MIOMA UTERI Background

Uterine leiomyomas are among the most common problems encountered by the obstetrician/gynecologist. They are a frequent cause of pain and abnormal bleeding and are thought to be involved in infertility. Uterine leiomyomas are the most frequent indication for hysterectomy in the United States. Many patients develop myomas but still desire to retain the option of future childbearing or simply want to preserve their uterus. For these women, myomectomy, the removal of the myomas with reconstruction and preservation of the uterus, is an important option. For excellent patient education resources, visit eMedicineHealth's Women's Health Center. Also, see eMedicineHealth's patient education article Uterine Fibroids.

History of the Procedure

Successful abdominal myomectomy was reported as early as 1845 by brothers Washington and John Atlee in the American Journal of Medical Science. Washington, the older brother, eventually published his experience with 14 abdominal myomectomies, winning the annual prize essay award of the American Medical Association despite the death of 5 of the patients.[1] The operation was slow to gain widespread use. In 1875, W.H. Byford gave the Chairman's address to the American Medical Association Section on Obstetrics and Gynecology and said abdominal myomectomy was "so dangerous and difficult as not to be thought of except in desperate conditions." [1] At the turn of the 20th century, abdominal myomectomy was associated with a mortality rate of 40%, compared with 6-7% for abdominal hysterectomy. Victor Bonney is credited for advocating and popularizing the procedure in the 1920s.[2]

Problem
Uterine leiomyomata, or fibroids as they are more frequently but less correctly known, affect more than 20% of reproductive-aged women. Patients can have a single myoma or numerous myomas. They are benign growths in the wall of the uterus (see the image below). Most are small, do not cause symptoms, and are noted as incidental findings during routine pelvic examinations or pelvic imaging studies. When they enlarge, they can cause a mass effect, resulting in pelvic pressure or pain or a distortion of the uterine wall or endometrial cavity, which leads to abnormal uterine bleeding. At times they can cause other problems; for instance, they can prolapse through the cervix or may be confused for an ovarian mass. They are one of the most frequently encountered problems by the obstetrician/gynecologist. They can also cause problems in pregnancy, and, in some patients, myomas are thought to be linked to infertility.

Small uterine myomas visualized at laparoscopy.

For related information on pregnancy, see Medscape's Pregnancy Resource Center.

Epidemiology
Frequency
Uterine leiomyomata occur in 20-40% of reproductive-aged women.[3] Results from some ultrasonographic studies indicate the presence of at least 1 small myoma in 51% of women. Of these women, 10-35% of

Caucasian women and 30-50% of African American women have fibroids of clinical significance.[4] Myomas grow in response to estrogen stimulation and regress after menopause. Thus, they are most frequently found in women in their fifth decade of life and are quite rare in those younger than 20 years. In 2001, Schwartz reviewed the epidemiology of leiomyomas. The risk is 2-3 times higher in African American women than in white women, increases with age, decreases with having a live-born child, may increase with body mass index, and may decrease with cigarette smoking. Risk may also increase with diets high in red meat and ham and it may decrease with diets high in intake of green vegetables.[5] Most myomas are asymptomatic and inconsequential. Nonetheless, many women have significant symptoms from myomas, and myomas are the most frequent indication for hysterectomy in the United States. This indication constituted 38.1% of all hysterectomies (1.36 million) from 1994-1999.[6] Figures for myomectomy are older, but, in 1984, 18,000 myomectomies were performed, compared with 112,000 hysterectomies, suggesting approximately 1 myomectomy per 6 hysterectomies among women aged 1544 years.[7] The symptoms of fibroids, along with both surgical and medical treatments, result in enormous costs for affected women and society. To date in the United States, few data exist regarding the annual economic burden of uterine fibroids.[8]

Etiology
Leiomyomas are smooth muscle tumors that form in the uterine wall. The development and growth of uterine fibroids are influenced by multiple features including autocrine and paracrine growth factors, genetic abnormalities, race, and environmental estrogen exposure related to age of menarche, obesity, and parity.[9] The precise etiology is not known, although many cytogenetic and genetic studies have been performed. Approximately 40-50% of myomas have karyotypic abnormalities, particularly involving chromosomes 6, 7, 12, and 14. Within a myoma, all cells are identical and a monoclonal origin has been confirmed. In patients with multiple myomas, different karyotypes are noted, which suggests that each myoma arises as an individual event.[10] Other changes noted include increased expression of estrogen, progesterone, and insulinlike growth factor 1 and 2 receptors and abnormalities in the myometrium adjacent to the myoma. [11]

Pathophysiology
Although myomas are common, relatively few actually cause symptoms. Whether symptoms are present depends largely on a combination of size, number, and location of the myomas. In general, myoma growth is a result of the stimulation of estrogen, which is present until menopause. Over time, previously asymptomatic myomas may grow and become symptomatic. Conversely, many myomas begin to shrink as menopause removes the estrogen stimulation and many myoma-related symptoms resolve spontaneously shortly after menopause. Myomas are generally categorized by location. Intramural myomas are entirely or mostly contained within the myometrium. Subserosal myomas project outward from the uterus (see the first image shown below). Submucosal myomas project into the endometrial cavity (see the second image shown below). Pedunculated myomas are attached to the uterine wall by stalks and can be directed into either the peritoneal or the uterine cavity.

Small uterine myomas visualized at laparoscopy.

Submucosal myoma visualized at hysteroscopy.

Pelvic pressure and pain symptoms are usually the result of mass effect. This can occur either from a single large myoma or from a combination of multiple smaller myomas. A fibroid uterus can grow to be quite large, at times reaching the size of a term gravid uterus. Interestingly, perhaps due to the slow growth and accommodation by the patient, some extremely large uteri are well tolerated by patients and do not require intervention. Some large myomas that impinge on the ureters can cause hydronephrosis and, very rarely, ureteral obstruction. Bleeding abnormalities are usually the result of distortion of the endometrial cavity by myomas. Unlike pain, which is usually caused by large or multiple myomas, some patients have significant intermenstrual bleeding or menorrhagia from a single, small, strategically placed myoma. A submucosal myoma sometimes can prolapse through the cervix and may cause no symptoms or may cause significant bleeding. Acute pain resulting from myomas is uncommon and usually stems from 1 of 2 possibilities. Some pedunculated myomas can undergo torsion, causing the same severe pain as torsion of the ovary. Large myomas can also outgrow their blood supply, leading to infarction (degenerating myoma), which can be extremely painful. Although general agreement is lacking on the mechanism, myomas are also thought to be related to infertility, fetal malpresentations, preterm labor, and IUGR. Possible mechanisms for infertility include distortion of the endometrial cavity and abnormal endometrial surface, thereby affecting both sperm transport and embryo implantation.[12] Very rarely, myomas can be associated with erythrocytosis. This triad of myomatous uterus, erythrocytosis, and restoration and maintenance of normal hematologic values after hysterectomy is called myomatous erythrocytosis syndrome.[13] A number of etiologies have been hypothesized, but alterations in erythropoietin levels seem likely.

