Polycystic Ovarian Syndrome in Infertility
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112 Ameet Patki Reviews Polycystic ovarian syndrome in infertility Ameet Patki1 Sri Lanka Journal of Obstetrics and Gynaecology 2012; 34: 112-119 Introduction Polycystic ovarian syndrome (PCOS) is a condition of unexplained hyperandrogenic chronic anovulation that most likely represents a heterogenous disorder. About 10% of women in the reproductive age group suffer from this disorder. Many adolescent girls and young adults seek consultation because of this disorder. It’s etiology is as yet undefined, and therapy remains largely symptomatic and empirical. PCOS is associated with metabolic sequelae including risk of diabetes and cardiovascular disorders and hence needs attention to these sequlae. Till 2003 diagnostic criteria for PCOS were varied and often confusing. However the Joint European Society of Human Reproduction and Embryology and The American Society for Reproductive Medicine ESHRE/ASRM Figure 1. USG showing polycystic ovary. sponsored consensus meeting in Rotterdam in 2003 accepted that PCOS consists of the presence of any 2 Etiology: Genetic studies have demonstrated a link of the 3 criteria. Oligo- and/or anovulation, clinical between PCOS and metabolic disturbances such as and /or biochemical evidence of hyperandrogenism disordered insulin metabolism indicating that the and the presence of polycystic ovaries on ultrasound PCOS may be a manifestation of a complex genetic examination. Other etiologies like congenital adrenal disorder. No gene or specific environmental substance hyperplasia, Cushing’s syndrome, and androgen has been identified. Selective insulin resistance may 1 secreting tumours need to be excluded . Ultrasonographic be central to the etiology of PCOS5. Thus compensatory scanning of women with unexplained hyperan- hyperinsulinaemia may result in decreased levels of drogenic chronic anovulation frequently reveal serum hormone binding globulin (SHBG), and serve 2 ovaries that are polycystic . Sonography shows ovarian as a trophic stimulus to androgen production in the enlargement, multiple (>10 mm) small follicles at the adrenals and ovaries and have a direct effect on the periphery with increased echogenicity. However hypothalamus causing an abnormally stimulated polycystic ovaries are a non-specific finding often noted appetite and increased gonadotropin secretion. in women with no endocrine or metabolic abnormalities. Presently, the view held for the occurrence of Incidence: The incidence is influenced by the nature PCOS attributes it to enhanced serine phosphorylation of the population being assessed. Studies in which unification theory which in turn leads to increased ultrasound examination for presence of polycystic CYP17 activity in the ovary (hyperandrogenism) ovaries were conducted reveal a prevalence rate of and reduced insulin receptor activity peripherally approximately 20 to 30% in Caucasian women in the (insulin resistance) leading in turn to the endocrine 3 reproductive age . There are significant racial dysfunction of PCOS6. difference, and as, compared to white population the prevalence of PCOS is found to be higher in the ethnic groups. In the South Asians living in the UK the Normal ovulation requirements: prevalence reported was 52%4. • Competent hypothalamic-pituitary-ovarian axis • Coordinated activities of gonadotropins, 1 Consultant Obstetrician and Gynaecologist, Sir steroids, inhibin, activin, insulin-like growth Harkisondas Hospital and Research Centre, Mumbai, factor and their binding proteins, proteases and India. prostaglandins. Sri Lanka Journal of Obstetrics and Gynaecology Polycystic ovarian syndrome in infertility 113 Pathophysiology: Until date there is no accepted Clinical Manifestations: These women commonly theory as to the pathogenesis of PCOS. Because of the present with infertility or menstrual disturbances like diverse nature of the findings, it is unlikely that any oligomenorrhoea and amenorrhoea, obesity and single factor will explain the entire gamut of changes hirsutism. associated with PCOS. It appears more plausible that many factors trigger the occurrence of PCOS, some A great deal of attention has been focused on the more common than others. Once established, there is risks of ovulation induction in these women with a well described chronicity and self perpetuating PCOS because of the enhanced risks of ovarian hyper- mechanism of the syndrome. It is clear therefore that stimulation, multiple pregnancy, and first trimester PCOS is a lifelong situation in which possibly genetic pregnancy losses. During pregnancy there is an factors, endocrine dysfunction and metabolic sequelae increased risk for gestation diabetes, hypertension, play a significant role. The PCOS state may be tem- and preterm