Transvaginal ultrasound showing endometrial polyp. Grayscale image shows a thickened endometrial stripe, which can be a nonspecific finding. Hysterosonogram or MRI is recommended to classify lesion.
Hysterosonogram image after balloon deployed and saline infused into endometrial cavity. An endometrial polyp is seen with a stalk, and fluid is noted around the majority of the polyp.
Sonohysterography is performed by placing a small balloon catheter intracervically through which saline is injected at the time of TVUS. This is well tolerated by patients and provides immediate information regarding location, size, and depth of intracavitary myomas as well as endometrial polyps. An additional advantage of SIS is the ability to classify the type of submucosal myoma based on the degree of intramural involvement. This information is pivotal for surgical planning and counseling.
Hysteroscopy provides direct visualization of the endometrial cavity and can be performed in the office or operating room. Directed biopsies can be performed if indicated, and hysteroscopy has the advantage of being both a diagnostic and therapeutic modality depending on the instruments available.
MRI is relatively noninvasive, provides excellent tissue delineation, and provides multiplanar images. MRI can provide detailed information regarding size, location and number of uterine masses. MRI can also identify junctional thickening, which is suggestive of adenomyosis. Figures 16-3 shows an example of adenomyosis on t-2 weighted MRI image.
Algorithm to evaluate nonpregnant women for AUB.
Histologic assessment
Histologic assessment of the endometrium is easy to perform in the office and may provide information about the presence of premalignant and malignant conditions of the endometrium (AUB-M). Endometrial specimens may be obtained using an endometrial pipelle, dilation and curettage (D&C), or hysteroscopically directed biopsies. Endometrial biopsy can be performed in the office and is excellent for detecting hyperplasia with atypia and endometrial cancer with a sensitivity and specificity of 82.3% and 98% for hyperplasia with atypia and 91% and 98% in detecting endometrial cancer, respectively.[19] However, endometrial sampling using a pipelle is a blind evaluation of the endometrium, has been shown to sample an average of 4% of the endometrium, and may miss a focal endometrial lesion.[20] For this reason, hysteroscopy with direct biopsies may be more appropriate for investigation of focal endometrial lesions. In clinical situations where a larger sample of tissue is needed, the endometrial biopsy is nondiagnostic, or an endometrial biopsy is unable to be performed in the office, dilation and curettage with or without hysteroscopy can be performed.
Endometrial sampling should be performed in women who have an increased risk for endometrial hyperplasia or cancer (Table 16-3). In women older than 45 years, endometrial sampling is recommended by ACOG for any AUB. In women older than 19 years and younger than 45 years, endometrial sampling should be considered in women with a history of chronic anovulatory cycles or persistent AUB unrelieved by medical therapy. In adolescents younger than 19 years, endometrial sampling is rarely necessary for evaluation given the limited cases of hyperplasia or malignancy in this population.[21]
Management
Medical management
Several factors should be considered in the management of AUB. Clinical diagnosis determines the appropriate treatment options. Additionally, one should clarify the patients’ perspective on severity of symptoms, desire for future fertility or contraception, and preferences for treatment. These factors allow for shared decision to clarify options, review patient values, and potentially increase compliance of treatment.[22]
Figure 16-5 summarizes the evaluation to direct treatment. In cases where the treatment is related to ovulatory dysfunction, medical management is first line therapy. Medical management is also useful for structural etiologies as a long-term treatment or to temporarily manage symptoms. Medical treatment is useful as a bridge to menopause in a perimenopausal patient, and in the preoperative period to optimize comorbid conditions, such as anemia and diabetes.
UAE flush pelvic aortogram.
Medical treatments are hormonal or nonhormonal. A patient may have risk factors or comorbidities where certain treatments are contraindicated and should not be used to treat AUB. For example, contraindications to combined oral contraceptives include previous thromboembolic event or stroke, history of an estrogen dependent tumor, active liver disease, pregnancy, hypertriglyceridemia, migraine with aura, tobacco use of more than 15 cigarettes per day, and age greater than 35 years. The Centers for Disease Control and Prevention (CDC) released medical eligibility criteria for contraceptive use, which can be found at www.cdc.gov/mmwr/preview/mmwrhtml/rr5904a1.htm?s_cid=rr5904a1_e. This site is an excellent resource for patients that have comorbidities or contraindications that preclude a particular treatment regimen.
