pcoss.pptx all india institute of medical sciences

POLYCYSTIC OVARIAN SYNDROME
Dr.Surbhi Bansal
Ist year Resident
Department of Obstetrics and
Gynaecology
Under guidance of
-Dr. Neelam Bhardwaj
-Dr.Pawan Agarwal
-Dr.Lata Ratnoo

• PCOS is one of the most common endocrine disorders in
women of reproductive age, affecting 5% to 10% of women
worldwide
• It is characterized by a combination of
– Hyperandrogenism (either clinical or biochemical),
– Chronic anovulation and
– Polycystic ovaries.
• associated with
– Insulin resistance
– Obesity.
1.Endocrine disorder, PCOSIn: Berekand NovaksGynecology,Fifteen Edition , New Delhi ,Wolter Kluwer,2012pp1075 t01090

NovaksGynecology,Fifteen Edition ,New
Delhi ,Wolter Kluwer,2012 pp1075 t01090
Pathophysiology and laboratory finding
• The hyperandrogenism and anovulation that accompany
in four
PCOS may be caused by abnormalities
endocrinologically active compartments:
– (i) the ovaries
– (ii) the adrenal glands
– (iii) the periphery (fat)
– (iv) the hypothalamus–pituitary compartment
1.Endocrine disorder, PCOSIn: Berekand

• In patients with PCOS, the ovarian compartment is the most
consistent contributor of androgens.
• Dysregulation of CYP17, this hormone relates to ovarian
androgenic activity in PCOS in a number of ways.
– Total and free testosterone levels correlate directly with LH
levels.
– The ovaries are more sensitive to gonadotropic stimulation,
possibly as a result of CYP17 dysregulation.

NovaksGynecology,Fifteen Edition , New
• The same number of primordial follicles are present, but the
number of growing and atretic follicles is doubled. Each ovary
may contain 20 to100 cystic follicles.
• A one-third increase in cortical stromal thickness and a 5-fold
increase in subcortical stroma are noted.
• The increased stroma is due to both hyperplasia of theca cells and
increased formation subsequent to the excessive follicular
maturation and atresia.

• The peripheral compartment, defined as the skin and the
adipose tissue, manifests its contribution to the development of
PCOS in several ways.
– Aromatase and 17β-hydroxysteroid dehydrogenase activities are
increased in fat cells.
– The presence and activity of 5α-reductase in the skin largely
determines the presence or absence of hirsutism .
-With obesity the metabolism of estrogens is decreased.
-Whereas estradiol (E2) is at a follicular phase, estrone (E1) levels
are increased as a result of peripheral aromatization of
androstenedione.
– A chronic hyperestrogenic state, with reversal of the E1-to-E2
ratio, results and is unopposed by progesterone.

The hypothalamic–pituitary compartment participates in
aspects to the development of PCOS.
– An increase in LH pulse frequency relative to those in the
normal follicular phase is the result of increased GnRH pulse
frequency.
– This increase in LH pulse frequency explains the frequent
observation of an elevated LH and LH-to-FSH ratio.
– FSH is not increased with LH, likely because of the
combination of increased gonadotropin pulse frequency.
with PCOS exhibit mildly
• About 25% of patients
elevated prolactin levels.

Functional Genetic Variation in the Anti-Müllerian Hormone Pathway in Women with
Polycystic Ovary Syndrome.
Gorsic LK1, Dapas M1, Legro RS2, Hayes MG1,3,4, Urbanek M1,2.
Author information
Abstract
CONTEXT:
PCOS is a highly heritable, common endocrine disorder characterized by
hyperandrogenism, irregular menses and polycystic ovaries. PCOS is often
accompanied by elevated levels of anti-Müllerian hormone (AMH). AMH inhibits follicle
maturation. AMH also inhibits steroidogenesis through transcriptional repression of
CYP17A1. We recently identified 16 rare PCOS-specific pathogenic variants in AMH.
OBJECTIVE:
To test whether additional members of the AMH signaling pathway also contribute to
the etiology of PCOS.
PARTICIPANTS/METHODS:
Targeted re-sequencing of coding and regulatory regions of AMH and its specific type 2
receptor, AMHR2 was performed on 608 PCOS-affected women and 142 reproductively
normal control women. Prediction tools of deleteriousness and in silico evidence of
epigenetic modification were used to prioritize variants for functional evaluation. Dual
luciferase reporter assays and splicing assays were used to measure the impact of
genetic variants on function.

