Aetiology

The precise aetiology of fibroids remains unknown. It is known that each fibroid is monoclonal, developing from a single cell. Electrophoresis patterns of glucose-6-phosphate dehydrogenase isoenzyme (A or B) demonstrated this in early studies (Townsend et al 1970). Later, polymerase chain reaction experiments confirmed monoclonality by the pattern of inactivation of the X-chromosome-linked phosphoglycerokinase gene (Hashimoto et al 1995). In the development of fibroid tumours, some form of initiation event must transform a normal myometrial cell into an abnormal ‘founding’ cell. Possible factors initiating this change include intrinsic myometrial abnormalities, elevated oestrogen receptors in the myometrium, hormonal changes and ischaemic injury (Parker 2007).

The initial transformation of the myometrial cell is likely to be accompanied in many cases by some form of cytogenetic or molecular alteration. Non-random chromosomal changes, such as translocations, duplications and deletions, can be identified in almost 50% of fibroids. The most frequent cytogenetic changes are translocations involving chromosomes 7, 12 and 14, and deletions in chromosome 7. The critical region affected in chromosome 7 appears to be on the long arm (7Q21–22). Several known genes are coded in this apparently critical region. These include genes for collagen type 1a 2, the MET proto-oncogene and the cytochrome P450 gene. There are rare instances of fibroids being due to mutations in a single gene, such as the mitochondrial enzyme, fumarate hydratase, involved in Krebs cycle and responsible for Reed’s syndrome (multiple cutaneous and uterine leiomyoma syndrome). However, in the vast majority of cases, uterine fibroids are not a single gene disorder. Once the fibroid tumour has been initiated, growth of the tumour occurs under the influence of sex steroid hormones (oestrogen and progesterone), peptide growth factors and the alteration of processes such as angiogenesis, apoptosis and extracellular matrix production.

It has long been known that fibroid growth is dependent on both oestrogen and progesterone. Fibroids only occur after the menarche, and they normally show a reduction in size after the menopause. They display reversible shrinkage after treatment with gonadotrophin-releasing hormone (GnRH) agonists. Although circulating serum oestradiol and progesterone levels are not altered in women with fibroids, fibroids have increased local oestrogen levels relative to the surrounding normal myometrium, partly due to increased fibroid expression of the aromatase enzyme (Parker 2007). They also have increased oestrogen receptor levels and increased responsiveness to oestrogen compared with normal myometrial cells. As for progesterone, the receptor levels have been shown to be increased in fibroids relative to the myometrium (Brandon et al 1993), and to upregulate the levels of some proteins which influence cell proliferation, such as the antiapoptotic protein Bcl-2 (Matsuo et al 1999). During the secretory phase of the menstrual cycle, when serum progesterone levels are at their peak, the highest mitotic activity is seen in fibroids. Similarly, high mitotic activity is seen during pregnancy. Treatment with the antiprogestin, mifepristone, has been shown to cause a marked decrease in fibroid tumour volume.

A large number of growth factors are produced locally in uterine fibroids and the myometrium. Some of them are overexpressed in fibroids, partially due to an exaggerated response to oestrogen. Some of the growth factors that have been found to have a potential role in the promotion of fibroid growth include: transforming growth factor-β, epidermal growth factor, basic fibroblast factor, insulin-like growth factor, platelet-derived growth factor and vascular endothelial growth factor (VEGF). The differential effects of these growth factors on cell proliferation, angiogenesis, extracellular matrix production and apoptosis are due to a variety of mechanisms including altered receptor levels and signalling pathways. For a detailed review, see Fleischer et al (2008).

Epidemiology

Age is the most common risk factor for uterine fibroids (Marshall et al 1997), although many of the studies examining incidence are cross-sectional or retrospective, rather than prospective and longitudinal. Race has been identified as an epidemiological factor in fibroid development. Black women are three to five times more likely to have uterine fibroids than White, Asian or Hispanic women (Marshall et al 1997). In addition, the fibroids in Black women are larger, more numerous, more symptomatic and diagnosed at an earlier age.

There is evidence of hereditary factors influencing fibroid development, despite no specific gene being identified. The development of fibroids clusters in families, and ‘familial’ fibroids appear to be more likely to cause symptoms than ‘non-familial’ fibroids (Okolo 2008). Twin studies show an increased incidence of fibroids in monozygotic twin pairs compared with dizygotic twin pairs.

