RESUMO
RESEARCH QUESTION: Is conducting a randomized control trial (RCT) to assess the effectiveness of whole-system naturopathy in improving pregnancy rates among women with diminished ovarian reserve (DOR) feasible? DESIGN: A two-arm, parallel group, assessor-blinded feasibility RCT was conducted. Women with DOR, trying to conceive naturally or by ART, were randomly assigned to naturopathy plus usual care, or usual care alone for 16 weeks. Primary outcomes were feasibility (recruitment, adherence, retention rates), acceptability and safety. Secondary outcomes included ongoing pregnancy rates, live birth rates and health-related outcomes (mental health, quality of life, diet, exercise, sleep and weight). Statistical significance of the differences between the two groups (P-values) were exploratory. RESULTS: One hundred and fifteen women completed the screening survey between March and November 2022. Of these, 66 women were assessed for eligibility and 41 (62%) consented. Recruitment resulted in seven enrolments each month. All 41 participants (100%) adhered to the intervention, 38 (93%) completed end-point questionnaires, 32 (78%) found study participation to be acceptable and 18 out of 21 (86%) from the intervention group would recommend a naturopathic intervention to other women with DOR. The naturopathic treatment was associated with only mild and temporary adverse events. No between-group differences were observed for pregnancy and live birth rates. CONCLUSION: The evaluation of whole-system naturopathy through a RCT was feasible and the treatment was acceptable and well tolerated according to women with DOR. Outcomes from this study will help inform sample size calculations powered for fertility outcomes for future RCTs on this topic.
Assuntos
Estudos de Viabilidade , Naturologia , Reserva Ovariana , Taxa de Gravidez , Humanos , Feminino , Gravidez , Adulto , Reserva Ovariana/fisiologia , Qualidade de Vida , Infertilidade Feminina/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Women with diminished ovarian reserve (DOR) have fewer eggs than would be expected at their age. It is estimated that 10% of women seeking fertility treatment are diagnosed with DOR. However, the success rate of medically assisted reproduction (MAR) is significantly lower in women with DOR, thus many seek additional approaches. AIM: To explore the health needs of women with DOR, treatment options and experience of treatment including traditional complementary integrative medicine (TCIM). METHODS: Anyone with a diagnosis of DOR, living in Australia or New Zealand, aged over 18 were invited to complete an online survey distributed via fertility support networks and social media platforms from April to December 2021. RESULTS: Data from 67 respondents were included. The main aspects of health that were impacted by DOR were fertility (91.0%) and mental health (52.2%). The main treatment recommended was MAR with most women either currently using MAR (38.8%) or having previously used MAR (37.3%). TCIM was widely used with 88.1% of women utilising supplements, 74.6% consulting with TCIM practitioners, and 65.7% adopting self-care practices. The main reasons for using TCIM were to improve fertility or support pregnancy, and to support general health and well-being. CONCLUSIONS: Women with DOR have additional health needs apart from infertility, most notably mental health support. The main form of treatment utilised is MAR, despite DOR being challenging for fertility clinicians. TCIM was widely used, and respondents perceived benefits related to improving fertility, supporting pregnancy, or improving well-being through use of acupuncture, meditation, naturopathy, massage, yoga.
Assuntos
Terapias Complementares , Reserva Ovariana , Humanos , Feminino , Adulto , Estudos Transversais , Terapias Complementares/estatística & dados numéricos , Austrália , Medicina Integrativa , Nova Zelândia , Inquéritos e Questionários , Infertilidade Feminina/terapia , Técnicas de Reprodução Assistida , Pessoa de Meia-Idade , Necessidades e Demandas de Serviços de SaúdeRESUMO
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 priorities. 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 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 (â¼6000 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-Müllerian 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 remains generally 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 consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program 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 Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and European 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 partnering organizations. 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 Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. 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.
