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    Differential Expression Patterns of Glycolytic Enzymes and Mitochondria-Dependent Apoptosis in PCOS Patients with Endometrial Hyperplasia, an Early Hallmark of Endometrial Cancer, and the Impact of Metformin . Wang Tao,Zhang Jiao,Hu Min,Zhang Yuehui,Cui Peng,Li Xin,Li Juan,Vestin Edvin,Brännström Mats,Shao Linus R,Billig Håkan International journal of biological sciences The underlying mechanisms of polycystic ovarian syndrome (PCOS)-induced endometrial dysfunction are not fully understood, and although accumulating evidence shows that the use of metformin has beneficial effects in PCOS patients, the precise regulatory mechanisms of metformin on endometrial function under PCOS conditions have only been partially explored. To address these clinical challenges, this study aimed to assess the protein expression patterns of glycolytic enzymes, estrogen receptor (ER), and androgen receptor (AR) along with differences in mitochondria-dependent apoptosis in PCOS patients with and without endometrial hyperplasia and to investigate the effects of metformin in PCOS patients with endometrial hyperplasia . Here, we showed that compared to non-PCOS patients and PCOS patients without hyperplasia, the endometria from PCOS patients with hyperplasia had a distinct protein expression pattern of glycolytic enzymes, including pyruvate kinase isozyme M2 isoform (PKM2) and pyruvate dehydrogenase (PDH), and mitochondrial transcription factor A (TFAM). In PCOS patients with endometrial hyperplasia, increased glandular epithelial cell secretion and infiltrated stromal cells in the glands were associated with decreased PDH immunoreactivity in the epithelial cells. Using endometrial tissues from PCOS patients with hyperplasia, we found that in response to metformin treatment , hexokinase 2 (HK2) expression was decreased, whereas phosphofructokinase (PFK), PKM2, and lactate dehydrogenase A (LDHA) expression was increased compared to controls. Although there was no change in PDH expression, metformin treatment increased the expression of TFAM and cleaved caspase-3. Moreover, our study showed that while endometrial ERβ expression was no different between non-PCOS and PCOS patients regardless of whether or not hyperplasia was present, ERα and AR protein expression was gradually increased in women with PCOS following the onset of endometrial hyperplasia. Our study showed that treatment with metformin inhibited ERα expression without affecting ERβ expression. Our findings suggest that decreased glycolysis and increased mitochondrial activity might contribute to the onset of ERα-dependent endometrial hyperplasia and that metformin might directly reverse impaired glycolysis and normalize mitochondrial function in PCOS patients with endometrial hyperplasia. 10.7150/ijbs.31425
    Effects of electroacupuncture on anxiety and depression in unmarried patients with polycystic ovarian syndrome: secondary analysis of a pilot randomised controlled trial. Wang Zhi,Dong Haoxu,Wang Qing,Zhang Lina,Wu Xiaoke,Zhou Zhongming,Yang Li,Huang Dongmei Acupuncture in medicine : journal of the British Medical Acupuncture Society OBJECTIVE:To evaluate the efficacy of electroacupuncture (EA) for the treatment of anxiety and depression in unmarried patients with polycystic ovarian syndrome (PCOS) by secondary analysis of a randomised controlled trial. METHODS:A prospective pilot randomised controlled trial of unmarried women with PCOS was conducted from November 2012 to March 2016. Participants were assigned to the acupuncture group (receiving EA for 16 weeks) or the control group (receiving sham acupuncture for 16 weeks), with 27 patients in each group. The pre-specified primary outcomes and all secondary outcomes, with the exception of serum levels of neurotransmitters including norepinephrine (NE), epinephrine (AD), serotonin (5-HT) and γ-aminobutyric acid (GABA), will be reported separately. Additional outcome measures selected for this secondary analysis included anxiety and depression scale scores (Zung-SAS and Zung-SDS), 36-Item Short Form (SF-36) scale scores, PCOS Quality of Life (PCOSQOL) scale scores and Chinese Quality of Life (CHQOL) scale scores. RESULTS:After the16-week intervention, an increase in serum NE and reduction in 5-HT were observed in the acupuncture group (P=0.028 and P=0.023, respectively). The serum level of GABA decreased in both groups after the interventions (both P<0.001). However, there were no significant differences between