Presentation
Most leiomyomata are small and do not cause symptoms. Many are found as incidental findings after an obstetric or gynecologic ultrasonographic examination (see the following image) or after a routine pelvic examination.

Uterine leiomyoma as seen on ultrasound imaging. Courtesy of Rick Doherty, MD.

However, myomas can cause a number of symptoms. They can cause menstrual irregularities, particularly intermenstrual bleeding or menorrhagia. This bleeding usually begins gradually and progressively worsens as the responsible myoma enlarges. A regular menstrual pattern should be discernible within the extra bleeding. If no regular pattern is noted, an etiology such as chronic anovulation is more likely. Bleeding from chronic anovulation can be severely compounded if concomitant myomas are present. Some patients present with progressive pelvic pressure, pelvic pain, or low back pain. The problems can also have many other possible etiologies; however, if they are noted in someone with a medium- or largesized uterus (>14-15 weeks' size), the myomas are likely contributing. Some fibroid uteri can grow out of the pelvis and into the abdomen, where they can be palpated by the patient. This can be disturbing, even if the patient is having mild or no symptoms. Some are visible, distorting the abdominal wall and, at times, making the patient appear pregnant. Most myomas grow slowly, and some remain relatively unchanged over prolonged periods. In the past, rapid growth was considered worrisome for leiomyosarcoma. In 1994, Parker et al showed that sarcoma was quite rare (0.27%), even in rapidly growing uteri, and that this risk was identical to stable myomas (0.21%).[14]However, most of the patients were premenopausal. Rapid growth in postmenopausal women should be treated with greater caution. The diagnosis of degenerating myoma should be considered in a patient with known fibroids and an acute onset of pelvic pain. This pain is generally acute in onset and can be quite severe. The patient can also develop fever and an elevated white blood cell count (without a left shift) that can be confused with infection. Upon examination, tenderness is usually quite specific and localized to the exact region of the degenerating myoma. Infertility evaluations usually include an investigation for myomas, specifically submucosal myomas. Ultrasonography, hysterosalpingography (HSG), sonohysterography, or hysteroscopy are used frequently because submucosal myomas may not be detectable during pelvic examination. Several unusual presentations can also occur. A prolapsed myoma (as depicted below) is sometimes found after a routine speculum examination. A pedunculated myoma is a possible cause for an adnexal mass.

Prolapsed uterine myoma visualized through a speculum. Courtesy of Kris Strohbehn, MD.

Indications
The American College of Obstetricians and Gynecologists previously had criteria for hysterectomy for leiomyomata. Although this technical bulletin has been superseded by more recent ones that do not specify indications, these criteria are also reasonable for myomectomy. They are as follows: Asymptomatic leiomyomata that are palpable abdominally and are a concern to the patient Excessive uterine bleeding o Profuse bleeding o Anemia Pelvic discomfort caused by myomata o Acute and severe o Chronic lower abdominal or low back pressure o Bladder pressure with urinary frequency not due to a urinary tract infection All of these criteria are directed at relieving symptoms or improving quality of life by decreasing the patient's concerns. No indications exist for removing asymptomatic fibroids. Most of these patients never develop symptoms, and evidence does not support that earlier intervention improves long-term outcomes. An older argument proposed as an indication for hysterectomy, that the removal of uteri larger than 12 weeks' size improves the capability to detect adnexal masses, is also fallacious or obviated by ultrasonography. No evidence shows that routine pelvic examination improves the early detection of ovarian cancer. Similarly, no reason exists to believe that removing large uteri in an effort to make adnexa easier to examine would alter long-term ovarian cancer risk, detection, or outcome. Additional criteria include the patient's interest in preserving her fertility or a personal preference of retaining her uterus. A definite risk exists for myoma recurrence after myomectomy and, with it, the need for a repeat surgical procedure in the future. If the patient no longer desires to retain her fertility or her uterus, hysterectomy is the usual procedure of choice. Interestingly, a number of women who have completed childbearing still request myomectomy for management of symptomatic myoma. This decision is usually motivated by patient preference and a desire to retain organs. Because the short-term risks of myomectomy compare favorably with hysterectomy[15] and despite the risk of recurrence (ie, most patients do not require future surgery), a myomectomy is not unreasonable for appropriately counseled patients. Although controversial, myomectomies are also performed for patients with infertility in the presence of uterine fibroids. Several papers suggest that patients with fibroids who are undergoing assisted reproductive technology procedures may have lower success rates compared with patients without fibroids.[16, 17] On the other hand, a retrospective evaluation of donor oocyte cycles in patients with IVF revealed no difference in pregnancy rates between women without fibroids and women with noncavitydistorting fibroids.[18] Importantly, no randomized studies have been performed to show improved pregnancy success rates after myomectomy. Current recommendations include consideration of myomectomy in infertile women after eliminating other causes of infertility and in patients with cavity-distorting submucosal myomas prior to IVF.[12]

Relevant Anatomy
Leiomyomata are usually confined to the myometrium but can occur in the lower uterine segment or cervix or can project out into the broad ligament. These myomas are frequently the most difficult to remove and are problematic during both hysterectomy and myomectomy. Within the uterus, the myomas can be at any level within the uterine wall. Those mostly confined to the wall are termed intramural. Myomas projecting into the endometrial cavity are termed submucosal (as shown in the first image below), whereas myomas projecting outward from the uterus are subserosal (as shown in the second image below).

Submucosal myoma visualized at hysteroscopy.

Small uterine myomas visualized at laparoscopy.

Some myomas are attached by pedicles, which can extend outward into the abdomen and may be confused with adnexal masses or can project into the endometrial cavity and cause bleeding. Some prolapse through the cervix (see the following image).

Prolapsed uterine myoma visualized through a speculum. Courtesy of Kris Strohbehn, MD.

Contraindications
Myomectomy has a number of important contraindications. Myomectomy is not reasonable in the management of symptomatic leiomyomata in patients who no longer desire fertility or uterine preservation. It should not be performed if the patient possibly has endometrial cancer or uterine sarcoma. It should be avoided if the patient is pregnant. With the possible exception of otherwise unexplained infertility, it should not be performed in asymptomatic patients. No evidence whatsoever supports prophylactic myomectomy of asymptomatic myomas for decreasing the risk of any adverse outcome later in life. Relative contraindications include the strong possibility that a functional uterus could not be reconstructed after excision of the myomas. For myomectomy to be considered successful, reconstructing the uterus with patent tubes must be possible. Leiomyomata located in the region of the uterine vessels or broad ligament are sometimes difficult to remove without performing a hysterectomy. If the patient has numerous small myomas, removing them and reconstructing the uterus in such a way as to support a future pregnancy may be impossible. Excision of very large leiomyomata that constitute the entire anterior or posterior wall of the uterus may leave defects so large that closure is prohibited. In addition, if adenomyosis is present, it is not amenable to resection and cannot be treated by myomectomy.

Laboratory Studies
Pregnancy test: No patient should have a myomectomy until the possibility of pregnancy is excluded.

