• IMB is extremely common — up to 10–15% of gynaecology referrals relate to abnormal uterine bleeding (AUB), of which IMB forms a significant proportion.
• Irregular/anovulatory bleeding is most common at the extremes of reproductive age ^[1] — adolescence (immature HPO axis) and perimenopause (declining ovarian reserve).
• PCOS occurs in ~5–10% of reproductive-aged women and is the most common endocrinopathy in reproductive-age women, accounting for ~75% of all anovulatory disorders causing infertility and ~90% of women with oligomenorrhoea ^[3].
• Cervical cancer (a cause of IMB) is a significant concern in Hong Kong. The age-standardised incidence rate is approximately 5–7 per 100,000 women. The Hong Kong Cervical Screening Programme recommends screening from age 25 for sexually active women.
• Endometrial cancer incidence in Hong Kong has been rising, now the most common gynaecological malignancy, linked to obesity and metabolic syndrome.

The uterus is a hollow muscular organ composed of three layers:

1. Perimetrium (serosa) — outermost
2. Myometrium — thick smooth muscle layer; relevant for fibroids (leiomyomas) and adenomyosis
3. Endometrium — the inner mucosal lining, further divided into:
   • Functionalis (superficial 2/3): the layer that proliferates, secretes, and sheds during menstruation. This is the dynamic, hormone-responsive layer.
   • Basalis (deep 1/3): the regenerative layer that remains after menstruation and regenerates the functionalis. It is supplied by straight arteries (not hormone-responsive).

The functionalis is supplied by spiral arteries, which are exquisitely sensitive to progesterone. When progesterone is withdrawn (at the end of the luteal phase), these spiral arteries undergo rhythmic vasoconstriction → ischaemia → necrosis → shedding = menstruation.

Why does this matter for IMB/irregular bleeding?

• If there is no ovulation, there is no corpus luteum, therefore no progesterone. The endometrium is exposed to unopposed oestrogen only → it proliferates but never undergoes secretory transformation → it becomes thick, fragile, and vascular → it outgrows its blood supply → random, unpredictable shedding = irregular bleeding (anovulatory or "breakthrough" bleeding).
• If a structural lesion (polyp, fibroid, carcinoma) distorts the endometrial surface, it can erode, ulcerate, or have abnormal vasculature → bleeding between otherwise normal cycles = IMB.

The cervix has two types of epithelium:

• Ectocervix: stratified squamous epithelium (tough, multi-layered)
• Endocervix: columnar epithelium (single-layered, fragile, mucus-secreting)
• Squamocolumnar junction (SCJ): where these two meet; this is the transformation zone — the site where metaplasia occurs and where cervical carcinoma and CIN arise.

Ectropion (previously called "erosion") occurs when the columnar epithelium extends onto the ectocervix — it appears red and bleeds easily on contact. This is common with oestrogen exposure (pregnancy, COC use). It is benign but causes contact/post-coital bleeding and must be distinguished from cervical carcinoma.

Understanding the normal menstrual cycle is essential:

Key points:

• Follicular phase (Day 1–14): FSH drives follicular growth → rising oestrogen → endometrial proliferation
• Ovulation (Day 14): LH surge
• Luteal phase (Day 14–28): Corpus luteum produces progesterone → endometrial secretory transformation → stable, compact endometrium
• Menstruation: Corpus luteum regresses → progesterone withdrawal → spiral artery vasoconstriction → endometrial shedding

Physiological mid-cycle bleeding may be related to rapid decrease in oestrogen after LH surge with low progesterone level shortly after ovulation ^[1]. This is a brief, self-limited spotting around Day 14 — the endometrium momentarily loses oestrogen support before progesterone takes over.

Relevant for ectopic pregnancy — the most common site is the ampulla (70%), followed by isthmus (12%), fimbria (11%), and cornua (2%). The narrow lumen means a growing gestational sac quickly outgrows its blood supply or erodes into tubal vasculature → bleeding (both vaginal and intra-abdominal).

The PALM-COEIN system (FIGO 2011, updated 2018) classifies causes of AUB in non-pregnant reproductive-age women:

From the lecture slides ^[1], a practical clinical classification:

Structural causes:

• Endometrial: polyps, fibroid polyps, hyperplasia, carcinoma
• Cervical: polyps, ectropion, carcinoma
• Infection: PID, vaginitis/STDs
• Pregnancy-related: ectopic, miscarriage, molar, implantation

Non-structural causes:

• Ovulatory dysfunction (AUB-O)
• Iatrogenic (hormonal contraceptives, breakthrough bleeding)
• Physiological mid-cycle bleeding
• Coagulopathy

Physical examination should include general examination, abdominal examination, and pelvic examination (speculum + bimanual).

