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Endometriosis

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Definition

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Epidemiology

• Prevalence: ~10% of women of reproductive age; up to 20–90% of women with pelvic pain or infertility; up to 50% of women with unexplained infertility.
• Found in women of all ethnic and social groups; reported in adolescents and postmenopausal women on HRT.
• Economic burden is comparable to diabetes mellitus, Crohn's disease, and rheumatoid arthritis (WERF EndoCost study).

Risk Factors

Protective Factors

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Etiology / Pathogenesis

1. Retrograde menstruation / Ectopic transplantation (Sampson's theory) — the most widely accepted. Viable endometrial cells shed retrogradely via the fallopian tubes implant on peritoneal surfaces. Not all women with retrograde menstruation develop endometriosis, suggesting immune factors play a role.
2. Coelomic metaplasia — peritoneal mesothelial cells undergo metaplastic transformation into endometrial-like tissue.
3. Lymphovascular spread — explains distant/extrapelvic sites.

Immunologic Factors

Genetic Factors

• ~5–8× increased risk in first-degree relatives.
• Genome-wide studies show association with SNPs on chromosomes 1p36, 2p25, 6p24, 7p15, 9p21, 10q26, 12q22.
• Somatic mutations (ARID1A, PIK3CA, KRAS) found in endometriotic lesions, especially those co-occurring with clear-cell or endometrioid ovarian carcinoma.

Environmental Factors

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Clinical Presentation

Symptoms

1. Dysmenorrhea — most common; progressive, starting days before menstruation
2. Dyspareunia (deep) — especially with uterosacral/rectovaginal disease
3. Chronic pelvic pain — found in 15–40% of laparoscopies for CPP
4. Dyschezia — pain on defecation; associated with rectovaginal and posterior cul-de-sac disease
5. Infertility — endometriosis found in 33% of infertile women vs 4% of fertile women
6. Dysuria / urinary symptoms — with bladder involvement
7. Cyclic rectal bleeding, hemoptysis, or hemothorax — with bowel or thoracic endometriosis (rare)

Important: There is no correlation between the stage of disease and severity of pain. Up to 30–50% of patients have no pain regardless of stage.

Endometriosis-Related Pain Syndrome

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Clinical Examination

• Nodularity or tenderness of the uterosacral ligaments and posterior cul-de-sac
• Fixed, retroverted uterus ("frozen pelvis") in advanced disease
• Tender adnexal masses (endometriomas)
• 40–60% of patients have no tenderness on examination regardless of stage

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Imaging

Ultrasound

MRI

CA-125

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Macroscopic & Laparoscopic Findings

Types of Lesions

• Peritoneal endometriosis: most common form; variable appearance
• Ovarian endometriomas ("chocolate cysts"): thick, viscous dark-brown fluid; typically on the anterior ovarian surface with adhesions to posterior peritoneum
• Deep infiltrating endometriosis (DIE): penetrates >5 mm beneath the peritoneum; involves rectovaginal septum, uterosacral ligaments, bowel, ureters, bladder

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Diagnosis

• Positive histology confirms the diagnosis; negative histology does NOT exclude it
• Histology is recommended for endometriomas >4 cm and deep endometriosis (to exclude malignancy)
• Visual inspection alone is usually adequate for peritoneal disease

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Classification / Staging

rASRM Staging (Revised American Society for Reproductive Medicine)

⚠️ The rASRM system correlates poorly with pain and fertility outcomes (subjective, high inter-observer variability). The World Endometriosis Society still recommends its use for standardization.

Endometriosis Fertility Index (EFI)

• Historical factors: age, years of infertility, prior pregnancies
• Surgical factors: total rASRM score, ASRM endometriosis score, "least function score" (fallopian tube, fimbriae, ovary functionality)

ENZIAN Score

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Endometriosis and Infertility

1. Prevalence 33% in infertile women vs 4% in fertile women
2. Reduced monthly fecundity rate (MFR) in women and primates with endometriosis
3. Endometriomas negatively affect spontaneous ovulation rates
4. Dose-effect relationship: higher rASRM stage → lower MFR and cumulative pregnancy rate
5. Reduced implantation rate per embryo in IVF compared to tubal-factor infertility

No good evidence that endometriosis increases spontaneous abortion rates.