RESULTS:
We identified 20 additional variants in/near AMH and AMHR2 with significantly
reduced signaling activity in in vitro assays. Collectively, from our previous study
and reported herein, we have identified a total of 37 variants with impaired
activity in/near AMH and AMHR2 in 41 women affected with PCOS, or 6.7% of
our PCOS cohort. Furthermore, no functional variants were observed in the 142
phenotyped controls. The functional variants were significantly associated
with PCOS in our cohort of 608 women with PCOS and 142 controls (p=2.3 x 10-5)
and very strongly associated with PCOS relative to a larger non-Finnish European
(gnomAD) population-based control cohort (p<1x10-9).
CONCLUSIONS:
AMH signaling cascade plays an important role in PCOS etiology.

Diagnostic criteria
National Institute of Health 1990 Criteria (both 1 and 2)
1. Chronic anovulation and
2. Clinical and/or biochemical signs of hyperandrogenism and
exclusion of other etiologies.
Revised 2004 Rotterdam’s criteria (2 out of 3)
1. Oligoovulation or anovulation
2. Clinical and/or biochemical signs of hyperandrogenism
3. Polycystic ovaries
( exclusion of other etiologies -congenital adrenal
hyperplasia, androgen-secreting tumors, Cushing’s
syndrome)
1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New

Hyperandrogenemia
Blood androgen levels are increased
1. S. Testosterone –
• Normal value in female-70ng
• Pcos- mildly increased - 70-150 ng but <200ng
2. S.Dehydroepiandrosterone
• Secreted by adrenal gland and ovary
3. S. Dehydroepiandrosterone sulphate(DHEA-S)
• Secreted by adrenal gland only
• Pcos- mildly increased-<700ug
4. Androstenedione

Hyperandrogenism
Clinical evidence of hyperandrogenism includes
hirsutism,acne and androgenic alopecia
1) Hirsutism- growth of coarse,thick terminal hair on face or
body in male pattern
• Most obvious clinical indicator of androgen excess
• Seen by modified ferriman gallway scoring
system(hirsutism>8)
2. Acne- usually resistant to treatment
3. Androgenic alopecia- scalp hair loss in women
• Limited to crown
• Does not involve frontal hair line.

Hirsutism, alopecia, and acne.

Accuracy of anti-Müllerian hormone and total follicles count to diagnose polycystic ovary
syndrome in reproductive women.
Wongwananuruk T
Abstract
OBJECTIVE:
Recently, there was a new recommendation of ultrasonographic criteria to diagnosis
polycystic ovary syndrome (PCOS). In addition, serum anti-Müllerian hormone (AMH) was
proposed as a surrogate marker for diagnosis of PCOS, but AMH cut-off level for diagnosis
of PCOS is unclear. This study aimed to investigate the accuracy of serum AMH and
evaluate new ultrasonographic criteria, follicle number per ovary (FNPO) threshold ≥ 25
follicles and ovarian volume (OV) > 10 mL, for diagnosis of PCOS.
MATERIALS AND METHODS:
A cross-sectional study was conducted. Fifty-five PCOS women and sixty-three normal
ovulatory, non-hyperandrogenic women were recruited. Transvaginal or transrectal
ultrasonography was performed in all participants to evaluate follicle number and OV.
Serum AMH was evaluated in both study groups.

RESULTS:
The mean age of the participants was 25.1 ± 5.3 years old in PCOS group
and 29.7 ± 7.2 years old in control group. Mean AMH, FNPO and OV
in PCOS women were significantly higher than those in non-PCOS women.
The area under the receiver-operating characteristic (ROC) curve of AMH
was 0.903. The threshold of AMH at 4.7 ng/mL offered the best compromise
between 80% sensitivity and 77.8% specificity. The appropriated threshold
values for FNPO, follicle number per cross-section (FNPS) and OV were 15
follicles, 7 follicles and 6.5 mL, respectively. Serum AMH level was
significantly positively correlated with FNPO, FNPS and OV in both PCOS and
control groups. In PCOS women, serum AMH showed strongly correlation
with FNPO (r = 0.53, p < 0.001) and weakly correlation with total
testosterone (r = 0.283, p = 0.036).
CONCLUSION:
Serum AMH had a good diagnostic performance for diagnosis
of PCOS presenting with oligo/anovulation and hyperandrogenism. AMH
threshold at 4.7 ng/mL was the best compromise level for diagnosis
of PCOS. FNPO ≥15, FNPS ≥7 and OV ≥ 6.5 mL were reliable threshold for
detecting polycystic ovaries in women with frank manifestation of PCOS.

