Rajesh Varma MA PhD MRCOGConsultant Obstetrician and Gynaecologist

Guy’s and St.Thomas’ NHS Foundation Trust

1415-1515: Tue 25th November 2008Hot Topics in Clinical Practice

Postgraduate Centre, Gassiot House, St.Thomas’ Hospital 1

Fibroids

Benign, but have 0.2% risk of malignant transformationOccur in 10% of HMBRecurrence risk after myomectomy (10% at 5 years)

May undergo degeneration (hyaline, fatty, Red during pregnancy)May become acutely painful (torsion, haemorrhage, sepsis, degeneration)

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Wamsteker K et al. Transcervical hysteroscopic resection of submucous fibroids for abnormal uterine bleeding: results regarding the degree of intramural extension. Obstet Gynecol 1993; 82(5):736-740.

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Do all women with fibroids need treatment?1. Asymptomatic

2. Abnormal Uterine Bleeding (AUB)

Menorrhagia, anaemia

Pelvic pressure effects (renal tract-ureter, bladder)

Pelvic Pain

3. Improve fertility (reduce risk of miscarriage)

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Myomectomy and AUBRemoval of the intracavity component of the submucous

fibroid improves AUB (70-80% improvement)

(Level II evidence)

Parker WH. Uterine myomas: management. Fertil Steril. 2007 Aug;88(2):255-71. 2007 Jul 20.

Varma R et al. Hysteroscopic myomectomy for menorrhagia using Versascope™ bipolar system: efficacy and prognostic factors at a minimum of one year follow up. In Press 2008, EJOG.

Paradox: Post operative adhesions may cause pain and infertility

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Klatsky PC et al. Fibroids and reproductive outcomes: a systematic literature review from conception to delivery. Am J Obstet Gynecol. 2008 Apr;198(4):357-66.

ASRM. Myomas and reproductive function. Fertility and Sterility, Volume 90, Issue 5, Supplement 1, November 2008, Pages S125-S130

Pritts EA et al. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril. 2008 Mar 11

Removal of the intracavity component of the submucous f ibroid improves fert i l i ty (RR 1.72; 95% CI 1.13-2.58)

Subserosal fibroids do not affect fertility outcome

Intramural fibroids appear to decrease fertility, but the results of therapy are unclear.

(Level II evidence)

Myomectomy and Fertility

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NICE (Jan 2007) HMB

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MEDICAL THERAPIESFIBROID SIZE AUB FERTILITY

NSAIDs No effect fibroid size

Decrease 30% No effect

COC No data Decrease 20-30% Contraceptive

GNRHa * (3m-6m)

Decrease 30%Decrease uterine volume by 35%

Decrease >80% Contraceptive

Progestins

LARC

LNG-IUSMirena(uterine cavity<12cm)

Decrease 30%

Decrease uterine volume by 35%

Decrease>60%

Breakthrough bleeding

systemic side effects

Contraceptive

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GnRHaSide effects Experienced by 95%Hot flushes; vaginal dryness; frontal headaches10% women stop treatment due to side effectsOsteopenia: >6m use

Prevented with add-back (tibilone, raloxifene)

Suitable women?

1. 3-4 m prior to myomectomy (hysteroscopic, abdominal) or hysterectomy (anaemia, transfusion, avoid midline entry) (concern: recurrence of small myomas & surgical dissection)

2. Late perimenopause as “short-term” treatment (+/- add-back)

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NEW MEDICAL THERAPIES (UNDER TRIAL)

FIBROID SIZE AUB FERTILITY

GnRH antagonist Ganirelix(sc daily/6m)

Decrease 30-40% Decrease Contraceptive

Mifepristone(5mg daily/6m)

Decrease 40%Decrease uterine size 40%

Decrease(risk of endometrial hyperplasia)

Contraceptive

SPRMAsoprisnil(10mg daily/6m)

Decrease Decrease Contraceptive

Aromatase Inhibitors

Decrease Decrease Contraceptive

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Fibroids >3cm size

Fertility preserved

Contraceptive

Fertility is potentiallyretained

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Abdominal Myomectomy>80% improvement in AUBVery low conversion rate to hysterectomyComparable risk to hysterectomy (organ damage,

transfusion)Correct pre-operative anaemia (EPO, GnRHa)TourniquetTransverse uterine incisions (parallel to arcuate vessels)Anti-adhesion : limit number of uterine incisions, anti-

adhesion barrier, drainageRe-treatment rates after myomectomy over 5-10 years

(symptom +/-fibroid recurrence):

10% single myomectomy vs. 25% multiple myomectomy

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Abdominal Myomectomy

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Value of adhesion prevention ?

