Infertility and PCOS
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Slide 1 :
Infertility and PCOS Erinn Myers, M4 Department of Obstetrics and Gynecology University of Tennessee Health Science Center January 28, 2007
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Learning Objectives Following the presentation “Infertility and PCOS” participants should be able to: Diagnose PCOS. Understand the differences between PCO, PCOS and PCOM. Decide on possible treatment. Exclude other problems.
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DEFINITION Inability to conceive after a year of exposure to conception. Six months > 35 years old. A disability and a disease…NOT an elective condition. Great societal and demographic impact
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Factors Male Ovarian Cervical Peritoneal Tubal Uterine Unexplained
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Ovulation An LH (luteinizing hormone) surge occurs 24 to 36 hours prior to ovulation (Follicular rupture = It is the ovary’s job to make a cyst and rupture it.) Progesterone is increasingly produced after the LH surge Secretory changes occur in the endometrium due to progesterone.
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Ovulation Pregnancy is absolute proof of ovulation. Serum progesterones are 99%+ proof of ovulation. These are done: 8 days after a positive ovulation test 7 days after ovulation on a monitor Day 21 and 24 if ovulation day is uncertain.
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Ovulation Disorders PCOS Hypothyroidism Hyperprolactinemia Weight Loss / Weight Gain
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PCOS Diagnosis Somatic Hyperandrogenism Lab Hyperandrogenism Oligo-anovulation PCOM (polycystic ovarian morphology)
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1990 NIH/NICHD PCOS diagnosis Ovulatory dysfunction Clinical hyperandrogenism and/or hyperandrogenemia Exclusion of other disorders such as Non-classical adrenal hyperplasia Androgen secreting tumor Hyperprolactinemia Thyroid
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2003 ESHRE/ASRM PCOS diagnosis At least 2 of the following features Oligoovulation or anovulation Clinical and/or biochemical signs of hyperandrogenism Polycystic ovarian morphology (sonography) Exclusion of other disorders 2003 Rotterdam ESHRE/ASRM Consensus. Fertil Steril 81:19, 2004
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PCOS Diagnosis is more clinical than lab. Androgenism (hirsute, acne, central obesity) Oligo-anovulatory PCOM (polycystic ovarian morphology) Elevated androgens Androgens decrease with age Decreased HDL and SHBG
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PCOM PCOM (polycystic ovarian morphology) > 12 follicles at 2 - 9 mm in at least 1 ovary Volume > 10cc Does not apply if on BCPs If a follicle is >10mm, repeat scan next cycle. 2003 Rotterdam ESHRE/ASRM Consensus. Fertil Steril 81:19, 2004
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PCOM PCOM (polycystic ovarian morphology)
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PCOM PCOM (polycystic ovarian morphology)
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PCOM vs. Follicles PCOM (polycystic ovarian morphology) vs. Pre- ovulatory Follicles
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Screening Tests FSH and E2 Prolactin TSH 17-OHP Lipids / HDL decreased SBHG decreased 2 hour glucose to screen for diabetes
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Exclude Non-classical 17-hydroxylase deficiency can look like PCOS HAIRAN - hyperandrogenic insulin resistance and acanthosis nigricans Adrenal tumor Cushing’s Prolactin Thyroid Pituitary insufficiency Hypothalamic amenorrhea
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Stop Using “Inappropriate LH" as a diagnosis LH / FSH ratio as it is not sufficiently predictive Fasting insulin as it is not sensitive Dexamethasone therapy can induce insulin resistance
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Utility of LH/FSH Ratio Study designed to understand the biological variability of the LH/FSH ratio in women with PCOS vs. women with normal menstruation over one full cycle Will assess the diagnostic utility of the LH/FAH ratio 10 consecutive blood samples were taken at 4 day intervals in 12 PCOS patients and 11 age and weight matched controls Cho, LW, et. al. Bio variation of the LH/FSH ratio in normal women and those with PCOS. Endocrine Abstracts (2005) 9 p80
