Uterine Fibroids (Leiomyoma)

1. Clinical Overview

Definition and Importance

Uterine fibroids (leiomyomas) are benign monoclonal tumours arising from the smooth muscle cells (myometrium) of the uterus. They represent the most common pelvic tumour in women and the most common indication for hysterectomy in many healthcare systems. [1]

The clinical significance of fibroids extends beyond their high prevalence. They are responsible for substantial morbidity through heavy menstrual bleeding (HMB), pelvic pain, pressure symptoms, and reproductive complications. The economic burden is considerable, with estimated annual costs exceeding $34 billion in the United States alone when accounting for treatment costs and lost productivity. [2]

Despite their benign nature, fibroids can profoundly impact quality of life, fertility potential, and obstetric outcomes. Understanding their classification, natural history, and evidence-based management options is essential for gynaecologists at all levels.

Key Clinical Message

Fibroids are oestrogen and progesterone dependent. They enlarge during reproductive years and pregnancy, then typically shrink after menopause. The cardinal symptom is heavy menstrual bleeding, but symptom severity correlates with location rather than size. A small submucosal fibroid can cause torrential bleeding, while a large subserosal fibroid may be asymptomatic. Management is individualized based on symptoms, fertility desires, fibroid characteristics, and patient preferences.

Clinical Pearls

Location Matters More Than Size: The anatomical relationship to the endometrial cavity is the primary determinant of symptoms. A 2cm submucosal fibroid protruding into the cavity causes more bleeding than a 10cm subserosal fibroid on the uterine surface. The FIGO classification system (see below) is essential for surgical planning.

Red Degeneration in Pregnancy: A classic MRCOG scenario. Pregnant woman at 18-20 weeks presents with acute severe localized abdominal pain, low-grade pyrexia, vomiting, and leucocytosis. The fibroid has outgrown its blood supply and undergone haemorrhagic infarction. Management is conservative: analgesia (paracetamol, opioids), rest, reassurance, and antiemetics. Surgery (myomectomy) during pregnancy carries significant haemorrhage risk and is reserved for absolute emergencies. Most cases resolve within 4-7 days. [3]

The "Shrinking" Fibroid: Any fibroid that grows rapidly in a post-menopausal woman (when it should be regressing due to low oestrogen) raises suspicion of leiomyosarcoma. This rare malignancy (less than 1% of uterine fibroids) has a poor prognosis. MRI with gadolinium can help differentiate (irregular borders, heterogeneous enhancement, necrosis), but definitive diagnosis requires histology.

Fertility Paradox: Intramural and subserosal fibroids that do not distort the uterine cavity have minimal impact on fertility. However, submucosal fibroids reduce implantation rates and increase miscarriage risk. ESHRE/ASRM guidelines recommend myomectomy for submucosal fibroids in women with otherwise unexplained subfertility. [4]

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2. Epidemiology

Prevalence and Incidence

Uterine fibroids are extraordinarily common, though precise prevalence estimates vary based on detection methods:

The cumulative incidence by age 50 is estimated at 70% for White women and > 80% for Black women of African descent. [6] Importantly, only 20-50% of women with fibroids develop symptoms requiring treatment.

Risk Factors

Non-Modifiable Risk Factors

1. Ethnicity: Black women have 2-3 times higher risk, earlier age of onset (5-10 years younger), larger fibroids, more numerous fibroids, and more severe symptoms compared to White women. The biological basis remains incompletely understood but may involve genetic polymorphisms affecting oestrogen metabolism and growth factors. [6]

2. Age: Incidence increases with age during reproductive years, peaking in the fifth decade (40-50 years). Rare before menarche and new fibroids uncommon after menopause.

3. Family History: First-degree relative with fibroids increases risk 2.5-fold. Twin studies suggest heritability of approximately 25-30%. [7]

4. Early Menarche: Age at menarche less than 10 years associated with increased risk due to longer cumulative oestrogen exposure.

Modifiable Risk Factors

1. Nulliparity: Pregnancy appears protective. Each full-term pregnancy reduces risk by approximately 20%. Proposed mechanisms include apoptosis of fibroid precursor cells during post-partum uterine involution and tissue remodeling. [8]

2. Obesity: BMI > 30 kg/m² increases risk. Adipose tissue converts androgens to oestrogens via aromatase, increasing systemic oestrogen exposure.

3. Dietary Factors:

   • High red meat consumption associated with increased risk
   • High intake of green vegetables and fruit may be protective
   • Vitamin D deficiency implicated in some studies [9]

4. Hormonal Factors:

   • Combined oral contraceptive use: Protective if started before age 16; neutral or slightly protective if used long-term
   • Progestogen-only contraceptives: Data conflicting
   • Hormone replacement therapy: May stimulate growth

Protective Factors

• Multiparity
• Cigarette smoking (possibly via anti-oestrogenic effects; not recommended as intervention)
• Long-term DMPA (depot medroxyprogesterone acetate) use

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3. Aetiology and Pathophysiology

Cellular Origin

Fibroids are monoclonal tumours arising from a single transformed myometrial smooth muscle cell. Cytogenetic abnormalities are found in 40-50% of fibroids, most commonly:

• Deletion of chromosome 7q
• Rearrangements involving chromosome 12q15 (HMGA2 gene)
• Trisomy 12
• Deletion of chromosome 3

These genetic alterations are somatic (acquired), not inherited.

Hormonal Dependence

Fibroids are exquisitely sensitive to ovarian steroid hormones:

Oestrogen Effects:

• Stimulates fibroid growth via oestrogen receptors (ER-α and ER-β)
• Upregulates production of local growth factors (EGF, IGF-1, TGF-β)
• Increases extracellular matrix (ECM) production
• Fibroids have higher ER density than normal myometrium [10]

Progesterone Effects:

• Initially thought protective, now recognized as growth-promoting
• Progesterone receptor (PR) expression higher in fibroids
• Stimulates mitotic activity during luteal phase
• Selective progesterone receptor modulators (SPRMs) like ulipristal acetate effectively shrink fibroids by blocking PR [11]

Growth Factors and Molecular Pathways

Local paracrine factors amplify hormonal signals:

• TGF-β (Transforming Growth Factor-beta): Promotes ECM deposition, contributing to fibrous nature
• bFGF (basic Fibroblast Growth Factor): Angiogenesis
• VEGF (Vascular Endothelial Growth Factor): Neovascularization
• IGF-1 (Insulin-like Growth Factor-1): Cell proliferation
• EGF (Epidermal Growth Factor): Mitogenesis

Classification: FIGO Leiomyoma Subclassification System (2011)

The International Federation of Gynecology and Obstetrics (FIGO) system classifies fibroids by relationship to the uterine wall and endometrial cavity. This classification guides surgical planning and predicts symptomatology. [12]

Submucosal Fibroids (0-2):

• Type 0: Pedunculated intracavitary (entirely within cavity, attached by stalk)
• Type 1: less than 50% intramural (> 50% projecting into cavity)
• Type 2: ≥50% intramural (less than 50% projecting into cavity)

Other (3-8):

• Type 3: 100% intramural, contacts endometrium
• Type 4: Intramural, no endometrial contact
• Type 5: Subserosal ≥50% intramural
• Type 6: Subserosal less than 50% intramural
• Type 7: Subserosal pedunculated
• Type 8: Other (cervical, broad ligament, parasitic)

Hybrid Fibroids: Many fibroids impact both surfaces (e.g., "2-5" indicates a Type 2 submucosal component with Type 5 subserosal extension).