Endometrial aspirate (EA): a simple outpatient procedure ^[6]

Indications — mainly when suspicious for endometrial pathologies: ^[6]

Process: to be done during speculum exam → insertion of endometrial suction curette (e.g. Pipelle) to aspirate endometrial tissue → send for histopathology ^[6]

Why is EA so useful? It is a blind sampling technique — quick, cheap, can be done in clinic without anaesthesia. The Pipelle device has a sensitivity of ~90–99% for endometrial carcinoma (high detection rate for diffuse disease) but is less reliable for focal lesions like polyps (may miss them because it samples randomly). This is why hysteroscopy is superior for focal pathology.

Hysteroscopy ± endometrial biopsy: diagnostic and therapeutic ^[6]

Indication: superior to EA but limited availability ^[6]

Setting: under GA or LA (outpatient procedure) ^[6] Process: insertion of a 3mm endoscope through cervix into uterus → ± targeted biopsy at suspicious endometrial sites → ± removal of lesion, e.g. polyp ^[6]

Pelvic US when suspect structural pathology ^[6][7]

Indications: ^[6][7]

Blood tests ^[6][7]:

Endometrial aspirate/sampling (EA): a simple outpatient procedure ^[6]

How it works:

• A thin, flexible plastic catheter (Pipelle de Cornier) is inserted through the cervical os into the uterine cavity
• The inner plunger is withdrawn, creating negative suction pressure → aspirates a strip of endometrial tissue
• The tissue is placed in formalin → sent to histopathology
• Takes ~1–2 minutes; usually performed without anaesthesia (some cramping is expected)
• Can be completed in 5 minutes without anaesthesia ^[8]

What it tells you:

Limitations:

• Blind technique → can miss focal lesions (polyps, small submucosal fibroids)
• Sensitivity for endometrial carcinoma: ~90–99% (very good for diffuse disease)
• Sensitivity for polyps: only ~10–30% (poor — polyps are focal and the catheter may miss them)
• Cannot be done if cervical stenosis (common in postmenopausal women)
• Should not be done if pregnant (pregnancy test first!)

The gold standard for endometrial cavity assessment.

How it works:

• A thin rigid or flexible endoscope (typically 3–5mm diameter) is inserted through the cervix into the uterine cavity
• The cavity is distended with saline or CO₂ to allow visualisation
• Direct visualisation of the entire endometrial surface → can identify polyps, submucosal fibroids, hyperplasia, carcinoma, adhesions, septa
• Targeted biopsy can be taken from suspicious areas (unlike EA which is blind)
• Therapeutic: polyps can be removed, submucosal fibroids resected, adhesions lysed — "see and treat" approach

Advantages over EA:

• Directly visualises focal lesions (polyps, fibroids) that EA may miss
• Allows targeted biopsy → higher diagnostic accuracy for focal pathology
• Can treat at the same time (polypectomy, myomectomy)

Disadvantages:

• More invasive, requires trained operator
• Limited availability (not available in every clinic)
• May require GA (though outpatient/office hysteroscopy under LA is increasingly common)
• Risk (rare): uterine perforation (~0.1%), infection, fluid overload (if excessive distension media)

Pelvic US when suspect structural pathology ^[6][7]

Two approaches:

• Transabdominal US (TAUS): requires full bladder as acoustic window. Good for large fibroids, general pelvic survey. Less resolution for endometrium.
• Transvaginal US (TVUS): probe placed in vagina → closer to uterus → higher resolution. Preferred for endometrial assessment, adenomyosis, early pregnancy, adnexal masses.

Key USS Findings and Their Interpretation:

Saline Infusion Sonography (SIS) / Sonohysterography:

• Saline is infused into the uterine cavity during TVUS → distends the cavity → better delineation of intracavitary lesions (polyps, submucosal fibroids)
• Acts as a "poor man's hysteroscopy" — less invasive than hysteroscopy but better than plain TVUS for focal lesions
• Sensitivity for polyps: ~90% (much better than plain TVUS)

Rotterdam criteria: ≥ 2 of the following met ^[3]:

1. Oligo- or anovulation ^[3]
2. Hyperandrogenism: biochemical or clinical ^[3]
3. PCOS features in US defined as ≥ 1 ovary meeting criteria of ≥ 20 follicles measuring 2–9mm and/or increased ovarian volume > 10mL (by 0.5 × length × width × thickness) ^[3]

AND exclusion of other aetiologies with similar features, e.g. thyroid disorders, hyperprolactinaemia, CAH, Cushing's syndrome, adrenal tumours ^[3]

Diagnosed histologically (EA or hysteroscopy biopsy → confirmed at hysterectomy).

Key staging relevant to diagnosis:

• Stage I: Confined to uterine corpus
  • IA: < 50% myometrial invasion
  • IB: ≥ 50% myometrial invasion
• Stage II: Cervical stromal invasion
• Stage III: Local/regional spread (serosa, adnexa, vagina, lymph nodes)
• Stage IV: Distant metastases (bladder/bowel mucosa, distant organs)

Staging requires surgical pathology (total hysterectomy + bilateral salpingo-oophorectomy + lymph node assessment).

