Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume

doi:10.1093/HUMREP/DET062

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Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume

Journal Article•DOI•

Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume

Marla E. Lujan¹, Brittany Y Jarrett¹, Eric D. Brooks¹, Jonathan K. Reines¹, Andrew K. Peppin², Narry Muhn², Ehsan A. Haider², Roger A. Pierson³, Donna R. Chizen³ - Show less +5 more•Institutions (3)

Cornell University¹, McMaster University², University of Saskatchewan³

01 May 2013-Human Reproduction (Oxford University Press)-Vol. 28, Iss: 5, pp 1361-1368

TL;DR: A substantially higher threshold of follicle counts throughout the entire ovary (FNPO) is required to distinguish among women with PCOS and healthy women from the general population using newer ultrasound technology and a reliable grid system approach to count follicles.

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Abstract: main results: Diagnostic potential for PCOS was highest for FNPO (0.969), followed by FNPS (0.880) and OV (0.873) as judged by the area under the ROC curve. An FNPO threshold of 26 follicles had the best compromise between sensitivity (85%) and specificity (94%) when discriminating between controls and PCOS. Similarly, an FNPS threshold of nine follicles had a 69% sensitivity and 90% specificity, and an OV of 10 cm 3 had a 81% sensitivity and 84% specificity. Levels of intra-observer reliability were 0.81, 0.80 and 0.86 when assessing FNPO, FNPS and OV, respectively. Inter-observer reliability was 0.71, 0.72 and 0.82, respectively.

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Journal Article•DOI•

Epidemiology, diagnosis, and management of polycystic ovary syndrome

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Susan M Sirmans¹, Kristen A. Pate¹•Institutions (1)

University of Louisiana at Monroe¹

18 Dec 2013-Clinical Epidemiology

TL;DR: Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications.

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Abstract: Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%-20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%-70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications.

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996 citations

Cites background or methods from "Updated ultrasound criteria for pol..."

...However, since that time, significant advancements in ultrasound image technology have been made, improving resolution and allowing for the detection of smaller follicles.(21) This has prompted calls for revisiting the criteria used to define polycystic ovarian morphology....
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...Lujan et al measured FNPO, follicle counts in a single cross section, and ovarian volume in images that were digitally archived for offline analysis.(21) In their analysis, a FNPO threshold of...
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Journal Article•DOI•

The physiology and clinical utility of anti-Müllerian hormone in women

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Didier Dewailly¹, Claus Yding Andersen², Adam H. Balen, Frank J. M. Broekmans³, Nafi Dilaver⁴, Renato Fanchin, Georg Griesinger, Tom Kelsey⁵, Antonio La Marca⁶, C.B. Lambalk⁷, Helen D. Mason⁴, Scott M. Nelson⁸, Jenny A. Visser⁹, W. Hamish B. Wallace¹⁰, Richard A. Anderson¹¹ - Show less +11 more•Institutions (11)

university of lille¹, University of Copenhagen², University Medical Center Utrecht³, St George's, University of London⁴, University of St Andrews⁵, University of Modena and Reggio Emilia⁶, VU University Medical Center⁷, University of Glasgow⁸, Erasmus University Rotterdam⁹, Royal Hospital for Sick Children¹⁰, University of Edinburgh¹¹

01 May 2014-Human Reproduction Update

TL;DR: There is a linear relationship between AMH and oocyte yield after ovarian stimulation, which is of value in predicting ovarian hyperstimulation, and the submerged part of the iceberg of follicle growth, i.e. the intrinsic, so-called 'acyclic' ovarian activity is measured.

