An Update on Fibroid Treatment
Fibroids or Leiomyomas are the most common benign tumours of the uterus. They are often detected at screening ultrasound in asymptomatic patients. Fibroid will continue to grow until menopause and shrink thereafter. When fibroids enlarge, they can cause heavy menstruation, pain and pressure on the bladder and bowel. Some fibroids can also impair fertility and affect pregnancy outcome. All these can negatively impact the women’s quality of life and put a strain on society in general. [Hum Reprod Update 2016;22:665-686]. The treatment of fibroid includes surgical, non-surgical and medical therapy.
Surgery for fibroids (Myomectomy)
Fibroids that are huge, extending to above the umbilicus are best dealt with by open surgery (Laparotomy Myomectomy). To avoid the morbidity of open surgery, medication can be used to reduce the fibroid size to one that is amenable for laparoscopic surgery.
Most fibroids are now removed with laparoscopic surgery of 3-4 abdominal cuts. In selected cases, Myomectomy can be done by Single Incision Laparoscopy, the latest in laparoscopic surgery. Single Incision Laparoscopy is done with just one cut of 3cm at the umbilicus, avoiding the risks, pain and morbidity of additional cuts. The single 3cm incision eventually heals into an inconspicuous fold, giving Single Incision Laparoscopy the nickname of scarless surgery.
Single Incision Laparoscopy also allows for fibroid to be removed more efficiently; the fibroid is cut with a standard surgical scalpel at the umbilicus, into a thick strip of tissue for removal (C-cut technique). This technique is quick, clean and complete. In contrast, convention laparoscopy requires a power morcellator with a spinning blade to remove the fibroid. The power morcellator is cumbersome and can leave behind bits of fibroid tissue if a morcellator bag is not used.
Surgery for fibroid entails a period of womb recovery before pregnancy is advised. Ultrasound studies have shown this period to be between 6 to 9 months where the uterine muscle integrity and blood flow velocity recovering back to normal. [Gynecol Obstet Invest 2006;61(2):106-10] With good womb recovery, the dreaded risk of uterine scar rupture in pregnancy can be kept to that of women with one previous caesarian section delivery.
Transcervical Resection of Myoma (TCRM)
In some women, the fibroid that is causing menorrhagia is found within the endometrial cavity, called submucosal fibroid. Submucosal fibroid is best removed by TCRM, which is a special procedure done through the vagina with no abdominal cuts. Although TCRM can be done as a day procedure, it is a challenging procedure that requires special instruments and advanced endoscopic training.
Non-surgical fibroid treatment
Non-surgical fibroid treatment consists of Uterine Artery Embolization (UAE) and High Intensity Focus Ultrasound (HIFU). These treatments can reduce menorrhagia in up to 90% of cases and shrink fibroids by up to 50% of initial volume over 6 to 12 months.
Uterine Artery Embolization is carried by blocking both left and right uterine arteries, depriving the uterus and fibroid of blood supply. There is a small risk of causing early menopause as the ovarian blood supply is inadvertently blocked as well. Pregnancies after UAE have been reported though some with complications of abnormal placenta attachment.
High Intensity Focus Ultrasound is now available at Farrer Park Hospital, Singapore. The procedure involves focusing high intensity ultrasound beam into the fibroid to cause coagulative necrosis. The treatment can last 45 minutes to 3 hours, depending on the size of fibroids. HIFU has been shown to be safe for women wishing to get pregnant. However, it may not be suitable for women with abdomen or pelvic surgical scars.
Medical therapy for fibroids
Medical treatment generally aims to reduce heavy menstruation from fibroids. Apart from Gonadotropin-Releasing Hormone (GnRH) Agonist and Selective Progesterone Receptor Modulators (SPRM), they do not make fibroid smaller.
Tranexamic Acid (cyklokapron) is a non-hormonal medication that blocks the plasminogen activator of the endometrium to prevent fibrin and clotting complexes from breaking down, leading to reduced menstruation. The efficacy of Tranexamic Acid treatment is depending on the size and location of the fibroids. It tends to be less effective when fibroids are large.
