Pathophysiology
- Benign tumors arising from smooth muscles of myometrium.
- Composed of whorls of smooth muscle and connective tissue.
- Within uterus new blood vessel formation occurs in response to cyclical fluctuation of steroids.
- Fibroid contains increased levels of both oestrogen and progesterone receptors compared to normal myometrium.
- Fibroids are relatively avascular. But there is abnormal proliferation of surrounding blood vessles.
- So abnormal angiogenesis has a key role.
Within fibroid there is abnormal expression of angiogenic factors.
- EGF
- Vascular EDF
- Transforming growth factor β
Genetic factors- rearrangements of chromosome 6 and 12 found. (Robin’s)
Epidemiology
Life time risk is 30%
Prevalence- 25% among women presents with symptoms within reproductive age group (actual prevalence much higher)
Rates among black women 2-3times greater than white
In a USA community study showed overall prevalence- 70% white women
(at age 50 yrs) 80% in black women
Risk factors
- Younger age at menarche
- Nulliparity/reduced parity (but longer the duration from last pregnancy higher risk)
- Family history
- High BMI
- Reduce physical exercise
- High consumption of red meat
Protective factors
- High parity
- Smoking
- Long term use of OCP, Depoprovera
- Reduced incidence in women with LNG-IUS than copper IUCD
Clinical presentation
Only 1 in 4 fibroids become symptomatic
History
AUB- HMB, intermenstrual bleeding,
Pain during menstruation
Lower back pain- stretching uterosacral
Dragging sensation
Increased prevalence of fibroids in women comes with HMB.
40% if blood loss>200ml
10% if blood loss below 100ml
Size of the submucous or intramural myoma related to degree of bleeding
Reason for HMB in fibroids ( ARUL KUMARAN)
- Increased endometrial surface, greater shedding area
- Increased uterine vasculature
- Changes in the uterine contractility pattern
- Exposure and ulceration of submucosal myoma surface
- Degeneration of myomatous nodule
- Uterine venous ectasia by compression of venous plexus by fibroides
Presentation ( STRAT OG)
- gynaecological – AUB, HMB, pelvic pain, dyspareunia, pelvic/abdominal mass
- anaemia due to HMB
- obstetric – infertility, miscarriage, abdominal pain (red degeneration of fibroids midtrimester), preterm labour, malpresentation, caesarean delivery, postpartum haemorrhage
- compression of organ systems – abdominal pressure-like effects on gastrointestinal and urological tract and nerve entrapment like symptoms.
Complications
- Hyaline degeneration is relatively common and presents as painful enlarged fibroids due to hyaline/cystic degeneration pathological process.
- Red degeneration (necrobiosis) occurs typically during pregnancy due to infarction at mid-pregnancy.
- Calcification (‘womb stone’) – usually in postmenopausal women.
- Sarcomatous (malignant) change. Generally presents as a 0.2% risk. There is a greater risk in women with multiple or rapidly growing fibroids, at advanced age, and if there is a histology is leiomyosarcoma
- Infection (abscess) – relatively rare.
- Torsion of pedunculated fibroids.
Examination
Palpably enlarged uterus in abdominal and pelvic examination
Leiomyosarcoma
- Overall incidence-0.64/100000 per year
- Estimated prevalence in a fibroid- 0.14%
- Risk increased with age
- Extremely low below 40 yrs.
Signs
- rapidly growing fibroid
- Fibroid growing during GnRH agonist Rx or during menopause.
- Solitary lesion
- Oval shape
- Size >8 cm,high vascularity
- Central necrosis
- Absent calcification
Investigation
TVS is the preliminary investigation. But may have inter-observer variations.
TAS – if uterus> 12 week size
Document number, size, and position of individual fibroids
Document overall uterine dimensions
MRI
- No advantage over ultrasound in detection of fibroids
- But greater accuracy
- Less inter-observer variations
MRI is indicated in
- Suspicious uterine mass- to exclude LMS
- Before proceeding to UAE
If submucous fibroid present
Combining MRI ,hysteroscopy or saline infusion sonography with TVS has improved accuracy.
Classification of fibroids
- Submucous
- Intramural
- Subserosal
- Subserosal pedunculated.