the two groups in the levels of any neurotransmitters (p>0.05). After EA treatment, SAS and SDS scores were decreased in the acupuncture group (P=0.007 and P=0.027, respectively) and were lower than those of the control group (P=0.003 and P=0.004, respectively). The SF-36 domain scores for mental health, vitality, social functioning, general health and health transition, the total CHQOL scores, and the infertility problems and body hair domains of the PCOSQOL improved significantly after EA (P<0.05). CONCLUSION:EA appears to improve symptoms of anxiety/depression and quality of life in PCOS patients and may influence serum levels of NE and 5-HT. These findings should be interpreted with caution, given the secondary nature of the outcome measures reported herein. TRIAL REGISTRATION NUMBER:NCT01812161; ChiCTR-TRC-12002529. 10.1136/acupmed-2017-011615
    Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway. Journal of integrative medicine OBJECTIVE:Moxibustion, a common therapy in traditional Chinese medicine, has potential benefits for treating decreased ovarian reserve (DOR). The present study investigates the protective effect of moxibustion in a rat model of DOR and explores the possible mechanisms. METHODS:Sixty-four female Sprague-Dawley rats were randomly divided into four groups: control, DOR, moxibustion (MOX), and hormone replacement therapy (HRT). The DOR rat model was established by intragastric administration of 50 mg/kg Tripterygium glycoside suspension (TGS), once daily for 14 days. MOX and HRT treatments were given from the day TGS administration was initiated. The ovarian reserve function was evaluated by monitoring the estrus cycle, morphological changes in ovaries, levels of serum estradiol (E), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), pregnancy rate and embryo numbers. Terminal-deoxynucleotidyl transferase-mediated nick-end-labeling staining was used to identify ovarian granulosa cell apoptosis, while the protein and mRNA expressions of Bax, B-cell lymphoma-2 (Bcl-2), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in ovarian tissues were examined by immunohistochemistry, Western blot and quantitative reverse transcription-polymerase chain reaction. RESULTS:Compared with the DOR group, MOX improved the disordered estrous cycle, promoted follicular growth, reduced the number of atresia follicles, increased the concentrations of serum E and AMH, and decreased serum FSH and LH concentrations. More importantly, the pregnancy rate and embryo numbers in DOR rats were both upregulated in the MOX treatment group, compared to the untreated DOR model. Further, we found that the MOX group had reduced apoptosis of ovarian granulosa cells, increased Bcl-2 expression and reduced expression of Bax. Furthermore, the PI3K/AKT signaling pathway was triggered by the moxibustion treatment. CONCLUSION:Moxibustion improved ovarian function and suppressed apoptosis of ovarian granulosa cells in a rat model of DOR induced by TGS, and the mechanism may involve the PI3K/AKT signaling pathway. 10.1016/j.joim.2022.01.007
    The effect of Bushen Culuan Decoction on anovulatory infertile women among 6 different diseases: a study protocol for a randomized, double-blinded, positively controlled, adaptive multicenter clinical trial. Trials BACKGROUND:Anovulation is one of the main causes of female infertility. This study will evaluate the effectiveness and safety of Bushen Culuan Decoction for anovulatory infertility caused by six diseases, including anovulatory abnormal uterine bleeding, polycystic ovarian syndrome, hyperprolactinemia, luteinized unruptured follicle syndrome, corpus luteum insufficiency, and premature ovarian insufficiency. METHODS:This is a randomized, double-blinded, double-dummy, parallel, positively controlled, adaptive, multicenter clinical trial. All participants will be randomly allocated by a central randomization system to the treatment group or the control group in a 1:1 ratio. The treatment group will undergo a 14-day treatment with Bushen Culuan Decoction 13 g three times a day and a 5-day treatment with clomiphene citrate placebo tablets 50 mg once a day starting on day 5 of every menstrual period. The control group will undergo a 14-day treatment with Bushen Culuan Decoction placebo 13 g three times a day and a 5-day treatment with clomiphene citrate tablets 50 mg once a day from day 5 in every menstrual period. The whole treatment will last through 3 menstrual periods or 6 menstrual periods, depending on whether