TECHNOLOGY, INNOVATION AND IMAGES OF HEALTH AND AGING Background Demographic aging is among the most striking societal changes advanced societies facetoday. It is clear that aging poses social care and public health systems with severechallenges, but also that aging market places ask for changes in current practices oftechnology and innovation. Older adults will become an increasingly importan
Acog practice bulletin, number 96, august 2008, replaces practice bulletin 16, may 2000 and committee opinion number 293, february 2004PRACTICE
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIAN–GYNECOLOGISTS Replaces Practice Bulletin Number 16, May 2000 and Committee Opinion Number 293, February 2004 Alternatives to
Hysterectomy in the
Uterine leiomyomas (also called fibroids) are the most common solid pelvic tumors in women and the leading indication for hysterectomy. Although many women with uterine leiomyomas are asymptomatic and can be monitored with- out treatment, some will require more active measures. Hysterectomy remains the most common surgical treatment for leiomyomas because it is the only definitive treatment and eliminates the possibility of recurrence. Many women seek an alternative to hysterectomy because they desire future childbearing or obstetric and gynecologic care.
These guidelines should not be con- wish to retain their uteri even if they have completed childbearing. As alterna- tives to hysterectomy become increasingly available, the efficacies and risks of these treatments are important to delineate. The purpose of this bulletin is to review the literature about medical and surgical alternatives to hysterectomy and to offer treatment recommendations. individual patient, resources, andlimitations unique to the institutionor type of practice.
The two most common symptoms of uterine leiomyomas for which womenseek treatment are abnormal uterine bleeding and pelvic pressure. The mostcommon kind of abnormal uterine bleeding associated with leiomyomas isheavy or prolonged menstrual bleeding, which frequently results in iron defi-ciency anemia (1). This heavy flow may result in significant disruption of a THE AMERICAN COLLEGE OF
woman’s daily activities. However, not all bleeding is caused by leiomyomas; OBSTETRICIANS AND
therefore, other causes of abnormal bleeding should be ruled out. The pelvic GYNECOLOGISTS
and abdominal discomfort that women experience with leiomyomas often is WOMEN’S HEALTH CARE PHYSICIANS
described as pressure. In addition to pelvic pressure, leiomyomas may interfere with adjacent structures, leading to dyspareunia and dif- and uterine size is recommended. Epidemiologic studies ficulty with urination or defecation.
also suggest that both combined oral contraceptives and Uterine leiomyomas are very common, with some progestin-only contraceptives also may decrease the risk studies reporting leiomyomas in 70% of white women of developing clinically significant leiomyomas (11, 12).
and more than 80% of black women by age 50 years (2).
Nonsteroidal antiinflammatory drugs are effective in Leiomyomas can vary greatly in size and may be present reducing dysmenorrhea, but there are no studies that in subserosal, submucosal, intramural, pedunculated, or document improvement in women with dysmenorrhea combined locations. Symptoms and treatment options are affected by the size, number, and location of the The levonorgestrel intrauterine system leads to min- leiomyomas. The lack of a simple, inexpensive, and safe imal systemic effects, and the localized endometrial long-term medical treatment means that most sympto- effect is beneficial for treatment of menorrhagia (3).
matic leiomyomas are still managed surgically.
Small studies suggest that the levonorgestrel intrauterinesystem may be effective for treatment of heavy uterine Alternatives to Hysterectomy
bleeding in women with leiomyomas (13). However, In choosing an alternative to hysterectomy, both safety these women may have a higher rate of expulsion and and efficacy need to be considered for each treatment. It must be recognized that all alternatives to hysterectomyallow the possibility for new leiomyomas to form, and Gonadotropin-Releasing Hormone Agonists
preexisting small or undetected leiomyomas may exhibit Gonadotropin-releasing hormone agonists lead to amen- significant growth, necessitating another treatment. The orrhea in most women and provide a 35–65% reduction risk of recurrence must be balanced against the potential in leiomyoma volume within 3 months of treatment (14).
benefits of uterine-sparing procedures, such as decreased The GnRH agonist leuprolide acetate is approved by the rates of morbidity and continued fertility. However, pro- U.S. Food and Drug Administration (FDA) for preoper- cedural complications may rarely lead to an unanticipated ative therapy in women with anemia in conjunction with supplemental iron, and it is most useful in women withlarge leiomyomas. The effects of GnRH agonists are Medication
temporary, with gradual recurrent growth of leiomyomasto previous size within several months after cessation of Contraceptive Steroids and Nonsteroidal
treatment. In addition, the significant symptoms of Antiinflammatory Drugs
pseudomenopause and adverse impact of the induced Contraceptive steroids (estrogen and progestin combina- hypoestrogenism on bone density limit their suggested tions and progestin alone) are widely used for the control use to no more than 6 months without hormonal add- of abnormalities of menstruation. These agents often are first-line therapy for control of abnormal bleeding and If treatment is continued for more than 6 months, painful menstruation in women with and without leio- low-dose steroidal add-back therapy should be consid- myomas. However, evidence-based reviews suggest that ered to minimize continued bone loss and vasomotor current medical therapies tend to give only short-term symptoms. Whereas contraceptive steroid add-back ther- relief, and the crossover rate to surgical therapies is high apy can be used for some diseases, for leiomyomas only low-dose preparations, equivalent to menopausal Data are limited about the effects of estrogen and hormonal therapy, have been studied. It also appears that progestin treatment of leiomyomas. Estrogen and prog- using a sequential regimen, in which a GnRH agonist is estin treatment, usually with oral contraceptives, may first used to achieve down regulation to which steroids control bleeding symptoms without stimulating further are added after 1–3 months of therapy, gives maximal leiomyoma growth. However, studies of progestin ther- results. However, the addition of progestin add-back apy have demonstrated mixed results. Although several therapy results in an increase in mean uterine volume to small studies have shown a decrease in leiomyoma size during progestin therapy (4, 5), other studies using prog-estin therapy alone or in conjunction with a gonad- Aromatase Inhibitors
otropin-releasing hormone (GnRH) agonist identify an Aromatase inhibitors block ovarian and peripheral estro- increase in leiomyoma volume or uterine volume during gen production and decrease estradiol levels after 1 day therapy (6–10). Therefore, when contraceptive steroid of treatment (15). Based on their mechanism of action, therapy is initiated, close monitoring of both leiomyoma these agents may have fewer side effects than GnRH analogues, with the benefit of a rapid effect. Several small studies suggest that abdominal myomectomy sig- small studies and case reports have identified reductions nificantly improves menorrhagia symptoms (overall in leiomyoma size and symptoms with the use of aro- 81% resolution; range 40–93%), with similar results for matase inhibitors (16–18). Overall, little data exist about resolution of pelvic pressure (29). Therefore, abdominal the use of aromatase inhibitors to treat uterine leiomy- myomectomy is a safe and effective option for treatment omas, and further research is necessary to elucidate their of women with symptomatic leiomyomas.
clinical use. These medications are not FDA approved However, women choosing myomectomy face the risk of recurrence of leiomyomas. A number of studieshave examined the use of ultrasonography to assess the Progesterone Modulators
recurrence risk of leiomyomas after abdominal myomec- Antiprogesterone agents act at the level of the proges- tomy, but the accuracy of the estimate depends on the terone receptors found in high concentration in leiomy- sensitivity of the measuring instrument (10, 30–32).
omatous uteri (19, 20). Mifepristone is the most Studies have indicated that women who experience extensively studied progesterone-modulating compound; childbirth after a myomectomy appear to have a recent studies have shown its usefulness in controlling decreased recurrence risk (30, 31). There have been con- leiomyoma symptoms (21, 22). Several studies of high- flicting reports over whether the preoperative use of dose mifepristone have reported a reduction of leiomy- GnRH agonists affects recurrence risk (10, 32). oma volume of 26–74% (23, 24). This reduction is The clinically relevant endpoint is whether a second comparable to those achieved through the use of ana- surgical procedure is needed after conservative surgery.
