The influence of Myoinositol to improve biochemical manifestations of the serum and follicular fluid and ICSI outcomes in patients with PCOS: A prospective randomized research

The influence of Myoinositol to improve biochemical manifestations of the serum and follicular fluid and ICSI outcomes in patients with PCOS: A prospective randomized research | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The influence of Myoinositol to improve biochemical manifestations of the serum and follicular fluid and ICSI outcomes in patients with PCOS: A prospective randomized research Zeynab Yazdanpanah, Ebrahim Cheraghi, Mitra Heydari Nasrabadi, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4172354/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The research investigated the capacity of Myo-inositol (MI) in order that it improves biochemical markers in serum and follicular fluid, and ultimately, intracytoplasmic sperm injection (ICSI) outcomes of women with PCOS. Methods Sixty infertile patients with PCOS who were undergoing ovulation induction for ICSI, were randomly divided to two groups. The MI group received 2000 mg Myo-inositol + 1 mg folic acid twice a day for 6 weeks with starting the ICSI cycle. For the same period, the control group received a placebo containing only folic acid (1 mg). Levels of hormonal profiles in serum and follicular fluid, as well as oxidative stress markers (MDA, TAC, GPx, and SOD) were estimated using an ELISA assay. Primary end points were ICSI cycle outcomes. Results Compared to the placebo group, the MI group demonstrated significant reduction in serum and follicular fluid levels of LH, LH/FSH ratio, total testosterone, AMH, and Androstenedione. Furthermore, the MI group exhibited meaningful increases in TAC, GPx, and SOD, but MDA significantly decreased. While the number of recovered and mature oocytes is not similar statistically among the groups, the MI group showed significant improvements in the percentage of immature oocytes, cleavage rate, and good embryo quality. A meaningful correlation was checked between follicular fluid AMH level and LH, FSH, total testosterone, Androstenedione, insulin, MDA, the number of recovered oocytes, and immature oocytes. Conclusion Our outcomes indicate that Myo-inositol administration in women with PCOS undergoing ART helps to improve their hormonal profiles, and the quality of oocytes and embryos. ( Trial registration : IRCT202220921056008N1) Myoinositol Polycystic ovarian syndrome Intracytoplasmic sperm injection Reproductive outcomes Figures Figure 1 Figure 2 Figure 3 What does this study add to the clinical work? Myo-inositol administration in women with PCOS undergoing ART could improve their hormonal profile, and the quality of oocytes and embryos. Introduction A complex and heterogeneous endocrine disorder is polycystic ovary syndrome (PCOS). It affects 7–14% of women in their reproductive years. This manifests as infertility, ovarian dysfunction, menstrual irregularity, and androgen excess, often accompanied by typical ovarian ultrasound features [ 1 ]. The etiology and diagnosis of PCOS remain disputed, with many contributing factors suspected, including the hypersecretion of luteinizing hormone (LH), hyperinsulinemia due to insulin resistance, ovarian hyperandrogenism, polycystic ovaries, and decreased fertility [ 2 ]. In recent years, extensive research efforts have been directed towards understanding the underlying mechanisms and developing effective treatments for PCOS [ 3 ]. Two key factors could be responsible for the low success rate of assisted reproductive techniques (ART) in patients with PCOS: (1) the limited quantity and poor quality of oocytes recovered following ovarian stimulation, and (2) the exact poor fertilization rate following intracytoplasmic sperm injection (ICSI) [ 4 ]. Various interventions explored reproductive consequences in inadequate responders undergoing ART, but unfortunately, convincing evidence for their effectiveness remains elusive. This includes insulin-sensitizing agents like pioglitazone, rosiglitazone, troglitazone, D-chiro-inositol, and most notably, metformin [ 5 ]. Therefore, any treatment capable of enhancing oocyte quality holds immense promise for achieving a "crowning achievement" in ART for PCOS patients [ 6 ]. Myo-inositol (MI), a cyclic sugar with six hydroxyl groups, acts as a precursor to inositol triphosphate, also known as an intracellular second messenger, that regulates hormones, such as follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and insulin [ 7 , 8 ]. Beyond its role as a second messenger, inositol regulates exocrine gland secretion (pancreas, ovaries) and shows promise for assisted reproduction [ 9 ]. Notably, it may improve insulin sensitivity in PCOS, leading to raised glucose uptake [ 10 ]. MI supplements have shown promise in improving both the metabolic characterization and hyperandrogenism in PCOS patients, while also developing clinical pregnancy rates in infertile patients experiencing ICSI [ 11 ]. Prior investigations have provided evidence for its efficacy in restoring spontaneous ovarian activity and fertility in numerous patients diagnosed with PCOS [ 12 ]. MI has a vital role in different cellular functions, such as growth, survival, and reproduction [ 13 , 14 ]. Evidence suggests that MI administration can enhance ovarian function, potentially reducing the FSH needed for ovarian stimulation and enhancing the quantity and quality of retrieved oocytes [ 15 ]. Notably, research has shown that MI can reinstate spontaneous ovulation and fertility in most PCOS patients [ 16 , 17 ]. Furthermore, its potential benefits for insulin sensitivity, oocyte maturation, and embryo quality, have established MI as a clinical treatment for PCOS and a promising intervention for spontaneous ovulation restoration [ 18 , 19 , 11 , 20 ]. While ART remains crucial for many PCOS women, poor oocyte quality is a major obstacle to successful ICSI cycles, with over two-thirds failing to achieve pregnancy [ 21 ]. Therefore, any treatment capable of enhancing oocyte quality would be a significant advancement in ART procedures. The research is aimed at estimating the impacts of MI on hormonal profiles, oxidative stress markers in serum and follicular fluid, and ICSI consequences in women of PCOS. Methods Study population Researchers at Qom Infertility Treatment Center conducted a rigorous clinical test (randomized, double-blinded, and placebo-controlled) on a new infertility treatment from May 2022 to May 2023. Sixty infertile PCOS women with 25–35 years, experiencing Intracytoplasmic sperm injection (ICSI) were enrolled. Patients met the Rotterdam consensus criteria for PCOS (2003) [ 22 ]: two out of three clinical/biochemical hyperandrogenism, chronic oligo/anovulation, or polycystic ovaries on ultrasound. Criteria of prohibition were hypersensitivity to Myo-inositol, male infertility, infertility beyond anovulation, congenital adrenal hyperplasia, pelvic pathologies, thyroid dysfunction, androgen-secreting neoplasia, diabetes mellitus, Cushing's syndrome, hyperprolactinemia, medications influencing carbohydrate metabolism, severe hepatic/renal diseases, and hormonal analogues (except progesterone) within 2 months. Before the enrollment of patients, informed consent was obtained after approval through the Research Ethics Committee of Islamic Azad University, Varamin Pishva Branch (IR.IAU.VARAMIN.REC.1400.033). Treatment design Gynecologists conducted blinded examinations of all participants. Neither patients nor physicians knew which treatment regimen was administered. Throughout the study, participants were instructed to maintain their current levels of physical activity and nutriment and avoid taking new medication. Myo-inositol dosage and duration followed established protocols from Nazari et al. (2020) and Papaleo et al. (2009) [ 23 , 5 ]. Eighty patients were randomly separated into two groups (n = 40): 1) Myo-inositol group (MI group): 40 patients received 2000mg Myo-inositol (Fairhaven Health-LLC, UK) and 1mg folic acid (Raha Co., IRAN) twice daily for 6 weeks. 2) Placebo group: 40 patients received 1mg folic acid only. Patients reported any side effects throughout the treatment period, and these were estimated at the end for frequency and severity. Twenty patients (10 per group) dropped out (Fig. 1 ), leaving 60 for the final analysis. A sample range of 60 was determined based on a 95% confidence interval and 80% power [ 24 ]. Controlled ovarian induction Ovarian stimulation involved daily injections of recombinant gonadotropins (Cinal-F 75IU-CinnaGen, Iran) starting at 150–75 IU on the 2nd or 3rd day of menstruation, either spontaneous or induced. The dose was modified based on ultrasound monitoring of ovarian response. Once a controlling follicle got to 14 mm in diameter, a daily dose of GnRH antagonist (Cetroide, Merck Serono, Germany) was started and continued until ovulation was triggered. At least three follicles exceeding 18 mm in diameter were required for ovulation triggering with HCG injection (PDpreg5000IU-pooyesh darou, Iran). Oocytes were recovered 34–36 hours following hCG injection. Before treatment, fasting blood samples were gathered twice: on day 3 of the menstrual cycle before the previous ovulation pick-up (OPU) and again during follicular aspiration. Each peripheral blood sample was directly centrifuged at 3000 rpm (10 min) (EBA20, Hettich, UK), and the serum was stored (at -70°C) for later examination. Coming after follicular aspiration and OPU, the follicular fluid (FF) was saved from the first aimed follicle without observable blood contamination. FF samples were centrifuged at 3000 rpm (10 min) using an EBA20 centrifuge (Hettich, UK). For further analysis, the supernatants were then saved at -70°C. Oocyte retrieval, ICSI, and embryo culture Semen analysis followed World Health Organization (WHO) guidelines [ 25 ]. Oocyte retrieval performed under ultrasound guidance using a thin, single-lumen needle (Reproline medical GmbH, Germany) inserted through the vagina. To prepare the oocytes for subsequent analysis, cumulus cells were enzymatically dislodged via a 30-second incubation in 20 IU/mL hyaluronidase (ART-4007A, SAGE BioPharma) followed by gentle mechanical pipetting. Mature oocytes, characterized by the presence of a first polar body, were then identified and isolated under a stereo microscope (Olympus Co, Japan). Only fertilized oocytes with two pronuclei (2PN), identified after overnight culture, were selected for embryo transfer. These embryos were then transferred to a pre-equilibrated cleavage medium (ART-1526, SAGE BioPharma) and cultured for three days. Finally, using an embryo transfer catheter (Cook Medical LLC, USA), the embryos were transferred back into the patient's uterus. Each patient received a maximum of three embryos during transfer. Fertilization was evaluated 12–16 hours following ICSI by confirming two different pronuclei. Cleavage rate was estimated 24–36 hours following fertilization. Quality of embryo was graded during third day of insemination using a three-point system [ 26 ]: Grade I: Symmetrical blastomeres without fragmentation; Grade II: irregular blastomeres with less than 25% fragmentation; Grade III: irregular blastomeres with over 25% fragmentation. Pregnancy was confirmed by serum β-HCG levels measured on days 14–15 after transfer. Clinical pregnancies were defined by the presence of both a gestational sac and heartbeat on ultrasound scans performed at 6 weeks post-transfer. Assessment of clinical features and hormonal assays Weight and height of patients were assessed for defining their body mass index (BMI). Obesity was defined as having a BMI greater than 30. The waist circumference was divided by the hip circumference to estimate the waist-to-hip ratio (WHR). The study measured blood pressure of patients. At the treatment conclusion, during the early follicular phase, participants' weight, waist and hip peripheries, and blood pressure were all reassessed. Serum and follicular fluid levels of the following hormones were evaluated by ELISA based on the manufacturer's guidance: total testosterone (TT, ng/dl; Abcam ab108666), thyroid stimulating hormone (TSH, mIU/ml; Abcam ab100660), follicle provoking hormone (FSH, mIU/ml; Abnova KA0213), luteinizing hormone (LH, mIU/ml; Abcam ab178658), estradiol (E2, pg/ml; Abcam ab108667), androstenedione (AE, ng/ml; Abcam ab178609), anti-Mullerian hormone (AMH, ng/ml; Abcam ab267629), prolactin (PRL, ng/ml; Abcam ab226901), and insulin (INS, mIU/ml; Abcam ab278123). Measurements were performed in duplicate on samples gathered during third day of the