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Management

Principles

• Goal: relieve symptoms (pain/infertility), prevent progression, preserve fertility
• Severe/deep endometriosis should be managed in a multidisciplinary center with advanced laparoscopic expertise
• ESHRE guidelines are the primary reference

Treatment of Endometriosis-Associated Pain

1. NSAIDs

• First-line for dysmenorrhea; evidence is weak for endometriosis specifically
• Mechanism: local antinociceptive + anti-inflammatory effects; reduces central sensitization
• Avoid at ovulation if pregnancy desired (PG-dependent follicle rupture)

2. Hormonal (Medical) Treatment

Duration: 6 months of ovarian suppression is the standard evidence-based duration for pain relief. Pain often recurs after cessation of medical treatment.

3. Surgical Treatment (Pain)

• Conservative surgery (laparoscopic ablation/excision of lesions + adhesiolysis): more effective than diagnostic laparoscopy alone for pain relief in minimal–mild disease
• Deep endometriosis: complete surgical excision in a single procedure is recommended; involves possible bowel/bladder/ureter resection
• Radical surgery (hysterectomy ± oophorectomy): last resort; reserved for women who have completed childbearing with refractory disease
• Preoperative hormonal therapy is not recommended (no evidence of benefit on outcomes)

Treatment of Endometriosis-Associated Infertility

• Surgical treatment: Ablation/excision of minimal–mild disease improves fertility over diagnostic laparoscopy alone (↑ live birth rate)
• Medical treatment alone: Not effective for improving fertility — conception is impossible during hormonal suppression
• Postoperative medical treatment: Not indicated (delays spontaneous conception; highest pregnancy rates occur in first 6–12 months post-surgery)
• ART/IVF: Method of choice when tubo-ovarian anatomy is distorted; also used when surgery has failed
• Expectant management: Reasonable for minimal–mild disease in younger women

Management of Recurrent Endometriosis

• Risk factors for recurrence: young age at initial surgery, incomplete excision, no postoperative hormonal suppression
• Prevention: continuous OCs or progestins post-surgery
• Medical treatment of recurrence: same agents as primary treatment; GnRH agonists with add-back
• Surgical re-treatment: possible, but carries increased risk of complications

Management in Adolescents

• Most common symptom: cyclic pelvic pain
• Laparoscopy indicated for chronic pelvic pain not responding to NSAIDs/OCs
• Endometriosis found in up to 70% of adolescents with refractory CPP
• Stages I–II are most common in this age group; red/clear/white lesions (subtle) predominate
• GnRH agonists reserved for adolescents >17 years who have completed bone maturation

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Endometriosis and Cancer

• Modest increased risk of endometrioid and clear-cell ovarian cancer (OR 1.3–1.9); causal relationship recognized but absolute risk is low
• Possible association with melanoma and non-Hodgkin lymphoma (requires confirmation)
• Endometriosis itself should not be regarded as a condition with clinically relevant cancer risk

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Key Points Summary (from Berek & Novak's)

1. Diagnosis requires laparoscopic visualization ± histology; negative histology does not exclude it.
2. Associated with infertility, dysmenorrhea, dyspareunia, non-menstrual pain, and reduced QoL.
3. Severe/deep disease must be managed in a multidisciplinary center.
4. rASRM staging correlates poorly with pain and infertility outcomes.
5. EFI predicts non-IVF pregnancy rates after surgical treatment.
6. All hormonal drug classes are equally effective for pain; choice depends on side effects and cost.
7. Surgical excision in minimal–mild disease improves fertility over diagnostic laparoscopy alone.
8. Hormonal suppression does NOT improve fertility.

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Endometriosis

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Definition

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Epidemiology

• 10% of reproductive-age women
• 33% of infertile women; 20–90% of women with pelvic pain
• Found in all ethnic groups; also in adolescents and postmenopausal women on HRT

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Pathogenesis — Three Theories

Not all women with retrograde menstruation develop disease → immune factors (↓NK cell activity, ↓macrophage clearance) determine susceptibility.

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Clinical Features — "5 Ds"

⚠️ No correlation between stage and severity of pain. 30–50% of patients have no pain regardless of stage.