logues, and leiomyomas appear to have a slower rate of In a relatively large series (125 patients monitored at recurrent growth after cessation of mifepristone treat- least 5 years and up to 23 years), there was evidence that ment (23). Amenorrhea also is a common result of recurrence depended on the number of leiomyomas pres- mifepristone use, with rates up to 90%, coupled with sta- ent. Of those women who had a single leiomyoma, 27% ble bone mineral density and improvements in pelvic had recurrent tumors and 11% required hysterectomy. Of those women who had multiple leiomyomas, 59% expe- Potential side effects of mifepristone include rienced recurrent tumors. Of the women in the multiple endometrial hyperplasia without atypia (14–28%) and leiomyoma group, 26% required repeat myomectomy, transient elevations in transaminase levels (4%) necessi- tating liver-function monitoring (23, 25). In addition, Another risk of myomectomy is the possibility of mifepristone requires a compounding pharmacy to pro- undergoing an unexpected hysterectomy because of duce clinically relevant doses and, thus, has limited intraoperative complications. This risk appears to be low availability. Significantly lower doses may be effective (less than 1%) even when uterine size is substantial (28, without increasing the risk of atypical hyperplasia (21, 34–37). Blood loss and the risk of transfusion may be 22). Antiprogesterone agents may have a short-term role increased in women with larger uteri (28, 37).
in the preoperative management of leiomyomas, but fur-ther study is needed.
Endoscopic myomectomy is a treatment option for some Myomectomy
women (38). Laparoscopic myomectomy minimizes the For women who desire uterine preservation, myomec- size of the abdominal incision, resulting in a quicker tomy may be an option. The goal of a myomectomy postoperative recovery. Because of the complex nature procedure is to remove the visible and accessible leio- of laparoscopic dissection and suturing, special surgical myomas and then reconstruct the uterus. Traditionally, most myomectomies have been performed by lapa- There are a number of case series of laparoscopic rotomy; however, endoscopic options increasingly are myomectomies, the largest reporting on more than 2,000 patients over a 6-year period (39). These cohorts reportoverall complication rates between 8% and 11%, with Abdominal Myomectomy
subsequent pregnancy rates between 57% and 69% (39, Although early studies suggested that the rate of mor- bidity associated with myomectomy was increased com- Two randomized controlled trials including a total pared with hysterectomy, subsequent research suggests of 284 patients have compared laparoscopic myomec- that the risks of the two procedures are similar (26–28).
tomy with a minilaparotomy myomectomy (41, 42). The Clinical experience and pooled results of numerous first trial demonstrated shorter operating room duration for minilaparotomy. Laparoscopic myomectomy resulted fication has been shown to be predictive of the likelihood in less blood loss, reduced length of postoperative ileus, of complete surgical resection, which is the most predic- a shorter time to hospital discharge, reduced analgesic tive indicator of surgical success. Uterine size and the requirements, and a more rapid recuperation (41). A sec- number of leiomyomas also have been shown to be inde- ond trial compared minilaparotomic myomectomy and pendent prognostic variables for recurrence (50).
laparoscopic myomectomy in patients with unexplained Studies have shown successful removal of the infertility and concluded that both techniques improve leiomyoma at the initial hysteroscopy at a rate of reproductive outcomes to a similar degree (42).
65–100%, with most ranging from 85–95% (51). Sub- Recommendations differ regarding cases amenable sequent surgery is needed in approximately 5–15% of to a laparoscopic approach. Previous recommendations cases, and most of these cases involve a second hystero- have suggested avoiding laparoscopy for leiomyomas scopic procedure. As with abdominal leiomyomectomy, larger than 5–8 cm, multiple leiomyomas, or the pres- the effectiveness of the procedure decreases over time.
ence of deep intramural leiomyomas (43, 44). A prospec- One study of 274 procedures, with follow-up of more tive study compared laparoscopic myomectomy for the than 5 years, reported a success rate of 94.6% at 1 year, management of leiomyomas greater than 80 g with which decreased to 76.3% at 5 years (52).
laparoscopic myomectomy in those smaller than 80 g.
Leiomyoma classification is an important predictor Operative time (121 minutes versus 79 minutes) and esti- of the ability to achieve complete resection, although mated blood loss (346 mL versus 123 mL) were signifi- there have been some reports of success with type II cantly greater in the group with the larger uterine leiomyomas. One retrospective study of 235 patients leiomyomas. However, no difference was seen in length reported a 95% rate of complete leiomyoma resection in of stay or overall complication rates (45). a population that included 70% type II leiomyomas. The A large retrospective series of 512 patients reported 3-year success rate was reported as 97%; however, 36% a leiomyoma recurrence rate of 11.7% after 1 year and underwent concomitant endometrial ablation (52). up to 84.4% after 8 years, but a reoperation rate for The reported complication rate for hysteroscopic recurrence of 6.7% at 5 years and 16% at 8 years (46). A myomectomy ranges between 1% and 12%, with rates of case series described a 33% recurrence risk at 27 months 1–5% reported in most studies (51). Potential surgical (47). Successful outcomes from laparoscopic myomec- complications include fluid overload with secondary tomy have been reported primarily by surgeons with hyponatremia, pulmonary edema, cerebral edema, intra- expertise and advanced laparoscopic skills, including operative and postoperative bleeding, uterine perfora- laparoscopic myomectomy, and may not be generaliz- able to surgeons with less laparoscopic experience.
Robot-assisted laparoscopic surgery also has been Uterine Artery Embolization
used to perform myomectomy (48). It may have the Uterine artery embolization for the treatment of leiomy- advantage of improved optics, including a three-dimen- oma, performed primarily by interventional radiologists, sional view, and enhanced surgeon dexterity. Disadvan- is a procedure in which the uterine arteries are embolized tages with robot-assisted surgery in general include via a transcutaneous femoral artery approach, resulting diminished haptic (tactile) sensation, additional operat- in uterine leiomyoma devascularization and involution.
ing room time, and increased cost. Further studies, The uterine arteries are embolized using polyvinyl alco- including randomized clinical trials, are needed to better hol particles of trisacryl gelatin microspheres.
determine clinical outcomes and cost-effectiveness. Supplemental metal coils also may be used to assist withvascular occlusion.
A large multicenter study of more than 500 patients Hysteroscopic myomectomy is an accepted method for undergoing uterine artery embolization reported favor- the management of abnormal uterine bleeding caused by able 3-month outcomes for dominant leiomyoma volume submucous leiomyomas. Submucosal leiomyomas are reduction (42%) and decreased median leiomyoma life- estimated to be the cause of 5–10% of cases of abnormal impact scores, mean menstrual duration, dysmenorrhea, uterine bleeding, pain, and subfertility and infertility (4).
