Uterine Fibroids (Leiomyomas)

1. Overview

Uterine leiomyomas, commonly known as fibroids, are benign monoclonal tumours arising from the smooth muscle cells of the myometrium. They represent the most common solid pelvic tumour in women and are a significant public health burden due to their high prevalence and association with morbidity, including heavy menstrual bleeding (HMB), pelvic pain, and infertility.

While the majority of fibroids are asymptomatic, they are the leading indication for hysterectomy worldwide. Their growth is strictly dependent on ovarian steroids (oestrogen and progesterone), meaning they typically regress after menopause. Management has evolved significantly from traditional surgical approaches to include sophisticated medical therapies and minimally invasive interventional radiology techniques like Uterine Artery Embolisation (UAE).

The key clinical challenge lies in tailoring management to the patient's reproductive wishes, symptom severity, and fibroid characteristics (size, number, location). The FIGO classification system provides the standard language for describing fibroid location, which dictates the optimal therapeutic approach. Understanding the nuanced relationship between fibroid location and symptomatology is critical for MRCOG candidates, particularly in counselling scenarios and surgical planning stations.

2. Epidemiology

Fibroids are ubiquitous in the female population, with prevalence increasing with age until menopause. There are significant ethnic disparities in incidence and clinical severity.

Risk Factors

Geographic and Ethnic Variations

Women of African ancestry develop fibroids earlier (20s vs 30s), have larger fibroids, more numerous fibroids, and more severe symptoms. Proposed mechanisms include differences in vitamin D receptor polymorphisms, genetic variants (particularly in genes regulating cell proliferation), and environmental factors. This has important implications for screening and early intervention strategies.

3. Aetiology & Pathophysiology

Fibroids are monoclonal tumours, meaning each fibroid arises from the clonal expansion of a single myometrial stem cell. The transformation from normal myocyte to leiomyoma is driven by a complex interplay of genetic abnormalities, steroid hormones, and growth factors.

Genetic Factors

Cytogenetic abnormalities are found in approximately 40-50% of fibroids. These chromosomal changes appear to be driver mutations that initiate tumorigenesis.

• MED12 mutation: Found in up to 70% of fibroids. MED12 is a component of the Mediator complex, a key regulator of RNA polymerase II-mediated transcription. Mutations cluster in exon 2, affecting the Mediator's interaction with transcription factors and leading to dysregulated gene expression. [11,12]
• HMGA2 overexpression: Associated with rearrangements of chromosome 12q14-15. HMGA2 (High Mobility Group AT-hook 2) is an architectural transcription factor that binds to AT-rich DNA regions and alters chromatin structure, affecting genes involved in cell proliferation and differentiation.
• Deletion of 7q: Common in smaller fibroids. This region may contain tumour suppressor genes.
• Fumarate Hydratase (FH) mutations: Associated with Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) syndrome. Germline mutations in FH lead to multiple, large, symptomatic fibroids at young age plus risk of aggressive renal cell carcinoma. Suspect in young women (less than 30) with rapidly growing or multiple large fibroids.
• Chromosomal rearrangements: Various other chromosomal aberrations involving 6p, 10q, and 13q have been described.

Exam Detail: Genetic Heterogeneity and Clinical Implications

Different genetic subtypes may have distinct clinical behaviours:

• MED12-mutated fibroids: Tend to be smaller, more cellular, and located submucosally or intramurally.
• HMGA2-altered fibroids: Often larger and may have more pronounced extracellular matrix deposition.
• FH-deficient fibroids (HLRCC): Aggressive growth, often symptomatic at young age. Distinctive eosinophilic nucleoli with perinuclear halos on histology (important differential from leiomyosarcoma).

MRCOG Key Point: If a woman less than 30 presents with large, multiple, rapidly growing fibroids, always consider HLRCC syndrome. Family history, skin leiomyomas (painful subcutaneous nodules), and renal imaging are essential investigations. Genetic counselling and germline FH testing are indicated.

Hormonal Dependence

Fibroids are strictly oestrogen and progesterone dependent. Both hormones are essential for fibroid growth, and neither alone is sufficient.

• Oestrogen: Promotes growth via upregulation of IGF-1 (insulin-like growth factor-1), EGFR (epidermal growth factor receptor), and TGF-beta (transforming growth factor-beta). Fibroids contain higher concentrations of oestrogen receptors (ER-alpha and ER-beta) than normal myometrium. Oestrogen also upregulates progesterone receptors, priming the tissue for progesterone action.

• Progesterone: Equally critical, if not more so. Progesterone stimulates proliferation through upregulation of EGF (epidermal growth factor) and BCL-2 (anti-apoptotic protein). This explains why:

  • Fibroids do not shrink (and may grow) during treatment with progestogens alone
  • Fibroids often grow during the luteal phase of the menstrual cycle
  • Progesterone receptor modulators (SPRMs) are highly effective therapies
  • Pregnancy (high progesterone) can cause fibroid growth

Molecular Pathways

Exam Detail: Detailed Molecular Mechanisms of Extracellular Matrix (ECM) Accumulation

Fibroids are not just cellular tumours; they are characterised by excessive deposition of disordered collagen and ECM, which can constitute up to 50% of tumour volume. This gives fibroids their characteristic firm, whorled appearance on cut section.

Key Cytokines and Growth Factors:

• TGF-beta 3: The key cytokine driver. It induces the transformation of myometrial cells into a fibrotic phenotype by:

  • Stimulating fibroblast differentiation into myofibroblasts
  • Upregulating collagen types I, III, and V production
  • Increasing fibronectin and proteoglycan synthesis
  • Inhibiting matrix metalloproteinases (MMPs) that would normally degrade ECM

• Mechanotransduction: The stiff ECM itself promotes further growth via mechanosensing pathways involving:

  • Rho/ROCK signalling: Mediates actin cytoskeleton reorganisation and cellular contractility in response to mechanical stress
  • YAP/TAZ pathway: These transcriptional co-activators translocate to the nucleus in response to mechanical stiffness, driving proliferative gene expression
  • This creates a self-perpetuating cycle: stiffness → mechanotransduction → proliferation → more ECM → increased stiffness

• Hypoxia and Angiogenesis: The dense ECM compresses blood vessels, creating a hypoxic microenvironment. Paradoxically, hypoxia stimulates:

  • HIF-1alpha (hypoxia-inducible factor) activation
  • VEGF (vascular endothelial growth factor) production, promoting aberrant angiogenesis
  • Survival pathway activation despite low oxygen

• Local Steroid Metabolism: Fibroids express higher levels of:

  • Aromatase (CYP19A1): Converts androgens to oestrogens locally (intracrine mechanism)
  • 17beta-HSD type 1: Converts less potent oestrone (E1) to more potent oestradiol (E2)
  • PR-A and PR-B isoforms: Progesterone receptor isoforms with differing transcriptional activities

Clinical Relevance: Understanding these pathways explains:

• Why aromatase inhibitors (e.g., letrozole) can be effective
• Why GnRH agonists/antagonists (suppressing ovarian steroid production) cause fibroid shrinkage
• Why SPRMs (blocking progesterone signalling) are highly effective
• Why fibroids regress after menopause (loss of steroid stimulus)

Stem Cell Hypothesis

Recent evidence suggests that fibroids may arise from somatic stem cells in the myometrium. These stem cells:

• Have high self-renewal capacity
• Can differentiate into smooth muscle and fibroblast lineages
• Accumulate genetic mutations over time
• Under hormonal stimulation, undergo clonal expansion

This model explains why:

• Each fibroid is monoclonal (single stem cell origin)
• Multiple fibroids are polyclonal (independent origins)
• Fibroids can recur after myomectomy (residual stem cells)

4. Clinical Presentation

Approximately 50% of women with fibroids are asymptomatic. Symptoms depend heavily on the location and size of the fibroids rather than the absolute number. A single 3cm submucosal fibroid can cause more severe bleeding than ten 5cm subserosal fibroids.

Symptoms

1. Abnormal Uterine Bleeding (AUB) - Most Common Presentation

• Heavy Menstrual Bleeding (HMB): Specifically associated with submucosal (FIGO type 0, 1, 2) and intramural fibroids that distort the endometrial cavity.

• Mechanisms of HMB:

  1. Increased endometrial surface area: A distorted cavity has greater surface area to shed
  2. Aberrant angiogenesis: Increased VEGF expression leads to fragile, dilated venules in the overlying endometrium
  3. Impaired haemostasis: Fibroids interfere with normal myometrial contraction, which is essential for compressing spiral arteries and achieving haemostasis after menstruation
  4. Altered endometrial receptivity: Local inflammatory mediators and altered prostaglandin ratios
  5. Ischemic ulceration: Submucosal fibroids can undergo surface ulceration and bleeding

• Consequences:

  • Iron deficiency anaemia (Hb less than 110-120 g/L)
  • Chronic fatigue and reduced quality of life
  • Requirement for blood transfusion in severe cases
  • Social impact (flooding through protection, restricting activities)

2. Bulk/Pressure Symptoms

These correlate with fibroid size and position.

