The consensus committee in July 19, 2018

What aberrations in menst cyclicity will pinpoint for PCO??   . The consensus committee in July 19, 2018:--This committee in contrast to NIH, Rotterdam ,Androgen Excess Society, & And Excess & PCOS committee  It was framed by  total   37   societies and organizations covering   71  countries  engaged  in the process of consensus statement  released in July 2018. .This consensus was headed by  “The Australian centre   for Research Excellence in PCOS” and  funded by NHMRC  led and   primarily funded  the guideline development. They partnered with the American  Society   for Reproductive  Medicine     and the European  society of Human    Reproduction and Embryology    in this  Endeavour. Thirty five   other societies partnered including FOGSI and   the PCOS  society of India.

Coming back to diagnosing PCO based on menst irregularities the point of consideration was which kind of irregular   cycles is to be considered  relevant ? The committee members  more clearly stressed on  gynecological   age in this issue..

Irregular menstrual cycles are defined as :

A) Cycles were normal   in the first year post menarche as part of the pubertal transition , 1 to < 3 years post menarche  with  cycle length < 21  or > 45 days .B) Three  years post menarche  to perimenopause  < 21 or  > 35   days or < 8 cycles per   year C) one year  post menarche > 90 days for any   one cycle.

II. Primary   amenorrhea     by age 15 or > 3   years post thelarche

When irregular menstrual cycles   are present   a diagnosis   of PCOS   should be considered

Androgens to be   measured in the diagnosis of biochemical hyperandrogenism are specified along with optimal assays.

Calculated  free  testosterone,  free androgen   index or  calculated bioavailable  testosterone  should be  used in assess  biochemical hyperandrogenism in the diagnosis of PCOS  .High quality   assays such  as liquid chromatography mass  spectrometry  and extraction chromatography immunoassays   should be used for the most  accurate   assessment of total   or free testosterone in PCOS.

Androstenedione and dehydroepiandrosterone   sulfate   could be considered if total or free testosterone are not elevated however these provide limited additional information in the diagnosis  of PCOS. C) In women on hormonal  contraception drug  withdrawal is recommended for  3 months  or longer  before   measurement .

How  important is AMH in the diag of PCO??

AMH levels   should  not yet  to be used  as an alternative test  for PCOM or single test for diagnosis  of PCOS,

Cardiovascular   disease risk

All women    with PCOS should be assessed for  cardiovascular    risk factors  including  A) obesity  B) cigarette  smoking C)  dyslipidemia D)  hypertension E) impaired glucose  tolerance and F)  lack of physical  activity. Weight height   and ideally waist circumference should be measured  and  BMI must be calculated. Overweight   and obese women   with PCOS   regardless of age should have   a fasting lipid profile. Blood pressure  must be measured annually .Gestational  diabetes   glucose tolerance   and type2  diabetes are common and PCOS   women are at 5 fold increased risk for these complications.

Glycemic status should be assessed in all women   with PCOS. A) An oral  glucose   tolerance test  B)  fasting plasma  glucose or C) HbA1c  should be performed to assess glycemic  status .  In high   risk  women with  PCOS  an OGTT is  recommended.

 Anxiety  depressive  symptoms  psychosexual health and impact on body  image should   be routinely screened in all adolescents and women   with PCOS  at diagnosis.

Lifestyle  modifications : Preferably multi component including  diet   exercise and behavioral strategies should be recommended

Achievable goals such as   5%- 10%   weight loss in 6  months in those with excess  weight  yields significant clinical   improvements.

Exercise

Health professional should encourage  and advise   exercise for the prevention of weight  gain and  maintenance of health .

Pharmacological  treatment for non fertility indications A) For  hyperandrogenism and / or irregular   menstrual cycles  .Combined oral contraceptive  pills  should  be recommended to manage hyperandrogenism and / or irregular   menstrual cycles  preferably lower   dose and natural    estrogen  preparations.

 Metformin When in PCOS?? Ans;- women with  BMI > 25 kg / m² and most beneficial in women with impaired OGTT or high risk  ethnic groups when   should be considered if COCP  and lifestyle   changes alone are not   successful. Metformin can be  considered in PCOS   women with  BMI > 25 kg / m and most beneficial in women with impaired OGTT or high risk  ethnic groups. 

Starting at a low dose with 500 mg increments   one two  weekly and extended  release  preparation may minimize side effects.

Antiandrogens when ??  Ans;-Antiandrogens should only be considered to treat hirsutism if 6 months or more of  cop and cosmetic  therapy   have  been unsuccessful

Inositol should currently be considered  as an experimental therapy in PCOS with emerging evidence  on efficacy highlighting the need for  further research

Assessment and treatment of infertility

Ovulation  induction Principles

The use of  ovulation  induction  agents including A) letrozole B) metformin and C) clomiphene citrate are  off label in many countries. Where off  label  use of ovulation induction agents  is allowed women   need to be informed  of the evidence concerns and side effects.

