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Sandeep Sahu et al., Endocrinol Metab Syndr 2016, 5:5(Suppl) http://dx.doi.org/10.4172/2161-1017.C1.015 conferenceseries.com 2nd World Congress on Polycystic Ovarian Syndrome October 05-07, 2016 Orlando, Florida, USA

Successful management of ovarian hyerstimulation syndrome in a patient with PCOD Sandeep Sahu and Indu Lata Sanjay Gandhi Postgraduate Institute of Medical Sciences, India

novulation and are the predominant problems in the majority of women with polycystic syndrome (PCOS). AIt constitutes a high risk for the development of ovarian hyperstimulation syndrome (OHSS) due to unacceptable rate of excessive follicle development with an increased incidence of OHSS. Ovarian hyperstimulation syndrome is an iatrogenic complication of assisted reproduction technology. The syndrome is characterized by cystic enlargement of the and a fluid shift from the intravascular to the third space. Treatment of mild to moderate OHSS is supportive; consists of observation, bed rest, provision of adequate fluids and sonographic monitoring of the size of cysts. Treatment of severe OHSS is needed ICU admission and directed at maintaining intravascular blood volume by correction of the disturbed fluid and electrolyte imbalance, relieving secondary complications of ascites and hydrothorax and preventing thromboembolic phenomena. Better outcome is with Intensive monitoring and organ support care with multidisiplinary team. We report a 35 year old nullipara presented with history of 2 year infertility with PCOD. induction with and intrauterine insemination was done. Moderate ovarian Hyperstimulation syndrome developed, that was conservatively managed. In the same cycle, patient became pregnant. Bed rest and progesterone support was advised in view of threatened abortion in early pregnancy. At around 28 weeks, etamethasone coverage and tocolysis started due to preterm labor pains which continued up to 35 weeks. At 36 weeks, emergency caesarean section was done under combined spinal epidural anesthesia, in view of absent diastolic flow in fetal umbilical artery. A live healthy male baby weighing 2.5 kg was delivered.

Biography Sandeep Sahu, MD, PDCC, MNAMS, FACEE, FICCM, ICMR-International Fellow (USA) is an Additional Professor of the Department of Anesthesiology and Critical Care & Emergency Medicine at Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow-UP. He has published 55 publications in national & international journals, Book chapters: Five in three textbooks. He presented more than 30 paper presentation and delivered more than100 lectures. He is a life member of various national & international academic societies and Editorial Board Member of IJAA , IJCA, JETS, UPISA, The Indian Anaesthetists' Forum. His Honours & Awards include: KPR Young Anaesthesiologist Award India 2014, Y. G. Bhojraj Award of ISA for best review article in IJA 2015, Betul Bursary Award and ICMR Intern Fellow Award for Biomedical Young Scientist India 2015-16.

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Notes:

Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

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Alternative splicing of the receptor in PCOS with ovulatory dysfunction Hefeng Huang Shanghai Jiao Tong University, China

ndrogen receptor is essential for healthy developing follicle, while excess intra-ovarian impair follicle growth. AHyperandrogenism is the main characteristic of polycystic ovary syndrome (PCOS), a highly prevalent endocrine disorder and major threat to women’s health. However, the etiology of is poorly understood. We describe the specific transcription of two AR splice variants, insertion (ins) and deletion (del) isoforms, in granulosa cells (GCs) of women with PCOS. Wild-type (wt) AR existed in each individual; surprisingly its transcription is comparable between PCOS and control group. Women with AR ins or del isoforms showed distinct hyperandrogenism, attenuated androgen metabolism, enhanced androgen synthesis and altered expression corresponding enzymes, and steroid 17α-hydroxylase, in GCs, particularly the former. In vitro over-expression of different AR variants in primarily cultured human GCs not only confirmed the in vivo results, but also revealed notable change of expression of folliculogenesis, steroidogenesis and ovarian structure modeling-related genes. Its underlying mechanism is an inferior ability of nuclear shuttle and DNA binding, including U1 androgen response element (ARE) of CYP19A1 gene, of AR as nuclear receptor. In conclusion alternative splicing of AR in GCs is a cause of hyperandrogenism leading to follicular arrest in PCOS.

