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Metformin in Step-down Regimen Versus Conventional Low Dose Step-up Protocol in Patients With PCOS Undergoing IVF

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ClinicalTrials.gov Identifier: NCT01438190
Recruitment Status : Unknown
Verified July 2013 by Stefano Palomba, University of Modena and Reggio Emilia.
Recruitment status was:  Active, not recruiting
First Posted : September 22, 2011
Last Update Posted : July 12, 2013
Information provided by (Responsible Party):

Study Description
Brief Summary:

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 or disease Intervention/treatment Phase
Infertility PCOS Drug: Metformin, gonadotropins in step-down regimen Drug: Placebo, gonadotropins in step-up regimen Phase 4

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (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
Study Start Date : June 2013
Estimated Primary Completion Date : December 2013
Estimated Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :
  1. OHSS rate [ Time Frame: one month ]
    Ovarian hyperstimulation syndrome

Secondary Outcome Measures :
  1. cancellation rate [ Time Frame: one month ]
    rate of cancelled cycle for high risk of OHSS or low response

  2. pregnancy rate [ Time Frame: one month ]
  3. live-birth rate [ Time Frame: nine months ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • PCOS
  • Infertility
  • High responders

Exclusion Criteria:

  • Poor responders
  • Major medical conditions
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01438190

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

Responsible Party: Stefano Palomba, MD, University of Modena and Reggio Emilia
ClinicalTrials.gov Identifier: NCT01438190     History of Changes
Other Study ID Numbers: 09/2011
First Posted: September 22, 2011    Key Record Dates
Last Update Posted: July 12, 2013
Last Verified: July 2013

Additional relevant MeSH terms:
Genital Diseases, Male
Genital Diseases, Female
Hypoglycemic Agents
Physiological Effects of Drugs