Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome (2023)
WHAT DOES THIS MEAN FOR THOSE WITH PCOS?
Building on the 2018 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome (PCOS), this Guideline updates and expands clinical questions, aiming to ensure that women with PCOS receive optimal, evidence-based care that meets their needs and improves health outcomes. The guideline and translation program were developed with full consumer participation at all stages including priority topics and outcomes for those with PCOS. The aim is to support women and their healthcare providers to optimize diagnosis, assessment and management of PCOS. There is an emphasis on improved education and awareness of healthcare professionals, partnership in care, and empowerment of women with PCOS. Personal characteristics, preferences, culture and values are considered, in addition to resource availability across different settings. With effective translation, the Guideline will address priorities identified by women with PCOS, upskill healthcare professionals, empower consumers, improve care and outcomes, identify key research gaps, and promote vital future research.INTRODUCTION
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-aged women, with impacts across the lifespan from adolescence to post menopause. PCOS prevalence is between 10 to 13% as demonstrated in the guideline process.1,2 PCOS aetiology is complex; clinical presentation is heterogeneous with reproductive, metabolic, and psychological features.1,2 Women internationally experience delayed diagnosis and dissatisfaction with care.3-5 Clinical practice in the assessment and management of PCOS remains inconsistent, with ongoing key practice evidence gaps. Following on from the 2018 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome,6,7 independently evaluated as high quality, this extensive update integrates current literature with previous systematic reviews and extends to new clinical questions prioritized by consumers. Ultimately, we aim to update, extend and translate rigorous, comprehensive evidence-based guidelines for diagnosis, assessment and treatment, to improve the lives of those with PCOS worldwide.To do so, the Guideline leverages substantive government and society investment and brings together extensive consumer engagement and international collaboration with leading societies and organizations, multidisciplinary experts, and primary care representatives. This comprehensive evidencebased Guideline is constructed from a rigorous, Appraisal of Guidelines for Research and Evaluation-II (AGREEII)- compliant, evidence-based guideline development process. It provides a single source of international evidence-based recommendations to guide clinical practice with the opportunity for adaptation in relevant health systems. Together with an extensive translation program, the aim is to reduce worldwide variation in care and promote high quality clinical service provision to improve health outcomes and quality of life inwomen with PCOS. The Guideline is supported by a multifaceted international translation programme with co-designed resources to enhance the skills of healthcare professionals and to empower women with PCOS, with an integrated comprehensive evaluation program. Here, we summarize recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of PCOS.
MATERIALS AND METHODS
Best practice evidence-based guideline development methods were applied and are detailed in the full Guideline and the technical reports, which are available online (www.monash.edu/ medicine/mchri/pcos).8 In brief, extensive healthcare professional and consumer or patient engagement informed the Guideline priority areas. International society-nominated panels fromacross three leading entities, four partner organizations and thirty-two collaborating entities included consumers and experts in paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, psychology, dietetics, exercise physiology, sleep, bariatric/ metabolic surgery, public health, other co-opted experts, project management, evidence synthesis and translation. Governance included an international advisory and a management committee, five guideline development groups (GDGs) with 56 members, and paediatric, consumer, and translation committees. The five GDGs covered i) Screening, diagnostic and risk assessment and life stage; ii) Psychological features and models of care; iii) Lifestyle management; iv) Management of nonfertility features; and v) Assessment and management of infertility. The leading entities; the Australian National Health and Medical Research Council (NHMRC) Centres for Research Excellence in Women’s Health in Reproductive Life and in Polycystic Ovary Syndrome, led byMonash University, partneredwith the American Society for Reproductive Medicine, the Endocrine Society, the European Society of Endocrinology and the European Society of Human Reproduction and Embryology and collaborated with 32 other entities. With international meetings over 12 months fifty-five prioritized clinical questions involved 52 systematic and three narrative reviews, generating evidence-based and consensus recommendations with accompanying practice points. Committee members nominated by partner and collaborator organizations provided international peer review, and independent experts reviewed methods which were then submitted to NHMRC for independent review. The target audience includes multidisciplinary healthcare professionals, consumers or patients, policy makers, and educators. The Guideline includes a focus on equity, cultural and ethnic diversity, avoidance of stigma and inclusivity (see full guideline for details).Processes aligned with all elements of the AGREE-II tool for quality guideline assessment,9 with extensive evidence synthesis and meta-analysis. Integrity assessment was integrated into guideline evidence synthesis processes and followed the Research Integrity in Guideline Development (RIGID) framework, with studies assessed against criteria from the Research Integrity Assessment (RIA) tool and the Trustworthiness in RAndomised Controlled Trials (TRACT) checklist.10-12 Evidence synthesis methods are outlined in the full guideline and followed best practice9,13,14 Guideline recommendations are presented by category, terms used, evidence quality and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework considerations. Category includes evidence-based (sufficient evidence in PCOS) or consensus (insufficient evidence in PCOS, hence evidence in general or relevant populations was considered) recommendations and accompanying practice points (implementation considerations) (Table 1).
Table 1. Categories of PCOS guideline recommendations
| EBR | Evidence Based Recommendations: Evidence sufficient to inform a recommendation made by the guideline development group. |
| CR | Consensus Recommendations: In the absence of adequate evidence, a consensus recommendation has been made by the guideline development group, also informed by evidence from the general population. |
| PP | Practice Points: Evidence not sought. A practice point has been made by the guideline development group where important issues arose from discussion of evidence-based or consensus recommendations. |
| PCOS, polycystic ovary syndrome. | |
The terms include ‘‘should’’, ‘‘could’’ and ‘‘should not’’, which are informed by the nature of the recommendation (evidence or consensus), the GRADE framework and the evidence quality and are independent descriptors reflecting GDG judgement. They refer to overall interpretation and practical application of the recommendation, balancing benefits and harms. ‘‘Should’’ is used where benefits of the recommendation exceed harms and where the recommendation can be trusted to guide practice. Conditional recommendations are reflected using the terms ‘‘could’’ or ‘‘should/could consider’’ which are used where evidence quality was limited or available studies demonstrate little clear advantage of one approach over another, or the balance of benefits to harms was unclear. ‘‘Should not’’ applies when there is a lack of appropriate evidence, or harms may outweigh benefits.
Evidence quality was categorized according to the GRADE framework, with judgments about the quality of the included studies and/or synthesized evidence incorporating risk of bias, inconsistency, indirectness, imprecision and any other considerations (e.g., publication bias) that may influence evidence quality. These judgments considered study number and design, statistical data and importance of outcomes (Table 2). The quality of evidence reflects the confidence that the estimate of the effect is adequate to support each recommendation,13 largely determined by the expert evidence synthesis team. GRADE acknowledges that evidence quality is a continuum; any discrete categorization involves some arbitrary decisions; nevertheless, the advantages of simplicity, transparency, and clarity outweigh these limitations.13
The GRADE framework enabled structured and transparent consideration across evidence quality, feasibility, acceptability, cost, implementation, and ultimately recommendation strength13 and was completed at face to face guideline group meetings for all clinical questions (Table 3).15
Notably, certainty of evidence varied across outcomes within each question. Here evidence certainty reflects the lowest certainty for the critical outcomes. Evidence was often stronger for the top ranked outcome, and high quality randomized controlled trials (RCTs) were often present, despite overall low quality of evidence. These nuances were considered by the GDG for all question as per the technical report, with any apparent discrepancy between recommendation strength and evidence certainty justified in the full Guideline. Finally, we note that this is a living Guideline with annual evidence review in rapidly evolving areas.
The recommendations (Table 4) apply the category, descriptive terms, GRADE of the recommendations and the quality of the evidence. The full Guideline, technical evidence and administrative reports are available online (www.monash.edu/ medicine/mchri/pcos). The Guideline outlines the clinical need for the question, the clinical question, the evidence summary, the recommendations and practice points, and a summary of the justification developed by the GDGs using the GRADE framework. Extensive international peer review from across the 39 organizationswas then considered by eachGDGand recommendations were reconsidered applying the GRADE framework if justified. The comprehensive evidence reviews, profiles, andGRADEframeworks supporting each recommendation can be found in the Technical Report. The administrative report on guideline development, disclosure of interest process and declarations, peer review feedback and responses can also be found online. Here, we present the evidence-based and consensus recommendations and practice points (Table 4). This summary, the full Guideline and technical reports are supported by a comprehensive co-designed translation program to optimize dissemination and impact with resources freely available online (www.monash.edu/medicine/mchri/pcos).
Two algorithms are provided to support recommendations on diagnosis (Figure 1) and infertility management (Figure 2).
Evidence quality was categorized according to the GRADE framework, with judgments about the quality of the included studies and/or synthesized evidence incorporating risk of bias, inconsistency, indirectness, imprecision and any other considerations (e.g., publication bias) that may influence evidence quality. These judgments considered study number and design, statistical data and importance of outcomes (Table 2). The quality of evidence reflects the confidence that the estimate of the effect is adequate to support each recommendation,13 largely determined by the expert evidence synthesis team. GRADE acknowledges that evidence quality is a continuum; any discrete categorization involves some arbitrary decisions; nevertheless, the advantages of simplicity, transparency, and clarity outweigh these limitations.13
The GRADE framework enabled structured and transparent consideration across evidence quality, feasibility, acceptability, cost, implementation, and ultimately recommendation strength13 and was completed at face to face guideline group meetings for all clinical questions (Table 3).15
Notably, certainty of evidence varied across outcomes within each question. Here evidence certainty reflects the lowest certainty for the critical outcomes. Evidence was often stronger for the top ranked outcome, and high quality randomized controlled trials (RCTs) were often present, despite overall low quality of evidence. These nuances were considered by the GDG for all question as per the technical report, with any apparent discrepancy between recommendation strength and evidence certainty justified in the full Guideline. Finally, we note that this is a living Guideline with annual evidence review in rapidly evolving areas.
OTHER PCOS RESOURCES:Two algorithms are provided to support recommendations on diagnosis (Figure 1) and infertility management (Figure 2).
