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Metformin in Step-down Regimen Versus the Conventional Low Dose Step-up Protocol in Patients With Polycystic Ovary Syndrome Undergoing in Vitro Fertilization

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Stefano Palomba, University Magna Graecia
ClinicalTrials.gov Identifier:
NCT01438190
First received: September 19, 2011
Last updated: April 5, 2013
Last verified: April 2013
History of Changes
  Purpose

Because many women with Polycystic Ovary Syndrome (PCOS) are very sensitive to the use of gonadotropins, several strategies have been proposed to reduce the risk of Ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies.

The low dose step-up protocol and the step-down protocols in PCOS patients have been described in literature.

The step-down regimen is designed to achieve the follicle stimulating hormone (FSH) threshold through a loading dose of FSH with a subsequent stepwise reduction as soon as follicular development is observed on ultrasound. On the contrary the step-up regimen is based upon the principle of a stepwise increase in FSH supply to determine the FSH threshold for follicular development. After commencement of gonadotropin administration, if follicle development is not observed on ultrasound after 1 week, an increase in the dose is recommended. Once follicle growth is observed, the same FSH dose is maintained until follicular selection is achieved.

Preliminary studies report that both step-up and step-down regimens achieve similar high rates of monofollicular development. However, the largest study published so far has shown that the step-up regimen is safer in terms of monofollicular development.

Recent data demonstrate that metformin administration in infertile PCOS patients who are at high-risk for OHSS reduces the incidence and severity of OHSS during gonadotropin ovarian stimulation in a step-down regimen for in vitro fertilization (IVF) programs.

The aim of the present study will be to compare the conventional low dose step-up protocol and the combined protocol consisting in metformin and gonadotropin step-down regimen.


Condition Intervention Phase
Infertility
PCOS
 Drug: Metformin, gonadotropins in step-down regimen
Drug: Placebo, gonadotropins in step-up regimen
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Prevention
Official Title: A Comparison Study of a Novel Stimulation Protocol With Metformin in Step-down Regimen and the Conventional Low Dose Step-up Protocol in Patients With Polycystic Ovary Syndrome Undergoing in Vitro Fertilization

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Magna Graecia:

Primary Outcome Measures:
  • OHSS rate [ Time Frame: one month ] [ Designated as safety issue: Yes ]
    Ovarian hyperstimulation syndrome


Secondary Outcome Measures:
  • cancellation rate [ Time Frame: one month ] [ Designated as safety issue: Yes ]
    rate of cancelled cycle for high risk of OHSS or low response

  • pregnancy rate [ Time Frame: one month ] [ Designated as safety issue: No ]
  • live-birth rate [ Time Frame: nine months ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: June 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental
Metformin plus step-down protocol
 Drug: Metformin, gonadotropins in step-down regimen
Metformin 850 mg cps, two cps daily for 12 weeks. gonadotropins 75IU f, step-down regimen, starting dose of 225 IU daily.
Active Comparator: Control
Placebo and step-up protocol
 Drug: Placebo, gonadotropins in step-up regimen
Placebo cps, two cps daily. Gonadotropins 75IU f, step-up regimen, starting dose of 75 IU daily.

  Eligibility

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

Inclusion Criteria:

  • PCOS
  • Infertility
  • High responders

Exclusion Criteria:

  • Poor responders
  • Major medical conditions
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01438190

Locations
Italy
"Pugliese" Hospital
Catanzaro, Italy, 88100
Sponsors and Collaborators
University Magna Graecia
Investigators
Principal Investigator: Stefano Palomba, MD Department of Obstetrics and Gynecology, University "Magna Graecia" of Catanzaro
  More Information

No publications provided

Responsible Party: Stefano Palomba, MD, University Magna Graecia
ClinicalTrials.gov Identifier: NCT01438190     History of Changes
Other Study ID Numbers: 09/2011
Study First Received: September 19, 2011
Last Updated: April 5, 2013
Health Authority: Italy: The Italian Medicines Agency

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

ClinicalTrials.gov processed this record on June 18, 2013