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Polycystic ovary syndrome and infertility: An updated overview A Garavelas Genesis Athens Clinic, Greece

olycystic ovary syndrome, or PCOS, is the most common cause of female infertility related to the infertility anovulation. PIt is well known that many of the symptoms of PCOS are present before a girl has her first menstrual period and 5-10% of females age 18 to 44 are affected by PCOS in some way. PCO syndrome results from a combination of factors, including genes and environmental features. Many women are not aware that they have PCOS until they follow a diagnostic procedure on infertility or menstrual and ovulation irregularities such as amenorrhea or oligomenorrhea, heavy and anovulatory periods. The PCOS symptoms at 70% is hirsutism, severe acne, that does not respond to conventional treatments or that remains in spite of treatment, very oily skin and patches of thickened, dark brown or black skin, and 70-95% cysts on the ovaries. The hormone levels are out of balance in women with PCOS and they have, in fact, higher than normal levels of androgens and may have lower than normal levels of . The high levels of androgens can cause problems with ovarian follicle growth and development, make immature follicles on the ovaries forming large lumps or cysts. The current treatments for PCOS includes lifestyle changes, such as eating a lower calorie diet, losing weight, and getting more physical activity, oral contraceptives, antiandrogens and insulin sensitizing agents. Women with PCOS to succeed pregnancy are treated with clomiphene citrate, metformin, gonadotropins and can also try other forms of assistive reproductive technology, such as egg donation and in vitro fertilization. The surgical procedure, laparoscopic ovarian drilling, sometimes is also used. Nowadays, the PCOS related infertility, in most cases coexists with many well established male and female infertility factors, as the result for the inquiry of an infertility algorithm investigation and a step by step way of management and infertility treatment.

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Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

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Polycystic ovarian in adolescence, a neglected age! Bohaira El Geyoushi Fakih IVF, UAE

olycystic Ovarian Syndrome (PCOS) is an endocrine disorder that can affect females throughout their lifetime from puberty Pto menopause. As healthcare providers, we are aware of the long term effects of PCOS on women during their reproductive years and the co-morbidities later in life. PCOS symptoms can be quite distressing for any woman suffering with irregular periods, weight gain, acne, hair thinning and hirsutism. The impact of this symptom on young vulnerable girls growing up in this digital age, where image is everything is several folds. Many girls suffer with these symptoms in silence and do not receive a diagnosis until later in life. Puberty is a tumultuous time and with the additional burden of PCOS it can have a lasting psychological impact as well as long term health and fertility sequelae. We can empower these young girls by educating them once a diagnosis is made. This can assist in minimizing the burden of PCOS on women by providing them with the knowledge they need at an early age. It is our duty as healthcare providers both in primary care and as specialist to inform these young girls and their guardians about PCOS and its effects both in their early years and later on in life. This in turn will minimize the psychological and emotional exposure at this tender age. It will provide the future generations with the knowledge they need to deal with the burden of the disease as well the long term impact on health and fertility.

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Immunological aspects of PCOS: The road less travelled Dimitrios Kafetzis Assisted Reproduction and Gynaecology Centre (ARGC), UK

espite the significant progress made over the past decades towards defining the exact aetiology of polycyctic ovaries, Dwe are still not in a position to offer a plausible and life changing solution to women with PCOS (Polycystic Ovary Syndrome). Anovulation, subfertilty, pregnancy loss, weight control, hirsutism and diabetes keep affecting their quality of life, making PCOS a global problem. The scientific community has not focused on the immunogical side of PCOS until only a few years ago. Yet strong evidence is immunological factors that may be playing a significant role in the of the syndrome, and there is now enough studies to demonstrate that women with PCOS have increased circulatory levels of inflammatory cytokines, reduced T regulatory cell levels and higher risk of subclinical thyroidism. There are also studies to suggest that this immunological disregulation seen in women with PCOS affects early at the level of the decidua, a connection that could shed light to the higher risk of first trimester pregnancy loss experienced by PCOS patients. This presentation attempts to “join the dots” between current studies on Immunology of PCOS and everyday clinical practice and broaden the horizons of Ob/Gyns and REIs with consice and practical advice for the management of PCOS patient beyond the standard and unfortunately largely inefficient current care.