• Pelvic Pressure/Heaviness: Sensation of "something sitting low down" or pelvic fullness
• Urinary Symptoms:
  • Frequency and urgency: Anterior fibroids compressing bladder base (most common)
  • Urinary retention: Large fibroids causing acute urethral compression (rare but important emergency)
  • Hydronephrosis: Lateral fibroids compressing ureters at pelvic brim (silent until renal function affected)
• Bowel Symptoms:
  • Constipation or tenesmus (posterior fibroids compressing rectum)
  • Difficult defecation
• Venous Compression:
  • Lower limb oedema (compression of iliac veins)
  • Varicosities
  • Rarely, DVT risk increased
• Abdominal Distension: Women may notice increasing waist size, difficulty fitting into clothes

3. Pain

Fibroids are typically painless unless complications occur. Presence of significant pain should prompt consideration of:

• Dysmenorrhoea: Cramping pain during menstruation (uterus contracting to expel blood or trying to expel a submucosal fibroid through cervix)
• Dyspareunia: Deep pain during intercourse (large posterior fibroids in pouch of Douglas, or fibroids causing retroversion)
• Chronic pelvic pain: Uncommon; consider adenomyosis or endometriosis as alternative/coexisting diagnoses

Acute Pain Scenarios (RED FLAGS):

• Red Degeneration (haemorrhagic infarction):

  • Most common in pregnancy (rapid growth outstrips blood supply)
  • Presents as acute, localised abdominal pain over fibroid
  • Associated with low-grade fever, nausea, vomiting, leucocytosis
  • Uterus tender over fibroid; peritonism may be present
  • Diagnosis: Clinical + USS showing heterogeneous fibroid with haemorrhage

• Torsion of Pedunculated Subserosal Fibroid:

  • Acute severe pain, peritonism
  • Requires emergency laparoscopy/laparotomy
  • Risk of bowel adhesion to necrotic fibroid

• Prolapse/Expulsion of Submucosal Fibroid:

  • Pedunculated Type 0 fibroid protrudes through cervix
  • Severe cramping pain, vaginal bleeding, discharge
  • Visible at speculum examination
  • Management: Remove vaginally or hysteroscopically

4. Reproductive Dysfunction

The impact of fibroids on fertility and pregnancy is location-dependent and remains a subject of ongoing research.

Infertility:

• Submucosal fibroids: Strong evidence for reduced implantation rates. Mechanisms include:
  • Altered endometrial receptivity (inflammatory mediators, altered gene expression)
  • Mechanical distortion preventing embryo contact with endometrium
  • Impaired decidualisation
• Intramural fibroids: Effect depends on cavity distortion:
  • If distorting cavity: Likely impaired fertility
  • If not distorting: Controversial. Large fibroids (> 4-5cm) or numerous fibroids may reduce success rates in ART
• Subserosal fibroids: Minimal to no impact on fertility

Recurrent Miscarriage:

• Submucosal and large intramural fibroids associated with increased miscarriage risk
• Mechanisms: Disruption of placental blood flow, uterine contractility, mechanical distortion

Obstetric Complications (see also Section 9):

• Malpresentation (breech, transverse lie)
• Placental abruption
• Preterm labour
• Obstructed labour (cervical fibroids)
• Postpartum haemorrhage (PPH)
• Red degeneration in pregnancy

Exam Detail: Evidence Summary: Fibroids and IVF Outcomes

Meta-analyses suggest:

• Submucosal fibroids: 70% reduction in live birth rate; myomectomy improves outcomes
• Intramural fibroids distorting cavity: 50% reduction in implantation; myomectomy may benefit
• Intramural fibroids NOT distorting cavity: Controversial. Small effect (~15% reduction) may exist
• Subserosal fibroids: No significant impact

MRCOG Exam Point: In fertility clinics, saline infusion sonography or hysteroscopy is essential to assess cavity distortion. MRI can help pre-operatively plan myomectomy. Counsel that myomectomy for non-cavity-distorting intramurals is not evidence-based but may be considered in selected cases (e.g., failed IVF cycles, large fibroids).

Signs on Examination

General Inspection:

• Pallor (anaemia from chronic HMB)
• Abdominal distension

Abdominal Examination:

• Inspection: Visible midline swelling arising from pelvis (if uterus > 12-14 weeks size)
• Palpation:
  • Firm, irregular, non-tender mass arising from pelvis
  • Mobile side-to-side (unlike ovarian masses which are mobile superiorly)
  • Dull to percussion (solid mass)
  • Size measured in "weeks" (e.g., 16-week size uterus)

Bimanual Pelvic Examination:

• Uterus: Enlarged, irregular, "knobbly" or "bosselated" contour
• Mobility: Moves with the cervix (confirms uterine origin)
• Tenderness: Usually non-tender unless red degeneration or torsion
• Adnexa: Normal (helps exclude ovarian mass)

Speculum Examination:

• Cervix: Usually normal
• Occasionally: Prolapsed submucosal fibroid visible at external os (appears as pale, smooth mass)
• Assess bleeding source

5. Differential Diagnosis

The key diagnostic challenge is distinguishing fibroids from other pelvic masses, particularly in older women where malignancy risk increases.

Exam Detail: Distinguishing Leiomyoma from Leiomyosarcoma

This is a critical but challenging distinction. Leiomyosarcoma is rare (less than 1 in 400-1000 women undergoing surgery for presumed fibroids).

Features Suggesting Sarcoma:

• Post-menopausal presentation with new or growing mass
• Rapid growth (doubling in 6 months) - though note: rapid growth in pre-menopausal women is often benign
• Size > 8-10cm as sole mass
• Pain and systemic symptoms (weight loss, fever)

MRI Features (Not Diagnostic but Suggestive):

• Irregular, ill-defined margins
• Central necrosis (high T2 signal)
• Heterogeneous enhancement
• Intermediate T2 signal (vs. low T2 in typical fibroid)
• High cellularity on diffusion-weighted imaging (DWI)

Management Implications:

• Pre-operative diagnosis is nearly impossible
• Avoid morcellation if any suspicion (risk of disseminating occult sarcoma)
• If sarcoma suspected: Counselling, informed consent, en-bloc removal
• Frozen section is unreliable for distinguishing leiomyoma from sarcoma
• If sarcoma discovered post-operatively: Refer to sarcoma MDT, consider staging imaging (CT chest/abdo/pelvis), discuss need for completion surgery

MRCOG Point: The FDA (2014) and RCOG warnings on morcellation stem from risk of disseminating occult sarcoma. Always mention this in exam scenarios involving laparoscopic myomectomy.

6. Investigations

Diagnostic Pathway

Clinical Suspicion of Fibroids
         ↓
[1] Pelvic Ultrasound (TVUSS ± Abdominal)
         ↓
    ┌────────┴────────┐
    ↓                 ↓
Fibroids Confirmed   Uncertain Diagnosis
    ↓                 ↓
[2] FBC              MRI Pelvis
    ↓                 ↓
Assess Anaemia       Characterise Mass
    ↓
If Symptomatic → Further Assessment
         ↓
    ┌────────┼────────┐
    ↓        ↓        ↓
  HMB    Infertility  Pain
    ↓        ↓        ↓
Hysteroscopy SIS/HSG  MRI (adenomyosis vs fibroids)

First-Line Investigations

1. Transvaginal Ultrasound (TVUSS) ± Transabdominal Ultrasound (TAUS):

   • Sensitivity: > 95% for detection of fibroids
   • Role:
     • Diagnose fibroids (hypoechoic, well-defined masses)
     • Measure size and number
     • Assess location (intramural, submucosal, subserosal)
     • Exclude ovarian pathology
     • Assess endometrial thickness
   • Findings:
     • Well-circumscribed, hypoechoic (darker than myometrium) rounded masses
     • May show calcification (hyperechoic foci with acoustic shadowing)
     • Colour Doppler: Peripheral vascularity ("ring of fire" sign)
   • Limitations:
     • Less accurate for detailed mapping in large/multiple fibroids
     • Posterior fibroids may be obscured by anterior fibroids
     • Operator-dependent
     • Difficult to assess exact relationship to endometrial cavity

2. Full Blood Count (FBC):

   • To assess for anaemia (Hb less than 120 g/L in women)
   • Iron deficiency pattern: Low MCV, low ferritin
   • Guides need for iron replacement or transfusion pre-operatively

Second-Line / Specialist Investigations

1. MRI Pelvis (Gold Standard for Anatomical Mapping):

   • Indications:

     • Accurate pre-operative mapping prior to myomectomy or UAE
     • Large or multiple fibroids where USS is inadequate
     • Suspicion of sarcoma
     • Differentiating fibroids from adenomyosis
     • Assessment of fibroid vascularity and degeneration

   • Advantages:

     • Superior soft tissue contrast
     • Multiplanar imaging
     • Large field of view
     • No operator dependence

   • MRI Appearances:

     • Typical Fibroid: T1 isointense, T2 hypointense (dark) relative to myometrium. Well-circumscribed capsule.
     • Degeneration Types:
       • Hyaline degeneration (60%): High T2 signal centrally
       • Red degeneration: High T1 signal (blood) with peripheral low signal rim
       • Cystic degeneration: Very high T2 signal (fluid)
       • Myxoid degeneration: High T2, may mimic sarcoma
       • Calcification: Low signal on all sequences
     • Features Suggesting Sarcoma:
       • Irregular margins
       • Intermediate T2 signal (high cellularity)
       • Central necrosis
       • Rapid growth on serial imaging

Exam Detail: MRI Reporting for UAE vs Myomectomy

For UAE, radiologists assess:

• Fibroid vascularity (contrast enhancement pattern)
• Presence of pedunculated fibroids (may not infarct adequately; risk of detachment)
• Dominant fibroid location
• Uterine artery anatomy

For Myomectomy, surgeons need:

• Number, size, and exact location of each fibroid
• Depth of intramural extension (affects closure difficulty)
• Proximity to uterine vessels and cornua
• Prediction of cavity entry during enucleation

MRCOG Exam Tip: Be able to describe how MRI findings influence choice between UAE and myomectomy in a counselling scenario.

