Metformin in Infertile PCOS Patients

Overview[ - collapse ][ - ]

Purpose 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.
ConditionPolycystic Ovary Syndrome
InterventionDrug: Metformin
PhasePhase 4
SponsorUniversity Magna Graecia
Responsible PartyUniversity Magna Graecia
ClinicalTrials.gov IdentifierNCT00501904
First ReceivedJuly 12, 2007
Last UpdatedApril 5, 2013
Last verifiedApril 2013

Tracking Information[ + expand ][ + ]

First Received DateJuly 12, 2007
Last Updated DateApril 5, 2013
Start DateApril 2012
Estimated Primary Completion DateJune 2014
Current Primary Outcome MeasuresPregnancy rate [Time Frame: 12 months] [Designated as safety issue: No]
Current Secondary Outcome MeasuresOvulation rate Abortion rate Live-birth rate Adverse events [Time Frame: 21 months] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleMetformin in Infertile PCOS Patients
Official TitleEfficacy of Long- Versus Short-term Metformin Protocol in Infertile Anovulatory PCOS Patients
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.
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 TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionPolycystic Ovary Syndrome
InterventionDrug: Metformin
Study Arm (s)
  • Active Comparator: Group A
    Short protocol
  • Active Comparator: Group B
    Long protocol

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment20
Estimated Completion DateJune 2014
Estimated Primary Completion DateDecember 2013
Eligibility Criteria
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
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Stefano Palomba, MD
+39-0961-883234
stefanopalomba@tin.it
Location CountriesItaly

Administrative Information[ + expand ][ + ]

NCT Number NCT00501904
Other Study ID Numbers05/2006b
Has Data Monitoring CommitteeYes
Information Provided ByUniversity Magna Graecia
Study SponsorUniversity Magna Graecia
CollaboratorsNot Provided
Investigators Principal Investigator: Stefano Palomba, MD Department of Obstetrics & Gynecology, University "Magna Graecia" of CatanzaroPrincipal Investigator: Francesco Orio, MD Department of Endocrinology, University "Federico II" of NaplesPrincipal Investigator: Achille Tolino, MD Department of Obstetrics & Gynecology, University "Federico II" of Naples
Verification DateApril 2013

Locations[ + expand ][ + ]

Pugliese Hospital
Catanzaro, Catanzaro, CZ, Italy, Italy, 88100
Contact: Ingrid Tomaino, MD | +39-0961965097 | angela.falbo@libero.it
Principal Investigator: Stefano Palomba, MD
Recruiting