Recommendations from the 2023 International Evidence-based

Recommendations from the 2023

International Evidence-based

Guideline for the Assessment and

Management of Polycystic

Ovary Syndromey

Helena J. Teede,

a,b

Chau Thien Tay,

a,b

Joop Laven,

b,c

Anuja Dokras,

Lisa J. Moran,

a,b

Terhi T. Piltonen,

Michael F. Costello,

b,f

Jacky Boivin,

Leanne M. Redman,

Jacqueline A. Boyle,

b,i

Robert. J. Norman,

b,j

Aya Mousa,

and Anju E. Joham

a,b

on behalf of the International PCOS Network

Monash Centre for Health Research and Implementation, Monash University and Monash Health, Melbourne, Victoria,

Australia;

National Health and Medical Research Council Centre for Research Excellence in Women’s Health in

Reproductive Life, Australia;

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and

Gynaecology, Erasmus Medical Centre, Rotterdam, The Netherlands;

Obstetrics and Gynecology, University of

Pennsylvania, Philadelphia, Pennsylvania, U.S.A.;

Department of Obstetrics and Gynaecology, Medical Research Center

Oulu, Research Unit of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland;

University of

New South Wales, New South Wales, Australia;

Cymru Fertility and Reproductive Research, School of Psychology,

Cardiff University, Cardiff, Wales, United Kingdom;

Pennington Biomedical Research Center, Louisiana State

University, Baton Rouge, Louisiana, U.S.A.;

Eastern Health Clinical School, Monash University, Melbourne, Victoria,

Australia;

Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia

Abstract

STUDY QUESTION: What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based

on the best available evidence, clinical expertise, and consumer preference?

SUMMARY ANSWER: International evidence-based guidelines address prioritized questions and outcomes and include 254

recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes

in PCOS.

WHAT IS KNOWN ALREADY: The 2018 International PCOS Guideline was independently evaluated as high quality and integrated

multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based

on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared pri-

orities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis,

whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately

met, evidence quality was low and evidence-practice gaps persist.

STUDY DESIGN, SIZE, DURATION: The 2023 International Evidence-based Guideline update reengaged the 2018 network across

professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all

stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant

processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was

applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and

diversity and inclusion were considered throughout.

PARTICIPANTS/ MATERIALS, SETTING, METHODS: This summary should be read in conjunction with the full Guideline for

detailed participants and methods. Governance included a six-continent international advisory and management committee, ﬁve

guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and

guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics,

endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise

This article is simultaneously published in Fertility and Sterility, Journal of Clinical Endocrinology and Metabolism, European Journal of Endocrinology and

Human Reproduction.

Participants of the International PCOS Network are listed in the Appendix.

Correspondence: Helena J. Teede, Locked Bag 29, Clayton, Australia, 3168, VIC, Australia (E-mail: helena.teede@ monash.edu).

Fertility and Sterility® Vol. -, No. -, - 2023 0015-0282/$36.00

This article has been co-published with permission in Fertility and Sterility, Human Reproduction, European Journal of Endocrinology, and The Journal of

Clinical Endocrinology and Metabolism. © The Author(s) 2023. Published by Elsevier Inc. on behalf of the American Society of Reproductive Medicine.

This is an open access article under the CC-BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/). The articles are identical except for minor

stylistic and spelling differences in keeping with each journal's style.

https://doi.org/10.1016/j.fertnstert.2023.07.025

VOL. - NO. - / - 2023 1

physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians

and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty

meetings and ﬁve face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3

narrative reviews. Evidence-based recommendations were developed and approved via consensus across ﬁve guideline panels,

modiﬁed based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the

Australian Government National Health and Medical Research Council (NHMRC).

MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS has generally improved in

the past ﬁve years, but remains of low to moderate quality. The technical evidence report and analyses (6000 pages) underpins 77

evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further reﬁnement of

individual diagnostic criteria, a simpliﬁed diagnostic algorithm and inclusion of anti-M

€

ullerian hormone (AMH) levels as an

alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors,

cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes

during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional

education, evidence-based patient information, improved models of care and shared decision making to improve patient experience,

alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness

and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management.

LIMITATIONS, REASONS FOR CAUTION: Overall, recommendations are strengthened and evidence is improved, but remain gener-

ally low to moderate quality. Signiﬁcantly greater research is now needed in this neglected, yet common condition. Regional health

system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided.

WIDER IMPLICATIONS OF THE FINDINGS: The 2023 International Guideline for the Assessment and Management of PCOS provides

clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and con-

sumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation

programme supports the Guideline with an integrated evaluation program.

STUDY FUNDING/COMPETING INTEREST(S): This effort was primarily funded by the Australian Government via the National

Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Med-

icine, Endocrine Society, European Society for Human Reproduction and Embryology, and the Society for Endocrinology. The

Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund

(MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians

(RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the sponsoring organi-

zations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical

evidence report, peer review and responses (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 Arz-

neimittell 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 Boeh-

ringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was

independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development

groups and by the NHMRC. (Fertil Steril



2023;-:-–-. This article has been co-published with permission in Fertility and Sterility,

Human Reproduction, European Journal of Endocrinology, and The Journal of Clinical Endocrinology and Metabolism.  The Author(s)

2023. Published by Elsevier Inc. on behalf of the American Society of Reproductive Medicine. This is an open access article under the

CC-BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/). The articles are identical except for minor stylistic and spelling

differences in keeping with each journal's style.

