1. PCOS
Treatment Guidelines
&
Review of
Newer Medical Treatment in Infertility
Dr. Sharda Jain
Dr. Jyoti Agarwal
Dr. Jyoti Bhaskar

2. ESHRE/ ASRM sponsored PCOS
Consensus Workshop
• 1st workshop (2004) on Diagnosis
• 2nd workshop (2008) on Infertility
• 3rd workshop (2011) Women’s Health
Aspects of PCOS
Must Reading for all of you

3. PCOS Phenotypes as per Rotterdam criteria
PCOS Phenotype Oligo – or
an ovulation
Biochemical
hyperandrogene
mia or clinical
manifestation of
hyperandrogene
mia
Polycystic ovaries
in transvaginal
ultrasound
1- Severe PCOS + + +
2- Oligo – or
anovulation and
hyperandrogene
mia
+ + -
3- ovulatory PCOS - + +
4- MILD pcos + - +

4. MENSTRUAL DISORDERS: PCOS mostly produces oligomenorrhea
or amenorrhea.
INCREASED LH/FSH RATIO - Prevents follicular maturation
resulting in anovulation
HIGH LEVELS OF ANDROGEN HORMONE: The most common signs
are acne, acanthosis nigricans, androgenic alopecia & hirsutism.
METABOLIC SYNDROME: This appears as a tendency towards
central obesity and other symptoms associated with
insulin resistance.
Common Symptoms of PCOS
Other than INFERTILITY
Serum insulin, insulin resistance and homocysteine levels
are higher in women with PCO.

5. Look for C0- morbidities in PCOS
coming for infertility Treatment
•HERSUITISM & ACNE
•CENTRAL OBESITY
•TYPE-2 DIABETES
•HIGH BLOOD PRESSURE
•CHOLESTEROL ABNORMALITIES
•HYPOTHYROIDISM
•HYPERPROLACTINEMIA

6. Management of Infertility in PCOS
WHO Group – II Ovulation Disorder
Classic
PCOS
Anovulatory
PCOS
Ovulatory
PCOS
NICE/ ASRM Guidelines

7. Women with WHO group II anovulatory
infertility with PCOS who have a BMI of 30
or over must lose weight. Inform them that
this alone may restore ovulation, improve
their response to ovulation induction agents,
and have a positive impact on pregnancy
outcomes
Life style management
of Weight Reduction
(NICE 2013)

8. Life style management
of Weight Reduction
• 50% treatment of PCOS is simply – weight
control.
• Even if one loses 5-10 kg - the effect is
tremendous .
Experience

9. One of the following treatments taking into
account potential adverse effects, ease and
mode of use, the women’s BMI
• Clomifene Citrate or
• Metformin or
• A combination of the above
ESRE / ASRM consensus workshop on
PCOS Anovulatory Infertility
Cycle clinical follicle monitoring needed: (NICE 2013)

10. Clomifene Citrate
• For women who are taking clomifene
citrate, do not continue treatment for longer than 6
months
•Women prescribed metformin should be informed
of the side effects associated with its use (such
as nausea, vomiting and other gastrointestinal
disturbances)
(NICE 2004)
(NICE 2013)

11. Experience of Infertility Experts on
Role of Metformin in PCOS
• CC compared with metformin aloneresults
in higher ovulation , conception,
pregnancy & live birth rate
• CC + Metformin results in no substantial
benefits except, patients with BMI >35 or
abnormal GTT
Fertile sterile 2008,89;505

12. PCOS Patients with
Anovulation & Ovulation disorder
RESISTANT TO CLOMIFENE CITRATE:
For women with PCOS who are known to be resistant to
clomifene citrate, consider one of the following
SECOND – LINE TREATMENT, depending on clinical
circumstances and the women’s preference
• Laparoscopic Ovarian drilling or
• Combined treatment with clomifene citrate and metformin
if not already offered as fist – line treatment or
• Gonadotrophines
(NICE 2013)

13. CLOMIFENE CITRATE + Metformin
However, Recent Study showed
CC+ metformin combination therapy
results in hyper rates of LIVE BIRTHS
compared with other treatments.
Jungheim et. all fertil steril 2010;94:2659

14. Caution
Women with PCOD who are being treated
with gonadotrophins should not be offered
treatment with gonadotrophin – releasing
hormone agonist concomitantly because it
does not improve pregnancy rates and it is
associated with an increase risk of ovarian
hyperstimulation
(NICE 2004)

15. The use of Adjuvant Growth Hormone
treatment with gonadotrophins – releasing
hormone agonist and / or human
menopausal gonadotrophin during ovulation
induction in women with PCOS who do not
respond to clomifene citrate is not
recommended because it does not improve
pregancy rates
Caution
(NICE 2004)

16. INTRODUCING
Concepts & Rationale
of
A NEW LINE OF TREATMENT
↓
Still not approved by
NICE GUIDELINES
& ASRM

17. PATHOGENESIS of PCOS
INSULIN RESISTANCE
HYPERINSULINEMIA
THECA CELL
PROLIFERATION
HYPERANDROGENISM
PCOS
Infact, No Body Knows exact Cause !!

