• Affects approximately 10–15% of reproductive-age women globally ^[4].
• In women with chronic pelvic pain, prevalence rises to 40–60%.
• In women with infertility, prevalence is 25–50% ^[2][3].
• Peak incidence: 25–35 years old (prime reproductive years), because the disease is oestrogen-dependent.

• Rare before menarche and typically regresses after menopause (due to loss of cyclic oestrogen stimulation). However, post-menopausal endometriosis can occur with HRT or from residual disease producing its own oestrogen via local aromatase activity.
• More commonly diagnosed in women of higher socioeconomic status — this is likely a detection bias (greater access to healthcare and laparoscopy) rather than a true biological difference.
• Diagnostic delay is a major issue globally: average delay from symptom onset to diagnosis is 7–10 years, because symptoms overlap with "normal" dysmenorrhoea and IBS.

• Prevalence data from Hong Kong is broadly consistent with global figures (~10%).
• Important to note that in Hong Kong, later age of first pregnancy and lower parity are increasingly common — both of which increase cumulative oestrogen exposure and therefore endometriosis risk.
• The Chinese University of Hong Kong (CUHK) and the University of Hong Kong (HKU) have active research programmes on endometriosis, particularly on biomarkers and fertility outcomes.

The endometrium lines the uterine cavity and consists of:

• Functional layer (stratum functionalis): shed during menstruation, regenerated each cycle
• Basal layer (stratum basalis): contains stem/progenitor cells, NOT shed during menstruation

The endometrium responds to:

1. Oestrogen (proliferative phase) → proliferation of glands and stroma
2. Progesterone (secretory phase) → glandular secretion, decidualization of stroma
3. Progesterone withdrawal (late luteal phase if no implantation) → spiral arteriole constriction → ischaemic necrosis → shedding (menstruation)

Think about this anatomically: during retrograde menstruation, menstrual debris exits via the fallopian tubes and falls by gravity into the pelvis. The most dependent areas of the pelvis are affected first.

1. Ovaries (most common site, ~75%) → forms endometriomas ("chocolate cysts") — so-called because they contain thick, dark-brown altered blood (haemosiderin-laden)
2. Pouch of Douglas (rectouterine pouch) — the most dependent part of the peritoneal cavity in the upright position
3. Uterosacral ligaments — directly behind the uterus
4. Broad ligament
5. Fallopian tubes — causes tubal damage/occlusion → infertility
6. Pelvic peritoneum (including the vesicouterine pouch)
7. Rectosigmoid colon / rectovaginal septum — "deep infiltrating endometriosis" (DIE)
8. Bladder (detrusor muscle)
9. Round ligaments
10. Pelvic side wall

• Surgical scars (Caesarean section scars, episiotomy scars, laparoscopy port sites) — due to mechanical transplantation during surgery
• Umbilicus (Villar's nodule)
• Lungs / pleura → catamenial pneumothorax (pneumothorax occurring cyclically with menstruation; "catamenial" = Greek "katamenios" = monthly)
• Diaphragm
• Appendix, small bowel
• Ureters (can cause hydronephrosis)
• Nasal mucosa → catamenial epistaxis (cyclic nosebleeds)
• Brain (exceedingly rare)

This is the most widely accepted theory and explains the majority of pelvic endometriosis.

Concept: During menstruation, some menstrual blood containing viable endometrial cells flows backwards ("retrogradely") through the fallopian tubes and into the peritoneal cavity. These cells then implant on peritoneal surfaces, proliferate under oestrogen stimulation, and establish ectopic endometrial tissue.

Supporting Evidence:

• Retrograde menstruation is demonstrably common — occurs in 76–90% of women with patent tubes (seen at laparoscopy during menstruation)
• Endometriosis is more common in women with obstructed outflow tracts (cervical stenosis, imperforate hymen) — confirms that increased retrograde flow → increased disease
• Sites of disease correspond to gravity-dependent areas (Pouch of Douglas)

Limitations:

• If 90% of women have retrograde menstruation, why do only 10% develop endometriosis? → This implies additional factors are required:
  • Immune surveillance failure (defective clearance of ectopic cells)
  • Enhanced implantation capacity of shed cells
  • Genetic susceptibility
  • Altered peritoneal environment

Concept: The peritoneal mesothelium and the endometrium both derive from the coelomic epithelium (embryologically). Under certain stimuli (hormonal, inflammatory, environmental), peritoneal mesothelial cells can undergo metaplastic transformation into endometrial-like tissue.

