Metformin in High Responder Polycystic Ovary Syndrome (PCOS) Patients Undergoing IVF Cycles

Sponsor

University Magna Graecia (Other)

Overall Status

Completed

CT.gov ID

NCT01233206

Collaborator

(none)

120

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infertility Polycystic Ovary Syndrome (PCOS)	Drug: Metformin Drug: Placebo administration	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Metformin Addition to Gonadotropins Ovarian Stimulation in High Responder Patients With PCOS Undergoing In-vitro Fertilization

Study Start Date :

May 1, 2009

Actual Primary Completion Date :

Nov 1, 2010

Actual Study Completion Date :

Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental group Patients receiving metformin pretreatment and co-administration	Drug: Metformin Metformin pre-treatment and co-administration
Placebo Comparator: Control group Placebo	Drug: Placebo administration Placebo pre-treatment and co-administration

Arm

Intervention/Treatment

Experimental: Experimental group

Patients receiving metformin pretreatment and co-administration

Drug: Metformin

Metformin pre-treatment and co-administration

Placebo Comparator: Control group

Placebo

Drug: Placebo administration

Placebo pre-treatment and co-administration

Outcome Measures

Primary Outcome Measures

Rate of OHSS [one month]

Secondary Outcome Measures

Stimulation length [one month]
Gonadotropins dose [one month]
Dominant follicles on day of ovulation triggering [one month]
Ovulation rate [one month]
Peak estradiol levels on day of ovulation triggering [one month]
Embryo quality [one month]
pregnancy rate [one month]
multiple pregnancy rate [one month]
Live birth rate [ten months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

History of one previous cancelled cycle for high-risk of OHSS, or history of moderate/severe OHSS during their previous IVF cycle
Infertility
Polycystic ovary syndrome (PCOS)
insulin resistance
hyperandrogenism