Assuntos
Ginecologia , Síndrome do Ovário Policístico , Gravidez , Adulto , Feminino , Humanos , Criança , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/terapia , Síndrome do Ovário Policístico/epidemiologia , Qualidade de Vida , Austrália , Fatores de RiscoRESUMO
BACKGROUND: Statins are lipid-lowering agents with pleiotropic actions. Experts have proposed that in addition to improving the dyslipidaemia associated with polycystic ovary syndrome (PCOS), statins may also exert other beneficial metabolic and endocrine effects, such as reducing testosterone levels. This is an update of a Cochrane Review first published in 2011. OBJECTIVES: To assess the efficacy and safety of statin therapy in women with PCOS who are not actively trying to conceive. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHLs, and four ongoing trials registers on 7 November 2022. We also handsearched relevant conference proceedings and the reference lists of relevant trials for any additional studies, and we contacted experts in the field for any further ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated the effects of statin therapy in women with PCOS not actively trying to conceive. Eligible comparisons were statin versus placebo or no treatment, statin plus another agent versus the other agent alone, and statin versus another agent. We performed statistical analysis using Review Manager 5, and we assessed the certainty of the evidence using GRADE methods. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. Our primary outcomes were resumption of menstrual regularity and resumption of spontaneous ovulation. Our secondary outcomes were clinical and physiological measures including hirsutism, acne severity, testosterone levels, and adverse events. MAIN RESULTS: Six RCTs fulfilled the criteria for inclusion. They included 396 women with PCOS who received six weeks, three months, or six months of treatment; 374 women completed the studies. Three studies evaluated the effects of simvastatin and three studies evaluated the effects of atorvastatin. We summarised the results of the studies under the following comparisons. Statins versus placebo (3 RCTs) One trial measured resumption of menstrual regularity as menstrual cycle length in days. We are uncertain if statins compared with placebo shorten the mean length of the menstrual cycle (mean difference (MD) -2.00 days, 95% confidence interval (CI) -24.86 to 20.86; 37 participants; very low-certainty evidence). No studies reported resumption of spontaneous ovulation, improvement in hirsutism, or improvement in acne. We are uncertain if statins compared with placebo reduce testosterone levels after six weeks (MD 0.06, 95% CI -0.72 to 0.84; 1 RCT, 20 participants; very low-certainty evidence), after 3 months (MD -0.53, 95% CI -1.61 to 0.54; 2 RCTs, 64 participants; very low-certainty evidence), or after 6 months (MD 0.10, 95% CI -0.43 to 0.63; 1 RCT, 28 participants; very low-certainty evidence) Two studies recorded adverse events, and neither reported significant differences between the groups. Statins plus metformin versus metformin alone (1 RCT) The single RCT included in this comparison measured resumption of menstrual regularity as the number of spontaneous menses per six months. We are uncertain if statins plus metformin compared with metformin improves resumption of menstrual regularity (MD 0.60 menses, 95% CI 0.08 to 1.12; 69 participants; very low-certainty evidence). The study did not report resumption of spontaneous ovulation. We are uncertain if statins plus metformin compared with metformin alone improves hirsutism measured using the Ferriman-Gallwey score (MD -0.16, 95% CI -0.91 to 0.59; 69 participants; very low-certainty evidence), acne severity measured on a scale of 0 to 3 (MD -0.31, 95% CI -0.67 to 0.05; 69 participants; very low-certainty evidence), or testosterone levels (MD -0.03, 95% CI -0.37 to 0.31; 69 participants; very low-certainty evidence). The study reported that no significant adverse events occurred. Statins plus oral contraceptive pill versus oral contraceptive pill alone (1 RCT) The single RCT included in this comparison did not report resumption of menstrual regularity or spontaneous ovulation. We are uncertain if statins plus the oral contraceptive pill (OCP) improves hirsutism compared with OCP alone (MD -0.12, 95% CI -0.41 to 0.17; 48 participants; very low-certainty evidence). The study did not report improvement in acne severity. We are also uncertain if statins plus OCP compared with OCP alone reduces testosterone levels, because the certainty of the evidence was very low (MD -0.82, 95% CI -1.38 to -0.26; 48 participants). The study reported that no participants experienced significant side effects. Statins versus metformin (2 RCTs) We are uncertain if statins improve menstrual regularity compared with metformin (number of spontaneous menses per six months) compared to metformin (MD 0.50 menses, 95% CI -0.05 to 1.05; 1 RCT, 61 participants, very low-certainty evidence). No studies reported resumption of spontaneous ovulation. We are uncertain if statins compared with metformin reduce hirsutism measured using the Ferriman-Gallwey score (MD -0.26, 95% CI -0.97 to 0.45; 1 RCT, 61 participants; very low-certainty evidence), acne severity measured on a scale of 0 to 3 (MD -0.18, 95% CI -0.53 to 0.17; 1 RCT, 61 participants; very low-certainty evidence), or testosterone levels (MD -0.24, 95% CI -0.58 to 0.10; 1 RCT, 61 participants; very low-certainty evidence). Both trials reported that no significant adverse events had occurred. Statins versus oral contraceptive pill plus flutamide (1 RCT) According to the study report, no participants experienced any significant side effects. There were no available data for any other main outcomes. AUTHORS' CONCLUSIONS: The evidence for all main outcomes of this review was of very low certainty. Due to the limited evidence, we are uncertain if statins compared with placebo, or statins plus metformin compared with metformin alone, improve resumption of menstrual regularity. The trial evaluating statin plus OCP versus OCP alone reported neither of our primary outcomes. No other studies reported resumption of spontaneous ovulation. We are uncertain if statins improve hirsutism, acne severity, or testosterone. All trials that measured adverse events reported no significant differences between the groups.
Assuntos
Acne Vulgar , Inibidores de Hidroximetilglutaril-CoA Redutases , Metformina , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hirsutismo/tratamento farmacológico , Metformina/uso terapêutico , Acne Vulgar/tratamento farmacológico , Anticoncepcionais Orais/uso terapêutico , Testosterona/uso terapêuticoRESUMO
Translational frameshifting involves the repositioning of ribosomes on their messages into decoding frames that differ from those dictated during initiation. Some messenger RNAs (mRNAs) contain motifs that promote deliberate frameshifting to regulate production of the encoded proteins. The mechanisms of frameshifting have been investigated in many systems, and the resulting models generally involve single ribosomes responding to stimulator sequences in their engaged mRNAs. We discovered that the abundance of ribosomes on messages containing the IS3, dnaX, and prfB frameshift motifs significantly influences the levels of frameshifting. We show that this phenomenon results from ribosome collisions that occur during translational stalling, which can alter frameshifting in both the stalled and trailing ribosomes. Bacteria missing ribosomal protein bL9 are known to exhibit a reduction in reading frame maintenance and to have a strong dependence on elongation factor P (EFP). We discovered that ribosomes lacking bL9 become compacted closer together during collisions and that the E-sites of the stalled ribosomes appear to become blocked, which suggests subsequent transpeptidation in transiently stalled ribosomes may become compromised in the absence of bL9. In addition, we determined that bL9 can suppress frameshifting of its host ribosome, likely by regulating E-site dynamics. These findings provide mechanistic insight into the behavior of colliding ribosomes during translation and suggest naturally occurring frameshift elements may be regulated by the abundance of ribosomes relative to an mRNA pool.