Imaging Studies

Ultrasonography: Uterine leiomyoma can usually be detected on pelvic examination. If any doubt remains or if the uterine enlargement must be confirmed or differentiated from a pelvic mass, ultrasonography is very useful. Leiomyomas can also be detected with CT scanning or MRI, but, in general, these tests are more expensive and do not help visualize the uterus as well as ultrasonography does. Fortunately, uterine leiomyosarcomas are rare; imaging study findings are not usually helpful for differentiating them from the far more common leiomyoma; confirmation requires a tissue diagnosis. HSG or sonohysterography: In the evaluation of the endometrial cavity, if a strong possibility exists that myomas are present within the endometrial cavity, perform HSG or sonohysterography. This allows the preoperative detection of myomas that may be more amenable to hysteroscopic resection and may thereby preclude the need to enter the endometrial cavity during an abdominal procedure. MRI: Myomectomy is possible only for myomas; therefore, one must reasonably believe that the uterine enlargement is from leiomyoma and not from adenomyosis. The presence of myomas can usually be confirmed based on ultrasonography or physical examination findings by the characteristic irregularities of a uterus with multiple fibroids. If any doubt remains, MRI has been found useful in differentiating leiomyoma from adenomyosis.[19, 20]

Diagnostic Procedures
Endometrial biopsy: Myomectomy is not an acceptable option if the patient has an endometrial malignancy. An endometrial biopsy should be performed prior to performing myomectomy in any patient older than 35 years who has a history of irregular bleeding.

Medical Therapy
Management of symptomatic uterine fibroids includes a number of nonsurgical approaches. Of note, treatment is usually strictly for patient comfort, and withholding treatment is reasonable in patients with no symptoms or with mild, well-tolerated symptoms. While medical treatment does not currently allow a permanent cure for fibroids, therapy with nonsteroidal anti-inflammatory drugs, oral contraceptive pills, progestins, androgens, and gonadotropin-releasing hormone (GnRH) analogs is often attempted.[21] In a 2007 Cochrane review evaluating the effectiveness of SERMs in treating fibroids, evidence was insufficient to show any improvement in fibroid size or clinical symptoms. [22] In a review by the Agency for Health Care Research and Quality, the use of preoperative GnRH agonist was shown to decrease uterine size and increase hemoglobin. They comment about the "lack of highquality evidence supporting the effectiveness of most interventions for symptomatic fibroids." [23] No randomized trials compare medical management with surgery. In general, surgery is reserved for people in whom medical management has failed. Despite the lack of good randomized evidence for the use of nonsteroidal anti-inflammatory drugs and oral contraceptive pills, these seem to be appropriate options for properly selected women without contraindications. Many women with fibroids, particularly those who have fibroids that are compounding dysfunctional bleeding, can be treated successfully with a combination of nonsteroidal anti-inflammatory drugs, birth control pills, or cyclic progestins. A short course is reasonable for patients with fibroids before committing to surgery because some patients can be treated successfully with medical management. Most studies of medical management are short, from 3 months to 1 year, and long-term success remains uncertain. Patients who are treated expectantly are usually examined more frequently than once a year. If the myomas are large and extend laterally, consideration can be given to performing periodic ultrasonographic studies to monitor for the development of hydronephrosis or the rare occurrence of ureteral obstruction.

Surgical Therapy
A number of surgical therapies are available for the management of myomas, including hysterectomy, abdominal myomectomy, laparoscopic myomectomy, and hysteroscopic myomectomy. Myomas are most commonly treated with total abdominal hysterectomy. The following sections focus on conservative surgery for leiomyomas. The traditional procedure is abdominal myomectomy, although laparoscopic

myomectomy is an acceptable option for experienced laparoscopic surgeons. While embolectomy is usually regarded as an alternative to hysterectomy, there are less often circumstances where it may be an acceptable alternative to myomectomy.[24] Myomectomy can be performed laparoscopically under certain conditions. Development of this procedure was driven by the desire to create a minimally invasive approach that would obviate a major abdominal laparotomy. Numerous published series document the feasibility of laparoscopic myomectomy.[25, 26, 27, 28] The most recent American College of Obstetricians and Gynecologists Practice Bulletin suggests that it "may be a safe and effective option for women with a small number of moderately sized uterine leiomyomas who do not desire future fertility. Further studies are necessary to evaluate the safety of this procedure for women planning pregnancy."[29] However, a review of randomized studies and clinical series concluded that laparoscopic myomectomy is feasible in well-selected individuals and, with meticulous closure of the myometrium, is safe in women considering pregnancy in the future.[30] A randomized control trial revealed similar cumulative pregnancy and live birth rates in women with unexplained infertility following laparoscopic versus abdominal myomectomy.[31] Laparoscopic myomectomy is gradually becoming a more acceptable treatment for myomas. A third technique, hysteroscopic resection, can also be used selectively for myomas impinging on the endometrial cavity that are thought to contribute to abnormal bleeding or infertility. Over the last 30 years, hysteroscopic resection of fibroids has become the standard for conservative treatment for submucosal fibroids. With the recent improvements in smaller scopes, continuous flow monitoring systems, and operative resecting tools the procedure has become safer and less invasive and, in many cases, can be performed with minimal anesthesia and cervical dilation. Proper patient selection and correct surgical technique are essential for optimizing operative success and reducing risk of complications. [32] Women with submucosal fibroids often have symptoms related to menorrhagia or infertility. Most women have significant reduction in bleeding after undergoing hysteroscopic resection. Improved fertility is also seen after removal of submucosal fibroids, although the mechanism is not fully understood. [33]

Preoperative Details
Abdominal myomectomy
The use of GnRH analogues has been studied extensively in patients undergoing abdominal myomectomy and was the subject of a Cochrane review.[34] The systematic review noted increased preoperative hemoglobin levels (weighted mean difference, 1.3 g) and decreased uterine size (weighted mean difference in volume, 159 mL). Intraoperatively, they noted a lower incidence of vertical incisions (odds ratio 0.11; 95% confidence interval, 0.02-0.75). They did not find any difference in duration of surgery or incidence of transfusion. They noted decreased estimated blood loss (67 mL), but only in the trials that had a no pretreatment arm as opposed to a placebo arm. They noted no difference in terms of quality of life or postoperative complications. One of the most important questions is whether using a GnRH analog preoperatively may increase the risk of recurrence due to making small myomas harder to find at surgery. Using ultrasonographic detection as the outcome, they noted an increased risk, but the clinical significance of this is not clear. GnRH agonists are likely a useful adjunct in patients who need to correct anemia prior to surgery and may improve the likelihood of completing the procedure through a more cosmetic incision, but they do not appear to routinely improve other relevant clinical outcomes. Reported in 1997, Deligdisch et al performed a histologic study of the cleavage planes between the myoma and the myometrium in hysterectomy specimens in patients treated with GnRH analogues and a group of untreated controls. They noted that loss of the histologic cleavage plane occurred in 91% of patients pretreated with GnRH analogues and in 50% of controls.[35] Theoretically, by decreasing the size of fibroids, some fibroids may decrease in size to the point they are not detectable at the time of surgery, thus increasing the recurrence rate.

