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Polycystic ovary syndrome (PCOS) affects 8-13% of women. The Rotterdam diagnostic criteria include polycystic ovarian morphology (PCOM) on ultrasound, but given recognized challenges, serum anti-Müllerian hormone (AMH) is proposed as an alternative. To inform international PCOS guidelines, a systematic review was completed. Key identified gaps include large international studies in well-defined populations across the lifespan, clustering of AMH with PCOS features, relationships to long-term health outcomes, and improved quality, assay standardization, and sample handling, all needed to determine cut offs. Here we identify research priorities to address these gaps and enhance AMH utility in PCOS. Once issues are addressed, AMH levels could replace more costly and less accessible ultrasound in PCOS diagnosis., (Copyright © 2019. Published by Elsevier Ltd.)

This Consensus Opinion summarizes the main aspects of several techniques for performing ovarian antral follicle count (AFC), proposes a standardized report and provides recommendations for future research. AFC should be performed using a transvaginal ultrasound (US) probe with frequency ≥ 7 MHz. For training, we suggest a minimum of 20-40 supervised examinations. The operator should be able to adjust the machine settings in order to achieve the best contrast between follicular fluid and ovarian stroma. AFC may be evaluated using real-time two-dimensional (2D) US, stored 2D-US cine-loops and stored three-dimensional (3D) US datasets. Real-time 2D-US has the advantage of permitting additional maneuvers to determine whether an anechoic structure is a follicle, but may require a longer scanning time, particularly when there is a large number of follicles, resulting in more discomfort to the patient. 2D-US cine-loops have the advantages of reduced scanning time and the possibility for other observers to perform the count. The 3D-US technique requires US machines with 3D capability and the operators to receive additional training for acquisition/analysis, but has the same advantages as cine-loop and also allows application of different imaging techniques, such as volume contrast imaging, inversion mode and semi-automated techniques such as sonography-based automated volume calculation. In this Consensus Opinion, we make certain recommendations based on the available evidence. However, there is no strong evidence that any one method is better than another; the operator should choose the best method for counting ovarian follicles based on availability of resources and on their own preference and skill. More studies evaluating how to improve the reliability of AFC should be encouraged. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Study Question: Can cluster analysis be used to differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with polycystic ovarian morphology (PCOM) in a non-subjective manner?, Summary Answer: Cluster analysis can be used to accurately and non-subjectively differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with PCOM., What Is Known Already: Currently, PCOM is diagnosed using a fixed threshold level, i.e. 12 or more follicles per ovary, and is one of the diagnostic criteria of polycystic ovary syndrome (PCOS). However, PCOM is also encountered in normo-ovulatory women, suggesting that it could just represent a normal variant. On the other hand, recent studies have shown subtle endocrine abnormalities in women with isolated PCOM that resemble those found in women with PCOS. Because of the strong correlation between anti-Müllerian hormone (AMH) and follicle number, a high serum AMH level has been proposed as a surrogate marker for PCOM and could, therefore, be integrated in the diagnostic classifications for PCOS., Study Design, Size, Duration: This was a retrospective observational cohort study. Original cohorts had been recruited for previous studies between 1998 and 2010. Two hundred ninety-seven regularly cycling women and 700 women with PCOS were eligible for inclusion., Participants/materials, Setting, Methods: Cluster analysis was performed in 297 regularly cycling women. After exclusion of 'PCOM' clusters, each 'non-PCOM' cluster (young, n = 118 and old, n = 100) was included in the construction of a receiver operating characteristics curve to test the diagnostic performance of follicle number per ovary (FNPO) and serum AMH in discriminating similarly aged full-blown PCOS patients (n = 411 and 237, respectively) from normal regularly cycling non-PCOM women., Main Results and Role of Chance: The optimal number of clusters was four; age was the most important classifying variable, followed by the FNPO and serum AMH. Two distinct clusters of normo-ovulatory women with PCOM were isolated and differed solely by age, i.e. 