1.Endocrine disorder, PCOSIn: Berekand NovaksGynecology,Fifteen Edition , New Delhi ,Wolter
Kluwer,2012 pp1075 t0 1090

Pathology
• Macroscopically, ovaries in women with
PCOS are two to five times the normal size.
• A cross-section of the surface of the ovary
discloses a white, thickened cortex with
multiple cysts that are typically less than a
centimeter in diameter.
• Microscopically, the superficial cortex is
fibrotic and hypocellular and may contain
prominent blood vessel.
• The surface area is doubled, giving an average
volume increase of 2.8 times.

Clinical consequences
1. Infertility.
2. Menstrual bleeding problems, ranging from
amenorrhea to dysfunctional uterine bleeding.
3. Hirsutism, alopecia, and acne.

4. An increased risk of
- Diabetes mellitus in patients with insulin resistance.
- Coronary artery disease
- Endometrial cancer.
- Sleep apnea syndrome
- Nonalcholic steatohepatitis(NASH)
- Psychiatric problems-anxiety to depression
and eating disorders
- High risk pregnancy(abortions,pre-
eclampsia,gestational diabetes
mellitus,preterm labor,stillbirth)

Infertility
• The most common cause of oligo-ovulation and
anovulation among women presenting with infertility—is
polycystic ovarian syndrome (PCOS)

Menstrual bleeding problems
• The menstrual dysfunction in PCOS arises from anovulation
or oligo-ovulation.
• Ranges from amenorrhea to oligomenorrhea.
• Regular menses in the presence of anovulation in PCOS is
uncommon.
• A report found that among hyperandrogenic women with
regular menstrual cycles, the rate of anovulation is 21%.

Insulin resistance
• Patients with PCOS frequently exhibit insulin resistance and
hyperinsulinemia.(prevalence of 75-50%)
• Insulin resistance and hyperinsulinemia participate in the
ovarian steroidogenic dysfunction of PCOS.
• The most common cause of insulin resistance and
compensatory hyperinsulinemia is obesity and CYP 11 gene
mutation.
• obesity has its frequent occurrence in PCOS, obesity alone
does not explain this important association.

• Multiple other testing or screening scheme were proposed to assess
the presence of hyperinsulinemia and insulin resistance.
• the fasting glucose-to-insulin ratio is determined, and values less
than 4.5 indicate insulin resistance.
• A peak insulin level of over 150 μIU/mL or a mean level of over
84 μIU/mL over the three blood draws of a 2-hour GTT.
• Insulin resistance indicates an increased risk of diabetes mellitus
and cardiovascular disease.
• About 35% of obese PCOS patients have impaired glucose tolerance
and 7.5% to 10% have type 2 diabetes mellitus.

Metabolic Syndrome
• In addition to addressing the increased risk for diabetes.
• insulin resistance or hyperinsulinemia as a cluster syndrome called
metabolic syndrome or dysmetabolic syndrome X.
• The more dysmetabolic syndrome X criteria are present, the higher
the level of insulin resistance and its downstream consequences.
• Abnormal lipoproteins are common in PCOS.
• Obesity occurs in more than 50% of patients with PCOS.
• The body fat is usually deposited centrally (android obesity) and a
higher waist-to-hip ratio.

Metabolic Syndrome Diagnostic Criteria
(3 out of 5)
1) Female waist >35 inches
2) Triglycerides >150 mg/dL
3) HDL <50 mg/dL
4) Blood pressure >130/85 mmHg
5) Fasting glucose:>100mg/dl or previously
established diabetes mellitus.

The incidence of metabolic syndrome in adolescents with different
phenotypes of PCOS.
Altintas KZ,
Abstract
OBJECTIVES:
To evaluate the incidence of metabolic syndrome in Turkish
adolescents with different phenotypes of polycystic
ovary syndrome (PCOS).
MATERIAL AND METHODS:
This cross-sectional study was performed on the Youth Center clinic of
a tertiary referral hospital in Turkey. Adolescents with PCOS (n = 144)
were classified into four phenotype groups according to the presence
of oligo/anovulation (O), hyperandrogenism (H), and polycystic
ovarian morphology (P) as follows: Phenotype A (O + H + P),
Phenotype B (H + O), Phenotype C (H + P), Phenotype D (O + P). The
adolescents gave early follicular phase blood samples for endocrine
and metabolic tests. The incidence and the presence of parameters
of metabolic syndrome were assessed among the four groups.