Assuntos
Escherichia coli/genética , Mudança da Fase de Leitura do Gene Ribossômico/genética , RNA Mensageiro/genética , Fases de Leitura/genética , Ribossomos/metabolismo , Escherichia coli/metabolismo , Mutação da Fase de Leitura/genética , Conformação de Ácido Nucleico , Fatores de Alongamento de Peptídeos/metabolismo , Biossíntese de Proteínas/genética , Proteínas Ribossômicas/metabolismoRESUMO
Management of the coronavirus disease 2019 (COVID-19) pandemic requires widespread testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A main limitation for widespread SARS-CoV-2 testing is the global shortage of essential supplies, among them RNA extraction kits. The need for commercial RNA extraction kits places a bottleneck on tests that detect SARS-CoV-2 genetic material, including PCR-based reference tests. Here, we propose an alternative method we call PEARL (precipitation-enhanced analyte retrieval) that addresses this limitation. PEARL uses a lysis solution that disrupts cell membranes and viral envelopes while simultaneously providing conditions suitable for alcohol-based precipitation of RNA, DNA, and proteins. PEARL is a fast, low-cost, and simple method that uses common laboratory reagents and offers performance comparable to that of commercial RNA extraction kits. PEARL offers an alternative method to isolate host and pathogen nucleic acids and proteins to streamline the detection of DNA and RNA viruses, including SARS-CoV-2.
Assuntos
COVID-19 , SARS-CoV-2 , Teste para COVID-19 , Técnicas de Laboratório Clínico , DNA , Humanos , RNA Viral/genéticaRESUMO
The COVID-19 pandemic has created massive demand for widespread, distributed tools for detecting SARS-CoV-2 genetic material. The hurdles to scalable testing include reagent and instrument accessibility, availability of highly trained personnel, and large upfront investment. Here, we showcase an orthogonal pipeline we call CREST (Cas13-based, rugged, equitable, scalable testing) that addresses some of these hurdles. Specifically, CREST pairs commonplace and reliable biochemical methods (PCR) with low-cost instrumentation, without sacrificing detection sensitivity. By taking advantage of simple fluorescence visualizers, CREST allows a binary interpretation of results. CREST may provide a point-of-care solution to increase the distribution of COVID-19 surveillance.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Pandemias , Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da PolimeraseRESUMO
The association between the number of oocytes retrieved and fresh live birth rate (LBR) or cumulative LBR (CLBR), and whether an optimal number of oocytes are retrieved when LBR or CLBR are maximized, are highly relevant clinical questions; however published results are conflicting. A systematic review of all eligible studies (nâ¯=â¯16) published until January 2020 on MEDLINE, Embase, Scopus, CINAHL and Web of Science was conducted. Five studies evaluated only LBR from fresh cycles, five studies evaluated only CLBR from stimulated cycles and six evaluated both. A marked difference was observed between the oocyte yields at which LBR and CLBR were reportedly maximized in the individual studies. On the basis of nine studies, the optimal number of oocytes at which fresh LBR seems to be maximized is proposed to be between 12 and 18 oocytes (15 oocytes was the most common suggestion). On the other hand, CLBR continues to increase with the number of oocytes retrieved. This is the first systematic review on the topic, and it suggests that the retrieval of 12-18 oocytes is associated with maximal fresh LBR, whereas a continuing positive association is present between the number of oocytes retrieved and CLBR.
Assuntos
Coeficiente de Natalidade , Recuperação de Oócitos/estatística & dados numéricos , Feminino , Humanos , Síndrome de Hiperestimulação Ovariana , Indução da Ovulação/efeitos adversos , Indução da Ovulação/estatística & dados numéricosRESUMO
ISSUE ADDRESSED: Lifestyle modification plays a key role in weight management and chronic disease prevention in polycystic ovary syndrome (PCOS). Women with PCOS experience challenges in adopting and maintaining healthy lifestyle behaviours, which may be related to health literacy. The aims of this study were to explore the health literacy needs of women with PCOS in lifestyle and weight management to inform research and practice. METHODS: Ten women with PCOS participated in focus groups and semi-structured telephone interviews on lifestyle and weight management in PCOS. RESULTS: For functional health literacy, women with PCOS are highly motivated for lifestyle and weight management due to the long-term consequences of PCOS. For interactive health literacy, barriers included delayed diagnosis and poor communication. Women with PCOS were resourceful in accessing a wide range of weight management services but some experience barriers such as costs or the feelings of embarrassment associated with accessing relevant services. For critical health literacy, no facilitators and barriers could be identified for the domain of participation in making decisions for health. CONCLUSIONS: Women with PCOS experience facilitators and barriers in functional and interactive health literacy in lifestyle and weight management. SO WHAT?: Future interventions should seek to further understand and address these gaps in health literacy by increasing weight management skills through behaviour change techniques, improving health professional-patient communication through tools such as question prompt lists, enhancing peer support by increasing distributed health literacy in PCOS support groups and by providing opportunities for co-design of interventions.
