PCOS Patients Research Articles

The Effect Myo-Inositol and D-Chiro-Inositol Co-Supplementation in Women with PCOS: A review

PCOS is an endocrine condition caused mostly by infertility and menstrual abnormalities. The pathophysiology of PCOS is related to the lack of hormone, reproductive and metabolic regulation which were stimulated by a variety of factors, such as insulin resistance. PCOS treatment strategies are always oral contraceptive pill (OCP) combination oral contraceptive pill, which can cause metabolism and cardiovascular side effect and is difficult to comply with consistently. Several studies stated that the combination between Myo-inositol and D-chiro-inositol (MI-DI) as therapeutics alternative to improve PCOS condition in reproductive-age women. This study investigates combination of MI-DI on PCOS in reproductive-age women. A literature review was used to conduct this investigation through PubMed, ScienceDirect, and Google Scholar databases. 1382 publications were identified in the search results, and 6 studies were relevant and matched the requirements for this investigation. MI-DI co-supplementation is effective to ameliorate metabolic and clinical abnormalities of PCOS patients.

Association between hormonal Imbalance and Interleulin-10 level with Polycystic Ovarian Syndrome of Iraqi women

Objectives: To determine the level of interleukin-10 as inflammatory marker in PCOS patients and compared with healthy control and explore the correlation between IL-10 level and other biochemical markers in PCOS patients.
 Methods: Whole blood samples of 80 PCOS obese patients and 80 healthy people were collected in duration from Dec., 2021 to April, 2022, at the gynecological and obstetric teaching hospital, Kerbala health directorate, Iraq. The Rotterdam criteria-2003 was accepted to PCOS females with age range between (18-40 years), while the apparently control group with age ranged between (18-40 years). BMI and WHR and hormonal status (LH, FSH, LH/FSH ratio, Prolactin, Free Testosterone) were determined. Elabscience/USA ELISA kit uses the Sandwich-ELISA principle was used to determined IL-10 level in serum.
 Results: The obese PCOS women had a seriously decrease in IL-10 (pg/ml) level when compare with apparently healthy control group with mean ± SD for patients (2.192 ± 0.47) and for control group (4.532 ± 0.75) P value < 0.0001, and there are significant negative correlations between IL-10 and (BMI p<0.0001, r= -0.66), (WHR p<0.0001, r= -0.66), (LH p<0.0001, r= -0.63), (LH: FSH ratio p<0.0001, r= -0.72), (Prolactin p=0.008, r= -029). 
 Conclusion: Our findings indicate that the IL-10 level decrease in PCOS obese patients and has significant association with pathogenesis and progression of disease.

Immunological detection of Platelet-derived growth factor and Vascular endothelial growth factor in Iraqi women with Polycystic Ovarian Syndrome

Background: platelet-derived growth factor (PDGF) signaling controls a wide range of the mesenchymal cell origin lineages throughout the development and in the females with the polycystic ovarian syndrome. Vascular endothelial growth factor (VEGF) has an important impact on vascularization of the tissues generally, and in pathogenesis of a wide range of the illnesses. The PCOS has been found related to high VEGFexpression levels. Aims and Objectives: for the detection and studying of immunological effects of PDGF and VEGF in the Iraqi females with the PCOS. Materials and Methods: 250 Iraqi females, aged between 20 and 50 years have been divided to twogroups, which are: study group (n=125, PCOS) and control group (n=125, which mainly consisted from normal females), the samples of the blood have been obtained in 2ndmenstruate cycle day, VEGF and PDGF concentrations have been estimated for every one of the groups. Results: the PCOS patients have shown a considerable difference in comparison to the other group. The level has been 71.22±65.23Pg/ml and 243± 153.44Pg/ml, for the controls and PCOS patients respectively. In addition to that, the PCOS patients have shown a considerable difference in comparison to the other group. . The level has been 71.22±65.23Pg/ml and 243± 153.44Pg /ml, for the controls and PCOS patients respectively. Conclusions: Increases concentration of PDGF and VEGF in PCOS women related to ovulation lack and that lead to increases the risk of PCOS appearance.

Need to Introduce the Finding of Obesity or Normal Body Weight in the Current Diagnostic Criteria and in the Classification of PCOS.