ovulation is regained in the first 3 menstrual periods. All statistical analyses will be performed in SPSS 21.0 (SPSS, Chicago, Illinois, USA), and a p value < 0.05 will be considered statistically significant. DISCUSSION:The objective of this RCT is to evaluate whether Bushen Culuan Decoction enables a higher pregnancy rate than clomiphene citrate in women with anovulatory infertility and to identify the anovulatory diseases for which Bushen Culuan Decoction has higher effectiveness .This study has been approved by the Medical Ethics Committee of Xiyuan Hospital China Academy of Chinese Medical Sciences (No. 2017XLA037-2). The results of this study will be offered for publication in peer-reviewed journals. TRIAL REGISTRATION:ClinicalTrials.gov NCT03709849 . Registered on 19 November 2018. 10.1186/s13063-022-06289-7
    Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial. Wu Xiao-Ke,Stener-Victorin Elisabet,Kuang Hong-Ying,Ma Hong-Li,Gao Jing-Shu,Xie Liang-Zhen,Hou Li-Hui,Hu Zhen-Xing,Shao Xiao-Guang,Ge Jun,Zhang Jin-Feng,Xue Hui-Ying,Xu Xiao-Feng,Liang Rui-Ning,Ma Hong-Xia,Yang Hong-Wei,Li Wei-Li,Huang Dong-Mei,Sun Yun,Hao Cui-Fang,Du Shao-Min,Yang Zheng-Wang,Wang Xin,Yan Ying,Chen Xiu-Hua,Fu Ping,Ding Cai-Fei,Gao Ya-Qin,Zhou Zhong-Ming,Wang Chi Chiu,Wu Tai-Xiang,Liu Jian-Ping,Ng Ernest H Y,Legro Richard S,Zhang Heping, JAMA Importance:Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective:To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants:A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions:Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures:The primary outcome was live birth. Secondary outcomes included adverse events. Results:Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance:Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration:clinicaltrials.gov Identifier: NCT01573858. 10.1001/jama.2017.7217
    [Advantages of integrated Chinese and western medicine in diagnosis and treatment of anovulatory infertility due to kidney deficiency and blood stasis]. Ma Kun Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica Under the guidance of the theory of &quot;kidney governing reproduction&quot;, this study demonstrated the mechanism of six types of ovulatory infertility caused by kidney deficiency and blood stasis, including anovulatory bleeding, polycystic ovary syndrome, hyperprolactinemia, luteinized unruptured follicle syndrome, luteal phase deficiency, and primary ovarian insufficiency. A series of studies have confirmed that integrated Chinese and western medicine can increase the responsiveness of the ovaries to gonadotropins and improve ovarian function by regulating the effects of estradiol(E_2), prolactin(PRL), and reducing follicle-stimulating hormone(FSH), luteinizing hormone(LH), progestin(P), and testosterone(T). It can also improve ovulation rate and pregnancy success rate by promoting follicle development, discharging, and synchronizing endometrial growth. This study illustrated the diagnosis and treatment of ovulatory infertility caused by kidney deficiency and blood stasis with integrated traditional Chinese and Western medicine in the &quot;disease-syndrome-symptom&quot; research mode, and highlighted the traditional Chinese medicine(TCM) idea of differentiating diseases based on syndromes and unique advantages of the combination of disease differentiation and syndrome differentiation, and interpreted TCM principle of &quot;treating different diseases with the same method&quot;. 10.19540/j.cnki.cjcmm.20210319.501
    How does acupuncture affect insulin sensitivity in women with polycystic ovary syndrome and insulin resistance? Study protocol of a prospective pilot study. Zheng Yanhua,Stener-Victorin Elisabet,Ng Ernest H Y,Li Juan,Wu Xiaoke,Ma Hongxia BMJ open INTRODUCTION:Hyperinsulinaemia and insulin resistance (IR) are key features of polycystic ovary syndrome (PCOS) and metabolic syndrome. The effect of 5 weeks of acupuncture treatment has been investigated in a completed prospective pilot trial (Clinicaltrials.gov: NCT01457209), and acupuncture with electrical stimulation applied to insulin-resistant rats with dihydrotestosterone-induced PCOS was shown to improve insulin sensitivity. Therefore, we now aim to conduct a prospective pilot study to evaluate whether using the same acupuncture treatment protocol given over a longer period of time (6 months) than in the previous pilot trial will improve insulin sensitivity in women with PCOS and IR. Our hypothesis is that acupuncture with combined manual and