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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Infertility, PCOS

Intervention / Treatment
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* Drug: Metformin, gonadotropins in step-down regimen
* Drug: Placebo, gonadotropins in step-up regimen


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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Metformin plus step-down protocol | Drug: Metformin, gonadotropins in step-down regimen<br>* Metformin 850 mg cps, two cps daily for 12 weeks. gonadotropins 75IU f, step-down regimen, starting dose of 225 IU daily.<br>|
| Active Comparator: Control<br>Placebo and step-up protocol | Drug: Placebo, gonadotropins in step-up regimen<br>* Placebo cps, two cps daily. Gonadotropins 75IU f, step-up regimen, starting dose of 75 IU daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OHSS rate | Ovarian hyperstimulation syndrome | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cancellation rate | rate of cancelled cycle for high risk of OHSS or low response | one month | 
| pregnancy rate |  | one month | 
| live-birth rate |  | nine months |