Supporting Evidence:

• Explains endometriosis in women without a uterus (post-hysterectomy), in men treated with high-dose oestrogen (for prostate cancer), and in pre-menarchal girls
• Explains extra-pelvic endometriosis (e.g., pleural endometriosis)

Limitations:

• Does not explain why disease is concentrated in the pelvis if all peritoneum has the same embryological origin

Concept: Endometrial cells spread via lymphatic channels or blood vessels to distant sites.

Supporting Evidence:

• Explains endometriosis in distant organs (lungs, brain, lymph nodes)
• Endometrial cells have been identified in pelvic lymph nodes

Limitations:

• Cannot explain the predominant pelvic distribution

Concept: Endometrial tissue is mechanically transported to ectopic sites during surgery (Caesarean section, hysterotomy, episiotomy).

Supporting Evidence:

• Endometriosis in Caesarean section scars is well-documented
• Laparoscopic port-site endometriosis has been reported

Concept: Bone marrow-derived stem cells may differentiate into endometrial-like tissue at ectopic sites.

Supporting Evidence:

• Bone marrow transplant recipients have developed donor-derived endometriosis
• This is a more recent theory and is an area of active research

Pain in endometriosis is not simply due to bleeding from ectopic implants. The pain mechanisms are complex and multi-layered:

1. Nociceptive pain: Direct tissue damage from cyclic haemorrhage, inflammation, and adhesion traction
2. Inflammatory pain: Pro-inflammatory cytokines (PGE2, IL-1, TNF-α) directly sensitise peripheral nerve endings
3. Neuropathic pain: Endometriotic implants can invade nerves (neurotropism); nerve growth factor (NGF) is upregulated in implants, promoting nerve fibre growth INTO the lesions → this creates a "pain-generating" unit
4. Central sensitisation: Chronic peripheral nociceptive input leads to spinal cord "wind-up" → amplification of pain signals → hyperalgesia (increased pain sensitivity) and allodynia (pain from normally non-painful stimuli)
5. Viscero-visceral cross-talk: Because the uterus, bladder, and bowel share overlapping sensory innervation (via the hypogastric and pelvic splanchnic nerves), inflammation in one organ can cause referred pain in others — explaining why endometriosis patients often have concurrent IBS-like symptoms, interstitial cystitis-like symptoms, etc.

Endometriosis accounts for approximately 25% of female factor infertility ^[2][3]. Multiple mechanisms contribute:

The American Society for Reproductive Medicine (ASRM) revised classification (formerly the American Fertility Society, rAFS) is the most widely used staging system. It is a surgical staging system based on findings at laparoscopy.

Scoring is based on:

• Size, depth, and location of implants
• Presence and extent of adhesions (filmy vs. dense)
• Presence of endometriomas

The #Enzian (or revised ENZIAN) classification was developed specifically to describe deep infiltrating endometriosis (DIE) and complements the rAFS/ASRM system:

• Describes disease in three compartments:
  • A: Rectovaginal septum / vagina
  • B: Uterosacral ligaments → pelvic sidewall
  • C: Rectum / sigmoid colon
• Grades severity: 1 (< 1 cm), 2 (1–3 cm), 3 (> 3 cm)
• Additional notation for involvement of:
  • FA: Adenomyosis
  • FB: Bladder
  • FU: Ureter (intrinsic)
  • FI: Bowel (other than rectosigmoid)
  • FO: Other locations

• Developed to predict fertility outcomes after surgical treatment
• Incorporates both rAFS/ASRM score AND functional assessment (least function score of tubes, fimbriae, ovaries)
• More useful than rAFS stage alone for counselling on natural conception vs. IVF

• Symptoms are cyclical (worse around menstruation) — because ectopic endometrial tissue responds to hormonal cycling
• The "classic triad" of endometriosis: dysmenorrhoea + dyspareunia + infertility
• Symptoms often begin years before diagnosis (average diagnostic delay: 7–10 years)
• Up to 20–25% of women with endometriosis may be asymptomatic (incidental finding at surgery)

A presumed diagnosis of endometriosis can be made based on symptoms and signs + imaging + response to empirical treatment ^[1].