RESULTS:
In total, 54.9% of the adolescents with PCOS were overweight and
25.7% had metabolic syndrome. The incidence of metabolic
syndrome in Phenotypes A-D were as follows: 39.5%, 20.5%, 26.5%,
and 15.2%, respectively. Although body mass index was higher in the
Phenotype A group, insulin resistance was similar in all of the
phenotype groups. The most common dyslipidemia was low HDL-C
levels and this was present in more than half of the adolescents
with PCOS. Both body mass index and total testosterone levels were
significantly higher in adolescents with metabolic syndrome in
comparison to those without metabolic syndrome.
CONCLUSIONS:
Although low HDL-C levels and insulin resistance are
common PCOS findings in adolescents, the metabolic profile seems
to be worse in Phenotype A than the other phenotypes. Therefore,
screening programs should evaluate patients based on the known risk
factors and phenotypes for adolescents with PCOS.

Acanthosis nigricans
• Acanthosis nigricans is a reliable marker of insulin
resistance in hirsutate women.
• This thickened, pigmented, velvety skin lesion is most
often found in the vulva and may be present on the
axilla, over the nape of the neck, below the breast, and
on the inner thigh .
• The HAIR-AN syndrome consists of hyperandrogenism
(HA), insulin resistance (IR), and acanthosis nigricans
(AN).

Cancer
• In chronic anovulatory patients with PCOS, persistently
elevated estrogen levels.
• Uninterrupted by progesterone.
• Increase the risk of endometrial carcinoma.
• These endometrial cancers are usually well
differentiated, stage I lesions with a cure rate of more
than 90%.

Depression and Mood Disorders
• The clinical features of PCOS, such as infertility, acne,
hirsutism, and obesity, promote psychological morbidity.
• Women with PCOS face challenges to their feminine identity
that can lead to loss of self-esteem, anxiety, poor body image,
and depression.

Algorithm 1 : lifestyle modification
• Effectiveness of lifestyle interventions
1. Healthy eating and regular physical activity should be
recommended in all women with PCOS
2. 5-10% weight loss within 6 months restores ovulation and
fertility in >75% women.
3. SMART(Specific Measurable Achievable Realistic and
Timely goal setting can enable achievement of realistic
lifestyle goal
• Behavioural strategies
• Dietary intervention
Energy deficit of 30% or 500-750 kcal/day should be
prescribed.
• Exercise intervention
Minimum of 150 min/week moderate physical activity or
75min/week vigorous physical activity.

Algorithm 2 :pharmacological treatment for
non- infertility indication
Education + Lifestyle + first line pharmacological therapy fo hyperandrogenism and
irregular cycle
Low dose 20-30ug ethinyl
estradiol
COCP + Lifestyle + metformin
should be given in women with
metabolic feature
COCP + Anti androgen can be
consider after 6/12 cosmetic
treatment if they fail to reach
hirsuitism goals and in patient
with androgenic alopecia
First line COCP

Oral Contraceptives
• Combination oral contraceptives (OCs) decrease adrenal
and ovarian androgen production and reduce hair growth in
nearly two-thirds of hirsute patients .
• The progestin component suppresses LH, resulting in
diminished ovarian androgen production.
• The estrogen component increases hepatic production of
SHBG, resulting in decreased free testosterone concentration.
• Estrogens decrease conversion of testosterone to DHT in the
skin by inhibition of 5α-reductase.

Medroxyprogesterone Acetate
• Oral or intramuscular administration of medroxyprogesterone
acetate (MPA) successfully treats hirsutism.
Dose-150mg im depot inj every 3 months
• It directly affects the hypothalamic–pituitary axis by
decreasing GnRH production and the release of gonadotropins,
thereby reducing testosterone and,estrogen production by the
ovary.