A small, placebo-controlled, randomized trial suggests that administering misoprostol at 400 mcg intravaginally 1 hour before surgery significantly increases postoperative hemoglobin levels (9.7 g/dL vs 8.9 g/dL) and decreases estimated blood loss (472 mL vs 621 mL), operating time (48.5 min vs 58 min), and need for transfusion (15.3% vs 33.3%).[36] Preoperative bowel preparation is not necessary for these patients unless unusual adhesions are expected. No studies are available on prophylactic antibiotic use. Because this procedure is usually performed on patients who want to retain their fertility and because the consequences of infection on tubal function are severe, many providers administer prophylactic antibiotics empirically. A vaginal preparation is also a sensible precaution because 1-2% of these procedures, by necessity, are converted into abdominal hysterectomies.

Laparoscopic myomectomy
A number of authors have attempted to define who is a candidate for a laparoscopic myomectomy. The size, number, and location of the fibroids as well as the experience of the surgeon all must be factors in the decision to proceed with the laparoscopic approach. Although several suggestions have been made, opinions differ. In 1991, Nezhat et al reported on the laparoscopic removal of myomas as large as 15 cm in diameter.[37] Other authors are more conservative. In 1996, Dubuisson and Chapron suggested not removing any myoma larger than 8 cm and not performing laparoscopic myomectomy if more than 2 myomas are present.[38] In 1994, Parker and Rodi suggested limiting the procedure to patients with uteri smaller than 14 weeks' size, fibroids smaller than 8 cm, at least 50% of the myoma being subserosal, and myomas located in noncritical locations.[39] In 2003, Sinha et al reported on 51 laparoscopic myomectomies for large myomas ranging in size from 9-21 cm with a mean myoma weight of 700 g and concluded that the laparoscopic approach was a safe alternative to laparotomy. [40] GnRH analog use can slightly decrease operating time and blood loss during laparoscopic myomectomy.[41] Zullo et al noted that preoperative use of leuprolide acetate decreased estimated blood loss from 172 mL to 132 mL and operating time from 113 minutes to 99 minutes. On the other hand, longer operative times, 112 minutes versus 157 minutes, with preoperative GnRH analog use found by Campo and Garcia, were attributed to difficulty in detecting the myoma cleavage plane.[42] All patients undergoing laparoscopic myomectomy should also give consent for laparotomy because conversion to a laparotomy intraoperatively may be necessary in as many as 8% of procedures.[28]

Hysteroscopic myoma resection

Patient selection is essential to achieve resolution of bleeding symptoms, enhance fertility, and reduce surgical risks. Preoperative imaging with MRI, 3-dimensional ultrasonography or saline-infused sonohysterogram can provide a map of the uterine myomas and identify the intramural component of the fibroids. The European Society of Hysteroscopy designed a classification system for submucosal fibroids based primarily on this concept. Type 0 fibroids are pedunculated with no intramural component. Type I fibroids are sessile submucosal fibroids with less than 50% intramural component. Type II fibroids have a greater than 50% myometrial invasion.[43] When complete resection of the fibroid is accomplished, recurrence of bleeding is unlikely regardless of the type of fibroid resected. Incomplete resection of the fibroid is more likely in type II fibroids with more extensive intramural component. Calculated from one study was a 50% chance per procedure of complete resection of type II fibroids, 60% of type I fibroids, and 92% of type 0. After an incomplete resection, the residual intramural component is likely to be expelled into the cavity and a second procedure is often successful. The patient with type II fibroids should be counseled on the risk of failure and the procedure should be performed by experienced hysteroscopic surgeons. Preoperative treatment with danazol or a GnRH agonist has been shown to reduce surgical time, bleeding, and absorbed distension media.[44, 45] Some authors have recommended pretreatment with a

GnRH analogue for submucosal fibroids greater then 3 cm in diameter.[46] Other studies have found no benefit and have even suggested a longer operating time possibly due to difficulty with cervical dilation in the pretreated group. Whether the cost and side effects of pretreatment are outweighed by any potential benefit remains unclear.[47] The most common complications with hysteroscopic myomectomy are uterine perforation, false cervical canal, and excessive absorption of distension media.[48, 49] . Hemorrhage and infection are rare and antibiotic prophylaxis is not recommended routinely.[50] Preoperative cervical ripening with a prostaglandin analogue has been demonstrated to facilitate cervical dilation. Misoprostol 200 mcg applied vaginally 812 hours prior to surgery is well tolerated and can decrease surgical time and reduce the risk of surgical complications.[51]

Intraoperative Details
Abdominal myomectomy
Patients undergoing abdominal myomectomy require anesthesia adequate for a laparotomy, usually general endotracheal anesthesia. An incision is chosen that allows maximal exposure. Many myomectomies can be performed through a Pfannenstiel incision, but vertical incisions can be used when necessary. In some cases, better exposure could be the difference between the ability to stop hemorrhage and preserve the uterus and the need to proceed with hysterectomy to control bleeding. Several excellent atlases are available for full details of surgery.[52, 53] One important issue with myomectomy is controlling blood loss from the raw myoma beds after they have been excised. Several techniques have been studied. A randomized trial comparing vasopressin and saline injected into the serosa prior to the uterine incision showed that vasopressin is extremely effective for decreasing blood loss. In this study, 50% of patients receiving saline required transfusion, while none of those in the vasopressin group required transfusion (13% vs 5% decrease in hematocrit values). [54] Many providers place tourniquets to control bleeding.[55] This is usually performed by making a window in the broad ligament at the level of the internal cervical os bilaterally and passing a Foley catheter or red rubber catheter through the windows and around the cervix and then tightening it with a clamp to constrict the uterine vessels. In combination with this, vascular clamps are generally placed on the utero-ovarian ligaments. Two randomized trials compared vasopressin and tourniquet use. In 1996, Fletcher et al showed that vasopressin was associated with less blood loss and lower risk of either transfusion or blood loss of more than 1 L.[56] In 1993, Ginsberg et al noted no statistically significant difference between the groups, although their study was much smaller.[57] No studies are available comparing tourniquet use with no tourniquet use. Study results clearly suggest that vasopressin (usually 20 U in 50-100 mL normal saline) should be injected routinely prior to making the incision in the wall of the uterus. Whether additional use of a tourniquet further decreases blood loss remains unclear. A Cochrane review evaluating techniques to decrease intraoperative blood loss in both abdominal and laparoscopic approaches found that misoprostol, vasopressin, bupivacaine plus epinephrine, and pericervical tourniquet all lead to significant reduction in bloodloss.[58] After dilute vasopressin has been injected, an incision is made through the wall of the uterus into the myoma. Once the plane between the myometrium and myoma has been defined, it is dissected bluntly and sharply until the entire fibroid is removed. As many fibroids as possible are removed through a single incision. Once the fibroids have been removed, the defect is closed in layers with delayed absorbable suture. Proper placement of the incision is frequently overlooked but is important. Reported in 1993, Tulandi et al studied 26 women with uteri larger than 6-8 weeks' size. Abdominal myomectomies were performed, followed by a second-look laparoscopy 6 weeks later. Patients with incisions in the posterior wall of the uterus had a much higher likelihood of significant adhesions as measured by percentage with adhesions or American Fertility Society (AFS) adhesion score compared with patients with incisions in the fundus or

anterior wall of the uterus.[59] Use of adhesion barriers, including Interceed and Seprafilm, is associated with decreased incidence of adhesion formation.[60]

