5.1 Introduction

Uterine fibroids (also known as leiomyomas or myomas) are the most common benign uterine tumours in women, with an estimated incidence of 50–60% [1]. They are smooth muscle tumours originating from the myometrium [2]. The majority of uterine fibroids are asymptomatic but 30–40% are symptomatic, depending on the location and size, and can present with abnormal uterine bleeding, pressure symptoms, pelvic pain and infertility [3]. Additional symptoms include urinary problems and constipation. Uterine fibroids can also lead to reproductive problems like infertility, miscarriage, pre-term labour, fetal malpresentation, increased risk of caesarean section, low birth weight and postpartum haemorrhage [4].

Race, genetic, epigenetic and environmental factors, such as age, early menarche and nulliparity, play an important role in the development of uterine fibroids [5]. The incidence of uterine fibroids increases with advancing age and the cumulative lifetime incidence is estimated between 70% and 84% [1, 6]. There is a current trend of women delaying childbirth, and therefore women who wish to conceive are more likely to present with uterine fibroids. Uterine fibroids may be associated with 5–10% of infertility cases [7].

Black women have a greater incidence of uterine fibroids when compared to white Caucasian women; the fibroids also tend to be larger and found in multiple locations, and to lead to severe symptoms [8].

5.2 Fibroids and Infertility

Uterine fibroids may be associated with 5–10% of women presenting with infertility [7], and they are the sole abnormal finding in 1–2.4% of infertile women [3]. The impact of uterine fibroids on fertility is determined by location and size. However, there has been a debate whether uterine fibroids cause infertility or are associated with infertility [9], and whether removal of the fibroids in asymptomatic women improves fertility and pregnancy outcome.

There are a few explanations of how fibroids can impair fertility:

1. 
   

   1. Anatomic distortion of the uterine cavity [10]

   
   
2. 
   

   2. Increased uterine contractility and changes to the endometrial blood supply [3]

   
   
3. 
   

   3. Changes to the hormonal milieu within the uterine cavity that may have an effect on implantation [11, 12].

Fibroid location and fertility have been investigated in many studies. Unfortunately, most of them are only observational studies, with few well-designed randomized controlled trials. However, there is agreement that the greater the impact of the fibroid on the endometrial cavity, the greater the effect on fertility. Hence, submucosal, intramural and subserosal fibroids have a decreasing impact on fertility in that order.

5.3 Submucosal Fibroids and Fertility

Studies have demonstrated that submucosal fibroids have the most significant adverse effect on fertility by decreasing implantation rate and increasing the risk of miscarriage in spontaneous pregnancies and assisted reproduction cycles [13–15]. A systematic review from 2001 looking into the effect of fibroids and infertility demonstrated lower pregnancy rates (RR 0.30; 95% confidence interval [CI]: 0.13–0.70) and implantation rates (RR 0.28; 95% CI: 0.10–0.72) in women with submucosal fibroids when compared to infertile women without fibroids [13].

A newer meta-analysis from 2009 investigated the effect of submucosal fibroids on fertility [16]. The results showed that women with submucosal fibroids had significant lower fertility, clinical pregnancy and ongoing pregnancies/birth rates, and higher miscarriage rates [16].

Several studies have demonstrated an increase in spontaneous conception, reduced miscarriage rate and improved IVF outcomes following the removal of submucosal fibroids [17, 18]. Casini et al. demonstrated a significantly higher spontaneous pregnancy rate at 12 months following myomectomy compared to patients without myomectomy (43.3% vs. 27.2%) [19]. A randomized matched control study of 215 women with submucosal fibroids showed increased fertility rates following hysteroscopic myomectomy of grade 0 and 1 fibroids, but not of grade 2 fibroids [20].

5.4 Intramural Fibroids and Fertility

Infertility and recurrent miscarriage have been associated with submucosal fibroids or intramural fibroids distorting the uterine cavity [16, 21–23].

The greatest inconsistency has been on the effect of intramural fibroids not distorting the uterine cavity. The first systematic review on fibroids and infertility did not show an effect of intramural fibroids on infertility [13]. An updated systematic review by the same author demonstrated a possible negative effect of intramural fibroids on reproductive outcomes [16]. Women with intramural fibroids had significantly lower clinical pregnancy rates, implantation rates, ongoing pregnancy/live birth rates and significantly higher miscarriage rates [16]. However, most of the studies had a poor evaluation of the uterine cavity [16].

A more recent systematic review has suggested that the presence of intramural fibroids without cavity distortion has a negative impact on IVF outcomes [21].

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 [21]. 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 [19].

The most recent systematic review and meta-analysis initially showed a negative impact of intramural fibroids on clinical pregnancy rates, but not on live birth or miscarriage rates [24]. However, 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), when only the highest-quality studies were included [24]. This is in contrast to the two recent meta-analyses [16, 21], which can be explained by the way confounding factors such as age and 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 [24]. 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 [24]. High-quality studies are desperately needed regarding the effect of intramural fibroids on reproductive outcomes.

Even if intramural fibroids reduce fertility, the question is whether removal of those fibroids would improve reproduction.

Given the risks of surgery, including bleeding, infection, damage to internal organs and postoperative adhesions, the decision for a myomectomy should not be taken lightly if there is uncertain benefit. According to a systematic review there is no significant difference in reproductive outcomes when the laparoscopic and abdominal approaches for myomectomy are compared [25]. Nevertheless, removal of intramural fibroids did not seem to significantly improve fertility outcome [16, 19].

It is advisable to manage women with intramural fibroids on an individual basis, 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, it is important to check for any involvement of the uterine cavity. Many clinicians consider removing larger intramural fibroids (>5 cm). Future high-quality research is needed on the treatment of intramural fibroids, with a description of size and number of fibroids as well as their proximity to the endometrium.

5.5 Subserosal Fibroids and Fertility

A meta-analysis from 2009 did not reveal an effect of subserosal fibroids on fertility, implantation rates and clinical pregnancy rates [16], and there is currently insufficient evidence that removal of a subserosal fibroid improves fertility in women who are otherwise asymptomatic [26]. However, surgery may be considered if the subserosal fibroid is large and causing symptoms or is distorting the pelvic anatomy, leading to difficult access to the ovaries for egg retrieval.

5.6 Conclusion

Uterine fibroids are commonly found in women of reproductive age. They can lead to reduced fertility and adverse pregnancy outcomes. Fertility outcomes are decreased in women with submucosal fibroids, and removal seems to be beneficial. Subserosal fibroids do not affect fertility outcomes, and removal does not show any benefit. Intramural fibroids appear to decrease fertility, but there is still some uncertainty and controversy regarding the management of intramural uterine fibroids. Intramural fibroids with a submucosal component reduce reproductive outcomes, and myomectomy may be considered to increase the pregnancy chances. Therefore, it is important to exclude any involvement of the uterine cavity. More high-quality studies are needed to determine the impact of intramural fibroids on fertility and the effect of myomectomy on reproductive outcomes. Therefore, counselling and individualized planning is recommended when dealing with subfertile women diagnosed with uterine fibroids.