Gonadotropin-Releasing Hormone Agonists
• Administration of GnRH agonists may allow the differentiation
of androgen produced by adrenal sources from that of ovarian
sources .
• Treatment with leuprolide acetate given intramuscularly every
28 days decreases hirsutism and hair diameter in both idiopathic
hirsutism and hirsutism secondary to PCOS.
• Ovarian androgen levels are significantly and selectively
suppressed.

• Glucocorticoids
– Dexamethasone may be used to treat patients with PCOS
who have either adrenal or mixed adrenal and ovarian
hyperandrogenism.
– Doses of dexamethasone as low as 0.25 mg nightly or
every other night are used initially to suppress DHEAS
concentrations to less than 400 μg/dL.
• Ketoconazole
– Ketoconazole inhibits the key steroidogenic cytochromes.
– Administered at a low dose 200 mg per day.

Spironolactone
• specific antagonist of aldosterone, which competitively binds to the
aldosterone receptors in the distal tubular region of the kidney.
– Competitive inhibition of DHT at the intracellular receptor level.
– Suppression of testosterone biosynthesis by a decrease in the CYP
enzymes.
increased peripheral
– Increase in androgen catabolism (with
conversion of testosterone to estrone).
– Inhibition of skin 5α-reductase activity.
• The most common dose is 50 to 100 mg twice daily.

CyproteroneAcetate
• Cyproterone acetate is a synthetic progestin derived from 17-OHP,
which has potent antiandrogenic properties.
• The primary mechanism of cyproterone acetate is competitive
inhibition of testosterone and DHT at the level of the androgen
receptor
• Administered in a reverse sequential regimen cyproterone acetate
100 mg per day on days 5 to 15, and ethinyl estradiol 30 to 50 mg
per day on cycle days 5 to 26.
• This cyclic schedule allows regular menstrual bleeding, provides
excellent contraception.

• Flutamide
• Flutamide, a pure nonsteroidal antiandrogen, is approved for
treatment of advanced prostate cancer.
• Its mechanism of action is inhibition of nuclear binding of
androgens in target tissues.
• Although it has a weaker affinity to the androgen receptor than
spironolactone or cyproterone acetate, larger doses (250 mg
given two or three times daily) may compensate for the
reduced potency.

Finasteride
• Finasteride is a specific inhibitor of type 2 5α-reductase
enzyme activity.
• In a study in which finasteride (5 mg daily) was compared
with spironolactone (100 mg daily), both drugs resulted in
similar significant improvement in hirsutism, despite differing
effects on androgen levels .
• Most of the improvement in hirsutism with finasteride
occurred after 6 months of therapy with 7.5 mg of finasteride
daily.

Insulin Sensitizers
• Because hyperinsulinemia appears to play a role in PCOS-
associated anovulation.
• Treatment with insulin sensitizers may shift the endocrine
balance toward ovulation and pregnancy, either alone or in
combination with other treatment modalities.
Metformin (Glucophage) is an oral biguanide
antihyperglycemic drug used
dependent diabetes.
extensively for non–insulin-

• Metformin is pregnancy category B drug with no known human
teratogenic effect.
• It lowers blood glucose mainly by inhibiting hepatic
glucoseproduction and by enhancing peripheral glucose uptake.
• Metformin enhances insulin sensitivity at the postreceptor level and
stimulates insulin-mediated glucose disposal.
• Although the literature is conflicting, larger studies have suggested
that the live birth rate with metformin alone (7.2%) .
• Lower than that achieved with clomiphene, and the combination
does not confer additional benefit over clomiphene alone.

INFERTILITY DUE TO PCOS
• Ovulation Induction in Women with Polycystic Ovarian
Syndrome
• The goal of ovulation induction refers to the therapeutic
restoration of the release of one egg per cycle in a woman who
either has not been ovulating regularly or has not been
ovulating at all.

Clomiphene Citrate
• Clomiphene citrate is a selective estrogen receptor
modulator
that mimics the activity of an estrogen antagonist when
given at typical pharmacologic doses for the induction
of ovulation.
core
•Corrects LH/FSH ratio
•On clomiphene citrate 80% patient ovulate and 40%
conceive

• Multiple gestation rates with clomiphene citrate are approximately
8%, most of which are twins.
OHSS is rare <1%
• Treatment should be limited to 6 ovulatory cycles or 12 total cycles.
• the usual starting dose is 50mg per day for 5 days D2-D6
• Side effects of clomiphene citrate include vasomotor flushes, mood
swings, breast tenderness, pelvic discomfort, and nausea.