Key Words: Polycystic ovary syndrome, guideline, evidence-based, assessment, management, GRADE

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 clin-

ical 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 character-

istics, preferences, culture and values are considered, in addi-

tion 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 out-

comes, identify key research gaps, and promote vital future

research.

INTRODUCTION

Polycystic ovary syndrome (PCOS) is the most common endo-

crinopathy affecting reproductive-aged women, with impacts

across the lifespan from adolescence to post menopause.

PCOS prevalence is between 10 to 13% as demonstrated in

2 VOL. - NO. - / - 2023

the guideline process.

1,2

PCOS aetiology is complex; clinical

presentation is heterogeneous with reproductive, metabolic,

and psychological features.

1,2

Women internationally experi-

ence 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 Manage-

ment of Polycystic Ovary Syndrome,

6,7

independently evalu-

ated 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, comprehen-

sive 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 con-

sumer engagement and international collaboration with lead-

ing societies and organizations, multidisciplinary experts, and

primary care representatives. This comprehensive evidence-

based 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 rec-

ommendations 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 pro-

vision to improve health outcomes and quality of life in women

with PCOS. The Guideline is supported by a multifaceted inter-

national translation programme with co-designed resources to

enhance the skills of healthcare professionals and to empower

women with PCOS, with an integrated comprehensive evalua-

tion program. Here, we summarize recommendations from the

2023 International Evidence-based Guideline for the Assess-

ment 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 tech-

nical reports, which are available online (www.monash.edu/

medicine/mchri/pcos).

In brief, extensive healthcare profes-

sional and consumer or patient engagement informed the

Guideline priority areas. International society-nominated

panels from across three leading entities, four partner organiza-

tions and thirty-two collaborating entities included consumers

and experts in paediatrics, endocrinology, gynaecology, pri-

mary 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 interna-

tional 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 man-

agement; iv) Management of nonfertility features; and v)

Assessment and management of infertility. The leading en-

tities; 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 by Monash University, partnered with the American Society

for Reproductive Medicine, the Endocrine Society, the Euro-

pean 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 collab-

orator organizations provided international peer review, and

independent experts reviewed methods which were then sub-

mitted to NHMRC for independent review. The target audience

includes multidisciplinary healthcare professionals, consumers

or patients, policy makers, and educators. The Guideline in-

cludes a focus on equity, cultural and ethnic diversity, avoid-

ance of stigma and inclusivity (see full guideline for details).

Processes aligned with all elements of the AGREE-II tool

for quality guideline assessment,

with extensive evidence syn-

thesis and meta-analysis. Integrity assessment was integrated

into guideline evidence synthesis processes and followed the

Research Integrity in Guideline Development (RIGID) frame-

work, 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 practice

9,13,14

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) recommenda-

tions and accompanying practice points (implementation con-

siderations) (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.

Teede. International PCOS Guideline 2023. Fertil Steril 2023.

VOL. - NO. - / - 2023 3

Fertility and Sterility®

The terms include ‘‘ should’’, ‘‘could’’ and ‘‘ should not’’ ,

which are informed by the nature of the recommendation (ev-

idence 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 recommenda-

tion 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 avail-

able 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 evi-

dence 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,

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.

The GRADE framework enabled structured and trans-

parent consideration across evidence quality, feasibility,

acceptability, cost, implementation, and ultimately recom-

mendation strength

and was completed at face to face

guideline group meetings for all clinical questions (Table 3).

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 recommenda-

tion 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, descrip-

tive terms, GRADE of the recommendations and the quality of

the evidence. The full Guideline, technical evidence and admin-

istrativereportsareavailableonline(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

the39organizationswasthenconsideredbyeachGDGandrec-

ommendations were reconsidered applying the GRADE frame-

work if justiﬁed. The comprehensive evidence reviews,

proﬁles, and GRADE frameworks supporting each recommenda-

tion 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 comprehensiv e co-des igned trans lation program to

optimize dissemination and impact with resources freely avai l-

able online (www.monash.edu/med icine/ mchri/p cos).

Two algorithms are provided to support recommenda-

tions on diagnosis (Figure 1) and infertility management

(Figure 2).

DISCUSSION

The International Evidence-based Guideline for the Assessment

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 women with evidence-based informa-

tion. All recommendationswere formulated after an assessment

of the best available evidence, multidisciplinary clinical exper-

tise, 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

TABLE 2

Quality (certainty) of evidence categories (adapted from GRADE)

High 4444 Very conﬁdent that the true

effect lies close to that of the

estimate of the effect.

Moderate 444 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 44 Limited conﬁdence in the effect

estimate. The true effect may

be substantially different

from the estimate of the

effect.

Very Low 4 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.

Teede. International PCOS Guideline 2023. Fertil Steril 2023.

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.

Teede. International PCOS Guideline 2023. Fertil Steril 2023.