'young' and 'old'. Both 'PCOM' clusters had their similarly aged counterpart of 'non-PCOM' clusters. Likewise, two clusters comprised women younger than 30 years, with (n = 28, 'PCOM regularly cycling women') or without (n = 118, 'normal regularly cycling women') features of PCOM (increased FNPO and/or serum AMH). The two other clusters in older women could be labelled 'normal regularly cycling women' or 'PCOM regularly cycling women' (n = 100 and 51, respectively). The prevalence of PCOM was significantly greater in old than in young regularly cycling women controls. In the young population, after exclusion of the 'PCOM regularly cycling women', the diagnostic performance of AMH, expressed by area under the curve (AUC) (AUC = 0.903; CI (0.876-0.930)) to differentiate PCOS women from normal regularly cycling women was similar to that using the FNPO (AUC = 0.915, CI (0.891-0.940)) (P = 0.25), confirming results from earlier studies. In the old population, the diagnostic performance of AMH was greater than that of FNPO (AUCs = 0.948 (0.927-0.970) vs 0.874 (0.836-0.912), respectively, P = 0.00035). Cut-off levels of AMH and antral follicle count distinguishing regularly cycling non-PCOM women from PCOS women were higher in young women than in older women., Limitations, Reasons for Caution: Data of normal women were obtained from earlier studies, aiming to measure normal endocrine values. Apparently, the strong effect of age in cluster analysis revealed a dichotomy in the age distribution among the cohort of regularly cycling women included. This was involuntary since in none of the original studies, eligibility was limited by age and there was considerable overlap in age ranges of the cohorts. Transvaginal ultrasound was performed using a 6.5-8 mHz probe and our data confirm that this threshold level for FNPO is still valid if using such probe frequencies, although the use of devices with a maximum frequency lower than 8 mHz has become obsolete. Obviously, newer ultrasound scanner using higher transducer frequency will facilitate the detection of more follicles., Wider Implications of the Findings: Our data support the use of AMH as a surrogate for ultrasound to define PCOM, which is one of the three items of the Rotterdam classification. They also show that age should be taken into account to define the optimal threshold. The fact that the prevalence of PCOM was increased in the older regularly cycling women, may be due to 'attenuated' PCOS, a phenomenon that has been described in ageing women with PCOS. These women might have had anovulatory cycles in the past and have become ovulatory with increasing age, and were, therefore, eligible for this study. However, since most women included at older age have had spontaneous pregnancies in the past, PCOM at older age may be associated with a subclinical form of PCOS, which may also be present in young regularly cycling women., Study Funding/competing Interest(s): No funding was received for this study. J.S.E.L. has received grants and support from Ferring, MSD, Organon, Merck-Serono, Schering Plough and Serono during recruitment and analysis of data for this study. S.L.F., A.D. and D.D. do not have any conflict of interest., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Study Question: Does the use of the serum anti-Müllerian hormone (AMH) assay to replace or complement ultrasound (U/S) affect the diagnosis or phenotypic distribution of polycystic ovary syndrome (PCOS)?, Summary Answer: Combining U/S and the serum AMH assay to define polycystic ovarian morphology (PCOM) diagnoses PCOS (according to the Rotterdam classification) in more patients than definitions using one or the other of these indicators exclusively., What Is Known Already: Since 2003, PCOM, as defined by U/S, is one of the three diagnostic criteria for PCOS. As it is closely correlated with follicle excess seen at U/S, an excessive serum AMH level could be used as a surrogate for PCOM., Study Design, Size, Duration: Single-center retrospective study from a database of prospectively collected clinical, laboratory and ultrasound data from patients referred for oligo-anovulation (OA) and/or hyperandrogenism (HA) between January 2009 and January 2016., Participants/materials, Setting, Method: The standard Rotterdam classification for PCOS was tested against two modified versions that defined PCOM by either excessive serum AMH level alone (AMH-only) or a combination (i.e. 