and urinary frequency or urgency (53). The Uterine Submucous leiomyomas are classified based on the Artery Embolization in the Treatment of Symptomatic amount of leiomyoma within the uterine cavity, with Uterine Fibroid Tumors (EMMY) randomized trial com- type 0 leiomyomas completely intracavitary, type I pared uterine artery embolization to total abdominal hys- leiomyomas less than 50% intramural, and type II terectomy. In this trial, patients undergoing uterine artery leiomyomas more than 50% intramural (49). This classi- embolization had significantly less pain during the first 24 hours postoperatively and returned to work sooner focused ultrasound therapy. This noninvasive approach (28.1 versus 63.4 days) than patients who underwent uses high-intensity ultrasound waves directed into a hysterectomy (54). The rates of major complications focal volume of a leiomyoma. The ultrasound energy were similar, 4.9% for uterine artery embolization and penetrates soft tissue and produces well-defined regions 2.7% for hysterectomy. Minor complications, such as of protein denaturation, irreversible cell damage, and vaginal discharge, leiomyoma expulsion, and hematoma were higher in the group that had uterine artery Outcomes of 109 patients undergoing MRI-guided embolization compared with those that had hysterecto- focused ultrasound surgery were reported at 6 months and my (58% versus 40%) as well as higher readmission 12 months (62, 63). Although only modest uterine vol- rates for those undergoing uterine artery embolization ume reductions were noted (13.5% at 6 months and 9.4% (11.1% versus 0%) (55). Similar clinical findings were at 12 months, using intention to treat analysis), 71% of reported in a multicenter trial of uterine artery emboliza- patients reported symptom reduction at 6 months. At 12 tion versus myomectomy (56). Analysis of three random- months, 51% had symptom reduction. Adverse events ized clinical trials comparing uterine artery embolization included heavy menses, requiring transfusion (5); per- with myomectomy and hysterectomy confirmed that the sistent pain and bleeding (1); hospitalization for nausea uterine artery embolization resulted in shorter hospital (1); and leg and buttock pain caused by sonification of stay, quicker return to activities, and a higher minor com- the sciatic nerve in the far field (1), which eventually plication rate after discharge (57). The overall complica- resolved. Case series suggest that improvement in symp- tion rates for uterine artery embolization have been toms at 12 months and 24 months is related to the thor- oughness of treatment and that adverse events decrease Long-term outcomes have been reported in several with increasing experience (64–66). Whereas short-term studies. One case–control study comparing uterine artery studies show safety and efficacy, long-term studies are embolization with myomectomy reported a higher needed to discern whether the minimally invasive advan- reoperation rate of 29% in the uterine artery embolization tage of MRI-guided focused ultrasound surgery will lead group (15 of 51) compared with 3% (1 of 30) in the to durable results beyond 24 months. Protocols for treat- myomectomy group (59). However, when subjective vari- ing larger leiomyoma volumes are being studied.
ables, such as symptom worsening and patient dissatis-faction, were considered, 39% (20 of 51) in the uterine Clinical Considerations and
artery embolization group were considered clinical fail-ures, compared with 30% (9 of 30) in the myomectomy Recommendations
group. In 5-year follow-up results of 200 patients treatedwith uterine artery embolization, a 20% reoperation rate In women with leiomyomas who are candi-
(hysterectomy 13.7%, myomectomy 4.4%, repeat embol- dates for surgery, does the use of adjunctive
ization 1.6%) and failure to control symptoms in 25% medical treatment result in better outcomes?
were documented (60). Another trial reported a reinter-vention rate of 6% in the myomectomy group, compared Preoperative Adjuvants
with a rate of 33% for those undergoing uterine artery Gonadotropin-releasing hormone agonists have been embolization (61). Based on long- and short-term out- used widely for preoperative treatment of uterine comes, uterine artery embolization is a safe and effective leiomyomas, both for myomectomy and hysterectomy.
option for appropriately selected women who wish to They may be beneficial when a significant reduction in retain their uteri. Women who wish to undergo uterine uterine volume could change the surgical approach, such artery embolization should have a thorough evaluation as allowing a transverse incision, an endoscopic proce- with an obstetrician–gynecologist to help facilitate opti- mal collaboration with the interventional radiologists and By inducing amenorrhea, GnRH agonists have been to ensure the appropriateness of therapy, taking into shown to improve hematologic parameters, shorten hos- account the reproductive wishes of the patient.
pital stay, and decrease blood loss, operating time, andpostoperative pain when given for 2–3 months preopera- Magnetic Resonance Imaging-Guided
tively (67–69). However, no study has shown a signifi- Focused Ultrasound Surgery
cant decrease in transfusion risk or improvement in In 2004, the FDA granted approval for the use of a mag- quality of life, and the cost of these medications is sub- netic resonance imaging (MRI)-guided system for the stantial. Therefore, the benefits of preoperative use of localization and treatment of uterine leiomyomas with GnRH agonists should be weighed against their cost and side effects for individual patients. It also is worth noting A trial of labor is not recommended in patients at high that in a study that achieved hematologic improvement risk of uterine rupture, including those with previous with GnRH agonist treatment in 74% of women, there classical or T-shaped uterine incisions or extensive trans- was a 46% improvement rate in the placebo group with fundal uterine surgery. Because myomectomy also can iron supplementation alone (68). One surgical disadvan- produce a transmural incision in the uterus, it often has tage to preoperative GnRH agonist therapy is that it may been treated in an analogous way. There are no clinical make the leiomyomas softer and the surgical planes less trials that specifically address this issue; however, one distinct. Although many studies find the operative time study reports no uterine ruptures in 212 deliveries (83% equivalent for laparotomies, one study of laparoscopic myomectomies found that overall operating time Pooled data from several case series of laparoscopic decreased after GnRH agonist treatment. However, in the myomectomy involving more than 750 pregnancies subgroup in which the largest leiomyoma was hypoe- identified one case of uterine rupture (39, 40, 75–77).
choic, operative time was longer because of the difficulty Other case reports have described the occurrence of uter- ine rupture before and during labor (78–80), including Gonadotropin-releasing hormone antagonists are rare case reports of uterine rupture remote from term now available and have the advantage of not inducing an after traditional abdominal myomectomy (81, 82). Most initial steroidal flare as seen with GnRH agonists. The obstetricians allow women who underwent hysteroscopic rapid effect of the antagonist allows a shorter duration of myomectomy for type O or type I leiomyomas to go side effects with presurgical treatment. The antagonist through labor and give birth vaginally; however, there has been shown to reduce leiomyoma volume by are case reports of uterine rupture in women who expe- 25–40% in 19 days, thereby allowing surgery to be rienced uterine perforation during hysteroscopy (83–85).
scheduled sooner (70). As with the agonist, the reduction It appears that the risk of uterine rupture in pregnancy of leiomyoma and uterine volumes are transient.
after laparoscopic or hysteroscopic myomectomy is low.
Although GnRH antagonists are not currently FDA However, because of the serious nature of this complica- approved for preoperative treatment of leiomyomas, they tion, a high index of suspicion must be maintained when managing pregnancies after this procedure. Intraoperative Adjuvants
In women with leiomyomas who desire to
become pregnant, does surgical removal of
Several studies suggest that the infiltration of vasopressininto the myometrium decreases blood loss at leiomyomas increase the pregnancy rate?
the time of myomectomy. A study of 20 patients demon- As with any woman with asymptomatic leiomyomas, strated that vasopressin significantly decreased blood loss those who desire future fertility should be managed compared with saline injection in a randomized myomec- expectantly because they have no indication for surgery.
tomy study (71). Two studies compared the use of physi- For mildly symptomatic women, given the risk of recur- cal vascular compression, primarily a tourniquet around rence, intervening as close to the desired pregnancy as the lower uterine segment, with pharmacologic vasocon- practical is desirable. For symptomatic women, prior striction (vasopressin administration). In one study that treatment history should be considered, as well as possi- used a Penrose drain tourniquet and vascular clamps, ble benefit of normalization of the endometrial cavity, there was no significant difference between the two tech- the particular fertility consequences of each technique, niques (37). The other study, which compared the use of and the risk of pregnancy complications with untreated a Foley catheter tourniquet with vasopressin administra- tion, found significantly greater blood loss in the tourni- The contribution of leiomyomas to infertility is dif- quet group (72). There are no studies that compare ficult to assess because of the high prevalence of leiomy- tourniquet use with placebo. Additionally, one study omas in the general population and because the demonstrated that injection of vasopressin into the cervix incidence of leiomyomas increases with age, as does at the time of operative hysteroscopy decreased blood infertility. Furthermore, many women with uterine loss, fluid intravasation, and operative time (73).