low-frequency electrical stimulation of the needles will improve insulin sensitivity in women with PCOS and IR. METHODS/ANALYSIS:This is a prospective pilot trial. A total of 112 women with PCOS and IR will be recruited and categorised according to their body mass index (BMI) as normal weight (BMI=18.5-23 kg/m(2)) or as overweight/obese (BMI>23 kg/m(2)). Acupuncture will be applied three times per week for 6 months at 30 min per treatment. The primary outcome will be the change in insulin sensitivity before and after 6 months of acupuncture treatment, as measured by an oral glucose tolerance test. ETHICS/DISSEMINATION:Ethical approval of this study has been granted from the ethics committee of the First Affiliated Hospital of Guangzhou Medical University (No. 2013039). Written and informed consent will be obtained from each patient before any study procedure is performed, according to good clinical practice. The results of this trial will be disseminated in a peer-reviewed journal and presented at international congresses. TRIAL REGISTRATION NUMBERS:NCT02026323 and ChiCTR-OCH-13003921. 10.1136/bmjopen-2015-007757
    [Effects of Bushen Tongmai recipe on expression of IRS-1 Ser307 in polycystic ovarian syndrome rats accompanying with insulin resistance]. Xie Yang,Huang Dongmei,Li Qiong,Lu Fuer,Xu Lijun,Zou Xin,Zhao Yan Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica OBJECTIVE:To investigate the effects of Bushen Tongmai recipe on the phospharylation expression of insulin receptor substrate-1 Ser307 (IRS-1 Ser307) in insulin target tissues of polycystic ovarian syndrome (PCOS) rats accompanying with insulin resistance (IR). METHOD:Rats of model of PCOS accompanying with IR were randomly divided into the model group and the traditional Chinese medicine (TCM) group. Meanwhile, a group of 13 rats of the same age was considered as the normal control group. The TCM group was administered with BSTMR. Half of each group was given insulin injection through portal vein in late estrus. Another half didnt receive insulin injection. The phospharylation levels of IRS-1 Ser307 in liver and fatty tissues were measured by Western blot. The phospharylation level of IRS-1 Ser307 in ovary tissue was measured by immunohistochemistry. RESULT:The phospharylation expressions of IRS-1 Ser307 in liver, fat and ovary in the model group were higher than those in the normal group (P<0.05, P<0.01); those criteria in the TCM group were lower than those in the model group (P<0.05). After insulin stimulation, the phospharylation expressions of IRS-1 Ser307 were higher than those before insulin stimulation (P<0.05). CONCLUSION:Bushen Tongmai recipe could attenuate the phospharylation expression of IRS-1 Ser307 and then enhance insulin signal transduction, which may be one of the mechanisms of Bushen Tongmai recipe in improving PCOS accompanying with IR. 10.4268/cjcmm20100521
    Effectiveness of herb-partitioned moxibustion combined with electroacupuncture on polycystic ovary syndrome in patients with symptom pattern of kidney deficiency and phlegm-dampne. Zhao Qing-Yi,Sun Yi,Zhou Jing,Gao Yan-Ling,Ma Gui-Zhi,Hu Zhi-Hai,Wang Yi,Shi Yin Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan OBJECTIVE:To observe the effect of herb-partitioned moxibustion combined with electroacupuncture on polycystic ovary syndrome (PCOS) in patients with symptom pattern of kidney deficiency and phlegm-dampness. METHODS:Totally 62 PCOS patients who met the inclusion criteria were randomly divided into intervention group and control group. In the intervention group, acupoints were subjected to (43 ± 1) ℃ herb-partitioned moxibustion and electroacupuncture treatment. In the control group, acupoints were subjected to (37 ± 1) ℃ herb-partitioned moxibustion and sham electroacupuncture treatment. Treatment was provided 3 times per week for 12 weeks, and the treatment was stopped during menstruation. After the treatment, the clinical efficacy, the Traditional Chinese Medicine (TCM) symptom pattern score, basal body temperature (BBT) levels, menstrual cycle, and related sex hormone levels of the two groups were evaluated. RESULTS:Sixty patients were eventually included in the study (30 in the intervention group and 30 in the control group). There were not obvious between-group differences in the baseline efficacy parameters (all P > 0.05). (a) After treatment, the two groups have improved in terms of clinical efficacy, TCM symptom pattern score, menstrual cycle and, BBT (P < 0.01, < 0.05), and the intervention