Laparoscopic myomectomy
Unfortunately, a number of important unresolved technical issues remain regarding laparoscopic myomectomy. One difficulty is in the removal of the fibroids, which has been performed using morcellation[61] , minilaparotomy[62] , or colpotomy. Alternatives to these are to destroy the fibroids in place with cryotherapy[63] , bipolar cautery[64] , or laser[65] . No trials have compared these techniques to determine which is the safest or most effective. Articles by Peacock[66] and Parker[60] reviewed techniques for laparoscopic myomectomy. Intraoperative port placement depends on uterine size, and size and location of the fibroids. Often, 2 ports are used on the patients left or right side for fibroid enucleation and suturing, including a port 2 cm medial to the iliac crest, as well as a 5 mm port lateral to the umbilicus. For retraction and exposure purposes, another port is placed on the opposite side of these ports. An umbilical port site is made for the laparoscope; however, an upper quadrant port may be necessary for a large uterus. After vasopressin injection into the myoma, a transverse incision over the fibroid with the Harmonic scalpel or other cautery is extended down to the avascular myoma plane. A tenaculum is then used to grasp the myoma to create countertraction. The cleavage plane between fibroid and uterus is identified, and the myoma is dissected out of the uterus. One to three layers of delayed absorbable sutures are used to repair the myometrium and serosal defect. Morcellation of the myoma is followed by irrigation and placement of adhesion barrier. Closing the uterine defect left by the destruction or removal of the fibroid is a critical technical issue. This is much more difficult than during an open procedure. As reported in 1991 and 1996, Nezhat et al performed laparoscopic myomectomy and then performed a second-look laparoscopy on 28 women 6 weeks later. They had removed 37 myomas from these women and closed the defects with laparoscopically placed sutures. At the second look, indentations were visible at all of the sites where the myomas had been excised. In addition, 6 uterine fistulas were visible on postoperative HSG findings. [37, 67] Three prospective randomized trials comparing abdominal and laparoscopic myomectomy are as follows: In 2000, Seracchioli et al compared 65 women undergoing abdominal myomectomy with 66 women who underwent a laparoscopic procedure. They excluded patients with more than 3 myomas greater than 5 cm or uterine size extending above the umbilicus. They found significantly less febrile morbidity, lower transfusion rates, and shorter hospitalization stays in the group of women treated laparoscopically. [68] In 2001, Rossetti et al reported on 81 women randomized to laparotomy or laparoscopy for treatment of myomas greater than 3 cm, with no more than 7 myomas per patient. At 40-month follow-up, the recurrence rates were similar between the 2 groups.[69] Alessandri and colleagues randomly assigned 148 women to either laparoscopy or minilaparotomy for fibroid removal. Laparotomy resulted in shorter operative times and lower postoperative hemoglobin, while hospital stay and pain were less in the laparoscopic group. No recurrences were detected in either group after 6 months.[70]

Hysteroscopic resection of myomas

A thorough discussion of hysteroscopy can be found in Medscape Reference'sHysteroscopy article. Patients undergoing diagnostic hysteroscopy should also give consent for resection of myomas projecting into the endometrial cavity. Myoma resection is usually performed with a loop electrode by shaving the visible portion of the myoma into small pieces (see the image shown below). [71, 72, 73]Sometimes, myomas deeply embedded in the myometrium cannot be completely excised. Other techniques for removing the myoma hysteroscopically include using an Nd:YAG laser fiber [74] or electric myoma vaporizer[75] .

Submucosal myoma being resected hysteroscopically with a loop resectoscope.

Various sizes of operating hysteroscopes are now available, but they all include a telescope with a fiberoptic light source and camera. The angle of the telescope is either 0 or an acute angle of 12-30. The straight visual 0 scope might be helpful with fundal myomas but an angled perspective is more commonly used for fibroid resection. The telescope inserts through an external sheath and internal sheath for continuous outflow and inflow of distension media. The working element of the operating hysteroscope is the resecting loop that is available in many sizes and angles. The electrosurgical energy connected to the loop can be monopolar or bipolar. With the monopolar loops, using nonionic distension media such as glycene 5% or sorbitol 1.5% is necessary. With bipolar loops, both electrodes are within the cavity and normal saline can be used for distending solution. For hysteroscopic myomectomy, various laser types and mechanical loops without electrical energy have also been described. There are multiple methods of using the electrosurgical loop to optimize fibroid resection. To maintain good visualization, fragments of resected fibroid need to be removed during the procedure. The surgeon may transfer fragments out of the field of resection or retrieve them from the cavity by grasping the tissue with the resecting loop. An intrauterine morcellator has recently been introduced that may improve surgical time by aspirating fibroid fragments through the hysteroscope. [76]When applying the monopolar loop, currents as high as 75-150 W are required for smooth tissue cutting.[77] Current should only be applied while the loop is being retracted into the hysteroscope or while the entire resectoscope is being pulled away from the fundus. A combination of the 2 movements is used by the surgeon to safely and effectively slice through the tissue. Resection of type 0 fibroids can be accomplished in 1 step by most hysteroscopic surgeons since the border of the fibroid with the endometrium is easily identified.[78] Type I and type II fibroids require more surgical expertise as resection of the fibroid extends into the myometrial space. Intraoperative cervical injection of carboprost, a methyl analogue of prostaglandin F2-alpha, has been shown to cause uterine contractions and thereby squeeze the remaining fibroid into the cavity to facilitate a single step. Concomitantly performing laparoscopy with intramuscular injection of prostaglandin F2-alpha is also effective for resection of large fundal fibroids and provides transabdominal visualization. [79] In many circumstances, resection of large fibroids with significant intramural component is a 2-step approach since there is often further intracavitary expulsion of the fibroid after the initial surgery. The second procedure can be performed 3-6 weeks later when the residual fibroid has migrated into the submucosal space.[80]
Hysteroscopic myomectomy. A 24-year-old woman with menorrhagia and severe anemia in whom hormonal treatment failed. Sonohysterography showed multiple submucosal fibroids. She underwent hysteroscopic myomectomy after administration of Depo-Lupron. Part 1. Video courtesy of Tarek Bardawil, MD. Hysteroscopic myomectomy. A 24-year-old woman with menorrhagia and severe anemia in whom hormonal treatment failed. Sonohysterography showed multiple submucosal fibroids. She underwent hysteroscopic myomectomy after administration of Depo-Lupron. Part 2. Video courtesy of Tarek Bardawil, MD.