4 VOL. - NO. - / - 2023

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/QUAITY

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:

 Normal in the ﬁrst year post menarche as part of the pubertal transition.

 1to< 3 years post menarche: < 21 or > 45 days.

 3 years post menarche to perimenopause: < 21 or > 35 days or < 8 cycles

per year.

 1 year post menarche > 90 days for any one cycle.

 Primary amenorrhea by age 15 or > 3 years post thelarche (breast devel-

opment).

When irregular menstrual cycles are present a diagnosis of PCOS should be

considered and assessed according to these PCOS Guidelines.

❖❖❖❖

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.

❖❖❖❖

4

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.

❖❖❖

4

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.

❖❖❖❖

44

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.

❖❖❖❖

44

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 gonadotrophin-

dependent 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.

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TABLE 4

Continued.

NO. TYPE RECOMMENDATION GRADE/QUAITY

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:

 Determining laboratory normal values by either the range of values in a well

characterized healthy control population or by cluster analysis of the values

of a large general population.

 Applying the most accurate methods where available.

 Using extraction/chromatography immunoassays as an alternative to mass

spectrometry only where adequate expertise is available.

 Future improvements may arise from measurement of 11-oxygenated

androgens, and from establishing cut-off levels or thresholds based on

large-scale validation in populations of different ages and ethnicities.

1.3 Clinical hyperandrogenism

1.3.1 EBR The presence of hirsutism alone should be considered predictive of

biochemical hyperandrogenism and PCOS in adults.

❖❖❖

4

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.

❖❖❖

4

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:

 Be aware that standardized visual scales are preferred when assessing hir-

sutism, such as the mFG scale in combination with a photographic atlas.

 Consider the Ludwig or Olsen visual scales for assessing female pattern hair

loss.

 Note that there are no universally accepted visual instruments for assessing

the presence of acne.

 Recognize that women commonly treat clinical hyperandrogenism

cosmetically, diminishing their apparent clinical severity.

 Appreciate that self-assessment of unwanted excess hair growth, and

possibly acne and female pattern hair loss, has a high degree of validity and

merits close evaluation, even if overt clinical signs of hyperandrogenism are

not readily evident on examination.

 Note that only terminal hairs need to be considered in deﬁning hirsutism,

and these can reach >5 mm if untreated, vary in shape and texture, and are

generally pigmented.

 Note that new-onset severe or worsening hyperandrogenism, including

hirsutism, requires further investigation to rule out androgen-secreting

tumours and ovarian hyperthecosis.

 Monitor clinical signs of hyperandrogenism, including hirsutism, acne and

female pattern hair loss, for improvement or treatment adjustment during

therapy.

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.

❖❖❖❖

44

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.

❖❖❖❖

44

1.4.3 CR PCOM criteria should be based on follicle excess (FNPO, FNPS) and/or ovarian

enlargement.

❖❖❖❖

6 VOL. - NO. - / - 2023

TABLE 4

Continued.

NO. TYPE RECOMMENDATION GRADE/QUAITY

1.4.4 CR Follicle number per ovary (FNPO) R 20 in at least one ovary should be

considered the threshold for PCOM in adults.

❖❖❖❖

1.4.5 CR Ovarian volume (OV) R 10ml or follicle number per section (FNPS) R 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 R 10 ml or follicle number per section (FNPS) R 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:

 Last menstrual period (or stage of cycle).

 Transducer bandwidth frequency.

 Approach/route assessed.

 Total number of 2 – 9 mm follicles per ovary.

 Measurements in three dimensions (in cm) or volume of each ovary.

 Other ovarian features and/or pathology including ovarian cysts, corpus

lutea, dominant follicles (R10 mm) (which should not be included in

ovarian volume calculations).

 Reliance on the contralateral ovary FNPO for diagnosis of PCOM, where a

dominant follicle is noted.

 Uterine features and/or pathology including endometrial thickness and

pattern.

1.5 Anti-M

€

ullerian Hormone in the diagnosis of PCOS

1.5.1 EBR Serum anti-M

€

ullerian hormone (AMH) could be used for deﬁning PCOM in

adults.

❖❖❖

444

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.

❖❖❖❖

444

1.5.3 EBR We recommend that serum AMH should not be used as a single test for the

diagnosis of PCOS.

❖❖❖❖

444

1.5.4 EBR Serum AMH should not yet be used in adolescents. ❖❖❖❖

444

1.5.5 PP Either serum AMH or 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:

 Age: Serum AMH generally peaks between the ages of 20-25 years in the

general population.

 Body mass index (BMI): Serum AMH is lower in those with higher BMI in the

general population.

 Hormonal contraception and ovarian surgery: Serum AMH may be sup-

pressed by current or recent COCP use.

 Menstrual cycle day: Serum AMH may vary across the menstrual cycle.

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.

❖❖❖❖

44

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.

❖❖❖❖

44

1.6.3 PP Healthcare professionals should be aware that the presentation of PCOS may

vary across ethnic groups.

1.7 Menopause life stage

VOL. - NO. - / - 2023 7

Fertility and Sterility®

TABLE 4

Continued.

NO. TYPE RECOMMENDATION GRADE/QUAITY

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.