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Examination Findings

• Uterosacral ligament nodularity/tenderness
• Fixed retroverted uterus ("frozen pelvis")
• Adnexal masses (endometriomas)
• 40–60% have no tenderness on exam

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Diagnosis

• Positive histology → confirms; negative histology does NOT exclude
• Histology mandatory for endometriomas >4 cm and deep disease (to exclude malignancy)

Laparoscopic Lesion Types

Sites

• Peritoneal (most common)
• Ovarian endometrioma — "chocolate cyst": thick dark-brown fluid, anterior ovarian surface, adhesions to posterior peritoneum
• Deep infiltrating endometriosis (DIE) — penetrates >5 mm; rectovaginal septum, uterosacral ligaments, bowel, ureter, bladder

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Investigations

• TVUS: first-line; best for endometriomas ("ground-glass" cysts)
• MRI: best for mapping DIE preoperatively
• CA-125: low sensitivity; not for diagnosis — useful for monitoring

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Staging — rASRM Classification

⚠️ rASRM correlates poorly with pain and fertility outcomes (subjective, high inter-observer variability).

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Management

Pain — Medical Treatment

Duration: 6 months of suppression standard. Pain recurs after stopping treatment.

Pain — Surgical Treatment

• Laparoscopic ablation/excision + adhesiolysis: superior to diagnostic laparoscopy alone
• DIE: complete excision in one procedure; may require bowel/bladder/ureter resection; refer to specialized center
• Hysterectomy ± oophorectomy: last resort for refractory disease in women who have completed childbearing
• Preoperative hormonal therapy: NOT recommended (no evidence of benefit)

Infertility Treatment

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Endometriosis and Cancer

• Modest ↑ risk of endometrioid and clear-cell ovarian cancer (OR 1.3–1.9)
• Not considered a condition with clinically significant cancer risk overall

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High-Yield Exam Points

1. Definition: endometrial glands/stroma outside uterus
2. Diagnosis: surgical (laparoscopy); negative histology does not exclude
3. Best theory: Sampson's retrograde menstruation
4. Stage ≠ severity of pain — key examiner favourite
5. All hormonal agents equally effective for pain
6. Medical treatment does NOT improve fertility
7. Surgical excision (not suppression) improves fertility in minimal–mild disease
8. GnRH agonists: need add-back therapy >6 months
9. Danazol: androgenic side effects; voice change is irreversible
10. EFI: predicts non-IVF pregnancy rates (not pain outcomes)

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Endometriosis

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Definition

• Endometriosis interna (Adenomyosis) — endometrial tissue within the myometrium
• Endometriosis externa — endometrial tissue outside the uterus (this chapter deals with externa)

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Incidence

• Affects 10–15% of women of reproductive age
• Found in 25–35% of infertile women
• Peak incidence: 25–35 years (reproductive age)
• Rare before menarche; may occur postmenopausally in women on HRT

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Sites of Endometriosis

Pelvic (Common)

1. Ovaries — most common site (~60%); "chocolate cysts" (endometriomas)
2. Pouch of Douglas / posterior cul-de-sac
3. Uterosacral ligaments
4. Posterior surface of uterus and broad ligament
5. Fallopian tubes
6. Rectovaginal septum
7. Pelvic peritoneum
8. Sigmoid colon and appendix
9. Urinary bladder and ureters

Extrapelvic (Rare)

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Pathogenesis — Theories

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Morbid Anatomy

Ovarian Endometriosis ("Chocolate Cyst")

• Cyst contains thick, dark-brown tarry fluid (degenerated blood — hemosiderin)
• Wall is lined by endometrial epithelium
• Adhesions to surrounding structures (posterior uterine wall, broad ligament)
• Repeated bleeds → enlargement of cyst

Peritoneal Implants

• Early/Active: Red, flame-like vesicles — bleed cyclically
• Old/Inactive: Black "powder-burn" spots — hemosiderin deposits
• Fibrotic: White stellate scars — may mimic normal peritoneum

"Frozen Pelvis"

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Pathophysiology of Symptoms

• Produces prostaglandins → pain
• Inflammation damages pelvic structures → infertility

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Clinical Features

Symptoms — Classic Triad

1. Dysmenorrhea — congestive, progressive, spasmodic; starts 2–3 days before flow; key feature: worsens over years
2. Dyspareunia (deep) — due to involvement of rectovaginal septum and uterosacral ligaments
3. Infertility — in ~30–40% of cases

