locations

Country	Name	City	State
Italy	Pugliese Hospital	Catanzaro	Catanzaro, CZ, Italy

Sponsors (1)

Lead Sponsor	Collaborator
University Magna Graecia

Country where clinical trial is conducted

Italy, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pregnancy rate		12 months	No
Secondary	Ovulation rate Abortion rate Live-birth rate Adverse events		21 months	No