Tamoxifen
• Tamoxifen is an oral antiestrogen similar in structure to clomiphene
that is commonly used as an adjuvant therapy for breast cancer.
• Used off-label to induce ovulation.
• Ovulation and pregnancy rates are similar with tamoxifen and
clomiphene.
Aromatase Inhibitors
• These drugs include letrozole and anastrazole.
• Letrozole- drug of choice in obese patient with infertlity

Gonadotropin Therapy
• Anovulatory PCOS patients who fail to ovulate or conceive with oral
agents should be considered for ovulation induction with exogenous
gonadotropin injections

Risksof Exogenous Gonadotropin Treatment
• Multiple Pregnancy
– Twin births have risen by more than 50% and births of triplet and
higher order multiple pregnancies have more than quadrupled.
– When compared to other anovulatory patients, PCOS patients using
gonadotropins are at higher risk for multiple gestations (36%),
• Ovarian Hyperstimulation Syndrome
– Ovarian hyperstimulation syndrome is an iatrogenic
complication of ovulation induction with exogenous
gonadotropins.
– ovarian hyperstimulation syndrome (30%).
1.Endocrinedisorder,PCOSIn: Berek and Novaks Gynecology,FifteenEdition , New Delhi ,Wolter Kluwer,2012 pp1075t0 1090
2.Reproductive endocrinology,polycystic ovary in speroff’sendocrinologyin gynecology, 7th edition ,walter wilkinsons .

Ovarian Wedge Resection
• Bilateral ovarian wedge resection is associated with only a transient
reduction in androstenedione levels and a prolonged minimal decrease
in plasma testosterone .
• Although Stein and Leventhal’s original report cited a pregnancy rate
of 85% following wedge resection and maintenance of ovulatory
cycles.
• subsequent reports show lower pregnancy rates and a concerning
incidence of periovarian adhesions, premature ovarian failure and
infertility are reported.

LaparoscopicElectrocautery
• Laparoscopic ovarian electrocautery
is used as an alternative to wedge
resection in patients with severe
PCOS whose condition is resistant to
clomiphene citrate.
• In a recent series, ovarian drilling was
achieved laparoscopically with an
insulated electrocautery needle, using
100-W cutting current to assist entry
and 40-W coagulating current to treat
each microcyst over 2 seconds (8-mm
needle in ovary)
1.Endocrine disorder, PCOSIn: Berek and Novaks Gynecology,FifteenEdition , New Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
2.Jeffcoatsgynecology

Recentadvances
• Laproscopic ovarian surgery(LOS) is used for
ovulation induction in women with PCOS after
Clomiphene citrate failure.
• Evidence from RCT and metanalysis indicate
that LOS is as effective as gonadotrophins for
ovulation induction and has the advantage of
avoiding complication such as multiple
pregnancies and OHSS.
• Four punctures per ovary at 30w for 5seconds
per puncture using a monopolar diathermy
needle seems to be optimum amount of energy
required for LOS.

• About 2/3rd of women ovulate after LOSand 50%
conceive within 12months
• About one third of the patients continue to
benefit from LODfor manyyears.
• Postoperative
minimized by
adhesion formation can be
avoiding thermal injury to the
ovarian surface and by ampleirrigation.
• Women with BMI ≥ 35kg/m2 , testersterone ≥ 4.5
nmol/l, FAI15 and or infertility for >3year are
resistant to LOS

Vaginal ultrasound-guided ovarian needle puncture compared to
laparoscopic ovarian drilling in women with polycystic ovary syndrome.
Hatırnaz Ş1, Tan SL2, Hatırnaz E3, Çelik Ö4, Kanat-Pektaş M5, Dahan MH2.
Abstract
STUDY OBJECTIVE:
To compare pregnancy outcomes in PCOS women undergoing
transvaginal ovarian injury (TVOI) and laparoscopic ovarian drilling (LOD) DESIGN: 126
infertile patients with PCOS were included in this prospective cohort study CANADIAN
TASK FORCE CLASSIFICATION OF LEVEL OF EVIDENCE: IIA.
SETTING:
University-affiliated fertility center.
PATIENTS:
Sixty-seven infertile patients with the history of failed in vitro maturation underwent
follow-up as the TVOI group. Fifty-nine infertile women who underwent LOD acted as
controls. All subjects had PCOS with menstrual irregularity and were anovulatory by
repetitive serum progesterone levels.
.