Table 2. Quality (certainty) of evidence categories (adapted from GRADE)
| High | ⨁⨁⨁⨁ | Very confident that the true effect lies close to that of the estimate of the effect. |
| Moderate | ⨁⨁⨁◯ | Moderate confidence in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is different. |
| Low | ⨁⨁◯◯ | Limited confidence in the effect estimate. The true effect may be substantially different from the estimate of the effect. |
| Very Low | ⨁◯◯◯ | Very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of the effect. |
| GRADE, Grading of Recommendations, Assessment, Development, and Evaluation. | ||
Table 3. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework recommendation strength
| ❖ | Conditional recommendation against the option. |
| ❖ ❖ | Conditional recommendation for either the option or the comparison. |
| ❖ ❖ ❖ | Conditional recommendation for the option. |
| ❖ ❖ ❖ ❖ | Strong recommendation for the option. |
Table 4. Recommendations for the assessment and management of polycystic ovary syndrome (PCOS). Monash University on behalf of the NHMRC Centre for Research Excellence in Women's Health in Reproductive Life, 2023.
| NO. | TYPE | RECOMMENDATION | GRADE/QUALITY |
| 1 | Screening, diagnostic and risk assessment and life-stages General principles |
||
| PP | All diagnostic assessments are recommended for use in accordance with the diagnostic algorithm (Algorithm 1). | ||
| 1.1 | Irregular cycles and ovulatory dysfunction | ||
| 1.1.1 | CR | Irregular menstrual cycles are defined as:
|
❖ ❖ ❖ ❖ |
| 1.1.2 | PP | The mean age of menarche may differ across populations. | |
| 1.1.3 | PP | In adolescents with irregular menstrual cycles, the value and optimal timing of assessment and diagnosis of PCOS should be discussed with the patient and their parent/s or guardian/s, considering diagnostic challenges at this life stage and psychosocial and cultural factors. |
|
| 1.1.4 | PP | For adolescents who have features of PCOS, but do not meet diagnostic criteria, an ‘‘increased risk’’ could be considered and reassessment advised at or before full reproductive maturity, 8 years post menarche. This includes those with PCOS features before combined oral contraceptive pill (COCP) commencement, those with persisting features and those with significant weight gain in adolescence. |
|
| 1.1.5 | PP | Ovulatory dysfunction can still occur with regular cycles and if anovulation needs to be confirmed serum progesterone levels can be measured. | |
| 1.2 | Biochemical hyperandrogenism | ||
| 1.2.1 | EBR | Healthcare professionals should use total and free testosterone to assess biochemical hyperandrogenism in the diagnosis of PCOS; free testosterone can be estimated by the calculated free androgen index. | ❖ ❖ ❖ ❖ ⨁◯◯◯ |
| 1.2.2 | EBR | If testosterone or free testosterone is not elevated, healthcare professionals could consider measuring androstenedione and dehydroepiandrosterone sulfate (DHEAS), noting their poorer specificity and greater age associated decrease in DHEAS. |
❖ ❖ ❖ ⨁◯◯◯ |
| 1.2.3 | EBR | Laboratories should use validated, highly accurate tandem mass spectrometry (LC-MS/MS) assays for measuring total testosterone and if needed, for androstenedione and DHEAS. Free testosterone should be assessed by calculation, equilibrium dialysis or ammonium sulfate precipitation. |
❖ ❖ ❖ ❖ |
| 1.2.4 | EBR | Laboratories should use LC-MS/MS assays over direct immunoassays (e.g., radiometric, enzyme-linked, etc.) for assessing total or free testosterone, which have limited accuracy and demonstrate poor sensitivity and precision for diagnosing hyperandrogenism in PCOS. | ❖ ❖ ❖ ❖ ⨁⨁◯◯ |
| 1.2.5 | PP | For the detection of hyperandrogenism in PCOS, the assessment of biochemical hyperandrogenism is of greatest value in patients with minimal or no clinical signs of hyperandrogenism (i.e., hirsutism). | |
| 1.2.6 | PP | It is very difficult to reliably assess for biochemical hyperandrogenism in women on the combined oral contraceptive pill (COCP) as the pill increases sex hormone-binding globulin and reduces gonadotrophindependent androgen production. If already on the COCP, and assessment of biochemical androgens is imperative, the pill should be withdrawn for a minimum of three months and contraception should be managed otherwise during this time. |
|
| 1.2.7 | PP | Repeated androgen measures for the ongoing assessment of PCOS in adults have a limited role. | |
| 1.2.8 | PP | In most adolescents, androgen levels reach adult ranges at 12-15 years of age | |
| 1.2.9 | PP | If androgen levels are markedly above laboratory reference ranges, causes of hyperandrogenaemia other than PCOS, including ovarian and adrenal neoplastic growths, congenital adrenal hyperplasia, Cushing’s syndrome, ovarian hyperthecosis (after menopause), iatrogenic causes, and syndromes of severe insulin resistance, should be considered. However, some androgen-secreting neoplasms are associated with only mild to moderate increases in androgen levels. The clinical history of time of onset and/or rapid progression of symptoms is critical in assessing for an androgen-secreting tumour. |
|
| 1.2.10 | PP | Reference ranges for different methods and laboratories vary widely, and are often based on an arbitrary percentile or variances of the mean from a population that has not been fully characterized and is highly likely to include women with PCOS. Normal values should be determined either by the range of values in a well characterized healthy control population or by cluster analysis of general population values. |
|
| 1.2.11 | PP | Laboratories involved in androgen measurements in females should consider:
|
|
| 1.3 | Clinical hyperandrogenism | ||
| 1.3.1 | EBR | The presence of hirsutism alone should be considered predictive of biochemical hyperandrogenism and PCOS in adults. |
❖ ❖ ❖ ⨁◯◯◯ |
| 1.3.2 | EBR | Healthcare professionals could recognize that female pattern hair loss and acne in isolation (without hirsutism) are relatively weak predictors of biochemical hyperandrogenism. | ❖ ❖ ❖ ⨁◯◯◯ |
| 1.3.3 | CR | A comprehensive history and physical examination should be completed for symptoms and signs of clinical hyperandrogenism, including acne, female pattern hair loss and hirsutism in adults, and severe acne and hirsutism in adolescents. |
❖ ❖ ❖ ❖ |
| 1.3.4 | CR | Healthcare professionals should be aware of the potential negative psychosocial impact of clinical hyperandrogenism and should consider the reporting of unwanted excess hair growth and/or female pattern hair loss as being important, regardless of apparent clinical severity. |
❖ ❖ ❖ |
| 1.3.5 | CR | A modified Ferriman Gallwey score (mFG) of 4 – 6 should be used to detect hirsutism, depending on ethnicity, acknowledging that self-treatment is common and can limit clinical assessment. | ❖ ❖ ❖ ❖ |
| 1.3.6 | CR | Healthcare professionals should consider that the severity of hirsutism may vary by ethnicity but the prevalence of hirsutism appears similar across ethnicities. | ❖ ❖ ❖ |
| 1.3.7 | PP | Healthcare professionals should:
|
|
| 1.4 | Ultrasound and polycystic ovarian morphology | ||
| 1.4.1 | EBR | Follicle number per ovary (FNPO) should be considered the most effective ultrasound marker to detect polycystic ovarian morphology (PCOM) in adults. |
❖ ❖ ❖ ❖ ⨁⨁◯◯ |
| 1.4.2 | EBR | Follicle number per ovary (FNPO), follicle number per cross-section (FNPS) and ovarian volume (OV) should be considered accurate ultrasound markers for PCOM in adults. | ❖ ❖ ❖ ❖ ⨁⨁◯◯ |
| 1.4.3 | CR | PCOM criteria should be based on follicle excess (FNPO, FNPS) and/or ovarian enlargement. | ❖ ❖ ❖ ❖ |
| 1.4.4 | CR | Follicle number per ovary (FNPO) ≥ 20 in at least one ovary should be considered the threshold for PCOM in adults. |
❖ ❖ ❖ ❖ |
| 1.4.5 | CR | Ovarian volume (OV)≥10ml or follicle number per section (FNPS)≥10 in at least one ovary in adults should be considered the threshold for PCOM if using older technology or image quality is insufficient to allow for an accurate assessment of follicle counts throughout the entire ovary. |
❖ ❖ ❖ ❖ |
| 1.4.6 | PP | There are no definitive criteria to define polycystic ovary morphology (PCOM) on ultrasound in adolescents, hence it is not recommended in adolescents. | |
| 1.4.7 | PP | When an ultrasound is indicated, if acceptable to the individual, the transvaginal approach is the most accurate for the diagnosis of PCOM. |
|
| 1.4.8 | PP | Transabdominal ultrasound should primarily report ovarian volume (OV) with a threshold of ≥10 ml or follicle number per section (FNPS) ≥10 in either ovary in adults given the difficulty of assessing follicle counts throughout the entire ovary with this approach. | |
| 1.4.9 | PP | In patients with irregular menstrual cycles and hyperandrogenism, an ovarian ultrasound is not necessary for PCOS diagnosis. | |
| 1.4.10 | PP | Thresholds for PCOM should be revised regularly with advancing ultrasound technology, and age-specific cut-off values for PCOM should be defined. | |
| 1.4.11 | PP | There is a need for training in careful and meticulous follicle counting per ovary and clear standardized protocols are recommended for PCOM reporting on ultrasound including at a minimum:
|
|
| 1.5 | Anti-Müllerian Hormone in the diagnosis of PCOS | ||
| 1.5.1 | EBR | Serum anti-M€ullerian hormone (AMH) could be used for defining PCOM in adults. | ❖ ❖ ❖ ⨁⨁⨁◯ |
| 1.5.2 | EBR | Serum AMH should only be used in accordance with the diagnostic algorithm, noting that in patients with irregular menstrual cycles and hyperandrogenism, an AMH level is not necessary for PCOS diagnosis. |
❖ ❖ ❖ ❖ ⨁⨁⨁◯ |
| 1.5.3 | EBR | We recommend that serum AMH should not be used as a single test for the diagnosis of PCOS. | ❖ ❖ ❖ ❖ ⨁⨁⨁◯ |
| 1.5.4 | EBR | Serum AMH should not yet be used in adolescents. | ❖ ❖ ❖ ❖ ⨁⨁⨁◯ |
| 1.5.5 | PP | Either serum AMHor ultrasound may be used to define PCOM; however, both tests should not be performed to limit overdiagnosis. | |
| 1.5.6 | PP | Laboratories and healthcare professionals need to be aware of factors that influence AMH in the general population including:
|
|
| 1.5.7 | PP | Laboratories involved in AMH measurements in females should use population and assay specific cut-offs. | |
| 1.6 | Ethnic variation | ||
| 1.6.1 | EBR | Healthcare professionals should be aware of the high prevalence of PCOS in all ethnicities and across world regions, ranging from 10-13% globally using the Rotterdam criteria. | ❖ ❖ ❖ ❖ ⨁⨁◯◯ |
| 1.6.2 | EBR | Healthcare professionals should be aware that PCOS prevalence is broadly similar across world regions, but may be higher in South East Asian and Eastern Mediterranean regions. | ❖ ❖ ❖ ❖ ⨁⨁◯◯ |
| 1.6.3 | PP | Healthcare professionals should be aware that the presentation of PCOS may vary across ethnic groups. | |
| 1.7 | Menopause life stage | ||
| 1.7.1 | CR | A diagnosis of PCOS could be considered as enduring / lifelong. | ❖ ❖ ❖ |
| 1.7.2 | CR | Healthcare professionals could consider that both clinical and biochemical hyperandrogenism persist in the postmenopause for women with PCOS. | ❖ ❖ ❖ |
| 1.7.3 | CR | PCOS diagnosis could be considered postmenopause if there is a past diagnosis, or a long-term history of oligo-amenorrhoea with hyperandrogenism and/or PCOM, during the earlier reproductive years (age 20-40). |
❖ ❖ ❖ |
| 1.7.4 | CR | Further investigations should be considered to rule out androgen-secreting tumours and ovarian hyperthecosis in postmenopausal women presenting with new-onset, severe or worsening hyperandrogenism including hirsutism. |
❖ ❖ ❖ |
| 1.8 | Cardiovascular disease risk | ||
| 1.8.1 | EBR | Women with PCOS should be considered at increased risk of cardiovascular disease and potentially of cardiovascular mortality, acknowledging that the overall risk of cardiovascular disease in pre-menopausal women is low. |
