Myo-inositol Versus Clomiphene Citrate in PCOS

Study Overview
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Brief Summary
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Specific aim: To compare inositol and the golden standard first line treatment of ovulation induction, namely clomiphene citrate.

Official Title
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Myo-inositol Versus Clomiphene Citrate as First Line Treatment for Ovulation Induction in PCOS

Conditions
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Ovulation Induction, Polycystic Ovary Syndrome, Clomiphene, Inositol

Intervention / Treatment
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* Drug: Myo-inositol
* Drug: Clomiphene Citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rotterdam criteria for PCOS (cf. the recent ESHRE guidelines): at least 2 out of 3 criteria should be fulfilled: irregular cycle (shorter than 21 days or longer than 35 days); clinical (modified Ferriman-Gallwey score ≥ 6) or biochemical signs (elevated free testosterone) of hyperandrogenism (www.eshre.eu/Guidelines-and- Legal/Guidelines/Polycystic-Ovary-Syndrome.aspx); PCO ovaries on ultrasound (www.eshre.eu/Guidelines-and- Legal/Guidelines/Polycystic-Ovary-Syndrome.aspx): multiple small cysts (≥ 20 per ovary and/or an ovarian volume ≥ 10 ml, measured with a probe >8 MHz) in both ovaries. A first treatment cycle, possibly combined with intra uterine insemination (IUI) and this for (one of) the following reasons: mild male factor (as defined by each local center) endometriosis AFS score 1 or 2 Use of own or donor sperm. Exclusion Criteria: Tubal factors Uterine factors Endometriosis AFS score 3 or 4 Moderate to severe male factor (as defined by each local center) BMI > 35

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inositol group<br>Myo-inositol 4000 mg Dosing: 2 x 1 bag per day, per os (subjects can take myo-inositol during the meal but it is not obliged) during 3 consecutive treatment cycles. | Drug: Myo-inositol<br>* 2 x 1 bag per day, per os (subjects can take myo-inositol during the meal but it is not obliged).<br>|
| Active Comparator: Clomiphene citrate group<br>Each tablet contains 50 mg of clomiphene citrate Dosing: 1 tablet per day, per os, from cycle day 3 until 7 (extremes included), stepping up until a maximum dose of 3 tablets per day for 5 consecutive days during 3 consecutive treatment cycles. | Drug: Clomiphene Citrate<br>* Each tablet contains 50 mg of clomiphene citrate which means 33,9 mg of clomiphene. Other constituents are sucrose, lactose monohydrate, corn starch, pregelatinized starch, yellow iron oxide (E172) and magnesium stearate (E470b). Dosing: 1 tablet per day from cycle day 3 until 7 (extremes included), stepping up until a maximum dose of 3 tablets per day for 5 consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of cumulative ongoing pregnancy (a pregnancy diagnosed by ultrasonic visualisation of one or more gestational sacs with fetal heart beat) after 3 treatment cycles with inositol versus clomiphene citrate for ovulation induction. | Recently, a meta-analysis on the use of inositol in PCOS was published. This study showed that inositol leads to a more regular menstrual cycle and recovery of ovarian function. Less data are present on pregnancy rates. No RCT was found on the comparison between inositol and the golden standard first line treatment of ovulation induction, namely clomiphene citrate. Another advantage of inositol is that it doesn't have side effects compared to metformin and that there is no elevated risk on multiple pregnancies, which is the case with clomiphene citrate. | At 7 - 8 gestational weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of potential adverse events | The potential adverse events will be measured to determine whether the compliance for the patient is acceptable. | During 3 consecutive treatment cycles (each treatment cycle is up to 5 weeks) | 
| The occurrence of ovulation | The occurence of ovulation will be measured to determine whether the compliance for the patient is acceptable. | During 3 consecutive treatment cycles (each treatment cycle is up to 5 weeks) | 
| The number of cancelled treatment cycles | The number of cancelled treatment cycles will be measured to determine whether the compliance for the patient is acceptable. | During 3 consecutive treatment cycles (each treatment cycle is up to 5 weeks) | 
| The number of multiple pregnancies | The number of multiple pregnancies will be measured to determine whether the compliance for the patient is acceptable. | During 3 consecutive treatment cycles (each treatment cycle is up to 5 weeks) |