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Infertility and PCOS. Erinn Myers, M4 Department of Obstetrics and Gynecology University of Tennessee Health Science Center January 28, 2007. Learning Objectives. Following the presentation “Infertility and PCOS ” participants should be able to: Diagnose PCOS.

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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, hypothalamic amenorrhea

  • PCOS Concepts

    • Decreased HDL and SHBG

    • LH/FSH ratio is not useful.

  • Treatment

    • Weight loss, exercise, clomiphene, aromatase inhibitors, metformin, gonadotropins


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Acknowledgement

  • Dan C. Martin, MD, UTHSC, Memphis

  • ASRM PCOS Course, New Orleans, 2006