❖ ❖ ❖ ⨁◯◯◯ |
| 1.8.2 | EBR | All women with PCOS should be assessed for cardiovascular disease risk factors. | ❖ ❖ ❖ ❖ ⨁◯◯◯ |
| 1.8.3 | CR | All women with PCOS, regardless of age and BMI, should have a lipid profile (cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride level) at diagnosis. Thereafter, frequency of measurement should be based on the presence of hyperlipidaemia and additional risk factors or global cardiovascular risk. |
❖ ❖ ❖ ❖ |
| 1.8.4 | CR | All women with PCOS should have blood pressure measured annually and when planning pregnancy or seeking fertility treatment, given the high risk of hypertensive disorders in pregnancy and the associated comorbidities. | ❖ ❖ ❖ ❖ |
| 1.8.5 | CR | Funding bodies should recognize that PCOS is highly prevalent with multisystem effects including cardiometabolic disease and should diversify and increase research support accordingly. |
❖ ❖ ❖ ❖ |
| 1.8.6 | CR | Cardiovascular general population guidelines could consider the inclusion of PCOS as a cardiovascular risk factor. | ❖ ❖ ❖ |
| 1.8.7 | CR | Healthcare professionals, women with PCOS and other stakeholders should all prioritize preventative strategies to reduce cardiovascular risk. | ❖ ❖ ❖ ❖ |
| 1.8.8 | PP | Consideration should be given to the differences in cardiovascular risk factors, and cardiovascular disease, across ethnicities (see 1.6.1) and age, when determining frequency of risk assessment. | |
| 1.9 | Impaired glucose tolerance and type 2 diabetes risk | ||
| 1.9.1 | EBR | Healthcare professionals and women with PCOS should be aware that, regardless of age and BMI, women with PCOS have an increased risk of impaired fasting glucose, impaired glucose tolerance and type 2 diabetes. | ❖ ❖ ❖ ❖ ⨁⨁◯◯ |
| 1.9.2 | EBR | Glycaemic status should be assessed at diagnosis in all adults and adolescents with PCOS. | ❖ ❖ ❖ ❖ ⨁⨁◯◯ |
| 1.9.3 | CR | Glycaemic status should be reassessed every one to three years, based on additional individual risk factors for diabetes. | ❖ ❖ ❖ ❖ |
| 1.9.4 | CR | Healthcare professionals, women with PCOS and other stakeholders should prioritize preventative strategies to reduce type 2 diabetes risk. | ❖ ❖ ❖ ❖ |
| 1.9.5 | CR | Funding bodies should recognize that PCOS is highly prevalent, has significantly higher risk for diabetes, and should be funded accordingly. |
❖ ❖ ❖ ❖ |
| 1.9.6 | CR | Diabetes general population guidelines should consider the inclusion of PCOS as an independent risk factor for diabetes. | ❖ ❖ ❖ ❖ |
| 1.9.7 | PP | Healthcare professionals, adults and adolescents with PCOS and their first degree relatives, should be aware of the increased risk of diabetes and the need for regular glycaemic assessment. | |
| 1.9.8 | PP | Women with type 1 and type 2 diabetes have an increased risk of PCOS and screening should be considered in individuals with diabetes. | |
| Glycaemic testing | |||
| 1.9.9 | EBR | Healthcare professionals and women with PCOS should recommend the 75-g oral glucose tolerance test (OGTT) as the most accurate test to assess glycaemic status in PCOS, regardless of BMI. | ❖ ❖ ❖ ❖ ⨁◯◯◯ |
| 1.9.10 | EBR | If an OGTT cannot be performed, fasting plasma glucose and/or glycated haemoglobin (HbA1c) could be considered, noting significantly reduced accuracy. | ❖ ❖ ❖ ❖ ⨁◯◯◯ |
| 1.9.11 | EBR | An OGTT should be considered in all women with PCOS and without preexisting diabetes, when planning pregnancy or seeking fertility treatment, given the high risk of hyperglycaemia and the associated comorbidities in pregnancy. If not performed preconception, an OGTT could be offered at the first prenatal visit and all women with PCOS should be offered the test at 24-28 weeks gestation. |
❖ ❖ ❖ ❖ ⨁◯◯◯ |
| 1.9.12 | PP | Insulin resistance is a pathophysiological factor in PCOS, however, clinically available insulin assays are of limited clinical relevance and are not recommended in routine care (refer to 3.1.10). | |
| 1.10 | Obstructive Sleep Apnea | ||
| 1.10.1 | EBR | Healthcare professionals should be aware that women with PCOS have significantly higher prevalence of obstructive sleep apnea compared to women without PCOS, independent of BMI. |
❖ ❖ ❖ ❖ ⨁⨁⨁◯ |
| 1.10.2 | EBR | Women with PCOS should be assessed for symptoms of obstructive sleep apnea (i.e., snoring in combination with waking unrefreshed from sleep, daytime sleepiness or fatigue) and if present, screen with validated tools or refer for assessment. | ❖ ❖ ❖ ❖ ⨁⨁⨁◯ |
| 1.10.3 | PP | Simple obstructive sleep apnea screening questionnaires (such as the Berlin questionnaire, validated in the general population) can assist in identifying obstructive sleep apnea in women with PCOS, noting that diagnosis requires a formal sleep study. | |
| 1.10.4 | PP | Goals of treatment should target obstructive sleep apnea related symptom burden. | |
| 1.11 | Endometrial hyperplasia and cancer | ||
| 1.11.1 | EBR | Healthcare professionals should be aware that premenopausal women with PCOS have markedly higher risk of developing endometrial hyperplasia and endometrial cancer. | ❖ ❖ ❖ ❖ ⨁◯◯◯ |
| 1.11.2 | PP | Women with PCOS should be informed about the increased risk of endometrial hyperplasia and endometrial cancer, acknowledging that the overall chance of developing endometrial cancer is low, therefore routine screening is not recommended. | |
| 1.11.3 | PP | Long-standing untreated amenorrhea, higher weight, type 2 diabetes and persistent thickened endometrium are additional to PCOS as risk factors for endometrial hyperplasia and endometrial cancer. | |
| 1.11.4 | PP | Women with PCOS should be informed of preventative strategies including weight management, cycle regulation and regular progestogen therapy. | |
| 1.11.5 | PP | When excessive endometrial thickness is detected, consideration of a biopsy with histological analysis and withdrawal bleed is indicated. | |
| 1.12 | Risks in first degree relatives | ||
| 1.12.1 | EBR | Healthcare professionals could consider that fathers and brothers of women with PCOS may have an increased prevalence of metabolic syndrome, type 2 diabetes, and hypertension. | ❖ ❖ ❖ ⨁◯◯◯ |
| 1.12.2 | PP | The cardiometabolic risk in female first degree relatives of women with PCOS remains inconclusive. | |
| 2 | Prevalence, screening and management of psychological features and models of care General principles |
||
| PP | Psychological features are common and important component of PCOS that all healthcare professionals should be aware of. | ||
| PP | Funding bodies should recognize that PCOS is highly prevalent, has significantly higher psychological disorders which should be prioritized and funded accordingly. |
||
| 2.1 | Quality of Life | ||
| 2.1.1 | EBR | Healthcare professionals and women should recognize the adverse impact of PCOS and/or PCOS features on quality of life in adults. | ❖ ❖ ❖ ❖ ⨁⨁◯◯ |
| 2.1.2 | PP | Women with PCOS should be asked about their perception of PCOS relatedsymptoms, impact on quality of life, key concerns, and priorities for management. | |
| 2.2 | Depression and Anxiety | ||
| 2.2.1 | EBR | Healthcare professionals should be aware of the high prevalence of moderate to severe depressive symptoms and depression in adults and adolescents with PCOS and should screen for depression in all adults and adolescents with PCOS, using regionally validated screening tools. | ❖ ❖ ❖ ❖ ⨁⨁⨁⨁ |
| 2.2.2 | EBR | Healthcare professionals should be aware of the high prevalence of moderate to severe anxiety symptoms and anxiety disorders in adults and should screen for anxiety in all adults with PCOS, using regionally validated screening tools. |
❖ ❖ ❖ ❖ ⨁⨁⨁⨁ |
| 2.2.3 | CR | If moderate or severe depressive or anxiety symptoms are detected, practitioners should further assess, refer appropriately, or offer treatment. |
❖ ❖ ❖ ❖ |
| 2.2.4 | PP | Severity of symptoms and clinical diagnosis of depression or anxiety should guide management. The optimal interval for anxiety and depression screening is not known. A pragmatic approach could include screening at diagnosis with repeat screening based on clinical judgement, risk factors, comorbidities, and life events, including the perinatal period. Screening for mental health disorders comprises assessment of risk factors, symptoms, and risk of self-harm and suicidal intent. |
|
| 2.3 | Psychosexual function | ||
| 2.3.1 | CR | Healthcare professionals could consider the multiple factors that can influence psychosexual function in PCOS including higher weight, hirsutism, mood disorders, infertility and PCOS medications. | ❖ ❖ ❖ |
| 2.3.2 | CR | Permission to discuss psychosexual function should be sought noting that the diagnosis of psychosexual dysfunction requires both low psychosexual function combined with related distress. | ❖ ❖ ❖ ❖ |
| 2.4 | Body Image | ||
| 2.4.1 | EBR | Healthcare professionals should be aware that features of PCOS can have a negative impact on body image. | ❖ ❖ ❖ ❖ ⨁⨁◯◯ |
| 2.5 | Eating disorders | ||
| 2.5.1 | EBR | Eating disorders and disordered eating should be considered in PCOS, regardless of weight, especially in the context of weight management and lifestyle interventions (see sections 2.4 and 3.6). | ❖ ❖ ❖ ⨁⨁◯◯ |
| 2.5.2 | PP | If disordered eating or eating disorders are suspected, appropriately qualified practitioners should further assess via a full diagnostic interview. If an eating disorder or disordered eating is detected, appropriate management and support should be offered. |
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| 2.6 | Information resources, models of care, cultural and linguistic considerations |
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| 2.6.1 | Information needs | ||
| 2.6.1.1 | EBR | Tailored information, education and resources that are high-quality, culturally appropriate and inclusive should be provided to all with PCOS. | ❖ ❖ ❖ ❖ ⨁⨁⨁◯ |
| 2.6.1.2 | EBR | Information, education and resources are a high priority for patients with PCOS and should be provided in a respectful and empathic manner. | ❖ ❖ ❖ ❖ ⨁⨁⨁◯ |
| 2.6.1.3 | CR | Entities responsible for healthcare professional education should ensure that information and education on PCOS is systemically embedded at all levels of healthcare professional training to address knowledge gaps. | ❖ ❖ ❖ ❖ |
| 2.6.1.4 | PP | The diversity of the population should be considered when adapting practice paradigms. Healthcare professional education opportunities should be optimised at all stages of graduate and postgraduate training and continuing professional development and in practice support resources. |
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| 2.6.1.5 | PP | Women should be counselled on the risk of misinformation and guided to evidence-based resources. | |
| 2.6.2 | Models of care | ||
| 2.6.2.1 | CR | Models of care should prioritize equitable access to evidence-based primary care with pathways for escalation to integrated specialist and multidisciplinary services as required. | ❖ ❖ ❖ ❖ |
| 2.6.2.2 | PP | Strategies to deliver optimal models of care could include healthcare professional education, care pathways, virtual care, broader health professional engagement (e.g., nurse practitioners) and coordination tools. |
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| 2.6.3 | Support to manage PCOS | ||
| 2.6.3.1 | CR | Public health actors should consider increasing societal awareness and education on PCOS to reduce stigma and marginalization. |
❖ ❖ ❖ |
| 2.6.3.2 | PP | Culturally appropriate resources and education on PCOS across the life span for families of those with the condition should be considered. | |
| 2.6.4 | Patient care | ||
| 2.6.4.1 | EBR | Healthcare professionals should employ shared decision-making and support patient agency or ability to take independent actions to manage their health and care. | ❖ ❖ ❖ ❖ ⨁⨁⨁◯ |