❖❖❖

4

1.8.2 EBR All women with PCOS should be assessed for cardiovascular disease risk

factors.

❖❖❖❖

4

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.

❖❖❖❖

44

1.9.2 EBR Glycaemic status should be assessed at diagnosis in all adults and adolescents

with PCOS.

❖❖❖❖

44

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.

❖❖❖❖

4

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.

❖❖❖

4

8 VOL. - NO. - / - 2023

TABLE 4

Continued.

NO. TYPE RECOMMENDATION GRADE/QUAITY

1.9.11 EBR An OGTT should be considered in all women with PCOS and without pre-

existing 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.

❖❖❖

4

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.

❖❖❖❖

444

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.

❖❖❖❖

444

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.

❖❖❖❖

4

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.

❖❖❖

4

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.

❖❖❖❖

44

2.1.2 PP Women with PCOS should be asked about their perception of PCOS related-

symptoms, 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.

❖❖❖❖

4444

VOL. - NO. - / - 2023 9

Fertility and Sterility®

TABLE 4

Continued.

NO. TYPE RECOMMENDATION GRADE/QUAITY

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.

❖❖❖❖

4444

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.

❖❖❖❖

44

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).

❖❖❖

44

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.

2.6 Information resources, models of care, cultural and linguistic

considerations

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.

❖❖❖❖

444

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.

❖❖❖❖

444

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.

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.

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.

10 VOL. - NO. - / - 2023

TABLE 4

Continued.

NO. TYPE RECOMMENDATION GRADE/QUAITY

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.

❖❖❖❖

444

2.6.4.2 EBR The importance of being knowledgeable about PCOS, of applying evidence-

based practices when sharing news on diagnosis, treatment, and health

implications, and of ascertaining and focusing on patient priorities, should

be recognized.

❖❖❖❖

444

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 self-

esteem, 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:

 to avoid inappropriate treatment with antidepressants or anxiolytics.

 to limit use of agents that exacerbate PCOS symptoms, including weight

gain.

Healthcare professionals should be aware that not managing anxiety and

depression may impact adherence to PCOS treatment / management.

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.

❖❖❖❖

4

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.

3.1.5 PP There are beneﬁts to a healthy lifestyle even in the absence of weight loss.

VOL. - NO. - / - 2023 11

Fertility and Sterility®

TABLE 4

Continued.

NO. TYPE RECOMMENDATION GRADE/QUAITY

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:

 A lifelong focus on prevention of further weight gain.

 If the goal is to achieve weight loss, a tailored energy deﬁcit could be pre-

scribed for women, considering individual energy requirements, body

weight and physical activity levels.

 The value of improvement in central adiposity (e.g., waist circumference,

waist-hip ratio) or metabolic health.

 The need for ongoing assessment and support.

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.

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 goal-

setting, 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, self-

monitoring and reviewing, or SMART goals (Speciﬁc, Measurable,

Achievable, Realistic and Timely).

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.

❖❖❖

4

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.

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.

❖❖❖

4

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.

❖❖❖❖

12 VOL. - NO. - / - 2023

TABLE 4

Continued.

NO. TYPE RECOMMENDATION GRADE/QUAITY

3.4.3 CR Healthcare professionals should encourage and advise the following in

concordance with general population physical activity guidelines:

 All adults should undertake physical activity as doing some physical activity

is better than none.

 Adults should limit the amount of time spent being sedentary (e.g., sitting,

screen time) as replacing sedentary time with physical activity of any in-

tensity (including light intensity) provides health beneﬁts.

 For the prevention of weight gain and maintenance of health, adults (18-64

years) should aim for a minimum of 150 to 300 minutes of moderate in-

tensity activities or 75 to 150 minutes of vigorous intensity aerobic activity

per week or an equivalent combination of both spread throughout the

week, plus muscle strengthening activities (e.g., resistance/ﬂexibility) on

two non-consecutive days per week.

 For promotion of greater health beneﬁts including modest weight-loss and

prevention of weight-regain, adults (18-64 years) should aim for a

minimum of 250 min/week of moderate intensity activities or 150 min/

week of vigorous intensities or an equivalent combination of both, plus

muscle strengthening activities (e.g., resistance/ﬂexibility) ideally on two

non-consecutive days per week.

 Adolescents should aim for at least 60 minutes of moderate- to vigorous-

intensity physical activity per day, including activities that strengthen muscle

and bone at least three times per week.

❖❖❖❖

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.

❖❖❖

4

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:

 Underpin greater challenges with weight management.

 Highlight the importance of lifelong healthy lifestyle strategies and pre-

vention of excess weight gain.

 Assist women with PCOS and healthcare professionals in forming realistic,

tailored lifestyle goals.

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.

❖❖❖❖

44

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.

❖❖❖❖

VOL. - NO. - / - 2023 13

Fertility and Sterility®

TABLE 4

Continued.

NO. TYPE RECOMMENDATION GRADE/QUAITY

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:

 Acknowledging that whilst higher weight is a risk factor for PCOS and its

complications, it is only one indicator of health and broader factors should

be assessed.

 Asking permission to discuss and measure weight and using strategies to

minimize discomfort (e.g., blind weighing).