Uterine fibroids are more common in nulliparous women, presumably due to the increased number of cycles over their premenopausal lifespan compared with parous women. Increasing parity decreases the incidence and number of fibroids. It is a myth that fibroids increase in size during pregnancy. In pregnancy, fibroids initially increase in size in the first trimester, but then decrease in size for the remaining two trimesters, with an overall volume that is either reduced or unchanged throughout the pregnancy (Hammoud et al 2006). Obesity, diabetes mellitus, polycystic ovary syndrome and hypertension all appear to be associated with an increased risk of uterine fibroids. In these conditions, a combination of insulin resistance, increased androgen levels and increased peripheral conversion of circulating androgens to oestrogen may alter the ovarian steroid hormonal stimulus to the fibroids. Smoking decreases the risk of uterine fibroids, presumably through a reduction in oestrogen levels.

The effects of exogenous sex steroid hormones on fibroid growth are particularly important as they comprise some of the most common treatments for menorrhagia, itself the most common symptom of uterine fibroids. Use of the combined oral contraceptive pill (COCP) has been associated with fibroid growth in some earlier studies (particularly older pill formulations with a higher oestrogen dosage), although the majority show no association or even a reduced risk of developing fibroids with COCP use. Therefore, fibroids are not a contraindication to the use of the COCP to treat menorrhagia. Both systemic and local administration of progestins to the uterus have been shown to be safe with fibroids. Depot medroxyprogesterone acetate injections reduce the risk of fibroids, and the levonorgestrel-containing intrauterine system (LNG-IUS; Mirena) reduces the overall volume of fibroid uteri. The LNG-IUS is also an effective treatment for menorrhagia associated with fibroids, although it is less effective than for dysfunctional uterine bleeding. In some patients, it may be difficult to insert the LNG-IUS due to cavity distortion by the fibroids. The effect of hormone therapy in postmenopausal women on fibroids has been reviewed by Ang et al (2001). They found that use of hormone therapy in women with fibroids caused continued fibroid growth, especially in the first 6 months of therapy, or at least a failure in normal postmenopausal regression. However, this did not correspond to an increase in symptoms.

Macroscopic appearance

Fibroids have a characteristically firm fibrous texture, from which the clinical term ‘fibroid’ is presumably derived. They frequently become calcified; rarely, they become ossified so that they are rock hard. Fibroids are round or oval-shaped tumours with a characteristic white whorled appearance on cross-section. They may be single but are more commonly multiple, present in varying sizes and in different sites (Figure 32.1). Tiny ‘seedling’ fibroids are commonly seen in association with larger tumours, possibly accounting for the high recurrence rate after surgical removal at myomectomy. Surgical removal of over 120 individual fibroids from a single patient has been recorded in the literature!

Figure 32.1 Uterus enlarged by multiple fibroids. The patient presented at 43 years with menorrhagia; she had a 13-year history of primary infertility. Septate vagina and double cervix (marked with rods).

Clinical classification

Subserosal fibroids

Subserosal fibroids project outwards from the uterine surface, covered with peritoneum, and may reach a very large size. Greater than 50% of the fibroid mass must project beyond the myometrium for the fibroid to be classified as subserosal. Many subserosal fibroids are pedunculated (Figure 32.2), making torsion a potential, although rare, complication. Sessile subserosal fibroids projecting from the fundal region may adhere to omentum or bowel, particularly if there has been coincidental inflammatory disease. Fibroids rarely become attached to the omentum; if they develop an alternative blood supply, they may become separated from the uterus, forming a so-called ‘parasitic’ fibroid. Subserosal fibroids arising from the lateral uterine wall may lie between the layers of the broad ligament where large tumours may displace the ureters, or bulge between the layers of the sigmoid mesocolon. Broad ligament fibroids arising from the lateral uterine wall differ from true broad ligament fibroids, which have no attachment to the uterus but have their origin in smooth muscle fibres within the broad ligament; for example, from the round ligament, ovarian ligament or perivascular connective tissue.

Figure 32.2 Multiple subserous fibroids, some pedunculated. Specimen width 350 mm.

Submucosal fibroids

Submucosal fibroids are less common, comprising approximately 5% of all leiomyomata. By definition, more than 50% of the fibroid mass projects into the uterine cavity and is covered by endometrium. Submucosal fibroids may cause abnormal uterine bleeding and infertility. Uterine enlargement is not usually evident unless other fibroids are also present. Submucous fibroids are regarded as suitable for hysteroscopic resection. Pedunculated submucous fibroids on a long stalk may prolapse through the cervix (Figure 32.3), where they may cause intermenstrual bleeding or become ulcerated and infected.

Figure 32.3 Submucous fibroid protruding through cervix. The patient, aged 44 years, presented with a 3-week history of continuous bleeding; haemoglobin level was 6.9 g/dl.