Medical management of AUB consists of hormonal therapies and non-hormonal therapies. Medical management options are described in Figure 16-6 and the specific medications are listed in Table 16-6.
Algorithm for medical management of AUB.
| Medication | Dosage | Additional information |
|---|---|---|
| Estrogen-progestin contraceptives | Estrogen 20 mcg–35 mcg ethinyl estradiol Progestin: norethindrone or norethindrone acetate (>1 mg) or levenogestrel (≥150 mcg) | Regimen may either be cyclic or continuous |
| Levonorgestrel IUD | Levonorgestrel 20 mcg/24 hours | May be used for 5 years |
| Progestin | Medroxyprogesterone acetate 20 mg–40 mg daily Megestrol acetate 40 mg–80 mg daily Norethindrone acetate 5 mg–10 mg | Regimen may be continuous or taken 14 days of the month; however, it is not effective to reduce blood flow when taken in the luteal phase in ovulatory women |
| Nonsteroidal anti-inflammatory drugs | Mefenamic acid 500 mg three times daily Naproxen 500 mg, repeat dose in 3–5 hours, then 250 mg–500 mg twice daily Ibuprofen 600 mg daily | Regimen is taken during menses only |
| Antifibrinolytic | Tranexamic acid 1,300 mg three times daily | Regimen is taken for a maximum of 5 days, during menses |
Estrogen-progestin oral contraceptive pills (OCPs) have been shown to regulate bleeding patterns and reduce blood flow compared to placebo (47% vs. 9%) and may be taken cyclically or continuously.[23] When OCPs were compared to levenorgestrel IUD, the IUD resulted in less blood loss (87% vs. 35%).[24] The levonorgestrel IUD has been demonstrated to decrease menstrual blood loss by 74%–97% after one year of use in patients with AUB/HMB and has been shown to increase hemoglobin levels.[25, 26] The levonorgestrel IUD is well tolerated with adherence rates of 79.5%.[26] The most common reason for discontinuing use was irregular bleeding, which is most common for women in the first three months. After six months, most women report no bleeding to very light bleeding.[27] Oral progestin is effective for AUB but is less effective than OCPs or the levenogestrel IUD. The progestin only pill is useful for patients that have a contraindication for combination OCPs. [For a detailed list of contraindications associated with contraceptive methods, refer to www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm for the US Medical Eligibility Criteria (US MEC).]
Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce menstrual blood volume by reducing prostaglandin synthesis in the endometrium. This leads to vasoconstriction and decreased blood flow. NSAIDs have been shown to reduce HMB compared to placebo, but are not as effective as the hormonal methods. In a systematic review of seven studies, there was no evidence of a difference between different NSAIDs in a reduction of HMB.[27]
Transexamic acid, an antifibrinolytic agent, was approved by the Food and Drug Association (FDA) in 2009 for the treatment of menorrhagia. Antifibrinolytics inhibit plasminogen activators that normally cause fibrinolysis and are more abundant in women with HMB. Antifibrinolytics have been shown to reduce blood loss and improve limitation of physical activities, work inside and outside of the home, and perceived blood loss when compared to placebo.[28] There is a concern for thrombosis associated with transexamic acid and it is contraindicated in patients with a history of thrombosis or with concurrent use of a combination hormonal contraception.
Surgical management
Some causes of AUB are amenable to medical therapy, whereas some are best managed surgically. Furthermore, some women are unsatisfied with or do not desire long-term medical management of their AUB. Several surgical options exist and are discussed here.