The diagnosis of PCOS is based on the Rotterdam guidelines: chronic anovulation, hyperandrogenism (biologic or clinical) and polycystic ovaries on ultrasound. Two of these three criteria are sufficient for making diagnosis of PCOS. However, one characteristic that is often associated to PCOS (obesity with severe insulin resistance and metabolic alteration regarding glucose metabolism and lipid pattern) has remained out of the current classification of PCOS. Because of this, patients with different metabolic and cardiovascular risk may be included in the same phenotype, and it makes more difficult to establish clear strategies of follow-up and treatment of the patients with increased risks, and also may hide genetic or environmental differences between PCOS patients. Our recent study has shown that metabolic alterations are linked to the weight and not to the Rotterdam phenotypes. Because of this, we suggest a new classification of PCOS phenotypes that divides each Rotterdam phenotype in obese (ob) or lean (l) sub-phenotype. An improved classification of PCOS may be essential for permitting new progress in our understanding of pathogenesis and treatment of PCOS (or of the different disorders that are part of PCOS).

Qi Gong Wan ameliorates adipocyte hypertrophy and inflammation in adipose tissue in a PCOS mouse model through the Nrf2/HO-1/Cyp1b1 pathway: Integrating network pharmacology and experimental validation in vivo

Ethnopharmacological relevanceInitially recorded in Yifang Jijie (an ancient Chinese text), Qi Gong Wan (QGW) is used to treat obese women with infertility. QGW can help promote follicular development and maturation, regulate the balance of serum hormones between testosterone and estradiol, enhance endometrial receptivity, improve waist circumference, and ameliorate insulin resistance. It contains eight herbs: Pinellia ternata (Thunb.) Makino (Banxia), Citrus maxima (Burm.) (Juhong), Poria cocos (Schw.) Wolf. (Fuling), Atractylodes macrocephala Koidz (Baizhu), Cyperus rotundus L. (Xiangfu), Conioselinum anthriscoides 'Chuanxiong' (Chuanxiong), Massa Medicata Fermentata (Shenqu), and Glycyrrhiza uralensis Fisch. ex DC. (Gancao). However, the underlying mechanism of how QGW affects women with PCOS remains unclear.Aim of the study: QGW has been widely used to treat PCOS patients with obesity clinically. This study was designed to identify its chemical and pharmacological properties. Materials and methodsNetwork pharmacology was used to predict the active compounds, potential targets, and pathways of QGW. Female C57BL/6J mice were injected with letrozole and fed a high-fat diet to establish a PCOS-insulin resistance (PCOS-IR) model. Body weight, estrous cycles, ovarian pathology, and serum insulin resistance were measured. qRT-PCR was used to examine the inflammation-related and steroid hormone biosynthesis-related mRNA expression in adipose tissue. Western blotting was used to determine the protein levels of Nrf2, HO-1, and Cyp1b1 in adipose tissue. Molecular docking was used to reveal the key chemical compounds of QGW. ResultsNetwork pharmacology revealed a total of 91 active ingredients in QGW that were associated with 167 targets. QGW could potentially treat PCOS-IR via nitrogen metabolism, steroid hormone biosynthesis, and ovarian steroidogenesis pathways. In the PCOS-IR mouse model, we found that QGW decreased the mean diameter of adipocytes and the total adipocyte area. Furthermore, QGW was found to significantly lower the expression of inflammation-related genes including Tnfɑ and C4a/b and the steroid hormone biosynthesis-related gene Cyp1b1. QGW showed a tendency to improve cystic follicles, fasting insulin, and HOMA-IR index in the PCOS-IR mouse model. Combining these findings with the results of KEGG analysis, we conclude that QGW promotes the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue under conditions of PCOS. Molecular docking revealed that rutin, nicotiflorin, and baicalein may be the key chemical compounds of QGW through which it improves adipocyte hypertrophy and inflammation. ConclusionsQGW improved adipocyte hypertrophy and inflammation in the PCOS-IR mouse model by activating the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue. Our work thus provides a new research avenue for the study of traditional Chinese medicine in the treatment of PCOS.

MiR-93-5p promotes granulosa cell apoptosis and ferroptosis by the NF-kB signaling pathway in polycystic ovary syndrome.

KGN cells have similar ovarian physiological characteristics and are used to study the function and regulatory mechanism of GCs. In this study, KGN cells were transfected with si-NC, si-miR93-5p, oe-NC and oe-miR93-5p. A cell counting kit-8 assay, flow cytometry and western blotting were performed to observe the proliferation and apoptosis of KGN in different groups. Subsequently, the levels of reactive oxygen species, malondialdehyde, GPX4, SLC7A11 and Nrf2, which are indicators of ferroptosis, were measured by a dihydroethidium fluorescent dye probe, biochemical kit, western blotting and reverse transcription quantitative polymerase chain reaction. Ultimately, bioinformatic analysis and experimental methods were used to examine the interaction between miR-93-5p and the NF-κB signaling pathway. miR-93-5p was upregulated in the GCs of PCOS patients. Overexpression of miR-93-5p promoted apoptosis and ferroptosis in KGN cells, while knockdown of miR-93-5p showed the reverse effect. Biological analysis and subsequent experiments demonstrated that miR-93-5p negatively regulates the NF- κB signaling pathway. miR-93-5p promotes the apoptosis and ferroptosis in GC by regulating the NF-κB signaling pathway. Silencing of miR-93-5p protects against GC dysfunction. Our study identified miR-93-5p as a new molecular target for improving the function of GCs in PCOS patients.

