Several studies have looked into the effect of intramural fibroids on IVF outcome [14–19], although the results are controversial. Some studies have reported a negative impact of intramural fibroids on IVF outcomes [17, 19] whereas other studies did not find an effect on IVF outcomes [16, 20–22]. The first systematic review on fibroids and infertility did not show an effect of intramural fibroids on infertility [23]. However, a shortage of good quality studies were noticed [23]. An updated systematic review by the same author demonstrated a possible negative effect of intramural fibroids on reproductive outcomes [2]. They found significantly lower clinical pregnancy rates, implantation rates, ongoing pregnancy/ live birth rates and significantly higher miscarriage rates in women with intramural fibroids [2]. Unfortunately most of the studies had a poor evaluation of the uterine cavity [2]. Nevertheless, removal of intramural fibroids did not seem to improve significantly fertility outcome [2, 24]. A more recent systematic review has suggested that the presence of intramural fibroids without cavity distortion has a negative impact on IVF outcomes [14]. A significant decrease in clinical pregnancy (RR = 0.85, 95 % CI 0.77–0.94, p = 0.002) and live birth rates (RR = 0.79, 95 % CI: 0.7–0.88, p < 0.0001) after IVF treatment has been found in women with intramural fibroids without uterine cavity involvement when compared to women without fibroids [14]. A significant negative effect of intramural fibroids for conception (OR = 0.8, 95 % CI: 0.6–0.9) and delivery (OR = 0.7, 95 % CI: 0.5–0.8) was also reported in a different systematic review of fibroids in female reproduction [15].

The most recent systematic review and meta-analysis on this subject initially showed a negative impact of intramural fibroids on clinical pregnancy rates, but not on live birth or miscarriage rates [3]. However, when only the highest quality studies were included, there was no significant effect of intramural fibroids without cavity distortion on clinical pregnancy rate (OR = 0.74, 95 % CI: 0.5–1.04), live birth rate (OR = 1.17, 95 % CI: 0.62–2.22) or miscarriage rate (OR = 1.88, 95 % CI: 0.61–4.2) [3]. This is in discrepancy to the two recent meta-analyses [2, 14], which can be explained by the way confounding factors like age, involvement of the uterine cavity were analysed. In addition, a low number of high quality studies and significant statistical heterogeneity between the included studies were identified [3]. The same review could not identify a significant effect on clinical pregnancy rates (OR = 1.88, 95 % CI: 0.57–6.14) or miscarriage rates (OR = 0.89, 95 % CI: 0.14–5.48) following myomectomy for intramural fibroids [3]. This study highlights the need for high quality studies regarding the effect of intramural fibroids on reproductive outcomes.

The management of women with intramural fibroids needs to be individualised as there is insufficient evidence about the effect of intramural fibroids on fertility. Age and other reasons for infertility as well as number, size, location and presence of other fibroids need to be taken into consideration. In addition, any involvement of the uterine cavity needs to be excluded. Many clinicians consider removal of intramural fibroids larger than 4 cm.

Even though intramural fibroids may have a negative impact on fertility, it is not clear whether myomectomy is helpful. It is possible that myomectomy may prevent abnormal myometrial contraction and endometrial inflammatory reactions associated with the presence of intramural fibroids and thereby increase implantation rates. Currently, there are not enough studies addressing the effect of removal of intramural fibroids on fertility outcome. Nevertheless, it is important to explore this area as complications of surgery may impair future fertility and outweigh any benefits. A recent Cochrane review examined the effect of myomectomy on fertility outcomes and compared different surgical approaches [25]. Three randomised controlled studies were included in the Cochrane review. One randomised controlled study looked at the location of fibroids and the effect of myomectomy on clinical pregnancy or miscarriage rate and did not find a benefit of removal of intramural fibroids [24]. This study only included women with a single fibroid and a maximum size of 4 cm and did not report live birth rates [24]. Furthermore, the sample size was relatively small and insufficient to draw a firm conclusion [25]. The Cochrane review also examined the type of surgical approach and did not find a significant difference between open and laparoscopic myomectomy regarding fertility outcomes [25]. However, the evidence should be viewed with caution as only two randomised controlled studies were included [26, 27]. Both studies did not have a sample size calculation and may have been underpowered. The Cochrane review concludes that there is currently inadequate evidence regarding the effect of myomectomy on fertility outcomes. Furthermore, the current evidence did not show a significant difference in fertility outcome in regards to the type of myomectomy (open or laparoscopic approach). Therefore, the surgical approach should be determined by the surgical skills and expertise.