Vascular supply

Perfusion studies with injections of ¹³³Xe radiocontrast and gadolinium-enhancement contrast material during magnetic resonance imaging (MRI) show reduced blood flow through fibroids compared with myometrium, but increased blood flow in a compressed rim around the fibroid. Immunohistochemical studies of the microvascular density of fibroids demonstrate reduced vessel area staining in fibroids compared with the myometrium (Casey et al 2000), and with the difference increasing after the menopause (Weston et al 2005); this is probably due to relatively faster collapse of the myometrial cellular and extracellular matrix volume relative to that of the fibroid. Electron microscopy of corrosion vessel casts of fibroids performed by Walocha et al (2003) shed even greater insight into the vasculature of fibroids. A single larger artery usually provides the major blood supply to the fibroid, sending small nutrient arteries to penetrate the capsule. The vasculature of fibroids is reduced compared with the surrounding myometrium, but is most markedly reduced in smaller fibroids, with the only area of greater vascularity than the myometrium being the compressed rim of perifibroid tissue around the periphery of larger fibroids. Walocha et al (2003) proposed an initial regression of the vasculature within smaller fibroids, followed by an intense proangiogenic response, whereby the vascular rim around the fibroid acts as the source for neovascularization of the growing fibroid.

The relative avascularity of the fibroid core appears to be at odds with the finding of increased VEGF in fibroids compared with the myometrium. However, the VEGF within the interior of the fibroid may be trapped in a biologically inactive fashion within the expanded extracellular matrix of the fibroid. A gene expression microarray experiment performed by Weston et al (2003) specifically targeting angiogenesis-related genes found a reduced level of two angiogenesis promoters (CTGF and CYR61) and increased expression of collagen IVa 2; a precursor for the angiogenesis inhibitor, canstatin. This triad of gene expression differences may, in part, explain the relatively avascular fibroid tissue.

Microscopic appearance

Microscopically, fibroids are composed of smooth muscle cell bundles, also arranged in whorl-like patterns (Figure 32.4A), admixed with a variable amount of connective tissue, although the latter rarely predominates. The relatively poor blood supply to individual fibroids may result in degenerative changes, particularly within large tumours. Hyaline degeneration (Figure 32.4B) is the most common, resulting in a smoother and more homogeneous consistency, which may become cystic if liquefaction occurs. Much more rarely, fatty change may develop. This is distinct from the true lipoma of the uterus, which is extremely uncommon. Calcification (Figure 32.5) is a later consequence of degeneration secondary to circulatory impairment. It characteristically occurs after the menopause, although it may occur earlier in subserosal fibroids with narrow pedicles.

Figure 32.4 Leiomyoma of uterus. (A) Bundles of elongated smooth muscle cells in both longitudinal (left) and transverse planes (×160). (B) Focal hyalinization. Smooth muscle bundles are separated by dense hyalinized connective tissue (×320).

Images courtesy of Dr K. Maclaren.

Figure 32.5 (A) Calcified fibroid seen on hysterosalpingogram. (B) Ultrasound appearance of the uterus: two fibroids seen in transverse plane with calcified fibroid to left (top); calcified fibroid shown in longitudinal plane (bottom).

Image (A) courtesy of Dr B. Muir.

There are a number of recognized histological variants of the usual microscopic appearance of uterine leiomyomata. The term ‘cellular leiomyoma’ is used when the density of the smooth muscle cells is significantly greater than usual, but there are no other atypical features such as increased mitotic activity or abnormal mitoses. Some pathologists use the term ‘neurilemmoma-like leiomyoma’ when there is striking lining-up or palisading of the tumour nuclei. This resembles nerve sheath tumours. Sometimes, fibroids are composed of polygonal cells rather than spindle cells. This type of nuclear pleomorphism is associated with giant cell formation; such tumours are called ‘symplasmic’, ‘bizarre’ or ‘atypical’ leiomyomas.

One differential diagnosis of uterine fibroids is that of adenomyosis, which may have a similar macroscopic appearance to uterine fibroids. However, in adenomyosis, there is no clear demarcation from the adjacent normal tissue. Leiomyosarcoma is a malignant tumour of the smooth muscle of the uterus. The macroscopic appearance of leiomyosarcoma shows an irregular invasive margin and a variegated cut surface. The microscopic appearance of leiomyosarcoma shows high cellularity, nuclear pleomorphism, a high mitotic rate with abnormal mitoses and areas of necrosis with infiltrating margins. Typically, the number of mitoses per 10 high-power fields in leiomyosarcoma is greater than 10, in contrast to standard leiomyoma where the number of mitoses per 10 high-power fields is less than five.

Finally, there are rare groups of uterine tumours with histological features intermediate between fibroids and leiomyosarcomas. These are termed ‘smooth muscle tumours of uncertain malignant potential’. Other rare tumours include endometrial stromal nodule, diffuse leiomyomatosis and endometrial stromal sarcoma.