Assuntos
Letramento em Saúde , Síndrome do Ovário Policístico , Feminino , Humanos , Estilo de Vida , Síndrome do Ovário Policístico/terapiaRESUMO
BACKGROUND: The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Metformin reduces hyperinsulinaemia and suppresses the excessive ovarian production of androgens. It is suggested that as a consequence metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy, and live birth rates. OBJECTIVES: To determine the effectiveness and safety of metformin as a co-treatment during IVF or intracytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, LILACS, the trial registries for ongoing trials, and reference lists of articles (from inception to 13 February 2020). SELECTION CRITERIA: Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment. TYPES OF PARTICIPANTS: women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors. Types of interventions: metformin administered before and during IVF or ICSI treatment. PRIMARY OUTCOME MEASURES: live birth rate, incidence of ovarian hyperstimulation syndrome. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, extracted the data according to the protocol, and assessed study quality. We assessed the overall quality of the evidence using the GRADE approach. MAIN RESULTS: This updated review includes 13 RCTs involving a total of 1132 women with PCOS undergoing IVF/ICSI treatments. We stratified the analysis by type of ovarian stimulation protocol used (long gonadotrophin-releasing hormone agonist (GnRH-agonist) or short gonadotrophin-releasing hormone antagonist (GnRH-antagonist)) to determine whether the type of stimulation used influenced the outcomes. We did not perform meta-analysis on the overall (both ovarian stimulation protocols combined) data for the outcomes of live birth and clinical pregnancy rates per woman because of substantial heterogeneity. In the long protocol GnRH-agonist subgroup, the pooled evidence showed that we are uncertain of the effect of metformin on live birth rate per woman when compared with placebo/no treatment (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.94 to 1.79; 6 RCTs; 651 women; I2 = 47%; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 28%, the chance following metformin would be between 27% and 51%. Only one study used short protocol GnRH-antagonist and reported live birth rate. Metformin may reduce live birth rate compared with placebo/no treatment (RR 0.48, 95% CI 0.29 to 0.79; 1 RCT; 153 women; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 43%, the chance following metformin would be between 13% and 34% (short GnRH-antagonist protocol). We found that metformin may reduce the incidence of OHSS (RR 0.46, 95% CI 0.29 to 0.72; 11 RCTs; 1091 women; I2 = 38%; low-quality evidence). This suggests that for a woman with a 20% risk of OHSS without metformin, the corresponding risk using metformin would be between 6% and 14%. Using long protocol GnRH-agonist stimulation, metformin may increase clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.32, 95% CI 1.08 to 1.63; 10 RCTs; 915 women; I2 = 13%; low-quality evidence). Using short protocol GnRH-antagonist, we are uncertain of the effect of metformin on clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.38, 95% CI 0.21 to 9.14; 2 RCTs; 177 women; I2 = 87%; very low-quality evidence). We are uncertain of the effect of metformin on miscarriage rate per woman when compared with placebo/no treatment (RR 0.86, 95% CI 0.56 to 1.32; 8 RCTs; 821 women; I2 = 0%; low-quality evidence). Metformin may result in an increase in side effects compared with placebo/no treatment (RR 3.35, 95% CI 2.34 to 4.79; 8 RCTs; 748 women; I2 = 0%; low-quality evidence). The overall quality of evidence ranged from very low to low. The main limitations were inconsistency, risk of bias, and imprecision. AUTHORS' CONCLUSIONS: This updated review on metformin versus placebo/no treatment before or during IVF/ICSI treatment in women with PCOS found no conclusive evidence that metformin improves live birth rates. In a long GnRH-agonist protocol, we are uncertain whether metformin improves live birth rates, but metformin may increase the clinical pregnancy rate. In a short GnRH-antagonist protocol, metformin may reduce live birth rates, although we are uncertain about the effect of metformin on clinical pregnancy rate. Metformin may reduce the incidence of OHSS but may result in a higher incidence of side effects. We are uncertain of the effect of metformin on miscarriage rate per woman.
