Polycystic ovarian morphology and the diagnosis of polycystic ovary syndrome: redefining threshold levels for follicle count and serum anti-Müllerian hormone using cluster analysis.

Accuracy of anti-Müllerian hormone and total follicles count to diagnose polycystic ovary syndrome in reproductive women

Are serum levels of anti-Müllerian hormone (AMH) normal in patients with functional hypothalamic anovulation (FHA)? Our study confirms that in the general FHA population, serum AMH levels are not decreased, but if patients with polycystic ovarian morphology (PCOM) are excluded, levels become significantly lower, as in other situations of gonadotropic insufficiency. In most situations of low LH (physiological, pharmacological or pathological), serum AMH levels are low. However, paradoxically, many publications have reported normal or even increased serum AMH levels in FHA patients. Retrospective observational study conducted in an academic centre. The data concerning the study population was collected between 2006 and 2015 from a database including clinical, biological and ultrasound information. A total of 45 FHA patients were compared to 37 controls matched based on age and body mass index (BMI). Serum LH, FSH, androstenedione, total testosterone, prolactin and AMH levels were measured by immunoassay. We defined PCOM with strict criteria: a follicle number per ovary (FNPO) ≥ 12 or ≥ 19 per ovary, depending on the date on which the assessment was carried out and the ultrasound device. An AMH level ≥ 35 pmol/l could be a substitute for an excess FNPO. Controls meeting these criteria were not included in this study. There was no significant difference in the ranges of AMH levels between FHA and controls. Using strict criteria to define PCOM status, 46.7% of FHA patients had PCOM. After excluding these patients, the levels of AMH were significantly lower (P < 0.002) in FHA patients compared to controls. Within the FHA group, patients with PCOM had significantly higher ranks of AMH levels and BMI than those without PCOM. However, within the PCOM+ subgroup, the ranks of LH, FSH and A levels were still lower than in controls (P < 0.0001, <0.002 and <0.05, respectively). The positive correlation between AMH and LH was significant in the controls but not in the FHA group. However, in the FHA PCOM+, there was a strong positive correlation between BMI and LH. This is a retrospective study; our controls did not represent the general population as they were recruited in an ART centre; we used a modified classification for PCOM using follicle count and/or AMH level with in-house thresholds to define the follicle excess; the AMH assay used is no longer commercially available. Besides biasing the results of AMH assay in FHA patients, the presence of PCOM in FHA patients despite low gonadotropin and androgen levels raises the issue of epigenetically acquired amplification of androgen and/or FSH sensitivity within granulosa cells from polycystic ovaries. In terms of clinical practice, it seems important not to diagnose a low ovarian reserve in FHA patients too quickly on the basis of a decreased AMH level alone. On the contrary, a high AMH level in the context of a menstrual disorder and PCOM should not lead to a misdiagnosis of polycystic ovary syndrome (PCOS) if the basal LH is low. None. N/A.

