Uterine fibroids are benign tumors originating from smooth muscle cells of the uterus. They are composed of both smooth muscle cells and fibrous tissues. Uterine fibroids may be solitary but are more commonly multiple, and may be coming from the myometrium (intramural fibroid) or extending through the serosa of the uterus [subserous fibroids] or they may reach into the uterine cavity [submucous fibroids.] Fibroids may even be pedunculated and extend from the uterus into the abdominal cavity on a stalk or extend from the uterine cavity into the cervix. Uterine fibroids are referred to simply as myomas, fibroids, fibromyoma, leiomyoma, leiomyofibroma, and fibroleiomyoma. All of those names represent the same type of tumor. Fibroids are very common and are predominantly an issue in women of reproductive age. They are usually found in 20 to 40% of all women and can become quite large and create a considerable distortion of the uterine anatomy.

Fibroids are estrogen dependant tumors and grow as a response to the female hormone estrogen. They have the greatest growth phase in the reproductive years when the estrogen levels are high. They are also known to have growth spurts during pregnancy. Careful follow-ups during pregnancy indicate that approximately 1/3 of the fibroids increase in size, 1/3 do not change in size, and 1/3 may in fact decrease somewhat in size during pregnancy. In the menopause when estrogen secretion is diminished fibroids tend to decrease in size.

Most fibroids do not give women any symptoms. However the location of the fibroid may cause more pronounced symptoms to develop. Heavy periods, bleeding, and anemia are not unusual. Back pain extending into the lower abdomen with a fullness and pressure is a common finding. Also the development of an abdominal bump may be the first finding. Pain during sex and an urge to go to empty the bladder is also a common finding. Recurrent pregnancy loss and miscarriages are often associated with fibroids and it is also known to create difficulty to conceive.

The presence of uterine fibroids is well documented on a pelvic or abdominal examination. To further outline the size and position of the fibroid a vaginal or abdominal sonogram is often helpful. The sizes and positions of the fibroids can be documented, its size measured but it is also well known that the size of fibroid is frequently overestimated with the use of sonography. Diagnostic testing with a hysterosalpingogram [HSG] or sono-hysterosalpingogram [S-HSG] may be necessary to evaluate the presence of intra-uterine fibroids and position of fibroids that may impair the function of the fallopian tubes. Magnetic resonance imaging (MRI) is frequently employed to document size and position of the fibroids. It is more precise but much more complicated procedure to perform than a regular sonogram. The MRI can in addition document the presence of adenomyosis which may complicate the presence of fibroids. Adenomyosis is an extended growth of endometrial glands into the myometrial tissue. Adenomyosis is frequently causing pelvic pain and is often difficult to diagnose.

Most fibroids do not need any treatment, but continuous follow-up and documentation of growth may be necessary. After a fibroid has been detected, and its location evaluated, a repeat exam 3 – 6 months later may be advised to ensure that there is no rapid growth in the fibroid.

After a woman has completed her childbearing a common treatment for fibroids is a hysterectomy. The hysterectomy is a very common operation and several hundred thousand hysterectomies are performed in the United States every year. Approximately 1/3 of all women have had a hysterectomy by age 65. The hysterectomy indications are approximately 33 % for fibroids, 20 % for endometriosis, 20 % for uterine prolapse, and about 10 % for malignant changes in the uterus. At the time of a hysterectomy the ovaries may be removed or left behind. It is becoming more common nowadays not to remove the ovaries. Hysterectomy is also a reasonable procedure if there is an extensive fibroid production [myomatosis] where it may be technically difficult to preserve a normal uterus after removal of many fibroids.

Hysterectomies are not free of complications. Anatomical distortions of the pelvic structure caused by fibroids may increase the risk of damage to the bowel and urinary tract during surgery. The presence of adhesions may increase the technical difficulties and fibroids may extend into the broad ligament that may at surgery increase the risk to damage the ureter which passes just next to the uterus. Infections and bleedings are also factors to be concerned about.