Assuntos
Fertilização in vitro , Hiperandrogenismo/tratamento farmacológico , Hiperinsulinismo/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Nascido Vivo/epidemiologia , Metformina/uso terapêutico , Síndrome do Ovário Policístico/complicações , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/prevenção & controle , Viés , Intervalos de Confiança , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Síndrome de Hiperestimulação Ovariana/epidemiologia , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação/métodos , Placebos/uso terapêutico , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Injeções de Esperma IntracitoplásmicasRESUMO
BACKGROUND: Metformin has been proposed as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome (PCOS). It is important to directly compare the efficacy and safety of metformin versus OCP in the long-term treatment of women with PCOS. This is an update of a Cochrane Review comparing insulin sensitising agents with the OCP and only includes studies on metformin. OBJECTIVES: To assess the effectiveness and safety of metformin versus the OCP (alone or in combination) in improving clinical, hormonal, and metabolic features of PCOS. SEARCH METHODS: In August 2019 we searched the Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and CINAHL, the trial registers, handsearched references of the identified articles, and contacted experts in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of the use of metformin versus the OCP (alone or in combination) for women with PCOS. DATA COLLECTION AND ANALYSIS: We used standard methods recommended by Cochrane. The primary review outcomes were the clinical parameters of hirsutism and adverse events, both severe (requiring stopping of medication), and minor. In the presence of substantial heterogeneity (I2 statistic > 50), which could be explained by pre-specified subgroup analyses on the basis of BMI, we reported the subgroups separately. MAIN RESULTS: This is a substantive update. We identified 38 additional studies. We included 44 RCTs (2253 women), which comprised 39 RCTs on adult women (2047 women) and five RCTs on adolescent women (206 women). Evidence quality ranged from very low to low. The main limitations were risk of bias, imprecision and inconsistency. Metformin versus the OCP In adult women, we are uncertain of the effect of metformin compared to the OCP on hirsutism in subgroup body mass index (BMI) < 25 kg/m2 (mean difference (MD) 0.38, 95% confidence interval (CI) -0.44 to 1.19, 3 RCTs, n = 134, I2 = 50%, very low-quality evidence) and subgroup BMI > 30 kg/m2 (MD -0.38, 95% CI -1.93 to 1.17; 2 RCTs, n = 85, I2 = 34%, low-quality evidence). Metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m2 to 30 kg/m2 (MD 1.92, 95% CI 1.21 to 2.64, 5 RCTs, n = 254, I2 = 0%, low-quality evidence). Metformin may increase severe gastro-intestinal adverse events rate compared to the OCP (Peto odds ratio (OR) 6.42, 95% CI 2.98 to 13.84, 11 RCTs, n = 602, I2 = 0%, low-quality evidence). Metformin may decrease the incidence of severe other adverse events compared to the OCP (Peto OR 0.20, 95% CI 0.09 to 0.44, 8 RCTs, n = 363, I2 = 0%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, we are uncertain whether there is a difference between Metformin and the OCP, on hirsutism and adverse events. Metformin versus metformin combined with the OCP In adult women, metformin may be less effective in improving hirsutism compared to Metformin combined with the OCP (MD 1.36, 95% CI 0.62 to 2.11, 3 RCTs, n = 135, I2= 9%, low-quality evidence). We are uncertain if there was a difference between metformin and metformin combined with the OCP for severe gastro-intestinal adverse events (OR 0.74, 95% CI 0.21 to 2.53, 3 RCTs, n = 171, I2 = 0%, low-quality evidence), or for severe other adverse events (OR 0.56, 95% CI 0.11 to 2.82, 2 RCTs, n = 109, I2 = 44%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, there were no trials for this comparison. The OCP versus metformin combined with the OCP In adult women, the OCP may be less effective in improving hirsutism compared to metformin combined with the OCP (MD 0.54, 95% CI 0.20 to 0.89, 6 RCTs, n = 389, I2= 1%, low-quality evidence). The OCP may decrease the incidence of severe gastro-intestinal adverse events compared to metformin combined with the OCP (OR 0.20, 95% CI 0.06 to 0.72, 5 RCTs, n = 228, I2 = 0%, low-quality evidence). We are uncertain if there is a difference between the OCP and metformin combined with the OCP for severe other adverse events (OR 1.61, 95% CI 0.49 to 5.37, 4 RCTs, n = 159, I2 = 12%, low-quality evidence). The OCP may decrease the incidence of minor (gastro-intestinal) adverse events compared to metformin combined with the OCP (OR 0.06, 95% CI 0.01 to 0.44, 2 RCTs, n = 98, I2 = 0%, low-quality evidence). In adolescents, we are uncertain whether there is a difference between the OCP, compared to metformin combined with the OCP, on hirsutism or adverse events. AUTHORS' CONCLUSIONS: In adult women with PCOS, metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m2 to 30 kg/m2 but we are uncertain if there was a difference between metformin and the OCP in subgroups BMI < 25 kg/m2 and BMI > 30kg/m2. Compared to the OCP, metformin may increase the incidence of severe gastro-intestinal adverse events and decrease the incidence of severe other adverse events with no trials reporting on minor adverse events. Either metformin alone or the OCP alone may be less effective in improving hirsutism compared to metformin combined with the OCP. We are uncertain whether there is a difference between the OCP alone and metformin alone compared to metformin combined with the OCP for severe or minor adverse events except for the OCP versus metformin combined with the OCP where the OCP may decrease the incidence of severe and minor gastro-intestinal adverse events. In adolescent women with PCOS, we are uncertain whether there is a difference between any of the comparisons for hirsutism and adverse events due to either no evidence or very low-quality evidence. Further large well-designed RCTs that stratify for BMI are needed to evaluate metformin versus the OCP and combinations in women with PCOS, in particular adolescent women.