'and/or') of the latter and U/S. The PCOS phenotypes were defined as A (full phenotype, OA+HA+PCOM), B (OA+HA), C (HA+PCOM) and D (OA+PCOM)., Main Results and the Role of Chance: PCOS was more frequently diagnosed when PCOM was defined as the combination 'positive U/S' and/or 'positive AMH' (n = 639) than by either only U/S-only (standard definition, n = 612) or by AMH-only (n = 601). With this combination, PCOM was recognized in 637 of the 639 cases that met the Rotterdam classification, and phenotype B practically disappeared. In this population, U/S and AMH markers were discordant for PCOM in 103 (16.1%) cases (9% U/S-only, 7.1% AMH-only, P = 0.159). The markers used had no other significant impact on the phenotypic distribution (except for phenotype B). However, the percentage of cases positive by U/S-only was significantly higher in phenotype D than in phenotype A (14.1% vs. 5.8%, P < 0.05). Furthermore, in the discordant cases, plasma LH levels were significantly higher in the AMH-only group than in the concordant cases, and fasting insulin serum levels tended to be higher in the U/S-only group., Limitations, Reasons for Caution: This is a retrospective study. A referral bias explains the relatively high proportion of patients with phenotype D (28%). PCOM was defined by in-house thresholds. The AMH assay used is no longer commercially available., Wider Implications of the Findings: Our results suggest that ideally both U/S data and serum AMH level should be integrated to define PCOM in the Rotterdam classification. In a cost-effectiveness approach, the choice of one or the other has little impact on the diagnosis and the phenotyping of PCOS., Study Funding/competing Interest(s): No external funding. The authors have no conflict of interest to declare., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Study Question: Can cluster analysis can be used to identify a homogeneous subpopulation of women with polycystic ovarian morphology (PCOM) within a very large population of control women in a non-subjective way?, Summary Answer: Identification and exclusion of the cluster corresponding to women with PCOM from controls improved the diagnostic power of serum anti-Müllerian hormone (AMH) level and follicle number per ovary (FNPO) in discriminating between women with or without polycystic ovary syndrome (PCOS)., What Is Known Already: There is disagreement as to whether women with PCOM should be excluded from the control population when establishing FNPO and AMH diagnostic thresholds for the definition of PCOS and how to identify such women. It has been demonstrated that cluster analysis can detect women with PCOM within the control population through a set of classifying variables among which the most relevant was AMH. The adequacy of this approach has not been confirmed in other clinical settings., Study Design, Size, Duration: This was a retrospective study using clinical and laboratory data derived from the computerized database. The data were collected from March 2011 to May 2013., Participants/materials, Setting, Methods: The study included 893 patients referred for routine infertility evaluation and treatment. The patients were divided into three groups: (i) the control group (n = 621) included women with regular menstrual cycles and no signs of hyperandrogenism (HA), (ii) the full-blown PCOS group (n = 95) consisted of women who were diagnosed as having PCOS based on the presence of both HA and oligo/amenorrhoea (OA), (iii) the mild PCOS group included women with only two items of the Rotterdam classification, i.e. PCOM at ultrasonography according to the FNPO threshold of 12 or more and either OA (n = 110) or HA (n = 67)., Main Results and the Role of Chance: After exclusion of women with PCOM from the controls, the AMH threshold of 28 pmol/l with specificity 97.5% and sensitivity 84.2% [area under the curve (AUC) 0.948 (95% confidence interval (CI) 0.915-0.982)] and FNPO threshold of 12 with specificity 92.5% and sensitivity 83.2% [AUC 0.940 (95% CI 0.909-0.971)] for identifying PCOS were derived from the receiver operating characteristic curve analysis. The AMH threshold of 28 pmol/l had the same specificity for discriminating the mild and the full-blown PCOS phenotypes from controls., Limitations, Reasons for Caution: There was no selection bias other than being evaluated for infertility treatment, however, this could also be considered as a limitation of the study as these women may not necessarily be a representative sample of the general population. The study demonstrated that serum AMH has intrinsically a very high potency to detect women with PCOM within a control group. However, the AMH threshold is specific for this method and clinical setting., Wider Implications of the Findings: AMH threshold value for the definition of PCOM is method specific and cannot be universally applied. This study confirmed the results of previous studies that cluster analysis can identify women with PCOM within the very large control population without using a predefined diagnostic threshold for FNPO, and that AMH can detect women with PCOM with a high specificity. The exclusion of PCOM women from the controls by using a cluster analysis should be considered when establishing reference intervals and decision threshold values for various parameters used to characterize PCOS., Study Funding/competing Interests: The authors have no funding/competing interest(s) to declare., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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., (© 2014 European Society of Endocrinology.)