Diagnostic value of total testosterone and free androgen index measured by LC-MS/MS for PCOS and insulin resistance.

The objective of the study was to explore the clinical significance of steroid hormones in the diagnosis of PCOS and PCOS-related insulin resistance through liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and chemiluminescent immunoassay (CLIA). The study included 114 patients with PCOS and 100 controls. Steroid hormone levels in serum were measured using LC-MS/MS and CLIA. The Bland-Altman method was used to check the consistency between the two methods. The diagnostic value of the LC-MS/MS method for female hyperandrogenemia and PCOS was evaluated. Women with PCOS were younger than controls on average (p < 0.001). PCOS patients had higher luteal hormone (LH, p < 0.001), insulin (p=0.002), estradiol (E2, p < 0.001), total testosterone (TT, p < 0.001), free androgen index (FAI, p=0.021), dehydroepiandrosterone sulfate (DHEA, p=0.021), insulin resistance index (HOMA-IR) (p=0.034), and fasting glucose (p=0.017) levels than controls as measured by CLIA. The diagnostic value of TT was the best, and the area under the AUC curve was 0.766. Women with PCOS had higher androstenedione (A2, p < 0.001), FAI (p < 0.001), TT (p < 0.001), and 17-hydroxyprogesterone (17-OHP, p < 0.001) levels than controls as measured by LC-MS/MS. The ROC curve showed that the diagnostic efficacy of A2, TT, and 17-OHP was 0.830, 0.851, and 0.714, respectively. The consistency of TT detected by LC-MS/MS and CLIA was poor according to the Bland-Altman method. Detected TT by LC-MS/MS had the highest diagnostic efficiency for PCOS. The diagnostic power of the LC-MS/MS results for PCOS-related insulin resistance was analyzed. The results showed that the FAI had the highest diagnostic power, with an ROC curve of 0.798. LC-MS/MS is more sensitive and accurate than CLIA in the determination of serum TT and FAI. TT is more effective for the diagnosis of PCOS, whereas FAI is more valuable in the diagnosis of insulin resistance.

Increased Prevalence of Elevated DHEAS in PCOS Women with Non-Classic (B or C) Phenotypes: A Retrospective Analysis in Patients Aged 20 to 29 Years.

It is well known that a subgroup of women with PCOS present an excessive adrenal androgen production, generally associated with ovarian hyperandrogenism. In the past, it has been impossible to correlate adrenal hyperandrogenism to any clinical or hormonal pattern of PCOS. However, adrenal androgens are strictly dependent on age and their blood values reduce by 40% in patients moving from their twenties to thirties. Due to this, serum DHEAS values are strongly influenced by the age distribution of studied populations. To avoid this bias, in this study we retrospectively analyzed the clinical and hormonal data of PCOS women in their twenties (age between 20 and 29 years). Data of 648 young hyperandrogenic women with PCOS were evaluated. Serum DHEAS was increased in a third (33%) of studied patients and was associated with higher values of testosterone (T) and androstenedione (A). In each phenotype, patients with high DHEAS had higher values of T and A than patients with normal DHEAS of the same phenotype. Therefore, a DHEAS increase is generally part of a generalized higher androgen production in a subgroup of PCOS patients, independently of the finding of anovulatory or ovulatory cycles or of polycystic or normal ovaries. However, our study showed some important differences between PCOS phenotypes. A lower prevalence of increased DHEAS in A phenotype PCOS patients who generally have the highest androgen levels, versus non-classic (B or C) PCOS phenotypes, was observed. It was also found that patients with A phenotype PCOS present significantly lower BMI and serum insulin than patients with normal DHEAS of the same phenotype while, in patients with the B or C phenotype, the opposite occurs. We conclude that adrenal hyperandrogenism is more common in patients with non-classic (B and C) phenotypes of PCOS and is generally part of a generalized higher production of androgens in a subgroup of PCOS patients. However, other factors may increase the adrenal androgen production and influence the clinical expression of the syndrome. More studies in large, selected for age, populations of PCOS women with different phenotypes are needed.