 Recognizing that the terms ‘‘overweight’’ and ‘‘obese/obesity’’ can be

stigmatizing with suggested alternatives including ‘‘ higher weight’’ .

 If weighing, explaining how weight information will be used to inform risks,

prevention and treatment and how not knowing may impact on

recommendations.

 Ensuring appropriate equipment is available for women of all sizes.

 Offering options of weight-centric care (promoting intentional weight loss)

or weight-inclusive care (promoting healthy lifestyle change without

focusing on intentional weight loss) tailored to individual goals and

preferences.

 Offering all women best practice assessment, treatment and support

regardless of weight, acknowledging that weight may be a non-modiﬁable

risk factor when using lifestyle modiﬁcation alone.

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

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

4.2.3 EBR Healthcare professionals could consider that there is no clinical advantage of

using high dose ethinylestradiol (R 30 mg) versus low dose

ethinylestradiol (< 30mg) when treating hirsutism in adults with PCOS.

❖❖❖

4

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

4.2.5 EBR The 35mg 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

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

14 VOL. - NO. - / - 2023

TABLE 4

Continued.

4.2.7 PP When prescribing COCPs in adults and adolescents with PCOS, and

adolescents at risk of PCOS

 It is important to address main presenting symptoms and consider other

treatments such as cosmetic therapies.

 Shared decision-making (including accurate information and reassurance

on the efﬁcacy and safety of COCP) is recommended and likely to improve

adherence.

 Natural estrogen preparations and the lowest effective estrogen doses

(such as 20-30mg of ethinyl estradiol or equivalent), need consideration,

balancing efﬁcacy, metabolic risk proﬁle, side effects, cost, and availability.

 The relatively limited evidence on COCPs speciﬁcally in PCOS needs to be

appreciated with practice informed by general population guidelines.

 The relative and absolute contraindications and side effects of COCPs

need to be considered and be the subject of individualized discussion.

 PCOS speciﬁc features, such as higher weight and cardiovascular risk

factors, need to be considered.

4.3 Metformin

4.3.1 EBR Metformin alone should be considered in adults with PCOS and a BMI R 25

kg/m2 for anthropometric, and metabolic outcomes including insulin

resistance, glucose, and lipid proﬁles.

❖❖❖

4

4.3.2 EBR Metformin alone could be considered in adolescents at risk of or with PCOS

for cycle regulation, acknowledging limited evidence.

❖❖❖

4

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:

 Shared decision making needs to consider feasibility and effectiveness of

active lifestyle intervention. Women should be informed that metformin

and active lifestyle intervention have similar efﬁcacy.

 Mild adverse effects, including gastrointestinal side-effects are generally

dose dependent and self-limiting.

 Starting at a low dose, with 500mg increments 1-2 weekly and extended-

release preparations may minimize side effects and improve adherence.

 Suggested maximum daily dose is 2.5g in adults and 2g in adolescents.

 Use appears safe long-term, based on use in other populations, however

indications for ongoing requirement needs to be considered.

 Use may be associated with low vitamin B12 levels, especially in those with

risk factors for low vitamin B12 (e.g., diabetes, post bariatric / metabolic

surgery, pernicious anaemia, vegan diet etc.), where monitoring should be

considered.

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

4.4.2 EBR Metformin could be used over COCP for metabolic indications in PCOS. ❖❖❖

4

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/m

❖❖❖

4

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/m

, 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 glucagon-

like 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

VOL. - NO. - / - 2023 15

Fertility and Sterility®

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Continued.

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

4.6.2 CR Given the negative psychological impact of female pattern hair loss, anti-

androgens 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.

4.6.5 PP

When prescribing anti-androgens, based on general population

recommendations, healthcare professionals should consider that:

 Spironolactone at 25-100mg / day appears to have lower risks of adverse

effects.

 Cyproterone acetate at doses R 10mg is not advised due to an increased

risk including for meningioma.

 Finasteride has an increased risk of liver toxicity.

 Flutamide and bicalutamide have an increased risk of severe liver toxicity.

 The relatively limited evidence on anti-androgens in PCOS needs to be

appreciated with small numbers of studies and limited numbers of

participants.

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

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

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

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

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:

 Wavelength and delivery of laser treatment varies by skin and hair colour.

 Laser is relatively ineffective in women with blond, grey or white hair.

 The addition of combined oral contraceptive pills (COCP), with or without

anti-androgens, to laser treatment may provide greater hair reduction and

maintenance compared to laser alone.

 Low and high ﬂuence laser appear to have similar efﬁcacy in reducing facial

hair, while low ﬂuence laser has reduced associated pain.

16 VOL. - NO. - / - 2023

TABLE 4

Continued.

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.

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

4.10.2 EBR

Healthcare professionals should recognize that pregnant women with PCOS

have an increased risk of:

 Higher gestational weight gain.

 Miscarriage.

 Gestational diabetes.

 Hypertension in pregnancy and preeclampsia.

 Intrauterine growth restriction, small for gestational age babies and low

birth weight.

 Preterm delivery.

 Caesarean section.

❖❖❖❖

4

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

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

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.

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.

