Dr.

Padma Rekha Jirge MRCOG (UK), FICOG, MBA (Healthcare Mx)

• Clinical research fellow – in ART; from University of Glasgow 1995 – 1997

• Trained in Operative Laparoscopy and Hysteroscopy, Glasgow 1994-1995

• Scientific Director – 1.Sushrut Assisted Conception Clinic, & Shreyas Hospital , Kolhapur

• Publications - 2 manuscripts on role of LH in ovulation induction - in Human Reproduction

- infection and IVF - in Fertility Sterility
- author of 15 chapters on various aspects of ART in textbooks
- Stem Cells - FAQ and answers –FOGSI Focus Jan 2008
- Comparative study of Letrozole vs Clomiphene – Fertility Sterility, Jan 2010
- Ovarian Reserve Tests – A review, Journal of Human Reproductive Sciences,
Jan 2012
- DHEA supplementation in poor responders…. JHRS, Sep 2014
- Co-editor of World Clinics in O&G (Ovulation Induction) November 2015
- Poor Ovarian Reserve – JHRS
- Preparing and Publishing Scientific Manuscripts – A review - JHRS

• Sushrut IVF Clinic: Recognised by ICOG for fellowship course in IVF

 Chairperson, Research Committee, PCOS Society of India
 Co-opted Member, Managing Committee, ISAR
 National corresponding Editor – Journal of O&G of India
• On Editorial board of Austin Journal of Reproductive Medicine & Infertility; and Journal of IVF Lite
 Reviewer for 1. Journal of Human Reproductive Sciences
2. Reproductive Biology & Endocrinology Journal (RB&E)
3. Journal of Assisted Reproduction & Genetics
 Clinical secretary, Maharashtra Chapter of ISAR
 Editor & Founder member of Fertility Preservation Society of India
What are the
different Phenotypes
of PCOS?
Its importance in
Management

Dr. Padma Rekha Jirge MRCOG(UK), FICOG, MBA (Healthcare Mx)

Shreyas Hospital & Sushrut Assisted Conception Clinic,

Kolhapur
PCOS

 Multitude of symptoms – endocrine / metabolic

 Multifactorial in origin

 Diagnosis – important clinical implications for the

individual and relatives
 PCOS – Diagnosis
NIH Criteria (1999)

Exclusion:
congenital adrenal hyperplasia, androgen secreting tumours, hyperprolactinaemia, and thyroid disorders.
PCOS – Rotterdam Criteria
NIH and Rotterdam Criteria

Rotterdam Criteria
expanded the definition of PCOS
Introduced different subgroups
 PCOS: AE-PCOS Society
Criteria

FIGURE 1
Proposed criteria for the diagnosis of the PCOS. aPossibly including 21-hydroxylase deficient nonclassic adrenal
hyperplasia, androgen-secreting neoplasms, androgenic/anabolic drug use or abuse, Cushing’s syndrome, the
Hyperandrogenic-Insulin Resistance-Acanthosis Nigricans syndrome, thyroid dysfunction, and
hyperprolac tinemia.
 • Use of Rotterdam Criteria for diagnosis
• Ovulation to be confirmed and not to be
relied upon regularity of the cycle
• If clinical HA is present, then serum androgens
need not be evaluated
• If HA and Ovulatory dysfunction, no need for
USG
Phenotypes of PCOS

 Oligo /anovulation+HA+PCO (Classic PCOS)

 Oligo / anovulation + HA (NIH PCOS)

 HA+PCO (Ovulatory PCOS)

 Oligo / anovulation+PCO (Non-androgenic

PCOS)
Risks Associated with PCOS
 Infertility

 Hypertension, cardiovascular morbidity

 Insulin resistance and type 2 DM

 Dyslipidemia

 Metabolic syndrome

 Endometrial Carcinoma

 Implications for mothers, sisters, brothers and

offspring
Phenotypes and Clinical
Implications

 Do different phenotypes influence the severity of the

condition?