Objective: To evaluate the utility of a hypersensitive assay for measuring low antimüllerian hormone (AMH) levels in young cancer patients during the ovarian recovery phase of their chemotherapy., Design: Retrospective study., Setting: Academic medical center., Patient(s): Fifty-eight samples drawn at least 3 months after the end of chemotherapy in 30 women having either breast cancer (n=13) or hematologic malignancies (n=17) were selected to constitute two equally size groups: amenorrhea (n=30 samples) or spontaneous cycle (n=28 samples)., Intervention(s): None., Main Outcome Measure(s): Serum AMH levels were measured by a conventional AMH ELISA (EIA AMH/MIS) and a hypersensitive ELISA (PicoAMH, AnshLabs) on the same sample., Result(s): Using a conventional assay, serum AMH was detectable (≥3 pmol/L) in 6.7% and in 10.7% of the samples corresponding to amenorrheic or cycling patients, respectively (nonsignificant). By contrast, with PicoAMH, serum AMH was detectable (≥0.07 pmol/L) in 71.4% of the samples from cycling women vs. 16.7% of the samples from amenorrheic patients. Multivariate regression analysis showed that among putative contributors, only the menstrual status (r=0.307) and serum FSH level (r=-0.546) were independently correlated to a detectable serum AMH with the picoAMH assay exclusively., Conclusion(s): The picoAMH assay, allowing measurement of very low AMH concentrations in human serum, should refine postchemotherapy ovarian follow-up in young women., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Context: In the general population, about 30% of asymptomatic women have polycystic ovary-like abnormalities (PCO-L), i.e. polycystic ovarian morphology (PCOM) at ultrasound and/or increased anti-Müllerian hormone (AMH) serum level. PCOM has also been reported in 30-50% of women with functional hypothalamic amenorrhea (FHA)., Objective: The aim of this study was to verify whether both PCOM and excessive AMH level indicate PCO-L in FHA and to elucidate its significance., Design: We conducted a retrospective analysis using a database and comparison with a control population., Setting: Subjects received ambulatory care in an academic hospital., Patients: Fifty-eight patients with FHA were compared to 217 control women with nonendocrine infertility and body mass index of less than 25 kg/m(2)., Interventions: There were no interventions., Main Outcome Measures: We measured serum testosterone, androstenedione, FSH, LH, AMH, and ovarian area values. The antral follicle count (AFC) was used as a binary variable (i.e. negative or positive) because of the evolution of its sensitivity over the time of this study. The ability of these variables (except AFC) to detect PCO-L in both populations was tested by cluster analysis., Results: One cluster (cluster 2) suggesting PCO-L was detected in the control population (n = 52; 24%), whereas two such clusters were observed in the FHA population (n = 22 and n = 6; 38 and 10%; clusters 2 and 3, respectively). Cluster 2 in FHA had similar features of PCO-L as cluster 2 in controls, with higher prevalence of positive AFC (70%) and PCOM (70%), higher values of ovarian area and higher serum AMH (P < 0.0001 for all), and testosterone levels (P < 0.01) than in cluster 1. Cluster 3 in FHA was peculiar, with frankly elevated AMH levels. In the whole population (controls + FHA), PCO-L was significantly associated with lower FSH values (P < 0.0001)., Conclusion: PCO-L in FHA is a frequent and usually incidental finding of unclear significance, as in controls. The association of PCO-L with hypothalamic amenorrhea should not lead to a mistaken diagnosis of PCOS.