TVUS endometrial thickness: should be ≤ 4mm in postmenopausal women (NPV 99.4–100%) ^[9]

Performance: ^[8]

• At 4mm: sensitivity 96%, specificity 53% ^[8]
• At 5mm: sensitivity 96%, specificity 61% ^[8]

Why 4mm? The goal is to rule out endometrial carcinoma with high confidence. A thin endometrium (≤ 4mm) has a very high NPV — essentially no cancer is lurking behind a thin endometrial stripe. The trade-off is low specificity (many false positives — benign thickened endometrium still needs biopsy), but this is acceptable because missing a cancer is far worse than doing an unnecessary biopsy.

Note: NOT routinely performed in asymptomatic patients with incidental finding of thickened endometrium unless > 11mm and associated with other US findings or risk factors ^[9]. This is important — don't over-investigate incidental findings in asymptomatic women.

Breakthrough bleeding in combined regimens: ^[10]

• Those occurring in the first 6 months of treatment require no immediate intervention ^[10]
• For combined cyclical regimen: if bleeding is not around time of progestogen withdrawal / persistently irregular → endometrial biopsy ^[10]
• For continuous combined regimen: if bleeding occurs after achievement of amenorrhoea → endometrial biopsy ^[10]

Why? The first 6 months of HRT allow the endometrium to "settle" into the new hormonal environment. Breakthrough bleeding during this period is usually benign (endometrial adjustment). However:

• In cyclical regimens, bleeding should occur predictably during the progestogen-free/withdrawal period. If it occurs at other times → suspicion of endometrial pathology
• In continuous combined regimens, the goal is endometrial atrophy → amenorrhoea. If bleeding recurs after amenorrhoea was established → something has changed (new pathology?) → investigate

A special algorithm because it is a time-critical, potentially fatal diagnosis:

Combined OC pills: 1st line treatment unless contraindicated ^[7]

How COCs work for irregular/anovulatory bleeding:

• COCs contain both oestrogen (ethinylestradiol, EE) and progestogen (e.g. levonorgestrel, desogestrel, drospirenone)
• The oestrogen component stabilises the endometrium (promotes growth and healing of the functionalis layer) and provides a predictable hormonal milieu
• The progestogen component opposes oestrogen-driven proliferation, induces secretory transformation, and stabilises the endometrial vasculature (spiral arteries)
• Together, they suppress the HPO axis (suppress GnRH → suppress FSH/LH → suppress folliculogenesis → suppress erratic ovarian hormone production)
• During the pill-free interval (or placebo pills), the withdrawal of both hormones triggers an organised, predictable withdrawal bleed
• Net effect: transforms chaotic, unpredictable anovulatory bleeding into regular, predictable, lighter withdrawal bleeds

Why COCs are first-line:

• Regulate the cycle
• Reduce bleeding volume
• Provide contraception (many of these patients are reproductively active)
• Protect the endometrium from unopposed oestrogen (the progestogen component prevents hyperplasia)
• Treat associated dysmenorrhoea
• In PCOS: also improve acne and hirsutism (especially with anti-androgenic progestogens like cyproterone acetate or drospirenone)

Contraindications to COCs (UKMEC Category 4 — absolute contraindications):

High-dose progestogen: when contraindicated to COC pills ^[7]

Regimens:

• Cyclical oral progestogens: e.g. Primolut N (norethisterone) 5mg TDS on day 5–26 of each cycle ^[11]
• Medroxyprogesterone acetate (MPA) 10mg daily for 10–14 days per cycle (luteal phase supplementation)

How cyclical progestogen works:

• In anovulatory cycles, the endometrium is exposed to oestrogen only (no progesterone because no ovulation). The progestogen mimics what the corpus luteum would normally do:
  1. Converts the proliferative endometrium to secretory (compact, stable)
  2. When the progestogen is stopped (e.g. after day 26), withdrawal triggers an organised, predictable bleed — essentially an "artificial period"
  3. Repeated cyclical use prevents the endometrium from becoming dangerously thick → protects against endometrial hyperplasia
• Why "day 5–26"? This covers most of the cycle, giving the endometrium a prolonged progestogen exposure (mimicking a long luteal phase) to ensure adequate secretory transformation before withdrawal

When to use:

• COC contraindicated (VTE risk, migraines with aura, etc.)
• Patient does not need/want contraception (cyclical progestogen at standard doses does NOT reliably inhibit ovulation — it is not a contraceptive unless used in specific POP formulations)
• PCOS patients who need endometrial protection but cannot take COCs

Side effects: bloating, mood changes, breast tenderness, acne (androgenic progestogens like norethisterone), weight gain

Levonorgestrel-releasing IUCD: alternative to COC pills ^[7]

How the LNG-IUS works:

• Releases 20μg/day of levonorgestrel (LNG) directly into the uterine cavity
• Local progestogenic effect on the endometrium:
  • Profound decidualisation and atrophy of endometrial glands → very thin, inactive endometrium → dramatically reduced bleeding
  • Thickens cervical mucus → barrier to ascending infection and sperm (provides contraception)
  • Does NOT reliably suppress ovulation (unlike COCs) — ~50% of cycles are still ovulatory
• Why it's excellent for AUB: The local drug delivery means very high endometrial progestogen concentration with minimal systemic absorption → fewer systemic side effects than oral progestogens, yet powerful endometrial suppression
• Reduces menstrual blood loss by ~90% at 12 months
• Effective for 5 years (Mirena) or 8 years (updated data for contraception; 5 years for HMB indication)
• Also provides highly effective contraception (> 99%)
• Can be used if fibroids < 3cm with no cavity distortion ^[11]

Advantages:

• "Fit and forget" — excellent compliance (no daily pills to remember)
• Combined endometrial protection + contraception
• Fewer systemic side effects
• Can be used in women with contraindications to oestrogen

Disadvantages/Considerations:

• Irregular spotting/bleeding is common in the first 3–6 months (as the endometrium atrophies — counselling is essential)
• Not suitable if uterine cavity is distorted (large submucosal fibroids → may be expelled or malpositioned)
• Requires insertion procedure (minor)
• Small risk of expulsion (~5%), perforation (very rare, ~0.1%), infection (slightly increased risk in first 20 days)

Iron supplement: FeSO₄ 300mg BD × 12 weeks ^[7]

2nd line: Ferrum Hausmann chewable tablet BD or 3mL droplet QD × 12 weeks ^[7]

3rd line: IV iron ^[7]

Why iron?

• Chronic abnormal bleeding → iron deficiency anaemia. The body's iron stores (ferritin) are depleted faster than they can be replenished from diet alone
• Oral iron replaces depleted stores. Ferrous sulphate (FeSO₄) 300mg contains ~60mg elemental iron per tablet; BD provides ~120mg elemental iron/day. Only ~10% is absorbed, so ~12mg/day enters the bloodstream
• Why 12 weeks? It takes 2–3 months to replenish iron stores after correcting the Hb. Even after Hb normalises, continue iron to refill ferritin

Ferrous sulphate vs Ferrum Hausmann:

• FeSO₄ is a ferrous (Fe²⁺) salt — cheap, effective, but causes significant GI side effects (nausea, constipation, black stools, abdominal pain) because free Fe²⁺ is irritating to the GI mucosa
• Ferrum Hausmann (iron polymaltose complex) is a ferric (Fe³⁺) preparation — non-ionic iron complex that releases iron slowly → fewer GI side effects but slightly lower absorption. Used when FeSO₄ is not tolerated
• IV iron (e.g. ferric carboxymaltose / Ferinject, iron sucrose): bypasses GI absorption entirely. Used when: oral iron not tolerated, non-compliant, severe anaemia requiring rapid correction, malabsorption, or ongoing losses exceeding oral replacement capacity

Polyp can be observed (1/4 chance to spontaneously resolve if < 1cm) ^[7]

• Small, asymptomatic polyps (< 1cm): Observation is reasonable. ~25% resolve spontaneously (slough off)
• Symptomatic polyps or > 1cm: Hysteroscopic polypectomy — "see and treat." The polyp is visualised and excised under direct vision, then sent for histology (to exclude hyperplasia/malignancy within the polyp)
• Why histology is essential: ~1–3% of polyps harbour malignancy (higher in postmenopausal women, those on tamoxifen). You cannot tell benign from malignant by appearance alone

Medical treatment: ^[11]

Non-hormonal drugs:

• Tranexamic acid: oral Transamin 1g TDS up to 4 days, max 4g daily ^[11]

  • "Trans-" = across, "examic" from "examic acid" — an antifibrinolytic
  • Mechanism: Competitively inhibits plasminogen activation → prevents plasmin from breaking down fibrin clots → stabilises clots in the endometrial vasculature → reduces blood loss
  • Why for fibroids? Fibroids cause HMB partly through increased local fibrinolysis (↑tPA). Tranexamic acid directly counters this
  • Contraindication: Active thromboembolic disease (because you're inhibiting fibrinolysis → theoretically ↑clot risk, though evidence for increased VTE is weak)

• Iron supplement: oral ferrous sulphate 300mg TDS × 6 months if Hb < 10g/dL ^[11]

• ± Mefenamic acid: oral Ponstan 250–500mg TDS ^[11]

  • An NSAID (fenamate class) — inhibits cyclooxygenase → reduces prostaglandin synthesis
  • Note: does NOT appear to decrease blood loss in fibroids but can decrease painful menses ^[11]
  • Why doesn't it reduce bleeding in fibroids? In AUB-E (dysfunctional bleeding without fibroids), excess prostaglandins (PGE₂, PGI₂) cause vasodilation and increased bleeding, so NSAIDs help. In fibroids, the bleeding is mechanical (increased surface area, distorted vasculature) — prostaglandin inhibition doesn't address this

