Metformin in Infertile PCOS Patients

Sponsor

University Magna Graecia (Other)

Overall Status

Unknown status

CT.gov ID

NCT00501904

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome	Drug: Metformin	Phase 4

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2012

Anticipated Primary Completion Date :

Jun 1, 2016

Anticipated Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group A Short protocol	Drug: Metformin
Active Comparator: Group B Long protocol	Drug: Metformin

Arm

Intervention/Treatment

Active Comparator: Group A

Short protocol

Drug: Metformin

Active Comparator: Group B

Long protocol

Drug: Metformin

Outcome Measures

Primary Outcome Measures

Pregnancy rate [12 months]

Secondary Outcome Measures

Ovulation rate Abortion rate Live-birth rate Adverse events [21 months]

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)
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pugliese Hospital	Catanzaro	Catanzaro, CZ, Italy	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