menstrual cycle and once during follicular aspiration. Estimating the oxidative stress biomarkers This study measured malondialdehyde (MDA), a biomarker of lipid peroxidation (LPO) [ 26 ], in both serum and follicular fluid using the thiobarbituric acid (TBA) colorimetric assay (TBARS Assay Kit, Abcam ab233471). MDA levels were expressed in micromoles per liter (µM). Additionally, total antioxidant capacity (TAC, µM; Abcam ab288592) and levels of activity in superoxide dismutase (SOD, IU/ml; Abcam ab277415) and glutathione peroxidase (GPx, ng/ml; Abcam ab123158) were measured in both samples by ELISA methods based on the manufacturers' guidance. Samples collected on the third day of the menstrual cycle and once during follicular aspiration were measured in duplicate. Statistical analysis Kolmogorov-Smirnov was used to test the distribution of changes in the two groups for normality. Demographic and experimental data were then presented as mean ± SEM if normally distributed, or reported using other descriptive statistics if not. For normally distributed data, Statistical comparisons were conducted with Student's t-tests for repeated measures, with a two-tailed p-value < 0.05 considered significant. Chi-square tests analyzed categorical data when appropriate, while Pearson's correlation coefficients assessed relationships between variables. SPSS software (version 24.0) was used for all analyses. Results Clinical and demographic features Before treatment, the two groups demonstrated no significant differences in any baseline characteristics, including age, marital duration, infertility duration, waist circumference, BMI, hip circumference, waist-to-hip ratio, or prevalence of oligomenorrhea and hirsutism (Table 1). Hormonal, biochemical characteristics, and oxidative stress markers in the serum After a comparison of the MI group with the placebo group, serum levels of LH (P = 0.001), LH/FSH ratio (P = 0.001), total testosterone (P = 0.001), androstenedione (P = 0.01), and AMH (P = 0.001) showed significant changes, while levels of FSH (P = 0.085), estradiol (P = 0.574), prolactin (P = 0.124), insulin (P = 0.230), and TSH (P = 0.459) remained stable (Table 2 ). Similarly, Table 3 indicates meaningful differences in the adjusted change of serum MDA (P = 0.001), TAC (P = 0.001), SOD (P = 0.01), and GPx (P = 0.01) between the MI and placebo groups. Table 1. Baseline and clinical characteristics of the two groups of PCOS patients (n=80). Data are shown as mean ± SEM. Analysis was performed by Student’s t- test. NS . No differences were observed between the mean of variables in the two groups (P > 0.05). * Analysis was performed by Pearson Chi-Squared test for comparisons. Placebo group, folic acid; MI group, Myo-inositol plus folic acid; BMI, body mass index. Parameters Treatment groups MI Placebo p value Age (25-35 years) 27.77±3.3 28.43±3.07 0.423 NS Duration of marriage (year) 6.8±2.46 7.18±3.24 0.608 NS Duration of infertility (year) 5.93±2.36 5.22±2.37 0.246 NS Waist size (cm) 90.9±13.2 91.7±15.4 0.931 NS Hip size (cm) 106.4±13.1 108.4±13.4 0.970 NS Waist/Hip ratio (WHR) 0.84±0.04 0.83±0.05 0.366 NS BMI (kg/m 2 ) 27.32±3.48 28.13±2.99 0.853 NS No. of Oligomenorrhea patients (%) * 8 (26.7) 7 (23.3) 0.677 NS No. of Hirsute patients (%) * 7 (23.3) 6 (20) 0.654 NS Table 2. Oxidative stress markers and hormonal profile of baseline and after treatment in the serum of PCOS patients and their adjusted changes. Data are shown as mean ± SEM. Analysis was performed by Student’s t- test. Significant differences for the comparison between treatments are in bold type. Placebo, folic acid group; MI, Myo-inositol plus folic acid group; FSH, Follicle stimulating hormone; LH, luteinizing hormone; PRL, Prolactin; AMH, Anti-Mullerian hormone; TSH, Thyroid stimulating hormone; E2, estradiol. MDA, malonaldehyde; TAC, Total Antioxidant Capacity; SOD, Superoxide Dismutase; GPx, Glutathione Peroxidase. Parameters Treatment groups MI (n=30) Placebo (n=30) p value for change comparison Baseline After treatment change Baseline After treatment change LH (mIU/ml) 9.3±0.25 5.7±0.24 - 3.6±0.31 10.9±0.24 10.4±0.18 1.07±0.18 0.001 FSH (mIU/ml) 4.9±0.15 4.8±0.9 - 0.13±0.19 5.01±0.17 5.3±0.18 0.33±0.17 0.085 LH/FSH ratio 1.9±0.06 1.2±0.05 - 0.7±0.07 2±0.05 2.1±0.07 0.11±0.08 0.001 Total Testosterone (ng/dl) 65.28±1.8 49.58±2.3 - 15.7±1.3 64.32±1.7 82.53±1.5 18.2±1.2 0.001 E2 (pg/ml) 56.5±1.9 61.15±2.1 4.7±1.5 54.8±2.1 57.9±2.5 3.12±2.1 0.574 PRL (ng/ml) 17.8±0.7 16.7±0.7 - 1.1±0.35 18.23±0.7 18.07±0.7 - 0.16±0.5 0.124 Androstenedione (ng/ml) 2.9±0.2 2.09±0.16 - 0.86±0.14 2.85±0.19 3.1±0.16 0.24±0.13 0.01 Insulin ( mIU/ml ) 19.67±0.7 19.07±0.6 - 0.6±0.2 19.44±0.6 19.28±0.6 - 0.16±0.2 0.230 AMH (ng/ml) 8.5±0.27 6.9±0.2 - 1.6±0.25 9.03±0.27 11.78±0.3 2.7±0.3 0.01 TSH ( mIU/ml ) 2.2±0.2 2.01±0.2 - 0.19±0.07 2.3±0.25 2.2±0.27 - 0.08±0.1 0.459 MDA (μM) 1.9±0.1 1.2±0.09 - 0.7±0.04 2.06±0.09 4.02±0.09 1.9±0.13 0.001 TAC (μM) 0.79±0.09 1.64±0.1 0.85±0.05 0.77±0.06 0.3±0.05 - 0.47±0.07 0.001 SOD (IU/ml) 44.4±0.7 48.4±0.8 3.97±0.2 44.1±0.6 29.1±0.9 - 14.9±1.1 0.01 GPx (ng/ml) 35.39±0.6 39.31±0.6 3.92±0.3 35.91±0.5 27.74±0.5 - 8.17±0.5 0.01 Table 3. Comparison of the hormonal profile and oxidative stress markers in the follicular fluid of patients with polycystic ovary syndrome. Data are shown as mean ± SEM. Analysis was performed by Student’s t- test. Significant differences for the comparison between treatments are in bold type. Placebo, folic acid group; MI, Myo-inositol plus folic acid group; FSH, Follicle stimulating hormone; LH, luteinizing hormone; PRL, Prolactin; AMH, Anti-Mullerian hormone; TSH, Thyroid stimulating hormone; E2, estradiol; MDA, malonaldehyde; TAC, Total Antioxidant Capacity; SOD, Superoxide Dismutase; GPx, Glutathione Peroxidase. Parameters Treatment groups MI (n=30) Placebo (n=30) p value LH (mIU/ml) 0.89±0.05 1.18±0.07 0.03 FSH (mIU/ml) 6.04±0.28 5.6±0.32 0.350 LH/FSH ratio 0.16±0.01 0.24±0.02 0.01 Total Testosterone (ng/dl) 6.8±0.37 8.2±0.6 0.047 E2 (pg/ml) 483.43±32.7 451.33±26.3 0.448 PRL (ng/ml) 18.5±0.8 18.9±0.8 0.753 Androstenedione (ng/ml) 404.73±25.6 487.23±27.9 0.034 Insulin ( mIU/ml ) 6.6±0.4 7.73±0.5 0.082 AMH (ng/ml) 438.9±23.6 526.07±29.4 0.024 TSH ( mIU/ml ) 1.63±0.1 1.6±0.1 0.794 MDA (μM) 1.96±0.09 4.7±0.36 0.001 TAC (μM) 2.6±0.1 1.9±0.07 0.001 SOD (IU/ml) 42.91±0.9 39.64±0.9 0.02 GPx (ng/ml) 39.77±0.7 36.83±0.5 0.01 Table 4. Distribution of retrieved oocytes, the quality of oocytes and embryos, and pregnancy outcome in PCOS patients. Data are shown as mean ± SEM. Analysis was performed by Student’s t- test. Significant differences for the comparison between treatments are in bold type. * Analysis was performed by chi-square test for multiple comparisons (P 0.05). Parameters Treatment groups MI (n=30) Placebo (n=30) p value No. of oocytes retrieved 9.5±0.69 11.03±0.95 NS No. of immature oocytes (GV+MI) 2.2±0.2 3.1±0.37 0.038 No. of mature oocytes (MII) 7.33±0.68 7.93±0.67 NS MII/total oocytes retrieved 0.74±0.03 0.73±0.02 NS No. of fertilized oocytes (2PN) 7.01±0.6 5.7±0.4 NS No. of cleaved embryos 6.8±0.5 5.2±0.4 0.027 No. of embryos Grade I 3.27±0.42 1.53±0.15 0.001 No. of embryos Grade II 2.17±0.2 1.8±0.2 NS No. of embryos Grade III 1.33±0.17 1.83±0.18 NS (0.06) No. of Good quality of Embryos (I+II) 5.43±0.5 3.33±0.3 0.01 No. of clinical pregnancy (%) * 11 (36.6) 6 (20) NS Hormonal, biochemical characteristics, and oxidative stress biomarkers in the follicular fluid Similar to serum levels, follicular fluid (FF) concentrations of LH (P = 0.001), LH/FSH ratio (P = 0.01), total testosterone (P = 0.047), Androstenedione (P = 0.034), and AMH (P = 0.024) significantly increased in the MI group in comparison with the placebo group (Table 3 ). Conversely, levels of FSH (P = 0.350), estradiol (P = 0.448), prolactin (P = 0.753), insulin (P = 0.082), and TSH (P = 0.794) remained stable (Table 3 ). Furthermore, adjusted changes in FF levels of MDA (P = 0.001), TAC (P = 0.001), SOD (P = 0.02), and GPx (P = 0.01) were significantly different between the MI and placebo groups (Table 3 ). Estimation of oocytes morphology and embryos While the whole of oocytes recovered and mature oocytes did not indicate significant alteration between the MI and placebo groups (P > 0.05), the whole of immature oocytes (MI + GV) significantly reduced in the MI group (P < 0.01). Cleavage rates were significantly higher in the MI group in comparison with the placebo group (P 0.05). Notably, the MI group raised the formation of good quality embryos (Grade I) on day 3 (P < 0.01), with no significant difference detected in Grades II and III. Overall, the number of good quality embryos (Grade I + II) was significantly higher in the MI group (P 0.05) (Table 4 ). Correlations between follicular fluid variables In the placebo group, follicular fluid (FF) levels of AMH indicated significant positive correlations with LH (r = 0.766; p = 0.0001), insulin (r = 0.512; p = 0.004), total testosterone (r = 0.642; p = 0.0001), androstenedione (r = 0.773; p = 0.0001), MDA (r = 0.438; p = 0.016), the whole of retrieved oocytes (r = 0.569; p = 0.0001), and immature oocytes (MI + GV) (r = 0.739; p = 0.0001). Notably, a significant negative correlation was observed between FF AMH and FSH (r= -0.563; p = 0.001). However, in the MI group, these associations were attenuated or absent. FF AMH levels no longer exhibited significant correlations with LH (r = 0.283; p = 0.029), FSH (r= -0.037; p = 0.845), insulin (r = 0.098; p = 0.607), total testosterone (r= -0.015; p = 0.937), androstenedione (r = 0.096; p = 0.612), or MDA (r = 0.175; p = 0.345). Similarly, there were no significant correlations between AMH and the whole of retrieved oocytes (r= -0.126; p = 0.507), or immature oocytes (MI + GV) (r = 0.182; p = 0.335). These consequences indicated that MI treatment modifies the relationships between AMH and other follicular fluid factors, potentially contributing to improved ICSI outcomes in PCOS patients (Figs. 2 , 3 ). Discussion This study showed that Myo-inositol significantly reduced serum and follicular fluid (FF) levels of LH, LH/FSH ratio, full testosterone, AMH, and androstenedione in comparison with the placebo group. Conversely, significant increases were observed in the levels of TAC, GPx, and SOD in both serum and FF of the myo-inositol group compared to the placebo group. Additionally, Myo-inositol significantly lowered MDA levels in both serum and FF. Notably, there was no significant difference between two groups in serum or FF levels for FSH, TSH, prolactin, insulin, and estradiol. Because of the established link between insulin resistance and PCOS symptoms, insulin sensitizing agents are often used to address hormonal imbalances [ 3 ]. Artini et al. considered the impacts of myo-inositol (MI) in 50 obese PCOS women. Twelve weeks of treatment led to statistically significant decreases in blood levels of LH, prolactin, testosterone, and insulin, along with a reduction in the LH/FSH ratio. Moreover, insulin sensitivity significantly raised, and menstrual cyclicity was saved in the whole of amenorrheic and oligomenorrheic participants [ 27 ]. Similarly, Genazzani et al. presented similar findings in a study with 20 obese PCOS women. Following 12 weeks of MI administration, they observed significant decreases in plasma levels of LH, prolactin, testosterone, and insulin, as well as improved insulin sensitivity [ 28 ]. Our study investigated the efficacy of 6 weeks of myo-inositol (MI) treatment at 4 g/day on hormonal parameters in serum of PCOS patients. Compared to the placebo group, MI treatment significantly reduced total testosterone, androstenedione, LH, LH/FSH ratio, and AMH levels, while serum FSH, prolactin, TSH, estradiol, and insulin remained unchanged. Supporting the findings of previous studies [ 28 , 29 , 27 ], these results demonstrate that MI administration significantly improves hormonal and metabolic aspects in PCOS subjects. This confirms MI's potential as a safe and effective alternative for PCOS patients undergoing ICSI, with no observed side effects at the standard dosage. Notably, discrepancies with other studies may be attributed to differences in treatment duration of MI and genetic variations within the studied populations. Analyzing the molecular profile of follicular fluid (FF) offers valuable insights into PCOS and its impact on oocyte quality. Intricately intertwined with the oocyte, this biological complex harbors a diverse array of bioactive molecules, critically driving follicle development and maturation [ 30 ]. In PCOS, elevated FF insulin levels may trigger local androgen production, potentially compromising oocyte