Polycystic ovary morphology (PCOM) on ultrasonography is considered as a cardinal feature of polycystic ovarian syndrome (PCOS). Its relevance as a diagnostic criterion for PCOS was reaffirmed in the most recent International Evidence-Based Guideline for the Assessment and Management of PCOS. However, there remains a lack of clarity regarding the best practices and specific ultrasonographic markers to define PCOM. The aim of this systematic review and diagnostic meta-analysis was to assess the diagnostic accuracy of various ultrasonographic features of ovarian morphology in the diagnosis of PCOS. Relevant studies published from 1 January 1990 to 12 June 2023 were identified by a systematic search in PubMed, Web of Science, Scopus, CINAHL, and CENTRAL. Studies that generated diagnostic accuracy measures (e.g. proposed thresholds, sensitivity, specificity) for PCOS using the following ultrasonographic markers met criteria for inclusion: follicle number per ovary (FNPO) or per single cross-section (FNPS), ovarian volume (OV), and stromal features. Studies on pregnant or post-menopausal women were excluded. Risk of bias and applicability assessment for diagnostic test accuracy studies were determined using the QUADAS-2 and QUADAS-C tool for a single index test or between multiple index tests, respectively. Diagnostic meta-analysis was conducted using a bivariate model of pooled sensitivity and specificity, and visualized using forest plots and summary receiver-operating characteristic (SROC) curves. From a total of 2197 records initially identified, 31 studies were included. Data from five and two studies were excluded from the meta-analysis due to duplicate study populations or limited data for the index test, leaving 24 studies. Pooled results of 20 adult studies consisted of 3883 control participants and 3859 individuals with PCOS. FNPO was the most accurate diagnostic marker (sensitivity: 84%, CI: 81-87%; specificity: 91%, CI: 86-94%; AUC: 0.905) in adult women. OV and FNPS had similar pooled sensitivities (OV: 81%, CI: 76-86%; FNPS: 81%, CI: 70-89%) but inferior pooled specificities (OV: 81%, CI: 75-86%; FNPS: 83%, CI: 75-88%) and AUCs (OV: 0.856; FNPS: 0.870) compared to FNPO. Pooled results from four adolescent studies consisting of 210 control participants and 268 girls with PCOS suggested that OV may be a robust ultrasonographic marker for PCOS diagnosis albeit the current evidence remains limited. The majority of the studies had high risk of bias for the patient selection (e.g. lack of randomized/consecutive patient selection) and index test (e.g. lack of pre-proposed thresholds for comparison) domains across all ultrasonographic markers. As such, diagnostic meta-analysis was unable to determine the most accurate cutoff for ultrasonographic markers to diagnose PCOS. Subgroup analysis suggested that stratification based on previously proposed diagnostic thresholds, age, BMI, or technology did not account for the heterogeneity in diagnostic accuracy observed across the studies. Studies that diagnosed PCOS using the Rotterdam criteria had improved sensitivity for FNPO. Studies from North America had lower diagnostic accuracy when compared to Asian studies (FNPO: sensitivity) and European studies (OV: specificity, diagnostic odds ratio and positive likelihood ratio). Geographic differences in diagnostic accuracy may potentially be due to differences in age, BMI, and diagnostic criteria of the PCOS group across regions. This diagnostic meta-analysis supports the use of FNPO as the gold standard in the ultrasonographic diagnosis of PCOS in adult women. OV and FNPS provide alternatives if total antral follicle counts cannot be accurately obtained. Our findings support the potential for ultrasonographic evidence of PCOM in adolescents as more data becomes available. Subgroup analysis suggests the need to investigate any relative contributions of geographical differences on PCOS phenotypes. These findings may provide the basis for the development of strategies and best practices toward a standardized definition of PCOM and a more accurate ultrasonographic evaluation of PCOS.

Is intrinsic dysregulation of granulosa cells (GC) and consequent increases in the per-follicle production of anti-Müllerian hormone (AMH), correlated with the phenotypic presentation of women with polycystic ovaries? Involvement of intrinsic GC dysregulation in oligo-anovulation associated with polycystic ovary syndrome (PCOS) is likely because among women with PCOS, those with oligo-amenorrhea have higher per-follicle AMH production than those who ovulate normally, irrespective of their androgen and/or metabolic status. Women with PCOS have higher serum AMH level than non-PCOS women due to an increased follicle number and excessive AMH production per follicle, the latter reflecting a putative GC dysfunction that may vary between PCOS phenotypes. This is a retrospective analysis of data collected from 1021 women undergoing infertility evaluation from March 2011 to October 2013. The study included women with polycystic ovarian morphology (PCOM) who met the Rotterdam criteria for PCOS (n = 272), women with PCOM only (n = 168) and controls (n = 581). We used serum AMH to antral follicle count (AFC) ratio (AMH/AFC) as a marker of per-follicle AMH production and checked whether this ratio was associated with the PCOS phenotype and to the menstrual, androgen and metabolic status in women with PCOS, women with PCOM only and in controls. AMH/AFC was significantly higher in oligo-amenorrheic women with PCOS than in eumenorrheic women with PCOS or PCOM (P < 0.001) but also in the latter group compared with controls (P < 0.001) regardless of androgen status. Stepwise discriminant analysis yielded a significant score for the menstrual status with a discriminant power of 26.5% (P < 0.001). This score included AFC, AMH/AFC, waist circumference and LH with partial R(2) of 0.172, 0.042, 0.024 and 0.023, respectively. The AMH to AFC ratio as a surrogate marker for average AMH may be subject to error because follicles below the sensitivity limit of the ultrasonography used may also contribute to serum AMH concentration and secondly, AFC can be subjective. The higher AMH/AFC in women with PCOM only than in controls suggests that isolated PCOM may represent a PCOS-like phenotype in which an inherent dysfunction of GC exists but is too mild to affect the ovulatory process. No funding was obtained for this study. There are no conflicts of interest to be declared. Non-applicable.