Assuntos
Anticoncepcionais Orais Combinados/uso terapêutico , Hirsutismo/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Distúrbios Menstruais/tratamento farmacológico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Acne Vulgar/tratamento farmacológico , Adolescente , Adulto , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , Anticoncepcionais Orais Combinados/efeitos adversos , Quimioterapia Combinada , Neoplasias do Endométrio/prevenção & controle , Feminino , Humanos , Metformina/efeitos adversos , Síndrome do Ovário Policístico/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemRESUMO
BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a common female reproductive disorder with multiple manifestations. There are relatively few qualitative studies exploring the nature of living with PCOS despite its high prevalence. Qualitative research can enhance clinical practice via the provision of patient insights into the experience of living with their condition. METHODS: We conducted two focus groups and three semi-structured interviews of Australian overweight/obese women with PCOS aged 18-46 years between March and April 2017 who were recruited through social media advertising. Interviews and focus groups were audio recorded and transcribed verbatim. Thematic analysis was applied to the data, using the method of constant comparison. RESULTS: Ten women contributed data from two focus groups and two semi-structured interviews. Five themes emerged from the data: complexity of the condition with its multiple manifestations, difficulties with delayed diagnosis and lack of information provided after diagnosis, negative experiences on social media and online forums and the need for support, frustration over lack of a "cure"; and the impact of symptoms and concern about long-term sequelae. CONCLUSIONS: Living with PCOS appears to generate a significant degree of anxiety about the future, dissatisfaction with current treatment models, and loss of feminine identity. Gaps in timely diagnosis, information and support provision need to be addressed. This includes supporting weight management as a fundamental concern for women with PCOS.
Assuntos
Ansiedade , Obesidade/complicações , Sobrepeso/complicações , Síndrome do Ovário Policístico/complicações , Adolescente , Adulto , Austrália , Feminino , Grupos Focais , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Obesidade/psicologia , Sobrepeso/psicologia , Pesquisa Qualitativa , Adulto JovemRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) has a prevalence of 8%-13%. Given the prevalence, diverse health impacts and variation in care, rigorous evidence-based guidelines are needed in PCOS management. This systematic review with meta-analyses aimed to investigate the effect of the combined oral contraceptive pill (COCP) and/or metformin in the management of hormonal and clinical features of PCOS, to inform international guidelines. METHODS: Electronic databases were searched systematically from inception until 11 January 2017 to inform the guideline process. Eligible studies were randomized controlled trials which investigated the effect of COCPs and/or metformin alone or combined on hormonal and clinical features in women with PCOS. Outcomes were prioritized as critical for informing a decision about an intervention or important or not important, according to GRADE. Articles were assessed by one author against selection criteria, in consultation with a second author. Data were double extracted independently by four authors, and data quality appraisal was completed. Meta-analyses were conducted, where appropriate. RESULTS: Fifty-six studies were eligible for inclusion. Outcomes prioritized by women and health professionals included the following: irregular cycles, insulin resistance, weight, BMI, thromboembolic events and gastrointestinal effects. In low-quality evidence in adolescents, meta-analyses demonstrated that metformin was better than COCP for BMI (mean difference [MD] -4.02 [-5.23, -2.81], P < 0.001); COCP was better than metformin for menstrual regulation (MD -0.19 [-0.25, -0.13], P < 0.00001). In low-quality evidence in adults, meta-analyses demonstrated that metformin was better than placebo for BMI (MD -0.48 [-0.94, -0.02], P = 0.04); metformin was better than COCP for fasting insulin (MD 4.00 [2.59, 5.41], P = 0.00001), whereas COCP was better than metformin for irregular cycles (MD 12.49 [1.34, 116.62], P = 0.03). Combined oral contraceptive pill alone was better than the combination with an anti-androgen for BMI (MD -3.04 [-5.45, -0.64], P = 0.01). Metformin was associated with generally mild gastrointestinal adverse events. Differences in statistical significance were observed when outcomes were subgrouped by BMI. CONCLUSIONS: This review identified that COCP therapy has benefits for management of hyperandrogenism and menstrual regulation. Metformin combined with the COCP may be useful for management of metabolic features. There is minimal evidence of benefits of adding an anti-androgen to COCP therapy. Metformin alone has benefits for adult women for management of weight, hormonal and metabolic outcomes, especially for women with BMI ≥ 25 kg/m2 . There is inadequate evidence to suggest the optimal COCP formulation, or dosing regimen and formulation of metformin.
Assuntos
Anticoncepcionais Orais Combinados/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/uso terapêuticoRESUMO
BACKGROUND: Lifestyle modification targeting weight management is the first-line treatment for women with Polycystic Ovary Syndrome (PCOS) regardless of presenting symptoms. Women with PCOS are more likely to gain more weight compared with women without PCOS, which may be related to barriers in engaging in lifestyle modification. The aim of this study is to explore the experience of women with PCOS in weight management and to determine the facilitators and barriers to lifestyle modifications in women with PCOS. METHODS: Ten women with PCOS participated in focus groups and semi-structured telephone interviews on lifestyle and weight management in PCOS. Discussions were audio-recorded and transcribed verbatim. Thematic analysis of the transcripts was conducted. Thematic analysis of the transcripts were conducted using the method of constant comparison. RESULTS: Women in the current study attempted a wide range of weight loss interventions, but had difficulties losing weight and preventing weight regain. Women felt that having PCOS affected their ability to lose weight and to keep it off. Facilitators to lifestyle modification for weight management were reported as structured approaches such as having balanced meals and support by health professionals, peers, friends or family. Barriers to lifestyle changes in women with PCOS included logistical barriers such as time and cost, motivational barriers including tiredness or feeling unrewarded, environmental barriers such as not having access to safe places to exercise, emotional barriers such as having depressive and defeating thoughts, and relational barriers such as having unsupportive partner or prioritising children's meal preferences. CONCLUSIONS: Women with PCOS face a number of personal, environmental and social facilitators and barriers to lifestyle modification for weight loss. While many of these are also experienced by women without PCOS, women with PCOS face additional barriers in having low sense of self-confidence and high prevalence of negative thoughts which may impair their ability to maintain efforts in lifestyle modification over the long term. Future research should further explore the impact of the emotional and mental burden of PCOS on the management of weight and other aspects of PCOS. Future lifestyle intervention should also address the psychosocial aspect of PCOS.
