Infertilitas Wanita 2013

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    Early Signs: AdolescencePolycystic ovarian syndrome is the most commonendocrinopathy in adult women, and is emerging as a commoncause of menstrual disturbances in the adolescent population

    Normal pubertal events include:

    Oligomenorrhea, hirsutism, acne, and weight gain

    Insulin resistance has reportedly increased in last decade

    Pediatric Endocrinologists trending towards an earlier work-upthen compared to traditional practice of waiting 2-years post-menarche

    Guttmann-Bauman I, Journal of Pediatric Endocrinology &Metabolism, 2005.

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    Genetic Link Familial clustering of PCOS common

    1 st degree relatives of patients with PCOS may be at high risk fordiabetes and glucose intolerance

    Mothers and sisters of PCOS patients have higher androgen levelsthan control subjects

    Franks S et al, International Journal of Andrology, 2006.

    Yildiz BO et al, Journal of Clinical Endocrinology & Metabolism, 2003.

    PCOS is a genetically determined ovarian disorderthe heterogeneity can be explained on the basis of

    interaction of the disorder with other genes and withthe environment.

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    PCOS: Metabolic Disorder Insulin Resistance

    High association with PCOS

    10% have Type 2 Diabetes

    30%-35% have Impaired Glucose Tolerance (IGT)

    Obesity 50% of PCOD patients are obese

    Amplifies biochemical and clinical abnormalities of PCOS

    Dunaif A, Endocrinology Review, 1997.

    Ehrmann DA et al, Diabetes Care, 1999.

    Legro RS et al, Journal of Clinical Endocrinology & Metabolism, 1999.

    Goldzieher JW, Young RL, Endocrinology Metabolism Clinics of North America, 1992.

    Kiddy DS et al, Clinical Endocrinology, 1990.

    Wh h i f NAFLD

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    obesity

    ste tosis

    ste tohep titis

    cirrhosis

    liver-related morbidity and mortality

    fibrosis50%

    15%~30%

    30%~40%

    Patrick L. Altern Med Rev, 2002, 7:276-291

    50%

    33%

    What are the settings for NAFLD

    metabolic disorders

    T2DM

    CVD, malignancy

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    Relationship between Obesity and Immune Response:

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    Reciprocal mechanisms regulating immunity andhealth span

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    PCOS: Metabolic Disorder Endometrial Cancer

    Long-term follow-up of 786 PCOS women found an increased risk of endometrial cancer

    Women >50 yrs of age with endometrial cancer, PCOS (62.5%) more prevalent than not(27.3%; P=0.033 )

    Cardiovascular Disease PCOS is characterized by endothelial dysfunction and resistance to vasodilating action of

    insulin

    Increased risk of myocardial infarction in PCOS women than age-matched controls

    Wild S et al, Human Fertility, 2000.

    Pillay OC et al, Human Reproduction, 2006.

    Paradisi G et al, Circulation, 2001.

    Dahlgren E et al, Acta Obstetricia et Gynecologica Scandinavica, 1992.

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    Sleep Apnea Increased Sleep Disordered Breathing (SDB) and daytime

    sleepiness in PCOS vs. controls

    Depression Higher prevalence in PCOS patients, associated with higher

    body mass index (BMI, P=0.05) and greater insulin resistance(P=0.02)

    Vgontzas AN et al, Sleep Medicine Reviews, 2005.

    Rasgon NL et al, Journal of Affective Disorders, 2003.

    PCOS: Metabolic Disorder

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    Pregnancy Complications

    Spontaneous Abortions Increased in high BMI/PCOS patients

    Impaired Glucose Tolerance

    Gestational Diabetes

    Hypertension

    Small for Gestational Age

    Wang JX et al, Human Reproduction, 2001.

    Turhan NO et al, International Journal of Gynecology & Obstetrics, 2003.

    Bjercke S et al, Gynecologic and Obstetric Investigation, 2002.

    Weerakiet S et al, Gynecological Endocrinology, 2004.

    Sir-Petermann T et al, Human Reproduction, 2005.

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    Adip ose-immu ne interactions .2008 Jour n al of Leukocyte Biology 84:882-894.

    Comorbid conditions associated with obesity

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    Comorbid conditions associated with obesity

    Both Type I and Type 2

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    White Adipose Tissue (WAT) Adipocyte Production of Bioactive Substances

    I f ili

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    Infertility

    >75% of women with anovulation infertility

    Follicular arrest Impaired selection of dominant follicle

    Risk of multiple pregnancy with treatment

    Franks et al, International Journal of Andrology, 2006.

    Webber LJ et al, Lancet, 2003.

    Jonard S, Dewailly D, Human Reproduction Update, 2004.

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    PCOS: Weight Loss

    Frequency of obesity in women with anovulation and PCO:30%-75%

    Six month weight-loss program for overweight anovulatory

    women Lost an average of 6.3 kg (13.9 lbs) Decreased fasting insulin and testosterone levels

    92% resumed ovulation (12/13)

    85% became pregnant (11/13)

    Ehrmann DA, New England Journal of Medicine, 2005.

    Clark AM et al, Human Reproduction, 1995.

    I f ili T

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    Infertility Treatments

    Step-by-step. . . . If BMI elevated, loss of at least 5% body weight

    Ovulation induction (OI) with clomiphene citrate

    Insulin sensitizer as single agent

    Insulin sensitizer + clomiphene

    Gonadotropin therapy, FSH hormone

    Gonadotropins + insulin sensitizer

    In vitro fertilization (IVF) single embryo transfer

    Kim LH et al, Fertility and Sterility, 2000.

    PCOS: Stimulated Cycles

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    PCOS: Stimulated Cycles

    PCOS patients are often high responders to medications, Clomid and FSH

    High risk of multiple pregnancy

    Ovarian hyperstimulation syndrome (OHSS) IVFsingle embryo transfer

    .

    .

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    Conclusions

    PCOS is a multifaceted condition Varying presentations

    Begins in adolescence

    Long-term consequences Genetic and pre-natal implications

    Metabolic Disorder

    Cosmetic issues

    Reproductive complications. cycle irregularity / bleeding / endometrial cancer

    Infertility Common endocrinopathy in pre-menopausal women, causing menstrual

    irregularities and hirsutism

    Multiple treatments available with potentially successful outcomes

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    Thank you