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Hysteroscopic Myomectomy

Versapoint®Resectoscope

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Hysteroscopic myomectomy

Fibroid size Intracavity fibroid 90-100%

AUB Decrease >80%

Fertility Increase 40-60%

Secondary treatment (2yr 10%; 5yr 30%)

Complication rate 1-2% Uterine perforationSepsis; intrauterine adhesionsHaemorrhageHyponatraemic fluid overload

Additional treatment May be combined with endometrial resection or ablation-improved effect on AUB

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Hysteroscopic myomectomy:New developmentsUse of pre-operative GnRHa 3-4m

Improved video instrumentation

Bipolar resectoscopes: virtually eliminates risk of hyponatraeimc fluid overload syndrome

Outpatient microhysteroscopy and Versapoint®- concept of One Stop See-and-Treat gynaecology clinic

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3.5mm diameter disposable outer sheath 19

Video clip Outpatient fibroid resection

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New Interventional Technologies

Treatment in women with fibroid-related symptoms and not desiring future fertility

Uterine artery embolization (UAE)Magnetic resonance image-guided transcutaneous

focused ultrasound for uterine fibroids (MRgFUS)Magnetic resonance (MR) image-guided percutaneous

laser ablation of uterine fibroidsLaparoscopic or transvaginal uterine artery occlusionLaparoscopic cryomyolysis

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Aims: New Interventional TechnologiesImprovement in AUB, fertility and & QoL Avoid risks of major surgery (e.g. quicker recovery)Safety (lower complication rate)Sustained benefit (low re-treatment rate)Cost-effective

Insufficient evidence:

RCTs with long term data are lacking22

NICE (Oct 2004)

Audit and review clinical outcomes of allpatients having UAE.

Data should besubmitted to the British Society of Interventional Radiology registry (www.bsir.org).

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•Both uterine arteries are blocked by Interven. Radiol.•Contraindications :active genitourinary infection, genital tract malignancy•Relative contraindications:submucous myomas (check hysteroscopy prior to UAE), pedunculated myomas, recent GnRHa, previous UAE, postmenopausal status

Uterine artery embolisation (UAE)

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UAEFibroid size Reduced 30-50%

AUB Improved (>80% satisfaction)- sustained over 5yr

Fertility Reported case series: obstetric outcome uncertain

Secondary treatment

20-30% within 5yr

Complication rate

1-2w recovery back to work10-15% persistent vaginal discharge5% Post embolization syndrome (pain, fever, nausea, vomiting)10-15% risk premature ovarian failure (especially>45y)20% intra-abdominal adhesions<1% uterine necrosis/sepsis; death 1/10,000

•Gupta, JK et al. Uterine artery embolization for symptomatic uterine fibroids. Cochrane 2008. •G. Tropeano et al.Non-surgical management of uterine fibroids. Hum Reprod Update 2008;14(3): 259 – 274.•Agdi et al. Intraabdominal adhesions after uterine artery embolization. AJOG, Volume 199, Issue 5, November 2008, Pages 482.e1-482.e3 25

NICE (Sept 2007)

Audit and review clinical outcomes of allpatients having MRgFUS.

Data should besubmitted to the British Society of Interventional Radiology registry (www.bsir.org).

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Hindley, J. et al. Am. J. Roentgenol. 2004;183:1713-1719

Woman lying on ExAblate 2000 (InSightec) focused ultrasound system ready to be placed into MRI unit

MRI-guided focused ultrasound (MRgFUS)

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MRgFUS: outline of procedureClear pathway from the anterior abdominal wall to the

fibroid without passing through the bladder or the bowel Shaved anterior abdomenA urinary catheter is insertedUnsuitable for very large uteri (>24w) or fibroids (>10cm)IV analgesia and conscious sedationMaximum treatment time of 3 hr ; recovery 1-2 daysThermal ablation of selected fibroidReal time MR Thermometry (aiming >55 degrees C)Gadolinium-enhanced MRI performed immediately after

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Hindley, J. et al. Am. J. Roentgenol. 2004;183:1713-19

AFTER MRgFUS: Non-Perfused Volume (NPV) ratiocalculated from the gadolinium-enhanced MRI performed immediately after treatment

BEFORE

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MRgFUSFibroid size 20% at 2yr

AUB 60-70%

Higher NPV corresponds to greater fibroid size reduction and symptom relief at 12-month

Fertility Reported-mainly for single fibroid ablations

Secondary treatment ? 30%

Complication rate 10% (pain, vaginal discharge)

•E. A. Stewart et al. Sustained Relief of Leiomyoma Symptoms by Using Focused Ultrasound Surgery. Obstet. Gynecol., August 1, 2007; 110(2): 279 - 287.•Z. M. Lenard et al. Uterine Leiomyomas: MR Imaging-guided Focused Ultrasound Surgery--Imaging Predictors of Success. Radiology, Oct 1, 2008; 249(1): 187 – 194•Rabinovici J et al. Pregnancy outcome after magnetic resonance–guided focused ultrasound surgery (MRgFUS) for conservative treatment of uterine fibroids. Fertility &Sterility, In Press, 200830

ConclusionsMultiple treatment options existAdvances in hysteroscopyNew interventional technologies show early promise

However, • Several unanswered questions• Urgent need for further research• Need for increased consumer input

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