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Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

Page 61 Endocrinol Metab Syndr 2016, 5:5(Suppl) http://dx.doi.org/10.4172/2161-1017.C1.015 conferenceseries.com 2nd World Congress on Polycystic Ovarian Syndrome October 05-07, 2016 Orlando, Florida, USA

Amlodipine effect on pre-ovulatory follicle blood flow among women with polycystic ovarian syndrome: Randomized controlled trial Doaa Abdelmageed El Faham National Research Centre, Egypt

Aim: A reduction in intra-ovarian vascular resistance is necessary to achieve pregnancy in a natural cycle. The aim of this RCT was to detect whether a vasodilator calcium channel blocker like amlodipine could increase the pre-ovulatory follicular blood flow and enhance follicular maturation in women with PCOS and thus improve ovulatory outcome, which might give a better chance of conception. Patients & Methodology: 30 women received induction by clomiphene citrate (CC) were given amlodipine (amlodipine group) compared to the other 30 women who were given placebo instead of amlodipine. The pattern of pre-ovulatory follicle blood flow was studied by color and power Doppler ultrasonography pre and post drug administration on two consecutive cycles. Results: During the second cycles, the mean value of pulsatility index was lower but it didn't reach statistical significance, the mean value of resistant index of ovarian arteries was significantly lower (1.34±0.87 vs. 1.58±1.10, 0.61±0.17 vs. 0.74±0.18, respectively) in women of the amlodipine group when compared to those of the placebo group, respectively. At least one sonographically detectable mature follicle (≥18 mm) was observed in 54.5% (36/66) during the first cycle. At the second cycle, this proportion significantly rose to 86.7% (26/30) in the amlodipine group, but marginally and non-significantly to 56.7% (17/30) in the placebo group. Conclusion: Calcium channel blocker amlodipine is a promising drug that improves ovarian blood flow which we believe that it may increase the women's chance of conception.

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The genetic aspect of prevalence and phenotypic expression of polycystic ovarian syndrome Dimitrios Jim Belegris1, 2, 3 1University of Patras Medical School, Greece 2IASO, General Maternity and Gynecology Clinic, Greece 3Metropolitan Hospital, Greece

olycystic ovarian syndrome was first described in 1935, but according to scientific observations it well may be an ancient Pdisorder arising from ancestral gene variants maintained from the Paleolithic period. In modern era, there are several studies that highlight noted differences in the prevalence of the syndrome among ethnic groups. Furthermore, PCOS is a family affair. Male and female relatives and descendants of women with PCOS have been found to have a higher risk for exhibiting the hyper androgenic or metabolic characteristics of the disorder. Recently investigators from Northwestern medicine have managed to identify two new genetic susceptibility regions that appear to be unique to European women with PCOS, as well as one region also present in Chinese women with PCOS. It is remarkable that these new regions contain the gene for FSH and this indicates that the regulation of this pathway plays a significant role in the development of PCOS. Combination of knowledge and scientific observations and further research may enhance our understanding of the etiology of the polycystic ovarian syndrome, and facilitate the management of this condition. Moreover, due to the variation of the phenotypic expression of the syndrome, each patient has to be evaluated individually. A challenge remains the management of sub-fertility in women with PCOS. The Thessaloniki ESHRE/ASRM sponsored PCOS Consensus Workshop group proposed the value of therapy in women with anovulatory PCOS that may lead 70-90% of the occasions in ovulatory cycles and a conception rate of 15-20% respectively.

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Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

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Surgical management of polycystic ovary syndrome Jeffrey M Goldberg Cleveland Clinic, USA

aparoscopic ovarian drilling (LOD) has evolved from bilateral ovarian wedge resection by laparotomy, which was the only Lclinical treatment for polycystic ovary syndrome (PCOS) during the 3 decades prior to the introduction of clomiphene citrate and parenteral gonadotropins in the 1960s. Like ovarian wedge resection, LOD increases fertility by restoring ovulatory function but has the advantages of being a minimally invasive outpatient procedure with less ovarian destruction or clinically significant postoperative adhesions. It is very quick and easy to perform with common laparoscopic instruments. Unfortunately, the procedure has not been standardized as far as the number of punctures, the energy dose, duration and source or whether one or both ovaries should be treated. LOD has been shown to reverse many of the hormonal and ultrasonographic abnormalities associated with PCOS. It is indicated as an alternative to parenteral gonadotropin therapy for infertility due to anovulation which is unresponsive to oral agents such as clomiphene, letrozole and/or metformin. Pregnancy rates are similar to ovulation induction with gonadotropins but without the risk of multiple pregnancy and ovarian hyperstimulation syndrome. It is preferred by patients since multiple daily injections and frequent office visits for follicle monitoring are avoided. It has also been shown to be more cost effective. Despite these clear benefits, it is very infrequently performed in the US. More research is needed to determine the optimal surgical technique as well as long-term non-reproductive outcomes such has reduction in hirsutism, metabolic syndrome and endometrial cancer.

