Polycystic Ovary Syndrome (PCOS), Asherman, OHSS😍

Polycystic Ovary Syndrome (PCOS/PCOD)

Primary Pathology

1. Increased Androgen Production:
• Mainly by ovaries.
• Androgen levels in females: < 70 ng/dL (normal range: 10-50 ng/dL)
• PCOS levels: 70-200 ng/dL.

2. Abnormal Follicular Maturation
• (due to ↑ androgen level)
• No follicular maturation.
• No ovulation.
• No corpus luteum formation.
• No progesterone production.
• Leads to:
• Patient with chronic infertility.
• Secondary amenorrhea
• ↑↑ chances of abortion.

Associated Features

1. Insulin Resistance

2. Obesity:
• In obese E1:E2 = 2:1
• Normal ratio: 1:2
• Due to androgen in adipose tissue is converted into E1
• Also complains of menometrorrhagia

3. Abnormal Gonadotropin Secretion:
• LH is Increased.
• FSH is Normal
• Normal LH:FSH ratio = 1:1.
• In PCOS patients, this ratio is 2:1 or 3:1.
• FSH test is done on Day 2 or Day 3 of menstrual cycle.

HAIR - AN syndrome:

• HA: Hyperandrogenism

• IR: Insulin Resistance

• AN: Acanthosis nigricans
• hyperpigmented,
• velvety skin folds,
• common at the nape of the neck

Diagnostic Criteria (Rotterdam Criteria)

1. Increased Androgen Levels:

• Clinically (hirsutism) OR

• Biochemically (high testosterone or DHEA-S).

2. Oligovulation/Anovulation:

• Oligomenorrhea/Amenorrhea (< 9 cycles/year)

• Hirsuitism → Ferriman Gallaway score

• Infertility

3. On Ultrasound (USG):

 

• IOC

• "Necklace pattern / String of pearls"

• Most specific
• ↑↑ Stromal volume/echogenicity
• Volume of ovary: ≥ 10 cc.

• Follicles:
• ≥ 12 follicles per ovary (or in both ovaries)
• Size: ≤9 mm.
• Arranged in periphery
• No dominant follicles

OHSS or Theca Lutein Cyst.

• Large follicles present throughout the ovary
• OHSS (Ovarian Hyperstimulation Syndrome):
• Seen in patients on infertility treatment.
• Theca Lutein Cyst:
• Seen in molar or twin pregnancy.
• Increase in Beta HCG is observed.

Lab Findings

• Normal
• DHEA-S (Dehydroepiandrosterone sulfate)
• bcz produced from adrenal

• Increased:
• Testosterone
• <150 ng/dL → PCOD
• >150 ng/dL → androgen secreting tumor
• ↑↑ LH/FSH ratio
• Stromal volume ↑↑ → bcz ↑↑ LH act on theca cells present in stroma
• LDL
• Estrogen
• AMH
• Glycoprotein hormone
• Gene for MIS/AMH
• Chromosome 19
• Produced by
• Sertoli cells at 7 weeks
• Granulosa cells of preantral and small antral follicles
• Function: Regression of Mullerian Duct in males.
• Best test for Ovarian reserve
• Done any day
• 1 - 3 = Normal
• High AMH
• > 3: PCOS
• > 3.3: High risk of OHSS
• Good outcome of IVF
• Low AMH
• <1 = Suggestive of POI (Poor Ovarian reserve)
• <0.5 = Diagnostic of POI

• Decreased:
• Progesterone
• SHBG (Sex Hormone-Binding Globulin)

• Unchanged:
• FSH
• Prolactin

• Progesterone Challenge Test: 
• Positive (withdrawal bleeding after progesterone administration)

Differential Diagnosis (PCOS vs Late Onset CAH)

• Probable PCOS Diagnosis: 
• Exclude late-onset CAH

• Check 17-hydroxyprogesterone:
• < 200 ng: Rules out late-onset CAH.
• 200-800 ng: ACTH stimulation test required.
• ≥ 800 ng: Definitive diagnosis of late-onset CAH (rare).

Management of PCOS

First-Line Management (All Patients)

1. Lifestyle Modification:
• Weight management (diet & exercise).

2. Irregular Cycles:
• Oral Contraceptive Pills (OCPs).

3. Hirsutism:
• OCPs.
• Spironolactone > OCPs is not used if conception is desired.

4. Insulin Resistance:
• Metformin.

5. Overall DOC for PCOS:
• OCPs.

Note

• Indication for Metformin in PCOS
• Insulin resistance
• HMG use

• NOTE:
• HMG is always given with HCG
• HCG → ↑ risk of OHSS

Management of Infertility

1. First Step:
• Lifestyle modification & weight management.

2. First-Line (Anovulation):
• Both can be used only if FSH is Normal
  (Intact Hypothalamic-Pituitary-Ovarian axis).
1. DOC: Letrozole (aromatase inhibitor)
• T 1/2: 46 hours
• Higher chances of live birth rate
2. Clomiphene Citrate (CC).
• NOTE:
• FSH normal → Letrozole/Clomifene citrate
• FSH abn → hCG/HMG

3. Second-Line:
• If insulin resistant:
• CC + Metformin
• If DHEA increased:
• CC + Cortisol
• To decrease androgen levels:
• OCPs (After 2-3 cycles of CC) -> Then resume CC.
• After 2-3 cycles of CC:
• Human Menopausal Gonadotropin (hMG)
• Synthetic LH & FSH
• Obtained from urine of menopausal females.
• HMG stimulates follicular development,
• hCG is added to trigger ovulation.