Other Symptoms

• Menstrual abnormalities — menorrhagia, irregular bleeding (due to co-existing anovulation)
• Dyschezia (painful defecation) — rectal/rectovaginal disease
• Dysuria, hematuria — bladder involvement
• Cyclical rectal bleeding — bowel endometriosis
• Cyclical pain at scar sites — umbilical or incisional scar endometriosis
• Hemoptysis — rare; thoracic endometriosis

⚠️ "Pain is out of proportion to the disease" — extent of endometriosis does NOT correlate with severity of pain (DC Dutta emphasis)

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Signs on Examination

Abdominal Examination

• Usually normal in early disease
• Large endometrioma → palpable mass

Pelvic Examination (Bimanual + Speculum)

• Fixed retroverted uterus — classic finding
• Tender nodules along uterosacral ligaments (best felt during menstruation)
• Tender adnexal mass (endometrioma) — restricted mobility
• Tenderness in pouch of Douglas
• Blue-black spots visible in posterior vaginal fornix (rectovaginal endometriosis)

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Investigations

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Diagnosis

• Positive histology confirms; negative histology does NOT exclude
• Laparoscopy performed ideally during menstruation or premenstrual phase (lesions most active)

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Classification — American Fertility Society (AFS) / rASRM Scoring

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Treatment

Principles

• Depends on: age, symptoms, desire for fertility, stage of disease
• Options: Expectant / Medical / Surgical / Combined

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A. Expectant Management

• For asymptomatic minimal/mild disease and women actively trying to conceive (mild disease)
• Spontaneous remission can occur in mild disease

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B. Medical Treatment

1. Pseudopregnancy Regimen

• Combined OCP — continuous (not cyclic); 6–9 months
• Progestins — MPA (Medroxyprogesterone acetate) 10–30 mg/day; norethisterone
• Mechanism: decidualization and necrosis of implants

2. Pseudomenopause Regimen

• Danazol — 400–800 mg/day for 6 months
  • Mechanism: ↓GnRH/gonadotropins, ↓estrogen, ↑androgens → atrophy of implants
  • Side effects: weight gain, acne, hirsutism, voice change (irreversible), hepatotoxicity
• GnRH Agonists (Buserelin, Leuprolide, Goserelin) — 6 months
  • Mechanism: pituitary down-regulation → medical oophorectomy
  • Side effects: menopausal symptoms, osteoporosis (add-back therapy if >6 months)
  • Add-back therapy: low-dose estrogen + progestin or tibolone

3. Newer Agents

• Gestrinone (anti-progestin + anti-estrogen): 2.5 mg twice weekly
• LNG-IUS (Mirena): effective for pain, especially dysmenorrhea
• Aromatase inhibitors (Letrozole): refractory cases; combined with OCP or GnRH agonist

⚠️ Medical treatment does NOT improve fertility — it suppresses ovulation and conception is impossible during treatment

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C. Surgical Treatment

Conservative Surgery (fertility-preserving)

• Laparoscopic (preferred): ablation/fulguration/excision of implants, adhesiolysis, drainage of endometriomas (cystectomy preferred over drainage alone)
• Laparotomy: severe/complex disease
• Indications: desire for fertility, failed medical treatment, endometrioma >4 cm
• Post-op: highest pregnancy rates in first 6–12 months — attempt conception immediately

Semi-Conservative Surgery

• Hysterectomy + conservation of ovaries: for women who want to preserve ovarian function but have completed family

Radical Surgery

• TAH + BSO (Total Abdominal Hysterectomy + Bilateral Salpingo-Oophorectomy)
• For: severe disease, completed family, failed other treatments
• Curative in most cases

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D. Combined (Medical + Surgical)

• Pre-operative hormonal therapy (GnRH agonist × 3 months): reduces vascularity, makes surgery easier — though ESHRE guidelines do not support this
• Post-operative medical therapy: OCP/progestins to suppress recurrence (not if fertility desired)

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Endometriosis and Infertility

1. Mild disease → Laparoscopic surgery → expectant conception
2. Moderate–severe → Surgery → ART if spontaneous conception fails
3. Advanced age / bilateral endometriomas → Direct ART (IVF)