To assesse circulating levels of Anti-Müllerian hormone (AMH) as a predictor of oocyte number and their potential to mature in vitro in both normo-ovulatory (NO) women and in women with Polycystic Ovary Syndrome (PCOS) undergoing in vitro maturation (IVM) treatments. We prospectively studied NO women and women diagnosed with PCOS, (age range 21-39 years) underwent IVM treatments at our center. Serum AMH levels were quantified before each cycle and correlated to oocytes number, maturation and fertilization during in vitro maturation. 104 NO and 30 PCOS IVM cycles were followed with retrieval of a total of 672 and 491 oocytes, respectively. In NO women, the serum AMH level positively correlated with the number of oocytes retrieved, (R = 0.6; P <0.0001) the number of M2 oocytes at 24 and 48 h (R = 0.4; P <0.01; R = 0.26 p < 0.007, respectively) and with the total number of M2 oocytes (R = 0.47; P < 0.0001). In the PCOS group, the serum AMH level positively correlated only with the number of oocytes retrieved (R = 0.43; P <0.03). Receiver operating characteristic (ROC) analyses showed that a cutoff AMH level of 1.56 (ng/ml) could identify patients with 5 or more oocytes at OPU with a sensitivity of 83 % and a specificity of 75 %. An AMH level of 1.63 (ng/ml) was the threshold for 5 or more matured oocytes (sensitivity = 81 %, specificity = 53 %). Serum AMH may be used as a marker to identify candidates for IVM treatment in both NO and PCOS women.

Introduction: Increasing amount of research indicates that women with PCOS are more likely to have a shortage in vitamin D with abnormally high anti-Müllerian hormone (AMH) levels. This study aims to assess the correlation between vitamin D and Anti-Mullerian Hormone (AMH) levels in infertile women with polycystic ovarian syndrome (PCOS) and obesity. Method: This observational cross-sectional study examined all obese women with PCOS who sought infertility treatment at Dr. Mohammad Hoesin Hospital Palembang from August 2021 to November 2021. PCOS diagnosis was determined using the Rotterdam criteria. All research subjects underwent a physical examination and transvaginal ultrasound to evaluate body mass index (BMI) and polycystic ovary morphology. Blood samples were collected to evaluate their testosterone, AMH, and vitamin D levels. Statistical analysis was performed using the Spearman correlation test with IBM® SPSS Statistics version 24. Results: Thirty infertile women with PCOS and obesity were included in the study, with average age of 31.17±4.48 years and average BMI of 33.45±2.67 kg/m2. The majority of the subjects had polycystic ovary morphology (86.7%) and oligomenorrhea (76.7%). No correlation between BMI and vitamin D as well as AMH levels was found in infertile women with PCOS and obesity. The Spearman test showed moderate negative correlation (p = 0.011. r = -0.458) between vitamin D and AMH levels in infertile women with PCOS and obesity. Conclusion: There is a moderate negative correlation between vitamin D and AMH levels among infertile women with PCOS and obesity. Further research is required to comprehend the role of vitamin D in female fertility.Korelasi Vitamin D dan Kadar Hormon Anti-Müllerian pada Wanita Infertil dengan Sindrom Ovarium Polikistik dan ObesitasAbstrakPendahuluan: Semakin banyak penelitian melaporkan bahwa wanita dengan PCOS cenderung mengalami defisiensi vitamin D dengan penignkatan kadar hormon anti-Müllerian (AMH). Penelitian ini bertujuan untuk mengkaji hubungan vitamin D dan kadar AMH pada wanita infertil dengan sindrom ovarium polikistik (SOPK) dan obesitas.Metode: Penelitian ini merupakan studi observasional potong lintang terhadap seluruh wanita infertil dengan SPOK dan obesitas yang di RSUP Dr. Mohammad Hoesin Palembang pada bulan Agustus 2021 hingga November 2021. Diagnosis SOPK ditegakkan berdasarkan kriteria Rotterdam. Seluruh subjek penelitian menjalani pemeriksaan fisik dan ultrasonografi transvaginal untuk menilai indeks massa tubuh (IMT) dan morfologi ovarium polikistik. Sampel darah dikumpulkan dari semua wanita untuk mengukur kadar testosteron, AMH, dan vitamin D. Analisis statistik dilakukan dengan menggunakan uji korelasi Spearman menggunakan IBM® SPSS Statistics versi 24.Hasil: Tiga puluh wanita infertil dengan SOPK dan obesitas dilibatkan dalam penelitian ini dengan usia rata-rata 31,17±4,48 tahun dan rata-rata IMT 33,45±2,67 kg/m2. Mayoritas subjek memiliki morfologi ovarium polikistik (86,7%) dan oligomenore (76,7%). Tidak ada korelasi antara IMT dan vitamin D maupun kadar AMH pada wanita infertil dengan SOPK dan obesitas. Uji Spearman menunjukkan korelasi negatif sedang (p=0.011.r=-0.458) antara kadar vitamin D dan AMH pada wanita infertil dengan SOPK dan obesitas. Kesimpulan: Kadar vitamin D berkorelasi negatif dengan kadar AMH pada wanita infertil dengan SOPK dan obesitas. Penelitian lebih lanjut diperlukan untuk memahami peran vitamin D pada kesuburan wanita.Kata kunci: Anti-Müllerian Hormone, Indeks Massa Tubuh, Obesitas, Sindrom Ovarium Polikistik, Vitamin D

