Uterine fibroids or leiomyomata are smooth muscle cell tumours. They are the most common benign gynaecologic tumour in women of reproductive age. The lifetime prevalence is around 30%. They are rarely found before menarche and usually regress after menopause. They are hormonally responsive, and oestrogens appear to promote their growth. One in four women with fibroids is symptomatic. For women who are asymptomatic or with bearable symptoms, expectant management is usually sufficient. Median fibroid growth is around 9% over 6 months. Many women with fibroids have successful pregnancies. However, fibroids are often found as part of the investigation of a couple presenting with infertility. It is well established that submucosal fibroids have a negative impact on rates of implantation, clinical pregnancy, ongoing pregnancy, miscarriage, and live birth. Hence, an important aspect in evaluating fibroids is to determine if the fibroid is submucosal, and the degree to which it impinges on the endometrium. Imaging is important in the preoperative evaluation of fibroids, especially where fertility is a concern.1,2
Both infertility and age have been associated with the presence of fibroids and this may further confound results of
studies attempting to clarify the relationship between fibroids and infertility.
Many hypotheses have been generated to explain how fibroids might cause infertility. Perfusion studies have shown that blood flow to uterine fibroids is less than that to the adjacent myometrium. There may also be endometrial inflammation and an altered local hormonal environment which may affect embryo implantation. Large fibroids can potentially alter uterine contractility possibly interfering with sperm and ovum interaction or embryo migration.
In general, it appears that women with fibroids have decreased fertility. However, the impact appears to be related to fibroid location. Systematic reviews and meta-analyses published to date indicate that subserosal fibroids do not appear to have an impact on fertility. Available studies however are in agreement that submucosal fibroids (fibroids with endometrial impingement) have a negative impact on rates of implantation, clinical pregnancy, miscarriage, ongoing pregnancy and livebirth. The greatest question remains on the impact and treatment of intramural fibroids. The most recent good quality meta-analyses appear to show that intramural fibroids do seem to have an impact on both implantation and clinical pregnancy rates but less than that of submucosal fibroids. Most studies included intramural fibroids < 5 cm.
Another way of assessing whether a uterine pathology has an impact on conception rates is to evaluate whether pregnancy rates increase more after removal than after expectant management. However, studies on treatment for leiomyomas in women with infertility have been few and small. A meta-analysis of the small studies available found an apparent benefit of hysteroscopic myomectomy over fibroids left in situ on clinical pregnancy rates (RR 2.034, 95% CI 1.081 to 3.826, P = 0.028).6
Current medical therapy is essentially a treatment option for the control of symptoms. Tranexamic acid helps with reduction in menstrual blood loss. The other medical options available are primarily hormonal agents which act on the oestrogen and progesterone responsiveness of fibroids and are unsuitable for fertility. GnRH analogues cause hypo- oestrogenic side effects and bone loss. They may be suitable for pre- operative therapy but because of the side effects, should be limited to a maximum use of 6 months. Novel therapies that are under study include aromatase inhibitors, mifepristone, selective estrogen receptor modulators, and selective progesterone receptor modulators. These have shown promise in symptom improvement and fibroid regression without the hypoestrogenic symptoms associated with GnRH analogues.
Newer uterus-sparing treatments include uterine artery embolisation (UAE) and more recently, MRIGuided focused ultrasonography (MRgFUS). UAE is a procedure where an interventional radiologist uses a catheter to deliver small particles that block the blood supply to the uterine body. MRgFUS involves the use of high- frequency ultrasound waves to produce heat and denature proteins leading to cell death and shrinkage of fibroids. MRI is used to help guide the ultrasound beams to target the fibroids. However, these techniques have not been used on a large scale, and data on their reproductive outcomes in patients trying to conceive are insufficient to make recommendations. There is some concern regarding development of pelvic adhesions following such treatments. Furthermore, ovarian reserve may be adversely affected.
Well-designed surgical intervention trials for myomectomy and infertility are sparse, with a single randomised
controlled trial published to date.7 This study demonstrated an improvement in conception rates after the surgical
removal of submucosal fibroids, but pregnancy rates following the removal of intramural or subserosal fibroids were no
more improved than in the expectant management group of women with intramuralsubserosal fibroids in situ. A
meta-analysis demonstrated similar findings, with an improvement in pregnancy rates in infertile patients undergoing
surgical removal of submucosal fibroids, but not in those undergoing surgical removal of intramural fibroids.6
Depending on the fibroid size and location, the surgical approach to fibroids can be either vaginal or abdominal. The abdominal approach may be either by laparotomy or laparoscopy.
Two randomised controlled trials with a combined 267 patients compared reproductive outcomes of laparoscopic
myomectomy and myomectomy by laparotomy. In the first study of patients undergoing myomectomy for infertility and at
least 1 fibroid > 5 cm, pregnancy rates were similar following in the laparoscopy and laparotomy groups (53.6% vs.
55.9%). 10 There was lower febrile morbidity in the laparoscopy group (26.2% vs. 12.1%), shorter hospital stay, and a
lower postoperative drop in haemoglobin.
In the second study, 12 months postoperatively, cumulative pregnancy rates were similar in the laparoscopy and laparotomy groups (52.9% vs. 38.2%). 11 Again, the laparoscopic approach was associated with a quicker recovery, less postoperative pain, and less febrile morbidity.
Widespread use of the laparoscopic approach to myomectomy may be limited by the technical difficulty of this procedure. Patient selection should probably be individualized based on the number, size and location of uterine fibroids.
There may often, be instances when surgical removal of fibroids in an infertile patient is undertaken for reasons other than fertility enhancement, such as relief of pressure symptoms or surgical management of menstrual disturbances secondary to fibroids. However, surgical treatment of fibroids can be associated with morbidity. Where patients are asymptomatic, the decision for surgery should be weighed against potential risks.