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Abstract: BACKGROUND The measurement of circulating anti-Mullerian hormone (AMH) has been applied to a wide array of clinical applications, mainly based on its ability to reflect the number of antral and pre-antral follicles present in the ovaries. AMH has been suggested to predict the ovarian response to hyperstimulation of the ovaries for IVF and the timing of menopause, and to indicate iatrogenic damage to the ovarian follicle reserve. It has also been proposed as a surrogate for antral follicle count (AFC) in the diagnosis of polycystic ovary syndrome (PCOS). METHODS This paper is a summary of presentations at a European Society of Human Reproduction and Embryology campus workshop on AMH, with literature cited until September 2013. Published peer-reviewed medical literature about AMH was searched through MEDLINE and was subjected to systematic review and critical assessment by the panel of authors. RESULTS Physiologically, recent data confirm that AMH is a follicular gatekeeper limiting follicle growth initiation, and subsequently estradiol production from small antral follicles prior to selection. AMH assays continue to evolve and technical issues remain; the absence of an international standard is a key issue. The dynamics of circulating AMH levels throughout life can be split into several distinct phases, with a peak in the early 20s before a decline to the menopause, with a strong and positive correlation with non-growing follicle recruitment. There is a more complex rise during childhood and adolescence, which is likely to be more reflective of different stages of follicle development. AMH shows limited short-term variability, but the influence of states such as prolonged oral contraceptive use need to be considered in clinical assessment. There are only very limited data on relationships between AMH and natural fertility at different stages of reproductive life, and while it has a relationship to age at menopause the marked variability in this needs further exploration. AMH may be useful in assessing the need for fertility preservation strategies and detecting post-chemotherapy or surgical damage to the ovarian reserve. Long-term follow-up of patients to ascertain fully the value of post-cancer serum AMH in predicting long-term ovarian function is required. There is a linear relationship between AMH and oocyte yield after ovarian stimulation, which is of value in predicting ovarian hyperstimulation. AMH can also identify 'poor responders', but it seems inappropriate at present to withhold IVF purely on this basis. Women with PCOS show markedly raised AMH levels, due to both the increased number of small antral follicles and intrinsic characteristics of those granulosa cells, and this may contribute to anovulation. The value of AMH in the diagnosis of PCOS remains controversial, but it may replace AFC in the future. CONCLUSIONS For the first time in female reproductive biology, it is possible to measure the submerged part of the iceberg of follicle growth, i.e. the intrinsic, so-called 'acyclic' ovarian activity. An international standard for AMH and improved assay validity are urgently needed to maximize the clinical utility of this very promising biomarker of ovarian function in a large array of clinical situations, both in childhood and adulthood.

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727 citations

Cites methods from "Updated ultrasound criteria for pol..."

...With the latest generation of ultrasound equipment and using 601 well-defined populations, recent studies have proposed to increase this threshold to 19 or 25 (Dewailly, 602 et al., 2011, Lujan et al., 2013, respectively)....
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Journal Article•DOI•

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

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Gerard S. Conway¹, Didier Dewailly, Evanthia Diamanti-Kandarakis², Héctor F. Escobar-Morreale³, Stephen Franks⁴, Alessandra Gambineri, Fahrettin Kelestimur⁵, Djuro Macut, Dragan Micic, Renato Pasquali⁶, Marija Pfeifer⁷, Duarte Pignatelli, Michel Pugeat, Bulent O. Yildiz⁸ - Show less +10 more•Institutions (8)

University College London¹, National and Kapodistrian University of Athens², Complutense University of Madrid³, Imperial College London⁴, Erciyes University⁵, University of Bologna⁶, Ljubljana University Medical Centre⁷, Hacettepe University⁸

01 Oct 2014-European Journal of Endocrinology

TL;DR: A critical endocrine and European perspective on the debate on the definition of PCOS is offered and all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder are summarized.

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Abstract: Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.

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491 citations

Journal Article•DOI•

Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society

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Didier Dewailly¹, Marla E. Lujan², Enrico Carmina³, Marcelle I. Cedars⁴, Joop S.E. Laven⁵, Robert J. Norman⁶, Héctor F. Escobar-Morreale⁷ - Show less +3 more•Institutions (7)

university of lille¹, Cornell University², University of Palermo³, University of California, San Francisco⁴, Erasmus University Rotterdam⁵, University of Adelaide⁶, University of Alcalá⁷

01 May 2014-Human Reproduction Update

TL;DR: The Task Force recommends using FNPO rather than FNPO for the definition of PCOM setting the threshold at ≥25, but only when using newer technology that affords maximal resolution of ovarian follicles (i.e. transducer frequency ≥8 MHz).

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Abstract: BACKGROUND The diagnosis of polycystic ovary syndrome (PCOS) relies on clinical, biological and morphological criteria. With the advent of ultrasonography, follicle excess has become the main aspect of polycystic ovarian morphology (PCOM). Since 2003, most investigators have used a threshold of 12 follicles (measuring 2-9 mm in diameter) per whole ovary, but that now seems obsolete. An increase in ovarian volume (OV) and/or area may also be considered accurate markers of PCOM, yet their utility compared with follicle excess remains unclear. METHODS Published peer-reviewed medical literature about PCOM was searched using PubMed.gov online facilities and was submitted to critical assessment by a panel of experts. Studies reporting antral follicle counts (AFC) or follicle number per ovary (FNPO) using transvaginal ultrasonography in healthy women of reproductive age were also included. Only studies that reported the mean or median AFC or FNPO of follicles measuring 2-9 mm, 2-10 mm or <10 mm in diameter, or visualized all follicles, were included. RESULTS Studies addressing women recruited from the general population and studies comparing control and PCOS populations with appropriate statistics were convergent towards setting the threshold for increased FNPO at ≥25 follicles, in women aged 18-35 years. These studies suggested maintaining the threshold for increased OV at ≥10 ml. Critical analysis of the literature showed that OV had less diagnostic potential for PCOM compared with FNPO. The review did not identify any additional diagnostic advantage for other ultrasound metrics such as specific measurements of ovarian stroma or blood flow. Even though serum concentrations of anti-Mullerian hormone (AMH) showed a diagnostic performance for PCOM that was equal to or better than that of FNPO in some series, the accuracy and reproducibility issues of currently available AMH assays preclude the establishment of a threshold value for its use as a surrogate marker of PCOM. PCOM does not associate with significant consequences for health in the absence of other symptoms of PCOS but, because of the use of inconsistent definitions of PCOM among studies, this question cannot be answered with absolute certainty. CONCLUSIONS The Task Force recommends using FNPO for the definition of PCOM setting the threshold at ≥25, but only when using newer technology that affords maximal resolution of ovarian follicles (i.e. transducer frequency ≥8 MHz). If such technology is not available, we recommend using OV rather than FNPO for the diagnosis of PCOM for routine daily practice but not for research studies that require the precise full characterization of patients. The Task Force recognizes the still unmet need for standardization of the follicle counting technique and the need for regularly updating the thresholds used to define follicle excess, particularly in diverse populations. Serum AMH concentration generated great expectations as a surrogate marker for the follicle excess of PCOM, but full standardization of AMH assays is needed before they can be routinely used for clinical practice and research. Finally, the finding of PCOM in ovulatory women not showing clinical or biochemical androgen excess may be inconsequential, even though some studies suggest that isolated PCOM may represent the milder end of the PCOS spectrum.