quality. Dysregulated FF composition, characterized by high levels of LH, androgens, AMH, TSH, and leptin, and an imbalance between pro-oxidative (ROS) and antioxidant (TAC) molecules, hinders reproductive success by decreasing fertilization and implantation rates, increasing embryonic fragmentation, and raising miscarriage rates [ 31 ]. Our study demonstrates the significant effectiveness of 6-week MI treatment in reducing FF levels of LH, LH/FSH ratio, total testosterone, AMH, and androstenedione compared to the placebo group. While some contradictory reports exist [ 5 , 32 ], these discrepancies could likely stem from variations in patient selection criteria, drug dosage, as well as ovulation induction protocols. However, oxidative stress, an imbalance in free radicals and antioxidants of cells, plays a vital role in PCOS development. Numerous studies have demonstrated elevated levels of oxidative stress markers in both serum and follicular fluid (FF) of PCOS patients, potentially linking it to disruptions in cellular organelles and molecular and biochemical procedures [ 33 , 34 ]. Consistent with previous findings [ 35 , 26 , 33 , 36 ], our study confirms elevated oxidative stress in PCOS patients. We observed significant alterations in serum levels of MDA, TAC, SOD, and GPx activity in the MI group in compared to the placebo group. Several late researches have presented that myo-inositol, alone or combined with folic acid, can improve ovulation rates and regulate menstrual cycles [ 37 , 38 , 17 ]. This suggests that, beyond its known impact on fertilization rates, myo-inositol supplementation might also enhance overall oocyte quality and pregnancy outcomes in supported reproductive technologies (ART) [ 35 ]. In our research, we observed a significant development in the whole of immature oocytes in patients treated with myo-inositol. Additionally, both the percentage of grade I embryos (high quality) and the overall good quality embryo rate (grade I + II) significantly improved in the cured group, along with a higher cleavage rate. However, the difference was not statistically significant, although the pregnancy rate was higher in the treated group. This finding aligns with existing literature on the effects of MI [ 23 , 37 , 35 , 11 , 26 ]. One potential mechanism by which Myo-inositol enhances fertilization and embryo quality could be its ability to boost oocyte capacity for the crucial oscillatory Ca2 + response during fertilization and early embryonic improvement [ 5 ]. Calcium (Ca2+) oscillations is vital for normal fertilization and embryonic development [ 17 ]. Myo-inositol, an insulin-sensitizing molecule, has shown promise in PCOS women by improving insulin resistance, steroidogenesis, ovarian stimulation parameters, high-quality embryo formation, and even spontaneous ovulation [ 21 , 39 , 26 ]. However, some review studies suggest that patients may respond differently to myo-inositol therapy based on their specific PCOS phenotypes [ 32 ]. To optimize results, further research could explore adjustments in dose, treatment duration, sample size, patient inclusion criteria, and ovulation induction protocols. Anti-Müllerian hormone (AMH) makes a vital contribution to ovarian follicle improvement and is often elevated in PCOS, correlating with various reproductive and metabolic/endocrine alterations [ 40 ]. A better perception of this link could help us develop better treatments for PCOS [ 41 ]. Several studies have shown elevated AMH in PCOS women compared to healthy individuals, potentially due to abnormally high levels of LH, androgens, and insulin [ 41 ]. Additionally, research has established significant correlations between follicular fluid (FF) AMH and key factors in PCOS pathophysiology, including LH, FSH, testosterone, DHEA-S, BMI, insulin, and oxidative stress [ 42 , 43 , 40 ]. In our study, we observed these same correlations between FF AMH and the biochemical features (LH, FSH, insulin, total testosterone, androstenedione, MDA), immature oocytes, and total retrieved oocytes in the placebo group. These findings support previous studies [ 44 , 43 , 40 ]. Several lines of evidence extra provide the idea that AMH is in a causal way involved in PCOS pathophysiology, demonstrating a near link between alterations in AMH concentrations and improvements in PCOS symptoms in the answer to therapy [ 45 , 41 ]. This study strengthens that connection by showing that myo-inositol not only induced positive alterations in both serum and follicular fluid hormonal parameters but also led to reductions in LH, AMH, elevated androgenic values, and oxidative stress markers. Consequently, we observed improved oocyte and embryo quality. These findings solidify myo-inositol's position as a safe and effective alternative for managing ovulation, hyperandrogenism, and hormonal parameters in PCOS patients, potentially leading to better outcomes. Overall, myo-inositol offers a promising, side-effect-free treatment option. However, this study also has constraints. The sample size is underpowered, and we were unable to track individual ICSI outcomes for oocytes retrieved from the dominant follicles. Conclusions Based on current evidence, myo-inositol stands as an effective therapeutic option for PCOS patients. Its benefits extend beyond improving hormonal profiles in both serum and follicular fluid. It also promotes oocyte maturation, embryo quality, and potentially, ICSI outcomes. Notably, myo-inositol supplemental materials may raise the whole of embryos having more quality, potentially leading to increased pregnancy rates among PCOS women. This aspect warrants further investigation in future studies. Declarations Acknowledgments: The authors are grateful to the members of the IVF unit of the infertility treatment center of the ACECR, Qom. Author contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Zeynab Yazdanpanah, Ebrahim Cheraghi, Mitra Heydari Nasrabadi, and Masoud Salehipour. The first draft of the manuscript was written by Zeynab Yazdanpanah, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Funding : No funding was received for conducting this study. Availability of data: Data underlying this article will be shared on reasonable request to the corresponding author. Conflict of Interests: The authors have no relevant financial or non-financial interests to disclose. Consent to participate: Written, informed consent was obtained from the patients. Consent for Publication: No identifying details of the participants are published in this manuscript; hence, consent for publication is not obtained. Ethical approval: This study was approved by the research ethics committee (Islamic Azad University, Varamin Pishva Branch [IR.IAU.VARAMIN.REC.1400.033]). References Norman RJ, Dewailly D, Legro RS, Hickey TE (2007) Polycystic ovary syndrome. The Lancet 370(9588):685-97. Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO (2016) The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod 31(12):2841-55. Jin P, Xie Y (2018) Treatment strategies for women with polycystic ovary syndrome. Gynecol Endocrinol 34(4):272-77. Pandian Z, McTavish AR, Aucott L, Hamilton MP, Bhattacharya S (2010) Interventions for'poor responders' to controlled ovarian hyper stimulation (COH) in in‐vitro fertilisation (IVF). Cochrane Database Syst Rev 20(1):CD004379. Nazari L, Salehpour S, Hosseini S, Saharkhiz N, Azizi E, Hashemi T, et al. 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Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM (2008) Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol 24(3):139-44. Raffone E, Rizzo P, Benedetto V (2010) Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol 26(4):275-80. Bongrani A, Plotton I, Mellouk N, Ramé C, Guerif F, Froment P, et al. (2022) High androgen concentrations in follicular fluid of polycystic ovary syndrome women. Reprod Biol Endocrinol 20(1):1-16. Moreira MV, Vale-Fernandes E, Albergaria IC, Alves MG, Monteiro MP (2023) Follicular fluid composition and reproductive outcomes of women with polycystic ovary syndrome undergoing in vitro fertilization: A systematic review. Rev Endocr Metab Dis 24(6):1045-73. Unfer V, Russo M, Aragona C, Bilotta G, Montanino Oliva M, Bizzarri M (2023) Treatment with Myo-Inositol Does Not Improve the Clinical Features in All PCOS Phenotypes. Biomedicines 11(6):1759. Liu Y, Yu Z, Zhao S, Cheng L, Man Y, Gao X, et al. (2021) Oxidative stress markers in the follicular fluid of patients with polycystic ovary syndrome correlate with a decrease in embryo quality. J Assist Reprod Genet 38:471-77. Rudnicka E, Duszewska AM, Kucharski M, Tyczyński P, Smolarczyk R (2022) Oxidative Stress and Reproductive Function: Oxidative stress in polycystic ovary syndrome. Reproduction 164(6):145-54. Wdowiak A (2016) Myoinositol improves embryo development in PCOS patients undergoing ICSI. Int J Endocrinol 2016:6273298. Nawrocka-Rutkowska J, Szydłowska I, Jakubowska K, Olszewska M, Chlubek D, Rył A, et al. (2022) Assessment of the parameters of oxidative stress depending on the metabolic and anthropometric status indicators in women with PCOS. Life 12(2):225. Garg D, Tal R (2016) Inositol treatment and ART outcomes in women with PCOS. Int J Endocrinol 2016:1979654. Mendoza N, Pérez L, Simoncini T, Genazzani A (2017) Inositol supplementation in women with polycystic ovary syndrome undergoing intracytoplasmic sperm injection: a systematic review and meta-analysis of randomized controlled trials. Reprod Biomed Online 35(5):529-35. Lagana AS, Vitagliano A, Noventa M, Ambrosini G, D’Anna R (2018) Myo-inositol supplementation reduces the amount of gonadotropins and length of ovarian stimulation in women undergoing IVF: a systematic review and meta-analysis of randomized controlled trials. Arch Gynecol Obstet 298:675-84. Sacha CR, Chavarro JE, Williams PL, Ford J, Zhang L, Donahoe PK, et al. (2020) Follicular fluid anti-Müllerian hormone (AMH) concentrations and outcomes of in vitro fertilization cycles with fresh embryo transfer among women at a fertility center. J Assist Reprod Genet 37:2757-66. Garg D, Tal R (2016) The role of AMH in the pathophysiology of polycystic ovarian syndrome. Reprod Biomed Online 33(1):15-28. Mashiach R, Amit A, Hasson J, Amzalzg S, Almog B, Ben-Yosef D, et al. (2010) Follicular fluid levels of anti-Mullerian hormone as a predictor of oocyte maturation, fertilization rate, and embryonic development in patients with polycystic ovary syndrome. Fertil Steril 93(7):2299-302. Kohzadi M, Khazaei MR, Choobsaz F, Khazaei M (2020) Relationship between serum levels of anti-mullerian hormone, adiponectin and oxidative stress markers in patients with polycystic ovary syndrome. Int J Fertil Steril 14(1):27. Desforges-Bullet V, Gallo C, Lefebvre C, Pigny P, Dewailly D, Catteau-Jonard S (2010) Increased anti-Müllerian hormone and decreased FSH levels in follicular fluid obtained in women with polycystic ovaries at the time of follicle puncture for in vitro fertilization. Fertil Steril 94(1):198-204. Piltonen T, Morin-Papunen L, Koivunen R, Perheentupa A, Ruokonen A, Tapanainen JS (2005) Serum anti-Müllerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome. Hum Reprod 20(7):1820-26. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4172354","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":303662589,"identity":"6cd5175b-e82e-4ad5-af8d-0012b74ca8c9","order_by":0,"name":"Zeynab Yazdanpanah","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Zeynab","middleName":"","lastName":"Yazdanpanah","suffix":""},{"id":303662590,"identity":"1081ace4-6b3a-4c3c-9669-63c92451695b","order_by":1,"name":"Ebrahim 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Branch","correspondingAuthor":true,"prefix":"","firstName":"Mitra","middleName":"Heydari","lastName":"Nasrabadi","suffix":""},{"id":303662592,"identity":"a7dc17d2-f674-4c7c-87cc-694e95c980c3","order_by":3,"name":"Masoud Salehipour","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Masoud","middleName":"","lastName":"Salehipour","suffix":""}],"badges":[],"createdAt":"2024-03-26 22:20:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4172354/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4172354/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57707147,"identity":"3c924d2f-08b9-4a0f-b3e5-a522e6ffec4c","added_by":"auto","created_at":"2024-06-04 15:07:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":64178,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study participants.