FIGO classification
Cervical fibroids- 5% of all fibroid
Broad ligament fibroids
- Can associate with polycytheamia leading to thrombosis and poor hamosatsis
- Uterine artery and vein should be carefully avoided. Post op heamatoma are common
- Ureter should be identified and pushed lateral before eneucleation
Management of uterine fibroid
Decided on
- Symptoms
- Age
- Fertility wish
- Size and number of fibroids
- Location of fibroids
- Available facility and competence
| Conservative Mx | Asymptomatic fibroids doesn’t need treatment Iron deficiency anaemia- Rx with oral iron |
| Medical Mx – Non hormonal Rx | |
| NSAIDS -do not reduce bleeding with fibroid. But will reduce pain associated with fibroid degeneration Antifibronolytic- Tranexemic acid Reduce blood loss up to 50% in fibroids (Non RCT data) Induce necrosis and infarcts in large fibroids Preferable than NSAIDS as first line Mx MOA Competitively inhibits the activation of plasminogen to plasmin Plasmin is needed for degradation of fibrin. CI- history of ischeamic stroke or TIA | |
| Medical management hormonal Rx Perimenapausal women with symptoms whose fibroids will regress at the onset of menopause People unfit for surgery To preoperatively reduce fibroid size and optimize Hb by reducing blood loss | |
| COCP | Long term use is protective against fibroid occurrence. No evidence causing enlargement of fibroids. 50% reduction in blood loss with high COCP (30mcg ethinyl- estradiol +150mcg Levenogestral) COCP can use as the contraceptive method in women with fibroid, but not effective in controlling HMB complicated with anaemia |
| LNG-IUS | In uterus below 12 week size and with no cavity distortion LNG-IUS reduces HMB even with anemia ( in a RCT 91% reduction of bleeding with 12 months use) Reduces bleeding by inducing endometrial atropy Reduces uterine volume Doesn’t affect fibroid volume More effective than COCP Rate of expulsion of IUS 8%- with fibroid Vs 1% in uteri without fibroids |
| DMPA (Progestogens) Northisterone | Only reduce bleeding in fibroids in 6 months use. Does not shrink the fibroid size even in higher doses. Long term DMPA use reduces development of fibroids. Control HMB if used continuously 21days out of 28 days cycles Does not affect fibroid size |
| Danazole (androgen) | Reduce fibroid sizeReduce blood loss. MOA-multiple MOAs Inhibit enzymes needed for steroidgenesis Anti ostrogenicCompetitively binds steroid carrier proteins Inhibit gonadotropin secretion –esp. mid cycle surge Act as weak andogen Dose Danazol 100 mg daily for 6 months resulting in a mean myoma volume decrease of 38 % Side effects- virilization, permanent voice changes, weight gain, atherogenic effect, greasy skin |
| Gestrinone (androgenic antiprogessterone) | Reduce fibroid size and blood loss |
| Anti progesterone Mifepristone Telopristone and asoprisnil are also anti-progesterones | MOA Binds to PR in fibroid and reduce progesterone action Reduces number of PRDose -5mg-10mg daily 3-6months Significantly reduces blood loss No effect in fibroid or uterine volume. May induce hyperplastic endometrial changes due to PR inhibition.Has anti-glucocorticoid activity |
| Ulipristal acetate (SPRMs) | MOA Pure progesterone antagonist. Binds only PR, not to ER. Down regulate PR and growth factors on uterus. Study PEARL II & III trials 5mg-10mg daily given for 13 weeks 70% develop amenorrhea with increased Hb and haematocrit Median onset of amenorrhea is after 7 days Fibroid volume was reduced by 12-25%( with 5mg &10mg) Not superior to GnRH in bleeding control and fibroid volume Slower re-growth of fibroid after stop Oestrogen levels are kept in mid follicular level so no vasomotor symptoms. No effect on BMD Less anti-glucocrticoid effect Causes glandular dilatation and asymetrical glands and stroma growth in endometium due to unopposed E2 action. But reversible in 6months after stop UA Recommendation UA is effective for rapid control of HMB 2ry to fibroids Can used as 5mg daily for 3 months before hysterectomy – esp.women with anaemia Rx should be started in 1st week of menstrual cycle. 3 months courses of Rx can be repeated intermittently after Rx free intervals NICE 2020 MARCH—STOP RX IF PATIENTS ALREADY ON AND REPEAT LIVER FUNCTION AFTER 2-4 WEEKS DON’T START IN NEW PATIENTS—SERIOUS LIVER INJURY |
