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8/10/2019 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