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4172354/v1/93095751040720a3bafa3756.png"},{"id":57707148,"identity":"8c9d0ff0-4f2f-45b6-8949-b39c03328a0b","added_by":"auto","created_at":"2024-06-04 15:07:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":263969,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between AMH and insulin (a), LH (b), FSH (c), and total testosterone (d) of follicular fluid (FF) in the patients with PCOS.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4172354/v1/bed0c23c2be84bcab89bab5e.png"},{"id":57707149,"identity":"e96b4039-b0f1-43d6-8df2-a5d125cb8976","added_by":"auto","created_at":"2024-06-04 15:07:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":270760,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between AMH and Androstenedione (a), MDA (b), the number of recovered oocytes (c), and immature oocytes (d) of follicular fluid (FF) in the patients with PCOS.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-4172354/v1/9b5fb2101d431cfad51b0e65.png"},{"id":70752001,"identity":"6a291f17-c987-4b40-a1f5-b57eea88cd82","added_by":"auto","created_at":"2024-12-06 09:26:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1585887,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4172354/v1/4006b294-1048-4041-abfa-31cb735a3721.pdf"}],"financialInterests":"","formattedTitle":"The influence of Myoinositol to improve biochemical manifestations of the serum and follicular fluid and ICSI outcomes in patients with PCOS: A prospective randomized research","fulltext":[{"header":"What does this study add to the clinical work?","content":"\u003cp\u003eMyo-inositol administration in women with PCOS undergoing ART could improve their hormonal profile, and the quality of oocytes and embryos.\u003c/p\u003e\n"},{"header":"Introduction","content":"\u003cp\u003eA complex and heterogeneous endocrine disorder is polycystic ovary syndrome (PCOS). It affects 7\u0026ndash;14% of women in their reproductive years. This manifests as infertility, ovarian dysfunction, menstrual irregularity, and androgen excess, often accompanied by typical ovarian ultrasound features [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The etiology and diagnosis of PCOS remain disputed, with many contributing factors suspected, including the hypersecretion of luteinizing hormone (LH), hyperinsulinemia due to insulin resistance, ovarian hyperandrogenism, polycystic ovaries, and decreased fertility [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In recent years, extensive research efforts have been directed towards understanding the underlying mechanisms and developing effective treatments for PCOS [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTwo key factors could be responsible for the low success rate of assisted reproductive techniques (ART) in patients with PCOS: (1) the limited quantity and poor quality of oocytes recovered following ovarian stimulation, and (2) the exact poor fertilization rate following intracytoplasmic sperm injection (ICSI) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Various interventions explored reproductive consequences in inadequate responders undergoing ART, but unfortunately, convincing evidence for their effectiveness remains elusive. This includes insulin-sensitizing agents like pioglitazone, rosiglitazone, troglitazone, D-chiro-inositol, and most notably, metformin [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Therefore, any treatment capable of enhancing oocyte quality holds immense promise for achieving a \"crowning achievement\" in ART for PCOS patients [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMyo-inositol (MI), a cyclic sugar with six hydroxyl groups, acts as a precursor to inositol triphosphate, also known as an intracellular second messenger, that regulates hormones, such as follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and insulin [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Beyond its role as a second messenger, inositol regulates exocrine gland secretion (pancreas, ovaries) and shows promise for assisted reproduction [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Notably, it may improve insulin sensitivity in PCOS, leading to raised glucose uptake [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. MI supplements have shown promise in improving both the metabolic characterization and hyperandrogenism in PCOS patients, while also developing clinical pregnancy rates in infertile patients experiencing ICSI [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Prior investigations have provided evidence for its efficacy in restoring spontaneous ovarian activity and fertility in numerous patients diagnosed with PCOS [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. MI has a vital role in different cellular functions, such as growth, survival, and reproduction [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEvidence suggests that MI administration can enhance ovarian function, potentially reducing the FSH needed for ovarian stimulation and enhancing the quantity and quality of retrieved oocytes [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Notably, research has shown that MI can reinstate spontaneous ovulation and fertility in most PCOS patients [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Furthermore, its potential benefits for insulin sensitivity, oocyte maturation, and embryo quality, have established MI as a clinical treatment for PCOS and a promising intervention for spontaneous ovulation restoration [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. While ART remains crucial for many PCOS women, poor oocyte quality is a major obstacle to successful ICSI cycles, with over two-thirds failing to achieve pregnancy [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Therefore, any treatment capable of enhancing oocyte quality would be a significant advancement in ART procedures. The research is aimed at estimating the impacts of MI on hormonal profiles, oxidative stress markers in serum and follicular fluid, and ICSI consequences in women of PCOS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eResearchers at Qom Infertility Treatment Center conducted a rigorous clinical test (randomized, double-blinded, and placebo-controlled) on a new infertility treatment from May 2022 to May 2023. Sixty infertile PCOS women with 25\u0026ndash;35 years, experiencing Intracytoplasmic sperm injection (ICSI) were enrolled. Patients met the Rotterdam consensus criteria for PCOS (2003) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]: two out of three clinical/biochemical hyperandrogenism, chronic oligo/anovulation, or polycystic ovaries on ultrasound. Criteria of prohibition were hypersensitivity to Myo-inositol, male infertility, infertility beyond anovulation, congenital adrenal hyperplasia, pelvic pathologies, thyroid dysfunction, androgen-secreting neoplasia, diabetes mellitus, Cushing's syndrome, hyperprolactinemia, medications influencing carbohydrate metabolism, severe hepatic/renal diseases, and hormonal analogues (except progesterone) within 2 months. Before the enrollment of patients, informed consent was obtained after approval through the Research Ethics Committee of Islamic Azad University, Varamin Pishva Branch (IR.IAU.VARAMIN.REC.1400.033).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTreatment design\u003c/h2\u003e \u003cp\u003eGynecologists conducted blinded examinations of all participants. Neither patients nor physicians knew which treatment regimen was administered. Throughout the study, participants were instructed to maintain their current levels of physical activity and nutriment and avoid taking new medication. Myo-inositol dosage and duration followed established protocols from Nazari et al. (2020) and Papaleo et al. (2009) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Eighty patients were randomly separated into two groups (n\u0026thinsp;=\u0026thinsp;40): 1) Myo-inositol group (MI group): 40 patients received 2000mg Myo-inositol (Fairhaven Health-LLC, UK) and 1mg folic acid (Raha Co., IRAN) twice daily for 6 weeks. 2) Placebo group: 40 patients received 1mg folic acid only. Patients reported any side effects throughout the treatment period, and these were estimated at the end for frequency and severity. Twenty patients (10 per group) dropped out (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), leaving 60 for the final analysis. A sample range of 60 was determined based on a 95% confidence interval and 80% power [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eControlled ovarian induction\u003c/h2\u003e \u003cp\u003eOvarian stimulation involved daily injections of recombinant gonadotropins (Cinal-F 75IU-CinnaGen, Iran) starting at 150\u0026ndash;75 IU on the 2nd or 3rd day of menstruation, either spontaneous or induced. The dose was modified based on ultrasound monitoring of ovarian response. Once a controlling follicle got to 14 mm in diameter, a daily dose of GnRH antagonist (Cetroide, Merck Serono, Germany) was started and continued until ovulation was triggered. At least three follicles exceeding 18 mm in diameter were required for ovulation triggering with HCG injection (PDpreg5000IU-pooyesh darou, Iran). Oocytes were recovered 34\u0026ndash;36 hours following hCG injection.\u003c/p\u003e \u003cp\u003eBefore treatment, fasting blood samples were gathered twice: on day 3 of the menstrual cycle before the previous ovulation pick-up (OPU) and again during follicular aspiration. Each peripheral blood sample was directly centrifuged at 3000 rpm (10 min) (EBA20, Hettich, UK), and the serum was stored (at -70\u0026deg;C) for later examination. Coming after follicular aspiration and OPU, the follicular fluid (FF) was saved from the first aimed follicle without observable blood contamination. FF samples were centrifuged at 3000 rpm (10 min) using an EBA20 centrifuge (Hettich, UK). For further analysis, the supernatants were then saved at -70\u0026deg;C.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eOocyte retrieval, ICSI, and embryo culture\u003c/h2\u003e \u003cp\u003eSemen analysis followed World Health Organization (WHO) guidelines [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Oocyte retrieval performed under ultrasound guidance using a thin, single-lumen needle (Reproline medical GmbH, Germany) inserted through the vagina. To prepare the oocytes for subsequent analysis, cumulus cells were enzymatically dislodged via a 30-second incubation in 20 IU/mL hyaluronidase (ART-4007A, SAGE BioPharma) followed by gentle mechanical pipetting. Mature oocytes, characterized by the presence of a first polar body, were then identified and isolated under a stereo microscope (Olympus Co, Japan). Only fertilized oocytes with two pronuclei (2PN), identified after overnight culture, were selected for embryo transfer. These embryos were then transferred to a pre-equilibrated cleavage medium (ART-1526, SAGE BioPharma) and cultured for three days. Finally, using an embryo transfer catheter (Cook Medical LLC, USA), the embryos were transferred back into the patient's uterus. Each patient received a maximum of three embryos during transfer. Fertilization was evaluated 12\u0026ndash;16 hours following ICSI by confirming two different pronuclei. Cleavage rate was estimated 24\u0026ndash;36 hours following fertilization. Quality of embryo was graded during third day of insemination using a three-point system [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]: Grade I: Symmetrical blastomeres without fragmentation; Grade II: irregular blastomeres with less than 25% fragmentation; Grade III: irregular blastomeres with over 25% fragmentation. Pregnancy was confirmed by serum β-HCG levels measured on days 14\u0026ndash;15 after transfer. Clinical pregnancies were defined by the presence of both a gestational sac and heartbeat on ultrasound scans performed at 6 weeks post-transfer.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eAssessment of clinical features and hormonal assays\u003c/h2\u003e \u003cp\u003eWeight and height of patients were assessed for defining their body mass index (BMI). Obesity was defined as having a BMI greater than 30. The waist circumference was divided by the hip circumference to estimate the waist-to-hip ratio (WHR). The study measured blood pressure of patients. At the treatment conclusion, during the early follicular phase, participants' weight, waist and hip peripheries, and blood pressure were all reassessed. Serum and follicular fluid levels of the following hormones were evaluated by ELISA based on the manufacturer's guidance: total testosterone (TT, ng/dl; Abcam ab108666), thyroid stimulating hormone (TSH, mIU/ml; Abcam ab100660), follicle provoking hormone (FSH, mIU/ml; Abnova KA0213), luteinizing hormone (LH, mIU/ml; Abcam ab178658), estradiol (E2, pg/ml; Abcam ab108667), androstenedione (AE, ng/ml; Abcam ab178609), anti-Mullerian hormone (AMH, ng/ml; Abcam ab267629), prolactin (PRL, ng/ml; Abcam ab226901), and insulin (INS, mIU/ml; Abcam ab278123). Measurements were performed in duplicate on samples gathered during third day of the menstrual cycle and once during follicular aspiration.