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Twelve years after Rotterdam consensus: We are in need for a practical but not a political classification of PCOS Mohammad Emam Mansoura University, Egypt

our sub phenotypes of polycystic ovarian syndrome (PCOS) have emerged after the definition of the syndrome according Fto a joint ASRM/ESHRE consensus meeting, in Rotterdam, 2003. Many pitfalls have resulted after this consensus, like the heterogeneity of the sub phenotype groups which lead to controversy and debate of the results of any comparative studies. Also, this consensus has neglected the role of insulin resistance, although PCOS is now recognized as an important metabolic and reproductive disorder. On the other hand this classification cannot solve the problem of cases having PCO in the absence of anovulation or hyperandrogenism (asymptomatic PCO), where these cases are not considered as having PCOS. The use of Rotterdam diagnostic criteria in the studies of PCOS has ended the debate between ASRM/ESHRE groups from the political point of view, but we are still in need of a practical not a political classification, so we tried to introduce a proposal of a novel practical classification of PCOS to minimize the previous pitfalls.

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Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

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Properly addressing a patient’s weight is a necessary component to treat PCOS patients in infertility settings Monica Moore Fertile Health, LLC, USA

olycystic ovary syndrome (PCOS) is a common endocrine disorder found in reproductive age women. Although the cause Pis uncertain, it is hypothesized that insulin resistance (IR) , and then compensatory hyperinsulinemia, is responsible for generating many of the hormonal and metabolic abnormalities found in this subset of patients. High levels of insulin potentiate ovarian androgen production, resulting in a disordered ovarian environment which is detrimental to folliculogenesis and, therefore, ovulation. In addition, it generates the clinical and/or serum signs of hyperandrogenism that affect many of these patients and can contribute to a decreased quality of life. Interventions which reduce insulin resistance, then, can improve the metabolic, reproductive and psychological consequences of PCOS. More than half of patients with PCOS are overweight or obese. Excess weight (particularly abdominal obesity) is closely linked to IR. Abdominal adipose cells are metabolically active and contribute to insulin resistance and chronic . Therefore, weight management is crucial to patients with PCOS. For many clinicians, discussing weight in their practice can be so uncomfortable that it is not done properly or at all. Clinicians must overcome this discomfort in order to discuss weight in the office setting in a sensitive manner while still underscoring the importance of weight loss or maintenance. Reproductive endocrinology (RE) offices should also strongly consider partnering with an experienced nutritionist or dietician, particularly one with an endocrine background. Finally, since PCOS is a heterogeneous condition, a multidisciplinary approach is best. In addition to a nutritionist, clinicians need to form and cultivate a referral network of complimentary care providers.

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Endometriosis in PCOS patients; the call we missed Abu Marar E Campus Lübeck, Germany

COS (Polycystic Ovary Syndrome) and endometriosis might be superimposed by each other. The prevalence of both Pdiseases coexistence varies enormously according to authors. Subtle forms of endometriosis do exist, putting it in the front between IVF treatment seeking patients but having it associated with PCOS, complicates the treatment options. Do subtle forms of PCOS exist? Accurate diagnosis of the case is the key of successful treatment, although treatment modality of PCOS is different from endometriosis. Understanding both and treating them in one case seeking IVF treatment is an endless tunnel. Here we elucidate the typical image for such cases, presenting the treatment options and finally ending up with the optimum treatment.

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Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

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Physical therapy and female sexuality in PCOS treatment Laira Ramos1, 2, 3, 4 1Períneo: Lisbon, Portugal 2Períneo: Lisbon, Brazil 3Santa Joana Endometriosis Center, Brazil 4Federal University of São Paulo, Brazil

emale sexuality is controlled by psychosocial, biological and physical factors. Women with Polycystic ovarian syndrome F(PCOS) may feel like losing their feminine identity. This change could have a negative impact in quality of life, decreasing self-worth and sexual satisfaction. Obesity, hirsutism, acne, irregularity menses and subfertility are common factors for poor body image and affecting their sexuality, they may found themselves significantly less sexually attractive. In several studies, we find women with PCOS have worse sexual function and self-assessment of health condition in comparison to controls. Pelvic floor muscle rehabilitation cannot change their complains about PCOS and will not have any effect in this syndrome; however, this treatment can help these women understand how their intimacy works. They will have a better knowledge of their body and will learn how to control their pelvic floor muscles, so they will be able to have more pleasure and to give more pleasure to their partner. It will increase their self-worth and self-assurance that certainly will improve their sexual satisfaction. Pelvic floor muscle rehabilitation also increases vaginal lubrication, treat pelvic pain and dyspareunia.

