Polycystic ovary syndrome

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Polycystic ovarian syndrome
Prof. Yousef Gadmour Al- Fateh university Al-
Jalla Maternity Hospital Tripoli - Libya
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Polycystic ovarian syndrome

• Definition
• It is a clinical syndrome characterized by
  presence of polycystic ovary and symptoms such as
  
• 1. Infertility .
• 2. Hirsutism.
• 3. Oligo-amenorrhoea.
• 4. Obesity.
• 5. Dysfunctional uterine bleeding.
• 6. Verilisation.
• 7. Hyperprolactinaemia.
  

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Incidence

• - It is the Commonest endocrinal gynecologic
  disorder
• - About 2 of general population.
• - 4-10 based on clinical, biochemical and
  u/s criteria.
• - 10-20 based on U/s only.
• - 30 of infertility.
• - 90 of Hirsutism with regular cycle.
• - 87 of case of oligomenorrhea.
• - 82 of cases with recurrent miscarriage.

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Pathology

• The ovaries are enlarged and show
• Numerous small cystic follicles ( usually 2-8 mm
  in diameter and peripherally placed ) .
  
• Thickened white ovarian capsule .
• Theca cell hyperplasia ( due to increased LH ).
• Granulosa cell atresia ( due to low FSH ) .
• The cystic follicles and increased ovarian
  stroma can be demonstrated by ultrasound .

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Endocrine abnormalities ( cont.)

• Androgens ovarian androgens excretion
  (testosterone and
  androstenedione )is commonly increased but the
  adrenal (dehydroepiandrosterone-sulfate) is also
  involved in up to 40 of cases.
• Sex hormone binding globulin (SHBG) levels are
  reduced This result in an increase in unbound
  (and therefore active ) androgen and oestradiol
  levels.
• Insulin women with PCOS are hypre-insulinaemic
  but are insulin-resistant.
• ( Hyper-insulinaemia levels of
  SHBG)
• (? PC0S mechanism )

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Pathogenesis

• connective Tissue
• Androstenedione
  Oestradiol
  Oestrone
• ( ov. adrenal )
• Obesity Insulin
  SHBG Free Oestradiol
• 
  DUB
• 
  FSH Granulosa cell
  atresia
• 
  LH No LH surge No
  ovulation
• 
  
• 
  Theca cell hyperplasia
• 
  5 a-reductase
  
• Hirsutism DHT
  Androgens

Free Oestradiol
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High Follicular phase LH concentrations have
been found to be associate with

• Poor oocytes quality
• Reduced rate of fertilization
• Reduced pregnancy rate
• Increase incidence of miscarriage

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Diagnosis of PCOS

• Oligoamenorrhea or amenorrhea and subfertility.
• Symptoms of androgen excess.
• U /S (Adams criteria) 1-Many follicles 8-10
• 
  2-Follicles lt10mm diameter
• 
  3-Thickened white capsule
• 
  4-Hyperechogenic stroma
• Biochemical ?LH in 40 of cases (LH/FSHgt2)
• ?serum testosterone in
  30 of cases
• serum prolactin in 40
  of cases

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Management

• Principals of management
• Confirm diagnosis and identify category.
• Identify and manage concurrent illness.
• Identify and manage patient needs.
• There are numerous options for successful PCO
  management medical / surgical

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Preprocedural Considerations

• Endometrial Neoplasia
• Insulin Resistance
• Metabolic Syndrome
• Weight loss

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Endometrial Neoplasia

• Chronic anovulation associated with PCOS may lead
  to endometrial hyperplasia and sometimes to frank
  endometrial cancer (Meier and Schenker,1996).
• Endometrial biopsy is indicated in all women with
  H/O long term unopposed estrogen exposure and in
  those where endometrial thickness is greater than
  12mm.

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Insulin Resistance (IR)

• IR is defined as reduced glucose response to a
  given amount of insulin.
• It occurs in 80 of obese women and 30 to40 of
  women with normal wt. with PCOS .
• Peripheral target tissue insulin resistance can
  be due to decreased no of peripheral insulin
  receptors, decreased insulin binding or a post
  receptor failure.
• In PCOS it is caused by the post receptor defect
  due to excessive serine phosphorylation of beta
  chain of insulin receptor and of adrenal and
  ovarian cytochrome P450c enzyme . This enzyme is
  a rate limiting step in androgen biosynthesis
  thus leading to hyperandrogenemia .