 Metabolic risks – Hyperandrogenism or Insulin resistance

 Impact of obesity

 Age

 Influence of ethnicity
IR highest in IM/HA group; HDL lowest
Also, highest MetS related to weight
J Clin Endocrinol Metab. 2006 Oct;91(10):3922-7
Oligoanovulation with polycystic ovaries but not overt hyperandrogenism.
Dewailly D1, Catteau-Jonard S, Reyss AC, Leroy M, Pigny P.

OBJECTIVES:
Rotterdam definition recognizes four PCO syndrome (PCOS) phenotypes: HA+OA+PCO (full-blown
syndrome), HA+OA (former National Institutes of Health definition), HA+PCO (ovulatory PCOS), and
OA+PCO. However, the latter phenotype is controversial, and it is not known to what extent it shares
similarities with the others.
DESIGN:
The study was a comparative analysis of hormonal, metabolic, and ultrasound parameters obtained
from patients and controls that were consecutively included in a database.
PATIENTS AND METHODS:
Sixty-six patients having OA+PCO without hirsutism or elevated serum androstenedione and
testosterone levels were compared with 118 normally cycling nonhyperandrogenic age-matched
women without PCO (controls). These patients (phenotype D) were also compared with patients with
HA+OA+PCO (phenotype A, n = 246), HA+OA (phenotype B, n = 27), and HA+PCO (phenotype C, n =
67).
RESULTS:
Patients with phenotype D had higher mean values of waist circumference and higher mean levels of
serum testosterone, androstenedione, and LH than controls. Conversely, they had lower mean serum
levels of FSH and SHBG (P < 0.05 for each parameter). Variance analysis disclosed significant group
effects between the different patients' phenotypes for all parameters, except age, BMI, and FSH.
After multiple comparisons with post hoc analysis, phenotype D had milder endocrine and metabolic
abnormalities than phenotype A, although it did not differ from phenotype C, except for androgen
data, by definition. Phenotypes A and B were statistically similar, except for the ultrasound data, by
definition.
CONCLUSION:
Oligoanovulatory patients with PCO but without HA have mild endocrine and metabolic features of
 1550 women with
PCOS
• Raised BMI / Waist circumference
• Raised Testosterone
• Lower HDL
• Impaired OGTT
• Raised BP and hs CRP
Both HA and
NA PCOS –
higher BMI,
Waist Circum,
Sys BP and HA had
Insulin higher BMI &
Waist
Circum
 Low HDL &
High LDL
High
Triglycerides
GDM
PIH
Ethnicity & Phenotypes
 Asian women – lower BMI, central obesity, milder
HA but high prevalence of MetS and T2D

 African and Hispanic – more obese, Africans

more prone to hypertension and cardiovascular
disease; Hispanics more prone to MetS and T2D

 High prevalence of hirsutism in Mediterranean

and Middle Eastern women
Clinical Implications
 Different phenotypes may exhibit different range of
metabolic dysfunction.
 Those with HA have more severe metabolic abnormalities
 The phenotypic dysfunction may become less obvious
with age and in particular following menopause
 Obesity impacts the severity of metabolic dysfunction
 Ethnicity

(Endocrine Society and Amsterdam ESHRE / ASRM

Consensus
Management Implications
 Adolescent PCOS – Establishing diagnosis can be
challenging; AVOID over-diagnosis

 Hirsuitism: (underlying hyperandrogenism); needs long

term treatment

 Oligomenorrhoea: Severe form of HA in amenorrhoea;

associated with metabolic abnormalities (Level B); cycles
may become regular with increasing age

 Contraception: OCP use does not increase metabolic risk

(Level B)

 QoL: increased prevalence of psychological disorders in

all phenotypes of PCOS; (?disorder in itself ?its
manifestations); should be considered, counseled and
treated
Pregnancy:
Obesity

 Prevalence is increasing and has an important

influence on the phenotype of PCOS.

