Metformin in High Responder Polycystic Ovary Syndrome (PCOS) Patients Undergoing IVF Cycles

Study Overview
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Brief Summary
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The use of metformin pre-treatment and co-administration was recently proposed in infertile women affected by polycystic ovary syndrome (PCOS) treated with gonadotropins. Data from meta-analyses showed that metformin administration significantly reduced the stimulation length and the total dose of gonadotropins used in PCOS women undergoing gonadotropins stimulation for non in-vitro fertilization (IVF) cycles. On the other hand, in IVF cycles metformin was demonstrated to significantly reduce the ovarian hyperstimulation syndrome (OHSS) rate in infertile patients with PCOS treated with gonadotropins. The metformin regulating effect on the ovarian response was also observed in a randomized controlled trial (RCT) on young non-obese insulin-resistant women with PCOS receiving gonadotropins for mono-ovulation induction. In particular, metformin increased the mono-ovulatory cycles, the duration of stimulation and the amount of gonadotropins used, while it reduced the number of dominant follicles and the estradiol (E2) levels. The aim of the present study was to evaluate the effect of metformin administration in high responder PCOS patients undergoing gonadotropins ovarian stimulation for IVF cycles.

Detailed Description
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Infertile young non-obese insulin-resistant patients with PCOS who had a background of the first IVF treatment cycle cancelled because of high risk for OHSS will be enrolled and randomized in two treatment arms. In their second IVF attempt, the experimental group will receive metformin (500 mg, 3 times daily) pre-treatment for two weeks and co-administration during gonadotropins ovarian stimulation; the control group will be treated with placebo (2 cps daily) pre-treatment and co-administration by using the same schedule of the experimental group. In all patients, ovarian stimulation will be carried out with a personalized step-down gonadotropin in association with a minidose flare-up GnRH agonist protocol.

Official Title
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Metformin Addition to Gonadotropins Ovarian Stimulation in High Responder Patients With PCOS Undergoing In-vitro Fertilization

Conditions
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Infertility, Polycystic Ovary Syndrome (PCOS)

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of one previous cancelled cycle for high-risk of OHSS, or history of moderate/severe OHSS during their previous IVF cycle Infertility Polycystic ovary syndrome (PCOS) insulin resistance hyperandrogenism Exclusion Criteria: BMI>30 kg/m2 age >35 years FSH>9UI/L

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Patients receiving metformin pretreatment and co-administration | Drug: Metformin<br>* Metformin pre-treatment and co-administration<br>|
| Placebo Comparator: Control group<br>Placebo | Drug: Placebo administration<br>* Placebo pre-treatment and co-administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of OHSS |  | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stimulation length |  | one month | 
| Gonadotropins dose |  | one month | 
| Dominant follicles on day of ovulation triggering |  | one month | 
| Ovulation rate |  | one month | 
| Peak estradiol levels on day of ovulation triggering |  | one month | 
| Embryo quality |  | one month | 
| pregnancy rate |  | one month | 
| multiple pregnancy rate |  | one month | 
| Live birth rate |  | ten months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS, Polycystic ovary syndrome, Cancelled cycles, OHSS, Infertility