Intravoxel incoherent motion magnetic resonance imaging and derived parameters in the assessment for polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrinologic disorder in reproductive age. Diagnosis is based on clinical, laboratory, and ultrasonography findings. However, the application of ultrasound for the diagnosis of PCOS in overweight and sexually inactive patients may be limited. The purpose of this study was to display the imaging characteristics of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI)-derived parameters as Dtrue (slow diffusion coefficient), D* (perfusion-related diffusion), f (perfusion fraction), and apparent diffusion coefficient (ADC) in PCOS.ResultsA total of 43 women, 20 with PCOS (mean age, 24.09 ± 3.92 years) and 23 healthy control (mean age, 23 ± 1.67 years), were included. IVIM MRI-derived parameters of the ovarian stroma were measured by two observers. Mean D* and f values were found to be higher in PCOS patients than in individuals in the control group (p = 0.011 and p = 0.004, respectively). The ADC value was found to be significantly lower in the patient group (p = 0.003). There was no statistically significant difference between two groups in Dtrue (p = 0.742). The interclass correlation analysis of two observers for both groups showed a good-to-excellent agreement. The ROC produced an AUC of 0.521, a sensitivity of 50%, a specificity of 57%, and a cut-off value of 1.48 × 10−3 mm2/s for Dtrue; an AUC of 0.769, a sensitivity of 55%, a specificity of 67%, and a cut-off value of 22.25 × 10−3 mm2/s for D*; an AUC of 0.734, a sensitivity of 55%, a specificity of 62%, and a cut-off value of 20.87% for f; an AUC of 0.893, a sensitivity of 90%, a specificity of 33%, and a cut-off value of 1.37 × 10−3 mm2/s for ADC.ConclusionsIVIM MRI would be an alternative imaging tool in the diagnosis of PCOS with a good-to-excellent agreement and with acceptable sensitivity and specificity.

Associations between omega-3 fatty acids and insulin resistance and body composition in women with polycystic ovary syndrome.

BackgroundPolycystic ovary syndrome (PCOS) is strongly associated with abdominal obesity and insulin resistance and effective approaches to nutrition (e.g., omega-3 fatty acids intake) might improve the cardiometabolic risk profile. This study aimed to examine the associations of dietary and serum omega-3 fatty acids with insulin resistance (IR) and body composition among PCOS patients.MethodsA total of 185 patients with PCOS were included in our analysis. Dietary information was collected through face-to-face interviews using a 102-item food frequency questionnaire (FFQ). Serum omega-3 fatty acid levels were measured with the gas chromatography method. Body composition was measured by both dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance (BIA) methods. The multivariable linear regression model was applied to analyze the associations of dietary and serum omega-3 fatty acids with the levels of Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and body composition parameters among PCOS patients.ResultsOur results indicated that the dietary long-chain omega-3 polyunsaturated fatty acids (PUFA) intakes were negatively associated with HOMA-IR (β = –0.089, P = 0.040), fat mass (β = –0.022, P = 0.047), and body fat percentage (β = –0.026, P = 0.032). For serum biomarkers, higher total omega-3 PUFAs levels (β = –0.158, P = 0.021) and long-chain omega-3 PUFAs levels (β = –0.187, P < 0.001), particularly eicosapentaenoic acid (EPA) (β = –164, P = 0.011) and docosahexaenoic acid (DHA) (β = –0.158, P = 0.001) were also associated with decreased HOMA-IR. In addition, generally, dietary and serum long-chain omega-3 PUFA levels, DPA, and DHA levels were both positively associated with muscle mass measured by DXA; whereas serum total, long-chain and individual omega-3 PUFA levels (e.g., DPA, EPA, and DHA) were all negatively associated with fat mass and body fat percentage. These findings were further confirmed by the findings for body composition measured by the BIA method.ConclusionHigher levels of dietary and serum omega-3 PUFAs, particularly long-chain omega PUFAs (DPA and DHA), might have beneficial effects on metabolic parameters and body composition among PCOS patients.

The relationship of serum and follicular fluid pregnancy-associated plasma protein (PAPP-A) levels with endometrial thickness in PCOS and non-PCOS women undergoing ICSI-cycles