Objective: It is not known whether polycystic ovaries (PCO) are an ovarian appearance without pathological meaning or whether they share with polycystic ovary syndrome (PCOS) the same ovarian follicle abnormality. There are few studies including strictly selected women with PCO but without other criteria of PCOS. In order to address these issues, we compared hormonal, metabolic and ultrasound parameters obtained from patients with PCO only, patients with PCOS and controls., Methods: This was a comparative analysis including three age-matched groups of 95 patients, who were included consecutively in a database: controls, patients with sonographic PCO but no symptoms (PCO group) and patients with PCOS. A clinical examination, fasting serum sampling and pelvic ultrasound examination were performed between cycle days 2 and 5 and results were compared between groups., Results: The median serum anti-Mullerian hormone (AMH) level in the PCO group was intermediate between that in controls and that in the PCOS group (33.6 pmol/L, 19.8 pmol/L and 63.3 pmol/L, respectively), the differences being significant after adjustment for follicle number (P < 0.05), while the mean androgen serum level in the PCO group was similar to that in the control group and significantly lower than that in the PCOS group (P < 0.05) (median serum testosterone levels: 0.90 nmol/L, 0.79 nmol/L and 1.39 nmol/L; median androstenedione levels: 5.25 nmol/L, 4.37 nmol/L and 6.09 nmol/L, respectively). Body mass index, waist circumference and insulin levels had no effect on these differences., Conclusion: PCO is an abnormal condition, affected women showing no evidence of hyperandrogenism but having higher AMH serum levels compared with controls, suggesting a granulosa cell abnormality in PCO similar to that observed in PCOS. The absence of hyperandrogenism in PCO does not seem linked to the metabolic status., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Aims: This literature review attempts to answer the following questions: 1) When making an assessment of ovarian reserve (OR) in an infertile woman? and 2) what is the investigation that best identifies situations of low OR in order to guide patients towards appropriate care?, Results: Some elements of the clinical examination should prompt us to rapidly perform OR tests: patients over 35 years, with cycle disorders or a history of pelvic disease, chemotherapy or radiotherapy. The most widely used OR tests are FSH, estradiol, inhibin B, antral follicle count (AFC), ovarian volume, Antimüllerian hormone (AMH) and dynamic tests. Most studies evaluating these markers were performed within the frame of in vitro fertilization (IVF), and we have little information on their ability to predict spontaneous pregnancy. FSH seems an interesting marker to identify extreme situations of ovarian insufficiency when using a high threshold value. Estradiol assay must always be associated with it. The AFC and AMH both have a good ability to predict the response to ovarian stimulation in IVF. However, their association does not increase their strength of prediction. The ovarian volume, inhibin B as well as dynamic tests are not relevant markers. None of these markers can predict the chances of pregnancy in IVF., Conclusion: OR tests must be performed before assisted reproduction techniques (ART) and should include FSH, estradiol, and AMH or CFA. Each center must define its specific standards for the interpretation of results. This assessment will advise the couple about their chances of success in ART and the clinician to adapt its management., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objective: To review all available data and recommend a definition for polycystic ovary syndrome (PCOS) based on published peer-reviewed data, whether already in use or not, to guide clinical diagnosis and future research., Design: Literature review and expert consensus., Setting: Professional society., Patients: None., Intervention(s): None., Main Outcome Measure(s): A systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, to identify studies evaluating the epidemiology or phenotypic aspects of PCOS., Result(s): The Task Force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the Androgen Excess and PCOS (AE-PCOS) Society AE-PCOS Board of Directors. No section was finalized until all members were satisfied with the contents, and minority opinions noted. Statements were not included that were not supported by peer-reviewed evidence., Conclusion(s): Based on the available data, it is the view of the AE-PCOS Society Task Force that PCOS should be defined by the presence of hyperandrogenism (clinical and/or biochemical), ovarian dysfunction (oligo-anovulation and/or polycystic ovaries), and the exclusion of related disorders. However, a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism, but recognized that more data are required before validating this supposition. Finally, the Task Force recognized and fully expects that the definition of this syndrome will evolve over time to incorporate new research findings.