Postoperative Details
After abdominal myomectomy, patients are treated as any other patients who have had a laparotomy. Patients should attempt ambulation early, and the diet should be advanced at the surgeon's discretion. The patients tend to be young and healthy; therefore, recovery is usually fairly rapid. Postoperative vaginal bleeding is common. Fever is also common, particularly in the first 48 hours, but does not appear

to be due to infection.[81] No studies have determined the optimal amount of time patients should wait prior to attempting conception. A prudent plan is to allow patients to heal for at least several months prior to any attempts. Patients should not use tampons, douche, engage in sex, or place anything in their vagina for at least 4-6 weeks postoperatively. For hysteroscopic myoma resection, some authors advocate the postoperative administration of oral estrogen to decrease the chance of intrauterine synechiae formation, although no studies support this measure.[82, 83]

Follow-up
Patients who have had myomectomies should be monitored for recurrence of myomas. Patients are typically seen for a routine postoperative examination 2-6 weeks postoperatively. A pelvic examination at 3 months, 6 months, and 1 year to assess for myoma recurrence seems reasonable, although no studies have been performed to support this protocol. If no recurrence is observed in 1 year, annual examinations are likely adequate. In 1997, Vavala et al studied the use of GnRH analog for preventing the recurrence of myomas after myomectomy. The 65 patients who were studied were given leuprolide acetate (Lupron) depot for 3 months each year for 3 years. At the end of this time, the patients showed significantly reduced uterine volume and a reduced myoma recurrence rate compared with untreated patients. Although this suggests that GnRH analog might be useful, the authors did not present data on symptoms or the need for repeat surgery.[84] Further study clearly is needed.

Complications
Abdominal myomectomy
Abdominal myomectomy is associated with both short- and long-term problems. Short-term complications include all of the usual complications of gynecologic laparotomy, including bleeding, infection, visceral damage, and thromboembolism. Intraoperative blood loss is variable depending on the size and location of uterine fibroids. In 1996, Iverson et al reviewed the relative morbidity of abdominal myomectomy compared with abdominal hysterectomy in patients at Tufts Medical Center. Patients who underwent myomectomy had an average blood loss of 464 mL and a risk of transfusion of approximately 28%. However, nearly three quarters of these transfused units were autologous blood replacement, and many of these patients likely would not have received blood if only random donor blood had been available. Approximately 13% of patients had temperatures of at least 38.5C (101.3F) 48 hours postoperatively and were started on antibiotics for presumed infection. When compared with hysterectomy, operative times were nearly identical. The blood loss, traditionally thought to be more than with hysterectomy, was actually significantly lower.[15] No intraoperative visceral injuries occurred in patients who underwent myomectomy, although a number occurred in patients who underwent hysterectomy. In 1993, LaMorte et al noted similar complication rates in an uncontrolled series of patients at Yale[85] , and, in 2000, Sawin and coworkers noted similar results when hysterectomy and myomectomy were compared[86] . Patients undergoing myomectomy have an unusually high incidence of fever occurring in the first 48 hours postoperatively, a phenomenon that appears to be unique to this procedure. This was also studied by Iverson et al in 1999.[81] They noted a baseline risk of approximately 33% for fever of at least 38.5C (101.3F) within the first 48 hours. When compared with hysterectomy and using multivariate analysis to control for age, parity, estimated blood loss, and type of physician performing the surgery, they noticed a 3.9-fold increased risk. This "myomectomy fever" may be due to the release of unknown pyrogenic factors during the myoma dissection or from hematomas forming in defects left by the removed myomas. The most significant short-term risk is the potential need to convert a myomectomy to a hysterectomy intraoperatively. This occurs largely for 2 reasons. First, reconstructing the uterus may not always be possible because of the many defects left by the removal of multiple small fibroids or a single large

fibroid. Second, a hysterectomy may be necessary intraoperatively to control bleeding. In the Tufts series reported by Iverson et al in 1996, conversion to hysterectomy intraoperatively became necessary in 2 of 103 myomectomies..[15]In the Yale series reported by LaMorte et al in 1993, 1 of 128 required a hysterectomy.[85] All patients undergoing myomectomies should be apprised of this possibility as part of the consent process. Only one study separately examined complications in patients who underwent a second myomectomy. In 2002, Frederick et al reported on a study of 58 women who underwent repeat abdominal myomectomy, and they noted 33% febrile morbidity and 700 mL median blood loss. Of these women, 12% were transfused and 1 required hysterectomy.[87] Overall, data evaluating abdominal myomectomy and subsequent uterine rupture is lacking. However, 2 case reports revealed postabdominal myomectomy uterine rupture at 20 weeks' and 12 weeks' gestational age[88, 89] , and 1 study reported 3 uterine ruptures in 24 patients with prior myomectomies involving uterine cavity entry[90] .

Laparoscopic myomectomy
Laparoscopic myomectomy has all of the usual risks of laparoscopy, predominantly those related to trocar placement. This includes injury to bladder, bowel, ureter, and blood vessels, and the need to convert to a laparotomy. Rates of conversion vary from very low to 8-10%, largely depending on the complexity of the case. Suboptimal defect closures are of great concern for uterine rupture in future labor. A number of case reports have been published that describe uterine rupture after laparoscopic myomectomy. [91, 92, 93, 94, 60] Two retrospective analysis evaluating uterine rupture after laparoscopic myomectomy showed no cases of uterine rupture.[95, 96] The largest published series of laparoscopic myomectomy reported 1 uterine rupture per 213 patients.[28]

Hysteroscopic myoma resection

Complications of hysteroscopic myoma resection include hemorrhage, uterine perforation, damage to the cervix, and excessive absorption of the distention media (usually glycine) into the vascular system, which can cause metabolic disturbances.[97] The most serious potential complication with hysteroscopic myomectomy is excessive absorption of distension media, which can cause pulmonary edema, hyponatremia, cerebral edema, and even death.[98] This is especially true when using nonconducting distension solution with monopolar cautery. A surgeon should also be cautious with saline during resections with bipolar cautery since large volumes of fluid can lead to overload complications. A fluid management system that can accurately calculate the amount of absorbed fluid by measuring the inflow and outflow of distension fluid should be used. Intracervical injection of dilute vasopressin, in addition to reducing the force needed to dilate the cervix, has also been shown to decrease the absorption of distention fluid.[99, 100] In 1991, Corson and Brooks noted 1 case of heavy bleeding that required transfusion and 3 uterine perforations out of 92 patients undergoing hysteroscopic myoma resection.[71] In 1993, Indman noted distension media complications in 2 of 51 women.[101] Intrauterine synechiae can also occur after hysteroscopic myoma resection.[102]

Outcome and Prognosis

Despite a long history of using myomectomy and extensive literature on this procedure, data are actually poor because of 2 important issues related to outcome. In particular, both the recurrence rate and the impact on fertility have been poorly studied.