Crow et al (1995) examined the microscopic appearance of uterine fibroids after treatment with GnRH agonists. They found considerable variation between fibroids after a course of treatment and subsequent myomectomy or hysterectomy. Decreases in the extracellular matrix, in particular, cause extreme crowding of tumour nuclei, resulting in a densely cellular appearance of such fibroids on microscopic examination. For the inexperienced pathologist, this will be worrying in terms of possible malignancy. There should not, however, be mitotic activity, cytological atypia or coagulative necrosis.

Abnormal bleeding/menorrhagia

The proportion of uterine fibroids causing abnormal uterine bleeding — menorrhagia being the most common abnormal pattern observed — is uncertain but is usually quoted as 30–50%. The exact mechanism by which fibroids cause menorrhagia is unknown. The many theories include: increase in endometrial surface area (Figure 32.6), increased vascularity of the uterus, vascular congestion due to fibroid compression of the myometrial venous drainage, abnormal uterine contractility, dysregulation of growth factors causing disordered angiogenesis of the uterine vasculature, and ulceration of the endometrial layer overlying submucous fibroids.

Figure 32.6 Hysterosalpingogram showing enlargement of uterine cavity and filling defect from intramural fibroid. Extensive endometriosis had complicated laparoscopic sterilization (hence the two clips on the left tube).

Image courtesy of Dr B. Muir.

As fibroids are so common, and so often asymptomatic, menorrhagia in a woman with uterine fibroids should not automatically be ascribed to the fibroids themselves. Other possible aetiologies for menorrhagia should always be considered and excluded, including coagulopathies such as von Willebrand’s disease (Munro and Lukes 2005). In a study of self-reported bleeding patterns by 878 women (aged 35–49 years) screened for the presence and size of myomas, Wegienka et al (2003) reported findings on the association between fibroids and bleeding pattern. Of women with fibroids, 46% reported ‘gushing’ episodes during their periods, compared with 28% without fibroids. Gushing episodes and length of periods were related to the size of the myomas, but not to their number or location. The worst bleeding was found with fibroids over 5 cm in diameter, with women using three more pads or tampons on heavy bleeding days than women with smaller fibroids.

Pelvic pain and pressure symptoms

Fibroids do not usually give rise to pain. In a cohort study of 635 non-care-seeking women, symptoms of dyspareunia, dysmenorrhoea and non-cyclic pelvic pain were examined for their association with the presence and size of uterine fibroids (Lippman et al 2003). The 96 women with fibroids had only a slight increase in non-cyclic pain or dyspareunia, but no increase in dysmenorrhoea, and no relationship was found between the size or total volume of fibroids and pain symptoms. Where fibroids are associated with pain or abdominal discomfort, it is usually described as ‘pressure’ or a ‘dragging’ sensation. It is surprising that even in the presence of multiple fibroids, menstruation may be painless.

Exceptionally, the presentation of fibroids may be acute on account of torsion of a fibroid on a narrow pedicle, or degeneration. Attempted expulsion of a large submucous fibroid through the cervix causes uterine cramp associated with bleeding, and may be mistaken for spontaneous abortion, particularly with the finding of a dilated cervix and a protruding mass. This situation has been described as a complication of treatment with GnRH analogues. Rarely, it can result in uterine inversion. Torsion or painful degeneration presents with an acute abdomen, and is commonly confused with complications of ovarian neoplasia. Distinction between these conditions is particularly important in pregnancy complicated by red degeneration of a fibroid, in order to avoid subjecting the woman to unnecessary laparotomy.

The location and size of fibroids determines symptoms from pressure on adjacent organs. A posterior wall fibroid can cause lower back pain, or constipation and tenesmus if the rectosigmoid is compressed. Anterior wall fibroids compressing the bladder may cause urinary frequency, nocturia and urgency in some women. It has been shown that reduction in size of such fibroids after either GnRH agonists or uterine artery embolization (UAE) causes a decrease in associated urinary symptoms (Parker 2007). Cervical fibroids causing compression of the bladder outlet may present with acute retention of urine (Figure 32.7), although this is rare.

Figure 32.7 Cervical fibroid growing anteriorly in the supravaginal cervix. Presentation was with frequency of micturition followed by acute urinary retention.

Reproductive outcomes

Malignant transformation in fibroids: where is the evidence?