Histopathology

Macroscopic Appearance:

• Well-circumscribed, round/ovoid masses
• Whorled appearance on cut section (interlacing bundles)
• Pseudocapsule (compressed myometrium) allowing surgical enucleation
• Colour: white-tan to pink
• May show areas of degeneration (see below)

Microscopic Appearance:

• Whorled bundles of uniform smooth muscle cells
• Spindle-shaped cells with elongated nuclei
• Abundant eosinophilic cytoplasm
• Minimal mitotic activity (less than 5 mitoses per 10 high-power fields)
• Variable amounts of collagen/fibrous tissue

Degenerative Changes: Fibroids outgrow their blood supply, leading to various degeneration patterns:

1. Hyaline Degeneration (60%): Most common. Homogeneous, acellular, glassy appearance.
2. Cystic Degeneration: Liquefaction of hyaline areas.
3. Red (Carneous) Degeneration: Haemorrhagic infarction, typically in pregnancy. Appears red/purple.
4. Calcific Degeneration: Common post-menopause. May be visible on plain radiograph.
5. Myxoid Degeneration: Gelatinous change.
6. Fatty Degeneration: Rare.
7. Sarcomatous Change: Malignant transformation. Exceptionally rare (less than 0.1%).

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4. Clinical Presentation

Symptom Profile

Asymptomatic (50%): Incidental finding on imaging or examination. Natural history variable; many remain asymptomatic indefinitely.

Heavy Menstrual Bleeding (HMB)

The hallmark symptom, occurring in 30% of women with fibroids. Mechanism depends on location:

• Submucosal fibroids:

  • Increase endometrial surface area
  • Impair endometrial haemostasis (mechanical disruption)
  • Alter local prostaglandin and vasoconstrictor production
  • Cause venous ectasia and congestion

• Intramural fibroids (if large or numerous): Disrupt normal myometrial contractility needed for haemostasis

Clinical Impact:

• Menorrhagia (> 80ml blood loss per cycle; > 7 days duration)
• Flooding, clots, need for double protection
• Dysmenorrhoea (painful periods) from uterine distension
• Iron deficiency anaemia (30-40% of symptomatic cases)
• Fatigue, reduced quality of life
• Social embarrassment, impact on work/relationships

Pelvic Pressure and "Bulk" Symptoms

Large fibroids (> 10cm) or multiple fibroids cause mass effect:

• Urinary Symptoms:

  • Frequency (bladder compression)
  • Urgency, nocturia
  • Urinary retention (rare; large anterior cervical fibroid impacts bladder neck)
  • Hydronephrosis (very large fibroids compress ureters laterally)

• Bowel Symptoms:

  • Constipation (posterior fibroids compress rectum)
  • Tenesmus, difficulty evacuating
  • Rarely, bowel obstruction

• Other Pressure Symptoms:

  • Abdominal bloating/distension
  • Pelvic heaviness or dragging sensation
  • Lower back pain
  • Leg oedema (pelvic venous/lymphatic compression; very rare)

Pain

Fibroids are typically not painful unless complications occur:

• Acute Pain:

  • Red degeneration (pregnancy)
  • Torsion of pedunculated fibroid (acute abdomen)
  • Expulsion of submucous fibroid through cervix ("fibroid in labour")

• Chronic Pain:

  • Large fibroids causing pressure
  • Concomitant adenomyosis or endometriosis (common coexistence)

Reproductive Complications

Impact on Fertility (mechanism dependent on location): [4]

• Submucosal fibroids:

  • Reduce implantation rate (mechanical barrier, altered endometrial receptivity)
  • Double miscarriage risk
  • Surgical removal improves pregnancy rates (Level 2 evidence)

• Intramural fibroids > 3cm:

  • May reduce IVF success if distorting cavity
  • Evidence for myomectomy benefit is weaker

• Subserosal fibroids:

  • Minimal to no impact on fertility

Obstetric Complications:

• Recurrent pregnancy loss (submucosal/large intramural)
• Placenta praevia (if fibroid occupies lower segment)
• Malpresentation (breech, transverse lie)
• Obstructed labour (cervical fibroid blocking descent)
• Preterm labour (uterine irritability)
• Postpartum haemorrhage (impaired myometrial contractility)
• Red degeneration (carneous degeneration during pregnancy)

Examination Findings

Abdominal Examination

• Inspection: Abdominal distension if large fibroid (> 12-week size)
• Palpation:
  • Firm, irregular, non-tender pelvic/abdominal mass
  • Arises from pelvis, cannot "get below it"
  • Surface may be smooth (single large fibroid) or bosselated/knobbly (multiple fibroids)
  • "Percussion: dull over mass"
  • Measure size in "weeks" (e.g., 16-week-size fibroid uterus = palpable at umbilicus)

Pelvic (Bimanual) Examination

• Uterus:

  • Enlarged, irregular contour
  • Firm/hard consistency (versus soft in pregnancy, boggy in adenomyosis)
  • Mobile unless fixed by adhesions or endometriosis
  • Moves with cervix (distinguishes from ovarian mass)
  • Tenderness only if red degeneration or torsion

• Cervix:

  • May be displaced by fibroid bulk
  • Assess for cervical fibroid or polyp
  • Prolapsing submucous fibroid may be visible at os

• Adnexa: Normal unless coexistent pathology

Speculum Examination

• Exclude cervical pathology (polyp, malignancy)
• Rarely, see pedunculated submucous fibroid prolapsing through os

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5. Differential Diagnosis

Critical to distinguish fibroids from other pelvic masses and causes of HMB:

Pelvic Mass

Heavy Menstrual Bleeding (HMB)

Fibroids account for ~30% of HMB cases. Exclude:

1. Endometrial Pathology:

   • Endometrial polyps (hysteroscopy/saline sonography shows intracavitary lesion)
   • Endometrial hyperplasia/malignancy (pipelle biopsy if > 45 years or risk factors)