Abdominal myomectomy
In 1998, Vercellini et al extensively reviewed abdominal myomectomy as a fertility-enhancing procedure.[103] They noted that although numerous papers report on fertility outcomes after myomectomy,

they all share the same serious flaws. In particular, not a single study included controls or used randomization. Only a few of the studies used life-table analysis. All used differing definitions of infertility and included heterogeneous uses of other infertility treatments. Nonetheless, the studies were fairly consistent, with approximately two thirds of patients with myomas and otherwise unexplained infertility conceiving after myomectomy. Similar results were noted in both prospective and retrospective studies. However, results were inconsistent when subgroups were analyzed. Myomectomy continues to be offered routinely to patients with uterine fibroids and infertility, but until controlled studies with expectantly managed controls are performed, the benefit of this procedure for patients remains unclear. The risk of myoma recurrence is similarly poorly studied. Patients undergoing myomectomy should be counseled that they are at risk for fibroid recurrence and the potential for additional surgery in the future. Unfortunately, proper studies to determine recurrence risk are not available. Most studies are limited because they include heterogeneous study groups composed of a mixture of symptomatic patients who are treated for fibroids and asymptomatic patients who are treated for infertility. Follow-up in all of these studies is poor, with many patients lost to follow-up and most with short follow-up periods. Because fibroids may recur slowly over a long period, studies with short follow-up times do not yield the necessary information. In addition, the studies use different definitions of recurrence, some limited only to symptomatic recurrence and some including patients with asymptomatic fibroids detected after ultrasonographic or pelvic examination. Most do not use life-table analysis. Many women are likely to experience recurrence of myomas after myomectomy. In 1995, Fedele et al reported on the use of ultrasonography to help diagnose recurrences and noted a cumulative recurrence rate of 51% over 5 years.[104]However, asymptomatic recurrence is not generally a relevant outcome. Limiting to studies that look at patients who require reintervention after myomectomy and appreciating that most of these studies have short (< 5-y) follow-up, recurrence rates of 8-27% are noted (see Table 1). Most of the higher rates are noted in older studies, when hysterectomy was performed for much more liberal indications and was performed much more frequently. Looking at these studies, the medium-term risk for the need for repeat surgery after myomectomy is 5-10%. In the only study of risk factors for subsequent surgery, Stewart et al reported that the repeat surgery rate was 35%, with most of these being endoscopicprocedures.[105] Several studies established particular risk factors for reoperation. In 1969, Malone noted that removal of multiple myomas was a strong risk factor for reoperation.[106]Future repeat surgery was required in 26% of patients with multiple myomas, compared with 11% of patients with single myomas. Also, pregnancy after myomectomy appears to be protective. In 1991, Candiani et al noted that over 10 years following myomectomy, 15% of patients achieving pregnancy and 30% of patients not achieving pregnancy required repeat surgery.[107] In 2002, Stewart et al noted a decreased risk of repeat surgery if the uterus was greater than 12 weeks' size at the time of the initial surgery (hazard ratio, 0.1; 95% confidence interval, 0.01-0.4) and an increased risk with weight gain of more than 30 pounds since age 18 years. [105] In 2005, a retrospective analysis of 132 patients after myomectomy via laparotomy revealed a 62% 5-year recurrence rate and a 17% rate of reoperation for myomas. Lower recurrence rates were seen in patients with uterine size < 10 weeks, patients with a single myoma, and those who had a subsequent childbirth.[108] Table 1. Summary of Studies Reporting Need for Future Surgery for Myomas After Myomectomy (Open Table in a new window) Study Finn and Muller[109] Year Follow-up, mo Reoperation Rate 1950 24-120+ 13%

Brown et al[110] Malone[106] Berkeley et al[111] Garcia and Tureck[112] Rosenfeld[113] Smith and Uhlir[114] Verkauf[115] Gehlbach et al[116]

1956 >72 1969 >60 1983 17 1984 >10 1986 >12 1990 NR 1992 42 1993 >12

17% 27% 8% 6% 4% 5% 6% 12% 8% 35% 17%

Acien and Querada[117] 1996 4-144 Stewart et al[105] Hanafi[108] 2002 84 35 2005 2-136

Another long-term complication that must be considered is the risk of uterine rupture during pregnancy. Fortunately, this is quite rare and is most likely to occur in labor. Although data are limited to support it, the usual recommendation is to offer cesarean delivery to patients who had myomectomies in which large defects in the active segment of the uterus were created by removal of the fibroids. Some recommend cesarean delivery any time the endometrial cavity is entered during the procedure, but what seems more likely is that the total extent of the defect, not entry into the endometrium, is the factor that presents the risk to the patient. Recommendations must be individualized for each patient. These recommendations are best made by the physician performing the myomectomy and should be clearly documented in the chart and conveyed to the patient so that the recommendations are clear in the event of future pregnancy.

Laparoscopic myomectomy
Regarding fertility, successful reproductive outcomes are possible after both laparoscopic and abdominal myomectomy. A retrospective study by Seracchioli et al in 2006 reported a 54% pregnancy rate and a 67% delivery rate postlaparoscopic myomectomy.[118] Cumulative pregnancy rates and live birth rates in a randomized controlled trial comparing laparoscopic myomectomy and abdominal myomectomy noted no difference between these 2 groups. However, the per cycle live birth rate and pregnancy rate were higher in patients who underwent laparoscopic fibroid removal.[31] In a 2006 Cochrane review that included only 1 randomized controlled trial, pregnancy rates were similar in infertile patients who underwent myomectomy via laparotomy compared to laparoscopic myomectomy. [119] A few studies have reported on the risk of recurrence after laparoscopic myomectomy. One study observed 114 women for a mean of 37 months and defined recurrence as the return of any myoma. The cumulative recurrence risk was 10.6% at 1 year, 31.7% at 3 years, and 51.4% at 5 years. Eight patients underwent repeat laparoscopic myomectomies. One patient underwent 2 laparoscopic myomectomies. One patient had a myomectomy and then a total abdominal hysterectomy, and 6 had total abdominal hysterectomies. Of the patients, 14% required repeat surgery.[67] Another group observed 192 women after laparoscopic myomectomy and found, based on symptoms and ultrasonographic findings, a cumulative recurrence risk of 16.7% at 5 years. Approximately 4% of the

patients required further surgery.[120]Interestingly, another study noted that the preoperative use of GnRH agonist increased the risk of myoma recurrence after laparoscopic myomectomy. [69] In 1992, Goldfarb presented data on patients who underwent myolysis with the Nd:YAG laser. He studied 75 patients and reported 50% shrinkage of the myomas at 6 months. This series, similar to most others on minimally invasive techniques, reported no medium- or long-term data on pregnancy or need for future procedures.[65] In 1998, Chapman reported on a similar procedure performed on 293 patients. Of these, 6 patients required hysterectomy and 30 had future pregnancies.[121] In 1995, Goldfarb reported on myolysis with bipolar cautery and reported 83% shrinkage over 6 months.[64] One series reported 2 of 3 patients with uterine rupture after they became pregnant within 3 months of the procedure. [122] Compared with abdominal myomectomy, patients having undergone laparoscopic myomectomy have less pain, shorter hospitalization[60, 123] , and fewer postoperative adhesions, but longer operative time.[123] Overall, no difference is apparent in postoperative complications or fibroid recurrence between the 2 groups.[66]