| 2.6.4.2 | EBR | The importance of being knowledgeable about PCOS, of applying evidencebased practices when sharing news on diagnosis, treatment, and health implications, and of ascertaining and focusing on patient priorities, should be recognized. | ❖ ❖ ❖ ❖ ⨁⨁⨁◯ |
| 2.6.4.3 | CR | Healthcare system leaders should enable system wide changes to support healthcare professional training, knowledge and practice in sharing news optimally, shared decision making and patient agency, including ensuring adequate consultation time and accessible resources. | ❖ ❖ ❖ ❖ |
| 2.6.4.4 | PP | Evidence-based strategies for shared decision making and for sharing news (such as the SPIKES framework) are readily available and should be used to inform PCOS care. All healthcare professionals partnering with women with PCOS should be knowledgeable in sharing news, in shared decision-making, and in supporting patient self-management. Evidence-based strategies and resources can be used to support patient activation, which refers to modifiable knowledge, skills, ability, confidence, and willingness to self-manage one’s own health and care. |
|
| 2.7 | Psychological therapy | ||
| 2.7.1 | CR | Women with PCOS diagnosed with depression, anxiety, and/or eating disorders should be offered psychological therapy guided by regional general population guidelines and the preference of the woman with PCOS. |
❖ ❖ ❖ ❖ |
| 2.7.2 | CR | Women with PCOS with disordered eating, body image distress, low selfesteem, problems with feminine identity, or psychosexual dysfunction should be offered evidence-based treatments (e.g., cognitive behaviour therapy) where appropriate. | ❖ ❖ ❖ ❖ |
| 2.8 | Antidepressant and anxiolytic treatment | ||
| 2.8.1 | CR | Psychological therapy could be considered first-line management, and antidepressant medications considered in adults where mental health disorders are clearly documented and persistent, or if suicidal symptoms are present, based on general population guidelines. | ❖ ❖ ❖ |
| 2.8.2 | PP | Lifestyle intervention and other therapies (e.g., COCP, metformin, laser hair removal) that target PCOS features should be considered, given their potential to improve psychological symptoms. Where pharmacological treatment for anxiety and depression is offered in PCOS, healthcare professionals should apply caution:
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| 3 | Lifestyle management | ||
| 3.1 | Effectiveness of lifestyle interventions | ||
| 3.1.1 | EBR | Lifestyle intervention (exercise alone or multicomponent diet combined with exercise and behavioural strategies) should be recommended for all women with PCOS, for improving metabolic health including central adiposity and lipid profile. | ❖ ❖ ❖ ❖ ⨁◯◯◯ |
| 3.1.2 | CR | Healthy lifestyle behaviours encompassing healthy eating and/or physical activity should be recommended in all women with PCOS to optimize general health, quality of life, body composition and weight management (maintaining weight, preventing weight gain and/or modest weight loss). | ❖ ❖ ❖ ❖ |
| 3.1.3 | PP | Healthcare professionals should be aware that lifestyle management is a core focus in PCOS management. | |
| 3.1.4 | PP | Lifestyle management goals and priorities should be co-developed in partnership with women with PCOS, and value women’s individualized preferences. |
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| 3.1.5 | PP | There are benefits to a healthy lifestyle even in the absence of weight loss. | |
| 3.1.6 | PP | In those with higher weight, weight management can be associated with significant clinical improvements and the following key points need to be considered including:
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| 3.1.7 | PP | Healthcare professionals should be aware of weight stigma when discussing lifestyle management with women with PCOS (see 3.6). | |
| 3.1.8 | PP | Healthy lifestyle and optimal weight management, in the context of structured, intensive, and ongoing clinical support, appears equally effective in PCOS as in the general population. |
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| 3.1.9 | PP | In those who are not overweight, in the adolescent and at key life points, the focus should be on healthy lifestyle and the prevention of excess weight gain. | |
| 3.1.10 | PP | Insulin resistance is a pathophysiological factor in PCOS, however, clinically available insulin assays are of limited clinical relevance and should not be used in routine care (refer to 1.9.12). | |
| 3.2 | Behavioural Strategies | ||
| 3.2.1 | CR | Lifestyle interventions could include behavioural strategies such as goalsetting, self-monitoring, problem solving, assertiveness training, reinforcing changes, and relapse prevention, to optimize weight management, healthy lifestyle and emotional wellbeing in women with PCOS. | ❖ ❖ ❖ |
| 3.2.2 | PP | Behavioural support could include: goal-setting, problem solving, selfmonitoring and reviewing, or SMART goals (Specific, Measurable, Achievable, Realistic and Timely). |
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| 3.2.3 | PP | Comprehensive healthy behavioural or cognitive behavioural interventions could be considered to increase support, engagement, retention, adherence, and maintenance of healthy lifestyle and improve health outcomes in women with PCOS. | |
| 3.3 | Dietary Intervention | ||
| 3.3.1 | EBR | Healthcare professionals and women should consider that there is no evidence to support any one type of diet composition over another for anthropometric, metabolic, hormonal, reproductive or psychological outcomes. | ❖ ❖ ❖ ⨁◯◯◯ |
| 3.3.2 | CR | Any diet composition consistent with population guidelines for healthy eating will have health benefits and, within this, healthcare professionals should advise sustainable healthy eating tailored to individual preferences and goals. | ❖ ❖ ❖ ❖ |
| 3.3.3 | PP | Tailoring of dietary changes to food preferences, allowing for a flexible, individual and co-developed approach to achieving nutritional goals, and avoiding unduly restrictive and nutritionally unbalanced diets, are important, as per general population guidelines. |
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| 3.3.4 | PP | Barriers and facilitators to optimize engagement and adherence to dietary change should be discussed, including psychological factors, physical limitations, socioeconomic and sociocultural factors, as well as personal motivators for change. The value of broader family engagement should be considered. Referral to suitably trained allied healthcare professionals needs to be considered when women with PCOS need support with optimizing their diet. | |
| 3.4 | Exercise Intervention | ||
| 3.4.1 | EBR | Healthcare professionals and women could consider that there is a lack of evidence supporting any one type and intensity of exercise being better than another for anthropometric, metabolic, hormonal, reproductive or psychological outcomes. | ❖ ❖ ❖ ⨁◯◯◯ |
| 3.4.2 | CR | Any physical activity consistent with population guidelines will have health benefits and, within this, healthcare professionals should advise sustainable physical activity based on individual preferences and goals. | ❖ ❖ ❖ ❖ |
| 3.4.3 | CR | Healthcare professionals should encourage and advise the following in concordance with general population physical activity guidelines:
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❖ ❖ ❖ ❖ |
| 3.4.4 | PP | Physical activity is any bodily movement produced by skeletal muscles that requires energy expenditure. It includes leisure time physical activity, transportation (e.g., walking or cycling), occupational (i.e., work), household chores, playing games, sports or planned exercise, or activities in the context of daily, family and community activities. | |
| 3.4.5 | PP | Aerobic activity is best performed in bouts of at least 10 minutes duration, aiming to achieve at least 30 minutes daily on most days. | |
| 3.4.6 | PP | Barriers and facilitators to optimize engagement and adherence to physical activity should be discussed, including psychological factors (e.g., body image concerns, fear of injury, fear of failure, mental health), personal safety concerns, environmental factors, physical limitations, socioeconomic factors, sociocultural factors, and personal motivators for change. The value of broader family engagement should be considered. Referral to suitably trained allied healthcare professionals needs to be considered for optimizing physical activity in women with PCOS. | |
| 3.4.7 | PP | Self-monitoring, including with fitness tracking devices and technologies for step count and exercise intensity, could be considered as an adjunct to support and promote active lifestyles and minimize sedentary behaviours. | |
| 3.5 | Factors affecting weight gain in PCOS | ||
| 3.5.1 | EBR | Healthcare professionals and women with PCOS could consider that there is a lack of consistent evidence of physiological or behavioural lifestyle differences, related to weight, in women with PCOS compared to women without PCOS. | ❖ ❖ ❖ ⨁◯◯◯ |
| 3.5.2 | PP | Whilst the specific mechanisms are unclear, it is recognized that many women with PCOS will have underlying mechanisms that drive greater longitudinal weight gain and higher BMI which may:
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| 3.6 | Weight Stigma | ||
| 3.6.1 | EBR | Many women with PCOS experience weight stigma in healthcare and other settings and the negative biopsychosocial impacts of this should be recognized. | ❖ ❖ ❖ ❖ ⨁⨁◯◯ |
| 3.6.2 | CR | Healthcare professionals should be aware of their weight biases and the impact this has on their professional practice and on women with PCOS. | ❖ ❖ ❖ ❖ |
| 3.6.3 | CR | Health policy makers, managers and educators should promote awareness of weight stigma and invest in weight stigma education and minimization strategies. | ❖ ❖ ❖ ❖ |
| 3.6.4 | PP | Healthcare professionals should be aware of weight-inclusive practices which promote acceptance of and respect for body size diversity and focus on improvement of health behaviours and health outcomes for people of all sizes. In PCOS this includes:
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| 3.6.5 | PP | Increasing awareness of weight stigma among family members of women and adolescents with PCOS should be considered. | |
| 4 | Management of non-fertility features | ||
| 4.1 | Pharmacology treatment principles in PCOS | ||
| PP | Shared decision making between the patient (and parent/s or guardian/s, if the patient is a child) and the healthcare professional is required. | ||
| PP | An individual’s characteristics, preferences and values must be elicited and considered when recommending any intervention alone or in combination. | ||
| PP | Understanding how individual adults and adolescents value treatment outcomes is essential when prescribing medications. | ||
| PP | Medical therapy is generally not approved for use specifically in PCOS and recommended use is therefore evidence-based, but off-label. Healthcare professionals need to inform adults, adolescents and their parents/s or guardian/s and discuss the evidence, possible concerns and side effects. Regulatory agencies should consider approval of evidence-based medications for use in PCOS. | ||
| 4.2 | Combined Oral Contraceptive Pills | ||
| 4.2.1 | EBR | Combined oral contraceptive pills (COCP) could be recommended in reproductive age adults with PCOS for management of hirsutism and/or irregular menstrual cycles. |
❖ ❖ ❖ ⨁◯◯◯ |