Steroid metabolome profiling of follicular fluid in normo- and hyperandrogenic women with polycystic ovary syndrome

Application of the newly introduced Rotterdam criteria for polycystic ovary syndrome (PCOS) generates four phenotypic subgroups, defined by the presence/absence of three diagnostic elements: polycystic ovarian (PCO) morphology (P); hyperandrogenism (H); and oligo-amenorrhoea (O). Whilst PCOS is associated with adverse metabolic features, the strength of the association within individual subgroups is not established. We characterized the metabolic and endocrine profiles of PCOS women who are oligomenorrhoeic but normoandrogenaemic, and compared these to other PCOS women and controls. Retrospective dataset analyses. A total of 309 Europid PCOS women, all with PCO morphology, of whom 191 were also hyperandrogenaemic and oligomenorrhoeic (PHO), 76 hyperandrogenaemic with normal menses (PH) and 42 oligomenorrhoeic but normoandrogenaemic (PO); plus 76 Europid control women without PCOS. Metabolic parameters: fasting insulin, lipids, homeostasis model assessment (HOMA) measures of insulin sensitivity; endocrine variables: LH, FSH; prevalence of metabolic syndrome. Insulin sensitivity: PO women were indistinguishable from controls, and markedly less insulin-resistant than PHO women (vs. controls, P = 0.38 after adjustment for BMI and age; vs. PHO, P = 0.003). Metabolic syndrome: the prevalence in PO women (7.1%) was similar to that in controls (3.9%), and lower than in PHO women (29.3%, P < 0.0001). LH levels: PO women were intermediate between controls (vs. controls, P = 0.008) and PHO women (vs. PHO, P = 0.06). Normoandrogenaemic, oligomenorrhoeic women with PCOS are metabolically similar to control women with significantly fewer metabolic features than PCOS women who are also hyperandrogenaemic. However, higher than normal LH and lower sex hormone-binding globulin (SHBG) concentrations in the PO women support the view that they form part of the spectrum of PCOS.

Circulating levels of anti-Mullerian hormone (AMH) have significantly increased in adolescent girls with polycystic ovary syndrome (PCOS) compared with that of normal girls. This is consistent with findings in adult PCOS and normal women. Previous studies in both adolescent girls and women with PCOS have shown a close correlation of circulating AMH levels to the antral follicle count, and it has been proposed that serum AMH may be a useful biological marker for the presence of PCOS. Adolescent girls with oligomenorrhea (OLIGO) without evidence of hyperandrogenism may show increased pulsatile LH secretion similar to girls with PCOS. Without ovarian imaging studies and in the absence of hyperandrogenism, it is unclear whether girls with OLIGO fulfill the criteria for diagnosis of PCOS. A finding of elevated AMH serum levels in adolescent girls with OLIGO would be strongly suggestive of PCOS. No studies are available comparing serum AMH concentrations among adolescent girls with PCOS or OLIGO without evidence of hyperandrogenism. This prospective study compared serum AMH levels in adolescent girls with OLIGO, PCOS, or regular menstrual cycles (normal controls). The comparison groups were comprised of 24 girls with OLIGO who had no evidence of hyperandrogenism, 153 girls with PCOS, and 39 normal controls, as well as 73 women with PCOS, and 36 normal adult women. Baseline blood samples were drawn on an arbitrary day in girls with OLIGO and PCOS, and from the early to mid-follicular phase of the menstrual cycle in adolescent normal controls. Blood samples were obtained similarly in adult women. There was no significant difference in the basal serum AMH levels of adolescent girls with OLIGO (5.33 ± 0.47 ng/mL) or PCOS (5.28 ± 0.26 ng/mL) girls or PCOS adults (6.36 ± 0.47 ng/mL). Similarly, there was no significant difference between normal control adolescents (3.05 ± 0.31 ng/mL) and normal control adults (2.33 ± 0.22 ng/mL). AMH levels were significantly lower among obese adolescents and PCOS women compared with lean controls (P < 0.02 for each comparison). These findings suggest that adolescent girls with OLIGO have elevated antral follicle number similar to adolescents with PCOS, which is suggestive for diagnosis of PCOS.