| GnRH analouges | MOA Inhibit HPO axis due to absence of GnRH pulses. Initially increase gonadotrophin transiently- ‘Flare up’ Reduce oestrogen and progesterone production later. Decreases expression of IGF-1,EGF, TGF-β- needed for fibroid Pre-operative use Induces amenorrhea and shrinkage of uterus- after 12 weeks Reduces fibroid size and vascularity When use 3-4 months prior to surgery- effective in prevent preoperative anaemia After cessation re-growth is rapid During surgery Reduced tumor size- less need for midline incision Make vaginal approach easy than abdominal Significantly reduce intra-operative blood loss During hysteroscopy- reduce procedure time, blood loss, failure rate & volume needed as distension medium Surgical planes difficult Medical Mx GnRH in combination with low dose HRT will achieve long term relief of HMB . ( in patient who decline surgery) HRT or Tibolone is added to relieve menopausal symptoms. Dose -Leuprolide (Depot) IM- 3.75mg monthly -11.25mg 3monthly Goserelin -3.6 mg monthly subcutaneous implant Naferalin- intra nasal spray Duration- should be GnRH alone for 3 months before adding HRT Add-back therapy with Tibolone- good fibroid shrinkage+ less SE SE- medical menopause Bone loss ( reduces BMD 6% annually ) Vasomortor symptoms, reduced libido Memory loss (reversible) Difficult surgical plain dissection in myomectomy |
Surgical management
| Myomectomy- Enucletion of uterine fibroids with reconstruction of uterus | |
| Risks with myomectomy | High intra-operative bleeding Post of anaemia, Need of blood Tx Febrile complications ,Post op ileus , Adhesion formation |
| Reducing surgical risks in myomectomy | Operative blood loss No benefit of using intra op oxytocin Myoma enucleation by morcellation- no effect Adhesion prevention Post op adhesion common- 59% after 2 years Dense small bowel adhesion to incision site Posterior wall incisions associates more than fundal or anterior wall incision Adhesion formation is less in laparoscopy than laparotomy Methods acceptable to use to prevent adhesions –(no evidence) Use anterior wall incisions where possible Minimal tissue handling Complete haemostasis Evacuating pelvic blood clots Less tissue handling, less drying Careful closer of uterine serosa to ensure no myometrium is exposed Use of omental, peritoneal, synthetic grafts over incisions. |
| Open abdominal myo mectomy | Temporary haemostasis of surgical field Tourniquet around cervix (through bilateral broad ligaments) Vassopressin 20 units in 100ml of N.saline (1ml vial-20units/ml ) Careful assessment of fibroids and plan the incisions. Transverse incisions better than longitudinal incisions- arteries of the uterus run transversely Avoid posterior wall incisions if possible- avoid bowel adhesion Avoid endometrial cavity entry Risk of Asherman syndromeRisk of inducing adenomyosisIf in doubt inject methyline blue vaginallyIf entered carefully suture with 3-0 vicryl Close myometrial defects in 2 or 3 layers with 1 vicryl. Close visceral peritoneum with PDS or non absorbable mono filament suture- promote healing and prevent adhesions Risk of emergency hysterectomy <1%Risk of blood Tx -8% |
| Laparoscopic myomectomy | Advantages Shorter hospital stay Fast recovery Less blood loss Less adhesions No difference in subsequent pregnancy, miscarriage, ectopic pregnancy, PTL or LSCS rates compared to open myomectomy No difference in scar rupture in pregnancy Limitations– fibroid size> 15cm, > 5fibroids Problems with morcellation Direct injury to intestine or blood vessels Seeding of fibroid particles leading to parasitic fibroid formation In case of LMS can disseminate the disease. |
| Hysteroscopic myomectomy I˚- HMB Infertility Recurrent miscarriage | Suitable for type 0,1 submucous fibroids (type2 with difficulty)Size less than 3-5cm Induce relief of menstrual symptoms 70-85% cases Even asymptomatic hysteroscopic resection of type 1,2 fibroids improves fertility (natural or IVF) Cost effective Methods Resectoscope slicing- for type 0Myolysis-electric currents passed through needle to destroy fibroidCryomyolysis-freezing probe is used. Risks Fluid overload Uterine perforationInfection |
| Uterine artery embolisation | Done under radiological screening with local anaesthesia First uterine arteries catheterized via femoral arteries Then Polyvinyl alcohol particles are injected to uterine arterial bed and occluded. Severe post procedure ischemic uterine pain can occur- need opiate analgesia Fibroid will shrink 60% in 6months. Pressure symptoms and pain symptoms improved in 80-90% cases. Median measured menstrual blood loss reduction following UAE has been 50% after 6–9 months and 80 % after 36–48 months. But re intervention rate 29% 25% if less than than 40yrs , 10% if above 40yrs Side effects puncture site bruising, pain and mild febrile reactions (post-embolisation syndrome) Treated with rest and NSAIDs and usually resolves within 10–14 days. Major side effects severe sepsis need hysterectomy < 1-2.9 % risk Later complications vaginal discharge in 30%- delayed passage of infarcted submucosal fibroids ovarian failure-1-2% mainly in women over 45. Pedunculated subserous fibroids may infarct and become detached into the peritoneal cavity Large submucosal fibroids may detach and cause cervical obstruction following embolisation, requiring surgical intervention Contraindication for UAE Suspicion of a sarcoma- MRI is mandatory prior to UAE Asymptomatic fibroid Current or recent pelvic infection relative CI – > 20weeks size UAE compared to hysterectomy/myomectomy shorter procedure and duration of hospital stay reduced risk of blood transfusion faster return to normal activities Need for further interventions higher in UAE. Up to 1/3 will need further intervention for fibroid in 5 yrs. But only 4-10% with surgery No difference in major complications But more minor complications No difference in ovarian failure in 5 yrs compared to TAH without BSO Less pregnancy rates compared to myomectomy (post procedure) Initial cost of UAE is much less compared to myomectomy. But overall 5 yr cost same due to need of repeat procedures. |