leiomyomas conceive and have uncomplicated pregnan-cies. Leiomyomas are present in approximately 5–10% In pregnant women who have undergone a
of women with infertility and are the sole factor identi- myomectomy, does a planned cesarean delivery
fied in 1–2.4% of women with infertility (29, 86, 87).
versus a trial of labor help prevent uterine
However, leiomyomas should not be considered the rupture?
cause of infertility, or significant component of infertility, without completing a basic fertility evaluation to assess addition, myomectomy should be considered for a woman with uterine leiomyomas who has undergone Intramural and submucosal leiomyomas can cause several unsuccessful IVF cycles despite appropriate distortion of the uterine cavity or obstruction of the tubal ovarian response and good quality embryos. There are ostia or cervical canal and, thus, may affect fertility or potential adverse effects of nondistorting leiomyomas on lead to pregnancy complications (88–90). When abdom- IVF outcomes, although these effects are unconfirmed. inal myomectomies have been performed on womenwith otherwise unexplained infertility, the subsequent In women with leiomyomas planning future
pregnancy rates have been reported to be 40–60% after pregnancies, what is the impact on future
1–2 years (29, 91–93). Studies of the effect of laparo- fertility of uterine artery embolization and
scopic or hysteroscopic myomectomy on fertility have magnetic resonance imaging-guided focused
shown similar results (94–96). However, the use of addi- ultrasonography?
tional fertility treatments may have contributed to thesemarked positive effects.
Successful pregnancies can occur following uterine Several studies have investigated the effect of artery embolization (101). Notably, early series demon- leiomyomas on reproductive outcomes after in vitro fer- strated successful term pregnancies in women who tilization (IVF). In the setting of an abnormal, distorted would be expected to have a high rate of infertility (102).
uterine cavity caused by leiomyomas (submucosal or There are two issues of specific concern related to uter- intramural), significantly lower IVF pregnancy rates were ine artery embolization for women intending to become identified (90–98). In addition, after myomectomy was pregnant. The first is that there appears to be an age- performed for submucosal leiomyomas, pregnancy rates related risk of impairment of ovarian function, as markedly increased (90). Subserosal leiomyomas have demonstrated by amenorrhea (53). Originally, this risk not been shown to have an impact on reproductive out- was attributed only to the circumstances of misem- comes (90). However, in the setting of a nondistorted bolization, but an understanding of the collateral blood uterine cavity, the impact of intramural leiomyomas on supply of the uterus suggests this can occur with techni- IVF outcomes remains unclear. Intramural, nondistorting cally correct uterine artery embolization. Although this leiomyomas may have a subtle impact on IVF outcomes risk is low in young women (3%), given the prevalence (97), but there are no definitive data supporting routine of decreased ovarian reserve as an infertility factor, long- prophylactic myomectomy before IVF for women with term studies are necessary. A recent report of antimüller- leiomyomas and normal uterine cavities (98). It should be ian hormone in women participating in a randomized noted that most studies included women with leiomy- clinical trial of uterine artery embolization versus hys- omas of 5 cm or less, and women with larger leiomyomas terectomy suggests that both procedures cause similar were often excluded from these studies (99). Therefore, impairment of ovarian reserve (103).
although leiomyomas that distort the uterine cavity clearly There are case reports of pregnancy complications affect reproductive outcomes, further data about leiomy- after uterine artery embolization, but this may represent oma size and reproductive outcomes are needed.
publication bias. However, the most significant data Some surgeons believe that a prophylactic myomec- come from the Ontario cohort that includes close follow- tomy may be appropriate for select women with large up (104). In this case series of 24 pregnancies occurring leiomyomas who wish to preserve future fertility. With a in women with prior uterine artery embolization, there skilled surgeon, the evidence demonstrates that the was a 12% risk of placentation problems (two placenta myomectomy complication rate is low even with sub- previa and one placenta accreta), and all occurred in nul- stantial uterine size; thus, surgery may be reasonable liparous patients who were otherwise unlikely to have (28, 30, 31, 34, 36). However, the high risk of recurrent this type of complication. Thus, because there is biologic leiomyomas makes this procedure a less effective treat- plausibility of uterine artery embolization causing com- ment (30, 31). Additionally, myomectomy can lead to promised endometrial perfusion resulting in abnormal pelvic adhesive disease, which could cause tubal impair- placentation in women not otherwise at risk, this ment or obstruction and, hence, infertility (100). approach should be used with caution for women who When assessing a woman with infertility and are pursuing pregnancy. The effect of uterine artery leiomyomas, targeted evaluation of the uterus and embolization on pregnancy remains understudied.
endometrial cavity to assess leiomyoma location, size, Case reports of pregnancy with term delivery have and number is indicated. The data suggest that before been reported after MRI-guided focused ultrasonogra- infertility treatment, surgical treatment for a distorted phy (65, 105–107). However, larger experience is neces- uterine cavity caused by leiomyomas is indicated. In In menopausal women with leiomyomas,
Although some studies have shown increased rates of what is the effect of hormone therapy on
morbidity, others show no differences in perioperative leiomyoma growth, bleeding, and pain?
complications (9, 27, 28, 111). This currently does notappear to be a cogent argument for intervention.
For many years, health care providers have counseled In rare circumstances, the uterus causes significant patients that leiomyomas are a self-limiting problem that compression of the ureters that could lead to compro- will resolve when a woman completes the transition to mised renal function. A small retrospective review menopause. Because leiomyomas are responsive to demonstrated ureteral dilation in 56% of patients with estrogen, the hypoestrogenism of menopause results in uterine size greater or equal to 12 weeks, but no dilation uterine shrinkage for most women. However, for women in patients with uterine size less than 12 weeks (112).
electing hormone therapy, there is the possibility that However, in no studies have the effects of uterine size on symptoms associated with leiomyomas may persist into If there is concern that the mass is not a leiomyoma There is some evidence that women with leiomy- but instead a sarcoma, further evaluation is warranted.
omas who take hormone therapy are more likely to have Traditionally, the major clinical sign used to make this abnormal bleeding. In a study using hysteroscopy to distinction was rapid growth in uterine size. However, in evaluate women with abnormal bleeding who were tak- a study of 1,332 hysterectomy specimens for which the ing hormone therapy (using women with no abnormal preoperative diagnosis was uterine leiomyomas, sarco- bleeding as controls), women with structural abnormali- mas were rare (2–3/1,000) and no more common in the ties of the cavity, including endometrial polyps and sub- subgroup of women who had experienced rapidly mucosal leiomyomas, had an increased likelihood of enlarging uterine size (113). The clinical diagnosis of rapidly growing leiomyomas should not be used as an A small pilot study examined whether hormone indication for myomectomy or hysterectomy.
therapy during menopause caused an increase in size of If a comparison is made between the prevalence of asymptomatic leiomyomas (109). This study showed a leiomyosarcomas discovered incidentally (1/2,000) and significant increase in leiomyoma dimension after 1 year the mortality rate for hysterectomy for benign disease of transdermal hormone therapy but no increase with (1–1.6/1,000 for premenopausal women), the decision to oral conjugated estrogens. Hormone therapy may cause proceed to hysterectomy to find potential sarcomas should some modest increase in uterine leiomyoma size, but it be made cautiously (111). Other risk factors for sarcomas, does not appear to have an impact on clinical symptoms.
including increasing age, a history of prior pelvic radia- Therefore, this treatment option should not be withheld tion, tamoxifen use, or having a rare genetic predisposi- from women who desire or need such therapy.
tion resulting in hereditary leiomyomatosis and renal cellcarcinoma syndrome may influence this decision (114).