2. Adenomyosis:

   • Overlap with fibroids common (in 20% of cases)
   • Dysmenorrhoea, boggy uterus, USS shows heterogeneous myometrium with cysts

3. Coagulopathy:

   • Von Willebrand Disease (13% of women with HMB since menarche)
   • Platelet disorders
   • Anticoagulant use

4. Iatrogenic:

   • Copper IUD
   • Anticoagulation

5. Dysfunctional Uterine Bleeding (DUB): Diagnosis of exclusion

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6. Investigations

First-Line Investigations

Pelvic Ultrasound

Transvaginal USS (TVUS) is first-line imaging:

• Sensitivity: 90-99% for detecting fibroids [13]

• Findings:

  • Hypoechoic (darker than myometrium) well-defined masses
  • May show calcification (acoustic shadowing)
  • Degenerative changes (heterogeneous, cystic areas)
  • Assess number, size (measure 3 dimensions), and location

• FIGO Mapping: Document relationship to endometrium

• Limitations:

  • Operator-dependent
  • Difficult if multiple fibroids or large uterus (> 12cm)
  • Cannot always differentiate fibroids from adenomyosis

Transabdominal USS: Used if uterus too large for transvaginal view; requires full bladder.

Saline Infusion Sonohysterography (SIS): Saline instilled into cavity during USS enhances visualization of submucosal fibroids. Useful for pre-operative mapping before hysteroscopic resection.

Laboratory Tests

• Full Blood Count (FBC):

  • Assess for anaemia (Hb, MCV)
  • "Iron deficiency anaemia: microcytic (low MCV), low ferritin"

• Ferritin: Assess iron stores if anaemic

• Thyroid Function Tests (TFTs): Hypothyroidism can cause menorrhagia

• Coagulation Screen: If HMB since menarche or family history (von Willebrand screen)

• Pregnancy Test (hCG): Exclude pregnancy if amenorrhoea or irregular bleeding

Second-Line Investigations

Magnetic Resonance Imaging (MRI)

Indications:

• Pre-operative mapping for myomectomy or UAE (especially if > 4 fibroids)
• Differentiating adenomyosis from fibroids
• Suspected leiomyosarcoma (rapid growth post-menopause)
• Large/complex fibroids where USS non-diagnostic

MRI Findings:

• Fibroids: T2-weighted imaging shows well-defined low signal masses
• Delineates fibroid borders, vascular supply, relationship to cavity
• Distinguishes adenomyosis (poorly defined junctional zone thickening)
• Leiomyosarcoma features: irregular borders, heterogeneous signal, central necrosis, high T2 signal [14]

Advantages: Superior soft tissue contrast, 3D mapping, no radiation.

Disadvantages: Expensive, limited availability, longer scan time.

Hysteroscopy

Direct visualization of uterine cavity:

• Gold standard for diagnosing submucosal fibroids
• Performed outpatient (Ambulatory Hysteroscopy) or under GA
• Technique: Distension medium (saline/CO₂), hysteroscope (rigid/flexible)

Findings:

• Submucosal fibroid appears as smooth, pale, rounded projection into cavity
• Assess size, location, degree of intramural extension (FIGO Type 0, 1, or 2)
• Rule out polyps, endometrial hyperplasia/cancer

Concurrent Procedures:

• Biopsy: Endometrial sampling (Pipelle)
• Polypectomy
• Small fibroid resection (MyoSure device or resectoscope)

Endometrial Sampling

Indications for biopsy (exclude endometrial malignancy/hyperplasia):

• Age > 45 years with HMB
• HMB with risk factors (obesity, PCOS, unopposed oestrogen)
• Persistent intermenstrual or post-coital bleeding
• Failed medical management

Methods:

• Pipelle biopsy: Outpatient, sensitivity 81% for cancer/hyperplasia
• Hysteroscopy + Biopsy: More sensitive
• Dilatation & Curettage (D&C): Rarely required; hysteroscopy preferred

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7. Management

Management is highly individualized, balancing:

• Symptom severity
• Desire for future fertility
• Fibroid characteristics (size, number, location)
• Patient preferences and values
• Surgical risks (age, comorbidities)

Management Algorithm

SYMPTOMATIC UTERINE FIBROIDS
              ↓
    Desire Future Pregnancy?
         ┌──────┴──────┐
        YES            NO
         ↓              ↓
    Submucosal?    Severity Assessment
         ↓              ↓
    HYSTEROSCOPIC  Mild-Moderate → MEDICAL
     MYOMECTOMY         ↓
         ↓         1. Mirena IUS (if cavity normal)
    Intramural/    2. Tranexamic Acid + NSAIDs
    Subserosal?    3. Combined Pill
         ↓         4. SPRMs (Ulipristal, Relugolix)
    ABDOMINAL           ↓
    MYOMECTOMY     Severe / Failed Medical
    (Open/Lap)          ↓
         ↓         Preserve Uterus?
         ↓              ├──────┬──────┐
    Post-op           YES           NO
    Fertility         ↓              ↓
    Counselling   UAE / HIFU    HYSTERECTOMY
                  Myomectomy    (definitive cure)

Expectant Management ("Watch and Wait")

Indications:

• Asymptomatic fibroids (50% of cases)
• Minimal symptoms not affecting quality of life
• Approaching menopause (fibroids will shrink)
• Medical comorbidities making intervention high-risk

Follow-up:

• Annual pelvic examination
• USS if symptoms develop or change
• FBC if menorrhagia (monitor for anaemia)

Natural History:

• 10% spontaneously regress
• 50% remain stable
• 40% grow slowly (average 9% volume increase per year)
• Post-menopause: 70-80% shrink by > 35% [15]

Medical Management

Medical therapy aims to control symptoms, not cure fibroids. Most effective for HMB and mild pressure symptoms.

1. Levonorgestrel Intrauterine System (LNG-IUS, Mirena)

Mechanism: Local endometrial suppression by progestogen.

Efficacy:

• Reduces menstrual blood loss by 71-96% [16]
• 64% of women amenorrhoeic by 12 months
• Does NOT shrink fibroids
• Effective if cavity not significantly distorted

Indications: First-line for HMB if cavity less than 12cm sound length, no large submucosal fibroid.

Insertion: Outpatient, at any time if not pregnant, ideally during menses.

Contraindications:

• Distorted cavity (may not retain device; expulsion rate 11% with fibroids vs 5% without)
• Current pelvic infection
• Breast cancer

Side Effects: Irregular bleeding first 3-6 months, progestogenic effects (acne, mood, bloating), ovarian cysts.

Duration: Licensed for 5 years; off-label use up to 7 years.