For the ‘worried well’, the diagnosis of a uterine fibroid naturally raises the issue ‘Can it become cancer, doctor?’. Some women continue to have a hysterectomy or a myomectomy ‘just in case’ the uterine fibroid grows into a uterine sarcoma. Gard et al (1999) reviewed uterine leiomyosarcomas in Australia, conducting a retrospective survey of major teaching hospitals in Sydney and Melbourne. They identified 49 patients treated over a 28-year period, equating to approximately one leiomyosarcoma of the uterus per million Australian women per year. There is considerable doubt regarding whether or not a myomectomy would be protective in any case, as most leiomyosarcomas are believed to arise de novo, unrelated to existing benign fibroids. Malignant transformation of fibroids is believed to be exceedingly rare; genetic differences between uterine fibroids and leiomyosarcomas point to distinct origins. Given that leiomyosarcomas can also arise outside the uterus, even a hysterectomy may not be completely protective of this rare tumour. Removing asymptomatic fibroids from women on this basis cannot be justified. Until proven otherwise, sarcomatous ‘change’ in a fibroid is a myth. Even rapid myoma growth almost never indicates a uterine sarcoma. No cases of sarcoma were found in a study of 198 fibroid uteri with an increase in size greater than 6 weeks over a 1-year period (Parker et al 1994).

There are many types of uterine sarcoma, all differing in their biological behaviour. The clinical benefits of oophorectomy, lymphadenectomy and cytotoxic chemotherapy remain controversial for these various types of leiomyosarcoma, not least because they are rare, even in the clinical experience of gynaecological oncologists.

Ultrasound

Ultrasound should always be used to confirm or clarify the nature of a pelvic mass. Both the transabdominal and transvaginal route should be taken in examining possible fibroids. Larger fibroid uteri may only be fully visible via the abdominal route, but smaller lesions and submucosal fibroids may be better visualized via the vagina. Ultrasound is rapid, inexpensive and uses no ionizing radiation, making it the undisputed first-line imaging investigation for fibroids. Even in relatively unskilled hands, it will diagnose pregnancy and differentiate between cystic and solid lesions (Figure 32.8). With appropriate training and experience, the site and nature of a pelvic mass may be predicted with accuracy in over 80% of cases. Fibroids appear as an enlarged uterus with patchy echogenicity. Serial ultrasound examination is of value in monitoring fibroid size during medical or conservative treatment. The volume of individual fibroids or of the whole uterus can be calculated by measuring the diameter in three planes at right angles and using the formula 4/3πr³, where r is the radius.

Figure 32.8 Ultrasound appearance of uterus enlarged by multiple fibroids, showing patchy echogenicity.

Image courtesy of Dr B. Muir.

Sonohysteroscopy, where the use of ultrasound is accompanied by the instillation of sterile saline into the uterine cavity via a balloon catheter, enables improved delineation of intrauterine pathology, such as submucosal fibroids. It also allows the diagnosis of endometrial polyps and intrauterine adhesions. Even large submucosal fibroids, up to 4–5 cm in diameter, can then be considered for hysteroscopic resection, especially if more than 50% of the volume of the tumour is projecting into the uterine cavity.

Magnetic resonance imaging

While it is an excellent imaging modality for mapping the precise location and size of uterine fibroids, the use of MRI is limited by its expense and availability. While the accuracy of ultrasound is operator dependent, MRI has an overall low interobserver variability. It allows the diagnosis of adenomyosis, a common differential diagnosis of uterine fibroids. Nonetheless, until the cost and access to this imaging modality improve, it will not be a routine investigation for the diagnosis of myomas.

Hysteroscopy

Hysteroscopy as an investigational procedure is very effective for the diagnosis of submucosal fibroids. Diagnosis and treatment can occur at the same time if the appropriate equipment (a resecting hysteroscope) is available. The use of hysteroscopy allows endometrial sampling to be performed at the same time to diagnose coexisting endometrial pathology (endometrial hyperplasia, cancer or polyps). However, it is an invasive procedure, with both surgical and anaesthetic risks that are not incurred by the use of ultrasound alone.

Laparoscopy

Diagnostic laparoscopy can be of clinical value if the uterus is not larger than a 12-week gestation size and there is associated infertility or pelvic pain. It may reveal the presence of coincidental endometriosis, pelvic adhesions or other tubal pathology. Laparoscopy will also differentiate between a pedunculated fibroid and an ovarian neoplasm if there is an individual patient where this diagnosis is unclear on the basis of clinical and ultrasound findings.

Expectant management

At least 50% of fibroids are asymptomatic, and provided that their nature can be determined with reasonable certainty, active treatment is unnecessary. While traditionally, surgical removal has been advocated when the uterine size exceeds that of a 12-week pregnancy, this policy has been challenged (Reiter et al 1992). The mere presence of a fibroid uterus carries no long-term detrimental effects; spontaneous regression of the fibroid(s) after the menopause may be anticipated. Sarcomatous change in fibroids if they are left in situ is a myth.