Hysteroscopic myoma resection

Many studies have assessed fertility rates after hysteroscopic myomectomy and have noted pregnancy rates similar to those after abdominal myomectomy, approximately 60% (see Table 2). Again, no studies include expectantly managed control groups. Table 2. Pregnancy Rates in Patients Undergoing Hysteroscopic Myomectomy(Open Table in a new window) Author Donnez et al[74] Year Study Size Pregnancy Rate 1990 24 67% 47% 37% 27% 35% 72%

Goldenberg et al[124] 1995 15 Vercellini et al[125] Fernandez et al[126] Bernard et al[127] Shokeir[128] 1999 40 2001 59 2000 31 2005 29

Reoperation after hysteroscopic myomectomy has also been studied. As usual, these studies are limited by short follow-up periods. In 1995, Ubaldi et al reviewed older studies, which had reoperation rates of 525% after as long as 3 years of follow-up.[83] In 1999, Vercellini et al studied 108 women who had hysteroscopic resection of submucous, pedunculated, sessile, or intramural leiomyomas. After a mean follow-up of 41 months, 27 patients had myoma recurrence based on ultrasonographic findings, with a 3year cumulative recurrence rate of 34%. Twenty women had recurrent menorrhagia, with a 3-year rate of 30%.[125] In 1999, Emanuel et al reported on 285 women who had submucous myomas treated with hysteroscopic myoma resection without endometrial ablation. Several patients required multiple procedures. Patients were monitored for a median of 46 months. Forty-one patients (14.5%) required repeat surgery. Patients who required repeat surgery were more likely to have larger uteri and higher numbers of submucous myomas. Hysterectomy was required in 20 of the 41 patients who required repeat surgery. Most (90.3%) patients with normal-sized uteri and 2 or fewer myomas did not require future surgery at 5 years. [129]

In a second series from Britain, also reported in 1999, Hart et al studied 122 women for a mean of 2.3 years. Of these women, 21% required repeat surgery by 4 years and 0% thereafter. Their regression analysis suggested that outcome was better in older women in whom the uterus was smaller than or equal to 6 weeks' gestational size or the fibroid was smaller than or equal to 3 cm and mainly intracavitary.[130] In 1994, Donnez et al studied the recurrence of menorrhagia based on the site of the myoma. They noted that women who had multiple submucosal myomas were much more likely to have recurrent symptomatic menorrhagia than women who had only 1-2 myomas. Having the largest diameter inside the uterine cavity and the largest portion of the uterine wall were less accurate predictors. [131] Although many reports exist regarding fertility after hysteroscopic myomectomy, currently no good randomized controlled trials have evaluated this outcome.[119]

Vaginal removal of a prolapsed myoma

Management of a prolapsed vaginal myoma can also be problematic. A single study noted that removal of prolapsed myomas represented 2.5% of all procedures for myomas. Approximately 93.5% of these procedures were successful with transvaginal removal, and 6.5% of patients needed a total abdominal hysterectomy. Of the failures, only 1 had very serious complications. After the initial vaginal myomectomy, 34 patients were monitored for a median of 5.5 years. In these patients, 79% had no further symptoms from their fibroids. Of those remaining, 21% developed other symptoms, of whom 6% required a hysterectomy, 6% had a single repeat prolapsed myoma, and 3% (1 patient) had multiple repeat procedures.[132]

Future and Controversies

Many questions remain regarding the natural course of untreated fibroids, the efficacy of medical management, and the unanswered questions regarding surgery as discussed. The 2007 Agency for Health Care Research and Quality evidence-based review provides a superb review of these topics.[23] Current controversies include the role of minimally invasive procedures. In particular, laparoscopic myomectomy has many theoretical advantages, including lower cost and avoidance of prolonged hospitalizations. However, whether the repair of the defect is as effective as that performed with abdominal myomectomy remains unclear, and the procedure may be associated with an increased risk of uterine rupture during pregnancy. Medical therapy is also being explored. At present, data for medical management, particularly new treatments such as tibolone or older treatments such as controlling symptoms with birth control pills, are very scant. The role of GnRH analogs also requires further clarification. The advantages in terms of making the fibroids smaller must be balanced against the high cost and the subsequent inability to locate fibroids that were previously reduced by treatment. A number of newer treatments are being explored. Uterine artery embolization (UAE), in particular, may be an especially promising minimally invasive approach to fibroids.[133, 134] In this procedure, angiographic catheters are introduced in the groin and passed to the uterine artery under fluoroscopic guidance. Microspheres are then injected, which lodge in the blood supply to the myomas and cause them to infarct. Significant pain from the acute infarction of the myomas usually requires hospital admission for pain control. A number of complications have been reported, including prolapsing myomas, infection, and hematoma at the catheter placement site in the groin, and bleeding and infection requiring hysterectomy. However, short-term results for relief of heavy bleeding and pelvic pain and pressure have been good. In a metaanalysis comparing uterine artery embolization to surgical interventions for fibroids, embolization offers a shorter hospital stay and quicker return to normal activities but failed to show any significant benefit in effectiveness or safety.[135] In the FIBROID registry, more than 1200 patients undergoing UAE were observed for 3 years after the procedure. More than 85% would recommend the procedure and about 15% of patients failed and underwent further surgery or repeat embolization.[136]

Although UAE is reserved for women who do not desire fertility, reports exist of pregnancies postembolization. One study suggested that women are able to achieve successful pregnancies after uterine fibroid embolization without significant adverse outcomes.[137] A review of studies observing pregnancy after embolization concluded that these patients may have higher rates of spontaneous miscarriage, preterm delivery, malpresentation, and abnormal placentation. [138] The ACOG Committee Opinion on UAE states that the procedure should be considered investigational or relatively contraindicated in women wishing to retain fertility.[29]Overall, data are extremely limited and larger prospective studies are needed. In 2004, the US Food and Drug Administration approved a new technology, ExAblate 2000. Use of highintensity focused ultrasonographic waves under MRI guidance to induce coagulation necrosis in fibroids has been shown to be effective for treating solid tumors like fibroids. In one study of 109 patients, 71% had significant improvement in symptoms at 6 months and 51% at 12 months.[139]More studies are needed for longer term analysis and evaluation of cost-effectiveness. Robotic surgery has become increasingly popular in gynecologic procedures involving cancer staging, hysterectomies, and myomectomies. Advantages to the da Vinci including 3-dimensional imaging and enhanced dexterity may help surpass the obstacles encountered while enucleating the fibroid, and repairing the uterine defect in laparoscopic myomectomy. More prospective trials are needed in this area of interest.[140]
Robotic myomectomy. A 32-year-old woman was found to have a large fibroid during pregnancy. Postpartum, the fibroid caused pelvic pain and dyspareunia. Pelvic ultrasonography revealed a 10-cm fundal transmural fibroid. Part 1. Video courtesy of Tarek Bardawil, MD. Robotic myomectomy. A 32-year-old woman was found to have a large fibroid during pregnancy. Postpartum, the fibroid caused pelvic pain and dyspareunia. Pelvic ultrasonography revealed a 10-cm fundal transmural fibroid. Part 2. Video courtesy of Tarek Bardawil, MD.

As more is learned about the genetics of leiomyomas, targeting the specific genetic defect to help prevent or treat myomas may eventually be possible.