NICE Recommendation: First-line medical treatment for fibroid-related HMB (NG88, 2018). [17]

2. Tranexamic Acid

Mechanism: Antifibrinolytic; inhibits plasminogen activation, stabilizes clot.

Dosage: 1g TDS-QDS during menses only (days 1-5 of cycle).

Efficacy: Reduces menstrual blood loss by 26-54% [18].

Advantages: Non-hormonal, taken only during menses, well-tolerated.

Side Effects: GI upset (nausea, diarrhea), rarely thromboembolic events.

Contraindications: Active thromboembolic disease, history of VTE, severe renal impairment.

Role: Second-line, often combined with NSAIDs or hormonal methods.

3. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Mechanism: Inhibit prostaglandin synthesis, reducing menstrual flow and dysmenorrhoea.

Examples: Mefenamic acid 500mg TDS, Ibuprofen 400mg TDS (during menses).

Efficacy: Reduces blood loss by 20-30%.

Advantages: Also treats dysmenorrhoea; non-hormonal.

Side Effects: GI upset, renal impairment, contraindicated in peptic ulcer disease.

4. Combined Oral Contraceptive Pill (COC)

Mechanism: Endometrial suppression.

Efficacy: Reduces menstrual flow, regulates cycle.

Evidence: Limited high-quality data for fibroids specifically; effective for general HMB.

Contraindications: Smoker > 35 years, VTE risk, migraine with aura, uncontrolled hypertension.

5. Selective Progesterone Receptor Modulators (SPRMs)

Ulipristal Acetate (Esmya): Previously widely used; withdrawn in EU (2020) due to rare hepatotoxicity. No longer available in UK.

Relugolix Combination Therapy (Ryeqo):

• Composition: Relugolix (GnRH antagonist) 40mg + Estradiol 1mg + Norethisterone acetate 0.5mg
• Mechanism: Suppresses gonadotropins (LH/FSH), reducing oestrogen and progesterone; "add-back" E+P prevents menopausal symptoms and bone loss
• Efficacy: Reduces fibroid volume by ~30-50%; rapid bleeding control (73% less than 2 months) [19]
• Indications: Moderate-severe symptoms, pre-operative to reduce fibroid size
• Duration: Licensed up to 24 months
• NICE Approval: TA832 (2022) recommended for moderate-severe symptoms
• Side Effects: Hot flushes (despite add-back), headache, alopecia
• Advantages: Oral (vs IM GnRH agonists), fewer menopausal symptoms, can use long-term

6. GnRH Agonists (Goserelin, Leuprorelin)

Mechanism: Chronic stimulation downregulates pituitary GnRH receptors → "medical menopause" (suppressed FSH/LH → low oestrogen/progesterone).

Efficacy:

• Shrink fibroids by 35-60% within 3 months [20]
• Amenorrhoea in 90%
• Improve pre-operative haemoglobin (correct anaemia)

Indications:

• Pre-operative (3-6 months before myomectomy/hysterectomy): reduce vascularity, allow anaemia correction, reduce operative blood loss
• Bridge to menopause in perimenopausal women

Administration: IM depot injection monthly (Goserelin 3.6mg) or 3-monthly (10.8mg).

Side Effects:

• Menopausal symptoms: hot flushes (80%), vaginal dryness, mood changes
• Bone density loss (2-6% after 6 months) → limits use to 6 months without add-back HRT [27]
• Symptoms return on cessation; fibroid regrowth within 3-6 months

Limitations: Not suitable long-term due to osteoporosis risk; expensive; fibroid rebound.

Add-Back Therapy: Tibolone or low-dose HRT can be added after 3 months to mitigate bone loss and vasomotor symptoms while maintaining fibroid shrinkage. [28]

Interventional Radiology

Uterine Artery Embolisation (UAE)

Procedure:

• Interventional Radiology technique
• Femoral artery catheterized under local anaesthesia + sedation
• Catheter advanced to uterine arteries bilaterally
• Embolic particles (polyvinyl alcohol, trisacryl gelatin microspheres 500-700μm) injected → occlude fibroid blood supply → ischaemic necrosis and shrinkage
• Day-case or overnight stay

Efficacy:

• Fibroid volume reduction: 40-75% at 12 months [21]
• Symptom improvement: 85-90% satisfaction at 1 year
• HMB resolves/improves in 85-90%
• Bulk symptoms improve in 70-80%

Advantages:

• Uterus-sparing: no hysterectomy
• Minimally invasive: no laparotomy, small groin puncture
• Treats all fibroids simultaneously
• Shorter recovery than surgery (1-2 weeks vs 6 weeks)

Disadvantages:

• Post-embolisation syndrome (50-80%): severe pain, nausea, low-grade fever for 24-72 hours (requires opioid analgesia, anti-emetics)
• Re-intervention rate: 20-30% at 5 years (fibroid regrowth, recurrent symptoms) [22]
• Fertility: traditionally considered contraindicated in women desiring pregnancy (risk of premature ovarian insufficiency 1-5%, reduced ovarian reserve). Recent data suggest pregnancy possible; HOPEFUL study showed 50% pregnancy rate post-UAE but higher miscarriage rate than myomectomy. [23,29]
• Small risk of infection/abscess (less than 1%), fibroid expulsion (5-10%)

Contraindications:

• Active pelvic infection
• Pregnancy
• Suspected malignancy
• Pedunculated subserosal fibroid (risk of detachment/"parasitic" fibroid)
• GnRH agonist use within 3 months (fibroids too small, uterine arteries too narrow)

NICE Guidance (NG88): UAE should be offered as alternative to surgery for women wishing to avoid hysterectomy. [17]

High-Intensity Focused Ultrasound (HIFU/MRgFUS)

Mechanism: Focused ultrasound waves generate thermal ablation of fibroid tissue under MRI guidance.

Efficacy:

• Symptom improvement: 70-80% at 12 months
• Volume reduction: 10-30% (less than UAE/myomectomy)

Advantages: Non-invasive, outpatient, preserves fertility.

Disadvantages:

• Limited availability
• Time-consuming (3-4 hours)
• Expensive
• Less effective for large/multiple fibroids
• 20-30% require further treatment

Current Status: NICE IPG413 (2012) supports use but availability remains limited in NHS.

Surgical Management

Surgery provides definitive treatment. Choice of procedure depends on fertility desires, fibroid characteristics, and patient preference.

Hysteroscopic Myomectomy

Indications: Type 0, 1, 2 submucosal fibroids (FIGO classification).