This is the approach used in the majority of cases in clinical practice. The rationale is that if a woman has typical symptoms (cyclical pelvic pain, dyspareunia, dyschezia), supportive imaging (endometrioma on TVUS, or negative sliding sign), and responds to empirical hormonal treatment (e.g., COCP, progestins, GnRH agonists), then the clinical diagnosis is sufficiently secure to continue management without laparoscopy.

The 2022 ESHRE (European Society of Human Reproduction and Embryology) guideline and the 2024 NICE guideline both support this approach — laparoscopy is no longer considered mandatory for diagnosis in all cases.

Diagnostic laparoscopy ± biopsy remains the gold standard for definitive diagnosis ^[1].

Indications for diagnostic laparoscopy ^[1]:

• Persistent pain not responding to medical treatment — if empirical treatment fails, you need to confirm the diagnosis and exclude other pathology
• Infertility workup — to assess and potentially treat pelvic disease simultaneously (diagnostic AND therapeutic)
• Diagnostic uncertainty — when the clinical picture is atypical or imaging is inconclusive
• Suspected deep infiltrating endometriosis — to map disease extent for surgical planning
• Pre-operative planning — before complex excisional surgery

At laparoscopy, the diagnosis is made by:

1. Visual identification of endometriotic lesions (red, black/powder-burn, or white lesions on peritoneal surfaces; endometriomas; adhesions)
2. Histological confirmation via biopsy — the presence of endometrial glands AND stroma in the biopsy specimen confirms the diagnosis

• Always the first investigation in any reproductive-age woman with pelvic pain or a pelvic mass
• ALWAYS exclude pregnancy — especially ectopic pregnancy ^[3][5]
• Urine β-hCG is rapid and sufficient for screening; serum β-hCG for quantification if positive

TVUS is the first-line imaging modality for endometriosis ^[1].

Why TVUS?

• Non-invasive, widely available, no radiation, relatively inexpensive
• Excellent for detecting endometriomas and deep infiltrating endometriosis
• Can be performed in the outpatient clinic
• Operator-dependent — expertise matters significantly

Key TVUS Findings in Endometriosis:

Pelvic examination should specifically assess ^[9][10]:

• Lower genital tract
• Uterus
• Adnexal mass — size, tenderness, mobility, arising from pelvis ^[10]
• Pouch of Douglas — nodularity, thickening, tenderness in endometriosis ^[10]
• Rectal examination ^[10]

The rationale for each:

• Adnexal mass: An endometrioma is typically fixed (due to adhesions), tender, and separate from the uterus. A functional cyst is mobile and non-tender.
• POD assessment: Palpable uterosacral nodularity or a tender, thickened rectovaginal septum is highly specific for DIE and may be the only clinical sign.
• Rectal examination: Allows palpation of the anterior rectal wall for nodules (rectovaginal DIE) and assessment of the rectovaginal septum.

MRI has increased specificity and sensitivity compared to TVUS, but is not considered first-line (ESHRE 2022) ^[1].

When to use MRI:

• Suspected DIE — to map the extent of disease before surgery (especially bowel, bladder, ureteric involvement)
• Indeterminate adnexal mass — to characterise when TVUS is inconclusive
• Surgical planning — to help surgeons anticipate the need for bowel resection, ureteric stenting, etc.
• Research / specialist centres — for comprehensive disease mapping

Key MRI Findings:

• What is it? Fluoroscopic X-ray imaging of the uterine cavity and fallopian tubes after injection of radio-opaque contrast through the cervix
• Role in endometriosis: Not used to diagnose endometriosis directly, but essential in the infertility workup to assess tubal patency

HSG is indicated for women with no comorbidities such as previous PID or ectopic pregnancy and no clinical signs/symptoms of endometriosis ^[11]. It is a less invasive and outpatient procedure ^[11] that can assess the uterine cavity ^[11].