4.11 Metformin in pregnancy

4.11.1 EBR

Healthcare professionals should be aware that metformin in preg-

nant women with PCOS has not been shown to prevent:

 Gestational diabetes.

 Late miscarriage (12 weeksþ1 day to 21 weeks þ6 days gesta-

tional age).

 Hypertension in pregnancy.

 Pre-eclampsia.

 Macrosomia or birthweight R 4000 g.

❖❖❖❖

44

VOL. - NO. - / - 2023 17

Fertility and Sterility®

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Continued.

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.

❖❖❖

444

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.

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

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.

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.

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.

❖❖❖❖

4

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.

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.

❖❖❖❖

4444

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.

18 VOL. - NO. - / - 2023

TABLE 4

Continued.

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.

❖❖❖

44

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.

❖❖❖

44

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.

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.

❖❖❖

44

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.

❖❖❖

44

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.

❖❖❖❖

4

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).

❖❖❖

44

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.

❖❖❖

44

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.

❖❖❖

4

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.

❖❖

44

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.

❖❖❖

44

5.5.6 PP Where gonadotrophins are to be prescribed, the following should be

considered:

 Cost of the intervention for ovulation induction.

 Expertise required for the use of the intervention for ovulation induction.

 The degree of intensive ultrasound monitoring that is required.

 A low dose step-up gonadotrophin protocol should be used to optimize the

chance of monofollicular development.

 Implications of potential multiple pregnancy.

5.5.7 PP There appears to be no difference in the clinical efﬁcacy of the available

gonadotrophin preparations.

VOL. - NO. - / - 2023 19

Fertility and Sterility®

TABLE 4

Continued.

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.

❖❖❖

44

5.6.2 PP When using laparoscopic ovarian surgery, the following should be

considered:

 Comparative cost of the intervention for ovulation induction.

 Expertise required for the safe use of the intervention for ovulation

induction.

 Both intraoperative and postoperative risks, which are higher in women

who are above healthy weight.

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:

 Commence metformin at the start of GnRH agonist treatment.

 Gradually titrate metformin up to a dose of between 1000mg to 2500mg

daily in order to minimize side effects.

 Stopping metformin therapy at the time of the pregnancy test or period,

unless the metformin therapy is otherwise indicated.

5.7.6 In vitro maturation

20 VOL. - NO. - / - 2023

FIGURE 1

Step 1: Irregular cycles + clinical hyperandrogenism

(exclude other causes)* = diagnosis

Step 2: If no clinical hyperandrogenism

Test for biochemical hyperandrogenism (exclude other causes)* = diagnosis

Step 3: If ONLY irregular cycles OR hyperandrogenism

Adolescents ultrasound is not indicated = consider at risk of PCOS and reassess later

Adults - request ultrasound for PCOM*, if posive (exclude other causes)* = diagnosis

* Exclusion of other causes = TSH, prolacn, 17-OH progesterone, FSH or if clinically indicated

exclude other causes (e.g. Cushing's Syndrome, adrenal tumours). For hypogonadotrophic

hypogonadism, usually due to low body fat or intensive exercise, exclude clinically and with LH/ FSH.

PCOM = polycysc ovarian morphology on ultrasound

Algorithm 1 - Diagnostic algorithm for polycystic ovary syndrome (PCOS). ª Monash University on behalf of the NHMRC Centre for Research

Excellence in Women's Health in Reproductive Life, 2023.

ª International 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.

*Exclusion of other causes ¼ TSH, prolactin, 17-OH progesterone, FSH or if clinically indicated exclude other causes (e.g. Cushing’s syndrome,

adrenal tumours). For hypogonadotrophic hypogonadism, usually due to low body fat or intensive exercise, exclude clinically and with LH and

FSH levels. TSH, thyroid stimulating hormone.

Teede. International PCOS Guideline 2023. Fertil Steril 2023.

TABLE 4

Continued.

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.

ª International 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.

Teede. International PCOS Guideline 2023. Fertil Steril 2023.

VOL. - NO. - / - 2023 21

Fertility and Sterility®

considerations (6000 pages). The evidence has generally

improved over the past ﬁve years but remains of low to moder-

ate 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 Evidence-

based 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 ultra-

sound; and here in 2023, alternatively anti-M

€

ullerian hor-

mone (AMH) can now be used instead of ultrasound, with

the exclusion of other aetiologies. Importantly, where irreg-

ular menstrual cycles and hyperandrogenism are present,

diagnosis is simpliﬁed and ultrasound or AMH are not

required for diagnosis. In adolescents, both hyperandrogen-

ism and ovulatory dysfunction are required, with ultrasound

and AMH not recommended due to poor speciﬁcity. AMH was

FIGURE 2

Letrozole

, increasing

dose as required

Central Blue Pathway follows best practice evidence and is preferred

Polycystic Ovary Syndrome

Diagnosis: International Guideline

criteria, building on Rotterdam criteria

Full baseline investigations

Ovulation

detected?

a. Baseline investigations (see narrative):

i. Diagnosis of PCOS - Endocrine profile and pelvic ultrasound scan

ii. Assessment of BMI, BP & glycemic status (OGTT / HbA1c)

iii. Routine preconception assessments (Rubella immunity, infection screen etc..), advice

and supplementation.