Background: We previously hypothesized that the excess of 2-5 mm follicles seen at ovarian ultrasonography might be involved in the follicular arrest (FA) of polycystic ovary syndrome (PCOS), independently from the main putative contributors of FA, namely hyperandrogenism and hyperinsulinism., Methods: A multivariate statistical analysis was applied retrospectively to clinical, biological and ultrasound data that were consecutively collected during 5 years in 457 patients with polycystic ovaries and in 188 age-matched non-hyperandrogenic and regularly cycling controls without PCO at ultrasound., Results: Stepwise discriminant analysis indicated that in PCOS the 2-5 mm follicle number (FN) gave the strongest correlation to severity of the FA, followed by age and then by fasting insulin level. The other variables [waist circumference (WC), 6-9 mm FN, serum testosterone, FSH, LH and ovarian area] were rejected by the analysis. Multiple linear regression indicated a significant and independent negative relationship between the 2-5 and 6-9 mm FN in the PCOS (r = - 0.186, P < 0.01) and control groups (r = - 0.281, P < 0.01). In PCOS only, the 6-9 mm FN was negatively and independently related to the WC (r = - 0.108, P < 0.05)., Conclusions: The size of the 2-5 mm follicle pool is an independent and important contributor to the FA of PCOS. This result could be explained by an exaggerated physiological inhibitory effect from this pool on the terminal follicle growth. The metabolic derangement of PCOS that also contributes to the FA would act through a different mechanism.

This study investigates the usefulness of serum inhibin B, progesterone, and AMH concentrations obtained during controlled ovarian hyperstimulation (COH) in predicting ovarian response and assisted reproductive treatment outcome in women undergoing ovarian stimulation under pituitary desensitization. The inhibin B rise, between day 6 and 8 of COH, is a good predictor of ovarian response (number of oocytes retrieved). Measuring AMH during COH has no superiority on the basal determination. The preovulatory increase in progesterone is not useful in predicting oocyte quality and pregnancy.

Background: This study revisited the ovarian volume (OV) as a diagnostic criterion for polycystic ovaries (PCO). Indeed, a threshold of 10 cm(3) for the OV, chosen at the polycystic ovary syndrome (PCOS) international consensus held at Rotterdam in 2003, was to date not based on appropriate studies such as receiver operator characteristic (ROC) curve analysis., Methods: This prospective study included 154 women with PCOS, selected by using the former National Institutes of Health criteria, who were compared with 57 women with normal ovarian function. Ultrasound examination was performed between cycle days 2 and 7 with a 7 MHz transvaginal transducer., Results: Mean OV, ovarian area (OA) and follicle number (FN) values were significantly higher in the PCOS group than in controls. The area under the ROC curve (AUC) was >0.9 for all three criteria, indicating a satisfactory diagnostic potency for each. Concerning the OV, setting the threshold at 7 cm(3) offered the best compromise between specificity (91.2%) and sensitivity (67.5%). In comparison, specificity and sensitivity were 98.2 and 45%, respectively, with a threshold at 10 cm(3). Nevertheless, the highest AUC was obtained for FN (0.956) and then for OA (0.941)., Conclusions: OV is a good diagnostic criterion for PCO but, on the basis of the present data, we propose to lower its threshold to 7 cm(3). The FN >12 still appears as the best diagnostic criterion. The OA could be used as a surrogate for OV in difficult situations.

Background: The purpose of this work was to revisit the gonadotrophin insufficiency of functional hypothalamic amenorrhoea (FHA) with the use of relevant ovarian markers., Methods: Serum anti-Mullerian hormone (AMH), estradiol (E2), inhibin B, LH and FSH were immunoassayed in 31 women with FHA and in 30 healthy women in early follicular phase. The ovarian antral follicle number (FN) was determined within two distinct diameter ranges (2-5 and 6-9 mm) by ultrasound in real time, the same day as the blood sampling., Results: The 2-5 mm FN was similar between the two groups, while the 6-9 mm FN was significantly less in FHA than in controls, in relation with lower serum FSH levels (r=0.428; P<0.024). Nine (29%) FHA patients had a low serum basal FSH level (i.e. <4.5 IU/l, 5th percentile of control values). In the 22 (71%) patients with apparently normal FSH, the mean 6-9 mm FN was similar to controls. However, in this sub-group, the mean AMH serum level and the AMH:2-5 mm FN ratio were significantly higher and the mean inhibin B serum level was significantly lower than in controls. No significant relationship was found between the serum LH levels and the FN, AMH or inhibin B values., Conclusion: Only a minority of patients with FHA have a low serum basal FSH level, and we show that this is associated with fewer 6-9 mm follicles at the ovarian level. Despite a normal serum FSH level and 6-9 mm FN in the majority of patients with FHA, the functional follicle markers are abnormal. This suggests that the FSH action on the ovary is incomplete and is not properly reflected by its serum level nor by FN at ultrasound.