Myomectomy is the preferred procedure if preservation of childbearing capacity should be maintained. It is also a preferred treatment for a solitary fibroid. Before a myomectomy is performed, careful preoperative evaluation is necessary. Hypermenorrhoa will necessitate an evaluation of the histology of the endometrial cavity to exclude malignancy. Hysteroscopy and a HSG may be necessary to evaluate the uterine cavity and the portion of the fallopian tube that enters into the uterine cavity to exclude that the fibroid interferes with the function of the fallopian tubes. After hysteroscopic examination and D&C, it is recommended that 1 menstrual cycle would pass before the myomectomy is performed. Patients with heavy bleeding or patients that have a low hemoglobin may have long term iron therapy before myomectomy and 2- 3 weeks prior to the surgery it is advisable to collect blood for a potential auto-transfusion. Since blood loss at myomectomy is correlated to uterine size, it is also advisable to use techniques to shrink the fibroid prior to surgery. The most commonly used technique is to use a gonadotrophin-releasing hormone agonist [GnRH-a] such as Depo-Lupron for up to 3 months prior to surgery. This shrinks the fibroid and decreases its blood supply making it technically easier to perform the surgery and since the bleeding is sometimes so heavy that a hysterectomy may be necessary the use of the GnRH-a may make the procedure safer. When an extensive incision into the uterus is performed during a myomectomy it is usually advisable to recommend a cesarean section for the delivery in subsequent pregnancies. There is a small risk that the distended uterus may rupture the scar during labor.

If the fibroid is protruding into the uterine cavity, a hysteroscopic myomectomy is the procedure of choice. Indications for hysteroscopic myomectomy are usually abnormal vaginal bleeding and pain, but it is also performed to address repeated pregnancy loss and infertility. Contraindications to a myomectomy is the presence of uterine cancer (this should be explored prior to surgery), lower reproductive tract infections, and an extension of the tumor deep into the myometrium.

Myomectomies using a laparoscopic technique can be performed when the fibroid is easily reachable such as with pedunculated fibroids as well as subserous fibroids. When the fibroids have been removed they can be morsellated or removed through a colpotomy incision. This removal is performed with an incision in the upper vagina that gives access to the abdomen. The fibroid can be pushed out from the abdomen into the vagina and then the incision is closed. Laparoscopic coagulation of a fibroid [myolysis] can be considered as a conservative approach instead of a myomectomy. This procedure is carried out through the laparoscope with the insertion of a neodymium-yttrium-aluminum-garnet (ND:YAG) laser. The technique denaturates and coagulates protein in the fibroid and destroys its vascularity. Bipolar coagulation and cryotherapy [cryomyolysis] have also been suggested as conservative therapy of uterine fibroids. Limited follow up of myolysis and cryomyolysis has been reported.

Patients contemplating a myomectomy should be aware of the possibility of finding extensive fibromatosis which makes the myomectomy impossible. If there are too many fibroids there may not be a normal uterine structure left after the myomectomy. Bleeding may be heavy at the time of the myomectomy and a hysterectomy may be necessary to stop the bleeding. Such situations can not be predicted preoperatively and may result in the change of a treatment pattern in the middle of the surgery. After a myomectomy it is recommended that 4 – 6 months would pass before a patient attempts to get pregnant. For infertility patients it is also a good approach to perform a HSG a few months after the surgery to confirm the normal appearing uterine cavity and the normality of the fallopian tubes.

Embolization of the uterine artery for the treatment of the uterine fibroid has been employed for a little over 10 years. The same technique has been available for treatment of pelvic bleeding for a longer time. During embolization, access to the uterine artery is obtained through a puncture of the femoral artery and a catheter is guided into the uterine artery where an infarction of the fibroid is created with the injection of small polyvinyl alcohol particles. They pass through the flouroscopically guided catheter into the myoma, obliterate the vascular path and cause an acute infarction of the fibroids. The procedure is performed during conscious sedation by an interventional radiologist. The procedure is usually recommended for women with larger symptomatic fibroids who do not want uterine surgery and in a patient who may be a poor candidate for the major surgery. Most patients require hospitalization for approximately 24 hours for pain control and pain may persist for up to 2 weeks after the procedure. Post embolization fever and the development of an infection in the uterine cavity may be complications of the procedure. When the embolization is performed, some degree of passage of the polyvinyl alcohol particles towards the ovarian artery is possible and infarction of part of the ovary has been known to occur. The development of a potential reduced ovarian follicular reserve makes this procedure inadvisable in people who are planning to conceive after the embolization.

