Metformin in High Responder Polycystic Ovary Syndrome (PCOS) Patients Undergoing IVF Cycles
The use of metformin pre-treatment and co-administration was recently proposed in infertile women affected by polycystic ovary syndrome (PCOS) treated with gonadotropins.
Data from meta-analyses showed that metformin administration significantly reduced the stimulation length and the total dose of gonadotropins used in PCOS women undergoing gonadotropins stimulation for non in-vitro fertilization (IVF) cycles. On the other hand, in IVF cycles metformin was demonstrated to significantly reduce the ovarian hyperstimulation syndrome (OHSS) rate in infertile patients with PCOS treated with gonadotropins.
The metformin regulating effect on the ovarian response was also observed in a randomized controlled trial (RCT) on young non-obese insulin-resistant women with PCOS receiving gonadotropins for mono-ovulation induction. In particular, metformin increased the mono-ovulatory cycles, the duration of stimulation and the amount of gonadotropins used, while it reduced the number of dominant follicles and the estradiol (E2) levels.
The aim of the present study was to evaluate the effect of metformin administration in high responder PCOS patients undergoing gonadotropins ovarian stimulation for IVF cycles.
Polycystic Ovary Syndrome (PCOS)
Drug: Placebo administration
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Metformin Addition to Gonadotropins Ovarian Stimulation in High Responder Patients With PCOS Undergoing In-vitro Fertilization|
- Rate of OHSS [ Time Frame: one month ] [ Designated as safety issue: Yes ]
- Stimulation length [ Time Frame: one month ] [ Designated as safety issue: No ]
- Gonadotropins dose [ Time Frame: one month ] [ Designated as safety issue: No ]
- Dominant follicles on day of ovulation triggering [ Time Frame: one month ] [ Designated as safety issue: No ]
- Ovulation rate [ Time Frame: one month ] [ Designated as safety issue: No ]
- Peak estradiol levels on day of ovulation triggering [ Time Frame: one month ] [ Designated as safety issue: No ]
- Embryo quality [ Time Frame: one month ] [ Designated as safety issue: No ]
- pregnancy rate [ Time Frame: one month ] [ Designated as safety issue: No ]
- multiple pregnancy rate [ Time Frame: one month ] [ Designated as safety issue: No ]
- Live birth rate [ Time Frame: ten months ] [ Designated as safety issue: No ]
|Study Start Date:||May 2009|
|Study Completion Date:||January 2011|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
Experimental: Experimental group
Patients receiving metformin pretreatment and co-administration
Metformin pre-treatment and co-administration
Placebo Comparator: Control group
Drug: Placebo administration
Placebo pre-treatment and co-administration
Infertile young non-obese insulin-resistant patients with PCOS who had a background of the first IVF treatment cycle cancelled because of high risk for OHSS will be enrolled and randomized in two treatment arms.
In their second IVF attempt, the experimental group will receive metformin (500 mg, 3 times daily) pre-treatment for two weeks and co-administration during gonadotropins ovarian stimulation; the control group will be treated with placebo (2 cps daily) pre-treatment and co-administration by using the same schedule of the experimental group. In all patients, ovarian stimulation will be carried out with a personalized step-down gonadotropin in association with a minidose flare-up GnRH agonist protocol.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01233206
|Catanzaro, Italy, 88100|
|Principal Investigator:||Stefano Palomba||University Magna Graecia|
|Study Chair:||Fulvio Zullo||University Magna Graecia|