Pregnancy-associated plasma protein (PAPP-A) is a metalloproteinase that binds and cleaves insulin-like growth factor-binding protein 4 (IGFBP4), then releases IGF-1 from the IGFBP4/IGF-1 complex, activating the IGF pathway. As a result, in the IGF system, PAPP-A is regarded as a bioactive IGF-1 enhancing enzyme. IGFs and IGF receptors are thought to play a role in endometrium receptivity. A critical endometrium receptivity biomarker was up-regulated by PAPP-A. The present study aimed to assess the relationship of PAPP-A levels in serum and follicular fluid with endometrial thickness in PCOS and non PCOS women enrolled in the ICSI cycle. Forty-five infertile Iraqi women with PCOS and non-PCOS criteria were nominated from those who were attending the Higher Institute for Infertility Diagnosis and Assisted Reproductive Technologies clinic. The age of the included women ranged between 20-45 years. PAPP-A level measures in serum (at pick-up day and embryo transfer day) and follicular fluid. In non-PCOS patients, PAPP-A has higher level in serum and follicular fluid but without statistically significant difference comparing with PCOS patients. Level of PAPP-A and endometrial thickness increased significantly at the day of embryo transfer in contract with pick up day. The result did not show any correlation between PAPPA levels and endometrial thickness in both days. While, there was insignificant increase in endometrial thickness at both pick up and transfer days between pregnant and non-pregnant women. In conclusion, level of PAPP-A (in serum and follicular fluid) and endometrial thickness at the time of embryo transfer were significantly higher than pick-up day, this study did not establish a statistical significant relationship between serum and follicular fluid in PAPP-A levels and endometrial thickness.

Genetic Polymorphisms in Polycystic Ovarian Syndrome

Polycystic ovarian syndrome can be defined as an endocrine disorder that most affects the reproductive system of women of childbearing age; its causes are not exactly known. However, the majority of the experts agree that it is a multifactorial entity with multiple factors. Genetics is becoming increasingly important. In recent years, several genes that are involved in the pathogenic processes of this syndrome have been identified. Within these, the most important ones are the ones that encode steroidogenesis enzymes and insulin receptors, as well as other hormones that are associated with the actions of insulin and gonadotropins and their receptors. The results obtained included 1) women with PCOS had significantly lower levels of adiponectin compared to controls. Adiponectin levels were significantly lower in both lean and obese women with PCOS compared to the control group. 2) PCOS women had significantly higher levels of LH, FSH, LH/FSH ratio, and total testosterone compared to controls. 3) Both lean and obese PCOS women had significantly higher levels of LH, LH/FSH ratio, and total testosterone compared to the control group, however, FSH levels were significantly increased only in obese PCOS women compared to controls. 4) PCOS women had significantly higher levels of total cholesterol, triglycerides, LDL cholesterol, VLDL cholesterol, and lower levels of HDL-cholesterol compared to controls. 5) Both lean and obese PCOS women had significantly higher levels of total cholesterol, triglycerides, LDL cholesterol, and VLDL cholesterol compared to controls. Only obese PCOS women had significantly lower levels of HDL-cholesterol compared to the controls. 6) The genotype analysis of FSHR gene polymorphism showed that the heterozygote Ala/Thr genotype was significantly more frequent in PCOS patients than in controls (64.1% versus 40%).

Effect of weight loss on pregnancy outcomes, neuronal-reproductive-metabolic hormones and gene expression profiles in granulosa cells in obese infertile PCOS patients undergoing IVF-ET.

ObjectiveTo investigate the effect of weight loss on pregnancy outcomes, PCOS related neuronal-reproductive-metabolic hormones and ovarian granulosa cell gene expression profiles in obese PCOS infertile patients undergoing in vitro fertilization-embryo transfer (IVF-ET).Methods75 patients undergoing IVF-ET due to tubal factors alone collected as the control group (group A), and 352 patients with obese PCOS infertility were divided into four groups according to the amount of weight loss before IVF: 0 kg (group B), 1-5 kg (group C), 5-10 kg (group D), and >10 kg (group E). Six cases of ovarian granulosa cells were collected randomly with the random number table method in each group for detecting mRNA profiling. Pathway networks and biological functions of the differentially expressed genes were analyzed. Validation by RT-PCR was performed.Results(1) The levels of luteinizing hormone(LH), testosterone(T) and homeostasis model assessment insulin resistance(HOMA-IR) in group E were significantly lower than those in groups B and C (P<0.05). (2) Compared with groups A and E, groups B and C showed increased total gonadotropin (Gn) and days of Gn stimulation (P<0.05), and the E2 level on trigger day and number of oocytes obtained in group B was significantly less than that in group E (P<0.05 or 0.01). Embryo implantation rate, clinical pregnancy rate and live birth rate were increased and miscarriage rate was decreased in groups A, D and E compared with group B (P<0.05 or 0.01). (3) There were significant differences among the control group and PCOS groups in some genes that are involved in neuronal-reproductive-metabolic endocrine, transcriptional regulation, cell proliferation and differentiation, etc (P<0.05). RNA-Seq results were validated by real time PCR analysis for the expression of follicle stimulating hormone receptor (FSHR), drosophila mothers against decapentaplegic protein 7(Smad7) and glutathione peroxidase 3(GPX3) genes that are known to have an important role in follicular development. Functional alterations were confirmed by the improvement in the ovarian responsiveness to Gn and embryo quality.ConclusionWeight loss more than 5kg may regulate the neuroreproductive endocrine hormone secretion, insulin resistance and gene expression profiles of ovarian granulosa cells, so as to improve the ovarian responsiveness to Gn, the embryo quality, embryo implantation rate, clinical pregnancy rate, live birth rate, and reduce the spontaneous abortion rate in obese infertile PCOS patients undergoing IVF-ET.Clinical trial registration www.chictr.org.cn, identifier ChiCTR1800018298.