ObjectivesThe aim of the present study was to evaluate the prevalence of polycystic ovary syndrome (PCOS), its phenotypical and cardio-metabolic features in a community sample of the Iranian population in comparison to healthy eumenorrheic, non-hirsute women without polycystic ovaries. The second aim was to assess the cardio-metabolic characteristics of women who suffered from one criteria of PCOS compared to those healthy eumenorrheic, non-hirsute women.MethodsIn this cross-sectional population-based study, a total of 1,960 eligible women, aged (18–45 years) were recruited from the Tehran-Lipid and Glucose-Study participants and were classified as the three groups of (i) women with PCOS by the Rotterdam criteria, (ii) non-PCOS women with one criteria of PCOS and (iii) healthy eumenorrheic, non-hirsute women without polycystic ovaries morphology (PCOM) as the control group. Further PCOS women were extended to four phenotypes of hyperandrogenism, oligo-anovulation, polycystic ovaries (phenotype A), hyperandrogenism, oligo/anovulation (phenotype B), hyperandrogenism, polycystic ovaries (phenotype C) and oligo-anovulation, polycystic ovaries (phenotype D). Cardio-metabolic profiles and the prevalence of comorbidities of metabolic syndrome (MetS) and lipid abnormalities were compared among these groups linear, and the median regression models adjusted for age and body mass index.ResultsThe prevalence of PCOS according to the diagnostic criteria of the NIH, Rotterdam and AE-PCOS Society were 13.6, 19.4, and 17.8, respectively. Among those who met the Rotterdam criteria, 23.9, 46.3, 21.6, and 8.2% had phenotypes A, B, C, and D, respectively. Among the remaining 1,580 women who did not fulfil the PCOS criteria, 108 (6.8%) suffered from only oligo/anovulation, 332 (21%) only hyperandrogenism/hyperandrogenemia, 159 (16.2%) only PCOM in ultrasound and 981 (62%) were healthy eumenorrheic, non-hirsute women without PCOM. The study revealed that some adiposity indices and lipid abnormalities in PCOS phenotypes with hyperandrogenism (A, B, and C) were worse than in healthy women. By contrast, women with phenotype D did not differ from the healthy ones in terms of adiposity and lipid abnormalities. However, the respective values for other cardio-metabolic profiles and MetS rates in different phenotypes of PCOS were similar to the healthy women. Only the prevalence of MetS in phenotype A was significantly higher than in the healthy women. There were no statistically significant differences between participants with one criteria of PCOS and healthy counterparts in terms of most adiposity indexes, cardio-metabolic factors, and comorbidity of MetS and its components. However, women with hyperandrogenism had a significantly higher level of the waist to height ratio (WHtR) and hypertriglyceridemia than their healthy counterparts.ConclusionPCOS, mainly classical phenotypes A and B, are common among Iranian women of reproductive age. Women with PCOS who had androgen excess exhibited the worst lipid profile, and those who had full three criteria of the syndrome exhibited the higher rate of MetS. However, women with only ovulatory dysfunction and only PCOM had similar cardio-metabolic characteristics, compared to healthy subjects. These data suggest that routine screening for metabolic disturbances may be needed in the prevention of cardio-metabolic disorders in patients with more serious phenotypes of PCOS.