Assuntos
Exercício Físico , Estilo de Vida , Obesidade/terapia , Sobrepeso/terapia , Síndrome do Ovário Policístico/terapia , Redução de Peso , Adulto , Austrália , Feminino , Seguimentos , Humanos , Obesidade/complicações , Obesidade/patologia , Sobrepeso/complicações , Sobrepeso/patologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/patologia , Prognóstico , Pesquisa QualitativaRESUMO
BACKGROUND: Current evidence suggests that preimplantation genetic testing for aneuploidy (PGT-A) used during assisted reproductive technology improves per-cycle live-birth rates but cumulative live-birth rate (CLBR) was similar to a strategy of morphological assessment (MA) of embryos. No study has assessed the cost-effectiveness of repeated cycles with PGT-A using longitudinal patient-level data. AIM: To assess the cost-effectiveness of repeated cycles with PGT-A compared to MA of embryos in older women. MATERIALS AND METHODS: Micro-costing methods were used to value direct resource consumption of 2093 assisted reproductive technology-naïve women aged ≥37 years undergoing up to three 'complete assisted reproductive technology cycles' (fresh plus cryopreserved embryos) with either PGT-A or MA in an Australian clinic between 2011 and 2014. Incremental cost-effective ratios were calculated from healthcare and patient perspectives with uncertainty assessed using non-parametric bootstrap methods. Cost-effectiveness acceptability curves were constructed to evaluate the probability of PGT-A being cost-effective over a range of willingness-to-pay thresholds. RESULTS: The CLBR and mean healthcare costs per patient were 30.90% and $22 962 for the PGT-A group, and 26.77% and $21 801 for the MA group, yielding an incremental cost-effective ratio of $28 103 for an additional live birth with PGT-A. At a willingness-to-pay threshold of $50 000 and above, there is more than an 80% probability of PGT-A being cost-effective from the healthcare perspective and a 50% likelihood from a patient perspective. CONCLUSION: This is the first study to use real-world patient-level data to assess the cost-effectiveness of PGT-A in older women from the healthcare and patient perspectives. The findings contribute to the ongoing debate on the role of PGT-A in clinical practice.
Assuntos
Aneuploidia , Testes Genéticos/economia , Custos de Cuidados de Saúde , Idade Materna , Diagnóstico Pré-Implantação , Técnicas de Reprodução Assistida , Adulto , Fatores Etários , Austrália , Estudos de Coortes , Análise Custo-Benefício , Feminino , HumanosRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) is complex with reproductive, metabolic and psychological features. Infertility is a prevalent presenting feature of PCOS with approximately 75% of these women suffering infertility due to anovulation, making PCOS by far the most common cause of anovulatory infertility. Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. AIMS: This review paper aims to provide a brief update on the best available and most current research evidence supporting the treatment of PCOS which informed the recommendations in the assessment and treatment of infertility section of the international evidence-based guideline on PCOS 2018. MATERIALS AND METHODS: International evidence-based guideline development engaged professional societies and consumer organisations with multidisciplinary experts and women with PCOS directly involved at all stages. RESULTS: Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. Letrozole should now be considered first-line pharmacological treatment for ovulation induction to improve fertility outcomes. Clomiphene citrate alone and metformin alone could also be used as first-line pharmacological therapy, although both are less effective than letrozole and metformin is less effective than clomiphene citrate in obese women. Gonadotrophins or laparoscopic ovarian surgery are usually second-line ovulation induction therapies. In the absence of an absolute indication for in vitro fertilisation (IVF) / intracytoplasmic sperm injection, women with PCOS and anovulatory infertility could be offered IVF as third-line therapy where first- or second-line ovulation induction therapies have failed. CONCLUSION: This review provides the best available evidence informing recommendations (along with clinical expertise and consumer preference) which provide clinicians with clear advice on best practice for the management of infertile women with PCOS.
Assuntos
Infertilidade Feminina/etiologia , Infertilidade Feminina/terapia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/terapia , Feminino , HumanosRESUMO
STUDY QUESTION: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? SUMMARY ANSWER: International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. WHAT IS KNOWN ALREADY: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. STUDY DESIGN, SIZE, DURATION: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. PARTICIPANTS/MATERIALS, SETTING, METHODS: Governance included a six continent international advisory and a project board, five guideline development groups (GDGs), and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis, and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: (a) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; (b) reducing unnecessary testing; (c) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and (d) emphasizing evidence based medical therapy and cheaper and safer fertility management. LIMITATIONS, REASONS FOR CAUTION: Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. WIDER IMPLICATIONS OF THE FINDINGS: The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program.