Aberrant BMP15/HIF-1α/SCF signaling pathway in human granulosa cells is involved in the PCOS related abnormal follicular development

Aims To investigate the regulatory mechanism of SCF expression in human GCs of PCOS related follicles. Materials and Methods SCF, BMP15 and HIF-1α were evaluated in human serums, follicular fluids (FFs) and GCs, which were collected from 69 PCOS patients and 74 normal ovulatory patients. KGN cell line was used in this study. Results Our results showed that the rate of MII oocyte and 2PN fertilization was lower in PCOS group, though PCOS patients retrieved much more oocytes. The level of BMP15 in FF and the level of SCF in serum and FF were also lower in PCOS patients. We found a weakened expression of HIF-1α and SCF in GCs from PCOS patients when compared with the non-PCOS patients. The expression of HIF-1α and SCF was significantly increased in KGN cells after treating cells with rhBMP15, however, this promotion effects of BMP15 on HIF-1α and SCF expression were obviously abolished by co-treatment with BMP-I receptor inhibitor (DM). Moreover, knock down of HIF-1α expression in KGN cells significantly reduced the expression of SCF in human GCs, in spite of activating BMP15 signaling pathway. Conclusions The present study suggest that BMP15 could induce SCF expression by up-regulating HIF-1α expression in human GCs, the aberrance of this signaling pathway might be involved in the PCOS related abnormal follicular development.

Effects of L-carnitine supplementation for women with polycystic ovary syndrome: a systematic review and meta-analysis.

BackgroundPolycystic ovary syndrome (PCOS) is a disorder in reproductive age women and is characterized by hyperandrogenic anovulation and oligo-amenorrhea, which leads to infertility. Anovulation in PCOS is associated with low follicle-stimulating hormone levels and the arrest of antral follicle development in the final stages of maturation. L-carnitine (LC) plays a role in fatty acid metabolism, which is found to be lacking in PCOS patients. This systematic review and meta-analysis aimed to determine the effectiveness of LC supplementation for patients with PCOS.MethodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Psychological Information Database (PsycINFO), and the World Health Organization International Clinical Trials Registry Platform for all randomized control trials, comparing LC alone or in combination with other standard treatments for the treatment of PCOS from inception till June 2021. We independently screened titles and abstracts to identify available trials, and complete texts of the trials were checked for eligibility. Data on the methods, interventions, outcomes, and risk of bias from the included trials were independently extracted by the authors. The estimation of risk ratios and mean differences with a 95 percent confidence interval (CI) was performed using a random-effects model.ResultsNine studies with 995 participants were included in this review. Five comparison groups were involved. In one comparison group, LC reduced the fasting plasma glucose (FPG) (mean differences (MD) −5.10, 95% CI [−6.25 to −3.95]; P = 0.00001), serum low-density lipoprotein (LDL) (MD −25.00, 95% CI [−27.93 to −22.07]; P = 0.00001), serum total cholesterol (MD −21.00, 95% CI [−24.14 to −17.86]; P = 0.00001), and serum triglyceride (TG) (MD −9.00, 95% CI [−11.46 to −6.54]; P = 0.00001) with moderate certainty of evidence. Another comparison group demonstrated that LC lowers the LDL (MD −12.00, 95% CI [−15.80 to −8.20]; P = 0.00001), serum total cholesterol (MD −24.00, 95% CI [−27.61 to −20.39]; P = 0.00001), and serum TG (MD −19.00, 95% CI [−22.79 to −15.21]; P = 0.00001) with moderate certainty of evidence.ConclusionThere was low to moderate certainty of evidence that LC improves Body Mass Index (BMI) and serum LDL, TG, and total cholesterol levels in women with PCOS.

The Disparity in the Management of Polycystic Ovary Syndrome between Obstetrician-Gynecologists in Different-Level Hospitals under the Hierarchical Medical System.