2. Hysteroscopy (Outpatient):

   • Indications:

     • Suspected submucosal fibroids (Type 0, 1, 2)
     • Investigation of HMB
     • Pre-operative assessment for hysteroscopic myomectomy
     • Exclude endometrial pathology

   • Procedure: Direct visualisation of uterine cavity with rigid or flexible hysteroscope

   • Findings:

     • Submucosal fibroids appear as smooth, pale, rounded projections into cavity
     • Assess percentage of fibroid that is intramural (Type 1 vs Type 2)
     • Biopsy endometrium if thickened or abnormal

   • Role: Defines feasibility of hysteroscopic resection:

     • Type 0: Easily resectable
     • Type 1 (less than 50% intramural): Resectable in one sitting
     • Type 2 (≥50% intramural): May require two-stage procedure or GnRH agonist pre-treatment

3. Saline Infusion Sonography (SIS) / Sonohysterography:

   • Alternative to hysteroscopy for assessing cavity distortion
   • Procedure: Instill saline into uterine cavity during TVUSS
   • Advantage: Less invasive than hysteroscopy; good visualisation of submucous component
   • Disadvantage: Cannot biopsy; may be uncomfortable

4. Hysterosalpingography (HSG):

   • Not for fibroid diagnosis per se
   • Used in infertility workup: May show cavity distortion or filling defects
   • Being superseded by SIS and hysteroscopy

Investigations to Exclude Differentials

• CA-125: If ovarian mass suspected (not specific; can be elevated in fibroids, endometriosis, PID)
• Serum hCG: Always in reproductive-age women with pelvic mass or bleeding
• Endometrial biopsy: If post-menopausal bleeding or endometrial thickening > 4mm
• Renal function (U&Es): If large fibroids (risk of hydronephrosis)
• Urinalysis: Exclude UTI if urinary symptoms

7. Classification (FIGO PALM-COEIN)

The FIGO classification system (2011) categorises abnormal uterine bleeding causes using the acronym PALM-COEIN:

• PALM: Structural causes (Polyp, Adenomyosis, Leiomyoma, Malignancy)
• COEIN: Non-structural causes (Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified)

For leiomyomas, the classification is based on relationship to the uterine wall and endometrial cavity. This is critical for management planning.

FIGO Leiomyoma Subclassification

Hybrid Lesions: Some fibroids span multiple categories (e.g., Type 2-5 means > 50% intramural component involving both endometrial and serosal surfaces). Notation: List both numbers.

Exam Detail: Clinical Application of FIGO Classification

MRCOG Scenario: "A 35-year-old woman with HMB has a 4cm fibroid. USS reports 'Type 2 submucosal fibroid'. How does this influence your management?"

Model Answer: "A Type 2 fibroid has ≥50% intramural component, which makes hysteroscopic resection technically challenging. Options include:

1. Two-stage hysteroscopic myomectomy: First procedure resects intracavitary portion; fibroid protrudes further over 6-8 weeks; second procedure completes resection
2. GnRH agonist pre-treatment (e.g., 3 months): Shrinks fibroid, increases intracavitary proportion, facilitates single-stage resection
3. Laparoscopic/open myomectomy: If hysteroscopic approach not feasible
4. Medical management or UAE: If fertility not a priority

I would refer to a specialist hysteroscopist to assess feasibility. If planning hysteroscopic approach, pre-treatment with GnRH agonist may be beneficial."

Exam Tip: Always mention that Type 2 fibroids are on the cusp between hysteroscopic and abdominal approaches, and individualised decision-making is needed.

8. Management

Management of fibroids is highly individualised. The cornerstone of decision-making is the patient's desire for future fertility. All management discussions should begin with this question.

Management Algorithm

Fibroids Diagnosed
       ↓
  Symptomatic?
       ↓
   ┌───┴───┐
   NO      YES
   ↓        ↓
Watch &   Assess
 Wait     Symptoms
           ↓
       ┌───┴────┬─────────┐
       HMB    Bulk/Pain  Infertility
       ↓        ↓          ↓
   [Algorithm continues below]

A. Conservative Management (Expectant)

Indications:

• Asymptomatic fibroids (discovered incidentally)
• Mild symptoms acceptable to patient
• Women approaching menopause (expect regression)
• Medical comorbidities precluding intervention

Monitoring:

• Annual pelvic examination and USS
• FBC if at risk of anaemia
• Advise to report symptoms (sudden pain, rapid growth, post-menopausal bleeding)

Natural History:

• 10-15% of fibroids show growth over 1 year
• Many remain static
• Post-menopause: 70-80% regress
• New growth or growth post-menopause is concerning for malignancy

B. Medical Management

Medical therapies aim to control symptoms (particularly HMB) or temporarily shrink fibroids. They do NOT cure fibroids; symptoms typically recur after cessation.

1. Non-Hormonal Therapies

Tranexamic Acid:

• Mechanism: Antifibrinolytic (inhibits plasminogen activation)
• Dose: 1g TDS-QDS during menstruation (max 4g/day)
• Efficacy: Reduces bleeding by 40-50%
• Side effects: Nausea, diarrhoea, thromboembolic risk (contraindicated if VTE history)
• Evidence: First-line for HMB (NICE NG88) [8]
• Note: Does not shrink fibroids; purely symptomatic relief

NSAIDs (Mefenamic Acid):

• Mechanism: Inhibits prostaglandin synthesis
• Dose: 500mg TDS during menstruation
• Efficacy: Reduces bleeding by 20-30%; reduces dysmenorrhoea
• Side effects: GI upset, renal impairment
• Note: Less effective than tranexamic acid for bleeding

2. Hormonal Therapies (Non-Fibroid-Specific)

Levonorgestrel Intrauterine System (LNG-IUS / Mirena):

• Mechanism: Local endometrial progesterone effect causes atrophy
• Efficacy: Reduces HMB by 80-90%
• Duration: Effective for 5 years
• Contraindications: Cavity distortion by submucosal fibroids (may expel device)
• Advantage: First-line for HMB; highly effective; long-acting
• Disadvantage: Does not shrink fibroids; irregular bleeding first 3-6 months
• Evidence: First-line for HMB per NICE NG88 [8]

Combined Oral Contraceptive Pill (COCP):

• Efficacy: May control bleeding; does NOT shrink fibroids
• Use: Symptom control in young women; contraception
• Limitation: Not suitable if contraindications (VTE risk, migraine with aura, > 35 + smoker)

Progestogen-Only Pill (POP) / Depo-Provera:

• Variable efficacy for HMB
• May cause irregular bleeding
• NOT recommended as fibroid-specific therapy

3. Fibroid-Specific Medical Therapies

These agents target the hormonal dependence of fibroids and can achieve significant shrinkage (30-60%).

GnRH Agonists (e.g., Goserelin, Leuprolide, Triptorelin):

• Mechanism:

  • Initial GnRH receptor stimulation ("flare" effect: temporary increase in FSH/LH/oestradiol for 7-10 days)
  • Subsequent receptor downregulation → hypogonadotropic hypogonadism ("medical menopause")
  • Oestradiol levels fall to post-menopausal range (less than 50 pmol/L)

• Administration:

  • Subcutaneous or intramuscular depot injection
  • Monthly (e.g., Goserelin 3.6mg SC) or 3-monthly (e.g., Goserelin 10.8mg SC)

• Efficacy:

  • Fibroid volume shrinks by 30-60% over 3-6 months
  • Amenorrhoea achieved in > 95%
  • Reduction in uterine size

• Indications:

  1. Pre-operative optimisation:
     • Correct anaemia (achieve Hb > 100-110 g/L pre-operatively)
     • Shrink fibroids to facilitate minimally invasive surgery (convert laparotomy to laparoscopy)
     • Reduce intra-operative bleeding
  2. Bridge to menopause: Older women (> 45 years) nearing menopause
  3. Pre-treatment for hysteroscopic myomectomy: Make Type 2 fibroids more amenable to hysteroscopic resection

• Duration: Limited to 6 months maximum due to adverse effects

• Side Effects:

  • Menopausal symptoms: Hot flushes, night sweats, vaginal dryness, mood changes
  • Bone mineral density (BMD) loss: 5-10% loss over 6 months (reversible but concern for long-term use)
  • Cardiovascular: Adverse lipid profile

• Add-Back Hormone Replacement Therapy (HRT):

  • Low-dose oestrogen + progesterone given concurrently
  • Reduces menopausal symptoms
  • Protects bone density
  • Does NOT significantly impair fibroid shrinkage

• Evidence: Cochrane review [14] supports pre-operative use for anaemia correction and facilitating surgery

• MRCOG Exam Point: Always mention the 6-month limit and need for add-back HRT. After stopping GnRH agonist, fibroids typically re-grow to baseline within 3-6 months unless definitive treatment is performed.