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Vitamin D supplementation decreases TGF-β1 bioavailability in PCOS: A randomized placebo- controlled trial Mohamad Irani Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, USA

Background: There is an abnormal increase in TGF-β1 bioavailability in women with polycystic ovary syndrome (PCOS), which might play a role in the pathophysiology of this syndrome. Vitamin D (VD) supplementation improves various clinical manifestations of PCOS and decreases TGF-β1 levels in several diseases including myelofibrosis. Aim: The objective of the study was to determine the effect of VD supplementation on TGF-β1 bioavailability in VD-deficient women with PCOS and assess whether changes in TGF- β1/soluble endoglin (sENG) levels correlate with an improvement in PCOS clinical manifestations. Method: Prospective, randomized, placebo-controlled trial was used. 68 VD-deficient women with PCOS who were not pregnant or taking any exogenous hormones were recruited between October 2013 and January 2015. Forty five women received 50000 IU of oral vitamin D3 and 23 women received oral placebo once weekly for eight weeks. Serum TGF-β1, sENG, lipid profile, testosterone, dehydroepiandrosterone sulfate, and insulin resistance were measured. The clinical parameters were evaluated before and two months after treatment. Results: The VD level significantly increased and normalized after VD supplementation (16.3±0.9 [SEM] to 43.2±2.4 ng/mL; P<.01), whereas it did not significantly change after placebo. After the VD supplementation, there was a significant decrease in the following: the interval between menstrual periods (80±9 to 60±6 d; P=.04), Ferriman-Gallwey score (9.8±1.5 to 8.1±1.5; P<.01), triglycerides (138±22 to 117±20 mg/dL; P=.03), and TGF-β1 to sENG ratio (6.7±0.4 to 5.9±0.4; P=.04). In addition, the TGF-β1 to sENG ratio was positively correlated with Δ triglycerides (r=0.59; P=.03). Conclusions: VD supplementation in VD-deficient women with PCOS significantly decreases the bioavailability of TGF-β1, which correlates with an improvement in some abnormal clinical parameters associated with PCOS. This is a novel mechanism that could explain the beneficial effects of VD supplementation in women with PCOS. These findings may support new treatment modalities for PCOS, such as the development of anti-TGF-β1 drugs. [email protected]

Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

Page 65 Endocrinol Metab Syndr 2016, 5:5(Suppl) http://dx.doi.org/10.4172/2161-1017.C1.015 conferenceseries.com 2nd World Congress on Polycystic Ovarian Syndrome October 05-07, 2016 Orlando, Florida, USA

Cycle segmentation with elective freeze-all, as a strategy to provide a safe and effective approach in women with PCOS undergoing IVF Nicholas Christoforidis Embryolab IVF Unit, Greece

olycystic ovarian syndrome is associated with a high risk of ovarian hyperstimulation syndrome (OHSS) in women Pseeking fertility treatment and undergoes assisted reproduction with IVF. OHSS is the single most serious complication of controlled ovarian stimulation with a wide range of manifestations, including life-threatening complications. The use of short protocols with gonadotropin releasing hormones (GnRH)-antagonists to achieve multiple follicular developments, has enabled the substitution of human chorionic gonadotropin (hCG) for final oocyte maturation with GnRH analogues, rendering the possibility of OHSS development extremely low. However, implantation rates in the same cycle following GnRH analogue trigger have not been satisfactory. In this context, the elective cryopreservation of embryos has been proposed as a safe means to avoid OHSS, at the same time, high implantation rates can be achieved with embryo transfer in a subsequent cycle, following endometrial preparation. The use of vitrification as a cryopreservation method of choice has been associated with extremely high post warming embryo survival rates. Our experience in Embryo lab Fertility Clinic is presented between 2012 and 2015, following the introduction of the "elective freeze-all strategy" as a means to provide a safe and effective IVF treatment in women with PCOS. Results suggest that moderate to severe OHSS can be eliminated, while embryo quality is not compromised following vitrification and warming of embryos for transfer. Clinical pregnancy rate appears at least as good as in fresh embryo transfers.