Medical management

There are two main objectives in the medical treatment of uterine fibroids: relief of symptoms associated with fibroids, and reduction in fibroid size. No medical treatment has been show to cause complete regression of fibroids. Where medical treatments cause fibroid shrinkage, there is a high rate of regrowth following cessation of treatment, as well as a recurrence of symptoms. This has severely limited the use of medical treatment for fibroids.

Hysterectomy

Management of symptomatic uterine fibroids has traditionally been surgical. Despite the existence of newer, less invasive techniques, their lack of availability in most centres means that, for most women, the decision for treatment continues to be between hysterectomy or myomectomy. The decision to perform a hysterectomy should not be undertaken without due consideration of the alternatives. For women who wish to preserve their reproductive function, myomectomy or medical treatment must be considered. Hysterectomy is clearly an effective treatment for fibroids, but it carries considerable risk of major complications (up to 10% with a large fibroid uterus).

The route selected for hysterectomy will depend on the size of the uterus, the situation of the fibroids and the history of any previous surgical procedures. Abdominal hysterectomy with ovarian conservation (Figure 32.9) will be the procedure of choice where fibroids are very large. For gynaecologists who favour vaginal hysterectomy, consideration should be given to preoperative shrinkage with a GnRH agonist, as described below. Similarly, a reduction in volume and vascularity may facilitate removal of a very large uterus by the abdominal route. Abdominal hysterectomy is rendered difficult in the presence of large fibroids arising from the cervix or situated in the broad ligament. It is also more complicated if there are adhesions from previous myomectomies, or from associated endometriosis or pelvic inflammatory disease. Difficult access to the pelvis during hysterectomy for large fibroids will be rendered easier by prior enucleation of the fibroids. The ureters may be vulnerable during an operation to remove a broad ligament fibroid, and their pathway must always be identified. Regardless of the direction of displacement, they are always extracapsular. In the case of a large cervical fibroid, an alternative approach is hemisection of the uterus, followed by enucleation of the fibroid in order to gain access to the uterine arteries and cervix. These techniques are described in detail elsewhere (Monaghan 1986).

Figure 32.9 Hysterectomy specimen from uterus enlarged to 16-week gestation size by single intramural fibroid and several small seedling fibroids. Uterine volume was 575 ml.

The increasing popularity of minimal access surgery has led to the use of laparoscopic-assisted methods of vaginal hysterectomy in women with large fibroids, sometimes following prior shrinkage with a GnRH agonist. Even a large fibroid uterus can be removed via the laparoscopic method, using a morcellator to remove the fibroid and/or uterus piecemeal. However, the place of laparoscopic-assisted or total laparoscopic hysterectomy in the treatment of uterine fibroids remains unclear due to the lack of comparative studies with more traditional surgical methods.

Abdominal myomectomy

Removal of individual fibroids was first reported in the middle of the 19th Century, although current surgical techniques are largely attributable to Victor Bonney who described a personal series of 403 cases. The main indication for myomectomy is a woman with symptomatic fibroids who wishes to retain her uterus.

Unless the fibroid uterus is exceptionally large (greater than a 20-week gestation uterus), a Pfannenstiel or lower transverse incision should provide adequate access, as the uterus can usually be mobilized through the wound with the assistance of a myoma screw. If it is a repeat myomectomy, however, bowel adhesions are common and may necessitate a vertical midline incision. The uterus with the fibroid(s) is exteriorized after careful inspection of the pelvis for coexistent pathology. The uterine incision is made with either cold knife or cutting diathermy, the fibroid(s) grasped with either a myoma screw or tenaculum, and the fibroid enucleated either with finger or scissors around the usually clear tissue plane of the pseudocapsule. Every effort should be made to remove all palpable fibroids. After removal, the cavities left behind should be closed meticulously with figure-8 sutures (the authors usually use absorbable Vicryl sutures) to prevent haematoma collection, and the serosal layer should be closed with a continuous subserosal suture.

Complications

The two major problems associated with abdominal myomectomy are intraoperative blood loss (which can be severe and may necessitate a hysterectomy to control bleeding in 1–2% of patients) and postoperative adhesion formation. The risk of adhesions is increased with posterior and multiple uterine incisions. They are usually a consequence of difficulties with haemostasis and oozing from incision lines. Adhesions after incisions on the posterior wall are potentially more serious because of involvement of the uterine tubes and ovaries. To minimize adhesion formation, as many fibroids as possible should be removed through a single incision (Figure 32.10), preferably at the fundus or anterior uterine wall. Some authorities recommend removal of posterior wall fibroids via the uterine cavity through an incision on the anterior abdominal wall, although this causes a deliberate breach of the uterine cavity and entails a risk of intrauterine adhesions. Bonney (Monaghan 1986) described a ‘hood’ method of closure of the cavity left after enucleation of a large single posterior tumour (Figure 32.11), suturing the redundant flap of serosal-covered myometrium over the fundus and low down on to the anterior abdominal wall to avoid adhesion formation. Keeping tissues moist, using wet packs to displace the bowel and minimal tissue handling is thought to reduce adhesions. The use of barrier agents, such as Interceed, Seprafilm and Gore-Tex, to reduce adhesions has been the subject of a recent Cochrane review (Ahmad et al 2008). While the use of Interceed does reduce postoperative adhesion formation after surgery, there is insufficient evidence to show that the reduced adhesion rates correspond with increased fertility and pregnancy rates.