GnRH Antagonists (e.g., Relugolix, Linzagolix, Elagolix):

• Mechanism:

  • Competitive GnRH receptor blockade
  • Rapid suppression of gonadotropins (no "flare" effect)
  • Dose-dependent suppression (can titrate to partial vs. full suppression)

• Administration: Oral (major advantage over agonists)

• Efficacy:

  • Similar fibroid shrinkage to agonists (40-50%)
  • Rapid onset (amenorrhoea within 1 month)

• Relugolix Combination Therapy:

  • Relugolix 40mg + Oestradiol 1mg + Norethisterone 0.5mg (fixed-dose combination)
  • Approved for up to 24 months (longer than agonists)
  • Add-back HRT is integral (protects bone, reduces hot flushes)

• Advantages over Agonists:

  • Oral administration (patient preference)
  • No flare effect
  • Longer approved duration with add-back
  • Reversible within 1 month (vs. 3 months for depot agonists)

• Evidence: LIBERTY trials [18] showed significant reduction in HMB and fibroid volume; FDA approved 2021

• Cost: Significantly more expensive than generic GnRH agonists (NHS commissioning variable)

Selective Progesterone Receptor Modulators (SPRMs) - Ulipristal Acetate:

• Mechanism: Partial progesterone agonist/antagonist (tissue-selective)

  • Blocks progesterone-driven fibroid proliferation
  • Induces apoptosis in fibroid cells
  • Causes amenorrhoea via direct endometrial effect (PAEC: Progesterone receptor modulator Associated Endometrial Changes - benign)

• Dose: 5mg once daily orally

• Efficacy:

  • Fibroid volume reduction: 45-50%
  • Amenorrhoea: 80-90% within 1 week

• Indications (Historical):

  • Pre-operative treatment (one 3-month course)
  • Intermittent long-term therapy (repeated 3-month courses)

• CURRENT STATUS (2020 onwards): RESTRICTED USE

  • EMA suspended use due to rare but serious cases of acute liver injury (including liver failure requiring transplant)
  • Currently available only under specialist supervision with strict liver monitoring in selected cases
  • Many jurisdictions have withdrawn it completely

• MRCOG Exam Point:

  • Acknowledge ulipristal acetate as an effective SPRM historically used
  • Mention the 2020 safety concerns and restrictions
  • State that GnRH agonists/antagonists are now preferred for pre-operative use
  • Other SPRMs (vilaprisan, linzagolix) are in development

Exam Detail: Comparison of Fibroid-Specific Medical Therapies

Exam Scenario: "A 42-year-old with large fibroids and severe anaemia (Hb 78 g/L) needs optimisation for surgery in 3 months. What medical therapy would you recommend?"

Model Answer: "I would recommend a GnRH agonist (e.g., Goserelin 3.6mg SC monthly for 3 months) because:

1. It will induce amenorrhoea rapidly, stopping further blood loss
2. It will allow correction of anaemia with oral iron supplementation or IV iron
3. It will shrink the fibroids by 30-50%, potentially converting a laparotomy to a laparoscopic approach
4. 3 months is within the safe duration limit

I would also prescribe add-back HRT to minimise menopausal symptoms and bone loss. Given her severe anaemia, I would consider IV iron infusion (e.g., Ferinject) for rapid correction rather than relying on oral iron alone.

Alternatively, a GnRH antagonist (e.g., Relugolix) could be used but is more expensive and may not be funded. Ulipristal acetate is no longer first-line due to liver toxicity concerns."

C. Interventional Radiology: Uterine Artery Embolisation (UAE)

UAE has become an established alternative to surgery for women wishing to avoid hysterectomy or myomectomy.

Procedure:

1. Femoral artery puncture (Seldinger technique)
2. Catheter advanced under fluoroscopy to internal iliac artery
3. Selective catheterisation of uterine artery (both sides)
4. Injection of embolic particles (PVA - polyvinyl alcohol, or Embospheres - trisacryl gelatin microspheres, 500-700 microns)
5. Particles lodge in fibroid arterioles, causing ischaemic infarction
6. Normal myometrium has collateral supply (ovarian artery, vaginal branches) and recovers

Patient Selection:

• Ideal Candidates:

  • Symptomatic fibroids (HMB, bulk symptoms)
  • Completed family or NOT planning pregnancy (see below)
  • Prefer to avoid major surgery
  • Fibroids less than 10-12cm (larger fibroids have higher failure rate)
  • Multiple intramural/subserosal fibroids

• Relative Contraindications:

  • Desire for future pregnancy (controversial - see below)
  • Pedunculated subserosal fibroids (risk of infarction and detachment → peritonitis)
  • Suspicion of malignancy
  • Active pelvic infection
  • Pregnancy
  • Severe contrast allergy

• Absolute Contraindications:

  • Pregnancy
  • Active PID
  • Malignancy

Efficacy:

• Symptom Improvement: 80-90% satisfaction at 1 year
• Fibroid Shrinkage: 40-60% volume reduction over 6-12 months
• Re-intervention Rate: 20-30% require further treatment within 5 years (EMMY trial)
• Amenorrhoea Rate: 5-10% (usually transient; permanent amenorrhoea 1-3%, higher in older women > 45)

Complications:

Fertility Considerations:

UAE and fertility is a contentious area. Current evidence suggests:

• Pregnancy is Possible: Many women have conceived post-UAE

• Increased Risks:

  • Miscarriage rate: Increased (20-30% vs. 15-20% baseline)
  • Preterm delivery: 15-20%
  • Placental abnormalities: Increased risk of morbidly adherent placenta (accreta spectrum), placenta praevia
  • Fetal growth restriction
  • Postpartum haemorrhage

• Proposed Mechanisms:

  • Impaired endometrial perfusion
  • Reduced uterine compliance
  • Adhesion formation

• Current Recommendations (RCOG, ACOG):

  • Myomectomy remains gold standard for women desiring fertility
  • UAE should NOT be routinely recommended for women planning pregnancy
  • UAE may be considered in selected cases (e.g., women who decline myomectomy, high surgical risk) with thorough counselling about obstetric risks
  • If pregnancy occurs post-UAE: High-risk obstetric follow-up, surveillance for fetal growth, placental imaging

Exam Detail: MRCOG Counselling Scenario: UAE vs Myomectomy

Scenario: 38-year-old nulliparous woman, multiple intramural fibroids (5-7cm), severe HMB, wishes to avoid "big surgery" but "might" want children in the future.

Approach:

1. Acknowledge her concerns: "I understand you want to avoid major surgery, and UAE is indeed a less invasive option. However, your future fertility wishes are important in deciding the best treatment."

2. Explain Myomectomy:

   • "This is the gold standard for women who may want children. We remove the fibroids surgically and repair the womb. It is a bigger operation—either laparoscopic (keyhole) or open, depending on size and number of fibroids. Recovery is 4-6 weeks. The advantage is that it gives the best chance for a future pregnancy."
   • "Risks include bleeding (may need transfusion), adhesions (which can affect fertility), and a small risk of needing hysterectomy if bleeding cannot be controlled (rare, less than 1%)."

3. Explain UAE:

   • "This is done by an interventional radiologist through a small puncture in your groin. Particles are injected to block the blood supply to the fibroids, causing them to shrink. Recovery is quicker (1-2 weeks)."
   • "The downside is that if you do decide to get pregnant later, there is evidence of increased risks: higher miscarriage rate, increased risk of placenta problems (which can cause heavy bleeding at delivery), and preterm birth."
   • "For this reason, UAE is generally not recommended as first-line if pregnancy is a possibility."

4. Explore her priorities:

   • "How strong is your desire for future pregnancy? If it's definite, I would recommend myomectomy. If you're uncertain or pregnancy is unlikely, UAE is a reasonable option."

5. Shared Decision-Making:

   • "Ultimately, the choice is yours. I would support either decision, but I want you to be fully informed of the implications. If you choose UAE, we would monitor any future pregnancy closely."

Exam Tip: Demonstrate non-directive counselling, respect patient autonomy, but clearly state evidence-based recommendations.

Evidence: FEMME Trial (NEJM 2020) [7] - RCT of UAE vs Myomectomy:

• Both groups had significant QoL improvement
• Myomectomy group had slightly better QoL at 2 years
• Complication rates similar
• Re-intervention rate higher in UAE group (32% vs 4% at 2 years for further surgery)
• Conclusion: Both effective; choice depends on patient priorities

D. Surgical Management

Surgery remains the most definitive treatment, particularly for women desiring fertility or those who have failed medical/interventional options.

1. Myomectomy (Uterus-Preserving)

Myomectomy is the gold standard for women desiring future fertility.

Indications:

• Symptomatic fibroids with desire for fertility preservation
• Failed medical management
• Patient preference to retain uterus
• Specific scenarios: Submucosal fibroids causing infertility

Routes:

A. Hysteroscopic Myomectomy

• Indication: Submucosal fibroids (Type 0, 1, and selected Type 2)

• Size Limit: less than 3-5cm generally (operator-dependent)

• Technique:

  • Performed under GA or spinal anaesthesia
  • Uterine distension with glycine 1.5% or normal saline (bipolar systems)
  • Wire loop resection or hysteroscopic morcellator
  • Fibroid sliced and removed in pieces

• Advantages:

  • Day case or overnight stay
  • Minimal external scarring
  • Rapid recovery (1 week)

• Complications:

  • Fluid overload / TUR syndrome: Absorption of glycine → hyponatraemia, pulmonary oedema, cerebral oedema. Monitor fluid balance carefully (max 1.5L deficit). Use bipolar systems with saline to minimise risk.
  • Uterine perforation: 1-2%. Higher risk with Type 2 fibroids. May require laparoscopy/laparotomy.
  • Haemorrhage: Usually controlled with intrauterine balloon or oxytocin.
  • Intrauterine adhesions (Asherman's syndrome): Risk 5-10%. Minimised by post-operative hormonal treatment (oestrogen) or IUD insertion.

