Medical treatment of fibroids is mainly restricted to their effect on short term symptomatic relief of menstrual disturbances and pain and for preoperative treatment of fibroids to reduce volume or correct anaemia but not as a stand alone treatment for fibroids associated with infertility.

GnRH agonists can be used for pre-operative correction of anaemia in severely anaemic patient or to reduce uterine/fibroid volume and to enable minimally invasive surgical approach as well as reduction in peri-operative blood loss [9]. They suppress the hypothalamic-pituitary-ovarian axis by inhibiting release of FSH and LH resulting in decreased oestrogen production. In addition, GnRH agonists also directly inhibit expression of aromatase P450 activity in the cells of the fibroid inhibiting local oestrogen production [80]. GnRH agonist treatment causes confluent nodular hyaline degeneration and hydropic degeneration necrosis of the fibroids [57, 81–83]. Administration of GnRHa for 3 months has been shown in various studies to significantly reduce the volume of fibroid by about 35–65 % [84] and induces amenorrhea significantly reducing symptoms in the short term.

The selective progesterone receptors modulator (SPRM) ulipristal acetate is currently being investigated for its role in the treatment of fibroids. A placebo controlled randomised control trial has shown that 91 and 92 % of women taking 5 and 10 mg of ulipristal acetate daily respectively for the symptomatic treatment of fibroids had significant reduction in uterine bleeding compared to 19 % in women taking placebo [85]. Another study comparing ulipristal acetate to GnRH agonist shows that ulipristal acetate (at both 5 and 10 mg) had comparable clinical outcomes and reduction in fibroid volume when compared to once-monthly injections (3.75 mg) of the GnRHa leuprolide acetate [86] an effect which persist up to 6 months of discontinuation of treatment [86]. The down side of these agents is the associated altered endometrial changes, the long term significance of which is not yet known.

Aromatase inhibitors have also been explored in the treatment of uterine fibroids. The use of aromatase inhibitors is based on their role in inhibiting aromatase p450 activity which is highly expressed in the fibroid tissue. A 3 month course of the aromatase inhibitor letrozole 5 mg daily has been shown in a prospective study to significantly reduce fibroid volume and improve fibroid associated symptoms but unlike GnRH agonist, does not affect bone mineral density [87]. A more recent randomised controlled trial showed that letrozole at 2.5 mg/day reduced fibroid size by 45.6 % versus 33.2 % compared with GnRH agonist triptorelin [88]. A Cochrane review did not find any evidence to support the use of aromatase inhibitors in the treatment of symptomatic uterine fibroids [89].

Myomectomy can be performed through the traditional abdominal route or a minimally invasive laparoscopic approach for intramural and subserosal fibroids whilst submucousal fibroids can be effectively resected hysteroscopically [62]. These surgical techniques are discussed in detail in the following chapters.

A more novel approach to myomectomy is that of Robotic-assisted surgery designed as an alternative to overcome the technical limitations of conventional laparoscopic myomectomy [90–92]. The surgeon uses a robotic system to control the instruments for laparoscopic instead of direct handling [93]. The main advantages of the robotic system compared with the traditional laparoscopic approach to surgery is improved ergonomics and precise vision [94]. The use of the robotic system offers the technical advantages of ability to remove large and more difficult uterine fibroids as well as improved closure of the myometrium compared with the conventional laparoscopic myomectomy [94]. Both robotic assisted laparoscopic myomectomy and traditional conventional laparoscopic myomectomy have been shown in several studies to reduce intraoperative blood loss, lower rate of postoperative adhesions and shorter hospital stay compared with laparoscopic and abdominal myomectomy [95–100]. Robotic-assisted laparoscopic myomectomy and abdominal myomectomy have comparable effectiveness in the symptomatic treatment of uterine fibroids [100]. Robotic-assisted laparoscopic myomectomy however is associated with greater residual fibroids when measured 12 weeks after surgery [100]. The major drawbacks of robotic-assisted laparoscopic myomectomy are the high cost of disposable instruments [101, 102] and the increased duration of operating time and the depth of surgical expertise required [103].

Long term pregnancy outcomes such as chances of conception, miscarriage rates and perinatal outcomes after robotic-assisted laparoscopic myomectomy have not yet been reported in large prospective series [104]. A small prospective observational study has quoted a conception rate of 69 % after robotic-assisted laparoscopic myomectomy [105]. A recent large multicentre retrospective study of 127 pregnancies showed that pregnancy outcomes are similar to the conventional laparoscopic myomectomy with Spontaneous miscarriage rate of 18.9 % (95 % CI 13.0, 26.6), Preterm delivery prior to 35 weeks of gestational age occurred in 17.4 % (95 % CI 10.9, 26.5) and 1.1 % risk of uterine rupture (95 % CI 0.3, 4.7) [106]. A large, well-designed prospective controlled study is needed to further ascertain fertility rates and pregnancy outcomes after robotic-assisted laparoscopic myomectomy.