Progesterone therapy has been reported to decrease the size of fibroids as long as medication is taken. Progesterone’s such as norethindrone, medrogestone, and medroxyprogesterone (Provera) have all been used to successfully decrease the size of fibroids. The progesterones are expected to produce a hypoestrogenic effect and in that way cause a decrease in the size of the uterine fibroid. Recent developments in pharmacology have produced antiprogesterones such as mifepristone can be used to shrink uterine fibroids. Low dose therapy of mifepristone may be employed and has been known to control uterine bleeding.

Therapy with gonadotrophin releasing hormone analogs causes the development of a hypoestrogenism and amenorrhea. This hypoestrogenism causes a rapid decrease in the size of the fibroid. During the GnRH-a therapy it is anticipated that approximately 50 – 70 % of the fibroid mass will disappear. The fibroids also show a decrease in vascularity. The amenorrhea is maintained as long as the therapy is continued but when the therapy is discontinued and the pituitary starts to function estrogen levels return to normal and then the fibroids grow back to the original size in approximately 3 months after the termination of the therapy. During the amenorrhea period, anemia can be corrected and definite therapy for the fibroid is recommended to take place. During the hypoestrogenic phase, hot flashes are common symptoms and the absence estrogen also increases the risk for the development of osteoporosis. Therefore the amenorrhea and the treatment period are not recommended to be extended beyond 6 months.

In November of 2004, the Food and Drug Administration [FDA] granted pre-market approval for a magnetic resonance [MR] guided focused ultrasound system [MRGFUS] for destruction of symptomatic fibroids. The Ex-Ablate 2000 system, as it is called, was initially intended for people who were not planning to get pregnant and who have a uterine fibroid less than 24 weeks in gestational size. This technique destroys the uterine tissue by repeatedly targeting and heating the fibroid tissue while the patient is lying inside a magnetic resonance imaging field. The process takes about 3 hours to complete and is performed with a transcutaneous sonogram where the ultrasound beam is guided and focused into the fibroid. The position of the focus point is controlled by the use of magnetic resonance field. Light sedation is used since the patient may be resting for 3 hours in the MRI machine and is not permitted to move. She is conscious at all times during the procedure and needs to be able to communicate with the surgeon. If the fibroid is close to the sacrum, or that the focused ultra sound beam has to pass though the bowel, the patient is not a candidate for this procedure. Allergies to the MRI contrast medium and metal in the pelvis such as clips and IUD are also contraindications for the procedure. The patient can leave the surgical room immediately after the procedure and is transported home by an assistant because of the light sedation that has been used. She is expected to be able to return to work a few hours later or the following day. The procedure is creating a fairly instantaneous relief of symptoms from the fibroid. The size of the fibroid will decrease gradually over a 6 month period. Post operative reaction to the focused ultrasound procedure has included paresthesia, burns or irritations on the abdomen and reactions to medication as well as irritations of the sciatic nerve as it passes next to the sacrum behind the fibroid.

Initial recommendation by the FDA was not to use the focused ultrasound ablation in patients who were subsequently wishing to conceive. The focused ultrasound can be applied in a small area of the uterus, and if we have a fibroid that is close to the uterine cavity it may interfere with the implantation process. A surgical procedure such as a myomectomy may damage the uterine lining and cause interference with the implantation. The very precise removal of the fibroid that the focused ultrasound can accomplish avoids trauma to the uterine endometrium. Several pregnancies have been reported to occur after focused ultrasound ablation. No uneventful outcomes have been reported but at this time as a precaution there could be the same concern for delivery as after a myomectomy and a weak scar may be present in the pregnant uterus after the fibroid ablation. Therefore a cesarean section may be recommended for the delivery following the focused ultrasound procedure in the same way that it is recommended after a myomectomy.

Infertility and the presence of fibroids are poorly understood in reproductive medicine. It is clear that the location and position of the fibroid is more important than the size of the fibroid. Fibroids located next to the tubal entrance into the uterus may cause obstruction and interference with the sperm transport and the embryo implantation in the uterus. It is generally thought that subserous fibroids only minimally interfere with fertility, intramural fibroids may affect fertility but mostly the submucous fibroids are the ones that are resulting in both infertility and recurrent pregnancy losses. Vascular, endocrine and the mechanical alterations may be more pronounced in submucous fibroids and may induce changes in the stroma that may result in atrophy of the overlying endometrium causing a less successful implantation.