| MRI Guided Focus Ultrasound (MRIg-FUS) | High frequency high energy US waves destroy fibroid by coagulative necrosis after MRI guided thermal mapping of the fibroid according to tissue temperature Less vascular fibroids responds more Performed as an outpatient procedure under light sedation Study findings up to now Significant improvement in fibroid-related symptoms in 50–80 % Reduction in fibroid volume of 10–25 % after 6–12 months Treatment failed in up to 30 % by 12 months Advantages OP procedure No anaesthesia/ surgical trauma Rapid recovery & less morbidity Disadvantages Currently done only in women who do not have fertility wish Time consuming –average2-4 hrs Potential risk of skin , nerve, bowel burns Only small proportion of the fibroid volume is treated at a time Not suitable for fibroids close to the bowel, bladder or sacrum or for non-enhancing or pedunculated fibroids Presence of surgical scars is a contraindication. Up to 40 per cent of women are not eligible for the treatment (UAE -90% eligible) |
| Hysterectomy Vaginal hysterectomy for larger uteri | Definitive cure in patient who have completed the family Can be achieved up to 18 week size uterus. Uterine size can be reduced in vivo by mymectomy, bivalving etc. |
UAE complications
HRT with fibroid
- Combined oral HRT and Tibolone doesn’t increase fibroid size,
- Transdermal HRT increase fibroid size
- HRT will induce HMB in patient with submucosal fibroids
- Oral continuous combined HRT preparations or tibolone can be used for the relief of vasomotor symptoms in postmenopausal women with fibroids
- They may increase bleeding problems
| Preoperative assessment | Size Mobility | Decide on incision Pfannansteil Midline |
| After entry – inspection of pelvic structures | Careful assessment of location, size, and number of fibroids Inspect tubes and ovaries Look for adhesions | |
| Measures to reduce the blood loss | PRE OP PATIENT PREPERATION- Group AND SERVE GNRH AGONIST/ UAE/MISOPROSTOL INTRAOP Vasopressin 20ml 0.05U/ml at the site of uterine incision Sling around cervix Booney’s myomectomy clamp TRANSVERSE INCISION DELIVER FIBROIDS THROUGH SINGLE INCISION TRANAXEMIC ACID IV | |
| Deliver the uterus | Deliver the uterus through the incision and fibroids are inspected to assess the best safest incisional approach for enucleation without compromising the fallopian tubes, the endometrial cavity or ovarian/uterine vessels | |
| Enucleation of fibroids | Primary incision made down to the tumour Anterior surface of uterus as can enucleate the posterior wall fibroids through same incision – trans cavity myomectomy . Transverse incision preferable Depth – until the pseudo capsule of the fibroid reached Find the natural plane of cleavage, Can hold the fibroid with Myoma screw Vulsellum | Carry out enucleation Digitally or blunt dissection with a curved mayo scissors , When all apparent fibroids have been removed, myometrium is symmetrically palpated for residual fibroids |
| Suturing the myometrium | Fibroid cavities fully explored and thoroughly obliterated by No1 polyglycolic acid Pass through full thickness of myometrium No dead space should remain Usually need closure in 2 0r 3 layers Interrupted or continuous Most superficial layer Continuous transverse stich Uterine serosal layer Continuous non-absorbable monofilament suture – polypropylene | If endometrial cavity entered close with 3-0 polyglycolic acid In doubt confirm with vaginal methylene blue dye test |
| Measures to avoid adhesion prevention | Atraumatic surgical technique and suturingMinimize blood lossPrevent tissues become dry Omental interposition Over sew the peritoneumInterceed | |
| Release tourniquet if applied Check hemostasis | ||
| Cervical fibroid | Anterior Transverse division of the uterovaginal peritoneumMay need bisection of uterus | |
PRINCIPLES OF MYOMECTOMY
symptomatic cure
Preservation of uterus
Removal of maximum possible fibroids and reconstruction of uterus to its near normal anatomy.
Retaining fertility
Minimizing the peritoneal trauma and adhesions
Minimize the blood loss.
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