Technique:

• Day-case or overnight
• General or regional anaesthesia
• Distension medium (glycine 1.5%, normal saline if bipolar)
• Resectoscopy: Loop electrode resects fibroid in strips ("slicing")
• MyoSure/Truclear: Hysteroscopic morcellator, removes fibroid intact

Efficacy:

• 90-95% successful resection (Type 0, 1)
• Type 2: may require two-stage procedure if > 50% intramural
• HMB resolution: 80-90%
• Fertility: improves implantation and reduces miscarriage in submucosal fibroids [4]

Complications:

• Fluid overload (1-2%): Glycine absorption → hyponatraemia, cerebral oedema
• Uterine perforation (1-2%)
• Haemorrhage (less than 1%)
• Intrauterine adhesions (Asherman syndrome) 2-5%

Size Limitations: Ideally less than 3cm Type 0/1; > 3cm or Type 2 may require pre-treatment with GnRH agonist or two-stage resection.

Abdominal Myomectomy (Open or Laparoscopic)

Indications:

• Intramural/subserosal fibroids causing symptoms
• Desire to preserve fertility
• Failed medical/conservative management

Open (Laparotomy) Myomectomy:

• Incision: Pfannenstiel or low midline
• Technique:
  • Vasopressin infiltration to reduce bleeding (or tourniquets)
  • Incise pseudocapsule, enucleate fibroid by traction/countertraction
  • Layered closure of myometrial defect
  • Adhesion barriers (Interceed)
• Indications for open approach: Multiple fibroids (> 4), large fibroids (> 10cm), intramural fibroids, posterior wall fibroids, limited laparoscopic expertise

Laparoscopic Myomectomy:

• Minimally invasive, faster recovery
• Requires advanced laparoscopic skills (suturing)
• Morcellation to remove fibroid (contained in bag to prevent spillage; concerns re: occult leiomyosarcoma dissemination)
• Indications: ≤4 fibroids, less than 10cm, anterior/fundal

Robotic-Assisted Myomectomy:

• Facilitates intracorporeal suturing
• Reduces conversion to laparotomy
• Expensive, limited availability

Efficacy:

• Symptom relief: 80-90%
• Fertility: pregnancy rates 50-70% post-myomectomy (if subfertility previously attributed to fibroids) [24]

Complications:

• Haemorrhage (1-5%): Fibroids are vascular; may require transfusion; rarely, emergency hysterectomy
• Adhesion formation (30-50%): Can impair fertility; use adhesion barriers
• Uterine rupture in pregnancy (0.2-1%): Risk depends on depth of myometrial incision; caesarean delivery often recommended if deep intramural fibroid removed
• Recurrence: 15-30% develop new fibroids within 5 years [25]
• Infection, VTE, anaesthetic risks

Post-operative Management:

• Recovery: 4-6 weeks (open), 2-3 weeks (laparoscopic)
• Advise waiting 3-6 months before attempting pregnancy (allow uterine healing)
• Mode of delivery: If deep myometrial breach, elective caesarean section at 37-38 weeks recommended

Hysterectomy

Definitive cure for fibroids; no recurrence.

Indications:

• Completed childbearing
• Failed/unsuitable for conservative management
• Patient preference for definitive treatment
• Severe symptoms impairing quality of life

Types:

• Total Abdominal Hysterectomy (TAH): Remove uterus and cervix via laparotomy
• Vaginal Hysterectomy (VH): Via vagina; faster recovery, less pain; requires uterine mobility and adequate vaginal access
• Laparoscopic Hysterectomy (TLH): Total laparoscopic; minimally invasive
• Subtotal Hysterectomy: Preserve cervix; requires ongoing cervical screening

Ovarian Conservation: In premenopausal women less than 65 years, ovaries typically conserved (unless pathology).

Efficacy: 100% symptom resolution; no recurrence.

Complications:

• Major: Haemorrhage (2-5%), bladder/ureteric injury (1-2%), bowel injury (less than 1%)
• VTE (0.5-2%)
• Infection (wound, pelvic, UTI) 5-10%
• Long-term: Vault prolapse (1-2%), sexual dysfunction (rare if ovaries conserved)

Recovery:

• Abdominal: 6-8 weeks
• Vaginal/Laparoscopic: 2-4 weeks

NICE Guidance: Hysterectomy should be discussed as option but UAE and myomectomy offered as uterus-conserving alternatives. [17]

Special Populations

Fibroids in Pregnancy

Management Approach: Conservative unless emergency.

Complications:

• Red degeneration (5-10% in pregnancy): Conservative (analgesia, rest)
• Pain: Usually responds to paracetamol/opioids
• Preterm labour: Tocolysis if indicated
• Malpresentation: ECV or caesarean for breech
• Obstructed labour: Caesarean if cervical fibroid

Myomectomy in Pregnancy: Rarely justified; high risk haemorrhage. Only for torsion of pedunculated fibroid or obstruction.

Delivery: Vaginal delivery preferred unless obstetric indication for caesarean.

Post-partum: Fibroids often shrink; reassess symptoms at 3-6 months post-partum before intervening.

Perimenopausal Women

Strategy: Bridge to menopause with medical therapy (Mirena, GnRH agonists, Relugolix) to avoid surgery. Fibroids shrink post-menopause.

Timeframe: If within 2-3 years of expected menopause (~51 years), consider temporizing.

Post-menopausal Women

New or Growing Fibroid: Suspicious for leiomyosarcoma. Requires MRI and gynaecological oncology referral.

Asymptomatic Fibroids: Often shrink; no intervention needed.

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8. Complications

Complications of Fibroids Themselves

Complications of Treatment

Medical Therapy:

• GnRH agonists: Bone loss, menopausal symptoms, fibroid rebound
• Mirena: Expulsion (11% with fibroids), irregular bleeding

UAE:

• Post-embolisation syndrome (80%)
• Re-intervention (20-30% at 5 years)
• Infection/abscess (less than 1%)
• Premature ovarian failure (1-5%, predominantly in women \u003e45 years) [29,30]

Myomectomy:

• Haemorrhage, transfusion (5%)
• Adhesions (30-50%)
• Uterine rupture in future pregnancy (0.2-1%)
• Recurrence (15-30% at 5 years)

Hysterectomy:

• Bladder/ureteric injury (1-2%)
• Haemorrhage (2-5%)
• VTE (0.5-2%)

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9. Prognosis

Natural History

• 50% asymptomatic throughout life
• 40% grow slowly during reproductive years (~9% volume increase/year)
• 10% spontaneously regress
• Post-menopause: 70-80% shrink by > 35% due to oestrogen withdrawal [15]

Treatment Outcomes

Medical Management:

• Mirena: 64% amenorrhoeic at 1 year; ongoing therapy required
• Relugolix: Effective while on treatment; fibroid regrowth 3-6 months after stopping

UAE:

• 85-90% satisfaction at 1 year
• 70-80% satisfaction at 5 years
• 20-30% require re-intervention by 5 years [22]

Myomectomy:

• 80-90% symptom relief
• 15-30% recurrence (new fibroid growth) at 5 years [25]
• Fertility: 50-70% pregnancy rate if fibroid was cause of subfertility

Hysterectomy:

• 100% cure
• High satisfaction (> 95%)

Impact on Quality of Life

Symptomatic fibroids significantly impair QoL:

• Physical: Pain, fatigue, anaemia
• Emotional: Anxiety, depression (30-40% in symptomatic women)
• Social: Work absence, social withdrawal, relationship impact
• Sexual: Dyspareunia, reduced libido

Treatment (medical or surgical) improves QoL scores significantly. [26]

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10. Prevention and Screening

Primary Prevention

No proven pharmacological prevention. Modifiable risk factor reduction:

• Maintain healthy BMI
• High vegetable/fruit intake, low red meat consumption [9]
• Multiparity (protective)
• Vitamin D supplementation (preliminary evidence; RCTs ongoing)

Screening

No population-based screening recommended. Fibroids often asymptomatic; screening would lead to over-treatment.

Case-finding: Pelvic USS in women with:

• Heavy menstrual bleeding
• Pelvic pain/pressure
• Subfertility (as part of investigation)

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11. Key Guidelines

National Institute for Health and Care Excellence (NICE)

NG88: Heavy Menstrual Bleeding (2018) [17]

Key Recommendations:

• First-line: Mirena IUS (if no distortion)
• Second-line: Tranexamic acid, NSAIDs, COC
• Referral to Gynaecology: If failed medical management, large fibroids (> 3cm submucosal), suspected pathology
• UAE: Offer as alternative to surgery for uterus preservation
• Informed choice: Discuss all options including hysterectomy, myomectomy, UAE

TA832: Relugolix for Fibroids (2022):

• Recommended for moderate-severe symptoms
• Maximum 24 months

Royal College of Obstetricians and Gynaecologists (RCOG)

Green-top Guideline No. 55: Fibroids in Pregnancy (2022):

• Red degeneration: Conservative management
• Avoid myomectomy in pregnancy unless emergency
• Caesarean delivery if obstructive fibroid

American College of Obstetricians and Gynecologists (ACOG)

Practice Bulletin No. 228 (2021):

• Individualized management based on symptoms, fertility, patient choice
• Myomectomy preferred over hysterectomy if fertility desired
• Power morcellation: contained extraction due to leiomyosarcoma risk

European Society of Human Reproduction and Embryology (ESHRE)

Management of Women with Fibroids Wishing to Conceive (2021) [4]:

• Submucosal fibroids: Recommend hysteroscopic myomectomy (improves pregnancy rates)
• Intramural > 3cm distorting cavity: Consider myomectomy
• Subserosal fibroids: No intervention needed for fertility

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12. Examination Focus

Common MRCOG Exam Questions

Written (SBA/EMQ)

1. "28-year-old nulliparous woman with HMB and 4cm submucosal fibroid. Desires pregnancy. First-line management?"

   • Answer: Hysteroscopic myomectomy (removes submucosal fibroid, preserves fertility, improves pregnancy outcomes)

2. "50-year-old woman, 14-week-size fibroid uterus, normal cavity on USS. First-line for HMB?"

   • Answer: Mirena IUS (NICE first-line if cavity not distorted; normal cavity on USS suggests no large submucosal component)

3. "Pregnant woman, 20 weeks, known fibroid, acute severe localized abdominal pain, low-grade fever. Diagnosis?"

   • Answer: Red (carneous) degeneration

4. "65-year-old post-menopausal woman, rapidly enlarging pelvic mass. Most likely diagnosis?"

   • Answer: Leiomyosarcoma (fibroids should shrink post-menopause; rapid growth suspicious for malignancy)

5. "Complication specific to UAE not seen with myomectomy?"

   • Answer: Premature ovarian failure (embolic particles can affect ovarian arteries)

OSCE Stations

History Taking:

• Heavy periods: quantify (pads/day, flooding, clots), duration, anaemia symptoms
• Fertility desires (critical for management planning)
• Pressure symptoms: urinary, bowel, pain
• Impact on quality of life

Counselling Stations:

• Consent for Myomectomy: Discuss risks (bleeding, adhesions, recurrence, pregnancy implications)
• UAE vs Hysterectomy: Compare pros/cons, fertility impact, recovery
• Managing Expectations: Recurrence rates, symptom resolution likelihood

Data Interpretation:

• USS report: FIGO classification, measure fibroids, assess cavity distortion

Viva Points

Opening Statement: "Uterine fibroids are benign smooth muscle tumours arising from the myometrium. They are the most common pelvic tumour, affecting up to 70-80% of women by age 50, though only 20-30% are symptomatic. They are oestrogen and progesterone dependent, growing during reproductive years and shrinking post-menopause. The cardinal symptom is heavy menstrual bleeding, particularly with submucosal fibroids. Management is individualized based on symptoms, fertility desires, fibroid characteristics, and patient preferences, ranging from expectant management through medical therapy to interventional radiology (UAE) and surgery (myomectomy or hysterectomy)."

Key Facts for Viva:

1. FIGO Classification: Be able to describe Type 0-8 and explain why Type 0-2 (submucosal) cause HMB.

2. First-Line Management:

   • HMB + normal cavity: Mirena IUS (NICE NG88)
   • Submucosal fibroid + fertility desires: Hysteroscopic myomectomy (ESHRE)

3. Recurrence Rates:

   • Myomectomy: 15-30% at 5 years (new fibroid growth)
   • UAE: 20-30% re-intervention at 5 years

4. Red Degeneration:

   • Pregnancy complication (5-10%)
   • Haemorrhagic infarction due to outgrowing blood supply
   • Management: Conservative (analgesia, rest)
   • Do NOT operate unless absolute emergency

5. Leiomyosarcoma:

   • less than 0.1% malignant transformation
   • Suspect if rapid post-menopausal growth
   • MRI + oncology referral

6. Fertility Impact:

   • Submucosal: Reduce implantation, increase miscarriage → remove (Level 2 evidence)
   • Intramural > 3 cm: May reduce IVF success → consider removal
   • Subserosal: No impact → leave alone

7. Power Morcellation Controversy:

   • Risk of disseminating occult leiomyosarcoma (1:350-500 women > 45yo)
   • FDA warning 2014
   • UK guidance: Use contained morcellation systems, counsel on risk

Common Mistakes (What Fails Candidates)

❌ Offering Mirena if large submucosal fibroid distorting cavity (will be expelled; ineffective)

❌ Recommending myomectomy in pregnancy for red degeneration (high bleeding risk; conservative management correct)

❌ Not discussing fertility implications before UAE (risk of ovarian failure, reduced pregnancy success vs myomectomy)

❌ Failing to mention FIGO classification when describing fibroids (examiners expect structured anatomical description)

❌ Stating "fibroids cause infertility" without qualifying by location (only submucosal and large cavity-distorting intramurals affect fertility)

❌ Not knowing NICE guidelines (Mirena first-line, offer UAE as uterus-conserving alternative)

Model Answers

Q: "How would you investigate a 35-year-old with heavy periods and an enlarged irregular uterus on examination?"