In asymptomatic women with leiomyomas,
Alternatively, both endometrial biopsy and MRI appear to does expectant management produce a better
be useful in diagnosing sarcomas and differentiating them outcome than surgical treatment in relation
from other intrauterine lesions (115–117).
to long-term morbidity?
In conclusion, there is insufficient evidence to sup- Expectant management in an asymptomatic patient port hysterectomy for asymptomatic leiomyomas solely should be the norm, but in some instances an asympto- to improve detection of adnexal masses, to prevent matic leiomyomatous uterus might require treatment.
impairment of renal function, or to rule out malignancy.
Historically, it has been argued that uterine size aloneshould be an indication for hysterectomy. The argumentusually has been twofold. The first issue was that a large Summary of
leiomyomatous uterus made assessment of the ovaries Recommendations
and early surveillance for ovarian cancer impossible.
However, the National Institutes of Health and National The following recommendations and conclusions
Cancer Institute Consensus Conference acknowledged are based on good and consistent scientific evi-
the futility of routine pelvic examinations in the identifi- dence (Level A):
Second, the argument is made that, because of the in- Abdominal myomectomy is a safe and effective creased rate of morbidity during surgery for a large uterus, alternative to hysterectomy for treatment of women surgery is a safer option when the uterus is smaller.
Based on long- and short-term outcomes, uterine Menstrual Agreement Process. Fertil Steril 2007;87: artery embolization is a safe and effective option for appropriately selected women who wish to retain 2. Day Baird D, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterineleiomyoma in black and white women: ultrasound evi- Gonadotropin-releasing hormone agonists have dence. Am J Obstet Gynecol 2003;188:100–7. (Level II- been shown to improve hematologic parameters, shorten hospital stay, and decrease blood loss, oper- 3. Marjoribanks J, Lethaby A, Farquhar C. Surgery versus ating time, and postoperative pain when given for medical therapy for heavy menstrual bleeding. Cochrane 2–3 months preoperatively. Benefits of preoperative Database of Systematic Reviews 2006, Issue 2. Art. No.:CD003855. DOI: 10.1002/14651858.CD003855.pub2.
use of GnRH agonists should be weighed against their cost and side effects for individual patients.
4. Wallach EE, Vlahos NF. Uterine myomas: an overview Several studies suggest that the infiltration of vaso- of development, clinical features, and management.
pressin into the myometrium decreases blood loss at Obstet Gynecol 2004;104:393–406. (Level III) 5. Venkatachalam S, Bagratee JS, Moodley J. Medical management of uterine fibroids with medroxyproges- The following recommendations are based on lim-
terone acetate (Depo Provera): a pilot study. J Obstet ited or inconsistent scientific evidence (Level B):
6. Harrison-Woolrych M, Robinson R. Fibroid growth in The clinical diagnosis of rapidly growing leiomy- response to high-dose progestogen. Fertil Steril 1995; omas should not be used as an indication for 7. Mixson WT, Hammond DO. Response of fibromyomas Hysteroscopic myomectomy is an accepted method to a progestin. Am J Obstet Gynecol 1961;82:754–60.
(Level III) for the management of abnormal uterine bleedingcaused by submucosal leiomyomas.
8. Carr BR, Marshburn PB, Weatherall PT, Bradshaw KD, Breslau NA, Byrd W, et al. An evaluation of the effect ofgonadotropin-releasing hormone analogs and medrox- The following recommendations and conclusions
yprogesterone acetate on uterine leiomyomata volume are based primarily on consensus and expert opin-
by magnetic resonance imaging: a prospective, random- ion (Level C):
ized, double blind, placebo-controlled, crossover trial. JClin Endocrinol Metab 1993;76:1217–23. (Level II-3) There is insufficient evidence to support hysterectomy 9. Friedman AJ, Haas ST. Should uterine size be an indica- for asymptomatic leiomyomas solely to improve tion for surgical intervention in women with myomas? detection of adnexal masses, to prevent impairment Am J Obstet Gynecol 1993;168:751–5. (Level III) of renal function, or to rule out malignancy.
10. Friedman AJ, Daly M, Juneau-Norcross M, Fine C, Rein Leiomyomas should not be considered the cause of MS. Recurrence of myomas after myomectomy in womenpretreated with leuprolide acetate depot or placebo.
infertility, or significant component of infertility, Fertil Steril 1992;58:205–8. (Level III) without completing a basic fertility evaluation to 11. Marshall LM, Spiegelman D, Goldman MB, Manson JE, Colditz GA, Barbieri RL, et al. A prospective study of Hormone therapy may cause some modest increase reproductive factors and oral contraceptive use in rela- in uterine leiomyoma size but does not appear to tion to the risk of uterine leiomyomata. Fertil Steril1998;70:432–9. (Level II-2) have an impact on clinical symptoms. Therefore,this treatment option should not be withheld from 12. Wise LA, Palmer JR, Harlow BL, Spiegelman D, women who desire or need such therapy.
Stewart EA, Adams-Campbell LL, et al. Reproductivefactors, hormonal contraception, and risk of uterine The effect of uterine artery embolization on preg- leiomyomata in African-American women: a prospective study. Am J Epidemiol 2004;159:113–23. (Level II-2) 13. Mercorio F, De Simone R, Di Spiezio Sardo A, Cerrota G, Bifulco G, Vanacore F, et al. The effect of a lev- References
onorgestrel-releasing intrauterine device in the treatmentof myoma-related menorrhagia. Contraception 2003;67:277–80. (Level III) 1. Fraser IS, Critchley HO, Munro MG, Broder M. A process designed to lead to international agreement on 14. Olive DL, Lindheim SR, Pritts EA. Non-surgical man- terminologies and definitions used to describe abnormal- agement of leiomyoma: impact on fertility. Curr Opin ities of menstrual bleeding. Writing Group for this Obstet Gynecol 2004;16:239–43. (Level III) 15. Iveson TJ, Smith IE, Ahern J, Smithers DA, Trunet PF, leiomyoma: a comparison of preoperative demography Dowsett M. Phase I study of the oral nonsteroidal aro- and postoperative morbidity. J Gynecol Surg 1995;11: matase inhibitor CGS 20267 in healthy postmenopausal women. J Clin Endocrinol Metab 1993;77:324–31.
29. Buttram VC Jr, Reiter RC. Uterine leiomyomata: etiolo- gy, symptomatology, and management. Fertil Steril 16. Shozu M, Murakami K, Segawa T, Kasai T, Inoue M.
Successful treatment of a symptomatic uterine leiomy- 30. Candiani GB, Fedele L, Parazzini F, Villa L. Risk of oma in a perimenopausal woman with a nonsteroidal aro- recurrence after myomectomy. Br J Obstet Gynaecol matase inhibitor. Fertil Steril 2003;79:628–31. (Level III) 17. Attilakos G, Fox R. Regression of tamoxifen-stimulated 31. Fedele L, Parazzini F, Luchini L, Mezzopane R, Tozzi L, massive uterine fibroid after conversion to anastrozole.
Villa L. Recurrence of fibroids after myomectomy: a J Obstet Gynaecol 2005;25:609–10. (Level III) transvaginal ultrasonographic study. Hum Reprod 1995; 18. Varelas FK, Papanicolaou AN, Vavatsi-Christaki N, Makedos GA, Vlassis GD. The effect of anastrazole onsymptomatic uterine leiomyomata. Obstet Gynecol 2007; 32. Fedele L, Vercellini P, Bianchi S, Brioschi D, Dorta M.