birth particularly in the presence of porarily interrupted by hormonal therapy, pregnancy multiple gestation7,8. Chronic anovulation, obesity, or ovarian ablative surgery. An important advance in carbohydrate intolerance, hyperinsulinaemia and our understanding of this syndrome has been the decreased levels of SHBG are all associated with realization of the pivotal role of insulin resistance in endometrial cancer in later years9. Hence the rational perpetuating the PCOS status. Insulin resistance represents a unifying component of the syndrome that approach should be to improve the carbohydrate is present as a common denominator not only in obese metabolism and thus reduce the endogenous pro- PCOS, but also in adolescent girls with hyperan- duction of excess of insulin. Metformin is effective in drogenism, in women with multi-follicular ovaries, improving the glucose metabolism by multivarious and in apparently normal women with polycystic approaches, and thus revert the PCOS subject to ovaries. The main characteristic of insulin resistance normal insulinaemic status. Once the axis has in PCOS is that it is a partial resistance which involves been down regulated, the hyperandrogenemia is metabolic activities of insulin but does not prevent effectively controlled permitting regular ovulation insulin effect on its receptors on the ovary, or the effect and conception. Hence there is absence of ovarian on insulin SHBG and the hepatic production of insulin hyperstimulation, less vigilante ovulation monitoring, growth factor-1 (IGF-1). The main effect of insulin on simplicity of drug administration and improved cost- the ovaries is not only to increase androgen pro- effectiveness of therapy. Further, there is a reduction duction, but also to derange the regulation of androgen in rates of pregnancy complications and an increase synthesis so as to prevent the down regulation of the in the take home baby rate. LH receptors leading to increased production of androgens and estrone which coupled with insulin Women and particularly obese women with effect of lowering SHBG leads to hyperestrogenism hyperinsulinaemia are at an increased risk of deve- and FSH levels. loping hypertension, dyslipidaemia and impaired glucose tolerance and type II diabetes meillutus. This A genetic basis for the development of PCOS has cluster of symptoms being referred to as the metabolic been suspected, however despite the high prevalence X syndrome may increase the risk of cardiovascular of PCOS within families, no clear cut mode of inheritance has been established. disease in later life. Summary of endocrine dysfunction: Differential diagnosis: The clinician must consider several possibilities including – • Hypersecretion /Elevation of LH • Exogenous androgens • Hyperinsulinemia • Nonclassical adrenal hyperplasia • Androgen excess • Androgen secreting tumours • Disturbed hypothalamic – pituitary – ovarian axis • Cushing’s syndrome • Ovarian hyperthecosis • Acromegaly • High levels of intraovarian androgens • Genetic defects in insulin action • Follicular atresia • Primary hypothalamic amenorrhoea • Anovulation • Primary ovarian failure • Menstrual irregularity • Thyroid dysfunction • Infertility. • Prolactin disorders. Vol. 34, No. 3, 2012 114 Ameet Patki Diagnostic evaluation and work-up: – Thickened tunica albugenea • Routine physical examination: – Multiple small cysts ( 12 foliclles) of 0.2-0.9 cms. in each ovary • BMI (Body Mass Index) – 25-30 is considered – Absence of dominant follicle overweight, > 30 is obese. – Thickened stroma (hyperthecosis) • Waist-Hip Ratio to determine body fat distri- – Resting or follicular endometrium bution. Values > 0.72 are abnormal. • Presence of stigmata of hyperandrogenism or Treatment of polycystic ovary syndrome: insulin resistance – acne, hirsutism, androgenic Goals: alopecia. – Prevent endometrial hyperplasia, atypia/ • Blood pressure recording cancer – Restore normal ovulation / fertility Laboratory investigations: – Restore normal menstruation • Demonstration of biochemical hyperandro- – Correct hirsutism genaemia. – Total testosterone (>200ng/dL)/ Free (1). Women with PCOS concerned with testosterone > 2.2pg/mL. menstrual disturbances – desirous of contraception – The commonest medication prescribed in practice is • S. Estradiol and FSH estimations. the O.C.Pill. – Exclude hypogonadotropic hypogonadism ( E2, FSH). Oral contraceptive pills: Oral contraceptive pills inhibit LH, diminish the circulating levels of – Exclude premature ovarian failure ( E2, and FSH). androgens and increase the levels of circulating SHBG. It is advisable to use a low dose combination • S. Dehydroepiandrosterone sulfate. pill containing low dose of synthetic estrogen in – Not of value if S. Testosterone is normal combination with a low-androgenic progestin. Oral –