Fibroids are hormone-sensitive tumours with sex steroid receptors [28] and respond to hormonal treatment. Medical treatment in the form of gonadotrophin-releasing hormone analogue (GnRHa) can be given prior to myomectomy in order to reduce the size of the fibroid and make surgery safer and easier. A Cochrane systematic review confirmed these findings [29]. However, smaller fibroids can be overlooked at the time of surgery and can grow again following the discontinuation of GnRHa. A drawback of this therapy is oestrogen deficiency and a decrease in bone mineral density after prolonged use [30]. In addition, loss of cleavage plane between the tumours and the healthy myometrium can make surgery more difficult [31].

Another medical option is the use of selective progesterone receptor modulators (SPRM) with mixed agonist/antagonist activity. It is already known that oestrogen promotes fibroid growth, but more recent studies have suggested that fibroid proliferation may be enhanced via progesterone and its receptor [32]. Studies have confirmed the efficacy and safety of the SPRM ulipristal acetate (Esmya®) for the treatment of fibroids preoperatively [33, 34]. The recommended dose is 5 mg daily for up to 12 weeks. Endometrial changes have been noticed when ulipristal acetate was administered for more than 12 weeks which is due to cystic glandular changes and not endometrial hyperplasia. However, long term studies are necessary to look into those outcomes [35]. Furthermore, it is yet unknown what the effect on subsequent fertility is.

Minimal invasive techniques are available for the treatment of intramural fibroids. Uterine artery embolisation (UAE) occludes the uterine blood flow to the fibroid leading to necrosis and shrinkage of the fibroid [36]. Complications include hematoma formation, thrombosis, post-embolisation syndrome (pain, nausea, flu-like illness), infection, vaginal discharge, temporary amenorrhoea. Evidence suggests a 50–60 % reduction in fibroid size and 85–95 % symptom relief after UAE [37]. The effect of UAE on ovarian reserve and pregnancy outcome is not entirely clear [38]. One study looked at the impact of UAE versus myomectomy on infertility [39, 40]. Twenty six women following UAE tried to conceive and the pregnancy rate was 50 %, delivery rate 19 % and miscarriage rate 53 %. This was significantly lower compared to women following myomectomy (n = 40) (p < 0.05). They had a pregnancy rate of 78 %, delivery rate of 48 % and miscarriage rate of 23 %. Another systematic review found increased miscarriage rates in women post UAE (35.2 %) when compared to women with no intervention (16.5 %), matched for age and fibroid location [41]. There was only very low level evidence suggesting that myomectomy may be associated with better fertility outcomes than UAE according to a Cochrane review [42]. Of note is that women after UAE have an increased likelihood for surgical interventions in the future [42].

Magnetic resonance guided focused ultrasound surgery (MRgFUS) is a new method of thermal ablation for the treatment of fibroids beneath the anterior abdominal wall. However, only few patients are eligible for this new technique. Nevertheless, reproductive outcomes following this procedure are promising. A miscarriage rate of 26 % and a live birth rate of 41 % have been reported in women following this procedure [43].

Surgical treatment for intramural fibroids in the form of myomectomy can be performed abdominally or laparoscopically dependent on the position of the fibroid and the skills of the surgeon. Risks of myomectomy are intra-operative bleeding and formation of postoperative adhesions. The advantages of the laparoscopic procedure over an abdominal approach are reduction in postoperative pain, hospital stay and recovery [44]. However, laparoscopic myomectomy is technically challenging and time consuming. According to a systematic review there is no significant difference between those two approaches and fertility outcome [25].