 Is associated with greater insulin resistance, IM

and HA

 Lifestyle management results in weight loss and

improves surrogate markers of MetS (Level A)

 (Screening: BMI and waist circumference)

Infertility

 Should be managed along the standard clinical

practice

 Obesity adversely affects the clinical outcomes and

lifestyle management is of importance

 Those with HA and chronic amenorrhoea – more

resistant to ovarian stimulation and ?lower pregnancy
rates
IR, DM and Met S
 IR is an important component of PCOS; most often
seen in classic / NIH PCOS phenotype

 Precursor for various metabolic consequences

including T2D and metabolic syndrome.

 Screening for DM – in adolescent and adult PCOS

– in those with obesity / visceral adiposity / FH of DM

- Fasting and 2 hr OGTT (HbA1C); Repeat every 3-5

years.

- Diet and lifestyle are important preventive measures

- Metformin
Cardiovascular Disease
Endometrial Carcinoma

 No specific recommendations for screening

 Based on age, length of amenorrhea,

dysfunctional uterine bleeding and endometrial
thickness.
Conclusions
 PCOS may present with different phenotypes in young
adulthood.

 Metabolic dysfunctions are more severe in those with HA.

 However, obesity and increasing age may obliterate the

distinction between various phenotypes.

 Pregnancy complications and psychological disorders

occur with similar frequency in all phenotypes.
Conclusions

 Lifestyle modification with diet and exercise

 Metformin

 Screening – BMI, waist circumference, BP, acanthosis, OGTT,

(lipid profile) and re-assessment at regular intervals

 Symptomatic treatment

 Vigilance for long term risks

 Improve awareness regarding risk for mothers, siblings and

offspring.
Thank You
Male Phenotype
PCOS and Sisters
 J Clin Endocrinol Metab. 2005 May;90(5):2545-9. Epub 2005 Feb 22.

 Phenotypic variation in hyperandrogenic women influences the findings of abnormal metabolic and
cardiovascular risk parameters.

 Carmina E1, Chu MC, Longo RA, Rini GB, Lobo RA.

 Author informatio

 Abstract

 In hyperandrogenic women, several phenotypes may be observed. This includes women with classic
polycystic ovary syndrome (C-PCOS), those with ovulatory (OV) PCOS, and women with idiopathic
hyperandrogenism (IHA), which occurs in women with normal ovaries. Where other causes have been
excluded, we categorized 290 hyperandrogenic women who were seen consecutively for this complaint
between 1993 and 2004 into these three subgroups. The aim was to compare the prevalence of obesity,
insulin resistance, and dyslipidemia as well as increases in C-reactive protein and homocysteine in these
different phenotypes with age-matched ovulatory controls of normal weight (n = 85) and others matched
for body mass index (BMI) with women with C-PCOS (n = 42). Although BMI affected fasting serum insulin
and the Quantitative Insulin-Sensitivity Check Index, these markers of insulin resistance were greatest in C-
PCOS (n = 204), followed by OV-PCOS (n = 50) and then IHA (n = 33). Androgen levels were similar in OV-
PCOS and IHA but were higher in C-PCOS, whereas gonadotropins were similar in all groups. Lipid
abnormalities were highest in C-PCOS and OV-PCOS and were normal in IHA. C-reactive protein was
elevated in C-PCOS and OV-PCOS but not IHA. Homocysteine was elevated only in C-PCOS. Overall, the
prevalence of obesity (BMI > 30) was 29% in C-PCOS, 8% in OV-PCOS, and 15% in IHA and insulin resistance
(Quantitative Insulin-Sensitivity Check Index < 0.33) was 68% in C-PCOS, 36% in OV-PCOS, and 26% in IHA.
The prevalence of having at least one elevated cardiovascular risk marker was 45% in C-PCOS 38% in OV-
PCOS and was not increased on IHA (6%). These results suggest that among hyperandrogenic women the
prevalence of abnormal metabolic and cardiovascular risk parameters is greatest in C-PCOS, followed by
OV-PCOS and then women with IHA. Moreover, in that in OV-PCOS and IHA, ages and weights were
similar yet the prevalence of metabolic and cardiovascular risk was greater in OV-PCOS, the finding of
polycystic ovaries may be a significant modifying factor.
J Clin Endocrinol Metab. 2005 May;90(5):2571-9. Epub 2005 Feb 15.
Polycystic ovaries are common in women with hyperandrogenic chronic anovulation but do
not predict metabolic or reproductive phenotype.
Legro RS1, Chiu P, Kunselman AR, Bentley CM, Dodson WC, Dunaif A.
Author information

Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unexplained
hyperandrogenic chronic anovulation. Experts have recommended including the
morphology and volume of the ovary in the diagnostic criteria for PCOS. We performed this
study to determine whether there was an association between the morphology and size of
the ovaries and markers of insulin sensitivity as determined by dynamic testing within women
with PCOS or compared with a group of control women. We then examined reproductive
parameters. We studied 88 unrelated PCOS women and 21 control women, aged 17-45 yr. All
were in the early follicular phase or its equivalent (no follicle with > 10 mm diameter and
anovulatory serum progesterone level < 3 ng/ml). Subjects underwent on the same day a
phlebotomy for baseline hormones, a 2-h oral glucose tolerance test, and transvaginal
ultrasound to determine the morphology and volume of the ovaries. Ninety-five percent (84
of 88) of women with PCOS and 48% (10 of 21) of the control women had polycystic ovaries
using the criteria of at least one ovary greater than 10 cm3 (PCOV) and/or polycystic ovary
morphology (PCOM) using the criteria of 10 or more peripheral follicular cysts 8 mm in
diameter or less in one plane along with increased central ovarian stroma. PCOM was a
better discriminator than PCOV between PCOS and control women. The odds of women with
PCOS having PCOM were elevated 50-fold compared with controls (odds ratio, 50; 95%
confidence interval, 10-240; P < 0.0001), whereas the odds of PCOV were elevated 5-fold in
women with PCOS (odds ratio, 4.6; 95% confidence interval, 1.7-12.6; P = 0.003). Neither the
insulin sensitivity index, fasting or 2-h values, or any integrated measures of glucose and insulin
varied in women according to either morphology or volume, nor was there an association
with circulating androgen levels. Women with PCOS and PCOM had lower FSH levels than
women with PCOS and non-PCOM. Women with PCOS and PCOV had a higher LH to FSH
ratio than women without PCOV and PCOS. These data support the hypothesis that
polycystic ovaries are an abnormal finding. However, neither the morphology nor the volume
of the ovaries is associated with distinctive metabolic or reproductive phenotypes in women
with PCOS.
 Diagnosis of PCOS:
New Consensus

Dr. Padma Rekha Jirge MRCOG(UK), FICOG, MBA (Healthcare Mx)

Shreyas Hospital & Sushrut Assisted Conception Clinic,

Kolhapur
KISAR 30 Apr-1 May 2016, Bangalore
Follicular numbers
Correlation bet FN and AMF
Additional Assessment
 Insulin Resistance

 Metabolic Syndrome
Conclusions
 Rotterdam criteria and AE-PCOS society criteria have
expanded the diagnosis of PCOS

 USG parameters have been under constant scrutiny with

changing technological aspects

 With the availability of fully automated assays for AMH,

there is a valid reason for it to be included as a diagnostic
criteria.

 Any defined phenotype should be a guiding factor

regarding long-term health concerns
Areas of Concern
 USG criteria - ? Need revised

No stromal measurement / doppler parameters

?3D USG

Lam et al. Human Reproduction Vol.21, No.9 pp.