Background PCOS is a prevalent endocrine and metabolic disorder in women characterized by abnormal blood glucose, dyslipidemia, and abnormal mental health. To improve patient care, the goal of our study is to find out if there are differences in how PCOS patients are treated at different hospital levels within the hierarchical medical system. Methods Obstetricians and gynecologists from primary, secondary, and tertiary hospitals were the participants in the survey. The responses provided and collected were analyzed using various statistical techniques like the chi-square test, Fisher exact test, and logistic regression with multiple variables. Results The investigation examined 2298 survey replies (13.1% primary hospitals, 52.4% secondary hospitals, and 34.5% tertiary hospitals). As hospital grade increases, more participants inquire about a patient's history of unfavorable pregnancies concerning hormone evaluation; the better the hospital's grade, the greater the number of participants who would undergo AMH and androgen-related tests. The higher the hospital level, the more participants would pick the oral glucose tolerance test (OGTT) to determine insulin resistance, the BMI Asian criteria for defining obesity, and blood lipids. Participants in primary (odds ratio (OR) = 0.383, 95% confidence interval (CI) 0.282-0.520) and secondary (OR = 0.607, 95% confidence interval (CI) 0.481-0.765) hospitals were significantly less likely to select OGTT than those in tertiary hospitals. Comparatively, fewer primary hospitals chose to do lipid profiling than tertiary hospitals (OR 0.689, 95% CI 0.523-0.909). With the increase in hospital level, participants were more knowledgeable about the multiple efficacies and dose alternatives of metformin and selected letrozole and assisted reproduction more frequently. Conclusion Our study uncovered differences in the endocrine evaluation, metabolic screening, and management of PCOS patients across obstetrics and gynecology at various hospital levels. Simultaneously, it underlines the need to improve the hierarchical medical system and close the knowledge gap across hospitals.

Evaluation of hormones level in infertility women because of polycystic ovary syndrome

Background: Polycystic ovary syndrome refers to an endocrine disruption in affected women during reproductive age. Objective: The current study was undertaken with the objective of investigating the effects of LH, FSH, LH/FSH, prolactin, AMH, and testosterone of secretion and correlate PCOS subjects. Materials and methods: The study included infertile women infected with PCOS and healthy women aged (20-45) collected from May to July 2022 in Iraq. Among 60 women were studied, 40 infected women with PCOS (Patients group) and 20 healthy women (Healthy group) in this study. In all subjects, hormone levels of FSH, LH, AMH, Testosterone, and prolactin samples were taken and tested by VIDAS using commercial kit (BIOMERIEUX-France). Results: The result shown the levels of LH, LH/FSH ratio, AMH, Testosterone, and Prolactin in patient group of women infected with PCOS significant difference compared with control group, as LH, LH/FSH ratio, AMH, Testosterone, and Prolactin higher level in patient group compared with control group. But the levels of FSH in group of women infected with PCOS shown nonsignificant difference compared with control group with decreased nonsignificant in patient group compared with control group.

IVM: What are the RCTs Telling Us So Far?

Background: In Vitro Maturation (IVM) is a Assisted Reproduction Technology (ART) widely applied in livestock breeding, first attempted in human in the early nineties. While very successful in animals, the IVM technology has so-far not been widely adopted in human ART. The variation in IVM applications are mainly based on the use of gonadotrophins (FSH and/or HCG-trigger before oocyte collection) by the patient. The choice of the laboratory IVM protocols is dictated by the clinical preparation of the patient for oocyte pick-up. In this lecture the use of GV oocytes from fully stimulated cycles (“rescue IVM”) will not be considered. Aim: Summarize the learning from published clinical IVM studies in human from recent years, with a focus on the few randomized control trials (RCT). Method: Review by Pubmed search. Results: So far, the use of HCG administration before oocyte retrieval has been used by most ART centers, which adopted IVM (often in combination with few days of FSH, which makes it a ‘truncated IVF’). The largest series of latter kind (in 921 PCOS patients was reported by Ho et al. 2018) and yielded a 33.4% cumulative live birth rate over 12 months after 1 cycle. However available Cochrane review found no conclusive evidence for a positive role of HCG on number of retrieved or matured oocytes, nor on clinical outcome results. The role of FSH priming is proven in animal IVM studies, but clinically yet unproven in human IVM. The latest studies from Vuong L et al. (2020) applied as low as 150 IU HP-HMG for 2 days to aspirate a sufficient number of cumulus oocyte complexes (COC; 42 hours after the last FSH dose) to vitrify sufficient embryos of excellent quality for deferred transfer. A next RCTs in 351 PCOS patients was announced to evaluate the clinical requirement of FSH (Zheng X et al., 2020), however those results are still not published. Recent clinical data focused on the use of biphasic IVM culture systems in order to be capable of maturing COC from follicles smaller than 6 mm. After minimal FSH (300 IU total dose) and omission of HCG the large majority (&gt;80%) of compacted COC are aspirated from smaller than 6 mm follicles (Sanchez et al., 2019). Using the biphasic IVM culture principle (called ‘capacitation IVM’) several RCTs have been conducted to prove its superiority over ‘standard IVM’ in PCOS and ovarian tissue COC onco-fertility practice (Vuong L et al., 2020; Kirilova A et al., 2021). The CAPA-IVM culture method showed its potential compared to classical IVF standard of care in PCOM patients in a large non-inferiority RCT (546 patients): live birth rate after the first deferred transfer after Capa-IVM was 35% and conventional IVF 43%. After having observed low clinical pregnancies after non-HCG IVM (DeVos et al., 2011; Walls et al., 2015), additional small RCTs have confirmed the advantage of frozen vs fresh embryo transfer after CAPA-IVM (Vuong et al., 2021). Conclusion: Recent developments of IVM have been validated in few RCTs and IVM has been recently declared non-experimental after an extensive analysis of currently available data (ASRM Opinion paper published in 2021). The development of adequate culture media improves developmental capacity prior to meiotic maturation and brings the clinical results very close to the level of conventional IVF. The improved safety, the hugely simplified clinical approach and reduced cost structure could enhance access to ART across the globe for economically defavorised infertile couples.

