Metformin in Infertile PCOS Patients
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Efficacy of Long- Versus Short-term Metformin Protocol in Infertile Anovulatory PCOS Patients|
- Pregnancy rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Ovulation rate Abortion rate Live-birth rate Adverse events [ Time Frame: 21 months ] [ Designated as safety issue: No ]
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Active Comparator: Group A
Active Comparator: Group B
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.
|Contact: Stefano Palomba, MDfirstname.lastname@example.org|
|Catanzaro, Catanzaro, CZ, Italy, Italy, 88100|
|Contact: Ingrid Tomaino, MD +39-0961965097 email@example.com|
|Principal Investigator: Stefano Palomba, MD|
|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|