A: "I would approach this systematically. First, I need to exclude other causes of heavy menstrual bleeding and assess the severity. My initial investigations would include:

Blood tests: Full blood count to assess for anaemia, ferritin for iron stores, thyroid function as hypothyroidism can cause menorrhagia, and a coagulation screen if there's HMB since menarche suggesting an underlying bleeding disorder.

Imaging: Transvaginal ultrasound is first-line. This would confirm the presence of fibroids, determine their number, size, and crucially their location using the FIGO classification system. I need to know if there are submucosal fibroids distorting the cavity, as this affects management options.

Endometrial assessment: If she's over 45 or has risk factors for endometrial pathology, I would perform endometrial sampling with Pipelle biopsy or hysteroscopy to exclude hyperplasia or malignancy.

If ultrasound confirms fibroids but is non-diagnostic regarding cavity distortion, I would consider saline infusion sonography or outpatient hysteroscopy to better visualize the cavity, particularly if I'm considering the Mirena coil as first-line treatment.

If surgical management is being considered and there are multiple fibroids, MRI pelvis would provide superior pre-operative mapping for surgical planning."

Q: "A 42-year-old nulliparous woman with a 5cm intramural fibroid wishes to conceive. What would you advise?"

A: "This requires a nuanced approach balancing fertility optimization with surgical risks. Key factors I need to establish:

1. Is the fibroid affecting the cavity? If the intramural fibroid is distorting the endometrial cavity, evidence from ESHRE suggests myomectomy may improve IVF success rates. However, if it's purely intramural without cavity distortion, the evidence for benefit is weaker and I'd need to weigh surgical risks against potential fertility gain.

2. Other fertility factors? I need to ensure a complete fertility work-up has been done (ovarian reserve, partner's semen analysis, tubal patency) to ensure the fibroid is the likely cause rather than an incidental finding.

3. Surgical counselling: If proceeding with myomectomy, I would counsel her on:

   • Adhesion formation (30-50%) which could paradoxically impair fertility
   • Post-operative recovery: Wait 3-6 months before conception to allow uterine healing
   • Pregnancy implications: May require caesarean section if deep myometrial incision
   • Recurrence: 15-30% at 5 years

4. Alternatives: If the fibroid is not cavity-distorting, I might suggest proceeding with IVF first and reserving myomectomy for cases where IVF fails, particularly if she has diminished ovarian reserve where time is critical.

I would refer her for joint consultation with a fertility specialist and gynaecological surgeon experienced in fertility-sparing surgery to make an informed decision."

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13. Patient and Layperson Explanation

What are fibroids?

Fibroids (also called leiomyomas or myomas) are non-cancerous growths that develop in the muscular wall of the womb (uterus). They're made of muscle and fibrous tissue and can range from the size of a pea to the size of a melon (though most are smaller). They are extremely common—by the age of 50, around 7 in 10 women have at least one fibroid, though many women never know because they cause no symptoms.

Why do I have fibroids?

We don't know exactly why some women get fibroids and others don't, but we know they're sensitive to the hormones oestrogen and progesterone. This is why they tend to grow during your childbearing years (when hormone levels are high) and shrink after menopause (when hormone levels drop). They're more common in women of African or Caribbean heritage, women who haven't had children, and those who are overweight.

What symptoms do they cause?

About half of women with fibroids have no symptoms at all. When symptoms occur, the most common are:

• Heavy periods: This is the main symptom. You might have prolonged bleeding (lasting more than 7 days), flooding, passing clots, and needing to change pads very frequently. This can lead to anaemia (low iron), making you feel tired and breathless.

• Pressure symptoms: If fibroids are large, they can press on your bladder (causing frequent urination) or bowel (causing constipation or bloating).

• Pain: Fibroids usually aren't painful, but they can cause pain if they lose their blood supply (called "red degeneration," which can happen in pregnancy) or if they twist on a stalk.

• Fertility problems: Fibroids that bulge into the cavity of the womb can make it harder to get pregnant or increase the risk of miscarriage.

Do I need treatment?

Not always. If your fibroids aren't causing symptoms, you don't need treatment—we can just keep an eye on them. If you're approaching menopause, your fibroids will likely shrink on their own once your periods stop.

If fibroids are causing heavy periods, we usually start with medications like:

• Mirena coil: A small device placed in the womb that releases hormone to thin the womb lining and reduce bleeding
• Tablets: Such as tranexamic acid (reduces bleeding) or hormonal tablets

If medication doesn't help, or if your fibroids are very large or causing severe symptoms, we can consider:

• Uterine artery embolisation (UAE): A procedure where tiny particles are injected to block the blood supply to fibroids, making them shrink
• Myomectomy: Surgery to remove fibroids while keeping the womb (important if you want to have children)
• Hysterectomy: Surgery to remove the womb (a permanent solution if you've completed your family)

Will they affect my pregnancy?

Most women with fibroids have normal pregnancies. However, fibroids can sometimes cause complications such as:

• Pain if the fibroid loses its blood supply ("red degeneration")
• The baby lying in an abnormal position (breech or sideways)
• Rarely, blocking the baby from being born (if a fibroid is in the lower part of the womb)

If you're pregnant and have fibroids, your midwife and doctor will monitor you more closely.

Could they be cancer?

It's extremely rare for a fibroid to be cancerous (less than 1 in 1,000 cases). However, if you've gone through menopause and notice a fibroid growing (when it should be shrinking), we would investigate further with scans to make sure.

What happens if I don't have treatment?

Many fibroids stay the same size or grow very slowly. Some shrink on their own. After menopause, most fibroids shrink significantly because hormone levels drop. However, if fibroids are causing heavy bleeding, it's important to treat or monitor for anaemia (low iron levels), which can make you very unwell if left untreated.