• Fertility Outcomes: Excellent. Most series report pregnancy rates 40-60%.

• Special Considerations for Type 2 Fibroids:

  • May require two-stage procedure (6-8 weeks apart for fibroid to prolapse into cavity after first stage)
  • GnRH agonist pre-treatment may facilitate single-stage resection

B. Laparoscopic Myomectomy

• Indication: Subserosal (Type 5, 6, 7) and selected intramural fibroids (Type 3, 4)

• Number: Typically suitable for ≤3-5 fibroids

• Size: Up to 8-10cm (operator-dependent)

• Technique:

  1. 3-4 port laparoscopy
  2. Identify and grasp fibroid
  3. Inject vasopressin (diluted 20 units in 100ml saline) to reduce bleeding
  4. Incise overlying serosa
  5. Enucleate fibroid along pseudocapsule (cleavage plane)
  6. Multi-layer closure (deep layer to obliterate dead space, superficial layer to re-approximate serosa)
  7. Morcellation: Fibroid removed via morcellator (see safety note below) or extended port

• Advantages:

  • Shorter hospital stay (1-2 days)
  • Faster recovery (2-4 weeks)
  • Less adhesion formation than open surgery
  • Less post-operative pain

• Complications:

  • Bleeding (may require conversion to laparotomy or hysterectomy if uncontrolled)
  • Uterine scar dehiscence in future pregnancy (risk less than 1%)
  • Adhesions
  • Morcellation risks (see below)

• Fertility Outcomes: Pregnancy rates 50-70%. Caesarean section often recommended due to uterine scar.

Exam Detail: Morcellation Safety Concerns

Power morcellation (grinding tissue to extract through small laparoscopic ports) became controversial after FDA warnings (2014) about risk of disseminating occult uterine sarcoma.

The Problem:

• Leiomyosarcoma cannot be reliably distinguished from leiomyoma pre-operatively
• Incidence: 1 in 400 to 1 in 1000 women undergoing surgery for presumed fibroids
• If morcellated, cancer cells spread throughout peritoneal cavity
• Converts stage I disease to stage IV (dramatically worsens prognosis)

FDA Recommendations:

• Contraindicated in peri/post-menopausal women (higher sarcoma risk)
• Contraindicated if any suspicion of malignancy
• Use "contained morcellation" (in-bag morcellation systems)
• Informed consent must include risk

RCOG Guidance:

• Prefer en-bloc removal where possible (mini-laparotomy, extended port)
• If morcellation needed: Use contained system
• Counsel patients about risks
• Frozen section is unreliable for diagnosing sarcoma intra-operatively

Alternatives:

• Mini-laparotomy with Pfannenstiel incision (4-6cm)
• In-bag morcellation
• Vaginal extraction

MRCOG Exam Point: In any scenario involving laparoscopic myomectomy, you MUST mention morcellation risks and how you would minimise them (consent, contained morcellation, or alternative extraction). This is a medico-legal hot topic.

C. Open Myomectomy (Laparotomy)

• Indication:

  • Large fibroids (> 8-10cm)
  • Multiple fibroids (> 5)
  • Deep intramural fibroids
  • Posterior wall fibroids (difficult laparoscopic access)
  • Previous abdominal surgery with adhesions

• Incision:

  • Pfannenstiel (transverse suprapubic) if uterus ≤16 weeks size
  • Midline (vertical) if larger or need extensive access

• Technique:

Exam Detail: Operative Steps: Open Myomectomy (MRCOG Focus)

1. Incision and Entry:

   • Pfannenstiel or midline incision
   • Open abdomen in layers
   • Assess uterus, adnexa, and pelvis

2. Exteriorisation:

   • Deliver uterus through wound if possible (improves access)

3. Haemostasis Preparation:

   • Inject Vasopressin (20 units in 100ml saline, inject 5-10ml into myometrium overlying fibroid)
   • Wait 3-5 minutes for vasoconstriction
   • Some surgeons use tourniquets around uterine vessels or infundibulopelvic ligaments (temporary)

4. Uterine Incision:

   • Single vertical midline anterior incision preferred (minimises adhesions, avoids cornua)
   • If multiple fibroids, enucleate through same incision if possible
   • Avoid transverse incisions (higher risk of lateral extension into uterine vessels)

5. Enucleation:

   • Identify fibroid pseudocapsule (avascular plane between fibroid and myometrium)
   • Use Allis forceps to grasp fibroid
   • Blunt and sharp dissection along cleavage plane
   • "Shell out" fibroid
   • Ligate any feeding vessels

6. Haemostasis:

   • Achieve meticulous haemostasis in fibroid bed
   • Use diathermy, suture ligation, or haemostatic agents

7. Closure:

   • Multi-layer closure essential:
     • Deep layer: Interrupted or continuous absorbable sutures (e.g., Vicryl 1 or 2-0) to close dead space and achieve haemostasis
     • Superficial layer: Continuous or interrupted sutures to re-approximate serosa (baseball stitch pattern to bury knots)
   • Ensure serosa well-approximated (reduces adhesion formation)

8. Adhesion Prevention:

   • Consider adhesion barriers (Interceed, Adept)
   • Thorough peritoneal lavage
   • Gentle tissue handling throughout

9. Closure of Abdomen:

   • Mass closure of fascia
   • Skin closure

10. Post-operative:

    • Analgesia, VTE prophylaxis
    • Mobilise early
    • Monitor Hb (may need transfusion if significant blood loss)

• Complications:

  • Haemorrhage: Most significant risk. Blood loss 200-500ml average; may be higher. Cross-match 2 units pre-operatively. Risk of requiring hysterectomy if uncontrolled bleeding (less than 1-2%).
  • Adhesions: 50-90% develop adhesions. May affect fertility, cause chronic pelvic pain, or bowel obstruction.
  • Uterine scar rupture in future pregnancy: Risk less than 1%, but higher than laparoscopic (due to deeper myometrial incisions). Recommend LSCS in most cases.
  • Infection: Endometritis, wound infection.

• Fertility Outcomes: Pregnancy rates 40-70%. Advise waiting 3-6 months before attempting conception. LSCS usually recommended.

• Recurrence: 15-30% at 5 years. Higher if multiple fibroids initially.

Comparison of Myomectomy Routes:

2. Hysterectomy (Definitive Treatment)

Hysterectomy is the only cure for fibroids. It eliminates the risk of recurrence but is irreversible.

Indications:

• Completed family (no desire for fertility)
• Failed conservative treatments (medical, UAE, myomectomy)
• Severe symptoms affecting quality of life
• Patient preference for definitive treatment
• Suspicion of malignancy (though aim for en-bloc removal without morcellation)

Routes:

• Vaginal Hysterectomy:

  • Preferred route if feasible (faster recovery, no abdominal scars)
  • Indications: Uterus ≤12-14 weeks size, good vaginal access, no adnexal pathology
  • Limitations: Large fibroids often preclude vaginal approach

• Laparoscopic Hysterectomy (Total Laparoscopic Hysterectomy - TLH):

  • Gold standard for most women
  • Advantages: Shorter stay, faster recovery, less pain, better cosmesis
  • Requires advanced laparoscopic skills
  • Morcellation considerations apply

• Abdominal Hysterectomy (Total Abdominal Hysterectomy - TAH):

  • Indications: Very large fibroids, suspected malignancy, dense adhesions, surgeon preference
  • Longer recovery (6-8 weeks)
  • Higher morbidity (infection, VTE, pain)

Oophorectomy Considerations:

• In pre-menopausal women: Conserve ovaries (avoid premature menopause unless other indications)
• In peri/post-menopausal women: Discuss risks/benefits of oophorectomy (reduced ovarian cancer risk vs. surgical menopause)

Outcomes:

• 95% satisfaction

• Definitive cure
• Operative mortality less than 0.1% (elective)

Complications:

• Bleeding, infection, VTE, ureteric injury (less than 1%), bladder injury (less than 1%), bowel injury (rare)

Exam Detail: MRCOG Viva Question: "When would you recommend hysterectomy over myomectomy for fibroids?"

Model Answer: "Hysterectomy is the only curative treatment for fibroids and is appropriate when:

1. Family complete: The patient has no desire for future fertility
2. Failed conservative management: Medical therapies, UAE, or myomectomy have been tried and failed, or are inappropriate
3. Severe symptoms: Quality of life is significantly impaired despite other treatments
4. Patient preference: After full counselling, the patient requests definitive treatment
5. Coexisting pathology: E.g., severe adenomyosis, endometrial hyperplasia, prolapse requiring surgical correction
6. High recurrence risk: Very large or multiple fibroids where myomectomy has low success and high recurrence

I would counsel the patient about:

• Irreversibility
• Routes of hysterectomy (vaginal preferred if feasible, otherwise laparoscopic or abdominal depending on uterus size and surgical factors)
• Ovarian conservation in pre-menopausal women
• Risks and benefits
• Recovery time

Ultimately, it is a shared decision, but hysterectomy offers definitive cure and high satisfaction in appropriately selected patients."

E. Special Populations

Pregnancy and Fibroids

Fibroids complicate 10-30% of pregnancies. Most remain asymptomatic, but complications can occur.

