What are fibroids?

Fibroids are caused by an overgrowth of muscle cells in the wall of the uterus. Each fibroid derives from a single cell which starts to divide more rapidly than normal. At least 40% of fibroids contain genetic abnormalities.

Different types of fibroid:

• Intracavity – fibroid on a stalk inside the uterus
• Submucus – fibroid partially protrudes into the cavity of the uterus
• Intramural – fibroid predominantly within the muscle wall of the uterus
• Subserous – fibroid growing away from the surface of the uterus

What makes fibroids grow?

Any woman in her reproductive years can grow fibroids, but they are more common in black women and in women where there is a family history of fibroids and in women who have never had children. They are common with increasing age, but not after the menopause. Fibroids are associated with obesity and also early age of the first period. Current, but not past use of the oral contraceptive pill has a protective effective. There are also two rare genetic disorders where fibroids are part of the syndrome.

Who is more likely to get fibroids?

The two main female sex hormones, oestrogen and progesterone, both promote the growth of fibroids. At the cellular level, the growth factors TGF-beta and bFGF are closely involved. Fibroids typically stop growing after the menopause, although hormone replacement therapy may sometimes promote their growth. A number of drug treatments will cause fibroids to reduce in size (see later).

Symptoms

1. Sudden onset of pain. This is called acute pain and happens if a fibroid dies (necrosis); if a subserous fibroid on a stalk twists (torsion); if it undergoes degeneration (sometimes seen in pregnancy) or if it becomes infected. Prolapse of an intracavity fibroid on a stalk through the cervix can also causes acute pain.
2. Long-standing pain. This is called chronic pain and is not typically seen with fibroids.
3. Increased menstrual bleeding. This happens with intracavity fibroids and submucus fibroids, or if the size of the cavity of the uterus is increased by the presence of intramural fibroids. However, increased menstrual bleeding is also seen when the cavity size and shape are normal.
4. Pressure symptoms. With very large fibroids, there will be pressure symptoms affecting the bowel, bladder (leading to increased urinary frequency) and the spine, causing backache. Some women will also find sexual intercourse uncomfortable.
5. Pregnancy complications. Degeneration of fibroids during pregnancy causes acute pain. The following are all common with fibroids:

• Preterm delivery
• Placenta praevia (where the placenta covers the cervix)
• Breech presentation
• Malposition (i.e. when the baby is facing upwards – occipto-posterior)
• Increased caesarean section rate
• Severe post-partum haemorrhage
• Miscarriage and implantation failure may be associated with intracavityand submucus fibroids.

6. Infertility (see later)
7. Asymptomatic. Some women with a fibroid uterus may be completely asymptomatic (no symptoms).

Do fibroids cause infertility?

Some, but not all fibroids, will reduce a woman’s fertility and their removal will enhance her fertility. This is always a controversial area but the consensus amongst fertility experts is that, in fertile women, fibroids should be removed when:

• They are causing significant symptoms
• They are intracavity or submucus
• There is a history of recurrent miscarriage
• There is persistent infertility when no other cause has been demonstrated
• Prior to first IVF treatmentPrior to successive IVF attempts when earlier attempts have been unsuccessful
• When there is concern that the fibroids may cause pregnancy complications.

How are fibroids assessed?

An experienced Gynaecologist will be able get some idea as to the size and location of fibroids from the clinical examination, but nowadays, transvaginal ultrasound and sometimes transabdominal ultrasound, will be used as part of the routine assessment of fibroids. Occasionally, 3-dimentional ultrasound will provide additional information, particularly with regards to the uterine cavity. Instilling fluid into the cavity of the uterus via a small catheter through the cervix can also help to delineate the uterine cavity. This technique is called sono-hysterography.

The x-ray technique of hysterosalpingography (HSG) has for many years been a vital tool for assessing the uterine cavity and for picking up intracavity fibroids and submucus fibroids. It will also help to determine whether or not the fallopian tubes are healthy, if they are disease, or if they are blocked. Magnetic Resonance Imagining (MRI), is an accurate if expensive way to assess uterine fibroids. It is particularly useful if the uterus is very large or if the ultrasound assessment of the uterus is difficult for any other reason. It is used routinely prior to laparoscopic myomectomy. MRI has the advantage of showing up generalised adenomyosis or focal adenomyosis and it will also give a clear view of the ovaries, which is not always possible with ultrasound in the presence of fibroids. Adenomyosis is a condition where small deposits of endometrium (lining of the uterus) are seen within the muscle wall of the uterus and this condition typically causes pain and heavy periods.

Hysteroscopy is a valuable tool for assessing intracavity and submucus fibroids and for helping with decision making as to how they should be removed. Sometimes a laparoscopy is performed at the same time, to evaluate the uterus and pelvic organs in more detail. Hysteroscopy is a technique which involves a look inside the uterus with a small instrument being introduced through the cervix.

