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

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

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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	Infertility PCOS
Intervention	Drug: Metformin, gonadotropins in step-down regimen Drug: Placebo, gonadotropins in step-up regimen
Phase	Phase 4
Sponsor	University of Modena and Reggio Emilia
Responsible Party	University of Modena and Reggio Emilia
ClinicalTrials.gov Identifier	NCT01438190
First Received	September 19, 2011
Last Updated	July 11, 2013
Last verified	July 2013

Tracking Information[ + expand ][ + ]

First Received Date	September 19, 2011
Last Updated Date	July 11, 2013
Start Date	June 2013
Estimated Primary Completion Date	December 2014
Current Primary Outcome Measures	OHSS rate [Time Frame: one month] [Designated as safety issue: Yes]Ovarian hyperstimulation syndrome
Current 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]

Descriptive Information[ + expand ][ + ]

Brief Title	Metformin in Step-down Regimen Versus Conventional Low Dose Step-up Protocol in Patients With PCOS Undergoing IVF
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
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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 4
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Prevention
Condition	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. Drug: Placebo, gonadotropins in step-up regimen Placebo cps, two cps daily. Gonadotropins 75IU f, step-up regimen, starting dose of 75 IU daily.
Study Arm (s)	Experimental: Experimental Metformin plus step-down protocol Active Comparator: Control Placebo and step-up protocol

Recruitment Information[ + expand ][ + ]

Recruitment Status	Active, not recruiting
Estimated Enrollment	120
Estimated Completion Date	December 2014
Estimated Primary Completion Date	December 2013
Eligibility Criteria	Inclusion Criteria: - PCOS - Infertility - High responders Exclusion Criteria: - Poor responders - Major medical conditions
Gender	Female
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Italy

Administrative Information[ + expand ][ + ]

NCT Number	NCT01438190
Other Study ID Numbers	09/2011
Has Data Monitoring Committee	No
Information Provided By	University of Modena and Reggio Emilia
Study Sponsor	University of Modena and Reggio Emilia
Collaborators	Not Provided
Investigators	Principal Investigator: Stefano Palomba, MD Department of Obstetrics and Gynecology, University "Magna Graecia" of Catanzaro
Verification Date	July 2013

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