18. Oxidative Stress & Infertility

19. Basis of Newer Drugs use

20. Summary of
Review of literature shows

21. MELATONIN
•Recent entry
•Melatonin is also known as N-acetyl-5 methoxytryptamine
•An hormone secreted during the dark hours by pineal gland.
•Regulates a variety of important central and peripheral
•actions related to circadian rhythms and reproduction.

22. However, the discovery of melatonin as a
direct free radical scavenger has greatly
broadened the understanding of
melatonin’s mechanisms
which benefit reproductive physiology.
MELATONIN

23. •It has been discovered that melatonin is a powerful
free radical scavenger and a broad-spectrum antioxidant.
Because of its small size and highly lipophilic & hydrophilic
properties, melatonin crosses all cell membranes & easily
reaches subcellular compartments,including mitochondria and
nuclei, where it seems to accumulate in high concentrations.
•Melatonin prevents lipid peroxidation, protein, and
DNA damage.
MELATONIN

24. Melatonin, secreted by pineal gland, is taken up into
the follicular fluid from the blood.
ROS produced within the follicles, especially during
the ovulation process, were scavenged by melatonin,
and reduced oxidative stress involved in oocyte
maturation and embryo development
Melatonin increases intra-follicular melatonin
concentrations, reduces intra-follicular oxidative damage
Elevates fertilization and pregnancy rates.
MELATONIN

26. Comes from the amino acid l-cysteine. Amino acids
are the building blocks of protein
Improves insulin sensitivity & decreases
androgen level
Prevents follicular cohort atresia
Improves quality of cervical mucus
N-ACETYLCYSTEINE

27. •Decreases circulating insulin & serum total
testosterone
•Reduces acne & weight
•Reduces hirsutism and hyperandrogenism and
ameliorates the abnormal metabolic profile of
women with hirsutism
After 3 months of inositol administration, free
testosterone, insulin and HOMA index resulted in
significantly reduced. Both hirsutism and acne
decreased after 6 months of therapy.
MYO-INOSITOL

28. Is an analogue of vitamin D used for supplementation
in humans .
More useful form of vitamin D supplementation,
mostly due to much longer half-life and lower kidney
load
Improves insulin secretion.
ALFACALCIDOL

29. Chromium polynicotinate consists of pure niacin-bound
chromium
Chromium polynicotinateis more effective than other
types of chromium, because it binds to niacin also know
as vitamin b-3.
This provides a biologically active form of chromium, and
makes it easier for the body to absorb
CHROMIUM POLYNICOTINATE

30. •Active component of glucose tolerance factor which
is responsible for binding insulin to cell membrane
receptor sites
•Improves insulin sensitivity
•Stimulates the metabolism of sugar, fat &
cholesterol
CHROMIUM POLYNICOTINATE:

31. Is the natural, active form of folic acid used at the
cellular level for DNA reproduction and the regulation
of homocysteine among other functions.
Reduces homocysteine levels and prevent
cardiovascular risk factors associated with PCOS.
The un-methylated form, folic acid (vitamin B9), is a
synthetic form of folate found in nutritional
supplements.
L-METHYLFOLATE

32. Recap
• 50% treatment of PCOS is simply – weight
control.
• Even if one loses 5-10 kg - the effect is
tremendous .
Experience

33. Please Remembers
There is NO approval of these drugs in NICE &
ASRM Guidelines
& Drugs controlled of India for Ovulation Induction
Few Drug House have stared marketing NAC
& combination of
NAC with these drugs
to be given with CC
Please Note

34. Summary
Infertility in PCOS
• Exclude other diseases & other fertility
disorders in the couple.
• Life style modification particularly weight loss
increase exercise, smoking cessation &
decrease alcohol consumption is highly recommended.
• The Pharmacological treatment approved by NICE/
ASRM is CC or CC+ metformin.
•Second line treatment i.e. gonadotrophines or
laparoscopic ovarian drill if medical treatment fails.
•NICE & ASRM do not endorse use of newer drugs (2013)

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