iv. Additional investigations: semen analysis and consider tubal patency assessment

b. Healthy lifestyle encompassing healthy eating and regular physical activity should be

recommended in all those with PCOS to limit adverse impacts on fertility and fertility

treatment outcomes and to optimize health during pregnancy

c. Off label prescribing: Letrozole, metformin and other pharmacological treatments are

generally off label in PCOS, as pharmaceutical companies have not applied for approval in

this condition. However, recommended off label use is evidence-based and allowed in

many countries. Where it is allowed, health professionals should inform women and discuss

the evidence, possible concerns and side effects of treatment.

d. Compared to letrozole, metformin has lower efficacy, cost and multiple pregnancy rate and

gonadotrophins have higher efficacy, cost and multiple pregnancy rate. Both may be an

alternative first line choice for informed women.

e. In vitro fertilization (IVF) - Third line unless other infertility factors (e.g. male, tubal). PCOS

specific protocols to minimise risk of ovarian hyperstimulation syndrome, consider invitro

maturation if available.

Yes

Repeated cycles– shared

decision-making

considering age and

resources then to IVF

Gonadotrophins

with

US monitoring. Adjusting

dose as required.

In vitro fertilization

Can consider Laparoscopic ovarian surgery,

noting need for facilities and experience

Can consider with full explanation of risks, benefits,

efficacy and costs: Clomiphene citrate + metformin

(preferred to clomiphene alone), clomiphene,

metformin (low cost/low efficacy/no monitoring) or

gonadotrophins (high cost/ multiple pregnancy/

high efficacy/ monitoring)

c,d

Second line

Medical

Treatment

Ovulation

detected?

Repeated cycles –

shared decision-making

considering age and

resources then to IVF

Yes

First line Medical

Treatment

Third line Medical

Treatment

Optimise preconception

health and lifestyle

Algorithm 2 - Infertility algorithm for polycystic ovary syndrome (PCOS). ª Monash University on behalf of the NHMRC Centre for Research

Excellence in Women's Health in Reproductive Life, 2023.

ª International 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.

Teede. International PCOS Guideline 2023. Fertil Steril 2023.

22 VOL. - NO. - / - 2023

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 re sistance is recognized as a key feature of

PCOS, yet routinely available measures of insulin resi stance

are inaccurate and clini cal measurement is not currently

recommended. Once diagnosed, assessment and manage-

ment should address reproductive, m etabolic, cardiova scu-

lar, dermatologic, sleep, and psychologic al features. A

lifelong health pla n i s re commended including a f ocus o n

healthy lifestyle, prevention of excess wei ght gain, optim i-

zation of fertility and p reconception risk factors, and pre-

vention and treatment of diverse clini cal features. These

include metabolic risk factors, diabetes, c ardiovascula r di s-

ease, and sleep disorders, which are all increased in PCOS.

PCOS should be c onsidered a high-risk condition i n p reg-

nancy with women identiﬁe d and monitored. A n increased

premenopausal r isk of endo metrial 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 disorde rs

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 profes-

sionals including high quality, evidence-based resources.

Shared decision making and self-empowerment are funda-

mental 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, preven-

tion 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 mini-

mized and healthcare professionals should seek permission to

weigh women, with explanation of weight-related risks.

Combined oral contraceptive pills are the ﬁrst line phar-

macological treatment for menstrual irregularity and hyper-

androgenism, 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 pri-

marily 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 under-

lying 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 copy-

right, however a clear process for adaption of guideline recom-

mendations 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-bas ed 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 infor-

mation available in multiple formats and in 15-20 languages.

Internationally accessible resources include education modules

for healthcare professionals at different career stages and disci-

plines, healthcare professional accredit ed courses, practice re-

sources 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 informa-

tion and of improved multi-discipl inar y 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 state-

ments, and codesign of best quality consistent guidelines with

processes for local adaption and healthcare impact. Key elements

include extensive collaboration, broad stakeholder representa-

tion, consumer partn ership, distributive leadership, adequate

funding, robust project management and governance, adher-

ence to best practice and integrated comprehensive translation,

and evaluation. We sincerely thank the partner and collabo-

rating 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

VOL. - NO. - / - 2023 23

Fertility and Sterility®

(www.monash.edu/medicine/mchri/pcos). Of named authors

HJT, CTT, AD, LM, LR, JBoyle, AM have no conﬂicts of inter-

est 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 Di-

agnostics and Ansh Labs; and sits on advisory boards for Fer-

ring, 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 advi-

sory boards for Roche Diagnostics. MC declares travels sup-

port 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 Arzneimit-

tell GmbH; travel support from Organon; and sits on an advi-

sory 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 contribu-

tion 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 Embry-

ology (ESHRE)

Collaborating and engaged societies and consumer

providing in-kind support include:

Androgen Excess and Polycystic Ovary Syndrome Soci-

ety (AEPCOS)

Asia Paciﬁc Paediatric Endocrine Society (APPES)

Asia Paciﬁc Initiative on Reproduction (ASPIRE)

Australia and New Zealand Society for Paediatric Endo-

crinology and Diabetes (ANZSPED)

Australian Diabetes Society (ADS)

Brazilian Society of Endocrinology and Metabolism (SBEM)

British Fertility Society (BFS)

Canadian Society of Endocrinology and Metabolism (CSEM)

Dietitians Association Australia (DA)

Endocrine Society Australia (ESA)

European Society for Paediatric Endocrinology (ESPE)

Exercise and Sports Science Aust ralia (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 so-

cieties

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 Gynaecol-

ogy (NFOG)

PCOS Challenge Inc: The National Polycystic Ovary Syn-

drome 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 (SA-

SOG)

Society for Endocrinology

Verity UK

Victorian Assisted Reproductive Technology Association

(VARTA)

Other relevant organizations are welcome to apply to

partner in guideline translation.

