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

This study has been completed.
Sponsor:
Information provided by:
University Magna Graecia
ClinicalTrials.gov Identifier:
NCT01233206
First received: October 8, 2010
Last updated: June 9, 2011
Last verified: June 2011
  Purpose

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 Intervention Phase
Infertility
Polycystic Ovary Syndrome (PCOS)
Drug: Metformin
Drug: Placebo administration
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University Magna Graecia:

Primary Outcome Measures:
  • Rate of OHSS [ Time Frame: one month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 120
Study Start Date: May 2009
Study Completion Date: January 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01233206

Locations
Italy
Pugliese" Hospital
Catanzaro, Italy, 88100
Sponsors and Collaborators
University Magna Graecia
Investigators
Principal Investigator: Stefano Palomba University Magna Graecia
Study Chair: Fulvio Zullo University Magna Graecia
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Department of Obstetrics and Gynecology, University Magna Graecia
ClinicalTrials.gov Identifier: NCT01233206     History of Changes
Other Study ID Numbers: 04/2010
Study First Received: October 8, 2010
Last Updated: June 9, 2011
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University Magna Graecia:
PCOS
Polycystic ovary syndrome
Cancelled cycles
OHSS
Infertility

Additional relevant MeSH terms:
Infertility
Polycystic Ovary Syndrome
Syndrome
Adnexal Diseases
Cysts
Disease
Endocrine System Diseases
Genital Diseases, Female
Genital Diseases, Male
Gonadal Disorders
Neoplasms
Ovarian Cysts
Ovarian Diseases
Pathologic Processes
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014