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEstimating the oxidative stress biomarkers\u003c/h2\u003e \u003cp\u003eThis study measured malondialdehyde (MDA), a biomarker of lipid peroxidation (LPO) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], in both serum and follicular fluid using the thiobarbituric acid (TBA) colorimetric assay (TBARS Assay Kit, Abcam ab233471). MDA levels were expressed in micromoles per liter (\u0026micro;M). Additionally, total antioxidant capacity (TAC, \u0026micro;M; Abcam ab288592) and levels of activity in superoxide dismutase (SOD, IU/ml; Abcam ab277415) and glutathione peroxidase (GPx, ng/ml; Abcam ab123158) were measured in both samples by ELISA methods based on the manufacturers' guidance. Samples collected on the third day of the menstrual cycle and once during follicular aspiration were measured in duplicate.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eKolmogorov-Smirnov was used to test the distribution of changes in the two groups for normality. Demographic and experimental data were then presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM if normally distributed, or reported using other descriptive statistics if not. For normally distributed data, Statistical comparisons were conducted with Student's t-tests for repeated measures, with a two-tailed p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered significant. Chi-square tests analyzed categorical data when appropriate, while Pearson's correlation coefficients assessed relationships between variables. SPSS software (version 24.0) was used for all analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003eClinical and demographic features\u003c/h2\u003e\n \u003cp\u003eBefore treatment, the two groups demonstrated no significant differences in any baseline characteristics, including age, marital duration, infertility duration, waist circumference, BMI, hip circumference, waist-to-hip ratio, or prevalence of oligomenorrhea and hirsutism (Table\u0026nbsp;1).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003eHormonal, biochemical characteristics, and oxidative stress markers in the serum\u003c/h2\u003e\n \u003cp\u003eAfter a comparison of the MI group with the placebo group, serum levels of LH (P\u0026thinsp;=\u0026thinsp;0.001), LH/FSH ratio (P\u0026thinsp;=\u0026thinsp;0.001), total testosterone (P\u0026thinsp;=\u0026thinsp;0.001), androstenedione (P\u0026thinsp;=\u0026thinsp;0.01), and AMH (P\u0026thinsp;=\u0026thinsp;0.001) showed significant changes, while levels of FSH (P\u0026thinsp;=\u0026thinsp;0.085), estradiol (P\u0026thinsp;=\u0026thinsp;0.574), prolactin (P\u0026thinsp;=\u0026thinsp;0.124), insulin (P\u0026thinsp;=\u0026thinsp;0.230), and TSH (P\u0026thinsp;=\u0026thinsp;0.459) remained stable (Table \u003cspan\u003e2\u003c/span\u003e). Similarly, Table \u003cspan\u003e3\u003c/span\u003e indicates meaningful differences in the adjusted change of serum MDA (P\u0026thinsp;=\u0026thinsp;0.001), TAC (P\u0026thinsp;=\u0026thinsp;0.001), SOD (P\u0026thinsp;=\u0026thinsp;0.01), and GPx (P\u0026thinsp;=\u0026thinsp;0.01) between the MI and placebo groups.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1. Baseline and clinical characteristics of the two groups of PCOS patients (n=80).\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eData are shown as mean \u0026plusmn; SEM. Analysis was performed by\u0026nbsp;Student\u0026rsquo;s t- test.\u003cstrong\u003e\u0026nbsp;NS\u003c/strong\u003e. \u0026nbsp;No differences were observed between the mean of variables in the two groups \u003cem\u003e(P\u0026nbsp;\u003c/em\u003e\u0026gt; 0.05). *\u003cstrong\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003eAnalysis was performed by Pearson Chi-Squared test for comparisons.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePlacebo\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003egroup, folic acid; MI group, Myo-inositol plus folic acid; BMI, body mass index.\u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"left\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.23809523809524%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"54.76190476190476%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment groups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.130434782608695%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMI\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.95652173913044%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlacebo\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.91304347826087%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.23809523809524%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (25-35 years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\"\u003e\n \u003cp\u003e27.77\u0026plusmn;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.238095238095237%\"\u003e\n \u003cp\u003e28.43\u0026plusmn;3.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\"\u003e\n \u003cp\u003e0.423\u003csup\u003e\u0026nbsp;NS\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.23809523809524%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of marriage (year)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\"\u003e\n \u003cp\u003e6.8\u0026plusmn;2.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.238095238095237%\"\u003e\n \u003cp\u003e7.18\u0026plusmn;3.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\"\u003e\n \u003cp\u003e0.608\u003csup\u003e\u0026nbsp;NS\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.23809523809524%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of infertility (year)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\"\u003e\n \u003cp\u003e5.93\u0026plusmn;2.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.238095238095237%\"\u003e\n \u003cp\u003e5.22\u0026plusmn;2.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\"\u003e\n \u003cp\u003e0.246\u003csup\u003e\u0026nbsp;NS\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.23809523809524%\"\u003e\n \u003cp\u003e\u003cstrong\u003eWaist size (cm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\"\u003e\n \u003cp\u003e90.9\u0026plusmn;13.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.238095238095237%\"\u003e\n \u003cp\u003e91.7\u0026plusmn;15.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\"\u003e\n \u003cp\u003e0.931\u003csup\u003e\u0026nbsp;NS\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.23809523809524%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHip size (cm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\"\u003e\n \u003cp\u003e106.4\u0026plusmn;13.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.238095238095237%\"\u003e\n \u003cp\u003e108.4\u0026plusmn;13.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\"\u003e\n \u003cp\u003e0.970\u003csup\u003e\u0026nbsp;NS\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.23809523809524%\"\u003e\n \u003cp\u003e\u003cstrong\u003eWaist/Hip ratio (WHR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\"\u003e\n \u003cp\u003e0.84\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.238095238095237%\"\u003e\n \u003cp\u003e0.83\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\"\u003e\n \u003cp\u003e0.366\u003csup\u003e\u0026nbsp;NS\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.23809523809524%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e27.32\u0026plusmn;3.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.238095238095237%\" valign=\"top\"\u003e\n \u003cp\u003e28.13\u0026plusmn;2.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003e0.853\u003csup\u003e\u0026nbsp;NS\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.23809523809524%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of Oligomenorrhea patients (%) \u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\"\u003e\n \u003cp\u003e8 (26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.238095238095237%\"\u003e\n \u003cp\u003e7 (23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\"\u003e\n \u003cp\u003e0.677\u003csup\u003e\u0026nbsp;NS\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.23809523809524%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of Hirsute patients (%) \u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\"\u003e\n \u003cp\u003e7 (23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.238095238095237%\"\u003e\n \u003cp\u003e6 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\"\u003e\n \u003cp\u003e0.654\u003csup\u003e\u0026nbsp;NS\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2. Oxidative stress markers and hormonal profile of baseline and after treatment in the serum of PCOS patients and their adjusted changes.\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eData are shown as mean \u0026plusmn; SEM. Analysis was performed by\u0026nbsp;Student\u0026rsquo;s t- test.\u0026nbsp;Significant differences for the comparison between treatments are in bold type.\u003c/p\u003e\n \u003cp\u003ePlacebo, folic acid group; MI, Myo-inositol plus folic acid group; FSH, Follicle stimulating hormone; LH, luteinizing hormone; PRL, Prolactin; AMH, Anti-Mullerian hormone; TSH, Thyroid stimulating hormone; E2, estradiol. MDA, malonaldehyde; TAC, Total Antioxidant Capacity; SOD, Superoxide Dismutase; GPx, Glutathione Peroxidase.\u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"630\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"80%\" colspan=\"7\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment groups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.857142857142854%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMI (n=30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.857142857142854%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlacebo (n=30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep value for change comparison\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eBaseline\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAfter treatment\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003echange\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eBaseline\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.59259259259259%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAfter treatment\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003echange\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLH (mIU/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e9.3\u0026plusmn;0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e5.7\u0026plusmn;0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e- 3.6\u0026plusmn;0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e10.9\u0026plusmn;0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e10.4\u0026plusmn;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e1.07\u0026plusmn;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFSH (mIU/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e4.9\u0026plusmn;0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e4.8\u0026plusmn;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e- 0.13\u0026plusmn;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e5.01\u0026plusmn;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e5.3\u0026plusmn;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e0.33\u0026plusmn;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLH/FSH ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e1.9\u0026plusmn;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e1.2\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e- 0.7\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e2\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e2.1\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e0.11\u0026plusmn;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Testosterone (ng/dl)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e65.28\u0026plusmn;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e49.58\u0026plusmn;2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e- 15.7\u0026plusmn;1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e64.32\u0026plusmn;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e82.53\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e18.2\u0026plusmn;1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eE2 (pg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e56.5\u0026plusmn;1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e61.15\u0026plusmn;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e4.7\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e54.8\u0026plusmn;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e57.9\u0026plusmn;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e3.12\u0026plusmn;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRL (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e17.8\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e16.7\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e- 1.1\u0026plusmn;0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e18.23\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e18.07\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e- 0.16\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAndrostenedione (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e2.9\u0026plusmn;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e2.09\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e- 0.86\u0026plusmn;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e2.85\u0026plusmn;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e3.1\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e0.24\u0026plusmn;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eInsulin (\u003c/strong\u003e\u003cstrong\u003emIU/ml\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e19.67\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e19.07\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e- 0.6\u0026plusmn;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e19.44\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e19.28\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e- 0.16\u0026plusmn;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAMH (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e8.5\u0026plusmn;0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e6.9\u0026plusmn;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e- 1.6\u0026plusmn;0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e9.03\u0026plusmn;0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e11.78\u0026plusmn;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e2.7\u0026plusmn;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSH (\u003c/strong\u003e\u003cstrong\u003emIU/ml\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e2.2\u0026plusmn;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e2.01\u0026plusmn;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e- 0.19\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e2.3\u0026plusmn;0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e2.2\u0026plusmn;0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e- 0.08\u0026plusmn;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e0.459\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMDA (\u0026mu;M)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e1.9\u0026plusmn;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e1.2\u0026plusmn;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e- 0.7\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e2.06\u0026plusmn;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e4.02\u0026plusmn;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e1.9\u0026plusmn;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTAC (\u0026mu;M)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e0.79\u0026plusmn;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e1.64\u0026plusmn;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e0.85\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e0.77\u0026plusmn;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e0.3\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e- 0.47\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSOD (IU/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e44.4\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e48.4\u0026plusmn;0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e3.97\u0026plusmn;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e44.1\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e29.1\u0026plusmn;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e- 14.9\u0026plusmn;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGPx (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e35.39\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e39.31\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e3.92\u0026plusmn;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e35.91\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.063492063492063%\"\u003e\n \u003cp\u003e27.74\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\"\u003e\n \u003cp\u003e- 8.17\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.428571428571429%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cdiv\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3. Comparison of the hormonal profile and oxidative stress markers\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;in the\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003efollicular fluid\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eof patients with polycystic ovary syndrome.\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eData are shown as mean \u0026plusmn; SEM. Analysis was performed by Student\u0026rsquo;s t- test. Significant differences for the comparison between treatments are in bold type.\u003c/p\u003e\n \u003cp\u003ePlacebo, folic acid group; MI, Myo-inositol plus folic acid group; FSH, Follicle stimulating hormone; LH, luteinizing hormone; PRL, Prolactin; AMH, Anti-Mullerian hormone; TSH, Thyroid stimulating hormone; E2, estradiol; MDA, malonaldehyde; TAC, Total Antioxidant Capacity; SOD, Superoxide Dismutase; GPx, Glutathione Peroxidase.\u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"65.85365853658537%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment groups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMI (n=30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlacebo (n=30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.37037037037037%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLH (mIU/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e0.89\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e1.18\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFSH (mIU/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e6.04\u0026plusmn;0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e5.6\u0026plusmn;0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e0.350\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLH/FSH ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e0.16\u0026plusmn;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e0.24\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Testosterone (ng/dl)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e6.8\u0026plusmn;0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e8.2\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.047\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eE2 (pg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e483.43\u0026plusmn;32.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e451.33\u0026plusmn;26.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRL (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e18.5\u0026plusmn;0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e18.9\u0026plusmn;0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e0.753\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAndrostenedione (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e404.73\u0026plusmn;25.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e487.23\u0026plusmn;27.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.034\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eInsulin (\u003c/strong\u003e\u003cstrong\u003emIU/ml\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e6.6\u0026plusmn;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e7.73\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAMH (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e438.9\u0026plusmn;23.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e526.07\u0026plusmn;29.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSH (\u003c/strong\u003e\u003cstrong\u003emIU/ml\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e1.63\u0026plusmn;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e1.6\u0026plusmn;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e0.794\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMDA (\u0026mu;M)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e1.96\u0026plusmn;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e4.7\u0026plusmn;0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTAC (\u0026mu;M)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e2.6\u0026plusmn;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e1.9\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSOD (IU/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e42.91\u0026plusmn;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e39.64\u0026plusmn;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.02\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.146341463414636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGPx (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.829268292682926%\"\u003e\n \u003cp\u003e39.77\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.609756097560975%\"\u003e\n \u003cp\u003e36.83\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.414634146341463%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cstrong\u003eTable 4. Distribution of retrieved oocytes, the quality of oocytes and embryos, and pregnancy outcome in PCOS patients.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eData are shown as mean \u0026plusmn; SEM. Analysis was performed by Student\u0026rsquo;s t- test. Significant differences for the comparison between treatments are in bold type.\u0026nbsp;*\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eAnalysis was performed by chi-square test for multiple comparisons \u003cem\u003e(P\u0026nbsp;\u003c/em\u003e\u0026lt; 0.05).\u003cstrong\u003e\u0026nbsp; NS\u003c/strong\u003e. \u0026nbsp; No differences were observed between the mean of variables in the MI group compared with the placebo group \u003cem\u003e(P\u0026nbsp;\u003c/em\u003e\u0026gt; 0.05).\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"62.7906976744186%\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment groups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.74074074074074%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMI (n=30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.888888888888886%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlacebo (n=30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.37037037037037%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of oocytes retrieved\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\"\u003e\n \u003cp\u003e9.5\u0026plusmn;0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\"\u003e\n \u003cp\u003e11.03\u0026plusmn;0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.790697674418604%\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of immature oocytes (GV+MI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\"\u003e\n \u003cp\u003e2.2\u0026plusmn;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\"\u003e\n \u003cp\u003e3.1\u0026plusmn;0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.790697674418604%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.038\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of mature oocytes (MII)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\"\u003e\n \u003cp\u003e7.33\u0026plusmn;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\"\u003e\n \u003cp\u003e7.93\u0026plusmn;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.790697674418604%\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMII/total oocytes retrieved\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\"\u003e\n \u003cp\u003e0.74\u0026plusmn;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\"\u003e\n \u003cp\u003e0.73\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.790697674418604%\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of fertilized oocytes (2PN)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\"\u003e\n \u003cp\u003e7.01\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\"\u003e\n \u003cp\u003e5.7\u0026plusmn;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.790697674418604%\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of cleaved embryos\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\"\u003e\n \u003cp\u003e6.8\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\"\u003e\n \u003cp\u003e5.2\u0026plusmn;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.790697674418604%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.027\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of embryos Grade I\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\"\u003e\n \u003cp\u003e3.27\u0026plusmn;0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\"\u003e\n \u003cp\u003e1.53\u0026plusmn;0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.790697674418604%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of embryos Grade II\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\"\u003e\n \u003cp\u003e2.17\u0026plusmn;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\"\u003e\n \u003cp\u003e1.8\u0026plusmn;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.790697674418604%\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of embryos Grade III\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\"\u003e\n \u003cp\u003e1.33\u0026plusmn;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\"\u003e\n \u003cp\u003e1.83\u0026plusmn;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.790697674418604%\"\u003e\n \u003cp\u003eNS (0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of Good quality of Embryos (I+II)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\"\u003e\n \u003cp\u003e5.43\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\"\u003e\n \u003cp\u003e3.33\u0026plusmn;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.790697674418604%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.2093023255814%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of clinical pregnancy (%) *\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\"\u003e\n \u003cp\u003e11 (36.