A Cochrane review of two trials involving 158 participants found no evidence of benefit of safety and effectiveness of robotic-assisted laparoscopic surgery compared with conventional laparoscopic surgery for benign gynaecological diseases. Both conventional and robotic-assisted laparoscopic surgery for benign gynaecological diseases have comparable rates of conversions to open surgery as well as intraoperative outcome, complications, length of hospital stay and quality of life. Robotic laparoscopic surgery however, is associated with longer operation time higher cost compared with the laparoscopic surgery [107].

In recent years, several other treatment modalities alternative to medical and surgical have been described in the management of symptomatic fibroids. These include bilateral uterine artery embolisation, laparoscopic or magnetic resonance imaging-guided cryomyolysis and magnetic resonance imaging guided focused ultrasound surgery and laparoscopic uterine artery ligation. Promising reductions in fibroid size and control of symptoms have been reported with these techniques but more data are necessary particularly regarding their effect on future fertility [84, 108–112].

Cryomyolysis is a new minimally invasive treatment modality for symptomatic fibroids [113, 114]. Liquid nitrogen is passed through a cryoprobe inserted directly into the uterine fibroid to create a temperature below −90 °C within the fibroid which results in the formation of an ice ball within the fibroid and subsequently undergoes necrosis. Cryomyolysis has been shown in studies to be an effective method of treatment for symptomatic fibroids [115, 116]. Traditionally, cryomyolysis has been performed by laparoscopy but in recent years, MRI-guided cryomyolysis has been used as a more precise and less invasive alternative to laparoscopic cryomyolysis. MRI-guided cryomyolysis has the added advantages of direct visualisation of the ice ball, monitor and maintain the temperature at the periphery of the ice ball at 0 °C to prevent damage to the surrounding structures [116, 117]. A mean fibroid volume reduction of 50–62 % and significant improvement in symptomatology have been reported [118]. The impact of cryomyolysis on fertility has not been evaluated but data from a small series of 9 women showed fertility may remain preserved [119]. The procedure should therefore not be recommended for women who desire future fertility.

MR-guided Focused Ultrasound (MRgFUS) is a new addition to the newer, more effective, minimally invasive methods of treating symptomatic fibroids. Under MRI guidance, high-intensity focused ultrasound is targeted on the fibroid to create thermal energy to precisely ablate fibroids and tissues within the focal zone sparing tissues within 2–3 mm of the focal zone. The technique utilises an abdominal transducer which is placed on the patient’s abdomen and the ultrasound energy focused to destroy fibroids within the focal zone. Apart from permitting direct visualisation of the fibroid, the MRI also records the temperature generated and precisely demarcate the normal and destroyed tissues. This technique has shown encouraging result in the treatment of symptomatic fibroids [120].

Apart from isolated case reports of successful pregnancies, the only report on pregnancy outcome in the literature at present is a small series of 54 pregnancies in 51 women after MRgFUS which suggested that post procedure normal pregnancy outcomes and deliveries are possible. The mean time to conception post-procedure was 8 months with a 41 % live birth rate, 28 % spontaneous miscarriages and 64 % vaginal deliveries. Eleven percent had elective termination of pregnancies and 28 % of spontaneous miscarriage after MRgFUS for the treatment of uterine fibroids [120]. Although the preliminary results are reassuring and viable intrauterine pregnancy, with a full-term vaginal delivery, the impact of this treatment modality on fertility has not been fully assessed and hence patients with desire for further fertility should receive appropriate counselling prior to embarking on treatment. In addition, the role of MRgFUS for enhancement of fertility in women with non hysteroscopically resectable uterine fibroid distorting the uterine cavity should be investigated further [120–125].

Laparoscopic uterine artery ligation is a fertility conserving, minimally invasive treatment option for symptomatic uterine fibroid performed as a laparoscopic procedure with very fewer associated complications and side effects. Significant reduction in fibroid volume have been reported with preservation of uterus and ovarian blood supply to permit possible pregnancy [126]. A study comparing this treatment approach to the more traditional uterine artery embolization found a slight reduction in fibroid at 3 and 6 months with an average volume reduction of 58 % [127].

Although the possibility of pregnancy has been proposed, there is currently no evidence of fertility and pregnancy outcome and therefore the authors concluded that patients contemplating pregnancy should be adequately counselled regarding the risk and benefits before performing this procedure [126]. Commonly reported adverse events include, minor skin burns (4 %), worsening of symptoms of menorrhagia (4 %), nausea requiring hospitalisation (1 %) and injury to the uterine serosa (1 %) [123]. Modest reduction in volume of fibroids have been reported in various studies and reduction in symptomatology [128] as well as improvement of quality of life reported to be within the range of 79.3–88 % 24 months after treatment [123, 129–131]. The effectiveness of this treatment modality in the symptomatic treatment of uterine fibroids has not been compared in randomised control trials with medical, surgical and other treatment modalities. The role of uterine artery embolisation will be discussed in detail in a later chapter.