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14. References

1. Stewart EA, Cookson CL, Gandolfo RA, Schulze-Rath R. Epidemiology of uterine fibroids: a systematic review. BJOG. 2017;124(10):1501-1512. doi:10.1111/1471-0528.14640

2. Cardozo ER, Clark AD, Banks NK, et al. The estimated annual cost of uterine leiomyomata in the United States. Am J Obstet Gynecol. 2012;206(3):211.e1-9. doi:10.1016/j.ajog.2011.12.002

3. Katz VL, Dotters DJ, Droegemueller W. Complications of uterine leiomyomas in pregnancy. Obstet Gynecol. 1989;73(4):593-596.

4. Bosteels J, Kasius J, Weyers S, et al. Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities. Cochrane Database Syst Rev. 2018;12(12):CD009461. doi:10.1002/14651858.CD009461.pub4

5. Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003;188(1):100-107. doi:10.1067/mob.2003.99

6. Marsh EE, Al-Hendy A, Kappus D, Galitsky A, Stewart EA, Kerolous M. Burden, prevalence, and treatment of uterine fibroids: a survey of U.S. women. J Womens Health. 2018;27(11):1359-1367. doi:10.1089/jwh.2018.7076

7. Cha PC, Takahashi A, Hosono N, et al. A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids. Nat Genet. 2011;43(5):447-450. doi:10.1038/ng.805

8. Laughlin SK, Baird DD, Savitz DA, Herring AH, Hartmann KE. Pregnancy-related fibroid reduction. Fertil Steril. 2010;94(6):2421-2423. doi:10.1016/j.fertnstert.2010.03.035

9. Wise LA, Radin RG, Palmer JR, Kumanyika SK, Rosenberg L. A prospective study of dairy intake and risk of uterine leiomyomata. Am J Epidemiol. 2010;171(2):221-232. doi:10.1093/aje/kwp355

10. Ishikawa H, Ishi K, Serna VA, Kakazu R, Bulun SE, Kurita T. Progesterone is essential for maintenance and growth of uterine leiomyoma. Endocrinology. 2010;151(6):2433-2442. doi:10.1210/en.2009-1225

11. Donnez J, Tatarchuk TF, Bouchard P, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012;366(5):409-420. doi:10.1056/NEJMoa1103182

12. Munro MG, Critchley HOD, Fraser IS; FIGO Menstrual Disorders Working Group. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertil Steril. 2011;95(7):2204-2208. doi:10.1016/j.fertnstert.2011.03.079

13. Dueholm M, Lundorf E, Hansen ES, Ledertoug S, Olesen F. Accuracy of magnetic resonance imaging and transvaginal ultrasonography in the diagnosis, mapping, and measurement of uterine myomas. Am J Obstet Gynecol. 2002;186(3):409-415. doi:10.1067/mob.2002.121725

14. Thomassin-Naggara I, Dechoux S, Bonneau C, et al. How to differentiate benign from malignant myometrial tumours using MR imaging. Eur Radiol. 2013;23(8):2306-2314. doi:10.1007/s00330-013-2819-9

15. Ishiko O, Yoshida H, Sumi T, Hirai K, Ogita S. Changes in volume of uterine myomas measured by three-dimensional ultrasonography in the perimenopausal period. Acta Obstet Gynecol Scand. 2001;80(2):130-133.

16. Zapata LB, Whiteman MK, Tepper NK, Jamieson DJ, Marchbanks PA, Curtis KM. Intrauterine device use among women with uterine fibroids: a systematic review. Contraception. 2010;82(1):41-55. doi:10.1016/j.contraception.2010.02.011

17. National Institute for Health and Care Excellence. Heavy menstrual bleeding: assessment and management (NG88). Published March 2018. Updated May 2021. https://www.nice.org.uk/guidance/ng88

18. Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev. 2000;(4):CD000249. doi:10.1002/14651858.CD000249

19. Al-Hendy A, Lukes AS, Poindexter AN, et al. Treatment of uterine fibroid symptoms with relugolix combination therapy. N Engl J Med. 2021;384(7):630-642. doi:10.1056/NEJMoa2008283

20. Lethaby A, Vollenhoven B, Sowter M. Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev. 2001;(2):CD000547. doi:10.1002/14651858.CD000547

21. van der Kooij SM, Bipat S, Hehenkamp WJ, Ankum WM, Reekers JA. Uterine artery embolization versus surgery in the treatment of symptomatic fibroids: a systematic review and metaanalysis. Am J Obstet Gynecol. 2011;205(4):317.e1-18. doi:10.1016/j.ajog.2011.03.016

22. Goodwin SC, Spies JB, Worthington-Kirsch R, et al. Uterine artery embolization for treatment of leiomyomata: long-term outcomes from the FIBROID Registry. Obstet Gynecol. 2008;111(1):22-33. doi:10.1097/01.AOG.0000296526.71749.c9

23. Mara M, Maskova J, Fucikova Z, Kuzel D, Belsan T, Sosna O. Midterm clinical and first reproductive results of a randomized controlled trial comparing uterine fibroid embolization and myomectomy. Cardiovasc Intervent Radiol. 2008;31(1):73-85. doi:10.1007/s00270-007-9195-2

24. Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril. 2009;91(4):1215-1223. doi:10.1016/j.fertnstert.2008.01.051

25. Hanafi M. Predictors of leiomyoma recurrence after myomectomy. Obstet Gynecol. 2005;105(4):877-881. doi:10.1097/01.AOG.0000156298.74317.b8

26. Spies JB, Coyne K, Guaou Guaou N, Boyle D, Skyrnarz-Murphy K, Gonzalves SM. The UFS-QOL, a new disease-specific symptom and health-related quality of life questionnaire for leiomyomata. Obstet Gynecol. 2002;99(2):290-300. doi:10.1016/s0029-7844(01)01702-1

27. Sánchez Martín MJ, Huerga López C, Cristóbal García I, Cristóbal Quevedo I. Efficacy of GnRH antagonists in the treatment of uterine fibroids: a meta-analysis. Arch Gynecol Obstet. 2025;311(3):685-696. doi:10.1007/s00404-025-07932-9

28. Palomba S, Affinito P, Di Carlo C, Bifulco G, Nappi C. Long-term administration of tibolone plus gonadotropin-releasing hormone agonist for the treatment of uterine leiomyomas: effectiveness and effects on vasomotor symptoms, bone mass, and lipid profiles. Fertil Steril. 1999;72(5):889-895. doi:10.1016/s0015-0282(99)00366-0

29. Kaump GR, Spies JB. The impact of uterine artery embolization on ovarian function. J Vasc Interv Radiol. 2013;24(4):459-467. doi:10.1016/j.jvir.2012.12.002

30. Amato P, Roberts AC. Transient ovarian failure: a complication of uterine artery embolization. Fertil Steril. 2001;75(2):438-439. doi:10.1016/s0015-0282(00)01678-2

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances and current guidelines. Always consult appropriate specialists and follow local protocols.