Hormonal drugs:

• GnRH agonists or antagonists: usually for pre-operative size reduction before hysteroscopic resection ^[11]

  • GnRH agonists (e.g. leuprolide, goserelin): Initially stimulate GnRH receptors → "flare" effect → then continuous exposure desensitises and downregulates the receptors → pituitary becomes unresponsive → profound suppression of FSH/LH → very low oestrogen ("medical menopause")
  • MoA: desensitisation → medically induce menopause → decrease size of fibroid, decrease menstrual-related symptoms ^[11]
  • Problem: rapid relapse following discontinuation, significant climacteric symptoms with menopause-related side effects (e.g. bone density) → therefore NOT for long-term use ^[11]
  • Why fibroids shrink: Fibroids are oestrogen-dependent — remove oestrogen and they shrink (by ~30–50% over 3 months). This makes surgery easier (smaller fibroid, less vascular)
  • GnRH antagonists (e.g. relugolix, elagolix): Directly block GnRH receptors without the initial flare → faster onset of suppression. Newer agents (relugolix with add-back oestrogen/progestogen) allow longer-term use by mitigating menopausal side effects while maintaining fibroid suppression

• Progesterone receptor modulators: e.g. ulipristal acetate, mifepristone ^[11]

  • MoA: modulate progesterone receptor in myoma tissues → decrease size of fibroids ^[11]
  • Side effects: risk of endometrial changes (mimic endometrial hyperplasia but uncertain long-term consequences), liver toxicity (ulipristal) ^[11]
  • NOT available for use in HK ^[11]

• Mirena IUCD if fibroids < 3cm with no cavity distortion ^[11]

Surgical treatment: ^[11]

Indications: NOT dependent on anatomical factor ^[11] — i.e., surgical indications are based on symptoms and clinical concern, not fibroid size alone.

• Symptomatic ^[11] (but warn patient that urinary frequency may not improve as it may be due to detrusor instability, not fibroid compression)
• Rapid growth or postmenopausal growth → worrisome of malignancy ^[11]
• Unexplained subfertility with significant submucosal component ^[11]

Alternative treatments:

• Uterine artery embolisation (UAE) ^[11][12]

  • How it works: Interventional radiology procedure — catheter inserted via femoral artery → guided to uterine artery → embolisation particles (PVA particles, gelfoam) injected → block blood supply to fibroids → ischaemic necrosis → shrinkage
  • Clinical indication: uterine fibroid embolisation ^[12]
  • Reduces fibroid volume by ~40–60% and improves symptoms in ~80–90% of patients
  • Not recommended if future fertility desired (may affect ovarian reserve and uterine blood supply)
  • Risks: post-embolisation syndrome (pain, fever, malaise), infection, fibroid expulsion, rarely premature ovarian insufficiency

• High-intensity focused ultrasound (HIFU) ^[11]

  • Focused ultrasound waves generate heat at a focal point within the fibroid → thermal ablation → coagulative necrosis → fibroid shrinks
  • Non-invasive (no incision, no anaesthesia needed)
  • Limited to certain fibroid locations/sizes

Management ^[13]:

Medical treatment: generally similar to endometriosis (unlike fibroids, where hormonal treatments are generally ineffective) ^[13]

• Oral contraceptive pills: little data on efficacy but still commonly used ^[13]
• Progestogen-only treatment: e.g. Mirena, Depo-Provera ^[13] — Mirena is particularly effective because local progestogen induces decidualisation and atrophy of the ectopic endometrial tissue within the myometrium
• Others: GnRH agonists, aromatase inhibitors ^[13]

Hysterectomy: definitive treatment ^[13]

• Only way to excise as there is no surgical plane for simple enucleation (even in adenomyoma) ^[13] — unlike fibroids which have a pseudocapsule allowing shelling out, adenomyosis diffusely infiltrates the myometrium
• Extent: subtotal hysterectomy as cervix and ovaries are not affected ^[13]
• Route: vaginal, laparoscopic, open, robotic ^[13]

Uterus-conserving procedures: ^[13]

• Uterine artery embolisation (UAE): reserved for failure or contraindication to medical + surgical therapy ^[13]
  • Effect: ~2/3 had long-term decreased symptom severity, but there is a high rate of additional intervention for persistent or recurrent symptoms ^[13]
• Ablative techniques: e.g. RFA, HIFU (investigational) ^[13]

Asymptomatic adenomyosis incidentally found does not require any treatment ^[13]

• Refer to Gynae-Oncology
• Standard treatment: Total hysterectomy + bilateral salpingo-oophorectomy (TH-BSO) ± pelvic/para-aortic lymph node dissection ± adjuvant therapy (radiotherapy ± chemotherapy depending on stage, grade, histological type)
• Fertility-sparing treatment possible in highly selected cases (Grade 1 endometrioid, Stage IA, no myometrial invasion, strong fertility desire): high-dose progestogen + very close surveillance