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Diagnostic criteria for metabolic syndrome

• Diagnosis is made when 3 or more of
• these risk criteria are met
• ? Glucose 6.1 mmol/l
• Waist circumference 88 cm.
• ? HDL-C 1.3 mmol/l
• ?BP 130 / 85 mm Hg
• ?TG 1.7 mmol/l
• (Shroff et
  al.,2007)

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Weight Loss

• Weight loss has advantage of being effective and
  cheap with no side effects and should be the
  first line of treatment .
• Weight loss improves endocrine profile and
  ovulation and subsequent healthy pregnancy
  (decreasing insulin and androgens and increasing
  SHBG ).
• Weight loss has been shown to improve the outcome
  of all forms of infertility treatments, including
  IVF (Clark et al.,1998).

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Various treatment modalities

• Pharmacological Treatment
• CC
• 
  
• Gonadotropin
  Hyperinsulinemia?
  
• hMG
  Insulin sensitizer
• uFSH GnRH-analogs
• HP-FSH
• rec-FSH

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A. Medical Treatment

• Infertility is treated by increasing the rate of
  ovulation, in part by reducing insulin drive
  through exercise and weight loss .
• Ovarian stimulation is used for those patients
  who do not ovulate, despite loosing weight by
  different drugs and different protocols.

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Medical Treatment (cont.)

• Treat Hyperprolactinaemia with Bromocriptine.
• Glucocorticoids for adrenal hyperplasia .
• ( 0.25mg Dexamethasone at night )
• COC pills or POP for dysfunctional uterine
  bleeding and to reduce the risk of endometrial
  carcinoma .

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Insulin sensitizing drugs

• Metformin
• Action
• -inhibit hepatic glucose production.
• -enhance sensitivity of peripheral tissues to
  insulin
• -? insulin secretion.
• ? Ovarian hyperstimulation in gonadotrophin
  therapy
• RCT- clomiphene -resistant pts., use of metformin
  CC produced significant improvement

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B. Surgical treatment modalities

• Surgical Treatment
• Cauterization Wedge resection
• ( laser, electric )

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Methods of Ovarian Surgery For Ovulation
Induction In PCOS

• Laparoscopic Techniques of Ovarian Surgery (LOS)
• Laparoscopic Ovarian Drilling (LOD)
• Diathermy / LASER.
• Transvaginal Techniques of Ovarian Surgery (TVOS)
• 1) Transvaginal mini-laparoscopy (Fertiloscopy)
• 2) Transvaginal ultrasound (TVS)-guided ovarian
  drilling.

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Indications

• I. Ovulation induction in the following cases
• a) C.C resistant PCO
• Defined as failure to ovulate on a dose of 100
  mg, for 5 days (recently in 3 cycles, in contrast
  to 6 cycles in the past ) or
• failure to ovulate on incremental doses of
  CC(50-150mg).
• b) C.C failure PCO
• Defined when pregnancy does not occur despite of
  regular ovulation on C.C for 6-9 cycles.
• c) C.C pregnancy failure
• Defined as failure to maintain pregnancy
  conceived with C.C.

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Indications( cont.)

• II. Other potential indications
• 1. LH hypersecretion.
• 2. Patient cannot follow treatment regularly.
• Prevention of long term morbidity in PCOS
  
  
  
  
• patient.
• 4. Menstrual irregularity in PCOS patient.
• 5. Acne and hirsutism resistant to treatment
  in
• PCOS patient.

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Mechanism of action Of LOS

• 1. Drainage of atretic follicles with high
  (Androgen inhibin) content.
• 2. Destruction of ovarian stroma that produce
  androgen.
• 3.LOS ? Postoperative ? of FSH ??Intra-follicular
  aromatase activity
• 1,2,3 ?
• ?Intra-follicular androgenic environment ? remove
  intraovarian block to follicular maturation that
  precedes ovulation.