Effect of Pregnancy on Fibroids:

• 20-30% grow (mostly 1st trimester due to high oestrogen/progesterone)
• 50-60% remain stable
• 10-20% shrink (mechanism unclear; possibly relative ischaemia)

Complications in Pregnancy:

Red Degeneration - Detailed:

• Presentation: Acute abdominal pain (localised over fibroid), low-grade fever (37.5-38°C), nausea, vomiting
• Examination: Localised tenderness over fibroid, +/- peritonism, uterus larger than dates
• Investigations:
  • USS: Heterogeneous fibroid, increased vascularity peripherally
  • FBC: Leucocytosis
  • Exclude other causes (abruption, appendicitis, pyelonephritis)
• Management:
  • Supportive: Admission, rest, IV fluids
  • Analgesia: Opiates (morphine, codeine). Avoid NSAIDs after 32 weeks (risk of premature ductus arteriosus closure).
  • Monitor: Fetal wellbeing (CTG if viable gestation), maternal obs
  • Reassurance: Self-limiting, usually resolves in 7-14 days
  • Avoid surgery: Myomectomy in pregnancy is generally contraindicated (risk of massive haemorrhage)

Delivery Planning:

• Mode of Delivery: Vaginal delivery usually feasible unless obstructive fibroid or obstetric indications for LSCS
• Myomectomy at Caesarean Section: CONTRAINDICATED in most cases
  • Risk of massive, uncontrollable haemorrhage (can lose 2-3L rapidly)
  • Only exception: Pedunculated subserosal fibroid that is easily accessible and on a narrow stalk (can be ligated and removed with minimal bleeding)
• Active Management 3rd Stage: Essential (high PPH risk)
• Senior Obstetrician: Should attend delivery if large fibroids

Adolescents

• Fibroids rare in adolescents
• If present: Consider HLRCC syndrome (genetic testing, renal imaging, family history)

Post-Menopausal Women

• Fibroids should regress after menopause (loss of hormonal stimulus)
• New growth or growth in post-menopausal women is highly suspicious for leiomyosarcoma
• Investigate urgently: MRI pelvis, CA-125, surgical removal with histology
• Avoid HRT if large fibroids (may stimulate growth)

9. Complications of Fibroids

10. Prognosis

Natural History (Untreated):

• 50% of fibroids remain asymptomatic throughout life
• 10-15% show growth annually
• Growth rate unpredictable; not related to initial size
• Post-menopause: 70-80% regress (shrink by 35-50% over 1-2 years)

After Medical Treatment:

• GnRH agonists/antagonists: Fibroid re-growth to baseline within 3-6 months of stopping (unless definitive treatment performed)
• LNG-IUS: Symptom control maintained while in situ; no effect on fibroid size

After UAE:

• 80-90% symptom improvement at 1 year
• 20-30% require further intervention within 5 years (repeat UAE, myomectomy, or hysterectomy)
• Fibroid shrinkage maintained in responders

After Myomectomy:

• Recurrence: 15-30% at 5 years, 50% at 10 years (cumulative recurrence risk)
• Recurrence higher if:
  • Multiple fibroids initially
  • Young age at surgery (less than 30 years)
  • Black ethnicity
  • Incomplete removal
• Recurrence represents either:
  • New fibroids (from residual stem cells)
  • Growth of small fibroids not removed initially
• Fertility: Pregnancy rates 40-70% after myomectomy (depends on age, other fertility factors)
• Obstetric Outcomes: Increased LSCS rate (uterine scar); uterine rupture risk less than 1%

After Hysterectomy:

• Definitive cure (0% recurrence)

• 95% satisfaction

• Quality of life improvement sustained long-term

Malignancy Risk:

• Leiomyosarcoma: less than 0.2% (1 in 400 to 1 in 1000)
• Rapid growth alone is a poor predictor in pre-menopausal women (many benign fibroids grow rapidly)
• Post-menopausal growth is highly suspicious and warrants urgent investigation

Prognostic Factors for Symptom Severity:

• Submucosal location → Severe HMB
• Large size (> 8-10cm) → Bulk symptoms, anaemia
• Multiple fibroids → Higher recurrence after myomectomy
• Black ethnicity → Earlier onset, larger size, more symptoms

11. Prevention & Screening

Primary Prevention:

• No proven strategies
• Theoretical:
  • Maintaining healthy BMI (obesity increases risk)
  • Early parity (protective)
  • Vitamin D supplementation (observational evidence; no RCT proof)

Secondary Prevention (Reducing Recurrence After Myomectomy):

• GnRH agonist for 3-6 months post-myomectomy (some evidence for reduced recurrence, but not routinely recommended)
• Avoid HRT if possible (may stimulate growth of residual/new fibroids)

Screening:

• No population-based screening recommended
• Incidental finding on USS for other indications is common
• High-risk women (HLRCC syndrome): Genetic counselling, surveillance USS

12. Landmark Evidence & Guidelines

Key Trials

1. The FEMME Trial (NEJM 2020) [7]

• Question: Quality of life (QoL) after UAE vs Myomectomy in women wishing to preserve uterus.
• Design: Multicentre RCT, n=254, UK-based.
• Participants: Women with symptomatic fibroids, uterus less than 16 weeks size, wishing to avoid hysterectomy.
• Interventions: UAE vs myomectomy (open or laparoscopic).
• Primary Outcome: QoL (SF-36 questionnaire) at 2 years.
• Results:
  • Both groups had significant and sustained QoL improvement from baseline
  • Myomectomy group had slightly better QoL scores at 2 years (small but statistically significant difference)
  • Complication rates: Similar (UAE 24%, myomectomy 29%)
  • Hospital stay: Shorter for UAE (median 2 days vs 4 days)
  • Re-intervention rate: Higher in UAE group (probability of needing further surgery 32% vs 4% at 2 years)
• Conclusion: Both UAE and myomectomy are effective for symptom control. Myomectomy offers slightly better long-term QoL and lower re-intervention rate, but UAE offers quicker recovery. Choice depends on patient priorities.
• MRCOG Relevance: Gold standard evidence for counselling women choosing between UAE and myomectomy.

2. EMMY Trial (2005)

• Comparison: UAE vs Hysterectomy.
• Findings: UAE had shorter hospital stay (3 vs 5 days), quicker return to work (21 vs 43 days), but 28% required hysterectomy within 5 years due to symptom recurrence or failure.
• Conclusion: UAE is an effective alternative to hysterectomy in selected women, but has higher re-intervention rate.

3. LIBERTY Trials (NEJM 2021) [18]

• Intervention: Relugolix combination therapy (GnRH antagonist + add-back HRT) vs placebo.
• Results: Significant reduction in HMB (73% vs 19% amenorrhoea); 50% reduction in fibroid volume; maintained efficacy over 24 months; minimal bone loss with add-back HRT.
• Conclusion: Relugolix is effective and safe for long-term (up to 24 months) medical management of fibroids.

4. Cochrane Reviews

• Pre-operative GnRH agonists (2017) [14]: Reduce fibroid size, improve Hb, reduce operative blood loss; facilitate surgery. Recommended for pre-operative optimisation.
• Myomectomy for subfertility (2020) [13]: Myomectomy for submucosal fibroids improves fertility; benefit less clear for intramural fibroids.

Guidelines Summary

13. Exam-Focused Sections

Common MRCOG Exam Scenarios

1. History Taking Station

Candidate Instructions: "Take a history from Mrs Jones, 38, who has been referred by her GP with a large pelvic mass."

Approach (Structured 10-minute consultation):

Opening (1 min):

• Introduce yourself, confirm patient identity
• Explain purpose: "Your GP has referred you because of a lump in your tummy. I'd like to ask some questions to understand more about this."

History of Presenting Complaint (3-4 mins):

1. Bleeding Pattern:

   • "Tell me about your periods."
   • Heavy? Flooding? Clots? Duration? Frequency? (Quantify: soaking through protection? Time off work?)
   • Intermenstrual or post-coital bleeding? (Exclude endometrial/cervical pathology)
   • Anaemia symptoms: SOB, fatigue, palpitations, dizziness?

2. Pressure Symptoms:

   • Urinary: Frequency (day/night)? Urgency? Hesitancy? Retention?
   • Bowel: Constipation? Tenesmus?
   • Abdominal swelling: "Have you noticed your tummy getting bigger? Difficulty fitting into clothes?"

3. Pain:

   • Dysmenorrhoea? (Severity, impact on life)
   • Dyspareunia?
   • Chronic pelvic pain?
   • Acute pain (Red Flag): Any sudden severe pain? Fever? (Degeneration/torsion)

4. Mass:

   • When first noticed? Growing?
   • Any discharge?

Gynaecological History (1-2 mins):

• LMP (establish menstrual status; exclude pregnancy)
• Smear history (exclude cervical pathology)
• Contraception
• Previous gynaecological surgery or treatments

Obstetric History (1-2 mins):

• Parity (G P)
• CRITICAL QUESTION: "Are you planning to have children in the future?" (Dictates management options)
• Previous pregnancy complications?

Past Medical History (1 min):

• VTE history (contraindication to some hormonal treatments, surgical risk)
• Bleeding disorders
• Anaemia
• Cardiovascular/respiratory (fitness for surgery)

Drug History & Allergies:

• Anticoagulants?
• Hormonal treatments tried?
• Allergies (especially contrast if UAE considered)

Social History (1 min):

• Occupation (impact of symptoms on work)
• Smoking, alcohol
• Impact on quality of life, relationships, sexual function

Ideas, Concerns, Expectations (ICE) (1 min):

• "What are you most worried about?"
• "What do you think might be causing this?"
• "What are you hoping we can do for you?"

