Subjects
This prospective, randomized, double-blind trial was conducted at Shariati hospital affiliated Tehran University of Medical Sciences in the Iran. The Subjects for this study were recruited through posters in hospital lobby from the Shariati hospital, Mohebe Yas hospital and Arash hospital in Tehran, Iran. The suitability assessments were conducted via telephone. OF the 275 women who responded, 41 were eligible to participate. Women were eligible for participation if fulfilled PCOS criteria, which was defined by the Rotterdam consensus and had at least two of the following: 1) clinical or chemical hyperandrogenism (either biochemical or clinical); 2) oligo- or amenorrhea; and/or 3) polycystic ovaries as viewed by transvaginal ultrasound (19). Oligomenorrhoea was defined as an average cycle length of more than 35 days. Polycystic ovarian morphology (PCOM) on ultrasonography was defined as follows: either volume > 10 cm3 in diameter per ovary and/or the presence of antral follicle count > 25 throughout the entire ovary in the absence of a dominant follicle(> 10 mm in diameter) (20). At baseline and at the end of study, all participants were checked for the PCOM criteria. Women were excluded if they had other disorders that mimic the PCOS (elevated prolactin and thyroid dysfunction), and Cushing’s disease, acromegaly, or diabetes mellitus. Patients with use of hormonal medication (such as oral contraceptives) or other medications that could modify the metabolism and ovarian function in the past month prior to enrollment were excluded. Also excluded were persons who transvaginal ultrasonography was inappropriate (due to virginity or patient refusal) or who were pregnant or lactating.
Women 18 to 40 years of age who presented with PCOS and met inclusion criteria were randomly assigned to receive resveratrol, at a dose of 1000 mg once daily after lunch for 3 months, or matching placebo. Patients and researcher, and personnel who assessed the trial outcomes were unaware of the intervention group’s allocation. Participants were contacted by telephone every 2 weeks and queried regarding adherence to study agents, illnesses, medication, supplement use, and pregnancy. Bottles of study tablets were sent to participants everyone months. During the medical examination, patients were specifically asked about their menstrual history. Clinical assessments included determination of body mass index (BMI), waist circumference, hirsutism (using ferriman and gallweyy score), acne score (using a four- point scale) and tansvaginal ultrasonography.
Patients provided written informed consent, and the institutional review board at Tehran University of medical sciences approved the trial protocol. The study was registered at www.irct.ir with the identifier IRCT2017061917139N2.
Ultrasound image assessment
Participants were evaluated by transvaginal ultrasonography (5–9 MHz) (Sonoline G40; Siemens Medical Solutions, USA, Inc.) in the early follicular phase on days 2–7 of the menstrual cycle and women with irregular menses were scanned at an unspecified time by one of two experienced ultrasonographers at Moheb Yas hospital. Ovarian volume and the number of antral follicles (2–9 mm) per ovary (FNPO), the number of 2–5 and 6–9 mm follicle, follicle distribution pattern, stromal area (SA) and mean total echogenicity were evaluated. The volume of each ovary was estimated using the equation: π/6 (transverse diameter) × (anteroposterior diameter) × (longitudinal diameter). For each ovary, the total number of all visible follicles with a diameter of 2–9 mm (antral follicles) were achieved by continuous scanning of the entire ovary (21). Ovarian data for each subject are presented as a mean recorded value for the left and right ovaries. When a dominant follicle (≥ 10 mm), corpus luteum or other abnormal ovarian mass was detected, only the data for the other ovary was reported (19). Ovarian stromal area measured by outlining the outer peripheral profile of the stromal with the caliper (22). Subjects were considered to have a peripheral distribution pattern by evaluating the largest cross-sectional plane if of both ovaries contained ≥ 9 follicles in a clear aggregation around the periphery with ≤ 1 central follicle.
Statistical analysis
Statistical analyses were performed by SPSS version 16.0 for Windows (SPSS Inc., Chicago, IL, USA). The Kolmogorov-Smirnov test and the Shapiro-Wilk’s W test were used to verify whether study variables were normally distributed. Non-normally distributed variables were transformed (log, inverse square root, square root, and inverse). Independent samples t- test and chi- square test were used to compare any differences between the two groups at the baseline. Repeated-measures of ANOVA were used to test the difference between study groups at the end of study. P < 0.05 was considered statistically significant.