Hysterosalpingo-contrast-ultrasonography (HyCoSy) may be an alternative to HSG ^[11].

Key HSG findings relevant to endometriosis:

• Tubal occlusion (proximal or distal) — suggests tubal damage from adhesions
• Hydrosalpinx — dilated, contrast-filled tube without peritoneal spill
• Irregular uterine cavity — may suggest adenomyosis or synechiae (but not specific for endometriosis)
• Localised contrast pooling — may suggest peritoneal adhesions (indirect sign)

Diagnostic laparoscopy ± biopsy is the gold standard for definitive diagnosis of endometriosis ^[1].

Procedure:

1. Under general anaesthesia, pneumoperitoneum is established (CO₂ insufflation)
2. A laparoscope is inserted through an umbilical port
3. Systematic inspection of the pelvis: peritoneal surfaces, ovaries, tubes, uterosacral ligaments, Pouch of Douglas, bladder peritoneum, bowel surfaces
4. Identification and documentation of lesions
5. Biopsy of suspicious lesions for histological confirmation
6. Staging using the rAFS/ASRM classification
7. Chromopertubation (dye test): methylene blue injected through the cervix → observed spilling from the fimbrial ends → confirms tubal patency. This is the gold standard for assessing tubal patency and is routinely performed during diagnostic laparoscopy for infertility.
8. Simultaneous therapeutic intervention if appropriate (excision/ablation of implants, adhesiolysis, ovarian cystectomy)

Visual appearances at laparoscopy:

Histological confirmation — what the pathologist looks for:

• Endometrial glands — columnar epithelium resembling uterine glands
• Endometrial stroma — spindle cells surrounding the glands
• Haemosiderin-laden macrophages — evidence of old haemorrhage
• At least two of the three features should be present for definitive histological diagnosis

NSAIDs and other analgesics are commonly used ^[12].

Contraindications to NSAIDs: peptic ulcer disease, NSAID allergy, renal impairment, aspirin-exacerbated respiratory disease, late pregnancy, concurrent anticoagulant use.

Key point: NSAIDs treat symptoms (pain) but do NOT suppress disease progression. They are first-line for pain relief but must be combined with hormonal therapy for disease control.

COCP is commonly used as first line ^[12].

Mechanism:

• Although endometriosis is an oestrogen-sensitive disease, COCP has a good oestrogen:progesterone balance ^[12]. The progestogenic component dominates the endometrial effect:
  • Suppresses the HPO axis (↓ GnRH pulsatility → ↓ FSH/LH → ↓ ovulation → ↓ endogenous oestrogen fluctuations)
  • Decidualisation and subsequent atrophy of both eutopic and ectopic endometrium
  • Reduces menstrual flow volume → reduces retrograde menstruation
  • The small oestrogen component prevents breakthrough bleeding and maintains bone density

Efficacy: Known to decrease endometriosis-associated dyspareunia, dysmenorrhoea, and non-menstrual pain ^[12].

Regimen: Consider continuous regimen to decrease menstruation-related discomfort ^[12]. Continuous use (skipping the pill-free interval) means no withdrawal bleed → no cyclical hormonal fluctuation → less cyclical pain. This is the preferred approach in endometriosis (unlike conventional cyclic use for contraception).

Advantages: Generally well-tolerated and associated with less side effects than alternatives ^[12]. Also provides contraception, cycle regularity, and may have a protective effect against ovarian and endometrial cancer.

Contraindications (WHO MEC Category 4 — absolute):

• History of venous thromboembolism (VTE)
• Active or history of arterial cardiovascular disease (stroke, MI)
• Migraine with aura
• Breast cancer (current)
• Severe liver disease
• Age > 35 years AND smoking ≥ 15 cigarettes/day
• Uncontrolled hypertension

Side effects: Nausea, breast tenderness, headache, mood changes, breakthrough bleeding, small increased risk of VTE.