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Prognosis and Recurrence

• Recurrence rate: 20–40% within 5 years after conservative surgery
• Definitive cure: radical surgery (TAH + BSO)
• Medical treatment: symptom relief only; disease recurs after cessation
• Malignant transformation: rare (~1%); → clear-cell or endometrioid ovarian carcinoma

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High-Yield Points (DC Dutta Style)

1. Most common site = Ovary
2. Gold standard diagnosis = Laparoscopy + histology
3. Pathognomonic finding = Chocolate cyst / powder-burn spots
4. Classic symptom triad = Dysmenorrhea + Dyspareunia + Infertility
5. Pain ≠ Stage — severity of pain does NOT correlate with extent of disease
6. Danazol: androgenic side effects; voice change is irreversible
7. GnRH agonists: need add-back therapy beyond 6 months
8. Medical Rx ≠ fertility improvement — cannot conceive during treatment
9. Post-op: attempt conception within 6–12 months (peak fertility window)
10. Definitive treatment: TAH + BSO

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Lactational Mastitis

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Definition

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Incidence

• Occurs in 2–10% of breastfeeding women
• Most common in the first 3–4 weeks postpartum (but can occur anytime during lactation)
• Right and left breast equally affected; upper outer quadrant most common

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Aetiology / Causative Organisms

Predisposing Factors

• Cracked/fissured nipples → entry point for bacteria
• Milk stasis / poor milk drainage
• Missed or infrequent feeds
• Tight-fitting bra / external pressure
• Poor breastfeeding technique / improper latch
• Poor maternal hygiene
• Maternal fatigue / stress
• Primiparity

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Pathogenesis

Cracked nipple / poor latch
        ↓
Bacteria enter via lactiferous ducts / skin breaks
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Milk stasis → ideal growth medium
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Inflammation → Mastitis
        ↓ (if untreated)
Abscess formation

Bacteria transmitted from infant's nasopharynx to mother's nipple during nursing — key mechanism.

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Clinical Features

Symptoms

• Breast pain — localised, throbbing
• Swelling and redness — wedge-shaped area (corresponding to one lobe)
• Fever (>38.5°C) with flu-like illness — malaise, myalgia, chills
• Onset usually sudden

Signs

• Red, hot, tender, indurated wedge-shaped area of breast
• Tender axillary lymphadenopathy
• Fever, tachycardia
• If abscess formed: fluctuant mass, peau d'orange skin, pointing

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Differential Diagnosis

⚠️ Always rule out inflammatory carcinoma if mastitis fails to resolve with antibiotics.

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Investigations

• No response to antibiotics within 48 hours
• Recurrent mastitis
• Hospital-acquired infection
• Suspicion of abscess

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DC Dutta's Classification of Mastitis

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Management

1. Supportive Measures (All Stages)

• Continue breastfeeding — most important; do NOT stop
• Frequent and effective milk removal from affected breast
• Warm compresses before feeding (↑ let-down); cold compresses after (↓ pain)
• Adequate rest, fluids, nutrition
• Analgesia: paracetamol or ibuprofen (safe in breastfeeding; NSAIDs also reduce inflammation)
• Proper breastfeeding technique; correct latch

⚠️ Stopping breastfeeding increases risk of abscess — milk stasis worsens infection.

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2. Antibiotics

• Duration: 10–14 days (no RCT evidence but widely recommended)
• All safe for breastfeeding infant
• Most common cause of recurrent mastitis = delayed or inadequate initial treatment

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3. Breast Abscess — Management

DC Dutta's Principles for Abscess Drainage:

• Incision radially (Langer's lines) → avoids cutting lactiferous ducts
• Alternatively, circumareolar incision for cosmesis
• Insert corrugated drain; pack loosely
• Send pus for culture & sensitivity
• Continue antibiotics post-drainage

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Suppression of Lactation

• Bilateral or recurrent severe abscess
• Patient's wish after counselling
• HIV-positive mother

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Complications

1. Breast abscess — most common complication of untreated mastitis
2. Lactiferous duct fistula — from poorly drained abscess
3. Recurrent mastitis / chronic abscess
4. Galactocele — milk-filled cyst from duct obstruction
5. Failure of lactation — if feeding abandoned
6. Septicaemia — rare; in immunocompromised/diabetics

