This trial is active, not recruiting.

Conditions infertility, pcos
Treatments metformin, gonadotropins in step-down regimen, placebo, gonadotropins in step-up regimen
Phase phase 4
Sponsor University of Modena and Reggio Emilia
Start date June 2013
End date December 2013
Trial size 120 participants
Trial identifier NCT01438190, 09/2011


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking single blind (investigator)
Primary purpose prevention
Metformin plus step-down protocol
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)
Placebo and step-up protocol
placebo, gonadotropins in step-up regimen
Placebo cps, two cps daily. Gonadotropins 75IU f, step-up regimen, starting dose of 75 IU daily.

Primary Outcomes

OHSS rate
time frame: one month

Secondary Outcomes

cancellation rate
time frame: one month
pregnancy rate
time frame: one month
live-birth rate
time frame: nine months

Eligibility Criteria

Female participants from 18 years up to 35 years old.

Inclusion Criteria: - PCOS - Infertility - High responders Exclusion Criteria: - Poor responders - Major medical conditions

Additional Information

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
Principal investigator Stefano Palomba, MD
Trial information was received from ClinicalTrials.gov and was last updated in July 2013.
Information provided to ClinicalTrials.gov by University of Modena and Reggio Emilia.