Authors’ Roles: HJT led the guidelines from funding,

engaging partners, coordinating processes, prioritizing clin-

ical questions, co-chairing guideline meetings, coordinating

peer review responses and leading writing, approval and pub-

lication 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 au-

thors were actively engaged as partner nominees and multi-

disciplinary GDG or consumer experts. The evidence

synthesis network was led by CTT AM, across search strate-

gies, 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.

The American Society for Reproductive Medicine, Endocrine So-

ciety, the European Society of Human Reproduction and Embry-

ology and the European Society for Endocrinology provided

partnership funding. Collaborating organizations provided in-

kind support. The Co mmonwealth Government of Australia

also supported Guideline Translation through the Medical

Research Future Fund (MRFCRI000266). HJT and AM are funded

by NHMRC fellowships and JT by an RACP fellowship.

REFERENCES

1. Teede H, Deeks A, M oran L. Polycystic ovary syndrome: a complex condition

with psychological, reproductive and metabolic manifestations that impacts

on health across the lifespan. BMC Med 2010;8:41.

24 VOL. - NO. - / - 2023

2. Azziz R, Carmina E, Chen Z, et al. Polycystic ovary syndrome. Nature reviews

Disease primers 2016;2:16057.

3. Gibson-Helm M, Teede H, Dunaif A, Dokras A. Delayed diagnosis and a lack

of information associated with dissatisfaction in women with polycystic

ovary syndrome. J Clin Endo & Metab 2017;102:604-12.

4. Dokras A, Saini S, Gibson-Helm M, Schulkin J, Cooney L, Teede H. Gaps

in knowledge among physicians regarding diagnostic criteria and man-

agement of polycystic ovary syndrome. Fertil Steril 2017;107(6),

1380_6.e1.

5. 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 .

6. Teede J Helena, Marie Misso, Michael Costello, et al. International evidence-

based guideline for the assessment and management of polycystic ovary

syndrome; 2018, Available at www.monash.edu/medicine/mchri/pcos.

7. Teede HJ, Misso ML, C ostello MF, et a l. R ecommendations from the

international evidence-based guideline for the assessment and man-

agement of p olycystic ovary syndrome. Hum Reprod 2 018;33(9),

1602_18.

8. Misso ML, Teede HJ. Evidence based guideline (EBG) development: A prac-

tical 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 .

9. 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.

10. Mousa A, Tay CT, Teede H. Technical Report for the International

Evidence-based Guideline f or the Assessm ent and Management of

Polycystic Ovary Syndrome. Monash University. 2023. Available at

https://doi.org/10.26180/23625288.v1

11. Weibel S, Popp M, Reis S, Skoetz N, Garner P, Sydenham E. Identifying and

managing problematic trials: A research integrity assessment tool for ran-

domized controlled trials in evidence synthesis. Research Synthesis Methods

2023;14(3):357–69.

12. Mol BW, Lai S, Rahim A, et al. Checklist to assess Trustworthiness in RAnd-

omised Controlled Trials (TRACT checklist): concept proposal and pilot.

Research Integrity and Peer Review 2023;8(1):6.

13. National Health and Medical Research Council. NHMRC levels of evidence

and grades for recommendations for developers of guidelines. Australia;

2009.

14. National Health and Medical Research Council. NHMRC standards

and procedures for externally developed guidelines. Australia;

2007.

15. GRADE working group. Grading of Recommendations Assessment, Devel-

opment and Evaluation (GRADE) guidelines.

APPENDIX

Members of the PCOS Network:

The inter national advisory panel, guideline technical

team, paediatric, c onsumer an d transl ation commit tees,

the Indigenous cultural advisor and the extended early

career support network who assisted with evi dence synthe-

sis, c an be foun d 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 T



atai 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 Lind



en Hirschberg, Karolinska Institutet, Karo-

linska University Hospital, Sweden

Tuong Ho, HOPE Research Centre, My Duc Hospital, Viet-

nam

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 Hos-

pital, South Africa

Loyal Pattuwage, Cochrane Australia, Monash University,

Australia

Alexia Pe

na, The Robinson Research Institute at the Univer-

sity 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; Cen tre 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

VOL. - NO. - / - 2023 25

Fertility and Sterility®

Mala Thondan, Harp Family Medical, Australia

Eszter Vanky, Norwegian University of Science and Tech-

nology; 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

International early career evidence synthesis network

leads

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,

Katrina Tan, Monash Health, Australia

26 VOL. - NO. - / - 2023