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\"\u003e\n \u003cp\u003e6 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.790697674418604%\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\u0026nbsp;Hormonal, biochemical characteristics, and oxidative stress biomarkers in the follicular fluid\u003cp\u003eSimilar to serum levels, follicular fluid (FF) concentrations of LH (P\u0026thinsp;=\u0026thinsp;0.001), LH/FSH ratio (P\u0026thinsp;=\u0026thinsp;0.01), total testosterone (P\u0026thinsp;=\u0026thinsp;0.047), Androstenedione (P\u0026thinsp;=\u0026thinsp;0.034), and AMH (P\u0026thinsp;=\u0026thinsp;0.024) significantly increased in the MI group in comparison with the placebo group (Table \u003cspan\u003e3\u003c/span\u003e). Conversely, levels of FSH (P\u0026thinsp;=\u0026thinsp;0.350), estradiol (P\u0026thinsp;=\u0026thinsp;0.448), prolactin (P\u0026thinsp;=\u0026thinsp;0.753), insulin (P\u0026thinsp;=\u0026thinsp;0.082), and TSH (P\u0026thinsp;=\u0026thinsp;0.794) remained stable (Table \u003cspan\u003e3\u003c/span\u003e). Furthermore, adjusted changes in FF levels of MDA (P\u0026thinsp;=\u0026thinsp;0.001), TAC (P\u0026thinsp;=\u0026thinsp;0.001), SOD (P\u0026thinsp;=\u0026thinsp;0.02), and GPx (P\u0026thinsp;=\u0026thinsp;0.01) were significantly different between the MI and placebo groups (Table \u003cspan\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\"\u003e\n \u003ch2\u003eEstimation of oocytes morphology and embryos\u003c/h2\u003e\n \u003cp\u003eWhile the whole of oocytes recovered and mature oocytes did not indicate significant alteration between the MI and placebo groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), the whole of immature oocytes (MI\u0026thinsp;+\u0026thinsp;GV) significantly reduced in the MI group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Cleavage rates were significantly higher in the MI group in comparison with the placebo group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), while the number of fertilized oocytes (2PN) remained similar (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Notably, the MI group raised the formation of good quality embryos (Grade I) on day 3 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), with no significant difference detected in Grades II and III. Overall, the number of good quality embryos (Grade I\u0026thinsp;+\u0026thinsp;II) was significantly higher in the MI group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). However, there was no significant difference in the clinical pregnancy rate between the groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table \u003cspan\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv\u003e\u003c/div\u003e\n \u003cdiv\u003e\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\"\u003e\n \u003ch2\u003eCorrelations between follicular fluid variables\u003c/h2\u003e\n \u003cp\u003eIn the placebo group, follicular fluid (FF) levels of AMH indicated significant positive correlations with LH (r\u0026thinsp;=\u0026thinsp;0.766; p\u0026thinsp;=\u0026thinsp;0.0001), insulin (r\u0026thinsp;=\u0026thinsp;0.512; p\u0026thinsp;=\u0026thinsp;0.004), total testosterone (r\u0026thinsp;=\u0026thinsp;0.642; p\u0026thinsp;=\u0026thinsp;0.0001), androstenedione (r\u0026thinsp;=\u0026thinsp;0.773; p\u0026thinsp;=\u0026thinsp;0.0001), MDA (r\u0026thinsp;=\u0026thinsp;0.438; p\u0026thinsp;=\u0026thinsp;0.016), the whole of retrieved oocytes (r\u0026thinsp;=\u0026thinsp;0.569; p\u0026thinsp;=\u0026thinsp;0.0001), and immature oocytes (MI\u0026thinsp;+\u0026thinsp;GV) (r\u0026thinsp;=\u0026thinsp;0.739; p\u0026thinsp;=\u0026thinsp;0.0001). Notably, a significant negative correlation was observed between FF AMH and FSH (r= -0.563; p\u0026thinsp;=\u0026thinsp;0.001). However, in the MI group, these associations were attenuated or absent. FF AMH levels no longer exhibited significant correlations with LH (r\u0026thinsp;=\u0026thinsp;0.283; p\u0026thinsp;=\u0026thinsp;0.029), FSH (r= -0.037; p\u0026thinsp;=\u0026thinsp;0.845), insulin (r\u0026thinsp;=\u0026thinsp;0.098; p\u0026thinsp;=\u0026thinsp;0.607), total testosterone (r= -0.015; p\u0026thinsp;=\u0026thinsp;0.937), androstenedione (r\u0026thinsp;=\u0026thinsp;0.096; p\u0026thinsp;=\u0026thinsp;0.612), or MDA (r\u0026thinsp;=\u0026thinsp;0.175; p\u0026thinsp;=\u0026thinsp;0.345). Similarly, there were no significant correlations between AMH and the whole of retrieved oocytes (r= -0.126; p\u0026thinsp;=\u0026thinsp;0.507), or immature oocytes (MI\u0026thinsp;+\u0026thinsp;GV) (r\u0026thinsp;=\u0026thinsp;0.182; p\u0026thinsp;=\u0026thinsp;0.335). These consequences indicated that MI treatment modifies the relationships between AMH and other follicular fluid factors, potentially contributing to improved ICSI outcomes in PCOS patients (Figs.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e, \u003cspan\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study showed that Myo-inositol significantly reduced serum and follicular fluid (FF) levels of LH, LH/FSH ratio, full testosterone, AMH, and androstenedione in comparison with the placebo group. Conversely, significant increases were observed in the levels of TAC, GPx, and SOD in both serum and FF of the myo-inositol group compared to the placebo group. Additionally, Myo-inositol significantly lowered MDA levels in both serum and FF. Notably, there was no significant difference between two groups in serum or FF levels for FSH, TSH, prolactin, insulin, and estradiol.\u003c/p\u003e \u003cp\u003eBecause of the established link between insulin resistance and PCOS symptoms, insulin sensitizing agents are often used to address hormonal imbalances [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Artini et al. considered the impacts of myo-inositol (MI) in 50 obese PCOS women. Twelve weeks of treatment led to statistically significant decreases in blood levels of LH, prolactin, testosterone, and insulin, along with a reduction in the LH/FSH ratio. Moreover, insulin sensitivity significantly raised, and menstrual cyclicity was saved in the whole of amenorrheic and oligomenorrheic participants [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Similarly, Genazzani et al. presented similar findings in a study with 20 obese PCOS women. Following 12 weeks of MI administration, they observed significant decreases in plasma levels of LH, prolactin, testosterone, and insulin, as well as improved insulin sensitivity [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study investigated the efficacy of 6 weeks of myo-inositol (MI) treatment at 4 g/day on hormonal parameters in serum of PCOS patients. Compared to the placebo group, MI treatment significantly reduced total testosterone, androstenedione, LH, LH/FSH ratio, and AMH levels, while serum FSH, prolactin, TSH, estradiol, and insulin remained unchanged. Supporting the findings of previous studies [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], these results demonstrate that MI administration significantly improves hormonal and metabolic aspects in PCOS subjects. This confirms MI's potential as a safe and effective alternative for PCOS patients undergoing ICSI, with no observed side effects at the standard dosage. Notably, discrepancies with other studies may be attributed to differences in treatment duration of MI and genetic variations within the studied populations.\u003c/p\u003e \u003cp\u003eAnalyzing the molecular profile of follicular fluid (FF) offers valuable insights into PCOS and its impact on oocyte quality. Intricately intertwined with the oocyte, this biological complex harbors a diverse array of bioactive molecules, critically driving follicle development and maturation [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In PCOS, elevated FF insulin levels may trigger local androgen production, potentially compromising oocyte quality. Dysregulated FF composition, characterized by high levels of LH, androgens, AMH, TSH, and leptin, and an imbalance between pro-oxidative (ROS) and antioxidant (TAC) molecules, hinders reproductive success by decreasing fertilization and implantation rates, increasing embryonic fragmentation, and raising miscarriage rates [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Our study demonstrates the significant effectiveness of 6-week MI treatment in reducing FF levels of LH, LH/FSH ratio, total testosterone, AMH, and androstenedione compared to the placebo group. While some contradictory reports exist [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], these discrepancies could likely stem from variations in patient selection criteria, drug dosage, as well as ovulation induction protocols. However, oxidative stress, an imbalance in free radicals and antioxidants of cells, plays a vital role in PCOS development. Numerous studies have demonstrated elevated levels of oxidative stress markers in both serum and follicular fluid (FF) of PCOS patients, potentially linking it to disruptions in cellular organelles and molecular and biochemical procedures [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Consistent with previous findings [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], our study confirms elevated oxidative stress in PCOS patients. We observed significant alterations in serum levels of MDA, TAC, SOD, and GPx activity in the MI group in compared to the placebo group.\u003c/p\u003e \u003cp\u003eSeveral late researches have presented that myo-inositol, alone or combined with folic acid, can improve ovulation rates and regulate menstrual cycles [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This suggests that, beyond its known impact on fertilization rates, myo-inositol supplementation might also enhance overall oocyte quality and pregnancy outcomes in supported reproductive technologies (ART) [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In our research, we observed a significant development in the whole of immature oocytes in patients treated with myo-inositol. Additionally, both the percentage of grade I embryos (high quality) and the overall good quality embryo rate (grade I\u0026thinsp;+\u0026thinsp;II) significantly improved in the cured group, along with a higher cleavage rate. However, the difference was not statistically significant, although the pregnancy rate was higher in the treated group. This finding aligns with existing literature on the effects of MI [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. One potential mechanism by which Myo-inositol enhances fertilization and embryo quality could be its ability to boost oocyte capacity for the crucial oscillatory Ca2\u0026thinsp;+\u0026thinsp;response during fertilization and early embryonic improvement [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCalcium (Ca2+) oscillations is vital for normal fertilization and embryonic development [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Myo-inositol, an insulin-sensitizing molecule, has shown promise in PCOS women by improving insulin resistance, steroidogenesis, ovarian stimulation parameters, high-quality embryo formation, and even spontaneous ovulation [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. However, some review studies suggest that patients may respond differently to myo-inositol therapy based on their specific PCOS phenotypes [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. To optimize results, further research could explore adjustments in dose, treatment duration, sample size, patient inclusion criteria, and ovulation induction protocols.