• Empirical broad-spectrum antibiotics covering Chlamydia, Gonorrhoea, and anaerobes
• Outpatient regimen (mild–moderate): Ceftriaxone 500mg IM single dose + Doxycycline 100mg BD × 14 days + Metronidazole 400mg BD × 14 days
• Inpatient (severe / tubo-ovarian abscess): IV cefoxitin + PO doxycycline, or IV clindamycin + IV gentamicin
• Contact tracing and partner treatment mandatory
• IUCD removal if present and clinically appropriate

Miscarriage management ^[14]:

Threatened miscarriage:

• Expectant management: preferred for all cases ^[14]
• Bed rest: commonly recommended but NOT evidence-based (associated with risk of DVT) ^[14]
• Avoid sexual intercourse, physical exertion: commonly recommended but NOT evidence-based ^[14]
• Progestogen treatment: promising with early evidence ^[14]

Complete miscarriage:

• Ensure complete passage of products of gestation ^[14]
• Routine suction curettage: not recommended ^[14]

Incomplete and missed miscarriage — approach (NICE guideline): ^[14]

• Expectant management × 7–14 days: 1st line due to cost-effectiveness and decreased risk of intervening and accidentally terminating a viable pregnancy ^[14]
• Medical management: 2nd choice if expectant management not acceptable ^[14] — vaginal misoprostol 800μg single dose ^[14]
• Surgical management: 3rd choice ^[14] — suction evacuation under LA or GA ^[14]

Indications for immediate surgical management: ^[14]

• Evidence of infection: always indicates need for surgical management ^[14]
• Increased risk of haemorrhage, e.g. late 1st trimester ^[14]
• Coagulopathies, unable to have blood transfusion ^[14]

Anti-D immunoglobulin: for Rh(D)-negative patients ^[14]

Ectopic pregnancy:

• Haemodynamically unstable / ruptured: Emergency surgery (laparoscopy or laparotomy) → salpingectomy (removal of affected tube)
• Haemodynamically stable, unruptured:
  • Surgical: Laparoscopic salpingectomy (preferred if no desire for future fertility or contralateral tube is healthy) or salpingotomy (if fertility desired and contralateral tube damaged)
  • Medical: Methotrexate (MTX) — a folate antagonist that inhibits rapidly dividing trophoblastic cells. Single-dose IM. Criteria: haemodynamically stable, unruptured, β-hCG < 5000 IU/L (some guidelines < 3000), no fetal heartbeat, no significant haemoperitoneum, compliant patient for follow-up
  • Expectant: If β-hCG is low and declining spontaneously → may resolve without intervention. Requires very close serial β-hCG monitoring

Molar pregnancy:

• Suction evacuation of the mole (NOT medical induction — risk of embolisation of trophoblastic tissue)
• Histological confirmation
• Serial β-hCG monitoring post-evacuation until undetectable (weekly then monthly for 6–12 months depending on complete vs partial mole)
• Contraception during surveillance (pregnancy would confound hCG monitoring)
• If hCG plateaus or rises → gestational trophoblastic neoplasia (GTN) → chemotherapy

Local oestrogen cream: for atrophic vaginitis/endometritis ^[9]

Regimen: Premarin cream 0.5g QD × 2 weeks then 3×/week for 6 months ^[9]

How it works: Topical oestrogen is applied directly to the vaginal mucosa → stimulates proliferation and maturation of vaginal epithelium → restores glycogen content → restores lactobacilli → normalises vaginal pH → mucosa becomes thicker, more resilient, better lubricated → resolves bleeding, dryness, and dyspareunia

Why local rather than systemic? Local application achieves therapeutic vaginal concentrations with minimal systemic absorption → avoids the risks associated with systemic HRT (VTE, breast cancer) while effectively treating the vaginal symptoms

Beyond the general COC/progestogen/LNG-IUS approach above, PCOS management includes:

• Endometrial protection is the priority in PCOS patients not trying to conceive — cyclical progestogen or COC to prevent unopposed oestrogen exposure and hyperplasia
• Weight loss (if overweight/obese): Even 5–10% weight loss can restore ovulatory cycles — reduces peripheral aromatisation of androgens, improves insulin sensitivity, reduces SHBG suppression
• Metformin (off-label): Improves insulin sensitivity → reduces hyperinsulinaemia → reduces androgen production → may restore ovulatory cycles. Not first-line for bleeding management but useful adjunct in metabolic phenotype
• Anti-androgens (if hirsutism/acne predominant): Cyproterone acetate (often combined with EE as co-cyprindiol / Diane-35), spironolactone
• If fertility desired: Ovulation induction — letrozole (first-line, aromatase inhibitor) or clomiphene citrate (SERM)

• First 3 months: Reassure — breakthrough bleeding is common as the endometrium adjusts. Check compliance.
• After 3 months:
  • Check compliance (most common cause of persistent breakthrough bleeding)
  • Check for drug interactions (enzyme-inducing drugs: rifampicin, carbamazepine, phenytoin reduce COC efficacy)
  • Consider increasing oestrogen dose (if on low-dose COC) or switching preparation
  • Exclude other pathology (STD screen, speculum exam, USS/EA if persistent > 3 months → irregular bleeding while on hormonal therapy for > 3 months → hysteroscopy ± endometrial biopsy ^[7])

Algorithm for managing bleeding on HRT: ^[10]

This is the single most common complication of chronic IMB/irregular bleeding.