Closing (1 min):

• Summarise
• "Thank you. Based on what you've told me, I think we need to do some tests including a scan to look at the lump. We'll then discuss the best way to help you."
• Offer opportunity for questions

MRCOG Examiner Mark Points: ✅ Systematic approach ✅ Identified Red Flags (acute pain, post-menopausal bleeding, rapid growth) ✅ Asked about future fertility wishes (critical for management) ✅ Assessed impact on quality of life ✅ Professional, empathetic communication

2. Counselling Station: UAE vs Myomectomy for Fertility

Scenario: 35-year-old nulliparous woman, multiple intramural fibroids (5-7cm), severe HMB (Hb 98 g/L), wishes to avoid "big surgery" but "might want children in the future."

Approach (12-14 minute station):

Opening (1 min):

• Introduce, confirm understanding of situation
• "I understand you have fibroids causing heavy bleeding, and you'd like to discuss your treatment options. Is that right?"

Agenda Setting (1 min):

• "Today I'd like to explain what fibroids are, discuss two main treatment options—myomectomy and uterine artery embolisation—and help you decide which is best for you. Does that sound okay?"

Explain Diagnosis (1 min):

• "Fibroids are very common non-cancerous growths in the womb. They're fed by hormones, which is why they cause heavy bleeding. The scans show you have several fibroids, which explains your symptoms."

Explore Her Priorities (2 mins):

• "You mentioned you might want children. Can you tell me more about that?"
• (Listen carefully; assess: Definite? Uncertain? Unlikely?)
• "How do you feel about the idea of major surgery?"
• "What's most important to you: keeping your fertility options open, or having a quicker recovery?"

Option 1: Myomectomy (3 mins):

• "This is an operation to remove the fibroids but keep your womb."
• "In your case, it would likely be either keyhole surgery or an open operation with a bikini-line cut, depending on the exact size and position of the fibroids. We'd decide that after looking at an MRI scan."
• Advantages:
  • "This is the gold standard if you want to keep your fertility. It gives you the best chance of getting pregnant and having a safe pregnancy."
  • "It removes the fibroids completely."
• Disadvantages:
  • "It's a bigger operation. You'd be in hospital for 2-4 days and recovery is 4-6 weeks."
  • "There's a risk of heavy bleeding during surgery (we'd have blood ready just in case)."
  • "There's a small risk that if bleeding can't be controlled, we might need to remove your womb to keep you safe. That's rare—less than 1 in 100."
  • "Fibroids can grow back—about 15-30% chance over 5 years."
  • "If you get pregnant later, you'd likely need a caesarean section because of the scar on the womb."

Option 2: Uterine Artery Embolisation (UAE) (3 mins):

• "This is done by a radiologist, not a surgeon. They put a tiny tube through a pinhole in your groin, block the blood supply to the fibroids, and the fibroids shrink."
• Advantages:
  • "Much smaller procedure—you'd be in hospital overnight and back to normal in 1-2 weeks."
  • "About 80-90% of women are happy with the results."
• Disadvantages:
  • "The first week after can be quite uncomfortable—you get cramping pain, nausea, sometimes fever as the fibroids die off. We give strong painkillers."
  • "There's a higher chance you'll need another treatment later—about 1 in 3 women need something else within 5 years."
  • "If you do want to get pregnant later, there are some concerns. Women who've had UAE have higher rates of miscarriage, premature birth, and problems with the placenta (the afterbirth). That's why we generally don't recommend UAE if pregnancy is a possibility."
  • "There's a small risk (1-2%) of the procedure affecting your ovaries and bringing on early menopause."

Recommendation (1 min):

• "Given that you might want children, I would recommend myomectomy as the safer option for your future fertility. However, if you're fairly certain you won't have children, or if avoiding major surgery is your absolute priority, UAE is a reasonable alternative—as long as you understand the pregnancy risks."

Shared Decision-Making (1-2 mins):

• "What are your thoughts?"
• (Explore concerns, answer questions)
• "Would you like some time to think about it? I can give you information leaflets about both options."
• "We can also do some more tests—an MRI scan to map the fibroids exactly—which will help us plan whichever option you choose."

Next Steps (1 min):

• "Before any treatment, we'll treat your anaemia with iron tablets or an iron drip."
• "We might also offer you a temporary hormonal treatment to stop your periods and let your blood count recover."
• "Let's book you for an MRI scan and see you back in 4-6 weeks to make a final decision."

Closing:

• "Do you have any questions?"
• "I know it's a lot to take in. Here are some leaflets, and you can call us anytime if you have more questions."

MRCOG Examiner Mark Points: ✅ Explored patient's priorities (fertility, recovery time) ✅ Explained both options clearly, covering risks and benefits ✅ Made evidence-based recommendation (myomectomy for fertility) ✅ Respected patient autonomy (shared decision-making) ✅ Mentioned FEMME trial findings (better long-term outcomes with myomectomy but higher re-intervention after UAE) ✅ Addressed anaemia management ✅ Offered information leaflets and follow-up

3. Data Interpretation / Investigation Station

Scenario: USS report describes "Type 2 submucosal fibroid 4cm, Type 5 subserosal fibroid 6cm, Type 4 intramural fibroid 3cm" in a 40-year-old woman with HMB and infertility (trying for 2 years).

Question: "Which fibroid is most likely responsible for her symptoms? What would be your management approach?"

Model Answer:

"The Type 2 submucosal fibroid (4cm) is most likely responsible for her heavy menstrual bleeding. Submucosal fibroids, particularly Types 0-2, distort the endometrial cavity and directly affect the endometrium, causing aberrant angiogenesis and impairing haemostasis.

The submucosal fibroid may also be contributing to her infertility by:

• Impairing embryo implantation (altered endometrial receptivity)
• Mechanically distorting the cavity

The Type 5 subserosal fibroid is unlikely to cause HMB or infertility. The Type 4 intramural fibroid's contribution depends on whether it contacts or distorts the endometrial cavity (this would need further assessment with hysteroscopy or MRI).

Management Approach:

1. Investigations:

   • FBC (assess anaemia)
   • Hysteroscopy or saline infusion sonography to assess the submucosal fibroid in detail and confirm cavity distortion
   • Consider MRI pelvis for detailed pre-operative mapping (particularly for the intramural fibroid's relationship to the cavity)
   • Partner's semen analysis and assessment of her ovulation/tubal status (complete infertility workup)

2. Treatment:

   • Target the submucosal fibroid as it is symptomatic and impacting fertility.
   • Hysteroscopic myomectomy for the Type 2 submucosal fibroid:
     • This is technically challenging as ≥50% is intramural
     • Options: Two-stage procedure, or GnRH agonist pre-treatment for 3 months to shrink it and increase the intracavitary proportion
   • Consider laparoscopic myomectomy to address the intramural fibroid if MRI/hysteroscopy shows cavity distortion
   • The Type 5 subserosal fibroid can be left alone (asymptomatic) or removed if already performing laparoscopic surgery

3. Fertility:

   • After hysteroscopic myomectomy: Wait 2-3 months before attempting conception
   • If laparoscopic/open myomectomy: Wait 3-6 months
   • If natural conception doesn't occur, consider fertility treatment (IVF) after 12 months

4. Anaemia Management (if present):

   • Correct anaemia pre-operatively with oral or IV iron
   • Consider GnRH agonist to induce amenorrhoea and allow Hb recovery

This approach prioritises her fertility while addressing her symptomatic fibroid."

Examiner Mark Points: ✅ Correctly identified Type 2 submucosal as causative ✅ Explained mechanism (cavity distortion, impaired implantation) ✅ Systematic investigation plan ✅ Appropriate treatment (hysteroscopic myomectomy) ✅ Acknowledged technical challenge of Type 2 (mentioned two-stage or pre-treatment) ✅ Considered fertility implications ✅ Multidisciplinary approach (fertility clinic involvement)

Viva Voce Preparation

Viva Point: Opening Statement (30 seconds): "Uterine fibroids are benign smooth muscle tumours affecting up to 70-80% of women by age 50. While often asymptomatic, they are a major cause of morbidity, particularly heavy menstrual bleeding, pelvic pressure symptoms, and infertility. They are the leading indication for hysterectomy worldwide. Management is highly individualised and depends on symptoms, fibroid characteristics—particularly location as defined by the FIGO classification—and the patient's desire for future fertility."

Key Facts to Mention:

1. Hormonal Dependence: "Fibroids are strictly oestrogen and progesterone dependent. They regress after menopause, which is why medical treatments targeting these hormones (GnRH agonists, SPRMs) are effective."
2. FIGO Classification: "The FIGO system classifies fibroids based on their relationship to the uterine wall. This is critical: submucosal fibroids (Types 0-2) cause HMB and infertility; subserosal fibroids (Types 5-7) cause bulk symptoms."
3. Red Degeneration: "This is haemorrhagic infarction, most common in pregnancy due to rapid growth outstripping blood supply. It presents with acute localised pain, fever, and tenderness. Management is conservative with analgesia and fluids."
4. Malignancy: "Leiomyosarcoma is rare—less than 0.2%. Pre-operative diagnosis is nearly impossible. This is the basis for the FDA morcellation warning."
5. UAE vs Myomectomy: "The FEMME trial (NEJM 2020) showed both are effective, but myomectomy offers better long-term QoL and lower re-intervention rates. UAE is not recommended for women planning pregnancy due to increased miscarriage and placental risks."
6. Recurrence: "After myomectomy, 15-30% recur at 5 years. Hysterectomy is the only cure."