Treatment with GnRH agonists before myomectomy andthe risk of short-term myoma recurrence. Br J Obstet 19. Englund K, Blanck A, Gustavsson I, Lundkvist U, Sjoblom P, Norgren A, et al. Sex steroid receptors inhuman myometrium and fibroids: changes during the 33. Malone LJ. Myomectomy: recurrence after removal of menstrual cycle and gonadotropin-releasing hormone solitary and multiple myomas. Obstet Gynecol 1969; treatment. J Clin Endocrinol Metab 1998;83:4092–6.
34. Smith DC, Uhlir JK. Myomectomy as a reproductive pro- 20. Nisolle M, Gillerot S, Casanas-Roux F, Squifflet J, cedure. Am J Obstet Gynecol 1990;162:1476–9; discus- Berliere M, Donnez J. Immunohistochemical study of the proliferation index, oestrogen receptors and progesterone 35. Chong RK, Thong PH, Tan SL, Thong PW, Salmon YM.
receptors A and B in leiomyomata and normal myometri- Myomectomy: indications, results of surgery and relation um during the menstrual cycle and under gonadotrophin- to fertility. Singapore Med J 1988;29:35–7. (Level III) releasing hormone agonist therapy. Hum Reprod 1999;14:2844–50. (Level II-3) 36. LaMorte AI, Lalwani S, Diamond MP. Morbidity associ- ated with abdominal myomectomy. Obstet Gynecol 21. Fiscella K, Eisinger SH, Meldrum S, Feng C, Fisher SG, Guzick DS. Effect of mifepristone for symptomaticleiomyomata on quality of life and uterine size: a ran- 37. Ginsburg ES, Benson CB, Garfield JM, Gleason RE, domized controlled trial. Obstet Gynecol 2006;108: Friedman AJ. The effect of operative technique and uter- ine size on blood loss during myomectomy: a prospectiverandomized study. Fertil Steril 1993;60:956–62. (Level I) 22. Eisinger SH, Bonfiglio T, Fiscella K, Meldrum S, Guzick DS. Twelve-month safety and efficacy of low-dose 38. Lefebvre G, Vilos G, Allaire C, Jeffrey J, Arneja J, Birch mifepristone for uterine myomas. J Minim Invasive C, et al. The management of uterine leiomyomas.
J Obstet Gynaecol Can 2003;25:396,418; quiz 419–22.
(Level III) 23. Steinauer J, Pritts EA, Jackson R, Jacoby AF. Systematic review of mifepristone for the treatment of uterine leiomy- 39. Sizzi O, Rossetti A, Malzoni M, Minelli L, La Grotta F, omata. Obstet Gynecol 2004;103:1331–6. (Level III) Soranna L, et al. Italian multicenter study on complica- 24. Murphy AA, Kettel LM, Morales AJ, Roberts VJ, Yen SS.
tions of laparoscopic myomectomy. J Minim Invasive Regression of uterine leiomyomata in response to the antiprogesterone RU 486. J Clin Endocrinol Metab 40. Altgassen C, Kuss S, Berger U, Loning M, Diedrich K, Schneider A. Complications in laparoscopic myomec- 25. Eisinger SH, Meldrum S, Fiscella K, le Roux HD, tomy. Surg Endosc 2006;20:614–8. (Level II-3) Guzick DS. Low-dose mifepristone for uterine leiomy- 41. Alessandri F, Lijoi D, Mistrangelo E, Ferrero S, Ragni N.
omata. Obstet Gynecol 2003;101:243–50. (Level I) Randomized study of laparoscopic versus minilaparo- 26. Hillis SD, Marchbanks PA, Peterson HB. Uterine size tomic myomectomy for uterine myomas. J Minim and risk of complications among women undergoing Invasive Gynecol 2006;13:92–7. (Level I) abdominal hysterectomy for leiomyomas. Obstet 42. Palomba S, Zupi E, Falbo A, Russo T, Marconi D, Tolino A, et al. A multicenter randomized, controlled study com- 27. Iverson RE Jr, Chelmow D, Strohbehn K, Waldman L, paring laparoscopic versus minilaparotomic myomec- Evantash EG. Relative morbidity of abdominal hysterec- tomy: reproductive outcomes. Fertil Steril 2007;88: tomy and myomectomy for management of uterine leiomyomas. Obstet Gynecol 1996;88:415–9. (Level II-2) 43. Dubisson JB, Chapron C, Levy J. Difficulties and com- 28. Ecker JL, Foster JT, Friedman AJ. Abdominal hysterec- plications of laparoscopic myomectomy. J Gynecol Surg tomy or abdominal myomectomy for symptomatic 44. Seinera P, Arisio R, Decko A, Farina C, Crana F.
Cochrane Database of Systematic Reviews 2006, Laparoscopic myomectomy: indications, surgical tech- Issue 1. Art. No.: CD005073. DOI: 10.1002/14651858.
nique and complications. Hum Reprod 1997;12: 58. Spies JB, Spector A, Roth AR, Baker CM, Mauro L, 45. Wang CJ, Yuen LT, Lee CL, Kay N, Soong YK.
Murphy-Skrynarz K. Complications after uterine artery Laparoscopic myomectomy for large uterine fibroids. embolization for leiomyomas. Obstet Gynecol 2002; A comparative study. Surg Endosc 2006;20:1427–30.
59. Broder MS, Goodwin S, Chen G, Tang LJ, Costantino 46. Yoo EH, Lee PI, Huh CY, Kim DH, Lee BS, Lee JK, MM, Nguyen MH, et al. Comparison of long-term out- et al. Predictors of leiomyoma recurrence after laparo- comes of myomectomy and uterine artery embolization.
scopic myomectomy. J Minim Invasive Gynecol 2007; Obstet Gynecol 2002;100:864–8. (Level II-2) 60. Spies JB, Bruno J, Czeyda-Pommersheim F, Magee ST, 47. Nezhat FR, Roemisch M, Nezhat CH, Seidman DS, Ascher SA, Jha RC. Long-term outcome of uterine Nezhat CR. Recurrence rate after laparoscopic myomec- artery embolization of leiomyomata. Obstet Gynecol tomy. J Am Assoc Gynecol Laparosc 1998;5:237–40.
61. Mara M, Fucikova Z, Maskova J, Kuzel D, Haakova L.
48. Advincula AP, Song A, Burke W, Reynolds RK.
Uterine fibroid embolization versus myomectomy in Preliminary experience with robot-assisted laparoscopic women wishing to preserve fertility: preliminary results myomectomy. J Am Assoc Gyecol Lapaosc 2004;11: of a randomized controlled trial. Eur J Obstet Gynecol 49. Wamsteker K, de Blok S, Galilnat A, Lueken RP.
62. Hindley J, Gedroyc WM, Regan L, Stewart E, Tempany Fibroids. In: Lewis BV, Magos AL, editors. Endometrial C, Hynyen K, et al. MRI guidance of focused ultrasound ablation. New York (NY): Churchill Livingstone; 1992.
therapy of uterine fibroids: early results. AJR Am J Roentgenol 2004;183:1713–9. (Level III) 63. Stewart EA, Rabinovici J, Tempany CM, Inbar Y, Regan 50. Emanuel MH, Wamsteker K, Hart AA, Metz G, Lammes L, Gostout B, et al. Clinical outcomes of focused ultra- FB. Long-term results of hysteroscopic myomectomy for sound surgery for the treatment of uterine fibroids [pub- abnormal uterine bleeding. Obstet Gynecol 1999;93: lished erratum appears in Fertil Steril 2006;85:1072].
Fertil Steril 2006;85:22–9. (Level III) 51. Jenkins TR. Hysteroscopic myomectomy: a review.