Laparoscopy is an investigative technique involving inserting the laparoscopy through a small incision in the umbilicus to permit a full examination of the uterus, fallopian tubes and ovaries

Can fibroids be treated with medicines?

A number of medical treatments are available for fibroids, but they all have one problem in common and that is that although the fibroids will reduce in size with treatment, as soon as the treatment is stopped, the fibroids return to their pre-treatment size within a few months and then may continue to grow. For this reason, medical treatment is normally only recommended prior to surgery. The advantage of medical treatment in this situation is that it reduces the size and vascularity of the fibroids, making their removal easier and safer.

Gonadatrophin Releasing Hormone Agonist

The abbreviation for this medical treatment is GnRHa. There are two suitable preparations for this, Zoladex and Prostap SR. Both are given as subcutaneous injections and there are two strengths, one lasting for 1-month and one lasting for 3-months.& The 1-month treatment is the one usually used in this context. These drugs work by switching off the production of FSH and LH from the pituitary gland, FSH and LH are the two principle gonadatrophin hormones which stimulate the ovaries. By suppressing FSH and LH production, the amount of oestrogen produced by the ovaries goes down to very low levels and this reduces the blood supply to the uterus. It is for this reason that this type of medication reduces the size and vascularity of the fibroids. Typically the volume of fibroids will reduce by 40%, but there is quite a variation on this point.

An inevitable side-effect of treatment is hypo-oestrogenic side effects, principally hot flushes and vaginal dryness. A hidden side effect is loss of strength from the bones. For all these reasons, it is standard practice to recommend add-back therapy with a very low dosage of HRT preparation called Tibolone (also known as Livial). The usual treatment regime is to use GnRHa injections for between 2 and 4 months. The first injection is given at the time of a menstrual period, with subsequent injections at 4-weekly intervals thereafter, regardless of the pattern of bleeding. Tibolone therapy normally starts at the time of the second injections.

After the second injection it is usual for the periods to stop altogether and this can be of great benefit to patients who have been experiencing problems with heavy periods, particularly if they have also been anaemic. There is normally a clinic visit between starting the GnRHa and admission for surgery, to discuss the final plans for the myomectomy surgery and to complete the consent form.

Other medical treatments

These are only mentioned briefly because they are used either very infrequently or are at an early stage in development.

• Mifepristone is an anti-progesterone medication, which reduces the size of fibroids.
• Asoprisnil (this is a selective progesterone receptor modulator-SPRM) is effective in reducing the size of fibroids, but is at the early stages of being used.
• The levonorgestrel intrauterine system also known as the Mirena IUS, is effective for reducing menstrual blood loss and will reduce the size of fibroids, but it is only suitable if the uterus is not particularly large and if the cavity of the uterus is normal. Furthermore, it is clearly not appropriate for an infertility patient.
• Raloxifene (this is a selective oestrogen receptor modulator-SERM) has been shown to reduce the size of fibroids.
• Prior to the introduction of GnRHa, Danazol and Gestrinone were used to reduce the size of fibroids and although effective, are infrequently used nowadays because of side effects.

Surgical Treatment

There are three surgical approaches for removal of fibroids.

1. Hysteroscopic – otherwise known as transcervical resection of fibroids (TCRF).
2. Laparotomy leading to myomectomy surgery.
3. Laparoscopy leading the laparoscopic removal of fibroids.

The chosen route for surgery recommended depends on the size of the fibroids, their number and their position. Putting it another way – LOCATION, LOCATION, LOCATION!

1. TRCF – This is an established technique for removing fibroids, which are either intracavity or submucosal. Some submucosal fibroids may require a second operative procedure to completely remove them. It is usual to give a pre-operative course of GnRHa injections but this may not be necessary if the fibroid is small or if it has a low blood supply. The surgical technique involves removing the fibroid by shaving it away in pieces using an electric loop cutter. In experienced hands the technique works well with subsequent pregnancy rates reported at between 30-60%.

   All surgical techniques carry with them the risk of complications and TCRF is no exception. However, in experienced hands complications are either very uncommon or rare. Occasionally the uterus is perforated during the procedure and if this happens the procedure will need to be abandoned. The fluid that is used to distend the uterus during the operation is always absorbed to a greater or lesser extent, but if too much is absorbed into the circulation this leads to a fluid overload situation. This is treated by careful management of fluid intake/output and occasionally diuretics are needed.

   As with all operations, haemorrhage and infection can be complications. Normally any haemorrhage is completely stopped at the time of the operation and antibiotics administered as routine during surgery to prevent infection occurring. A symptom, which is more a consequence of the operation rather than a complication of the operation, is vaginal discharge and this happens as a result of the uterus healing after the operation. Additional antibiotics are sometimes needed. Another potential problem from the operation is the occurrence of intrauterine adhesions. Steps can be taken during surgery to try and prevent this from happening – such as inserting an IUD or a small balloon device. Occasionally a follow-up hysteroscopy is necessary to check for adhesions and if there are any to divide them at the time.