Common Viva Questions & Model Answers

Q1: "What is the pathophysiology of fibroids?"

A: "Fibroids are monoclonal tumours, meaning each arises from a single myometrial smooth muscle cell. Approximately 40-50% have cytogenetic abnormalities, most commonly MED12 mutations found in up to 70%. These genetic changes interact with hormonal and growth factor signalling. Fibroids are strictly oestrogen and progesterone dependent—both hormones are necessary for growth. Oestrogen upregulates progesterone receptors and growth factors like IGF-1 and TGF-beta. Progesterone drives proliferation via EGF and BCL-2. At the molecular level, fibroids have excessive extracellular matrix deposition driven by TGF-beta 3, creating a stiff microenvironment that further promotes growth via mechanotransduction pathways like Rho/ROCK and YAP/TAZ. This explains why they regress after menopause when ovarian steroids decline."

Q2: "How do fibroids cause heavy menstrual bleeding?"

A: "Submucosal fibroids cause HMB via several mechanisms:

1. Increased endometrial surface area: Cavity distortion creates more endometrium to shed
2. Aberrant angiogenesis: Elevated VEGF expression leads to fragile, dilated venules in the overlying endometrium
3. Impaired myometrial contractility: Fibroids interfere with the uterus's ability to contract and compress spiral arteries, which is essential for haemostasis after menstruation
4. Local inflammatory mediators: Altered prostaglandin ratios and cytokines affect endometrial bleeding patterns
5. Surface ulceration: Submucosal fibroids can undergo ischaemic ulceration and bleed directly

This is why location is critical—subserosal fibroids rarely cause HMB because they don't affect the endometrium."

Q3: "A 28-year-old woman with a 3cm Type 1 submucosal fibroid and infertility for 2 years. What is your management?"

A: "This is a clear indication for hysteroscopic myomectomy because:

1. Submucosal fibroids impair fertility (70% reduction in live birth rates in IVF studies)
2. Meta-analyses show myomectomy restores fertility to near-normal levels
3. A Type 1 fibroid (less than 50% intramural, > 50% in cavity) is amenable to hysteroscopic resection in one stage
4. At 3cm, it's within size limits for hysteroscopic approach

Before surgery, I would:

• Complete her infertility workup (partner's semen analysis, confirm ovulation, check tubal patency with HyCoSy)
• FBC to assess for anaemia
• Outpatient hysteroscopy to confirm feasibility of resection

Post-operatively:

• Advise to wait 2-3 months before attempting conception (allow endometrial healing)
• Consider oestrogen therapy or IUD insertion for 6 weeks to prevent intrauterine adhesions
• If no conception after 12 months, consider fertility treatment

Evidence: Cochrane review (2020) supports myomectomy for submucosal fibroids in infertile women. The benefit is clear-cut for Types 0 and 1."

Q4: "What are the complications of UAE?"

A: "Complications of UAE include:

Common (60-80%):

• Post-embolisation syndrome: Pain, fever, nausea due to ischaemic necrosis. Lasts 7-10 days. Managed with analgesia, anti-emetics, hydration. Most women require 24-48h admission.

Uncommon (5-10%):

• Vaginal discharge: Necrotic material expelled. Can last weeks.
• Fibroid expulsion: Submucosal fibroids may necrose and prolapse through cervix, requiring hysteroscopic removal.

Rare but Serious (1-5%):

• Infection: Pyomyoma (infected necrotic fibroid) or endometritis. Requires IV antibiotics; occasionally hysterectomy.
• Ovarian failure: 1-5%, age-dependent (higher in > 45 years). Due to non-target embolisation or collateral damage. May require HRT.

Very Rare (less than 1%):

• Non-target embolisation: Buttock or leg claudication if particles enter internal iliac branches.
• VTE: Prolonged immobilisation.

Long-term:

• Re-intervention: 20-30% need further treatment within 5 years (EMMY trial).
• Fertility concerns: Increased miscarriage, preterm delivery, placental complications (not routinely recommended for women planning pregnancy).

Informed consent covering all these risks is essential before UAE."

Q5: "What safety issues surround laparoscopic morcellation?"

A: "Morcellation is the process of cutting tissue into small pieces to extract through small laparoscopic ports. The concern, highlighted by the FDA in 2014, is the risk of disseminating occult uterine sarcoma.

The Problem:

• Leiomyosarcoma cannot be reliably distinguished from leiomyoma pre-operatively (clinically, radiologically, or even with frozen section)
• Incidence: 1 in 400 to 1 in 1000 women undergoing surgery for presumed fibroids
• If a sarcoma is morcellated, cancer cells spread throughout the peritoneal cavity
• This converts localised stage I disease to disseminated stage IV disease, dramatically worsening prognosis

Risk Factors for Sarcoma:

• Peri/post-menopausal age
• Rapid growth (though this is a poor predictor in pre-menopausal women)
• Solitary mass
• Post-menopausal bleeding

Recommendations (FDA/RCOG):

• Avoid morcellation in peri/post-menopausal women
• Contraindicated if any suspicion of malignancy
• If morcellation necessary: Use contained morcellation (in-bag systems like Alexis bag)
• Alternative extraction: Mini-laparotomy, extended port, vaginal extraction
• Informed consent must include risk

In practice, many surgeons now favour mini-laparotomy for fibroid extraction, particularly for larger fibroids, to avoid morcellation altogether."

Q6: "When would you recommend hysterectomy over myomectomy?"

A: "Hysterectomy is the only curative treatment and is appropriate when:

1. Family complete: No desire for future fertility
2. Failed conservative treatment: Medical therapies, UAE, or previous myomectomy have failed
3. Severe symptoms: Significant impact on quality of life despite other treatments
4. Patient preference: After counselling, patient requests definitive treatment
5. Coexisting pathology: E.g., severe adenomyosis, endometrial hyperplasia, uterovaginal prolapse needing surgical repair
6. High recurrence risk: Very large or numerous fibroids where myomectomy success is low

Counselling Points:

• Irreversibility
• Route: Vaginal preferred if feasible (faster recovery), otherwise laparoscopic or abdominal depending on uterus size
• Ovarian conservation in pre-menopausal women (avoid premature menopause unless other indication for oophorectomy)
• Risks: Bleeding, infection, VTE, ureteric/bladder injury
• Recovery: 2-8 weeks depending on route
• Outcomes: > 95% satisfaction, definitive cure

It's a shared decision, but for appropriately selected patients (family complete, severe symptoms), hysterectomy offers excellent long-term outcomes."

Common Mistakes (What NOT to Do)

❌ Referring to a fibroid as a "cyst" → Fibroids are solid tumours, not cystic. Terminology matters in exams.

❌ Suggesting myomectomy during Caesarean Section → High risk of massive haemorrhage. Only exception: easily accessible pedunculated subserosal fibroid.

❌ Ignoring fertility wishes → Always establish if patient wants children before discussing management. This is the critical branch point.

❌ Forgetting to exclude pregnancy → uterine enlargement + amenorrhoea = pregnancy until proven otherwise. Always check hCG.

❌ Not mentioning morcellation risks → In any laparoscopic myomectomy scenario, you must discuss morcellation and how to minimise risk (consent, contained morcellation, or alternative extraction). This is a medico-legal hot topic.

❌ Recommending UAE as first-line for fertility → Myomectomy is gold standard for fertility. UAE has obstetric risks.

❌ Using GnRH agonist > 6 months without add-back HRT → Causes significant bone loss. Always mention the 6-month limit or use of add-back.

❌ Not recognising red degeneration in pregnancy → Acute pain in pregnant woman with known fibroids = red degeneration until proven otherwise. Conservative management, NOT surgery.

❌ Misinterpreting FIGO classification → E.g., thinking Type 2 is easily resectable hysteroscopically (it's not—≥50% intramural makes it challenging).

❌ Not counselling about recurrence after myomectomy → 15-30% recurrence at 5 years. Patients need realistic expectations.

14. Patient Explanation (Layperson Summary)

"Fibroids are very common non-cancerous growths that develop in the muscular wall of the womb. They're a bit like knots in wood—firm lumps made of muscle and fibrous tissue. They can vary in size from as small as a pea to as large as a melon. Many women have them and don't even know it because they cause no problems.

We only need to treat fibroids if they're causing symptoms. The most common problems are heavy periods (which can make you anaemic and tired), a feeling of pressure in your tummy or pelvis, needing to pass urine frequently, or difficulty getting pregnant.

Fibroids are fed by your hormones, particularly oestrogen and progesterone, which is why they tend to shrink naturally after the menopause when your hormone levels drop.

If you need treatment, we have several options depending on whether you want to have children in the future:

1. Tablets: To control heavy bleeding (like tranexamic acid) or to shrink the fibroids temporarily (hormonal treatments).

2. Uterine Artery Embolisation (UAE): A radiologist blocks the blood supply to the fibroids through a tiny tube in your groin, causing them to shrink. Recovery is quick (1-2 weeks), but it's not recommended if you're planning pregnancy.

3. Myomectomy: An operation to remove the fibroids but keep your womb. This is the best option if you want to have children. It can be done by keyhole surgery or through a cut in your tummy.

4. Hysterectomy: Removing your womb completely. This is the only permanent cure and is suitable if you don't want more children.

We'll work together to choose the best option for you based on your symptoms, whether you want children, and what matters most to you."

15. References

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