Progestin-only therapy is an alternative to COCP ^[12].

Mechanism:

• Creates a pseudo-pregnant state — high progesterone → decidualisation of ectopic endometrium → eventual atrophy
• Suppresses HPO axis (at sufficient doses) → anovulation
• Direct anti-proliferative effect on endometrial tissue
• Anti-inflammatory effects in the pelvic environment

Examples ^[12]:

Contraindications to progestins (fewer than COCP):

• Current breast cancer
• Severe liver disease / liver tumours
• Unexplained vaginal bleeding (must be investigated first)
• Active VTE (relative CI for some formulations)

Side effects: Irregular bleeding (especially initially), weight gain, bloating, mood changes, acne (depends on specific progestin), reduced libido, bone density loss (depot preparations with prolonged use).

What are they? GnRH agonists (e.g., leuprolide/Lupron, goserelin/Zoladex, nafarelin, triptorelin) are synthetic analogues of GnRH that, paradoxically, suppress the HPO axis when given continuously.

Mechanism — explained from first principles:

• Normal physiology: GnRH is released from the hypothalamus in a pulsatile fashion → stimulates anterior pituitary to release FSH and LH → stimulates ovaries to produce oestrogen and progesterone
• GnRH agonist effect: Continuous (non-pulsatile) exposure to a GnRH agonist initially causes a "flare" effect (transient increase in FSH/LH for 1–2 weeks → transient increase in oestrogen) → then the pituitary GnRH receptors become desensitised/downregulated → FSH/LH secretion drops to near zero → ovaries stop producing oestrogen → medical menopause
• This creates a profoundly hypo-oestrogenic environment → ectopic endometrial tissue atrophies → symptoms improve

Clinical use:

• Second-line therapy when COCP / progestins have failed
• Pre-operative adjunct to reduce disease bulk before surgery
• Maximum duration without add-back therapy: 6 months — because prolonged hypo-oestrogenaemia causes:
  • Hot flushes, night sweats (vasomotor symptoms)
  • Vaginal dryness, decreased libido
  • Accelerated bone density loss (osteoporosis risk)
  • Mood disturbance, depression

Add-back therapy: To mitigate hypo-oestrogenic side effects while maintaining efficacy, low-dose oestrogen + progestin "add-back" is co-administered. The principle (Barbieri's "oestrogen threshold hypothesis") is that there is a therapeutic window: endometriotic tissue requires higher oestrogen levels to proliferate than bone and cardiovascular tissue require for protection. So adding back a small amount of oestrogen protects bone/cardiovascular health WITHOUT reactivating endometriosis.

• Typical add-back: norethisterone 5 mg/day ± conjugated oestrogen 0.625 mg/day; or tibolone 2.5 mg/day
• With add-back, GnRH agonists can be used for longer durations (up to 2 years)

Contraindications: Pregnancy, breastfeeding, undiagnosed vaginal bleeding, metabolic bone disease (osteoporosis — already has low bone density).

Examples: Elagolix (oral), relugolix, linzagolix

Mechanism: Directly and competitively block GnRH receptors on the anterior pituitary → immediate suppression of FSH/LH → no initial "flare" effect (unlike agonists) → dose-dependent suppression of oestrogen

Advantages over GnRH agonists:

• Oral administration (vs. injection for most agonists)
• No flare effect
• Dose-dependent: can achieve partial oestrogen suppression (rather than full menopause) → fewer hypo-oestrogenic side effects
• Rapid reversibility on discontinuation

Current status: Elagolix (Orilissa) is FDA-approved (2018) for endometriosis-related pain. Relugolix combination (relugolix + E2 + norethindrone acetate, Myfembree) approved 2022. Increasingly used but not yet universally available in all regions including Hong Kong.