This review exposes the follicular abnormalities responsible for anovulation in polycystic ovary syndrome (PCOS). The putative pathophysiological explanations involve the principal intra- and extra-ovarian regulators which intervene during normal folliculogenesis to control the initial recruitment and growth and then the cyclic recruitment. We propose the hypothesis that the follicular problem in PCOS is 2-fold, but with the two abnormalities being linked. First, the intra-ovarian hyperandrogenism may promote early follicular growth, leading to a 2-5 mm follicle excess. Second, the ensuing excessive number of selectable follicles would inhibit the selection process, presumably through follicle-follicle interaction involving granulosa cell (GC) products such as the anti-Müllerian hormone (AMH). These factors would induce a reversible refractoriness to the FSH-induced differentiation of GC. This explanation challenges but does not exclude other hypotheses about the follicular arrest, such as the premature LH action on the GC of selectable follicles. Hyperinsulinism or insulin resistance would act as a second hit, worsening the follicular arrest either through amplification of the intra-ovarian hyperandrogenism or through dysregulation of the GC. The loss of cyclic rhythm would prevent the inter-cycle elevation of FSH, thus perpetuating the impairment of the ovulation process.

Along the menstrual cycle and during pregnancy, small blood vessels proliferate within the uterus and the ovulating ovary. Angiogenic factors such as VEGF are involved in this phenomenon. In the ovulating ovary, neo-angiogenesis spreads progressively inside the dominant follicle wall and plays a role in the maintenance of the corpus luteum, under the influence of LH (or HCG during pregnancy). In ART, the measure of the blood flow is interesting since it correlates to the number and quality of harvested oocytes. Follicle hypoxia may impair chromosomal organization and separation within the oocyte. This neo-angiogenesis is also important in endometrium, in particular for embryo implantation. Ultrasounds with Doppler allow to estimate the endometrial receptivity, especially in IVF cycles. It is assumed that chance for ongoing pregnancy is almost zero if: endometrial thickness is < 8 mm; uterine pulsatility index (PI) is > 3. Doppler ultrasounds are a useful and even mandatory complement to standard vaginal ultrasonoghraphy in ART. It can be viewed as an indicator of the endometrial and follicular "well-being".

Objective: To extend our previous findings on the diagnostic validity of ovarian stroma hypertrophy in women with hyperandrogenic and/or menstrual disorders., Design: Transvaginal ultrasonography was performed in 69 patients complaining of hyperandrogenism and/or menstrual disorders and in 48 normal ovulatory women in early follicular phase. To check the validity of stroma assessment by visual analysis, we used computer-assisted analysis, which allowed selective measurement of the stromal area on a longitudinal ovarian cut. Sensitivity and specificity of each method were estimated by using the normative data from the control group., Results: Stromal area was considered to be increased using visual analysis and computer-assisted analysis in 74% and 61% patients, respectively. Specificity of this sign was 84% and 96% by visual analysis and computer-assisted analysis, respectively. In patients, the increase in stromal area correlated very significantly with the one of total ovarian area, whose upper normal limit was 5.5 cm2 per ovary., Conclusion: Visual assessment of stroma may be misleading in some cases, with the risk of overestimating its hypertrophy. An increased total ovarian area > 5.5 cm2 (which can easily be detected by carefully shaping a strict longitudinal ovarian cut) has the same diagnostic value as an increased stromal area by computerized measurement.