| 4.2.2 | EBR | The COCP could be considered in adolescents at risk or with a clear diagnosis of PCOS for management of hirsutism and/or irregular menstrual cycles. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.2.3 | EBR | Healthcare professionals could consider that there is no clinical advantage of using high dose ethinylestradiol (≧ 30 μg) versus low dose ethinylestradiol (< 30μg) when treating hirsutism in adults with PCOS. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.2.4 | EBR | General population guidelines should be considered when prescribing COCP in adults and adolescents with PCOS as specific types or doses of progestins, estrogens or combinations of COCP cannot currently be recommended. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.2.5 | EBR | The 35μg ethinyl estradiol plus cyproterone acetate preparations should be considered as second-line therapy over other COCPs, balancing benefits and adverse effects, including venous thromboembolic risks. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.2.6 | EBR | Progestin only oral contraceptives may be considered for endometrial protection, based on general population guidelines, acknowledging that evidence in women with PCOS is limited. |
❖ ❖ ❖ ⨁◯◯◯ |
| 4.2.7 | PP | When prescribing COCPs in adults and adolescents with PCOS, and adolescents at risk of PCOS
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| 4.3 | Metformin | ||
| 4.3.1 | EBR | Metformin alone should be considered in adults with PCOS and a BMIR25 kg/m2 for anthropometric, and metabolic outcomes including insulin resistance, glucose, and lipid profiles. |
❖ ❖ ❖ ⨁◯◯◯ |
| 4.3.2 | EBR | Metformin alone could be considered in adolescents at risk of or with PCOS for cycle regulation, acknowledging limited evidence. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.3.3 | CR | Metformin alone may be considered in adults with PCOS and BMI < 25 kg/m2, acknowledging limited evidence. | ❖ ❖ ❖ |
| 4.3.4 | PP | Where metformin is prescribed the following need to be considered:
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| 4.4 | Metformin and combined oral contraceptive pills | ||
| 4.4.1 | EBR | COCP could be used over metformin for management of hirsutism in irregular menstrual cycles in PCOS. |
❖ ❖ ❖ ⨁◯◯◯ |
| 4.4.2 | EBR | Metformin could be used over COCP for metabolic indications in PCOS. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.4.3 | EBR | The combination of COCP and metformin could be considered to offer little additional clinical benefit over COCP or metformin alone, in adults with PCOS with a BMI ≦ 30 kg/m2. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.4.4 | PP | In combination with the COCP, metformin may be most beneficial in high metabolic risk groups including those with a BMI >30 kg/m2, diabetes risk factors, impaired glucose tolerance or high-risk ethnic groups. | |
| 4.4.5 | PP | Where COCP is contraindicated, not accepted or not tolerated, metformin may be considered for irregular menstrual cycles. For hirsutism, other interventions may be needed. | |
| 4.5 | Anti-obesity pharmacological agents | ||
| 4.5.1 | CR | Anti-obesity medications including liraglutide, semaglutide, both glucagonlike peptide-1 (GLP-1) receptor agonists and orlistat, could be considered, in addition to active lifestyle intervention, for the management of higher weight in adults with PCOS as per general population guidelines. | ❖ ❖ ❖ |
| 4.5.2 | PP | Healthcare professionals should ensure concurrent effective contraception when pregnancy is possible for women who take GLP-1 receptor agonists, as pregnancy safety data are lacking. | |
| 4.5.3 | PP | Gradual dose escalation for GLP-1 receptor agonists is recommended to reduce gastrointestinal adverse effects. | |
| 4.5.4 | PP | Shared decision making, when discussing GLP-1 receptor agonist use with women with PCOS, needs to consider side effects, and the potential need for long-term use in weight management, given the high risk for weight regain after discontinuation, and the lack of long-term safety data. | |
| 4.6 | Anti-androgen pharmacological agents | ||
| 4.6.1 | EBR | In combination with effective contraception, anti-androgens could be considered to treat hirsutism in women with PCOS, if there is a suboptimal response after a minimum of six months of COCP and/or cosmetic therapy. |
❖ ❖ ❖ ⨁◯◯◯ |
| 4.6.2 | CR | Given the negative psychological impact of female pattern hair loss, antiandrogens in combination with COCP could be trialed, acknowledging the lack of evidence in the PCOS population. | ❖ ❖ ❖ |
| 4.6.3 | PP | Whenever pregnancy is possible, healthcare professionals must educate and counsel women and adolescents, parents/s or guardian/s, regarding the risks of incomplete development of external genital structures of male fetuses (undervirilization) when anti-androgens are used. To prevent this, women who can get pregnant should be strongly counselled to use effective contraception (e.g., intrauterine device or COCPs). | |
| 4.6.4 | PP | Anti-androgens could be considered to treat hirsutism, in the presence of another effective form of contraception, for women with contraindications for COCP therapy or when COCPs are poorly tolerated. |
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| 4.6.5 | PP | When prescribing anti-androgens, based on general population recommendations, healthcare professionals should consider that:
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| 4.7 | Inositol | ||
| 4.7.1 | EBR | Inositol (in any form) could be considered in women with PCOS based on individual preferences and values, noting limited harm, potential for improvement in metabolic measures, yet with limited clinical benefits including in ovulation, hirsutism or weight. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.7.2 | EBR | Metformin should be considered over inositol for hirsutism and central adiposity, noting that metformin has more gastrointestinal side effects than inositol. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.7.3 | PP | Women taking inositol and other complementary therapies are encouraged to advise their healthcare professional. | |
| 4.7.4 | PP | Specific types, doses or combinations of inositol cannot currently be recommended in adults and adolescents with PCOS, due to a lack of quality evidence. | |
| 4.7.5 | PP | Shared decision making should include discussion that regulatory status and quality control of inositol in any form (like other nutrient supplements) can differ from those for pharmacological products and doses and qualities may vary. | |
| 4.7.6 | PP | Policy makers and healthcare professionals have a responsibility to ensure women have access to unconflicted, evidence-based information to inform shared-decision making, whilst also acknowledging and respecting individual values and preferences, including for complementary therapies. | |
| 4.8 | Mechanical laser and light therapies for hair reduction | ||
| 4.8.1 | EBR | Mechanical laser and light therapies should be considered for reducing facial hirsutism and for related depression, anxiety, and quality of life in women with PCOS. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.8.2 | EBR | A greater number of laser treatment sessions may be required in women with PCOS, compared to women with idiopathic hirsutism, to achieve hair reduction. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.8.3 | CR | Adverse effects appear limited in the hands of experienced and suitably qualified providers, and women should be encouraged to seek hair reduction therapies from such providers. | ❖ ❖ ❖ ❖ |
| 4.8.4 | PP | Where laser hair removal is prescribed, the following need to be considered:
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| 4.8.5 | PP | Mechanical hair removal with Intense Pulse Light (IPL) could be considered, albeit benefits may be less pronounced compared to laser treatment. There is no evidence to support the efficacy of home-based IPL kits. | |
| 4.8.6 | PP | Policy makers should consider funding this evidence-based effective therapy for women with PCOS to alleviate distressing symptoms of hirsutism, and related negative impact on quality of life, body image, and psychological health. |
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| 4.9 | Bariatric/ metabolic surgery | ||
| 4.9.1 | CR | Bariatric/ metabolic surgery could be considered to improve weight loss, hypertension, diabetes (prevention and treatment), hirsutism, irregular menstrual cycles, ovulation, and pregnancy rates in women with PCOS. | ❖ ❖ ❖ |
| 4.9.2 | CR | Bariatric/ metabolic surgery in women with PCOS should be informed by general population guidelines. | ❖ ❖ ❖ ❖ |
| 4.9.3 | CR | PCOS is a metabolic condition and could be considered an indication at a lower BMI threshold for bariatric/ metabolic surgery similarly to other metabolic conditions including diabetes. |
❖ ❖ ❖ |
| 4.9.4 | CR | Women should be strongly counselled on the likelihood of rapid return of fertility and the need to commit to effective contraception, ideally prior to surgery. Even when pregnancy is desired, contraception should be continued until a stable weight is achieved, usually after one year, to avoid significantly increased risk of growth restriction, prematurity, small for gestational age, pregnancy complications, and prolonged hospitalization of the infant. | ❖ ❖ ❖ ❖ |
| 4.10 | Pregnancy outcomes | ||
| 4.10.1 | EBR | Women with PCOS have higher risk pregnancies, and healthcare professionals should ensure that PCOS status is identified during antenatal care, and appropriate monitoring and support is provided. |
❖ ❖ ❖ ❖ ⨁◯◯◯ |
| 4.10.2 | EBR | Healthcare professionals should recognize that pregnant women with PCOS have an increased risk of:
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❖ ❖ ❖ ❖ ⨁◯◯◯ |
| 4.10.3 | EBR | Assisted reproductive technology in women with PCOS should be considered as not conferring additional risk of miscarriage, preterm birth, impaired fetal growth, and caesarean section, over that observed in women without PCOS. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.10.4 | EBR | Women with PCOS should be considered as not having an increased risk of large for gestational age babies, macrosomia and instrumental delivery. | ❖ ❖ ❖ ⨁◯◯◯ |
| 4.10.5 | PP | Early lifestyle intervention should be offered to pregnant women with PCOS, given the risk of higher baseline weight, excess gestational weight gain and pregnancy complications. | |
| 4.10.6 | PP | Blood pressure measurement should be performed when planning pregnancy or seeking fertility treatment, given the high risk of hypertensive disorders in pregnancy and the associated comorbidities in women with PCOS. |
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| 4.10.7 | PP | An OGTT should be offered to all women with PCOS when planning pregnancy or seeking fertility treatment, given the high risk of hyperglycaemia and the associated comorbidities in pregnancy. If not performed in the preconception phase, an OGTT should be offered at the first antenatal visit and repeated at 24-28 weeks gestation. |
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| 4.11 | Metformin in pregnancy | ||
| 4.11.1 | EBR | Healthcare professionals should be aware that metformin in pregnant women with PCOS has not been shown to prevent:
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❖ ❖ ❖ ❖ ⨁⨁◯◯ |
| 4.11.2 | EBR | Metformin could be considered in some circumstances (e.g., risk for preterm birth) to reduce preterm delivery and limit excess gestational weight gain, in pregnant women with PCOS. |
❖ ❖ ❖ ⨁⨁⨁◯ |
| 4.11.3 | PP | Women should be counselled that the consequences of metformin exposure on long-term offspring health remain unclear and there is a suggestion of increased childhood weight, although causality is not certain. |
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| 4.11.4 | PP | Side effects of metformin are mostly mild, transient gastrointestinal symptoms and are not worse in pregnancy. | |