Combined Oral Contraceptives (COC), Intrauterine Hormonal System (Mirena) and DepoProvera are all hormonal medication that will reduce menstruation or cause amenorrhoea. Although they can control menstrual bleeding in women with fibroids, there is a tendency for the hormone, especially progestogen to stimulate fibroid growth.
Gonadotropin-Releasing Hormone (GnRH) Agonist acts to induce a state of temporary menopause to stop menstrual bleeding and shrink the fibroid. However when treatment is stopped, the fibroid will grow back to its original size and heavy menstrual bleeding will return. There is a risk of osteoporosis if GnRH Agonist is for more than 6 months.
Selective Progesterone Receptor Modulators (SPRM) is the latest medical treatment for fibroid. Molecular studies have found abundant progestogen receptors within fibroids, and blocking these receptors to deprive the fibroid of progestogen influence, will cause cell death (apoptosis) and permanent fibroid shrinkage. SPRM also acts on the endometrium to induce amenorrhoea. This combined action of SPRM makes it a highly effective treatment option for women with fibroids. [Fertil Steril 2014;101:1565-1573]
Ulipristal is the first SPRM approved for the treatment of fibroids. It has minimal side effects of transient headache and hot flushes in 5-10% of women. It is feasible for long-term use because it does not cause osteoporosis. Ulipristal has also been shown to be safe in patients wishing to conceive, with no maternal complications related to fibroid during pregnancy or after delivery. Additionally, long-term follow-up of these women showed no significant regrowth of fibroids. [Fertil Steril 2014;102:1404-1409]
Ulipristal can shrink about 70% of fibroids permanently after 6 months of treatment. The reduction is measured by fibroid volume rather than fibroid diameter. Hence to the causal observer, a 50% reduction in fibroid volume will translate to a 1 to 1.5 cm reduction of fibroid diameter. Nonetheless, the alleviation of fibroid symptoms, which is dependant on the fibroid volume will be evident. [N Engl J Med 2012;366:421-432]
The most significant finding regarding the treatment efficacy of Ulipristal comes from real world data. [Premya Study : Eur J Obstet Gynecol Reprod Biol 2017;208:91-96] In this study, 1473 women awaiting fibroid surgery from 73 clinics in Europe were treated with Ulipristal for 3 months and followed up for 15 months. 60% of women found their symptoms of bleeding, pain and quality of life ‘much improved’ or ‘very much improved’ to the extend that surgery is no longer needed. This study brings tremendous hope to women with fibroids: that 3 months of Ulipristal can reduce the need for surgery in up to 60% of cases.
Monitoring patients on Ulipristal
In late 2017, sporadic cases of liver failure were reported in women using Ulipristal. A thorough investigation revealed up to 8 cases of associated liver injury, out of more than 765,000 women treated with Ulipristal. This constitute a Drug Induced Liver Injury (DILI) risk of 8:765,000 or 0.001%. This DILI risk is in fact lower than that of commonly prescribed medicines like statins (Zocor), fluconazole (Diflucan) and amoxicillin/clavulanic acid (Augmentin). [Data from livertox.nih.gov] Additionally, an in-depth review of the 8 women showed the majority of them having pre-existing liver conditions like viral hepatitis, cirrhosis and autoimmune hepatitis. Nonetheless, it is now advised that liver function tests be done before, during and after each treatment course, for the first 6 months of Ulipristal treatment. [European Medicines Agency (EMA), https://www.ema.europa.eu/en/medicines/human/referrals/esmya, accessed 24 April 2019]
There are now many viable treatment options for women with fibroids. It is important that patients are presented the correct facts of each treatment option so that they can make an informed decision on which treatment to proceed with best.
Dr Siow strongly feels that Ulipristal offers a real potential for complete fibroid treatment. It is effective in relieving heavy menstrual bleeding and has the potential to shrink fibroid permanently, allowing for an easier laparoscopic surgery, or in some cases, avoidance of surgery entirely. Where surgery is needed, Dr Siow performs more than 90% of his fibroid surgery by Single Incision Laparoscopy.
A Specialist’s Point of View – Written by Dr Siow Yew Ming Anthony