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

Infertility Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01438190
• Other study ID #: 09/2011
• Status: Active, not recruiting
• Phase: Phase 4
• First received: September 19, 2011
• Last updated: July 11, 2013
• Start date: June 2013
• Est. completion date: December 2014

Study information

• Verified date: July 2013
• Source: University of Modena and Reggio Emilia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: December 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• PCOS

• Infertility

• High responders

Exclusion Criteria:

• Poor responders

• Major medical conditions

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Infertility
• PCOS

Intervention

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.
• Placebo, gonadotropins in step-up regimen
Placebo cps, two cps daily. Gonadotropins 75IU f, step-up regimen, starting dose of 75 IU daily.

Locations

Country	Name	City	State
Italy	"Pugliese" Hospital	Catanzaro

Sponsors (1)

Lead Sponsor	Collaborator
University of Modena and Reggio Emilia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OHSS rate	Ovarian hyperstimulation syndrome	one month	Yes
Secondary	cancellation rate	rate of cancelled cycle for high risk of OHSS or low response	one month	Yes
Secondary	pregnancy rate		one month	No
Secondary	live-birth rate		nine months	No