| 5 | Assessment and treatment of infertility General principles |
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| PP | All fertility treatment in PCOS should be guided by the fertility treatment algorithm (Algorithm 2). | ||
| PP | Those with PCOS should be reassured that pregnancy can often be successfully achieved either naturally or with assistance. | ||
| PP | Prenatal vitamins supplementation should be commenced with ovulation induction therapy aligned to routine preconception care. | ||
| PP | Pregnancy should be excluded prior to ovulation induction therapy. | ||
| PP | The use of ovulation induction agents, including letrozole, metformin and clomiphene citrate, is off-label in many countries. Where off-label use of ovulation induction agents is allowed, healthcare professionals need to inform women and discuss the evidence, possible concerns, and side effects. |
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| PP | There should be ongoing monitoring of patients for adverse effects, and infants for congenital anomalies, in all studies conducted with ovulation induction agents and these should be reported in any published papers. |
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| 5.1 | Preconception risk factors | ||
| 5.1.1 | EBR | Women with PCOS should be counselled on the adverse impact of excess weight on clinical pregnancy, miscarriage, and live birth rates, following infertility treatment. | ❖ ❖ ❖ ❖ ⨁◯◯◯ |
| 5.1.2 | CR | Consistent with routine preconception care, in women with PCOS planning pregnancy, weight, blood pressure, smoking, alcohol, diet and nutritional status, folate supplementation (higher dose in those with BMI >30 kg/m2), exercise, sleep and mental, emotional and sexual health should be considered and optimized to improve reproductive and pregnancy outcomes and overall health. | ❖ ❖ ❖ ❖ |
| 5.1.3 | PP | A reproductive life plan and age-appropriate education on optimizing reproductive health is recommended in adolescents and women with PCOS, including healthy lifestyle, prevention of excess weight gain, and optimizing preconception risk factors. |
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| 5.1.4 | PP | Healthcare professionals are encouraged to seek permission and, if given, to assess weight and BMI and initiate a dialogue on the importance of weight and lifestyle on women's health before pregnancy. This requires caution to avoid weight stigma and needs to consider the cultural, social, and environmental determinants of health (see 3.6). | |
| 5.1.5 | PP | Chronic conditions such as diabetes, high blood pressure, anxiety, depression and other mental health conditions, should be optimally managed and women should be counselled regarding the risk of adverse pregnancy outcomes. | |
| 5.2 | Tubal patency testing | ||
| 5.2.1 | CR | In women with PCOS and infertility due to anovulation alone with normal semen analysis, the risks, benefits, costs and timing and techniques of tubal patency testing in relation to the cost and complexity of the treatment, should be considered on an individual basis, depending on personal history and population prevalence, prior to starting ovulation induction with timed intercourse or intrauterine insemination. | ❖ ❖ ❖ |
| 5.3 | Letrozole | ||
| 5.3.1 | EBR | Letrozole should be the first-line pharmacological treatment for ovulation induction in infertile anovulatory women with PCOS, with no other infertility factors. | ❖ ❖ ❖ ❖ ⨁⨁⨁⨁ |
| 5.3.2 | PP | The use of letrozole is still off- label in many countries. Where it is not allowed, clinicians should use other ovulation induction agents. | |
| 5.3.3 | PP | Letrozole should not be given where there is any possibility of a pre-existing pregnancy, though there is no evidence for increased teratogenicity compared to other ovulation induction agents. | |
| 5.4 | Clomiphene citrate and metformin | ||
| 5.4.1 | Metformin versus placebo | ||
| 5.4.1.1 | EBR | Metformin could be used alone, in women with PCOS with anovulatory infertility and no other infertility factors, to improve clinical pregnancy and live birth rates, whilst informing women that there are more effective ovulation agents. |
❖ ❖ ❖ ⨁⨁◯◯ |
| 5.4.1.2 | PP | Women should be counselled as to potential mild gastrointestinal side-effects with metformin. | |
| 5.4.1.3 | PP | Healthcare and resource burden including monitoring, travel and costs are lower with metformin. | |
| 5.4.1.4 | PP | Consideration of age and screening for other fertility factors needs to be discussed before prescribing metformin. | |
| 5.4.2 | Clomiphene citrate verses metformin | ||
| 5.4.2.1 | EBR | Clomiphene citrate could be used in preference to metformin in women with PCOS with anovulatory infertility and no other infertility factors, to improve ovulation, clinical pregnancy and live birth rates. | ❖ ❖ ❖ ⨁⨁◯◯ |
| 5.4.2.2 | PP | The risk of multiple pregnancy is increased with clomiphene citrate use (alone or in combination with metformin) and therefore clomiphene cycles may require ultrasound monitoring. |
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| 5.4.3 | Clomiphene citrate and metformin verses clomiphene citrate alone | ||
| 5.4.3.1 | EBR | Clomiphene citrate combined with metformin could be used rather than clomiphene citrate alone in women with PCOS with anovulatory infertility and no other infertility factors to improve ovulation and clinical pregnancy rates. | ❖ ❖ ❖ ⨁⨁◯◯ |
| 5.4.4 | Clomiphene citrate and metformin versus metformin alone | ||
| 5.4.4.1 | EBR | Clomiphene citrate combined with metformin could be used rather than metformin alone in women with PCOS with anovulatory infertility and no other infertility factors to improve live birth rates. | ❖ ❖ ❖ ⨁⨁◯◯ |
| 5.4.4.2 | PP | Monitoring of combined cycles will need to be equivalent to clomiphene citrate alone. | |
| 5.4.5 | Clomiphene citrate versus Letrozole | ||
| 5.4.5.1 | EBR | Letrozole should be used rather than clomiphene citrate in women with PCOS with anovulatory infertility and no other infertility factors to improve ovulation, clinical pregnancy and live birth rates. | ❖ ❖ ❖ ❖ ⨁◯◯◯ |
| 5.4.5.2 | PP | Current evidence demonstrates no difference in fetal abnormality rates between letrozole or clomiphene citrate ovulation induction or natural conception. |
|
| 5.5 | Gonadotrophins | ||
| 5.5.1 | EBR | Gonadotrophins alone could be considered rather than clomiphene citrate in therapy naïve women with PCOS with anovulatory infertility and no other infertility factors to improve ovulation, clinical pregnancy and live birth rates (refer to PP 5.5.6). | ❖ ❖ ❖ ⨁⨁◯◯ |
| 5.5.2 | EBR | Gonadotrophins alone could be used over gonadotrophins combined with clomiphene citrate in women with PCOS who are anovulatory and infertile with clomiphene citrate resistance or failure, and no other infertility factors. |
❖ ❖ ❖ ⨁⨁◯◯ |
| 5.5.3 | EBR | Gonadotrophins could be considered rather than the combination of clomiphene citrate and metformin in women with PCOS who are anovulatory and infertile, with clomiphene citrate-resistance and no other infertility factors. | ❖ ❖ ❖ ⨁◯◯◯ |
| 5.5.4 | EBR | Either gonadotrophins or laparoscopic ovarian surgery could be used in women with PCOS who are anovulatory and infertile, with clomiphene citrate-resistance and no other infertility factors, following counselling on higher live birth rate and higher multiple pregnancy rates with gonadotrophins. | ❖ ❖ ⨁⨁◯◯ |
| 5.5.5 | EBR | Gonadotrophins could be second-line pharmacological therapy for women with PCOS who are anovulatory and infertile, with no other infertility factors and who have failed first line oral ovulation induction. | ❖ ❖ ❖ ⨁⨁◯◯ |
| 5.5.6 | PP | Where gonadotrophins are to be prescribed, the following should be considered:
|
|
| 5.5.7 | PP | There appears to be no difference in the clinical efficacy of the available gonadotrophin preparations. | |
| 5.5.8 | PP | When using gonadotrophins, best clinical practice is to avoid multiple pregnancy. Considerations here include cancelling cycles when there is more than a total of two follicles greater than 14mm in diameter and advising avoidance of unprotected intercourse. |
|
| 5.5.9 | PP | Live birth rate, clinical pregnancy rate per patient and ovulation rate per cycle are higher with gonadotrophins than with clomiphene citrate. | |
| 5.5.10 | PP | A low dose gonadotrophin protocol should be used to optimize the chance of monofollicular growth and minimize multiple pregnancy. | |
| 5.5.11 | PP | Cycle monitoring and drug costs coupled with multiple injection will influence choice in gonadotrophin use. | |
| 5.6 | Laparoscopic ovarian surgery | ||
| 5.6.1 | EBR | Laparoscopic ovarian surgery could be second-line therapy for women with PCOS who are anovulatory and infertile, with clomiphene citrate resistance and no other infertility factors. |
❖ ❖ ❖ ⨁⨁◯◯ |
| 5.6.2 | PP | When using laparoscopic ovarian surgery, the following should be considered:
|
|
| 5.7 | In vitro fertilization and in vitro maturation | ||
| 5.7.0.1 | CR | In the absence of an absolute indication for in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI), IVF could be offered in women with PCOS and anovulatory infertility, if first- or second-line ovulation induction therapies have failed. |
❖ ❖ ❖ |
| 5.7.0.2 | PP | In women with anovulatory PCOS, the use of IVF is effective and when elective single embryo transfer is used, multiple pregnancies can be minimized. | |
| 5.7.0.3 | PP | Women with PCOS undergoing IVF/ICSI treatment should be counselled prior to starting treatment about the increased risk of ovarian hyperstimulation syndrome and options to reduce the risk should be offered. |
|
| 5.7.1 | Gonadotrophin releasing hormone protocol | ||
| 5.7.1.1 | PP | Gonadotrophin releasing hormone (GnRH) antagonist protocol cannot be recommended over GnRH agonist long protocol for women with PCOS undergoing IVF/ICSI to improve clinical pregnancy or live birth rate. | |
| 5.7.1.2 | PP | The use of a GnRH antagonist protocol for women with PCOS undergoing IVF/ICSI is recommended as it enables the use of an agonist trigger, with the freezing of all embryos generated if required, without compromising the cumulative live birth rate, to reduce the risk of significant ovarian hyperstimulation syndrome. |
|
| 5.7.2 | Trigger type | ||
| 5.7.2.1 | CR | Triggering final oocyte maturation with a GnRH agonist and freezing all suitable embryos is recommended, in an IVF/ICSI cycle with a GnRH antagonist protocol, where a fresh embryo transfer is not intended or where there is an increased risk of ovarian hyperstimulation syndrome. | ❖ ❖ ❖ ❖ |
| 5.7.3 | Choice of follicle stimulating hormone | ||
| 5.7.3.1 | CR | Either urinary or recombinant follicle stimulating hormone (FSH) could be used in women with PCOS undergoing (controlled) ovarian (hyper) stimulation for IVF/ICSI, with insufficient evidence to recommend a particular type of FSH preparation. | ❖ ❖ ❖ |
| 5.7.4 | Exogenous luteinising hormone | ||
| 5.7.4.1 | CR | Exogenous recombinant luteinising hormone (LH) treatment should not be routinely used in combination with FSH therapy in women with PCOS undergoing controlled ovarian hyperstimulation for IVF/ ICSI. | ❖ |
| 5.7.5 | Adjunct metformin | ||
| 5.7.5.1 | EBR | Adjunct metformin therapy could be used before and/or during FSH ovarian stimulation in women with PCOS undergoing IVF/ICSI treatment with GnRH agonist long protocol, to reduce the risk of developing ovarian hyperstimulation syndrome and miscarriage. | ❖ ❖ ❖ ⨁⨁◯◯ |
| 5.7.5.2 | PP | Good practice in PCOS and IVF is the use of a GnRH antagonist protocol as it gives the flexibility of using a GnRH agonist trigger, freeze all strategy to reduce the risk of ovarian hyperstimulation syndrome. However, if using a GnRH agonist long protocol then metformin could be considered. If using metformin, the following could be considered:
|
|
| 5.7.6 | In vitro maturation | ||
| 5.7.6.1 | EBR | The use of in vitro maturation (IVM) and ICSI) could be considered in women with PCOS as an alternative to a stimulated IVF / ICSI cycle, where an embryo is frozen and replaced in a subsequent embryo transfer cycle, acknowledging there is no risk of ovarian hyperstimulation syndrome, but a lower cumulative live birth rate. |
❖ ❖ ⨁⨁⨁◯ |
| 5.7.6.2 | CR | The use of IVM and ICSI could be considered prior to stimulated IVF/ ICSI cycles acknowledging both benefits and limitations. | ❖ ❖ |
| 5.7.6.3 | PP | IVM should only be considered in services with sufficient expertise, and advocacy is needed for regional or national centres of expertise. | |
| 5.7.6.4 | PP | IVM could be offered as an option in women with prior severe ovarian hyperstimulation syndrome and where the risk of severe ovarian hyperstimulation syndrome is deemed unacceptably high, provided that expertise in IVM techniques exists. |
|
| 5.7.6.5 | PP | Evidence suggests that IVM/ ICSI is less effective than standard IVF/ICSI in terms of clinical pregnancy per patient and live birth rate per patient. | |
| 5.8 | Inositol | ||
| 5.8.1 | EBR | Inositol in any form alone, or in combination with other therapies, should be considered experimental therapy in women with PCOS with infertility, with benefits and risks currently too uncertain to recommend the use of these agents as fertility therapies. | ❖ ❖ ❖ ⨁◯◯◯ |
| 5.8.2 | PP | There is limited evidence with uncertain results, on the effect of inositol on ovulation, clinical pregnancy and live birth rates. | |
| 5.8.3 | PP | Side effects and safety are not known for inositol. | |
| 5.8.4 | PP | Women need to be aware that these agents can have limited regulation with variable dose, quality, consistency, and combination with other agents. | |
| 5.8.5 | PP | Women’s personal goals and preferences should be considered when discussing complimentary therapies. | |
| 5.9 | Anti-obesity pharmacological agents | ||
| 5.9.1 | CR | We recommend using anti-obesity agents in PCOS for reproductive outcomes only in research settings to establish the efficacy and safety. | |
| See Table 1 for definition of CR, EBR and PP. ªInternational evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023, Helena Teede et al. Monash University (monash.edu/medicine/mchri/pcos), 2023, by permission of Monash University, on behalf of the NHMRC Centre for Research Excellence in Women’s Health in Reproductive Life. This image/content is not covered by the terms of the Creative Commons licence of this publication. For permission re reuse, please contact the rights holder. |
|||
Figure 1
Figure 2
DISCUSSION
The International Evidence-based Guideline for theAssessment and Management of PCOS and the related translation program aims to provide a high quality, reliable source of international evidence-based recommendations to guide consistent clinical practice and to empower womenwith evidence-based information. All recommendationswere formulated after an assessment of the best available evidence, multidisciplinary clinical expertise, consumer preferences and structured review by five GDGs. The guideline provides 77 evidence-based and 54 consensus recommendations, with 123 practice points underpinned by a technical report on evidence synthesis and GRADE detailed considerations (6000 pages). The evidence has generally improved over the past five years but remains of low to moderate quality, requiring significant research investment into this neglected, yet common condition.Key recommendations and updates include that PCOS should be diagnosed using the 2018 International Evidencebased Guideline criteria, which built on the consensus based 2003 Rotterdam criteria. This requires the presence of two of the following: i) clinical / biochemical hyperandrogenism; ii) ovulatory dysfunction; and iii) polycystic ovaries on ultrasound; and here in 2023, alternatively anti-M€ullerian hormone (AMH) can now be used instead of ultrasound, with the exclusion of other aetiologies. Importantly, where irregular menstrual cycles and hyperandrogenism are present, diagnosis is simplified and ultrasound or AMH are not required for diagnosis. In adolescents, both hyperandrogenism and ovulatory dysfunction are required, with ultrasound and AMH not recommended due to poor specificity. AMH was highlighted as a rapidly evolving area in 2018 and evidence is now strong enough to make this new recommendation. This will significantly change practice and offers women a low cost, convenient option, without evidence of overdiagnosis.
Insulin resistance is recognized as a key feature of PCOS, yet routinely availablemeasures of insulin resistance are inaccurate and clinical measurement is not currently recommended. Once diagnosed, assessment and management should address reproductive, metabolic, cardiovascular, dermatologic, sleep, and psychological features. A lifelong health plan is recommended including a focus on healthy lifestyle, prevention of excess weight gain, optimization of fertility and preconception risk factors, and prevention and treatment of diverse clinical features. These include metabolic risk factors, diabetes, cardiovascular disease, and sleep disorders, which are all increased in PCOS. PCOS should be considered a high-risk condition in pregnancy with women identified and monitored. An increased premenopausal risk of endometrial cancer should also be recognized, whilst absolute risks remain low.
Symptoms of depression and anxiety are significantly increased and should be screened for in all women with PCOS, with psychological assessment and therapy as indicated.Greater awareness of psychological features including eating disorders and impacts on body image and quality of life is needed.
Dissatisfaction with PCOS diagnosis and care is high and significant improvement in education and awareness is strongly recommended for women and healthcare professionals including high quality, evidence-based resources. Shared decision making and self-empowerment are fundamental and integrated models of care should be codesigned, funded and evaluated.
Supported healthy lifestyle remains vital throughout the lifespan in PCOS, with a strong focus on overall health, prevention of weight gain and, if required, on weight management. Recognizing the benefits of many diet and physical activity regimens, there is no one specific regimen that has benefits over others in PCOS. Weight bias and stigma should be minimized and healthcare professionals should seek permission to weigh women, with explanation of weight-related risks.
Combined oral contraceptive pills are the first line pharmacological treatment for menstrual irregularity and hyperandrogenism, with no specific recommended preparation and a preference for lower ethinyl estradiol dose preparations and those with less side-effects. Metformin is recommended primarily for metabolic features and has greater efficacy than inositol, which offers limited clinical benefits in PCOS. Metformin is not routinely recommended for use in pregnant women with PCOS. Mechanical laser therapy is effective for hair reduction in some subgroups, whilst anti-androgens have a limited role where other therapies are ineffective or contraindicated. Anti-obesity agents and bariatric/ metabolic surgery may be considered based on general population guidelines, balancing potential for benefits and side effects.
Letrozole is the preferred first line pharmacological infertility therapy, with clomiphene in combination with metformin; gonadotrophins or ovarian surgery primarily having a role as second line therapy. In vitro fertilization (IVF) could be offered, potentially with in vitro maturation, as third line therapy, where other ovulation induction therapies have failed and in the absence of an absolute indication for IVF in women with PCOS and anovulatory infertility. Given the underlying risk for pregnancy complications in PCOS, single embryo transfer should be preferred.
Overall, evidence in PCOS is low to moderate quality. Based on high prevalence and significant health impact, greater priority, education, models of care, funding, and research are recommended. Guideline translation will be extensive including multilingual education outputs and evidence-based resources for consumers (the ASKPCOS app), healthcare professionals and policy makers.
The guideline recommendations are protected under copyright, however a clear process for adaption of guideline recommendations to regional context is available by contacting the author for correspondence online (www.monash.edu/medicine/mchri/pcos). The translation program will be free and internationally accessible, building on the existing range of codesigned resources including the patient focused, evidence-based PCOS APP (AskPCOS), used in 186 countries and based on a rigorously developed question prompt list. Multi-faceted patient codesigned resources will aim to enhance health literacy with comprehensive PCOS-related health information available in multiple formats and in 15-20 languages. Internationally accessible resources include education modules for healthcare professionals at different career stages and disciplines, healthcare professional accredited courses, practice resources and tools, webinars with international expert panels, and e-health information resources that will be available online (www.monash.edu/medicine/mchri/pcos). Importantly, the Guideline and translation of the Guideline is expected to improve patient experiences through the provision of timely and accurate diagnosis, of accessible evidence-based information and of improved multi-disciplinary support. Ultimately, this international initiative may serve as an exemplar for large scale collaborative engagement, pooling of resources, avoidance of duplication and inconsistency with consensus-based statements, and codesign of best quality consistent guidelines with processes for local adaption and healthcare impact.Key elements include extensive collaboration, broad stakeholder representation, consumer partnership, distributive leadership, adequate funding, robust project management and governance, adherence to best practice and integrated comprehensive translation, and evaluation. We sincerely thank the partner and collaborating organizations, consumer groups and members of the GDGs for their substantive commitment to the international partnership to optimize health outcomes for women with this common, heterogeneous, and much neglected condition.
DATA AVAILABILITY
All data extracted and analyzed in the guideline is available in a repository and can be accessed via https://doi.org/10.26180/23625288.v1
Conflict of Interest: Disclosures of interest were declared at the outset and updated throughout the guideline process, aligned with National Health Medical Research Council (NHMRC) guideline processes. These are available online (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker’s fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker’s fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker’s fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker’s fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker’s fees from Novo Nordisk and Boehringer Ingelheim.
Acknowledgements: We gratefully acknowledge contribution of our partners and collaborating organizations:
The Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence in Women’s Health in Reproductive Life (CRE WHiRL) (APP1171592), Centre for Research Excellence in Polycystic Ovary Syndrome (CRE PCOS) (APP1078444) and the members of these Centres who coordinated this international guideline effort.