Assuntos
Síndrome do Ovário Policístico/diagnóstico , Feminino , Humanos , Infertilidade Feminina/fisiopatologia , Síndrome do Ovário Policístico/complicações , Qualidade de Vida , Fatores de RiscoRESUMO
STUDY QUESTION: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise and consumer preference? SUMMARY ANSWER: International evidence-based guidelines, including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. WHAT IS KNOWN ALREADY: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial, and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. STUDY DESIGN, SIZE, DURATION: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. PARTICIPANTS/MATERIALS, SETTING, METHODS: Governance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis and translation experts. In total, 37 societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: (i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; (ii) reducing unnecessary testing; (iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and (iv) emphasizing evidence based medical therapy and cheaper and safer fertility management. LIMITATIONS, REASONS FOR CAUTION: Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. WIDER IMPLICATIONS OF THE FINDINGS: The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTEREST(S): The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREE-II criteria, and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC.
Assuntos
Medicina Baseada em Evidências/normas , Síndrome do Ovário Policístico/terapia , Guias de Prática Clínica como Assunto , Medicina Baseada em Evidências/métodos , Feminino , Humanos , Infertilidade Feminina/etiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/psicologia , GravidezRESUMO
INTRODUCTION: We have developed the first international evidence-based guideline for the diagnosis and management of polycystic ovary syndrome (PCOS), with an integrated translation program incorporating resources for health professionals and consumers. The development process involved an extensive Australian-led international and multidisciplinary collaboration of health professionals and consumers over 2 years. The guideline is approved by the National Health and Medical Research Council and aims to support both health professionals and women with PCOS in improving care, health outcomes and quality of life. A robust evaluation process will enable practice benchmarking and feedback to further inform evidence-based practice. We propose that this methodology could be used in developing and implementing guidelines for other women's health conditions and beyond. Main recommendations: The recommendations cover the following broad areas: diagnosis, screening and risk assessment depending on life stage; emotional wellbeing; healthy lifestyle; pharmacological treatment for non-fertility indications; and assessment and treatment of infertility. Changes in management as a result of this guideline: â¢Diagnosis:âªwhen the combination of hyperandrogenism and ovulatory dysfunction is present, ultrasound examination of the ovaries is not necessary for diagnosis of PCOS in adult women;âªrequires the combination of hyperandrogenism and ovulatory dysfunction in young women within 8 years of menarche, with ultrasound examination of the ovaries not recommended, owing to the overlap with normal ovarian physiology; andâªadolescents with some clinical features of PCOS, but without a clear diagnosis, should be regarded as "at risk" and receive follow-up assessment.â¢Screening for metabolic complications has been refined and incorporates both PCOS status and additional metabolic risk factors.â¢Treatment of infertility: letrozole is now first line treatment for infertility as it improves live birth rates while reducing multiple pregnancies compared with clomiphene citrate.
Assuntos
Gerenciamento Clínico , Medicina Baseada em Evidências/normas , Internacionalidade , Síndrome do Ovário Policístico/terapia , Medicina Reprodutiva/normas , Adolescente , Adulto , Clomifeno/uso terapêutico , Medicina Baseada em Evidências/métodos , Feminino , Humanos , Infertilidade Feminina/tratamento farmacológico , Letrozol/uso terapêutico , Síndrome do Ovário Policístico/diagnóstico , Gravidez , Medicina Reprodutiva/métodos , Adulto JovemRESUMO
BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a common female reproductive disorder with multiple manifestations. Weight management is a key therapeutic goal. Acupuncture is a potential adjunctive weight loss treatment in non-PCOS populations. We aimed to engage patients in co-design and assess the feasibility and acceptability of methods for a randomised controlled trial (RCT) on acupuncture and telephone-based health coaching for weight management in overweight or obese women with PCOS using qualitative methods. METHODS: We recruited women who had PCOS and were aged 18-45 years and with a body mass index of 25 kg/m2 and over, using social media. Two face-to-face focus group meetings and three semi-structured telephone interviews were conducted (n = 10). We analysed data using thematic analysis and aimed to compare and contrast motivations for joining the trial between women who were actively trying to conceive (n = 7) and not trying to conceive (n = 3). Attitudes to, knowledge and experiences of acupuncture; perceptions and attitudes towards the interventions in the RCT (real acupuncture, sham acupuncture and telephone-based health coaching); the outcomes of importance; and barriers and facilitators to successful trial recruitment and retention were collected. RESULTS: Women were both acupuncture-naive and acupuncture-experienced. Overall, attitudes towards acupuncture were positive, and the trial design was acceptable with appointment flexibility requested. Ideal enrolment time, if women were trying to conceive, was six months prior to conception. Women supported three-month intervention and the use of sham acupuncture as a control. Financial incentives were not believed to be necessary, and women spoke of altruistic intentions in enrolling for such a trial. Women who were trying to conceive voiced a need for support from their family, health coaches, and peers. The telephone-based health coaching offered welcome support and accountability, noted as possible facilitators of weight loss. CONCLUSIONS: Our findings show that acupuncture is a likely acceptable adjunct to lifestyle interventions for weight loss in PCOS, and that a sham-controlled trial is feasible and acceptable to PCOS women. Further research is required in order to evaluate the efficacy of acupuncture together with lifestyle for weight management in PCOS.