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Does the gut microbiome play a role in the pathogenesis of PCOS? Varykina G Thackray University of California- San Diego School of Medicine, USA

omen with polycystic ovary syndrome (PCOS) have an increased risk of metabolic disease. Studies have shown that the Whuman gut microbiome is altered in humans with obesity or type 2 diabetes and that changes in the gut microbiome may cause metabolic dysregulation. Although the Western diet has been proposed to contribute to the development of PCOS, it is unknown whether the gut microbiome is disturbed in women with PCOS. Since there is considerable variation in the human gut microbiome, we investigated whether the gut microbiome was altered in a PCOS mouse model using letrozole, a nonsteroidal , to increase endogenous testosterone levels. Five weeks of letrozole treatment resulted in hallmarks of PCOS including elevated testosterone, acyclicity, polycystic ovaries and a metabolic phenotype. Using comprehensive lab animal monitoring system (CLAMS) metabolic cages, we demonstrated that food intake; respiration and energy expenditure were not changed, indicating that these factors are not responsible for the metabolic phenotype in the PCOS mouse model. Using 16S rRNA gene sequencing, we demonstrated changes in the gut microbiome of letrozole-treated mice including a substantial reduction in bacterial species and phylogenetic richness. In addition, letrozole treatment correlated with changes in the abundance of specific Bacteroidetes and Firmicutes bacteria implicated in other mouse models of metabolic disease. Understanding the role of the gut microbiome in PCOS may provide important insight into the pathogenesis of PCOS and lead to the development of novel treatment options for women with PCOS, including pre- or probiotic therapies.

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Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

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An integrative approach to healing PCOS and infertility Aumatma Shah University of Bridgeport, USA

COS is one of the leading causes of infertility in reproductive age women. One in 2 women with infertility has PCOS, so it Pis a growing problem that needs creative solutions. There are very few conventional treatment options, and many women with PCOS will never have families. However, PCOS is treatable and manageable effectively when treated in an integrative approach. In this talk, Dr. Aumatma Shah will share the most effective natural approaches to treating PCOS in young women, as well as treating PCOS in women actively trying to conceive to support their fertility. Data presented will be based on current scientific knowledge, as well as clinical experience. This talk will leave you with clinically relevant information and expertise in treating PCOS effectively.

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Marker for assessing insulin resistance in African woman with PCOS Chantal Amisi Anifa Università Campus Bio-Medico di Roma, Italy

olycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5-10% of women in reproductive age. PInsulin resistance (IR), a prominent feature of PCOS, is found in 35-80%. Without an adequate management, IR with its compensatory hyperinsulinemia contributes directly to reproductive dysfunction, increased risk of metabolic syndrome, type 2 diabetes and cardiovascular disease in PCOS women. Given this severe implications, it is important to diagnose and treat insulin resistance as early as possible. A study conducted in Congolese women with PCOS shows that almost 1 of 2 women with PCOS is insulin resistant. And this feature is independent from overweight and obesity. Considering this fact and its burden, there is a need of an accurate marker for early detection and assessment of IR in Sub-Saharan African PCOS women. A host of methods have been described for assessing insulin resistance. The hyperinsulinemic euglycemic clamp remains the gold standard for direct measurement of insulin sensitivity. However, it is not used routinely because of the complexity of its procedure. Consequently, there has been an urgent need of surrogate markers of IR which are more applicable in large population-based epidemiological investigations. However, there is no recommended screening method for assessing IR in PCOS women. This lecture aims to focus on current existing markers of IR. In depth knowledge of these markers will help to discover which can be an easy-to-detect marker that can be used efficiently for assessing IR in Sub-Saharan African women with PCOS.

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Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

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Criteria, prevalence and phenotypes of polycystic ovary syndrome Daria Lizneva Augusta University, USA

olycystic ovary syndrome (PCOS) is a highly prevalent disorder effecting reproductive-aged women worldwide. This Ppresentation addresses the evolution of the criteria used to diagnosis PCOS; reviews recent advances in the phenotypic approach, specifically in the context of the extended Rotterdam criteria; discusses limitations of the current criteria used to diagnosis, particularly when studying adolescents and women in the peri- and postmenopause; and describes significant strides made in understanding the epidemiology of PCOS. We would discuss that although there is a high prevalence of PCOS, there is increased variability when using Rotterdam 2003 criteria, owing to limitations in population sampling and approaches used to define PCOS phenotypes. Last, we discuss the distribution of PCOS phenotypes, their morbidity, and the role that referral bias plays in the epidemiology of this syndrome.