INTERVENTIONS:
The LOD group underwent six cauterizations of a single ovary with 30W for 4-6 s. Failed
IVM subjects with 20-30 needle punctures per ovary acted as the TVOI group. Subjects
were followed for six months.
MEASUREMENTS AND MAIN RESULTS:
There was not a significant difference between the groups when the cases were
evaluated in terms of spontaneous pregnancy or miscarriage rates. BMI levels decreased
in both the TVOI and the LOD groups in a similar fashion. However, serum AMH and AFC
decreased greater after LOD than they did with TVOI over the six-month duration of the
study (p < 0.001 in both cases).
CONCLUSIONS:
Preliminary data suggest that TVOI likely represents a safer, less costly and equally
effective manner of surgical ovulation induction in anovulatory PCOS women when
compared to LOD

Metformin during ovulation induction with gonadotrophins followed by timed
intercourse or intrauterine insemination for subfertility associated with
polycystic ovary syndrome.
Bordewijk EM1, Nahuis M2, Costello MF3, Van der Veen F4, Tso LO5, Mol BW6, van
Wely M4.
Clomiphene citrate (CC) is generally considered first-line treatment in women
with anovulation due to polycystic ovary syndrome (PCOS). Ovulation induction
with follicle-stimulating hormone (FSH; gonadotrophins) is second-line treatment
for women who do not ovulate or conceive while taking CC. Metformin may
increase the effectiveness of ovulation induction with gonadotrophins and may
promote safety by preventing multiple pregnancy.
Preliminary evidence suggests that metformin may increase the live birth rate
among women undergoing ovulation induction with gonadotrophins. At this
moment, evidence is insufficient to show an effect of metformin on multiple
pregnancy rates and adverse events. Additional trials are necessary before we can
provide further conclusions that may affect clinical practice.

2016 Dec;33(6):770-780. doi: 10.1016/j.rbmo.2016.08.024. Epub 2016 Sep 16.
Inositol as putative integrative treatment for PCOS.
Genazzani AD1.
Abstract
Studies over the last decade have demonstrated that some polycystic ovary syndrome
(PCOS) patients have abnormal insulin sensitivity (insulin resistance), independently
from being overweight or obese. This induces the risk of developing type 2 diabetes in
such PCOSpatients. The use of insulin sensitizers (i.e. metformin), reduces such
metabolic, and most hormonal, impairments. As metformin often induces side
effects, new integrative strategies have been proposed to treat insulin resistance, such
as the use of inositols. Such compounds are mainly represented in humans by two
inositol stereoisomers: myo-inositol (MYO) and d-chiro-inositol (DCI). MYO is the
precursor of inositol triphosphate, a second messenger that regulates thyroid-
stimulating hormone (TSH) and FSH as well as insulin. DCI derives from the conversion of
myo-inositol via an insulin-dependent pathway. Several preliminary studies have
indicated possible benefits of inositol therapy in PCOS patients, but to date no meta-
analysis has been performed. This review aims to give clinical insights for the clinical use
of inositol in PCOS.

Inositol: history of an effective therapy for Polycystic Ovary Syndrome.
Bizzarri M1, Carlomagno G.
Abstract
Inositol is a physiological compound belonging to the sugar family. The two inositol
stereoisomers, myo-inositol and D-chiroinositol are the two main stereisomers present
in our body. Myo-inositol is the precursor of inositol triphosphate, a second messenger
regulating many hormones such as TSH, FSH and insulin. D-chiroinositol is synthetized
by an insulin dependent epimerase that converts myo-inositol into D-chiro-inositol.
Polycistic Ovary Syndrome (PCOS) is a metabolic and hormonal disorder and a common
cause of infertility. Insulin resistance and the consequent hyperinsulinaemia contribute
to hyperandrogenism development, typical marker of PCOS. In these patients myo
and/or D-chiro-inositol administration improves insulin sensivity while only myo-
inositol is a quality marker for oocytes evaluation. Myo-inositol produces second
messengers for FSH and glucose uptake, while D-chiroinositol provides second
messengers promoting glucose uptake and glycogen synthesis. The physiological ratio
of these two isomers is 40:1 (MI/DCI) and seems to be an optimal approach for
the treatment of PCOS disorders.

pcoss.pptx all india institute of medical sciences

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