Our partner and co-funding organizations are:
- American Society for Reproductive Medicine (ASRM)
- Endocrine Society (ENDO)
- European Society for Endocrinology (ESE)
- European Society of Human Reproduction and Embryology (ESHRE)
- Androgen Excess and Polycystic Ovary Syndrome Society (AEPCOS)
- Asia Pacific Paediatric Endocrine Society (APPES)
- Asia Pacific Initiative on Reproduction (ASPIRE)
- Australia and New Zealand Society for Paediatric Endocrinology and Diabetes (ANZSPED)
- Australian Diabetes Society (ADS)
- Brazilian Society of Endocrinology andMetabolism (SBEM)
- British Fertility Society (BFS)
- Canadian Society of Endocrinology andMetabolism (CSEM)
- Dietitians Association Australia (DA)
- Endocrine Society Australia (ESA)
- European Society for Paediatric Endocrinology (ESPE)
- Exercise and Sports Science Australia (ESSA)
- Fertility Society Australia and New Zealand (FSA)
- International Federation of Fertility Societies (IFFS)
- International Federation of Gynecology and Obstetrics (FIGO)
- International Society of Endocrinology (ISE) - 40 partner societies
- Italian Society of Gynaecology and Obstetrics
- Japanese Society for Paediatric Endocrinology (JSPE)
- Latin American Society for Paediatric Endocrinology (SLEP)
- Nordic Federation of Societies of Obstetrics and Gynaecology (NFOG)
- PCOS Challenge Inc: The National Polycystic Ovary Syndrome Association
- PCOS Society of India
- PCOS Vitality
- Paediatric Endocrine Society (PES)
- Royal Australasian College of Physicians (RACP)
- Royal Australian New Zealand College of Obstetricians and Gynaecologists (RANZCOG)
- Royal Australian and New Zealand College of Radiologists (RANZCR)
- Royal College of Obstetricians and Gynaecologists (RCOG)
- South African Society of Gynaecology and Obstetrics (SASOG)
- Society for Endocrinology
- Verity UK
- Victorian Assisted Reproductive Technology Association (VARTA)
Authors’ Roles: HJT led the guidelines from funding, engaging partners, coordinating processes, prioritizing clinical questions, co-chairing guideline meetings, coordinating peer review responses and leading writing, approval and publication processes. Listed authors held senior leadership roles as chair or deputy chair of the five GDGs or leadership of the evidence team with roles from the management committee, chair/ co-chair of GDG or the early career evidence network, involvement at all stages, responding to feedback, providing input into and endorsing the guideline. All other included authors were actively engaged as partner nominees and multidisciplinary GDG or consumer experts. The evidence synthesis network was led by CTT AM, across search strategies, training, Covidence processes, quality appraisal and GRADE, meta-analysis, evidence integrity processes (with BM) and preparing the technical report. The listed members of this network led evidence synthesis across the clinical questions and had input into the technical report.
Funding: The Australian National Health Medical Research Council (NHMRC) (APP1171592) primarily funded this work. TheAmerican Society forReproductiveMedicine, Endocrine Society, the European Society of Human Reproduction and Embryology and the European Society for Endocrinology provided partnership funding. Collaborating organizations provided inkind support. The Commonwealth Government of Australia also supported Guideline Translation through the Medical Research Future Fund (MRFCRI000266). HJT andAMare funded by NHMRC fellowships and JT by an RACP fellowship.
REFERENCES
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- Dokras A, Saini S, Gibson-Helm M, Schulkin J, Cooney L, Teede H. Gaps in knowledge among physicians regarding diagnostic criteria and management of polycystic ovary syndrome. Fertil Steril 2017;107(6), 1380_6.e1.
- Teede H, Gibson-Helm M, Norman RJ, Boyle J. Polycystic ovary syndrome: perceptions and attitudes of women and primary health care physicians on features of PCOS and renaming the syndrome. J Clin Endocrinol Metab 2014;99(1), E107_11.
- Teede J Helena,Marie Misso, Michael Costello, et al. International evidencebased guideline for the assessment and management of polycystic ovary syndrome; 2018, Available at www.monash.edu/medicine/mchri/pcos.
- Teede HJ, Misso ML, Costello MF, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod 2018;33(9), 1602_18.
- Misso ML, Teede HJ. Evidence based guideline (EBG) development: A practical guide in Knowledge Transfer: Practices, Types and Challenges. In: D I, editor. Knowledge Transfer: Practices, Types and Challenges. New York: Nova Science Publishers, Inc.; 2012:141–74.
- Brouwers MC, Kho ME, Browman GP, et al. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ 2010; 182(18):E839–42.
- Mousa A, Tay CT, Teede H. Technical Report for the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Monash University. 2023. Available at https://doi.org/10.26180/23625288.v1
- Weibel S, Popp M, Reis S, Skoetz N, Garner P, Sydenham E. Identifying and managing problematic trials: A research integrity assessment tool for randomized controlled trials in evidence synthesis. Research Synthesis Methods 2023;14(3):357–69.
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- National Health and Medical Research Council. NHMRC levels of evidence and grades for recommendations for developers of guidelines. Australia; 2009.
- National Health and Medical Research Council. NHMRC standards and procedures for externally developed guidelines. Australia; 2007.
- GRADE working group. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.
APPENDIX
Members of the PCOS Network:- The international advisory panel, guideline technical team, paediatric, consumer and translation committees, the Indigenous cultural advisor and the extended early career support network who assisted with evidence synthesis, can be found online (www.monash.edu/medicine/mchri/pcos).
Guideline development members (in addition to listed authors)
- Wiebke Arlt, University of Birmingham, UK
- Ricardo Azziz, University of Alabama at Birmingham, USA
- Adam Balen, Leeds Teaching Hospital; British Fertility Society, UK
- Lisa Bedson, Repromed, Australia
- Lorna Berry, Polycystic Ovary Syndrome Association of Australia, Australia
- Jacky Boivin, Cardiff University, UK
- Jacqueline Boyle, Monash University, Australia
- Leah Brennan, Latrobe University, Australia
- Wendy Brown, Monash University, Australia
- Tania Burgert, University Missouri – Kansas School of Medicine, USA
- Maureen Busby, PCOS Vitality, Ireland
- Carolyn Ee, Western Sydney University, Australia
- Rhonda M. Garad, Monash University, Australia
- Melanie Gibson-Helm, Te Tatai Hauora o Hine, Victoria University of Wellington; NZ
- Cheryce Harrison, Monash University, Australia
- Roger Hart, The University of Western Australia; City Fertility, Australia
- Kim Hopkins, PCOS Challenge: National Polycystic Ovary Syndrome Association, USA
- Angelica Linden Hirschberg, Karolinska Institutet, Karolinska University Hospital, Sweden
- Tuong Ho, HOPE Research Centre, My Duc Hospital, Vietnam
- Kathleen Hoeger, University of Rochester, USA
- Cailin Jordan, Genea Hollywood Fertility, Australia
- Richard S. Legro, Penn State Clinical and Translational Institute, USA
- Rong Li, Peking University Third Hospital, China
- Marla Lujan, Cornell University, USA
- Ronald Ma, Chinese University of Hong Kong, Hong Kong/China
- Darren Mansfield,1 Monash and Epworth Health, Monash University, Australia
- Kate Marsh, Northside Nutrition & Dietetics, Australia
- Edgar Mocanu, Rotunda Hospital, Ireland
- Ben Mol, Monash University, Australia
- Rachel Mormon, Verity – PCOS Charity, UK
- Robert Norman, University of Adelaide, Australia
- Sharon Oberfield, Columbia University Medical Center, USA
- Malika Patel, University of Cape Town; Groote Schuur Hospital, South Africa
- Loyal Pattuwage, Cochrane Australia, Monash University, Australia
- Alexia Pe~na, The Robinson Research Institute at the University of Adelaide, Australia
- Leanne Redman, Pennington Biomedical Research Center, USA
- Luk Rombauts, Monash University, Australia
- Daniela Romualdi, Fondazione Policlinico Universitario Agostino Gemelli, Italy
- Duru Shah, PCOS Society of India; Centre for Women’s Health and Fertility, India
- Poli Mara Spritzer, Federal University of Rio Grande Do Sul, Brazil
- Elisabet Stener-Victorin, Karolinska Institutet, Sweden
- Fahimeh Ramezani Tehrani, Shahid Beheshti University of Medical Sciences, Iran
- Shakila Thangaratinam, University of Birmingham, UK
- Mala Thondan, Harp Family Medical, Australia
- Eszter Vanky, Norwegian University of Science and Technology; Norway
- Chandrika Wijeyaratne, University of Colombo, Sri Lanka
- Selma Witchel, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, USA
- Dongzi Yang, Reproductive Medical Centre, Sun Yat-Sen Memorial Hospital, China
- Bulent Yildiz, Hacettepe University, Turkey
- Simon Alesi, Monash University, Australia
- Snigdha Alur-Gupta, University of Rochester, USA
- Jodie Avery, University of Adelaide, Australia
- Mahnaz Bahri Khomami, Monash University, Australia
- Jamie Benham, University of Calgary, Canada
- Hugh Bidstrup, Australian Catholic University, Australia
- Su Jen Chua, Monash University, Australia
- Laura Cooney, University of Wisconsin, USA
- Thisara Coster, Monash University, Australia
- Carolyn Ee, Western Sydney University, Australia
- Victoria Fitz, Harvard University, USA
- Madeline Flanagan, Monash University, Australia
- Maria Forslund, University of Gothenburg, Sweden
- Geranne Jiskoot, Erasmus MC, Netherlands
- Maryam Kazemi, Icahn School of Medicine at Mount Sinai, USA
- Punith Kempegowda, University of Birmingham, UK
- Yvonne Louwers, Erasmus MC, Netherlands
- Marla Lujan, Cornell University, USA
- Johanna Melin, University of Helsinki, Finland
- Eka Melson, University of Leicester, UK
- Yitayeh Belsti Mengistu, Monash University, Australia
- Negar Naderpoor, Monash University, Australia
- Adriana Neven, Monash University, Australia
- Hester Pastoor, Erasmus MC, Netherlands
- Thais Rocha, University of Birmingham, UK
- Angelo Sabag, Western Sydney University, Australia
- Anuradhaa Subramanian, University of Birmingham, UK
- Katrina Tan, Monash Health, Australia
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Amenorrhea is the absence or abnormal cessation of the menses. View the Educational Bulletin
Fertility and Sterility On Air - Unplugged: May 2024
Topics include: counseling on pregnancy complications in PCOS patients, sorting early spermatocytes from testicular biopsies, and more. Listen to the Episode
Fertility and Sterility On Air - Unplugged: April 2024
Topics include: IVF in film, a rat model of fallopian tube torsion, comparing letrozole regimens for PCOS, and a review of chronic endometritis. Listen to the Episode
Fertility and Sterility On Air - TOC: April 2024
Topics this month include the use of ICSI, fertility treatments among reproductive-aged women after cancer, and more. Listen to the Episode
Journal Club Global en Español: Avances recientes en el tratamiento del síndrome de ovario poliquístico e Infertilidad
Un panel de expertos discutirá dos artículos recientes de Fertility and Sterility que estudian la infertilidad y el síndrome de ovario poliquístico. View the Video
Surgery Coding
I took the ASRM coding course, and in that course, coding for bilateral neosalpingostomies was coded using only a dx of N70.11 (hydrosalpinx). View the Answer
Ovulation Induction Monitoring With PCOS
We have a patient insisting that we code the ultrasound follicle monitoring with the PCOS diagnosis. View the Answer
Coding for Ovarian Drilling
Can you provide some information related to ovarian drilling that would assist non-physician administration (coders, billers)? View the Answer
PCOS
A summary of codes for PCOS as compiled by the ASRM Coding Committee. View the Coding Summary
Best practices of ASRM and ESHRE: a journey through reproductive medicine (2012)
ASRM and ESHRE are the two largest societies in the world whose members comprise the major experts and professionals working in reproductive medicine. View the Committee Joint Guideline