64. Fennessy FM, Tempany CM, McDannold NJ, So MJ, Female Patient 2006;31:37–44. (Level III) Hesley G, Gostout B, et al. Uterine leiomyomas: MR 52. Polena V, Mergui JL, Perrot N, Poncelet C, Barranger E, imaging-guided focused ultrasound surgery—results of Uzan S. Long-term results of hysteroscopic myomecto- different treatment protocols. Radiology 2007;243: my in 235 patients. Eur J Obstet Gynecol Reprod Biol 65. Morita Y, Ito N, Ohashi H. Pregnancy following MR- 53. Pron G, Bennett J, Common A, Wall J, Asch M, guided focused ultrasound surgery for a uterine fibroid.
Sniderman K. The Ontario Uterine Fibroid Embolization Int J Gynaecol Obstet 2007;99:56–7. (Level III) Trial. Part 2. Uterine fibroid reduction and symptom 66. Stewart EA, Gostout B, Rabinovici J, Kim HS, Regan L, relief after uterine artery embolization for fibroids.
Tempany CM. Sustained relief of leiomyoma symptoms Ontario Uterine Fibroid Embolization Collaboration by using focused ultrasound surgery. Obstet Gynecol Group. Fertil Steril 2003;79:120–7. (Level II-3) 54. Hehenkamp WJ, Volkers NA, Birnie E, Reekers JA, 67. Gerris J, Degueldre M, Peters AA, Romao F, Stjernquist Ankum WM. Pain and return to daily activities after uter- M, al-Taher H. The place of Zoladex in deferred surgery ine artery embolization and hysterectomy in the treat- for uterine fibroids. Zoladex Myoma Study Group.
ment of symptomatic uterine fibroids: results from the randomized EMMY trial. Cardiovasc Intervent Radiol2006;29:179–87. (Level I) 68. Stovall TG, Muneyyirci-Delale O, Summitt RL Jr, Scialli AR. GnRH agonist and iron versus placebo and 55. Hehenkamp WJ, Volkers NA, Donderwinkel PF, de Blok iron in the anemic patient before surgery for leiomy- S, Birnie E, Ankum WM, et al. Uterine artery emboliza- omas: a randomized controlled trial. Leuprolide Acetate tion versus hysterectomy in the treatment of symptomatic Study Group. Obstet Gynecol 1995;86:65–71. (Level I) uterine fibroids (EMMY trial): peri- and postprocedural 69. Zullo F, Pellicano M, De Stefano R, Zupi E, results from a randomized controlled trial. Am J Obstet Mastrantonio P. A prospective randomized study to eval- uate leuprolide acetate treatment before laparoscopic 56. Goodwin SC, Bradley LD, Lipman JC, Stewart EA, myomectomy: efficacy and ultrasonographic predictors.
Nosher JL, Sterling KM, et al. Uterine artery emboliza- Am J Obstet Gynecol 1998;178:108–12. (Level I) tion versus myomectomy: a multicenter comparative 70. Flierman PA, Oberye JJ, van der Hulst VP, de Blok S.
study. Fertil Steril 2006;85:14–21. (Level II-2) Rapid reduction of leiomyoma volume during treatment 57. Gupta JK, Sinha AS, Lumsden MA, Hickey M. Uterine with the GnRH antagonist ganirelix. BJOG 2005;112: artery embolization for symptomatic uterine fibroids.
71. Frederick J, Fletcher H, Simeon D, Mullings A, Hardie 86. Manyonda I, Sinthamoney E, Belli AM. Controversies M. Intramyometrial vasopressin as a haemostatic agent and challenges in the modern management of uterine during myomectomy. Br J Obstet Gynaecol 1994;101: fibroids. BJOG 2004;111:95–102. (Level III) 87. Olufowobi O, Sharif K, Papaionnou S, Neelakantan D, 72. Fletcher H, Frederick J, Hardie M, Simeon D. A ran- Mohammed H, Afnan M. Are the anticipated benefits of domized comparison of vasopressin and tourniquet as myomectomy achieved in women of reproductive age? A hemostatic agents during myomectomy. Obstet Gynecol 5-year review of the results at a UK tertiary hospital.
J Obstet Gynaecol 2004;24:434–40. (Level III) 73. Phillips DR, Nathanson HG, Milim SJ, Haselkorn JS, 88. Garcia CR, Tureck RW. Submucosal leiomyomas and Khapra A, Ross PL. The effect of dilute vasopressin solu- infertility. Fertil Steril 1984;42:16–9. (Level III) tion on blood loss during operative hysteroscopy: a ran- 89. Rice JP, Kay HH, Mahony BS. The clinical significance domized controlled trial. Obstet Gynecol 1996;88:761–6.
of uterine leiomyomas in pregnancy. Am J Obstet 74. Garnet JD. Uterine rupture during pregnancy. An analy- 90. Pritts EA. Fibroids and infertility: a systematic review of sis of 133 patients. Obstet Gynecol 1964;23:898–905.
the evidence. Obstet Gynecol Surv 2001;56:483–91.
75. Paul PG, Koshy AK, Thomas T. Pregnancy outcomes fol- 91. Babaknia A, Rock JA, Jones HW Jr. Pregnancy success lowing laparoscopic myomectomy and single-layer following abdominal myomectomy for infertility. Fertil myometrial closure. Hum Reprod 2006;21:3278–81.
92. Gehlbach DL, Sousa RC, Carpenter SE, Rock JA.
76. Seracchioli R, Rossi S, Govoni F, Rossi E, Venturoli S, Abdominal myomectomy in the treatment of infertility.
Bulletti C, et al. Fertility and obstetric outcome after Int J Gynaecol Obstet 1993;40:45–50. (Level III) laparoscopic myomectomy of large myomata: a random- 93. Sudik R, Husch K, Steller J, Daume E. Fertility and preg- ized comparison with abdominal myomectomy. Hum nancy outcome after myomectomy in sterility patients.
Eur J Obstet Gynecol Reprod Biol 1996;65:209–14.
77. Kumakiri J, Takeuchi H, Kitade M, Kikuchi I, Shimanuki H, Itoh S, et al. Pregnancy and delivery after laparoscopic 94. Ubaldi F, Tournaye H, Camus M, Van der Pas H, Gepts myomectomy. J Minim Invasive Gynecol 2005;12: E, Devroey P. Fertility after hysteroscopic myomectomy.
Hum Reprod Update 1995;1:81–90. (Level III) 78. Parker WH, Iacampo K, Long T. Uterine rupture after 95. Dubuisson JB, Fauconnier A, Chapron C, Kreiker G, laparoscopic removal of a pedunculated myoma. J Minim Norgaard C. Reproductive outcome after laparoscopic Invasive Gynecol 2007;14:362–4. (Level III) myomectomy in infertile women. J Reprod Med 2000;45:23–30. (Level III) 79. Banas T, Klimek M, Fugiel A, Skotniczny K. Sponta- neous uterine rupture at 35 weeks’ gestation, 3 years after 96. Campo S, Campo V, Gambadauro P. Reproductive out- laparoscopic myomectomy, without signs of fetal dis- come before and after laparoscopic or abdominal tress. J Obstet Gynaecol Res 2005;31:527–30. (Level III) myomectomy for subserous or intramural myomas. Eur J Obstet Gynecol Reprod Biol 2003;110:215–9. (Level 80. Grande N, Catalano GF, Ferrari S, Marana R. Spon- taneous uterine rupture at 27 weeks of pregnancy afterlaparoscopic myomectomy. J Minim Invasive Gynecol 97. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate? Hum Reprod 2002;17:1424–30. (Level III) 81. Golan D, Aharoni A, Gonen R, Boss Y, Sharf M. Early spontaneous rupture of the post myomectomy gravid 98. Surrey ES, Lietz AK, Schoolcraft WB. Impact of intra- uterus. Int J Gynaecol Obstet 1990;31:167–70. (Level mural leiomyomata in patients with a normal endometri- al cavity on in vitro fertilization-embryo transfer cycleoutcome. Fertil Steril 2001;75:405–10. (Level II-2) 82. Ozeren M, Ulusoy M, Uyanik E. First-trimester sponta- neous uterine rupture after traditional myomectomy: case 99. Rackow BW, Arici A. Fibroids and in-vitro fertilization: report. Isr J Med Sci 1997;33:752–3. (Level III) which comes first? Curr Opin Obstet Gynecol 2005;17:225–31. (Level III) 83. Hart R, Molnar BG, Magos A. Long term follow up of 100. Tulandi T, Murray C, Guralnick M. Adhesion formation hysteroscopic myomectomy assessed by survival analy- and reproductive outcome after myomectomy and sec- sis. Br J Obstet Gynaecol 1999;106:700–5. (Level II-3) ond-look laparoscopy. Obstet Gynecol 1993;82:213–5.
