In patients with polycystic ovary syndrome, insulin resistance increases, and since the extracts from cinnamon reduces insulin resistance by two mechanisms (1- increasing activation of the IRS/PI-3 kinase insulin signaling pathway and 2- stimulate auto phosphorylation of the insulin receptor and inhibit protein tyrosine phosphatase I). Through these two mechanisms cinnamon extract make adipocytes to increase the glucose uptake and glycogen synthesis. So this hypothesis arises that it can be effective in improving the symptoms of polycystic ovary syndrome.

This double-blind randomized clinical trial will be conducted in Royan Institute on patients with polycystic ovary syndrome undergoing in vitro fertilization cycle treatment to evaluate the effect of Cinnamon supplementation during controlled ovarian stimulation in patients with polycystic ovary syndrome.PCOS cases were diagnosed based on the Rotterdam criteria (4), and the presence of at least two of the following criteria: menstrual irregularity (cycle length <26 days or >35 days or variation between consecutive cycles of >10 days); clinical (presence of hirsutism evaluated by a Ferriman- Gallwey score >8, severe acne and alopecia) or biochemical (total testosterone concentration >0.5 ng/ml and/or free testosterone>3.5 pg/ml) hyperandrogenism; or ultrasound evidence of polycystic ovaries. Hirsutism was assessed according to the Ferriman-Gallwey-score and examination of nine body areas for coarse terminal hair, including upper lip, chin and chest, upper and lower areas of the abdomen, thighs and upper arms. In each part, the severity of hirsutism was graded from 1 to 4 and the participants with the total score of 8 and above considered as having hirsutism. PCOM was defined as the presence of 12 or more ovarian cysts with 2-10 mm diameter per ovary and/or ovarian volume ≥10 cm3. Vaginal ultrasound was performed by an ultrasound specialist and radiologist using an Aloka α-10 with a transvaginal 6-7.5 MHz probe (Medison Co., Japan).

The controlled ovarian stimulation method will be the same in all participants using the standard antagonist protocol. All patients diagnosed with polycystic ovary syndrome who are eligible based on the Rotterdam criteria and other inclusion and exclusion criteria stated in the general information section of the clinical trial and who have written consent to participate in the study will be examined. Patients will be randomly assigned into two groups using the block method in a size of 6, and each person will be given an exclusive code to keep the allocation hidden. The details of random allocation in terms of drug and placebo grouping are solely at the disposal of the project's pharmacist colleague, who have no role in the process of sampling and follow-up of patients.The medicine packages, as well as the appearance and smell of cinnamon and placebo tablets, are completely similar to each other. The methodologist prepared the drugs based on the block randomization method and prepared the coded list and put an English three-letter code label on the medicine cans. When an eligible patient is referred to a clinical physician, the principal investigator provides him with an envelope containing a drug code based on a randomized list, and the drug package with the same code is delivered to the patient. In this way, the patient and the clinical doctor following the patient will not know the type of drug (cinnamon or placebo).The method of ovarian stimulation and placebo consumption in the control group will be completely similar to the intervention group. In the intervention group, women will take 1500 mg daily (3500 mg cinnamon tablets, Sagepad Darou Pharmaceutical Company, Iran) that is, 4 weeks before the start of the new IVF cycle and 2 weeks during the ovarian stimulation process. Control group: patients take 3 placebo pills daily (containing white wheat flour, which is similar to cinnamon pills in terms of size, shape, color and smell, Sagepad Darou Pharmaceutical Company, Iran) 4 weeks before starting the ovarian stimulation/in vitro fertilization (COS/IVF) cycle and 2 weeks during the ovarian stimulation procedure, the ovary will be stimulated. Total number of retrieved oocytes and total number of MII oocytes will be compared between groups as primary outcomes.

Inclusion Criteria:

• Infertile women with polycystic ovary syndrome (PCOS) diagnosed according to the Rotterdam criteria who meet at least 2 of the following three criteria including: (1) oligomenorrhea or anovulation, (2) hyperandrogenism (clinical or biochemical ng/ dL 80 ≤ serum T level), (3) the presence of polycystic ovaries in ultrasound).
• The age range of 18 to 38 year.
• Written consent to participate in the study

Exclusion Criteria:

• Body mass index above 35 kg/m2
• Chronic and Endocrine disorders including diabetes mellitus, hyperprolactinemia, hypertension, Cushing's syndrome
• Autoimmune disorders
• History of recurrent pregnancy loss
• Genital, ovarian or uterine abnormalities
• Hydrosalpinx diagnosis
• Congenital adrenal hyperplasia, androgen-producing tumors or acromegaly
• Sensitivity to cinnamon
• Daily and frequent consumption of cinnamon to treat infertility
• Severe male factor infertility
• Moderate to severe endometriosis diagnosis Use of other hypoglycemic, insulin-sensitizing drugs (e.g. Metformin) or other antioxidant supplement (e.g. Myo-inositol) and β-blocker before or during the study