2. Myomectomy via laparotomy – This is the most commonly employed approach for the removal of fibroids. For women who are wishing to have future pregnancies, it is essential that the operation is carried out by an experienced Gynaecologist to ensure that all the fibroids are removed and to ensure that steps are taken to minimize any possibility of post-operative adhesion formation. Nearly all Gynaecologists recommend pre-operative GnRHa injections. Additional steps taken during surgery to minimize bleeding include the use of dilute Pitressin. Depending on the size, number and location of the fibroids, these operations can take a long time.

   Great care needs to be taken during the operation not to damage the peritoneum (the covering of the uterus) as this can lead to adhesion formation. During the operation it is routine to closely examine the fallopian tubes and ovaries and to ensure that the tubes are patent, by putting a blue dye into the uterine cavity with a catheter inserted through the cervix. At the end of the operation, adhesion barriers such as Interceed or Seprafilm can be used, or a fluid called Adept may be instilled into the peritoneal cavity.

   The chance of a pregnancy following on from myomectomy surgery, within the first 1-2 years, is between 40-60% in couples where there are no other contributory problems to fertility. Those who do not conceive naturally may be recommended to go on to IVF treatment and this is likely to be recommended if there are additional factors causing infertility. The chance of recurrence of fibroids depends on many factors, in particular the age of the woman and the number and size of fibroids removed. Up to a third of women may grow small fibroids 2-3 years after the initial operation, but overall only about 1 in 20 will develop fibroids over 5 cm in diameter.

   Complications - It is difficult to get accurate figures about the chance of adhesion formation after surgery, but without meticulous surgical technique and the use of adhesion barriers, the chance of adhesion formation is high. Another complication in myomectomy surgery is weakness of the uterine scar with the possible risk of breakdown of the scar during pregnancy (this is called uterine rupture). If the cavity where the fibroid has been is closed in two or three layers, the chance of this happening is minimized and overall is no higher than the risk of a caesarean scar opening up during pregnancy. After a complex myomectomy surgery, the Gynaecologist may commonly recommend that any future pregnancy is delivered by caesarean section. Other complications include haemorrhage and infection. Steps are taken during surgery to minimize any blood loss, particularly with the use of Pitressin and also antibiotics are routinely administered.

3. Laparoscopic myomectomy – Some fibroids are amenable to laparoscopic removal, particularly if they are located superficially, not too large and are not too many in number. The surgical technique, which has limited the use of this approach, is the ability to adequately close the myomectomy cavity with sutures and specialised theatre equipment is required. So long as this can be safely accomplished, the outcome in terms of risk of recurrence, pregnancies and complications is the same as for laparotomy.

Uterine Artery Embolisation

As an alternative to surgery, uterine artery embolisation has been developed since 1995. The technique involves inserting a catheter into the leg vein and tracing this all the way round to the uterus. Small particles are then fired into the uterine circulation, blocking the arteries. The main advantage of this technique is that the patient does not require an operation and because of this her initial recovery is much quicker.

However, up to 20% of patients will experience severe pain, still present at one week post-surgery and between 1-2% will require an emergency hysterectomy. In a further 2% of patients, the technique is technically unsuccessful and despite technical success, a further 10-15% of patients will experience no decrease in the size of their fibroids. Symptomatic improvement is initially excellent but unfortunately over time the risk of fibroids regrowing is as high as 60% at 5 years. The blood supply to the ovaries may be damaged as a result of the procedure and because of this uterine artery embolisation is not recommended for women wishing to retain their fertility. Many pregnancies have however been reported after uterine artery embolisation, but the complication rates in these pregnancies is overall much higher than seen after conventional myomectomy surgery.

Magnetic Resonance Imaging-Guided Focused Ultrasound (MRI-FUS)

This is a new non-invasive treatment for uterine fibroids and involves heating up the central part of the fibroid using a focused ultrasound beam. As it is a new technique we do not have any information regarding long-term success, recurrence rates, chances for pregnancy in women wishing to conceive and the chance of complications during pregnancy. For the time being at least, this technique should be regarded as experimental.

Following on from Myomectomy Surgery

Question:	How long does it take for the menstrual cycle to resume following on from medical therapy (GnRHa) prior to surgery?
Answer:	Three months from the last injection which generally means two months from the myomectomy surgery.
Question:	How long should you leave it before trying for a pregnancy following myomectomy surgery?
Answer:	The uterus heals fairly quickly so there is no particular delay recommended before trying for a pregnancy. This means you can start to try for a pregnancy as soon as you have recovered from the operation.