Examples: Letrozole, anastrozole

Mechanism:

• Aromatase is the enzyme that converts androgens → oestrogens. It is expressed in:
  • Ovary (main source in premenopausal women)
  • Adipose tissue, skin, brain (main source in postmenopausal women)
  • Endometriotic implants themselves (local oestrogen production — the "self-sustaining" loop)
• Aromatase inhibitors block this conversion → reduce both systemic AND local oestrogen levels
• Particularly useful because they target the local aromatase activity within endometriotic implants that is resistant to HPO axis suppression

Clinical use: Reserved for refractory cases not responding to first/second-line hormonal therapies; sometimes used in combination with COCP or progestins (to prevent the reflex increase in gonadotrophins that occurs in premenopausal women when oestrogen is suppressed — the pituitary senses low oestrogen and ramps up FSH/LH → ovarian stimulation → can cause ovarian cysts if aromatase inhibitor is used alone).

Side effects: Hot flushes, arthralgia, bone density loss, headache, ovarian cyst formation (if used alone in premenopausal women).

Conservative surgery is first line for surgical treatment, usually done together with diagnostic laparoscopy ("see and treat") ^[13].

Involves ^[13]:

• Excision or ablation of endometriotic lesions — no significant difference in outcome between excision and ablation ^[13] for superficial peritoneal disease (though excision is preferred for DIE and for histological confirmation)
• Ovarian cystectomy if ovarian endometrioma ^[13] — stripping of the endometrioma wall (pseudocapsule) from the ovarian cortex; preserves remaining ovarian tissue. Preferable to simple drainage (which has near-100% recurrence rate)
• Adhesiolysis if adhesions seen intra-operatively ^[13] — restoring normal tubo-ovarian anatomy to improve fertility potential

Outcomes ^[13]:

• Decreased overall pain: 73% vs. 21% compared to diagnostic laparoscopy alone
• Increased live birth or ongoing pregnancy: 30% vs. 18% compared to diagnostic laparoscopy alone
• However, higher rate of recurrent symptoms compared to definitive surgery: 58% vs. 19% re-operation rate over 7 years

Excision vs. Ablation — What's the Difference?

Special Considerations for Endometrioma Surgery:

• Cystectomy (stripping the cyst wall) is preferred over drainage + ablation — lower recurrence, better fertility outcomes
• However, cystectomy inevitably destroys some healthy ovarian cortex → reduces ovarian reserve (lower AMH, lower antral follicle count)
• Must balance: removing disease vs. preserving ovarian reserve — especially important in women planning IVF
• General recommendation: cystectomy for endometriomas > 4 cm; smaller ones may be observed or drained + ablated

Definitive surgery can be considered in patients with completed family and failure to respond to conservative treatment ^[13].

Involves ^[13]:

• Hysterectomy + bilateral salpingo-oophorectomy (BSO) + removal of all visible endometriotic lesions

Rationale: Removing both ovaries eliminates the main source of endogenous oestrogen → ectopic endometrial tissue atrophies. Removing the uterus addresses any concurrent adenomyosis and eliminates menstruation permanently. Removing all visible lesions addresses the local aromatase activity that can sustain residual disease even without ovarian oestrogen.

Outcomes ^[13]:

• Associated with less recurrence compared to conservative surgery
• But will NOT necessarily cure endometriosis-related symptoms ^[13] — because:
  • Central sensitisation may perpetuate pain independently of peripheral disease
  • Residual microscopic disease may persist
  • Exogenous oestrogen (HRT) may reactivate residual disease
  • Local aromatase activity in residual implants can produce oestrogen

Post-hysterectomy + BSO considerations:

• Patient will be in surgical menopause → needs HRT (oestrogen-only, as uterus has been removed) to prevent menopausal symptoms and osteoporosis
• HRT after definitive surgery for endometriosis: generally considered safe, but some authorities recommend combined oestrogen + progestin (even without a uterus) to reduce the theoretical risk of oestrogen-stimulated recurrence of residual disease. This is controversial, and practice varies.
• In women under 45, the benefits of HRT clearly outweigh the small risk of recurrence

Contraindications to definitive surgery:

• Desire for future fertility (absolute)
• Medical unfitness for major surgery
• Patient preference for conservative management

Presacral neurectomy can decrease endometriosis-associated midline pain, but is associated with significant risks ^[13].