Objectives: The aim of the present study was to evaluate the impact of polycystic ovarian morphology in the hormonal and metabolic features of the classical phenotypes of PCOS. Design: The study included 1275 Caucasian women with PCOS with a mean age of 24.25 ± 5.79 years and a mean BMI of 26.80 ± 7.03 kg/m2. Diagnosis of PCOS was based on the 2003 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus criteria. Two phenotypes, matched for age and BMI were compared: Phenotype I (n=620) which included PCOS women with biochemical hyperandrogenemia and/or clinical hyperandrogenemia, chronic anovulation and polycystic ovarian morphology on ultrasound (PCO). Phenotype II (n=400) which included PCOS women with biochemical hyperandrogenemia and/or clinical hyperandrogenemia and chronic anovulation, without PCO. These phenotypes were further subdivided in normal weight and obese PCOS women. Results: PCOS women of Phenotype I had higher LH/FSH ratio (p<0.001), higher Testosterone (p<0.01), Δ4 Androstenedione (p<0.001) and 17-OH progesterone levels (p<0.001), and higher Free Androgen Index (FAI) values (p<0.01) compared to Phenotype II. With the exception of fasting glucose levels, all other indices of insulin resistance (fasting insulin, fasting glucose/insulin ratio, QUICKI and HOMA2IR) document an association between Phenotype I and greater insulin resistance in overweight/obese PCOS women. Conclusions: In conclusion, in classical phenotypes of polycystic ovary syndrome (PCOS), polycystic ovarian morphology is associated with more severe hyperandrogenemia and deranged LH/FSH ratio. In overweight/obese PCOS subjects, PCO is positively correlated with insulin resistance.

Advancements in ultrasound technology have facilitated identifying polycystic ovarian morphology (PCOM) in women with and without polycystic ovary syndrome (PCOS), but it still has limitations due to follicle counting methods and variation of phenotypes according to ethnicity. Ethnicity-specific ovarian morphology may help to establish ethnicity-specific follicle count cut points for defining PCOM in women with PCOS. To investigate the prevalence and factors associated with PCOM in Thai women of a reproductive age with PCOS. This prospective cross-sectional study was conducted in our gynecology department at a tertiary teaching hospital from February 2016 to May 2017. We included women with PCOS, who were measured for weight, height, waist circumference, and blood pressure. Blood samples were taken to measure fasting blood glucose, lipid profile, testosterone level, and 2 h post-load 75 g oral glucose tolerance test (OGTT). Transvaginal or transrectal sonography was performed to evaluate their ovaries. All 143 patient participants we included had oligomenorrhea, 77.6% of them had acne, and 64.3% hirsutism. Their average total testosterone level was 0.47 ± 0.10 ng/mL. The prevalence of PCOM was 55.2%. The proportions of PCOM diagnosed by ovarian follicle and ovarian volume criteria were 36.4% and 42.0%, respectively. There were 20.0 ± 9.5 follicles per ovary, 8.3 ± 3.1 follicles per cross section, and the mean ovarian volume was 7.9 ± 3.0 mL. The overall prevalence of PCOM in Thai women of reproductive age with PCOS was 55.2%. Our univariate analysis found no factors significantly associated with PCOM.