Figure 32.10 Removal of subserous, intramural, submucous and posteriorly located intramural fibroids through a single anterior incision.

Reproduced with permission of the American Society for Reproductive Medicine, formerly the American Fertility Society.

Figure 32.11 (A) Closure of myomectomy through transverse posterior incision using Bonney’s ‘hood’, showing final anterior suture line and Bonney’s clamp in place. (B) Construction of Bonney’s hood showing the capsule after enucleation (left) and the hood in place (right).

EFFECTIVE GYNECOLOGICAL DAY SURGERY, DAVID HEALY & OSWALD PETRUCCO, 1998 LIPPINCOTT—RAVEN PUBLISHERS.

Both mechanical and medical methods have been described to reduce intraoperative blood loss. Preoperative treatment with GnRH analogues for at least 3 months prior to either hysterectomy or myomectomy has been shown to increase both preoperative and postoperative haemoglobin and haematocrit (Lethaby et al 2000). This also reduced the size of the fibroids by approximately 50%, and reduced pelvic symptoms, operating time, duration of hospital stay, blood loss and rate of requiring a vertical incision. Disadvantages of the use of GnRH analogues include the cost, menopausal symptoms during treatment and bone demineralization with prolonged use. While an increased risk of fibroid recurrence has been reported, due to shrinkage of smaller fibroids making them undetectable at surgery, this was not confirmed in a systematic review. While the use of GnRH analogues has been criticized for making the pseudocapsule plane of cleavage between the fibroid and the surrounding myometrium less well defined, this has not been the authors’ experience. Intraoperative interventions to reduce blood loss during myomectomy have undergone a Cochrane review by Kongnyuy and Wiysonge (2007). One such method is the use of Bonney’s myomectomy clamp (Figure 32.11A), which is placed across the lower uterus to occlude the uterine arteries. It can be used in conjunction with ring forceps to occlude the ovarian blood supply. An alternative is the use of a rubber tourniquet or catheter, placed around the uterus through an incision in the broad ligament at the level of the lower segment. During a long operation, intermittent release of the clamps or tourniquet is recommended every 10–20 min to prevent ischaemic damage to the tissues. Many intraoperative techniques have been advocated to reduce blood loss. Those that have been found to be effective (with weighted mean difference in blood loss with their use given in parentheses) include intramyometrial vasopressin (−299 ml), intramyometrial bupivacaine plus epinephrine (−69 ml), pericervical tourniquet (−1870 ml) and vaginal misoprostol (−149 ml).

The issue of mode of delivery in subsequent pregnancies following myomectomy where the uterine cavity has been breached is controversial. While common advice given to patients is that all myomectomies involving breach of the uterine cavity mandate caesarean sections in subsequent pregnancies, the evidence for this advice is limited (Parker 2007). During pregnancy and labour, rupture of the uterus after fibroid surgery is an extremely rare event. However, rupture after laparoscopic myomectomy may be higher than after abdominal myomectomy.

Hysteroscopic resection

Submucosal fibroids (such as those illustrated in Figure 32.12) are best removed hysteroscopically. Resection of the fibroid via the hysteroscope may be combined with endometrial ablation for the relief of menorrhagia if the woman has completed childbearing. Hysteroscopic surgery has been used for the removal of lesions measuring up to 7 cm in diameter, although many authorities would set a maximum of 3–4 cm (Agdi and Tulandi 2008). With larger fibroids, GnRH analogues can be used to shrink the tumour prior to surgery. Preoperatively, some surgeons use intravaginal misoprostol to soften and dilate the cervix, and allow easier insertion of the instruments. The uterine cavity is distended with a non-conductive glycine solution, and continuous irrigation with an infusion pump is employed to maintain visibility. A loop electrode is placed distal to the myoma, and sliced towards the cervix under vision. At all times, the loop should remain under vision to reduce the risk of perforation of the uterus and damage to bowel or other internal organs. Any uterine perforation necessitates abandoning the procedure. Lengthy procedures carry the risk of ‘water intoxication’ and electrolyte disturbances, and a strict check should be made on the amount of glycine absorbed. The major advantage of hysteroscopic resection is the avoidance of major surgery, as well as easier access to submucosal fibroids compared with the abdominal route.