Anaemic symptoms: headache, palpitation, SOB, dizziness, fatigue, pica ^[1]

Why does chronic uterine bleeding cause iron deficiency anaemia?

• Each mL of blood lost contains ~0.5mg of iron (bound to haemoglobin)
• Normal menstrual blood loss is 30–40mL/cycle (~15–20mg iron/cycle)
• With abnormal bleeding, losses may be 80–200mL+/cycle or continuous intermenstrual losses → iron losses far exceed dietary absorption (~1–2mg/day)
• The body's iron stores (ferritin in hepatocytes and macrophages) are progressively depleted
• Once stores are exhausted → iron supply to the bone marrow falls → inadequate haemoglobin synthesis → microcytic, hypochromic red blood cells → anaemia

Symptom pathophysiology:

Severity: Can range from mild (compensated, asymptomatic with low ferritin) to severe (Hb < 7g/dL, symptomatic, requiring blood transfusion in acute-on-chronic decompensation). Severe anaemia can precipitate high-output cardiac failure in elderly patients or those with underlying cardiac disease.

This occurs in acute, heavy bleeding — most commonly from:

• Ruptured ectopic pregnancy (haemoperitoneum)
• Incomplete miscarriage with retained products
• Acute heavy anovulatory bleeding (endometrium shedding massively after prolonged unopposed oestrogen)
• Profuse bleeding if fibroid polyp protrudes through cervix ^[5]

Why shock? Rapid blood loss exceeding ~15–20% of circulating blood volume (Class II haemorrhage) → inadequate venous return → reduced cardiac output → inadequate tissue perfusion → organ dysfunction. If uncorrected → Class III/IV haemorrhagic shock → multi-organ failure → death.

Signs: Tachycardia, hypotension, cold/clammy peripheries, prolonged capillary refill, oliguria, altered consciousness.

Why is ectopic pregnancy the most dangerous? Because bleeding is both external (vaginal) and internal (into the peritoneal cavity from the ruptured tube). The internal bleeding may not be immediately apparent. The patient can lose > 1L into the abdomen before haemodynamic compromise becomes clinically obvious.

Often underappreciated but very real:

• Anxiety: Unpredictable bleeding causes constant worry about soiling clothes, embarrassment, ability to participate in social/work activities
• Sexual dysfunction: Fear of bleeding during intercourse → avoidance → relationship strain
• Depression: Chronic symptoms, fatigue from anaemia, disruption of daily life
• Work/school absenteeism: Significant socioeconomic impact
• Fear of serious disease: Many women fear cancer when they experience abnormal bleeding — appropriate counselling is therapeutic

Excess risk of endometrial hyperplasia / carcinoma: due to chronic unopposed oestrogen exposure ^[3]

This is the most feared long-term complication of chronic anovulation.

Why? No ovulation → no corpus luteum → no progesterone → endometrium exposed to unopposed oestrogen continuously:

• Oestrogen drives endometrial proliferation (mitosis in glandular epithelium)
• Progesterone normally induces secretory differentiation AND promotes apoptosis of proliferating cells
• Without this braking mechanism → continuous proliferation → hyperplasia → accumulation of genetic mutations → atypical hyperplasia (EIN) → endometrioid adenocarcinoma (Type 1)
• This is the "hyperplasia–carcinoma sequence" — a stepwise progression driven by unopposed oestrogen

Clinical implication: Any woman with chronic anovulation (PCOS, hypothalamic amenorrhoea, perimenopause) must have endometrial protection — either cyclical progestogen or COCs to induce regular withdrawal bleeds and prevent endometrial build-up. Failure to do this exposes her to a preventable cancer.

