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

Infertility Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01233206
• Other study ID #: 04/2010
• Status: Completed
• Phase: Phase 4
• First received: October 8, 2010
• Last updated: June 9, 2011
• Start date: May 2009
• Est. completion date: January 2011

Study information

• Verified date: June 2011
• Source: University Magna Graecia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: January 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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

Exclusion Criteria:

• BMI>30 kg/m2

• age >35 years

• FSH>9UI/L

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility
• Polycystic Ovary Syndrome
• Polycystic Ovary Syndrome (PCOS)

Intervention

Drug:
• Metformin
Metformin pre-treatment and co-administration
• Placebo administration
Placebo pre-treatment and co-administration

Locations

Country	Name	City	State
Italy	Pugliese" Hospital	Catanzaro

Sponsors (1)

Lead Sponsor	Collaborator
University Magna Graecia

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Palomba S, Falbo A, Orio F Jr, Manguso F, Russo T, Tolino A, Annamaria C, Dale B, Zullo F. A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination. Hum Reprod. 2005 Oct;20(10):2879-86. Epub 2005 Jun 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of OHSS		one month	Yes
Secondary	Stimulation length		one month	No
Secondary	Gonadotropins dose		one month	No
Secondary	Dominant follicles on day of ovulation triggering		one month	No
Secondary	Ovulation rate		one month	No
Secondary	Peak estradiol levels on day of ovulation triggering		one month	No
Secondary	Embryo quality		one month	No
Secondary	pregnancy rate		one month	No
Secondary	multiple pregnancy rate		one month	No
Secondary	Live birth rate		ten months	No