A “One‐Stop Shop” Decision Tree for Diagnosing and Phenotyping Polycystic Ovarian Syndrome on Serum Metabolic Fingerprints

AbstractPolycystic ovary syndrome (PCOS) is a common endocrine disease regulated by metabolic disorders, the effective intervention of which depends on diverse phenotypes (e.g., insulin resistance). Serum metabolic fingerprint (SMF) holds promise in characterizing the pathogenesis stress related to diseases; yet, PCOS diagnosis and phenotyping are time‐consuming and challenging due to the lack of an integrated metabolic tool. Here, a nanoparticle‐enhanced laser desorption/ionization mass spectrometry platform is introduced for one‐time serum metabolic fingerprinting and to identify the metabolic heterogeneity associated with obesity in PCOS patients. A decision tree based on the acquired SMFs is constructed, and real‐world simulations on independent internal and external cohorts are performed. The decision tree yields the area under the receiver operating characteristic curves (AUC) of 0.967 for PCOS diagnosis and AUC of 0.898 for phenotyping, respectively. The technical robustness of the “one‐stop shop” decision tree across laboratories is validated for clinical utility. The decision tree aims to improve PCOS management in comparison to clinical assessment, leading to a potential reduction in multiple blood tests and physician workload.

Among high responders, is oocyte development potential different in Rotterdam consensus PCOS vs non-PCOS patients undergoing IVF?

To evaluate the oocyte potential to develop to blastocyst in Rotterdam consensus PCOS in women with hyper-responses requiring freeze-all embryos. Retrospective, single-academic center, cohort study of 205 patients who underwent freeze-all antagonist IVF cycles for OHSS risk between 2013 and 2019. Women in the PCOS group (n = 88) were diagnosed per the 2003 Rotterdam criteria. Control patients (n = 122) had no evidence of hyperandrogenism or menstrual disturbance. Data was compared by t-tests, chi-squared tests, or multivariate logistic regression (SPSS). Frozen blastocysts were Gardner's grade BB or better. There was no difference in terms of number of oocytes collected (PCOS vs non-PCOS 27.7 ± 9.4 vs 25.9 ± 8.2, p = 0.157), number of MII (20.7 ± 8.0 vs 19.1 ± 6.6, p = 0.130), number of 2PN fertilized (15.6 ± 7.4 vs 14.4 ± 5.9, p = 0.220), and number of frozen blastocysts (7.8 ± 4.9 vs 7.1 ± 3.8, p = 0.272). In addition, fertilization rates (74 ± 17% vs 75 ± 17%, p = 0.730), blastulation rates per 2PN (51 ± 25% vs 51 ± 25%, p = 0.869), and blastulation rates per mature oocytes (37 ± 18% vs 37 ± 15%, p = 0.984) were all comparable between PCOS and controls, respectively. Moreover, there was no difference when comparing PCOS and controls in pregnancy rates (45/81 vs 77/122, p = 0.28) and clinical pregnancy rates (34/81 vs 54/122, p = 0.75), respectively. Multivariate logistic regression controlling for confounders failed to alter these results. PCOS subjects do not seem to have altered oocyte potential as measured by number of MII oocytes collected, fertilization, and blastulation rates when compared to high-responder controls, with similar magnitude of stimulation.