Recurrent pregnancy loss defined as 3 consecutive pregnancy losses and is thought to affect approximately 0.5% of pregnancies. Uterine factors such as Müllerian anomalies, intrauterine synechia, and fibroids are the main uterine causes for these unfortunate events. It is also thought that major distortions of the uterine cavity causes recurrent pregnancy loss and removal of the fibroid to establish a more normal uterine cavity has been reported to result in a more favorable pregnancy outcome. Along with pregnancy loss more complicated pregnancies are also frequently encountered in patients with fibroids. Patients who are pregnant may develop pain, fibroid degeneration, bleeding, premature labor, fetal malpresentation, abruption of the placenta, and more of a need for operative delivery such as cesarean section. The occurrence of pain and premature labor seems to be related to the size of the fibroid.

A sonogram is usually the first appropriate step to do in evaluating the uterine fibroid size and location, but a more accurate and more precise testing is to do an MRI. A HSG or sHSG is appropriate to evaluate the intrauterine cavity fibroids as well as the position of the fibroid in relation to the fallopian tubes. A HSG that is showing a normal uterine cavity is a sign that no further evaluation is necessary whereas a patient with a uterine distortion needs a hysteroscopic evaluation to further examine the uterine cavity. When an abnormal HSG is seen, the preparation of a surgical hysteroscopy with removal of submucous fibroids is taken into consideration.

Medical treatment of fibroids may be performed with danazol and progesterone to control bleeding but the GnRH-a are more useful to shrink the fibroids. A 50 – 70% reduction in size is not unusual during a 3 month treatment with GnRH-a but it is essential to remember that fibroids return to their original size within about 3 – 6 months after therapy. Therefore a more definite therapy is appropriate after the shrinking has been performed for three months. Before a myomectomy is attempted it is important to emphasize for the patient that there are certain criteria that need to be met and some of these criteria may not be known until in the middle of the surgery. We do not have any studies that indicate the success on fertility before and after a myomectomy but follow up on patients who desires pregnancy has traditionally indicated that a submucous fibroid that is interfering with the uterine cavity will be a cause for infertility. Recently however follow up studies have been performed on patients who underwent removal of submucous, intramural and subserous fibroids may challenge this concept. Conception rates after the removal of submucous fibroids were reported to be 55 %, after removal of intramural fibroids 62 %, and subserous fibroids 43 %. Patients with secondary infertility had a higher chance to conceive than patients with primary infertility. As in many studies in infertility the age of the patient strongly influences the out come of the surgical procedure.

Evaluation of molecular determinants of endometrial receptivity that would be important for embryo implantation in patients with fibroids indicates that there is a general negative effect on the receptivity of the endometrium in the entire uterine cavity. Not only in the endometrial cavity immediately adjacent to the fibroid but receptors that could affect implantation were negatively affected throughout the entire uterine lining.

These studies indicate that fibroids are important to include in the evaluation in infertility. The direct association between the fibroids and infertility is not well established and therefore it is essential to do a thorough fertility evaluation with male factor, female factor, ovulatory dysfunction, and anatomical structures and correct these factors if necessary. It’s also appropriate to follow the patient for some time to prove that no other infertility factors are present before a myomectomy is discussed. When the myomectomy is performed, there is some concern about trauma to the endometrial cavity, and if the endometrial cavity is entered during the surgical procedure a subsequent formation of intrauterine adhesions could be another factor that could affect fertility. The use of magnetic resonance guided imaging with focused ultra-sound ablation of uterine fibroids is quite precise, and can therefore be considered a treatment of choice for infertility patients wishing to conceive. The FDA has not yet approved the procedure for fertility patients, but from clinical experience this looks like a promising approach. There is some evidence in the literature that the removal of smaller fibroids results in a better pregnancy outcome than if the fibroid had become large. Therefore the magnetic resonance guided ablation may be a technique that can be more easily performed and is more acceptable to patients since this is non-invasive surgery.

If a patient with a fibroid undergoes invitro fertilization and sonographically guided embryo transfer it may be quite possible that the position of the embryos during the transfer can be guided into an area that is far away from the fibroid.

In conclusion it is important to emphasize that the association between infertility and fibroids is far from proven, but indirect evidence indicates that they play an important role in the development of both infertility and repeated pregnancy loss. We therefore think a thorough investigation for an infertility patient is essential, but after no other infertility factors have been identified it is appropriate to consider a myomectomy.