Study question What mechanisms are involved in the ovarian alterations of Polycystic Ovary Syndrome (PCOS) and Morphology? Summary answer PCOS patients associated a distinctive impairment of oxidative phosphorylation and dysregulated complement system in their follicular compartments not found in Polycystic Ovarian Morphology (PCOM) women. What is known already PCOS is a major cause of female infertility characterized by aberrant follicular development and hormonal imbalances leading to reproductive symptoms such as anovulation, poor oocyte quality, and hyperandrogenism. Likewise, PCOM is present in 16-25% of women with regular menses, but the clinical relevance of this ovarian phenotype and its correlation with PCOS remains unclear. Therefore, to establish the specific molecular mechanisms underlying the ovarian alterations in PCOS using High-throughput techniques will allow us to provide a better clinical management and a differential diagnosis with PCOM women. Study design, size, duration Cross-sectional molecular study including samples from 26 patients undergoing an IVF cycle between 2019-2022 at Hospital La Fe (Valencia, Spain). Eight women were considered PCOS, eleven PCOM and seven were control fertile patients. Granulosa cells (GCs) and follicular fluid (FF) samples were obtained during oocyte retrieval to perform RNA-seq and proteomic analysis, respectively. Participants/materials, setting, methods Women with two or more Rotterdam-criteria were considered as PCOS, while PCOM was defined by polycystic ovarian morphology on ultrasound with regular ovulatory cycles. RNA from GCs was obtained and sequenced using NextSeq500-Illumina to identify differentially expressed genes (DEGs) using DESeq2 (R-software). The proteome of FF samples was established by LC-MS/MS and differentially expressed proteins (DEPs) analyzed with limma package. Functional enrichment analysis of DEGs and DEPs (FDR&amp;lt; 0.05) was performed based on KEGG database. Main results and the role of chance RNA-seq data revealed clear distinctions between GCs from PCOS and control women, with 526 DEGs. By contrast, the transcriptomes of PCOS and PCOM were more similar, with only 34 DEGs. Notably, oxidative phosphorylation emerged as the most enriched pathway in both comparisons, showing a differential expression in PCOS. Indeed, 6 out of 12 shared DEGs (MT-TP, MT-ND4L, MT-ND2, MT-ATP8, MT-ND4, and MT-ATP6), were mitochondrial genes found upregulated in PCOS vs. PCOM and control samples. These findings suggest that granulosa cells from PCOS present a dysregulation in oxidative phosphorylation, potentially linked to alterations in those genes associated with the mitochondrial electron transport chain. The proteomic analysis showed 37 DEPs in the FF of PCOS compared with controls, being these DEPs mainly involved in the complement and coagulation cascades, PI3K-AKT pathway, oocyte meiosis and ferroptosis. Furthermore, the PCOS vs. PCOM analysis revealed 42 DEPs, significantly enriched also in complement and coagulation cascades, ferroptosis and glutathione metabolism. Interestingly, fifteen proteins were differentially expressed in both comparisons, with four of them related to the complement system (PROS1, C1S, C1QB and MASP2), suggesting that an alteration in this system at follicular fluid level might be one of the hallmarks of PCOS. Limitations, reasons for caution Further experimental studies are required to validate the specific changes identified in our study. Moreover, to establish how these alterations in the follicular compartments affect the oocytes of PCOS patients should also be explored. Wider implications of the findings Our study focused on specific mechanisms involved in PCOS ovarian alterations, providing new insights into potential biomarkers for an accurate diagnosis and management of this pathology. Dysregulations in oxidative phosphorylation and complement system might play a crucial role in PCOS multifactorial nature, contributing to impaired folliculogenesis and decreased oocyte quality. Trial registration number Not Applicable

PCOSt: A non-invasive and cost-effective screening tool for polycystic ovary syndrome

Introduction: The frequency of polycystic ovarian syndrome (PCOS) has come to nearly epidemic extents in ladies of reproductive age around the world. Polycystic ovarian syndrome is one of the foremost common endocrinological problems in ladies. In expansion to chronic oligo-anovulation, the fundamental highlights of the PCOS incorporate raised levels of circulating androgens or clinical hyperandrogenism, polycystic ovary morphology, modified gonadotropin secretion, insulin resistance and compensatory hyperinsulinemia frequently related with obesity. Objective: The purpose of this study was to compare the affiliations of anti-Müllerian hormone (AMH) with biochemical characteristics between ladies with and without polycystic ovary syndrome (PCOS). Material &amp; Method: Study design: Quantitative cross sectional Settings: Lady Wallington Hospital Lahore Duration: Six months i.e. 1st July 2021 to 31st December 2021 Methodology: Quantitative cross sectional study was performed at lady Wallington hospital Lahore. The total numbers of patients were 150. Age of females was in between 18-35 years. The diagnosis of polycystic ovarian syndrome was made according to the Rotterdam ESHRE-ASRM criteria. The various parameters which include Body mass index, lipid profile, Blood sugar levels, FSH, LH, Prolactin, testosterone levels, AMH DHEA-S, HOMA-IR and adiponectin were measured. Collected data was entered in SPSS version 23 and analyzed. Results: Data for females with PCOS and control summarized briefly in table no 1. AMH level have significant p value 0.001 and clearly showed that it is higher in females with PCOS whether fatty or non-fatty than normal or control. Conclusion: In conclusion, AMH levels were essentially higher in ladies with PCOS, in any case of age and BMI, and exhibited no relationship with obesity, insulin resistance, or metabolic syndrome-related factors. Only testosterone shown an impact on serum AMH levels in PCOS group, whereas age, adiponectin as well as testosterone altogether related with AMH levels within the control group. Keywords: Polycystic ovarian syndrome, AMH, Gonadotrophin, TSH, Insulin