4. Third-Line:
• Pulsatile GnRH.
• Laparoscopic Ovarian Drilling (earlier done surgically).

Laparoscopic Ovarian Drilling (LOD)

• Principle:
• Burn stroma of ovary to destroy theca cells.
• Decreases androgen levels.

• Advantages:
• No increased chances of twin pregnancy.
• No increased risk of Ovarian Hyperstimulation Syndrome (OHSS).

• Disadvantages:
• May lead to premature ovarian insufficiency (POI).

Long-Term Complications of PCOS

• Due to Increased Androgen:
• Dyslipidemia (Increased LDL, decreased HDL).
• Increased CAD

• Due to Increased Estrogen:
• Endometrial Hyperplasia.
• Endometrial Carcinoma.
• Non-alcoholic Steatohepatitis.
• Ovarian Carcinoma (rare).

• Due to Obesity:
• Anxiety/Depression.
• Sleep Apnea Syndrome.
• Metabolic Syndrome.

• Note: Osteoporosis is generally not a complication,
• as estrogen levels are not significantly low in PCOS.

• Hirsutism Scoring: 
• Ferriman Gallwey score
• ≥ 8 is considered significant (>= 6 in Asian females).

Asherman Syndrome

• A condition characterized by:
• Intrauterine adhesions (scar tissue) within the uterus
• Leading to a thin, defective endometrium

Causes

• Most Common Cause:
• Excessive curettage

• Other Causes:
• Excessive Dilation and Curettage (D&C) procedures
• Genital Tuberculosis (TB)

• Highest Risk Period:
• Postpartum period

Clinical Presentation

• Group of Symptoms
• Menstrual Irregularities >
• Infertility (most common single symptom) >
• Secondary Amenorrhea >
• Hypomenorrhea: Scanty or very light bleeding

Diagnostic Approach

Lab Tests

• Hormone Levels (typically normal):
• Luteinizing Hormone (LH)
• Follicle-Stimulating Hormone (FSH)
• Estrogen

• Progesterone Challenge Test:
• Negative
• No bleeding occurs after progesterone administration

• Estrogen and Progesterone (E+P) Challenge Test:
• Negative
• No bleeding occurs after E+P administration
• Note: These negative results suggest the issue is with the uterine lining (endometrium), not hormone production.

1st Investigation:

• Hysterosalpingography (HSG)
• "Moth-eaten" appearance
• Presence of multiple filling defects
• With irregular margins
• Distinguish from Polyps/Fibroids:
• Polyps/Fibroids typically show a single filling defect
• With smooth, regular margins

Imaging & Treatment:

• Investigation of Choice (IOC): 
• Hysteroscopy (Diagnostic & Therapeutic)
• Can also be used therapeutically to treat the adhesions.
• Allows direct visualization of the uterine cavity.

Management

1. Hysteroscopic Adhesiolysis

2. Hysteroscopic Transection

3. Insert a Paediatric Foley's Catheter: 
• Prevents immediate reformation of adhesions.

4. Estrogen and Progesterone (E+P) Therapy:
• for 3 months post-procedure.
• To promote re-growth of endometrial lining.

Ovarian Hyperstimulation Syndrome (OHSS)

Overview

• Iatrogenic Complication: Induced by medical treatment.

• Max Risk with: HMG > Clomiphene Citrate

• Not caused by: Letrozole.

Etiopathogenesis

• HMG is always given with HCG

• β hCG (used as ovulation trigger with hMG use)
• Causes multiple follicles to mature.
• Leads to increased VEGF
• Results in increased capillary permeability → OHSS

Risk Factors

• PCOS.

• Thin females.

• Pregnancy.

• Young age.

• Serum E2 (Estrogen) > 2500 pg/mL.

• AMH > 3.3.

• More than 20 follicles

• > 10 mm size.

Prevention

• Monitor follicular number and estrogen (E2) levels.

• Stop gonadotropins if risks are high.

• Do not give injection hCG for ovulation if E2 > 2500 pg/mL.

• Give Cabergoline (Dopamine agonist) to decrease VEGF.

Classification of OHSS

USG Findings: 

• Large follicles,

• increased number of follicles,

• no stroma.

Comparison to Molar Pregnancy:

• If h/o infertility + Rx for infertility +/- IVF (hMG use)
• OHSS

• +ve UPT + bleeding in 1st or early 2nd trimester
• Molar pregnancy
• ↑ beta hCG → Theca Lutein Cysts