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Mechanism of action Of LOS (CONT.)

• 4.Surgical trauma to the ovary
• Production of non steroidal factors ? Restore
  hypothalamo-pitutary-ovarian function.
• Production of ovarian growth factorsIGF-1?
  Sensitize ovary to circulating FSH.

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Risks

• 1-Adhesion formation,
• 2-Potential surgical risks (bleeding and
  infection)
• 3-Anesthesia risks,
• 4-Premature ovarian failure (theoretical
  complication)

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Technique Of LOS

• Utero-ovarian ligament
• is grasped by atrumatic
• forceps moving the ovary
• (towards anterior
• abdominal wall in
• front of the uterus).

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LASER versus electrocautery for LOS

• Electrocautery IS superior why?
• 1) Less coast easy application.
• 2) Achieve higher ovulation and pregnancy rate.
• 3) Less surface injury than CO2 LASER ? Surface
  adhesion.
• 4 Effect of diathermy may last longer than the
  effect of LASER .

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Results

• Short term results
• In responders ovulation occur within 2-4 wk,
  menstruation within 4-6 wks.
• Ovulation rate 50-90.(Patient with high LH
  level respond better to LOS).
• Cumulative Pregnancy Live birth rates76-64
  respectively.
• Long term results
• Improvement in reproductive performance is
  sustained for many years. (49 Of women conceived
  within the 1st year after LOS)

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Conclusions

• Obesity plays a central role in development of
  PCOS leading to Hyperinsulinemia in susceptible
  individuals.
• This Hyperinsulinemia may alter androgen
  metabolism via a variety of mechanisms, the net
  result of which Hyperandrogenism.

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Conclusions

• The management of patients with PCOS depends upon
  the individual patients complaints.
• Hyperandrogenism is optimally dealt with by
  reducing insulin drive to the ovary, such as
  exercise and reducing diet

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Hirsutism

• Definition
• Excessive and inappropriate growth of facial and
  body hair .

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Causes

1. Endocrine- PCOS adrenal hyperplasia/Cushing's
   syndrome hypothyroidism acromegaly .
2. Androgen-secreting tumours of adrenal or ovary .
3. Drugs- phenytoin , diazoxide , danazol ,
   corticosteroids .
4. Idiopathic .

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Investigation

• 1. Check serum testosterone if lt 5 nmol /l no
  further investigation .If gt 5 nmol/l repeat
  and check urinary steroids in 24
  hour sample.
• 2. Check serum LH and FSH . An elevated LH
  suggests PCOS .
• 3. Pelvic ultrasound will demonstrate polycystic
  ovaries.
• 4. Check thyroid function .

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• 5. Measure serum 17-hydroxyprogesterone if
  congenital adrenal hyperplasia is suspected .
  If levels are high consider ACTH stimulation
  and dexamethasone suppression tests .
• 6. If urinary cortisol is elevated investigate
  for Cushing's syndrome .
• 7. If adrenal tumor is suspected carry out CT
  scans and consider direct catherisation of
  adrenal veins or surgical exploration .
  

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Treatment

• This will depend on the cause.
• Sympathetic handling and reassurance are
  necessary at all times.

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1. Polycystic ovary syndrome

• Induce ovulation if infertility is also a
  problem.
• combined oesrogen/progestogen pill to
  suppress androgen production. Response to
  treatment is slow at best. It may be 6 months to
  a year before any reduction in hirsutism is seen.
• Cyproterone acetate is an anti-androgen
  with progestogenic activity.
• Pregnancy must be avoided during its use.
• It is therefore best used cyclically (day
  5-15) in combination with ethinyl Oestradiol
  (day 5-26) which not only helps to inhibit
  ovulation but also increases SHBG
  concentrations.
• This lowers the levels of free androgens.

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• 2. Adrenal hyperplasia
• This is the only situation in which
  corticosteroid treatment remove after
  localisation.
• 3. Androgen producing tumours
• Remove after localisation.
• 4. Idiopathic hirsutism
• This may be due to end organ
  hypersensitivity. There may be some
  response to the
  oesrogen/progestogen pill or spironolactone
  and electrolysis is useful cosmetically.

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Thanks