group was better than the control group (P < 0.01, < 0.05). (b) In the intervention group, the estradiol (E2) and P450 aromatase (P450arom) levels were increased (all P < 0.05), the testosterone (T) level was decreased (P < 0.05), and the luteotropic hormone (LH) and anti-Müllerian hormone (AMH) levels were significantly decreased (P < 0.01). In the control group, E2 level was increased (P < 0.05), and LH level was decreased (P < 0.05). After treatment, the T, LH, and AMH levels of the intervention group were decreased compared with those of the control group (all P < 0.05), and the P450arom level was increased (P < 0.05). CONCLUSIONS:Herb-partitioned moxibustion combined with electroacupuncture can effectively improve the related clinical symptoms of PCOS patients with kidney deficiency and phlegm-dampness. Herb-partitioned moxibustion combined with electroacupuncture may inhibit the overexpression of AMH to increase the expression level of P450arom in ovarian granulosa cells, thereby reconstructing the dependence of follicular development on FSH, and finally improving abnormal follicular development and hyperandrogenism in PCOS patients with kidney deficiency and phlegmdampness. TRIAL REGISTRATION NUMBER:ChiCTR1900024182. 10.19852/j.cnki.jtcm.2021.06.017
    Network pharmacology integrated with experimental validation reveals the regulatory mechanism of action of Hehuan Yin decoction in polycystic ovary syndrome with insulin resistance. Wu Yuan-Yuan,Li Shu-Yu,Zhu Hui-Qing,Zhuang Zi-Ming,Shao Meng,Chen Fei-Long,Liu Chang-Shun,Tang Qing-Fa Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Hehuan Yin decoction (HHY), first recorded in the Jingyue Quanshu (published in 1624 A.D.), is composed of Albizia julibrissin Durazz. and Ampelopsis japonica (Thunb.) Makino. AIM OF THE STUDY:This study aimed to investigate the mechanism of action of HHY in treating polycystic ovary syndrome with insulin resistance (PCOS-IR). MATERIALS AND METHODS:Network pharmacology and molecular docking were used to predict active compounds, potential targets, and pathways for PCOS-IR treatment using HHY. Female Sprague-Dawley rats were administered letrozole (1 mg/kg) with a high-fat diet to establish a PCOS-IR model. Thereafter, symptoms, ovarian pathology, serum insulin resistance, and sex hormone levels were determined. Western blotting was used to determine the levels of PI3Kp85α, AKT, phospho (p)-AKT, and GSK3β in the ovaries of rats. RESULTS:Network pharmacology revealed 58 components in HHY and 182 potential targets that were shared between HHY and PCOS-IR. HHY could potentially treat PCOS-IR via the insulin resistance, PI3K/AKT, HIF-1, and steroid hormone biosynthesis pathways. Molecular docking revealed that PI3K, AKT1, GSK3β, IRS1, and EGFR had high affinities to HHY compounds. In the PCOS-IR rats, HHY significantly normalised the symptoms and ovarian pathology, increased follicle-stimulating hormone (FSH) and oestradiol levels in the serum, and decreased the levels of fasting plasma glucose and fasting insulin, as well as the insulin resistance index. HHY also decreased the luteinising hormone (LH) and testosterone levels and the LH/FSH ratio in the PCOS-IR rats and increased the levels of PI3K, p-AKT, and GSK3β in ovary tissue, which indicated the activation of the PI3K/AKT pathway. CONCLUSIONS:HHY can improve PCOS-IR symptoms via multiple pharmacological pathways and may be a potential alternative therapy for the treatment of PCOS-IR. 10.1016/j.jep.2022.115057
    The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Balen Adam H,Morley Lara C,Misso Marie,Franks Stephen,Legro Richard S,Wijeyaratne Chandrika N,Stener-Victorin Elisabet,Fauser Bart C J M,Norman Robert J,Teede Helena Human reproduction update BACKGROUND:Here we describe the consensus guideline methodology, summarise the evidence-based recommendations we provided to the World Health Organisation (WHO) for their consideration in the development of global guidance and present a narrative review on the management of anovulatory infertility in women with polycystic ovary syndrome (PCOS). OBJECTIVE AND RATIONALE:The aim of this paper was to present an evidence base for the management of anovulatory PCOS. SEARCH METHODS:The evidence to support providing recommendations involved a collaborative process for: (i) identification of priority questions and critical outcomes, (ii) retrieval of up-to-date evidence and exiting guidelines, (iii) assessment and synthesis of the evidence and (iv) the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation, the methodologist evaluated the quality of the supporting evidence that was then graded as very low, low, moderate or high for consideration during consensus. OUTCOMES:Evidence was synthesized and we made recommendations across the definition of PCOS including hyperandrogenism, menstrual cycle regulation and ovarian assessment. Metabolic features and the impact of ethnicity were covered. Management includes lifestyle changes, bariatric surgery, pharmacotherapy (including clomiphene citrate (CC), aromatase inhibitors, metformin and gonadotropins), as well as laparoscopic surgery. In-vitro fertilization (IVF) was considered as were the risks of ovulation induction and of pregnancy in PCOS. Approximately 80% of women who suffer from anovulatory infertility have PCOS. Lifestyle intervention is recommended first in women who are obese largely on the basis of general health benefits. Bariatric surgery can be considered where the body mass index (BMI) is ≥35 kg/m and lifestyle therapy has failed. Carefully conducted and monitored pharmacological ovulation induction can achieve good cumulative pregnancy rates and multiple pregnancy rates can be minimized with adherence to recommended protocols. CC should be first-line pharmacotherapy for ovulation induction and letrozole can also be used as first-line therapy. Metformin alone has limited benefits in improving live birth rates. Gonadotropins and laparoscopic surgery can be used as second-line treatment. There is no clear evidence for efficacy of acupuncture or herbal mixtures in women with PCOS. For women with PCOS who fail lifestyle and ovulation induction therapy or have additional infertility factors, IVF can be used with the safer gonadotropin releasing hormone (GnRH) antagonist protocol. If a GnRH-agonist protocol is used, metformin as an adjunct may reduce the risk of ovarian hyperstimulation syndrome. Patients should be informed of the potential side effects of ovulation induction agents and of IVF on the foetus, and of the risks of multiple pregnancy. Increased risks for the mother during pregnancy and for the child, including the exacerbating impact of obesity on adverse outcomes, should also be discussed. WIDER IMPLICATIONS:This guidance generation and evidence-synthesis analysis has been conducted in a manner to be considered for global applicability for the safe administration of ovulation induction for anovulatory women with PCOS. 10.1093/humupd/dmw025
    Translation and implementation of the Australian-led PCOS guideline: clinical summary and translation resources from the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Teede Helena J,Misso Marie L,Boyle Jacqueline A,Garad Rhonda M,McAllister Veryan,Downes Linda,Gibson Melanie,Hart Roger J,Rombauts Luk,Moran Lisa,Dokras Anuja,Laven Joop,Piltonen Terhi,Rodgers Raymond J,Thondan Mala,Costello Michael F,Norman Robert J, The Medical journal of Australia 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: •Diagnosis:▪when the combination of hyperandrogenism and ovulatory dysfunction is present, ultrasound examination of the ovaries is not necessary for diagnosis of PCOS in adult women;▪requires 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; and▪adolescents with some clinical features of PCOS, but without a clear diagnosis, should be regarded as "at risk" and receive follow-up assessment.•Screening for metabolic complications has been refined and incorporates both PCOS status and additional metabolic risk factors.•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. 10.5694/mja18.00656
    Fecundity among women with polycystic ovary syndrome (PCOS)-a population-based study. Persson S,Elenis E,Turkmen S,Kramer M S,Yong E-L,Sundström-Poromaa I Human reproduction (Oxford, England) STUDY QUESTION:Does the long-term fecundity of women with polycystic ovary syndrome (PCOS) differ from those without PCOS? SUMMARY ANSWER:Cumulative probability of childbirth is similar between women with and without PCOS. WHAT IS KNOWN ALREADY:PCOS is the main cause of anovulatory infertility in women after menarche. Previous studies indirectly suggest that fecundity in women with PCOS over the longer term may not be lower than in women without PCOS. STUDY DESIGN, SIZE, DURATION:This is a population-based study using four linked Swedish national registries. A total of 45 395 women with PCOS and 217 049 non-PCOS women were included. Follow-up began at the age of 18 years and continued for a maximum of 26 years, from 1989 to the end