2209–2215, 2006

 AMH
mark-type=disc
Chronic anovulation
Clinical and/or biochemical signs of
hyperandrogenism

(Exclusion of other etiologies) Both

criteria are necessary to establish
diagnosis list-behavior=unordered
prefix-word= mark-type=disc
Oligo- and/or anovulation
Clinical and/or biochemical signs of
hyperandrogenism
Polycystic ovaries

(Exclusion of other etiologies) Two of

three criteria are necessary to establish
diagnosis list-behavior=unordered
prefix-word= mark-type=disc
Clinical and/or biochemical signs of
hyperandrogenism
Ovarian dysfunction (oligo- and/ or
anovulation) and/or polycystic ovaries

(Exclusion of other etiologies) Both

criteria are necessary to establish
 21-hydroxylase deficient nonclassic adrenal
hyperplasia, thyroid dysfunction,
hyperprolactinemia, neoplastic androgen
secretion,
 or drug-induced androgen excess.
 Metabolic syndrome prevalence (A) in women with and without PCOS and subgroup meta-
analysis (B) of metabolic syndrome prevalence in women with and without PCOS with BMI-
matched study populations.

Moran L J et al. Hum. Reprod. Update 2010;16:347-363

© The Author 2010. Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology. All rights reserved. For Permissions, please email:
journals.permissions@oxfordjournals.org
PCOS and Phenotypes

Classic phenotype develops the most

severe form of metabolic dysfunction
at an early age.
Strong correlation between
 NIH workshop 2012, Draft statement
Recommend maintaining the broad, inclusionary diagnostic
criteria of Rotterdam (which includes the “classic NIH” and
AE‐PCOS criteria) while specifically identifying the phenotype:

Androgen Excess + Ovulatory

Dysfunction

Androgen Excess + Polycystic

Ovarian Morphology

Ovulatory Dysfunction + Polycystic

Ovarian Morphology

Androgen Excess + Ovulatory

Dysfunction + Polycystic Ovarian
Morphology
Ethnic Differences

Carmina et al 1992
J Clin Endocrinol Metab. 2006 Dec;91(12):4842-8. Epub 2006 Sep 26.
Characterizing discrete subsets of polycystic ovary syndrome as defined by the
Rotterdam criteria: the impact of weight on phenotype and metabolic features.
Welt CK1, Gudmundsson JA, Arason G, Adams J, Palsdottir H, Gudlaugsdottir G,
Ingadottir G, Crowley WF.

CONTEXT:
The Rotterdam criteria for polycystic ovary syndrome (PCOS) defines discrete
subgroups whose phenotypes are not yet clear.
OBJECTIVE:
The phenotypic characteristics of women in the PCOS subgroups defined by the
Rotterdam criteria were compared.
DESIGN:
The study was observational.
SETTING:
Subjects were studied in an outpatient setting in Boston and Reykjavik.
PATIENTS:
Four subgroups of subjects with PCOS defined by 1) irregular menses (IM),
hyperandrogenism (HA), and polycystic ovary morphology (PCOM, n = 298); 2)
IM/HA (n = 7); 3) HA/PCOM (n = 77); and 4) IM/PCOM (n = 36) and a group of
controls (n = 64), aged 18-45 yr, were examined.
INTERVENTION:
Subjects underwent a physical exam; fasting blood samples for androgens,
gonadotropins, and metabolic parameters; and a transvaginal ultrasound.
MAIN OUTCOME MEASURES:
The phenotype was compared between groups.
RESULTS:
Concerns and Criticism

 Oligo/anovulation: role in evaluating in non-

infertile women

 Hyperandrogenism: hirsuitism, acne, alopecia –

not universal

 Hyperandrogenaemia: which tests to do?

(Testo, SHBG, FAI; 17-OH P, androstenedione,

DHEAS)
Concerns and Criticism
Contd
 PCO: follicular number vary with age.

 Prognostic features – obesity, IR

 Role of age and ethnicity