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Utility of LH/FSH Ratio 7.6% of PCOS and 15.6% of controls had LH/FSH ratio above 3 Sensitivity 7.6% Specificity 33.7% Therefore, the biological variation of the LG/FSH ratio is at least as wide in the control group as in the PCOS group Cho, LW, et. al. Bio variation of the LH/FSH ratio in normal women and those with PCOS. Endocrine Abstracts (2005) 9 p80
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LH/FSH Ratio Study to determine the incidence of abnormal LH/FSH ratio in women with PCOS with normoinsulinemia and hyperinsulinemia Access the influence of elevated LH/FSH ratio on selected endocrine and biochemical parameters LH/FSH ratio119 patients with PCOS was calculated and underwent hormonal and metabolic analysis Banaszewska B, et. al., Incidence of elevated LH/FSH ration in PCOS women with normo- and hyperinsulinemia. Pocz Acad Med Bialymst. 2003;48:131-4
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LH/FSH Ratio 45.4% had an LH/FSH >2, Normal 55% had normal gonadotropin ratio Statistically significant differences between groups with normal and elevated LH/FSH BMI, serum insulin, LH levels Majority of women with elevated insulin had a normal LH/FSH ratio Banaszewska B, et. al., Incidence of elevated LH/FSH ration in PCOS women with normo- and hyperinsulinemia. Pocz Acad Med Bialymst. 2003;48:131-4
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LH/FSH Ratio LH/FSH ratio is not a characteristic attribute of ALL PCOS women This study found ratio to be elevated <50% Most of PCOS patients with normal gonadotropin levels also had hyperinsulinemia and obseity Patients with hyperinsulinemia and elevated LH had increased adrenal androgenic activity Banaszewska B, et. al., Incidence of elevated LH/FSH ration in PCOS women with normo- and hyperinsulinemia. Pocz Acad Med Bialymst. 2003;48:131-4
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PCOS Treatment Weight loss and exercise Clomid (clomiphene citrate) (3 months) Letrozole (Femara®) (aromatase inhibitor) (3 months) Metformin (6 months) Note that the combination of metformin and clomiphene are more productive at months 4-6 compared with months 1-3 . Gonadotropins
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PCOS Weight loss Poor results if BMI > 50 Requires a dedicated program of diet and exercise Use dieticians who work with diabetics Liposuction of cutaneous fat is not the same as loss of visceral weight Richard S. Legro, MD, Penn State College of Medicine, Hershey PCOS PG Course, ASRM, New Orleans, October 2006
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PCOS Medications BCPs may be better with thin patients that have normal HDL and SHBG Metformin causes more nausea and weight loss than metformin-XL Sibutrimine (Meridia ®) – for weight loss Androgen receptor antagonists for hirsutism Spironolactone (Aldactone®) and Flutemide (Propecia®) Ketaconazole (Nizoral®) Florinithine (Vaniqa®) cream
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Letrozole and ClomipheneBirth Defects There is no increase in birth defects for letrozole or clomiphene if used when not pregnant. Letrozole associated with fewer birth defects than clomiphene but this is not statistically significant. Tulandi T. Fertil Steril 85:1761, 2006
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PCOS Metformin Therapy – Long Term Weight Hyperandrogenism Increases Fertility Decreases Cardiac Disease Decreases Diabetes Monitor SHBG (decreased with PCO) HDL (decreased with PCO) 2 Hour Glucose
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Long Term Management BCPs may be better with a thin patient and normal HDL and SHBG
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Conclusions PCOS Diagnosis Somatic or Lab Hyperandrogenism Oligo-anovulation Polycystic Ovarian Morphology Exclude Non-classical 17-hydroxylase deficiency, HAIRAN, adrenal tumor, Cushing’s, prolactinemia, thyroid disorders, hypothal
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Department of Obstetrics and Gynecology. University of Tennessee Health Science Center. January 28,
Department of Obstetrics and Gynecology. University of Tennessee Health Science Center. January 28, 2007. Learning Objectives …www.memfert.com/PCOS%2029Jan07.ppt
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