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402 citations

Cites background or methods or result from "Updated ultrasound criteria for pol..."

...…of women with regular menstrual cycles and no evidence for hyperandrogenism, three recent studies (Bentzen et al., 2013; Deb et al., 2013; Lujan et al., 2013) yielded median values of FNPO between 11 and 13 (Table I), indicating that at least half of the controls aged 20–35 years had…...
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...This approach has been repeated recently in two studies comparing PCOS to controls by means of ROC curve analysis (Dewailly et al., 2011; Lujan et al., 2013)....
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...Interestingly, the FNPO 95th percentiles in most of these populations are quite similar to the FNPO thresholds proposed by the two recent studies that relied on ROC curve analysis (Dewailly et al., 2011; Lujan et al., 2013) (Table II), indicating that an FNPO threshold of around 25 follicles may be best used to distinguish normal ovarian morphology from PCOM in most populations (Table I)....
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...…appears to be higher in populations characterized by large prevalence of weight excess, such as those in Canada and the USA (Alsamarai et al., 2009; Lujan et al., 2013), intermediate in European countries (Carmina et al., 2005; Jonard et al., 2005), and lower in East-Asian countries (Chen et al.,…...
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...Noteworthy, this figure is very close to the FNPO ≥25 threshold showing excellent diagnostic performance as analysed by ROC curve analysis in two recent studies as described above (Dewailly et al., 2011; Lujan et al., 2013)....
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Journal Article•DOI•

Can anti-Mullerian hormone predict the diagnosis of polycystic ovary syndrome? A systematic review and meta-analysis of extracted data

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Stamatina Iliodromiti¹, Tom Kelsey², Richard A. Anderson³, Scott M. Nelson¹•Institutions (3)

University of Glasgow¹, University of St Andrews², University of Edinburgh³

17 Jun 2013-The Journal of Clinical Endocrinology and Metabolism

TL;DR: AMH may be a useful initial diagnostic test for PCOS subject to validation in prospective population cohorts and the true accuracy of AMH in the prediction of PCOS is assessed.

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Abstract: Context: Existing biochemical tests for polycystic ovary syndrome (PCOS) have poor sensitivity and specificity. Many women with PCOS have high anti-Mullerian hormone (AMH) concentrations; thus, this may be a useful addition to the diagnostic criteria. Objective: A systematic literature review was performed to assess the true accuracy of AMH in the prediction of PCOS and to determine the optimal diagnostic threshold. Data Sources: Published and gray literature were searched for all years until January 2013. Study Selection: Observational studies defining PCOS according to the Rotterdam criteria and assessing the value of AMH in diagnosing PCOS were selected. Ten studies of the initial 314 hits reporting AMH values in the diagnosis of PCOS were included in the meta-analysis and the construction of the summary receiver-operating characteristic curve. Four studies that plotted individual AMH serum levels of women with PCOS and controls on graphs were selected for individual data extraction. Data Extraction: T...

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239 citations

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References

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Journal Article•DOI•

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome

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Bart C.J.M. Fauser

01 Jan 2004-Fertility and Sterility

TL;DR: Since the 1990 NIH-sponsored conference on polycystic ovary syndrome, it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria.

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8,217 citations

Journal Article•DOI•

Men at risk: occupation and male infertility☆

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Paul Claman¹•Institutions (1)

University of Ottawa¹

01 Mar 2004-Fertility and Sterility

TL;DR: There is accumulating evidence that workplace exposure to toxic substances contributes to male infertility, and men suffering from infertility problems may do well to look at their occupations, where exposure to certain substances may be a contributory factor.