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Immature myeloid cells in reproductive system-versus tumor angiogenesis Ofer Fainaru Rambam Medical Center, Israel

n close resemblance to other inflammatory states, gonadotropin stimulation is accompanied by influx of inflammatory cells such as neutrophils and monocyte-derived effector cells, into the ovarian stroma. Ovarian follicular development and Icorpora lutea formation are examples of the few physiologic events in which the formation of new blood vessels form existing ones, i.e. angiogenesis takes place. We have previously shown that bone marrow derived immature myeloid cells (IMCs) promote angiogenesis in both health (placentas) and disease (malignant tumors) and thus express similar proangiogenic genes. Nevertheless, the unique properties of IMCs populating these physiologic- versus malignant tissues have not been explored. We sought to determine whether ovarian stimulation and placental development leads to an influx of proangiogenic immature myeloid cells as observed in tumors. We used 4-5 week old C57Bl6J-Cx3CR1GFP/+ transgenic mice, in which granulocytic (Ly6G+) and monocytic (Ly6C+) IMCs can be defined by . We analyzed placentas from timed pregnancies and tumor tissues from B16-melanomas that were implanted subcutaneously. For ovarian hyperstimulation, we treated mice with 20U pregnant mare serum gonadotropins (PMSG) for 2 days. On day 3, human chorionic gonadotropin (HCG) (5U) was injected to induce ovulation. Control unstimulated mice were treated with sham injections. Harvested tissues were weighed and enzymatically digested. Single cell suspensions were immune-stained using fluorescently labeled anti-CD11b, Gr-1, CD11c, major histocompatibility II (MHCII), CD45, Ly6G and Ly6C, and analyzed by flow cytometry. For global gene expression, IMCs were isolated by flow cytometry, RNA prepared and analyzed by affymetrix gene microarrays. Validation of single gene expression was performed by qPCR. Analysis of the subpopulations of IMCs revealed a significant enrichment (over 2-fold, P<0.01) of the Ly6Gmed/Ly6Chigh monocytic IMC fraction in tumor derived CD45+ hematopoietic cells compared to placenta, paralleled by a concomitant, more than 2-fold decrease (P<0.01) of the Ly6Ghigh/Ly6Cmed granulocytic IMC subpopulation. In gonadotropin stimulated ovaries, we observed a ~2.5 fold increase in Ly6Ghigh/Ly6Cmed granulocytic IMCs compared to unstimulated controls. Tumor derived- and gonadotropin- stimulated ovaries derived Ly6Gmed/Ly6Chigh IMCs expressed low levels of Cx3CR1 compared to the same cell population in placentas and unstimulated ovaries. Decreased expression of Cx3CR1 within IMCs has been shown to delineate a cellular population that actively contributes to tumor progression. We next assessed the global transcriptional signature of tumor derived IMCs (T-IMCs) compared to placental IMCs (P-IMCs). Analysis of the top overexpressed genes in T-IMCs revealed several key players in tumor angiogenesis including Sema3a, and matrix metalloproteinases such as Mmp2, Mmp3, Mmp13 and Mmp14, as well as genes that are involved in cancer progression and cell proliferation. Of note, various genes that were up-regulated in P-IMCs were shown to play a role in reproductive tissue angiogenesis, including Serpine1, Arg1, and Flt1. In conclusion - IMC subpopulations diverge in tumor versus reproductive tissues, favoring monocytic IMCs in the former and granulocytic IMCs in the latter. This divergence is associated with unique expression of proangiogenic genes. Selective targeting of these genes may thus be further investigated as selective angiogenic therapies for cancer, placental disease, and ovarian-hyperstimulation.

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Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

Page 68 Endocrinol Metab Syndr 2016, 5:5(Suppl) http://dx.doi.org/10.4172/2161-1017.C1.015 conferenceseries.com 2nd World Congress on Polycystic Ovarian Syndrome October 05-07, 2016 Orlando, Florida, USA

