Role of Melatonin Supplementation in Follicular Fluid of in Vitro Fertilization (IVF) Patients With Polycystic Ovarian Syndrome

Study Overview
=================
Brief Summary
-----------------
To evaluate the effects of melatonin supplementation on the main in vitro fertilization (IVF) outcomes during ovarian stimulation in patients with Polycystic ovarian syndrome (PCOS).

Detailed Description
-----------------
Polycystic ovarian syndrome (PCOS) is a common endocrine disorder that causes infertility due to anovulation in women of reproductive age. Anovulation and also decreased oocyte and embryo quality may be cause of infertility in women with PCOS. Furthermore, the reactive oxygen species (ROS) induce oxidative stress which may be responsible for poor oocyte quality. The ROS generation from mononuclear cells is elevated in women with PCOS and a significant increment of lipid peroxidation products in women with PCOS has been reported. Melatonin is a documented powerful free radical scavenger and a broad spectrum antioxidant. It has been observed that a non-PCOS group co-treated with inositol, folic acid, and melatonin (Inofolic Plus by LO.LI.Pharma) results in a significantly greater mean number of mature oocytes, and a lower mean number of immature oocytes in patients with low oocyte quality history when compared to treatment only with inositol and folic acid (Inofolic by LO.LI.Pharma). The aim of the study is to evaluate the possible effects of melatonin supplementation on the main IVF outcomes during ovarian stimulation of patients with PCOS. From July 2009 to December 2011, 358 patients with PCOS (Rotterdam criteria) were enrolled in this prospective randomized controlled trial.

Conditions
-----------------
Polycystic Ovary Syndrome

Intervention / Treatment
-----------------
* Dietary Supplement: Myo-inositol + folic acid + melatonin
* Dietary Supplement: Myo-inositol + folic acid


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diagnosis of PCOS irregular menstrual cycle (> than 28-30 days) normal uterine cavity body mass index of 20 to 26 Kg/m2 first IVF treatment Exclusion Criteria: presence of tubal, uterine, genetics and male causes of infertility diagnosis of cancer hormonal treatment in the last six months

Ages Eligible for Study
-----------------
Minimum Age: 27 Years
Maximum Age: 38 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inofolic plus<br>178 patients | Dietary Supplement: Myo-inositol + folic acid + melatonin<br>* Myo-inositol (2000mg)+ folic acid (200 mcg)+ melatonin(3 mg)<br>|
| Active Comparator: Inofolic<br>180 patients | Dietary Supplement: Myo-inositol + folic acid<br>* Myo-inositol (2000mg) + folic acid (200 mcg)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of mature oocytes |  |  | 
| embryo quality |  |  | 
| Pregnancy rate |  |  | 
| Implantation rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total dose of FSH administered |  |  | 
| Number of days of stimulation |  |  | 
| Serum estradiol levels |  |  | 
| Endometrial thickness | Endometrial thickness on the day of human chorionic gonadotropin (hCG) administration |  | 
| Cancellation rate |  |  | 
| Incidence of moderate or severe ovaric hyperstimulation syndrome (OHSS) |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
intrafollicular melatonin, PCOS, embryos quality, oocytes quality