of 2015. Childbirth was the main outcome, as identified from the Medical Birth Register. PARTICIPANTS/MATERIALS, SETTING, METHODS:All women born between 1971 and 1997 who were identified with a PCOS diagnosis in the Swedish Patient Registry between 1 January 2001 and 31 December 2016 were included in the study population. Five controls per women with PCOS were randomly drawn from the Total Population Registry. The control women were born in the same year and living in the same municipality as the patient. The fecundity ratio (FR) was calculated by clustered Cox regression using a robust variance, adjusted for maternal birth period, country of birth and level of education. MAIN RESULTS AND THE ROLE OF CHANCE:The cumulative probability of childbirth was 80.2% (95% CI, 79.5-80.9%) in women with PCOS and 78.2% (95% CI, 77.9-78.5%) in those without PCOS. Adjusted FR was 0.81 (95% CI, 0.80-0.82) for first childbirth and 0.58 (95% CI, 0.57-0.60) for first childbirth following a spontaneous pregnancy. The FR for second childbirth was 0.79 (95% CI, 0.77-0.80). Women with PCOS had more than one child less frequently than the comparison group. Within the PCOS group, early age at diagnosis, later birth year, Nordic country of origin and low educational level positively influenced the FR. LIMITATIONS, REASONS FOR CAUTION:Results are not adjusted for BMI, and time from intention to conceive to first childbirth could not be captured. Data on pregnancies, miscarriages or abortions and fertility treatment are unknown for women who did not give birth during the study period. Women with PCOS who did not seek medical assistance might have been incorrectly classified as not having the disease. Such misclassification would lead to an underestimation of the true association between PCOS and outcomes. WIDER IMPLICATIONS OF THE FINDINGS:While cumulative probability of childbirth is similar between groups, women with PCOS need longer time to achieve their first childbirth. Women with PCOS have a lower FR and give birth to fewer children per woman than women without PCOS. Early diagnosis of and information about PCOS may improve affected women's reproductive potential. STUDY FUNDING/COMPETING INTEREST(S):This study was funded by the Swedish Society of Medicine. Inger Sundström Poromaa has, over the past 3 years, received compensation as a consultant and lecturer for Bayer Schering Pharma, MSD, Gedeon Richter, Peptonics and Lundbeck A/S. The other authors declare no competing interests. 10.1093/humrep/dez159
    Improvement of Insulin Sensitivity Increases Pregnancy Rate in Infertile PCOS Women: A Systemic Review. Liu Yuqi,Li Juan,Yan Zhe,Liu Dan,Ma Jinfang,Tong Nanwei Frontiers in endocrinology Background:Polycystic ovary syndrome (PCOS) is the most common cause of infertility in reproductive-age women. Insulin increases steroidogenesis, deranges granulosa cell differentiation, and affects follicle growth. However, results from randomized control trials (RCTs) were heterogeneous, and little strong evidence associated actual achievement of insulin sensitivity (IS) improvement with reproductive outcomes. Objectives:To identify evidence of the reproductive benefit of IS improvement in infertile PCOS women by analyzing eligible RCTs. Search Strategy:Different search strategies with unlimited keywords, including treatment, therapy, intervention, polycystic ovary syndrome/PCOS, insulin resistance, pregnancy, conceive, live birth, and randomized controlled trials/RCT were used in databases including Pubmed, Embase, and Web of Science to November 20th, 2021. Data Collection and Analysis:Two authors independently abstracted study details and assessed study quality. Main Results:Ten RCTs that covered different races and met the inclusion criteria were included for analysis and discussion. Clinical pregnancy rate was increased in infertile PCOS women when they had significant improvement of IS after treatment regardless of the various interventions (non-surgical). The benefits of IS improvement appeared superior in PCOS women without severe obesity. The effect of IS improvement on pregnancy rate was independent of the change of BMI. Conclusions:Nonsurgical therapeutic strategies that promote superior IS improvement may aid infertile PCOS women to increase their possibility of successful pregnancy regardless of the various interventions. The improvement of IS might be more important than the reduction of BMI in the improvement of pregnancy rate in infertile PCOS women. 10.3389/fendo.2021.657889