84. Abbas A, Irvine LM. Uterine rupture during labour after hysteroscopic myomectomy. Gynaecol Endosc 1997;6: 101. Dutton S, Hirst A, McPherson K, Nicholson T, Maresh M. A UK multicentre retrospective cohort study compar- 85. Yaron Y, Shenhav M, Jaffa AJ, Lessing JB, Peyser MR.
ing hysterectomy and uterine artery embolisation for the Uterine rupture at 33 weeks’ gestation subsequent to hys- treatment of symptomatic uterine fibroids (HOPEFUL teroscopic uterine perforation. Am J Obstet Gynecol study): main results on medium-term safety and efficacy.
102. Ravina JH, Vigneron NC, Aymard A, Le Dref O, 110. Seltzer V. Screening for ovarian cancer: An overview Merland JJ. Pregnancy after embolization of uterine of the screening recommendations of the 1994 NIH myoma: report of 12 cases. Fertil Steril 2000;73:1241–3.
Consensus Conference. Prim Care Update Ob Gyns 103. Hehenkamp WJ, Volkers NA, Brokemans FJ, de Jong FH, 111. Reiter RC, Wagner PL, Gambone JC. Routine hysterec- Themmen AP, Birnie E, et al. Loss of ovarian reserve after tomy for large asymptomatic uterine leiomyomata: a uterine artery embolization: a randomized comparison with reappraisal. Obstet Gynecol 1992;79:481–4. (Level III) hysterectomy. Hum Reprod 2007;22: 1996–2005. (Level I) 112. Piscitelli JT, Simel DL, Addison WA. Who should have 104. Pron G, Mocarski E, Bennett J, Vilos G, Common A, intravenous pyelograms before hysterectomy for benign Vanderburgh L, et al. Pregnancy after uterine artery disease? Obstet Gynecol 1987;69:541–5. (Level III) embolization for leiomyomata: the Ontario multicenter 113. Parker WH, Fu YS, Berek JS. Uterine sarcoma in trial. Obstet Gynecol 2005;105:67–76. (Level II-3) patients operated on for presumed leiomyoma and rapidly 105. Rabinovici J, Inbar Y, Eylon SC, Schiff E, Hananel A, growing leiomyoma. Obstet Gynecol 1994;83:414–8.
Freundlich D. Pregnancy and live birth after focused ultrasound surgery for symptomatic focal adenomyosis: 114. Stewart EA, Morton CC. The genetics of uterine leiomy- a case report. Hum Reprod 2006;21:1255–9. (Level III) omata: what clinicians need to know. Obstet Gynecol 106. Gavrilova-Jordan LP, Rose CH, Traynor KD, Brost BC, Gostout BS. Successful term pregnancy following MR- 115. Schwartz LB, Diamond MP, Schwartz PE. Leiomyo- guided focused ultrasound treatment of uterine leiomy- sarcomas: clinical presentation. Am J Obstet Gynecol oma. J Perinatol 2007;27:59–61. (Level III) 107. Hanstede MM, Tempany CM, Stewart EA. Focused 116. Goto A, Takeuchi S, Sugimura K, Maruo T. Usefulness ultrasound surgery of intramural leiomyomas may facil- of Gd-DTPA contrast-enhanced dynamic MRI and itate fertility: a case report. Fertil Steril 2007;88: serum determination of LDH and its isozymes in the dif- ferential diagnosis of leiomyosarcoma from degenerated 108. Akkad AA, Habiba MA, Ismail N, Abrams K, al-Azzawi leiomyoma of the uterus. Int J Gynecol Cancer 2002; F. Abnormal uterine bleeding on hormone replacement: the importance of intrauterine structural abnormalities.
117. Tanaka YO, Nishida M, Tsunoda H, Okamoto Y, Obstet Gynecol 1995;86:330–4. (Level II-2) Yoshikawa H. Smooth muscle tumors of uncertain malig- 109. Sener AB, Seckin NC, Ozmen S, Gokmen O, Dogu N, nant potential and leiomyosarcomas of the uterus: MR Ekici E. The effects of hormone replacement therapy on findings. J Magn Reson Imaging 2004;20:998–1007.
uterine fibroids in postmenopausal women. Fertil Steril Copyright August 2008 by the American College of Obstetri- The MEDLINE database, the Cochrane Library, and cians and Gynecologists. All rights reserved. No part of this ACOG’s own internal resources and documents were used publication may be reproduced, stored in a retrieval system, to conduct a literature search to locate relevant articles pub- posted on the Internet, or transmitted, in any form or by any lished between January 1985 and December 2007. The means, electronic, mechanical, photocopying, recording, or search was restricted to articles published in the English lan- otherwise, without prior written permission from the publisher.
guage. Priority was given to articles reporting results oforiginal research, although review articles and commentar- Requests for authorization to make photocopies should be ies also were consulted. Abstracts of research presented at directed to Copyright Clearance Center, 222 Rosewood Drive, symposia and scientific conferences were not considered adequate for inclusion in this document. Guidelines pub- lished by organizations or institutions such as the National The American College of Obstetricians and Gynecologists
Institutes of Health and the American College of Obstetri- 409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
cians and Gynecologists were reviewed, and additionalstudies were located by reviewing bibliographies of identi- Alternatives to hysterectomy in the management of leiomyomas.
fied articles. When reliable research was not available, ACOG Practice Bulletin No. 96. American College of Obstetricians expert opinions from obstetrician–gynecologists were used.
and Gynecologists. Obstet Gynecol 2008;112:387–400.
Studies were reviewed and evaluated for quality accordingto the method outlined by the U.S. Preventive ServicesTask Force: Evidence obtained from at least one properlydesigned randomized controlled trial.
II-1 Evidence obtained from well-designed controlled II-2 Evidence obtained from well-designed cohort or case–control analytic studies, preferably from morethan one center or research group.
II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncon-trolled experiments also could be regarded as thistype of evidence.
Opinions of respected authorities, based on clinicalexperience, descriptive studies, or reports of expertcommittees.
Based on the highest level of evidence found in the data,recommendations are provided and graded according to thefollowing categories: Level A—Recommendations are based on good and con-sistent scientific evidence.
Level B—Recommendations are based on limited or incon-sistent scientific evidence.
Level C—Recommendations are based primarily on con-sensus and expert opinion.
Introduction of the levonorgestrel intrauterine system inKenya through mobile outreach: review of service statisticsand provider perspectivesDavid Hubacher,a Vitalis Akora,b Rose Masaba,a Mario Chen,a Valentine VeenaaLimited introduction of the LNG IUS through mobile outreach in Kenya, without any special promotion,resulted in good uptake. And providers viewed it positively, particularly becau