PCOS metabolic complications: ^[3]

• ~10% of PCOS patients have T2DM, 30% have impaired glucose tolerance ^[3]
• Metabolic syndrome: obesity, insulin resistance, NAFLD, dyslipidaemia, hypertension, sleep apnoea
• Cardiovascular disease: long-term increased risk due to metabolic syndrome constellation
• Why? The insulin resistance that drives PCOS also drives the metabolic syndrome — these are manifestations of the same pathophysiology

Fibroid-related complications: ^[5]

PID: associated with pelvic pain, fever, vaginal discharge ^[1]

• Tubal rupture: The growing gestational sac erodes through the tubal wall → massive intraperitoneal haemorrhage → haemodynamic shock → death if not treated emergently
• Tubal damage: Even with treatment (salpingotomy), the affected tube may be permanently damaged → reduced fertility, increased risk of recurrent ectopic
• Rh sensitisation: Feto-maternal haemorrhage in ectopic pregnancy can sensitise Rh-negative mothers → future pregnancies at risk of haemolytic disease of the newborn. This is why Anti-D immunoglobulin is given to Rh(D)-negative patients ^[14]

• Progression of hyperplasia without atypia: Low risk (~1–3%) but possible if untreated → atypical hyperplasia → carcinoma
• Progression of atypical hyperplasia: High risk (~30–40%) → endometrial carcinoma. Up to 40% of patients with atypical hyperplasia on biopsy already harbour concurrent carcinoma on hysterectomy specimen
• Endometrial carcinoma: Local invasion (myometrium, cervix), lymphatic spread (pelvic/para-aortic lymph nodes), distant metastases (lung, liver, bone). Early stage has excellent prognosis (Stage I five-year survival > 90%); advanced stage much worse

• Local invasion: parametrium, bladder (→ haematuria, vesicovaginal fistula), rectum (→ rectovaginal fistula)
• Lymphatic spread: pelvic → para-aortic → distant lymph nodes
• Ureteric obstruction: parametrial tumour compresses ureters → hydronephrosis → renal failure (a common mode of death in advanced cervical carcinoma)
• Lower limb lymphoedema: pelvic lymph node involvement → lymphatic obstruction
• VTE: cancer-associated hypercoagulability + pelvic venous compression

• Haemorrhage: Incomplete miscarriage → retained products prevent uterine contraction → ongoing heavy bleeding → haemodynamic compromise
• Infection (septic miscarriage): Retained necrotic products → ascending infection → endometritis → myometritis → septicaemia. Evidence of infection always indicates need for surgical management ^[14]
• Asherman's syndrome: Overly aggressive curettage (especially in the setting of infection) damages the basalis layer of the endometrium → intrauterine adhesions (synechiae) → amenorrhoea, infertility, recurrent miscarriage
• Rh sensitisation: As above — anti-D required for Rh-negative patients
• Psychological: Grief, guilt, anxiety, depression, post-traumatic stress — often underappreciated. Adequate counselling and follow-up are essential

• Gestational trophoblastic neoplasia (GTN): After evacuation, persistent trophoblastic activity (hCG fails to decline or rises) → can progress to invasive mole, choriocarcinoma, or placental site trophoblastic tumour. Why hCG monitoring is mandatory: hCG is produced by trophoblast; persistent/rising hCG after evacuation = persistent trophoblastic disease. Complete mole has ~15–20% risk of GTN; partial mole ~1–5%.
• Thyrotoxicosis: Very high hCG levels → structural similarity between hCG and TSH → hCG cross-reacts with TSH receptors on thyroid → thyroid hormone hypersecretion → clinical hyperthyroidism (tremor, tachycardia, weight loss)
• Hyperemesis: Markedly elevated hCG stimulates the vomiting centre
• Pre-eclampsia: Can occur in the first trimester (which is otherwise very rare and should raise suspicion for molar pregnancy) — mechanism involves abnormal trophoblastic invasion

LNG-IUS complications: ^[15]

Endometrial aspiration (Pipelle):

• Very safe; minor complications: cramping, vasovagal reaction, light bleeding, very rarely uterine perforation or infection
• Failed/inadequate sample: Not a complication per se, but a limitation — may necessitate hysteroscopy

Hysteroscopy:

• Uterine perforation (~0.1%) → may require laparoscopy to assess for intra-abdominal injury
• Infection (rare)
• Fluid overload (if excessive distension media absorbed) → hyponatraemia, pulmonary oedema (more relevant with monopolar resectoscope using glycine; less with bipolar using normal saline)
• Bleeding

Myomectomy:

• Haemorrhage (can be significant — myomectomy bed bleeds freely)
• Adhesion formation (especially after open myomectomy) → future infertility, bowel obstruction
• Uterine rupture in subsequent pregnancy (if full-thickness myometrial incision — must deliver by elective Caesarean section)
• Recurrence of fibroids (15–30%)

Hysterectomy:

Complications of hysterectomy (relevant to cervical carcinoma context but applicable generally): ^[16]

Uterine Artery Embolisation (UAE):

• Post-embolisation syndrome (pain, fever, malaise, nausea — in ~30–50%): inflammatory response to ischaemic necrosis of fibroid tissue
• Infection/abscess of necrotic fibroid (rare but serious)
• Fibroid expulsion (if submucosal — can cause heavy bleeding, infection)
• Premature ovarian insufficiency (non-target embolisation of ovarian arteries → follicular loss; risk increases with age > 40)
• Amenorrhoea (~5%)