What is it? Surgical transection of the superior hypogastric plexus (presacral nerve plexus) — the sympathetic nerve bundle that transmits visceral pain signals from the uterus and central pelvis.

Rationale: Interrupts the afferent pain pathway from the uterus → reduces midline (central) pelvic pain.

Limitations:

• Only effective for midline pain (the hypogastric plexus transmits midline sensation); does NOT help with lateral pelvic pain
• Significant risks: constipation (loss of sympathetic innervation to rectosigmoid), urinary urgency/dysfunction, painless labour in future pregnancies

Post-operative preventive therapy is used as secondary prevention to decrease recurrence of endometriosis-related symptoms ^[13].

Principle: long-term medical suppression of the HPG axis → decreased symptom recurrence and decreased re-operation ^[13].

Regimen: usually prefer levonorgestrel-releasing IUCD (Mirena) for ≥ 18–24 months ^[13].

Outcome: can decrease recurrence of endometriosis-associated dysmenorrhoea, but not for non-menstrual pelvic pain or dyspareunia ^[13].

Why Mirena? Because it provides continuous local progestogenic effect on the endometrium → atrophy → reduced menstrual flow → reduced retrograde menstruation → reduced disease recurrence. Minimal systemic side effects compared to oral progestins or GnRH agonists. Can be left in situ for 5 years.

Alternatives for post-operative suppression: Continuous COCP, dienogest 2 mg/day, depot medroxyprogesterone acetate.

Infertility affects approximately 25% of women with endometriosis ^[1][7][8] and is the second most common presentation after pain.

The pathophysiology of infertility has been detailed previously but, summarised as a complication, the mechanisms are:

Impact: Even after surgical treatment, only 30% achieve live birth or ongoing pregnancy (vs. 18% with diagnostic laparoscopy alone) ^[13]. Many patients ultimately require IVF/ICSI.

Women with endometriosis who do conceive have higher rates of certain pregnancy complications:

• Mechanism: The endometrioma wall is a pseudocapsule of fibrotic and inflamed tissue. As the cyst enlarges with accumulated old blood, the wall can become thin and rupture spontaneously or after trauma (including intercourse or straining).
• Presentation: Acute onset of severe lower abdominal pain, signs of peritonism (guarding, rebound tenderness), tachycardia. The thick "chocolate" fluid irritates the peritoneum intensely due to its high haemosiderin and inflammatory content.
• Differential diagnosis: Must be differentiated from ruptured ectopic pregnancy, ruptured corpus luteum cyst, and ovarian torsion — all acute gynaecological emergencies. Pregnancy test is critical.
• Management: Often requires emergency laparoscopy for washout + cystectomy or oophorectomy. Peritoneal lavage is important as the chocolate fluid causes intense chemical peritonitis and can promote further adhesion formation.

• Mechanism: Acute bleeding from the vascularised pseudocapsule INTO the cyst → rapid expansion → stretching of the ovarian capsule → pain
• Presentation: Sudden worsening of chronic pelvic pain; enlarging adnexal mass on serial imaging
• Management: Usually conservative (analgesia, observation) unless haemodynamically significant

• RARELY occurs with endometriomas ^[1] — because endometriomas are typically fixed by surrounding adhesions (adhesions tether the ovary, preventing it from twisting on its pedicle). This is in contrast to dermoid cysts and paraovarian cysts, which are mobile and therefore more prone to torsion.
• When it does occur: Acute severe unilateral pelvic pain, nausea/vomiting, absent Doppler flow on TVUS → surgical emergency requiring laparoscopic detorsion ± cystectomy/oophorectomy.

Thoracic endometriosis may cause chest pain, scapular pain, neck pain, pneumothorax, haemothorax, and haemoptysis ^[1].

• Characteristically right-sided (> 90% of catamenial pneumothorax occur on the right) — thought to be because retrograde peritoneal fluid preferentially flows to the right paracolic gutter and reaches the right hemidiaphragm via clockwise peritoneal circulation
• Diagnosis requires high index of suspicion — any young woman with recurrent right-sided pneumothorax timed with menstruation should be evaluated for thoracic endometriosis