...read moreread less

2,428 citations

Journal Article•DOI•

The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report

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Ricardo Azziz¹, Enrico Carmina², Didier Dewailly, Evanthia Diamanti-Kandarakis³, Héctor F. Escobar-Morreale, Walter Futterweit⁴, Onno E. Janssen, Richard S. Legro⁵, Robert J. Norman⁶, Ann Taylor⁷, Selma F. Witchel⁸ - Show less +7 more•Institutions (8)

University of California, Los Angeles¹, University of Palermo², National and Kapodistrian University of Athens³, Icahn School of Medicine at Mount Sinai⁴, Pennsylvania State University⁵, University of Adelaide⁶, Novartis⁷, Boston Children's Hospital⁸

01 Feb 2009-Fertility and Sterility

TL;DR: It is the view of the AE-PCOS Society Task Force that PCOS should be defined by the presence of hyperandrogenism, ovarian dysfunction, and/or polycystic ovaries, and the exclusion of related disorders.

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1,678 citations

"Updated ultrasound criteria for pol..." refers background in this paper

...Polycystic ovary syndrome (PCOS) is a complex endocrine condition in which ovulatory dysfunction and androgen excess are cardinal features (Azziz et al., 2009)....
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Journal Article•DOI•

Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone

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Judith M. Adams¹, D. W. Polson¹, N. A. Abdulwahid¹, David V. Morris¹, Stephen Franks¹, H. D. Mason¹, M. Tucker¹, Jackie F. Price¹, Howard S. Jacobs¹ - Show less +5 more•Institutions (1)

Imperial College London¹

28 Dec 1985-The Lancet

TL;DR: In MFO ovarian morphology reverted to normal in ovulatory cycles, whereas in PCO the polycystic pattern persisted despite the presence of a dominant follicle, suggesting MFO may represent a normal ovarian response to weight-related hypothalamic disturbance of gonadotropin control.

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767 citations

"Updated ultrasound criteria for pol..." refers methods in this paper

...Despite major advances in ultrasound image technology, the threshold proposed for FNPS by our current study is remarkably similar to that proposed by Adams et al. over 25 years ago using transabdominal ultrasonography (i.e. 9 versus 10 or more FNPS, respectively) (Adams et al., 1985)....
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...9 versus 10 or more FNPS, respectively) (Adams et al., 1985)....
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Journal Article•DOI•

Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries

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Didier Dewailly, H. Gronier, E. Poncelet, Geoffroy Robin, Maryse Leroy, Pascal Pigny, Alain Duhamel¹, Sophie Catteau-Jonard - Show less +4 more•Institutions (1)

university of lille¹

01 Nov 2011-Human Reproduction

TL;DR: For the definition of PCOM, the former threshold of >12 for FN is no longer valid and a serum AMH >35 pmol/l appears to be more sensitive and specific than a FN >19 and should be included in the current diagnostic classifications for PCOS.

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Abstract: background: Polycystic ovarian morphology (PCOM) at ultrasound is currently used in the diagnosis of polycystic ovary syndrome (PCOS). We hypothesized that the previously proposed threshold value of 12 as an excessive number of follicles per ovary (FN) is no longer appropriate because of current technological developments. In this study, we have revisited the thresholds for FN and for the

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411 citations

"Updated ultrasound criteria for pol..." refers background or methods or result in this paper

...…there is debate as to whether polycystic ovaries alone represent a variant of PCOS (Adams et al., 2004; Ng et al., 2006; Mortensen et al., 2009; Dewailly et al., 2011; CatteauJonard et al., 2012) or whether they reflect natural variations in ovarian function among women and/or across the…...
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...Others have recommended a re-evaluation of the ultrasound criteria based on recent improvements in ultrasound image technology (Allemand et al., 2006; Dewailly et al., 2011) and newly developed methods for reliably estimating follicle populations in polycystic ovaries (Lujan et al., 2010a)....
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...Dewailly et al. (2011) obtained control subjects from patients seeking evaluation at their reproductive endocrinology clinic (N ¼ 105) and applied a cluster analysis to this control cohort to exclude a population of women who could be considered as having functional evidence of PCOS (N ¼ 39…...
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...As such, there is debate as to whether polycystic ovaries alone represent a variant of PCOS (Adams et al., 2004; Ng et al., 2006; Mortensen et al., 2009; Dewailly et al., 2011; CatteauJonard et al., 2012) or whether they reflect natural variations in ovarian function among women and/or across the lifespan (Hassan and Killick, 2003; Murphy et al....
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...Our proposed threshold for FNPO is also higher than more recent reports of revised ultrasound criteria for PCOS (Allemand et al., 2006; Dewailly et al., 2011)....
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