\u003c/p\u003e \u003cp\u003eAnti-M\u0026uuml;llerian hormone (AMH) makes a vital contribution to ovarian follicle improvement and is often elevated in PCOS, correlating with various reproductive and metabolic/endocrine alterations [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. A better perception of this link could help us develop better treatments for PCOS [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Several studies have shown elevated AMH in PCOS women compared to healthy individuals, potentially due to abnormally high levels of LH, androgens, and insulin [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Additionally, research has established significant correlations between follicular fluid (FF) AMH and key factors in PCOS pathophysiology, including LH, FSH, testosterone, DHEA-S, BMI, insulin, and oxidative stress [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. In our study, we observed these same correlations between FF AMH and the biochemical features (LH, FSH, insulin, total testosterone, androstenedione, MDA), immature oocytes, and total retrieved oocytes in the placebo group. These findings support previous studies [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral lines of evidence extra provide the idea that AMH is in a causal way involved in PCOS pathophysiology, demonstrating a near link between alterations in AMH concentrations and improvements in PCOS symptoms in the answer to therapy [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. This study strengthens that connection by showing that myo-inositol not only induced positive alterations in both serum and follicular fluid hormonal parameters but also led to reductions in LH, AMH, elevated androgenic values, and oxidative stress markers. Consequently, we observed improved oocyte and embryo quality. These findings solidify myo-inositol's position as a safe and effective alternative for managing ovulation, hyperandrogenism, and hormonal parameters in PCOS patients, potentially leading to better outcomes. Overall, myo-inositol offers a promising, side-effect-free treatment option. However, this study also has constraints. The sample size is underpowered, and we were unable to track individual ICSI outcomes for oocytes retrieved from the dominant follicles.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eBased on current evidence, myo-inositol stands as an effective therapeutic option for PCOS patients. Its benefits extend beyond improving hormonal profiles in both serum and follicular fluid. It also promotes oocyte maturation, embryo quality, and potentially, ICSI outcomes. Notably, myo-inositol supplemental materials may raise the whole of embryos having more quality, potentially leading to increased pregnancy rates among PCOS women. This aspect warrants further investigation in future studies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eThe authors are grateful to the members of the IVF unit of the infertility treatment center of the ACECR, Qom.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Zeynab Yazdanpanah, Ebrahim Cheraghi, Mitra Heydari Nasrabadi, and Masoud Salehipour. The first draft of the manuscript was written by Zeynab Yazdanpanah, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: No funding was received for conducting this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data:\u003c/strong\u003e Data underlying this article will be shared on reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interests:\u0026nbsp;\u003c/strong\u003eThe authors have no relevant financial or non-financial interests to disclose.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u0026nbsp;\u003c/strong\u003eWritten, informed consent was obtained from the patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication:\u0026nbsp;\u003c/strong\u003eNo identifying details of the participants are published in this manuscript; hence, consent for publication is not obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e This study was approved by the research ethics committee (Islamic Azad University, Varamin Pishva Branch [IR.IAU.VARAMIN.REC.1400.033]).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNorman RJ, Dewailly D, Legro RS, Hickey TE (2007) Polycystic ovary syndrome. 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Cureus 12(5):e8079.\u003c/li\u003e\n\u003cli\u003eLesoine B, Regidor P-A (2016) Prospective randomized study on the influence of myoinositol in PCOS women undergoing IVF in the improvement of oocyte quality, fertilization rate, and embryo quality. Int J Endocrinol 2016:4378507.\u003c/li\u003e\n\u003cli\u003eRotterdam E (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81(1):19-25.\u003c/li\u003e\n\u003cli\u003ePapaleo E, Unfer V, Baillargeon J-P, Fusi F, Occhi F, De Santis L (2009) Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril 91(5):1750-54.\u003c/li\u003e\n\u003cli\u003eMachin D, Campbell MJ, Tan SB, Tan SH. Sample size tables for clinical studies. John Wiley \u0026amp; Sons; 2011.\u003c/li\u003e\n\u003cli\u003eWorldHealthOrganization. Examination and processing of human semen. Geneva: World Health. 2010.\u003c/li\u003e\n\u003cli\u003eAkbari Sene A, Tabatabaie A, Nikniaz H, Alizadeh A, Sheibani K, Mortezapour Alisaraie M, et al. (2019) The myo-inositol effect on the oocyte quality and fertilization rate among women with polycystic ovary syndrome undergoing assisted reproductive technology cycles: a randomized clinical trial. Arch Gynecol Obstet 299(6):1701-07.\u003c/li\u003e\n\u003cli\u003eArtini PG, Di Berardino O, Papini F, Genazzani A, Simi G, Ruggiero M, et al. (2013) Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol 29(4):375-79.\u003c/li\u003e\n\u003cli\u003eGenazzani AD, Lanzoni C, Ricchieri F, Jasonni VM (2008) Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol 24(3):139-44.\u003c/li\u003e\n\u003cli\u003eRaffone E, Rizzo P, Benedetto V (2010) Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol 26(4):275-80.\u003c/li\u003e\n\u003cli\u003eBongrani A, Plotton I, Mellouk N, Ram\u0026eacute; C, Guerif F, Froment P, et al. (2022) High androgen concentrations in follicular fluid of polycystic ovary syndrome women. Reprod Biol Endocrinol 20(1):1-16.\u003c/li\u003e\n\u003cli\u003eMoreira MV, Vale-Fernandes E, Albergaria IC, Alves MG, Monteiro MP (2023) Follicular fluid composition and reproductive outcomes of women with polycystic ovary syndrome undergoing in vitro fertilization: A systematic review. Rev Endocr Metab Dis 24(6):1045-73.\u003c/li\u003e\n\u003cli\u003eUnfer V, Russo M, Aragona C, Bilotta G, Montanino Oliva M, Bizzarri M (2023) Treatment with Myo-Inositol Does Not Improve the Clinical Features in All PCOS Phenotypes. 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Life 12(2):225.\u003c/li\u003e\n\u003cli\u003eGarg D, Tal R (2016) Inositol treatment and ART outcomes in women with PCOS. Int J Endocrinol 2016:1979654.\u003c/li\u003e\n\u003cli\u003eMendoza N, P\u0026eacute;rez L, Simoncini T, Genazzani A (2017) Inositol supplementation in women with polycystic ovary syndrome undergoing intracytoplasmic sperm injection: a systematic review and meta-analysis of randomized controlled trials. Reprod Biomed Online 35(5):529-35.\u003c/li\u003e\n\u003cli\u003eLagana AS, Vitagliano A, Noventa M, Ambrosini G, D\u0026rsquo;Anna R (2018) Myo-inositol supplementation reduces the amount of gonadotropins and length of ovarian stimulation in women undergoing IVF: a systematic review and meta-analysis of randomized controlled trials. Arch Gynecol Obstet 298:675-84.\u003c/li\u003e\n\u003cli\u003eSacha CR, Chavarro JE, Williams PL, Ford J, Zhang L, Donahoe PK, et al. (2020) Follicular fluid anti-M\u0026uuml;llerian hormone (AMH) concentrations and outcomes of in vitro fertilization cycles with fresh embryo transfer among women at a fertility center. J Assist Reprod Genet 37:2757-66.\u003c/li\u003e\n\u003cli\u003eGarg D, Tal R (2016) The role of AMH in the pathophysiology of polycystic ovarian syndrome. Reprod Biomed Online 33(1):15-28.\u003c/li\u003e\n\u003cli\u003eMashiach R, Amit A, Hasson J, Amzalzg S, Almog B, Ben-Yosef D, et al. (2010) Follicular fluid levels of anti-Mullerian hormone as a predictor of oocyte maturation, fertilization rate, and embryonic development in patients with polycystic ovary syndrome. Fertil Steril 93(7):2299-302.\u003c/li\u003e\n\u003cli\u003eKohzadi M, Khazaei MR, Choobsaz F, Khazaei M (2020) Relationship between serum levels of anti-mullerian hormone, adiponectin and oxidative stress markers in patients with polycystic ovary syndrome. Int J Fertil Steril 14(1):27.\u003c/li\u003e\n\u003cli\u003eDesforges-Bullet V, Gallo C, Lefebvre C, Pigny P, Dewailly D, Catteau-Jonard S (2010) Increased anti-M\u0026uuml;llerian hormone and decreased FSH levels in follicular fluid obtained in women with polycystic ovaries at the time of follicle puncture for in vitro fertilization. Fertil Steril 94(1):198-204.\u003c/li\u003e\n\u003cli\u003ePiltonen T, Morin-Papunen L, Koivunen R, Perheentupa A, Ruokonen A, Tapanainen JS (2005) Serum anti-M\u0026uuml;llerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome. Hum Reprod 20(7):1820-26.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Myoinositol, Polycystic ovarian syndrome, Intracytoplasmic sperm injection, Reproductive outcomes","lastPublishedDoi":"10.21203/rs.3.rs-4172354/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4172354/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe research investigated the capacity of Myo-inositol (MI) in order that it improves biochemical markers in serum and follicular fluid, and ultimately, intracytoplasmic sperm injection (ICSI) outcomes of women with PCOS.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eSixty infertile patients with PCOS who were undergoing ovulation induction for ICSI, were randomly divided to two groups. The MI group received 2000 mg Myo-inositol\u0026thinsp;+\u0026thinsp;1 mg folic acid twice a day for 6 weeks with starting the ICSI cycle. For the same period, the control group received a placebo containing only folic acid (1 mg). Levels of hormonal profiles in serum and follicular fluid, as well as oxidative stress markers (MDA, TAC, GPx, and SOD) were estimated using an ELISA assay. Primary end points were ICSI cycle outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eCompared to the placebo group, the MI group demonstrated significant reduction in serum and follicular fluid levels of LH, LH/FSH ratio, total testosterone, AMH, and Androstenedione. Furthermore, the MI group exhibited meaningful increases in TAC, GPx, and SOD, but MDA significantly decreased. While the number of recovered and mature oocytes is not similar statistically among the groups, the MI group showed significant improvements in the percentage of immature oocytes, cleavage rate, and good embryo quality. A meaningful correlation was checked between follicular fluid AMH level and LH, FSH, total testosterone, Androstenedione, insulin, MDA, the number of recovered oocytes, and immature oocytes.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur outcomes indicate that Myo-inositol administration in women with PCOS undergoing ART helps to improve their hormonal profiles, and the quality of oocytes and embryos. (\u003cb\u003eTrial registration\u003c/b\u003e: IRCT202220921056008N1)\u003c/p\u003e","manuscriptTitle":"The influence of Myoinositol to improve biochemical manifestations of the serum and follicular fluid and ICSI outcomes in patients with PCOS: A prospective randomized research","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-04 15:07:25","doi":"10.21203/rs.3.rs-4172354/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6bc7a45a-3123-4cc7-9101-95c3d0e8902a","owner":[],"postedDate":"June 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-06T09:18:35+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-04 15:07:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4172354","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4172354","identity":"rs-4172354","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}