Figure 32.12 Submucous fibroids (subtotal hysterectomy specimen).

Some authors (Donnez et al 1990) advocate the use of the neodynium:YAG laser for larger fibroids, after prior shrinkage with a GnRH analogue. Laser ablation can also be used for smaller fibroids.

Laparoscopic myomectomy

Despite laparoscopic myomectomy being performed for almost two decades, there is little evidence and considerable debate about its place in the treatment of uterine fibroids. It is still not clear how the complications of the procedure compare with open myomectomy, and reported results from studies and case series are highly operator dependent. The purported advantages of the technique include shorter hospital stay, less postoperative pain, faster recovery and better visualization of adjacent organs (Agdi and Tulandi 2008). However, there have been reports of a higher risk of recurrence of fibroids, due to the inability to palpate the uterus and remove smaller coexisting fibroids laparoscopically. There is also a possible increased risk of uterine rupture in pregnancy and labour. Larger fibroid uteri may be impossible to remove laparoscopically, although preoperative shrinkage with GnRH analogues may help in these cases. The procedure is challenging, with skills only available at a few centres, and is time consuming compared with an open myomectomy, subjecting the patient to a longer period of anaesthesia.

Generally, the procedure involves intramyometrial injection of epinephrine, followed by enucleation of the fibroid via diathermy incision, laparoscopic suturing in multiple layers of the remaining cavity, and morcellation and removal of the fibroid through one of the laparoscopic ports.

Recurrent fibroids after surgery

Reported cumulative recurrence rates after myomectomy are up to 50% at 5 years, with approximately 20% of women undergoing hysterectomy. It is not clear whether ‘recurrent’ fibroids after conservative treatment represent regrowth of existing tumours or de-novo development of additional fibroids. The literature is of poor quality with inconsistent reports regarding the definition of ‘recurrence’, the length of follow-up, the percentage of women lost to follow-up and why, and the use of other treatments which might affect recurrence. From the available literature, a larger preoperative fibroid size, an increased number of fibroid tumours, increasing fibroid penetration into the myometrium and any residual tissue at the completion of the procedure were all associated with increased risk of recurrence. These factors, leading to the development of further symptomatic fibroids after treatment, seem to occur with medical therapies, UAE or myomectomy.

Uterine artery embolization

Transarterial embolization for the successful treatment of obstetric and gynaecological haemorrhage has been practised for 30 years. It has also been used subsequently to treat uterine arteriovenous malformations. The initial report of the use of UAE to treat symptomatic fibroids was by Ravina et al in 1995. Its use has increased in popularity since then, and has been the subject of thorough recent reviews (Hickey and Hammond 2008, Tropeano et al 2008).

Technique

UAE is a percutaneous, image-guided procedure performed by an interventional radiologist. With regional anaesthesia or sedation, an angiographic catheter is placed under X-ray guidance into the uterine arteries via the common femoral artery. Embolic agents (usually polyvinyl alcohol particles or tris-acryl gelatin microspheres) are then injected into both uterine arteries to occlude them. Occlusion is confirmed angiographically and the catheters are removed (Figure 32.13). While the normal myometrium rapidly re-establishes its blood supply due to an extensive collateral circulation, the fibroids are supplied by end-arteries and undergo necrosis. The procedure takes approximately 1 h, and exposes the woman’s ovaries to 20 rads, the equivalent of most routine diagnostic imaging procedures. The date of the last menses should be assessed, and a urine pregnancy test should be performed prior to the procedure to exclude pregnancy. Pretreatment with GnRH agonists may hamper UAE treatment for fibroids and is contraindicated, unlike for surgery.

Figure 32.13 Catheter inserted via right femoral artery. The contrast medium clearly shows marked vasculature around a fibroid prior to embolization.

MRI-guided focused ultrasound

MRI-guided focused ultrasound uses high-intensity ultrasound waves directed to a precise area of tissue via MRI (performed concurrently), causing a temperature rise sufficient to induce coagulative necrosis in the tissue (Tropeano et al 2008). The aim is controlled localized thermal ablation of the fibroid tissue, while leaving the surrounding normal tissues undamaged. The ultrasound waves are delivered to the fibroids via the anterior abdominal wall while the patient is sedated and lying prone on the MRI table. The procedure takes approximately 3 h, but patients go home 1 h post procedure and return to work in 48 h.

Preliminary reports suggest that the procedure is associated with less pain and postoperative complications than UAE, but is less effective as the maximum volume of fibroid tissue that can be treated is limited. While there is theoretically less risk of collateral damage to the ovaries, larger scale studies need to be performed before the safety of this new procedure can be compared with UAE.