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Prevention

• Correct breastfeeding technique and proper latch from day 1
• Complete emptying of breast at each feed
• Nipple care — prevent cracks (lanolin cream)
• Avoid prolonged engorgement
• Good hand hygiene

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High-Yield Exam Points

1. Most common organism = S. aureus
2. Most common site = Upper outer quadrant
3. Key management = Do NOT stop breastfeeding
4. First-line antibiotic = Dicloxacillin / Flucloxacillin
5. Abscess imaging = Ultrasound
6. Abscess drainage = USG-guided aspiration (first-line); I&D if fails
7. Incision for drainage = Radial (DC Dutta) to avoid lactiferous duct injury
8. Stopping lactation increases abscess risk
9. Failure to respond to antibiotics → rule out inflammatory carcinoma
10. DC Dutta's 3 stages: Engorgement → Mastitis → Abscess

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Abnormal Uterine Bleeding (AUB)

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Definition

Normal Menstrual Parameters (to define "abnormal")

Heavy menstrual bleeding (HMB) = >80 mL/cycle → causes iron-deficiency anaemia

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Terminology — Old vs Current (FIGO/ACOG)

⚠️ DUB is an obsolete term — replaced by PALM-COEIN classification (Berek & Novak, FIGO 2011)

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Classification — PALM-COEIN System (FIGO 2011)

PALM = Structural causes
COEIN = Non-structural causes

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DC Dutta's Classification

By Pattern

By Cause (DC Dutta's Framework)

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Pathophysiology of Anovulatory AUB (AUB-O)

No ovulation → No corpus luteum → No progesterone
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Unopposed oestrogen → Endometrial proliferation
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Fragile, thickened endometrium → Irregular asynchronous breakdown
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Irregular, often heavy, unpredictable bleeding

• Most common cause of AUB in adolescents and perimenopausal women
• Classic associations: PCOS, thyroid disorders, hyperprolactinaemia, stress, obesity

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Causes by Age Group

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Investigations

Step 1 — Always First

• Urine β-hCG — exclude pregnancy
• CBC — assess anaemia, thrombocytopenia
• TFTs — thyroid disease
• Coagulation screen (PT, aPTT, vWF) — if heavy since menarche
• Prolactin, FSH, LH

Step 2 — Structural Assessment

Step 3 — Endometrial Sampling

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Management

A. Medical Management

Acute (Emergency) Heavy Bleeding

Chronic / Long-term Management

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B. Surgical Management

⚠️ D&C is NOT therapeutic — reduces bleeding for one cycle only; not indicated as primary treatment

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DC Dutta's Management Algorithm

AUB
  ├── Exclude pregnancy (β-hCG)
  ├── Exclude malignancy (endometrial biopsy if indicated)
  ├── Treat underlying cause (thyroid, PCOS, fibroids)
  └── If DUB (AUB-O):
        ├── Adolescent → OCP / progestins
        ├── Reproductive age → OCP / LNG-IUS / progestins
        ├── Perimenopausal → progestins / LNG-IUS / ablation
        └── Medical failure → Hysterectomy

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Postmenopausal Bleeding — Special Emphasis

1. Atrophic vaginitis/endometritis — most common benign cause
2. Endometrial carcinoma — most important to exclude
3. Endometrial polyp
4. Cervical carcinoma
5. Hormone replacement therapy (HRT)
6. Ovarian oestrogen-secreting tumours

Investigation of choice: TVUS (endometrial thickness) → if >4 mm → hysteroscopy + biopsy

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High-Yield Exam Points

1. PALM-COEIN = current FIGO classification; DUB is obsolete
2. Most common cause of AUB in adolescents & perimenopausal = anovulation (AUB-O)
3. Submucosal fibroids → most likely fibroid type to cause AUB
4. HMB defined as >80 mL/cycle
5. Most effective medical treatment = LNG-IUS (Mirena)
6. Tranexamic acid — antifibrinolytic; does NOT suppress ovulation (safe if TTC)
7. D&C = diagnostic, NOT therapeutic
8. Postmenopausal bleeding = carcinoma until proven otherwise
9. Endometrial biopsy mandatory: age >35 + AUB, all postmenopausal bleeding
10. Hysteroscopy = gold standard for intracavitary pathology