 Step 1:-Pregnancy   needs to be excluded before ovulation induction Step 2 :-Unsuccessful  and prolonged use of ovulation  induction agents should  be avoided due to poor  success rates. Step 3

 :-Letrozole should be considered the first line pharmacologic agent for ovulation induction in women with PCOS Step 4:-Clomiphene  citrate  could be used alone in women   with PCOS with anovulatory infertility and no other infertility factors. Step 5  :-Combining clomiphene   citrate with metformin improves  ovulation and pregnancy rates     in PCO  women  who are clomiphene resistance and  with   no other   cause of infertility  Step 6 :-Gonadotropins could be used as second line agents  in women   with PCOS  who have  failed  first line   oral ovulation induction therapy but before attempting at  gonadotrophins one should consider Cost and availability ,expertise  required for use in ovulation  induction. Degree of  intensive  ultrasound   monitoring  required. Of note that theta is lack   of difference in  clinical efficacy of available gonadotrophin  preparations.

Low   dose gonadotrophin  protocols to optimize monofollicular development, risk  and implications of potential multiple pregnancy

Laparoscopic ovarian surgery   when?? Ans:-Laparoscopic ovarian surgery   could be considered second line therapy for women   with PCOS who  are clomiphene citrate resistance with anovulatory infertility   and no their infertile factors ,.But where   laparoscopic  ovarian  surgery is to be recommended the following  need to be considered

Comparative cost  ,expertise required for use in  ovulation  induction ,intra  operative and post  operative risks   are higher in women   who are    overweight and obese ,there may be  a small associated risk of lower  ovarian reserve  or loss of ovarian function and peri adnexal  adhesion   formation  may be an  associated risk.

In vitro fertilization when in PCO?? Ans:-It is as third line therapy.  In vitro fertilization should be considered even in  the absence   of an absolute indication  for IVF / ICSI )say tubal block/ endometriosis) in those PCO   women with long   infertility    as third  line therapy where  first or  second   line ovulation  induction  therapies  have failed.

National Institutes of Health (NIH) 1990 Criteria for PCOS

The definition of PCOS most commonly used today arose from the proceedings of an expert conference sponsored by the NIH in April 1990 (i.e.NIH 1990 criteria). All those attending were queried regarding what they believed were diagnostic criteria of PCOS. Tabulation of the results indicated that 64%, 60%, 59%, 52%, and 48% thought that hyperandrogenemia, exclusion of other etiologies, exclusion of congenital adrenal hyperplasia (CAH), menstrual dysfunction, and clinical hyperandrogenism, respectively, were criteria that were definite or probable for the disorder (5). The proceeding then summarized these results into the following major research criteria (in order of importance): 1) hyperandrogenism and/or hyperandrogenemia, 2) oligoovulation, and 3) exclusion of known disorders, such as Cushing’s syndrome, hyperprolactinemia, and CAH (5) (Table 1). A fourth criterion, polycystic ovaries on ultrasound, was considered particularly controversial. In essence, the results of this expert conference identified PCOS as a disorder of ovarian androgen excess.

TABLE 1.

Current criteria for the definition of PCOS

Study	Criteria
NIH, 1990 (5 )	To include all of the following:
	1) Hyperandrogenism and/or hyperandrogenemia
	2) Oligoovulation
	3) Exclusion of related disorders
ESHRE/ASRM (Rotterdam), 2003 (6, 7 )	To include two of the following, in addition to exclusion of related disorders:
	1) Oligo- or anovulation
	2) Clinical and/or biochemical signs of hyperandrogenism
	3) Polycystic ovaries

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Rotterdam 2003 Criteria for PCOS: Introducing Two New Phenotypes

Another expert conference was organized in Rotterdam in May of 2003, sponsored in part by the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine (i.e.Rotterdam 2003 criteria). The proceedings of the conference noted that PCOS could be diagnosed, after the exclusion of related disorders, by two of the following three features: 1) oligo- or anovulation, 2) clinical and/or biochemical signs of hyperandrogenism, or 3) polycystic ovaries (6, 7) (Table 1).

We should note that the Rotterdam 2003 criteria did not replace the NIH 1990 criteria, because all women diagnosable by the NIH 1990 criteria would also meet the Rotterdam definition (Table 2). Rather, it expanded the definition of PCOS, adding two additional phenotypes as PCOS, including women with 1) polycystic ovaries and clinical and/or biochemical evidence of androgen excess, but without ovulatory dysfunction, and 2) polycystic ovaries and ovulatory dysfunction, but without hyperandrogenemia and/or hirsutism (i.e. no signs of androgen excess). To begin to determine whether these phenotypes truly represent PCOS, it is useful to review how syndromes are defined.