Successful PCOS weight loss; so much more than calories in, calories out Rebecca Harwin RMIT University, Austraila

ften, the advice for women with polycystic ovary syndrome trying to lose weight is the rehashed and over simplified; Oeat less and exercise more. This fails for most, contributing further to the disempowerment and low self-esteem already experienced by a large majority of sufferers of this common syndrome. So is a calorie a calorie? And what else can we do to transform the dismal rates of weight loss to maximize permanent success? And how do two of the major drivers of PCOS in insulin resistance and inflammation contribute to weight gain, and how can we use this knowledge to help women succeed in their weight loss journey? Research shows exercise including weights and interval training, receiving sufficient quality and quantity of sleep, reducing stress, ensuring sufficient nutrition to enable optimal insulin, thyroid and whole body function, are all critical. The right food types at the right time should be a focus, rather than simply calorie counting. Research shows protein increases satiation and naturally reduces calorie intake; sufficient magnesium, shown to be deficient in women with PCOS, helps regulate insulin function; selenium, iodine, zinc are critical for thyroid function, and with hypothyroidism more common in PCOS and contributing to weight gain, needs to be addressed. Prof Patrice Cani showed that altered gut function and dysbiosis increase obesity, and experience shows that improving digestive health can reduce inflammation, improve insulin sensitivity and aid weight loss.

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Age and insulin resistance in PCOS Sarantis Livadas Metropolitan Hospital, Athens, Greece

olycystic ovary syndrome (PCOS) represents a moving spectrum of hormonal to metabolic abnormalities, as women with Pthe syndrome are aging. Hormonal abnormalities, anovulation, and hyperandrogenic signs were predominant during the early years of PCOS and fade away with the years. Metabolic abnormalities and insulin resistance (IR) remain throughout the PCOS life cycle; however, it is unclear as to how they change, as women with the syndrome are aging. We have evaluated the changes in IR and its associations with clinical, biochemical, hormonal, and ultrasound findings in a large cohort of women with PCOS (1345) and controls (302), as they are aging. It was found that in PCOS, age was negatively and BMI positively associated with IR. Furthermore, when data were stratified with regard to the BMI status, a negative association of age with IR was found in lean, normal, and overweight patients, which was neutralized in obese patients. Free androgen index and BMI were positively associated with IR in all age quartiles. When IR values were plotted according to BMI subgroups at different age quartiles, a significant gradual decrease in IR was observed in normal and overweight but not obese women across age quartiles. This work shows for the first time that aging increases IR in obese but not in lean and overweight women with PCOS. As BMI and androgens are positively associated with HOMA-IR and androgens decline through time, it appears that if women with PCOS do not become obese they may exhibit a better metabolic profile during their reproductive years. Accordingly, the common belief that PCOS is leading to DM through years should be reconsidered in lean subjects. Furthermore, physicians should encourage life style modifications and weight loss to their young PCOS patients.

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Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

Page 69 Endocrinol Metab Syndr 2016, 5:5(Suppl) http://dx.doi.org/10.4172/2161-1017.C1.015 conferenceseries.com 2nd World Congress on Polycystic Ovarian Syndrome October 05-07, 2016 Orlando, Florida, USA

Metformin: Friend or foe of the polycystic ovary? Suman Rice St. George’s, University of London, UK

olycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in women. It is diagnosed by Phyperandrogenemia, menstrual disturbances i.e., oligo- or anovulation, and/or polycystic ovaries on ultrasound (Rotterdam criteria). It is associated with insulin resistance, hyperinsulinemia and obesity. In the USA, the medical cost of its diagnosis and treatment during 2005 was around $4 billion, with a similar prevalence in the UK. With increasing rates of obesity, the number of women diagnosed with PCOS is likely to rise. The defining abnormality and the morphological feature of the polycystic ovary is the increase in the number of follicles compared with normal ovaries. The follicles in these ovaries over-produce androgens, leading to hyperandrogenemia. The high insulin levels present in a substantial number of women with insulin-resistant PCOS further exacerbate the over-production of androgens. Metformin, an insulin sensitizer, is widely prescribed in PCOS is primarily aimed at improving insulin sensitivity. It is well established however, that metformin can decrease hyperandrogenemia, improve menstrual cycles and ovulation rates without major changes of systemic insulin sensitivity. Could metformin act directly on the ovary? This talk will outline numerous lines of evidence from in vitro studies on human ovarian cells, showing that metformin directly alters ovarian steroidogenesis- in terms of androgen and oestrogen output. It can also alter insulin signaling in these cells affecting glucose uptake and hence potentially follicle growth. We will discuss whether this can be translated to an evidence-based approach to metformin’s use in treating women with PCOS.

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Endocrinol Metab Syndr Volume 5, Issue 5(Suppl) ISSN: 2161-1017 EMS, an open access journal PCOS 2016 October 05-07, 2016

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