Endometrial ablation
Endometrial ablation is a procedure used to reduce uterine bleeding by destroying the endometrial lining. Historically, resectoscopic ablation was performed using a hysteroscope and roller ball or wire loop. Now global ablative techniques are more common and use bipolar radiofrequency, hot liquid-filled balloon, cryotherapy, circulating heated water or microwave energy. Endometrial ablation is contraindicated in women who desire future fertility, have known or suspected endometrial hyperplasia or cancer (AUB-M), have a pelvic infection, or have had previous transmyometrial uterine surgery. Endometrial ablation has been shown to reduce menstrual blood flow, and may cause amenorrhea. Patient satisfaction is high, approximately 90% in one year.[30] However, there is a risk of subsequent surgery in cases where AUB or dysmenorrhea persists. The rate of additional surgical treatment for AUB at two to five years postoperatively is 21%–25%, depending on the technique.[30] Success may be lower in women with adenomyosis (AUB-A) (RR or OR1.7).[31]
Myomectomy
Surgical options for patients who are diagnosed with AUB-L include myomectomy, myolysis, or hysterectomy. Myomectomy may be performed hysteroscopically, laparoscopically, robotic-assisted, or through a laparotomy incision (open myomectomy). A hysteroscopic approach is appropriate for type 0 (intracavitary) or type 1 (where greater than 50% of the myoma is intracavitary), but is less effective in completely removing a type 2 (less than 50% of the myoma is submucosal). Both laparoscopic and open myomectomy can access subserosal, intramural, and submucosal fibroids. Laparoscopic myomectomies are associated with less anemia, a shorter hospital stay and quicker recovery, and longer operative duration as compared to open procedures.[32] Regardless of the surgical approach for myomectomy, the risk of myoma recurrence is 20% after laparoscopic myomectomy and 18 percent of open myomectomies.[32] Recurrent myomas are more likely in women who have multiple myomas than single myomas at the time of surgery. One retrospective study reviewed myoma recurrence in 145 women after open myomectomy. The risk of recurrent myomas after five years was 74% in patients with multiple myomas and 11% in those with single myomas. The rate of reoperation after multiple and solitary myomectomy were 62% and 9%, respectively.[33] The potential need for cesarean after myomectomy due to the risk of uterine rupture is an important consideration.
Myolysis
A relatively new technique is laparoscopic ultrasound-guided radiofrequency volumetric thermal ablation for symptomatic fibroids. A prospective, single arm study of 31 women showed improved symptom severity scores of 59.7%, 71.7%, and 82.0% at 3, 6, and 12 months, respectively.[34] Thirty-six month data from a prospective trial of 135 women was published in 2013 which showed improved symptom severity scores. In this study, there was an 11% reintervention rate, which included 2 myomectomies, 11 hysterectomies, and 1 uterine artery embolization. This study was limited by the lack of a comparison group; however, there are currently studies underway which will compare a laparoscopic ultrasound-guided radiofrequency volumetric thermal ablation to other treatments for fibroids.[35]
Hysterectomy
Hysterectomy is the most common gynecologic surgical procedure and is the definitive treatment for AUB. After hysterectomy, 96% of patients have reported that surgery had somewhat or completely resolved the gynecological problem.[36] Hysterectomy can be performed with or without the removal of ovaries. The benefits of concomitant removal of ovaries include reduced need for subsequent surgery (estimated 3%–8% of women undergoing hysterectomy),[37] reduction of breast cancer in premenopausal women, and reduction of ovarian cancer in all ages. The decision to perform bilateral oophorectomy is based on age, pathologic findings, and risk factors and patient preference. The surgical approach depends on uterine size, uterine dimensions, past medical and surgical history, and the experience and expertise of the surgeon. If possible, a vaginal approach is preferable, followed by laparoscopic or robotic assisted hysterectomy, then total abdominal hysterectomy.[38, 39, 40]
Large uteri can be removed laparoscopically utilizing morcellation techniques. This has been performed vaginally and abdominally in a closed and open system. In April 2014, the FDA released a safety communication that discourages the use of power morcellation in women with uterine fibroids due to the risk of inadvertent spread of undiagnosed cancer.[41] In December 2013, the Society of Gynecologic Oncologists released a statement.[42] Soon after the FDA communication, the American College of Obstetricians and Gynecologists and the Association of Gynecologic Laparoscopists have also released statements addressing morcellation of uterine fibroids due to the risk of inadvertent spread of cancer.[43, 44] The risk of uterine sarcoma has been estimated as less than 1 in 1,000 [42] and as high as 1 in 350 women [41] As a result of this concern, there are a number of hospitals that are not performing open power morcellation because of this risk. Open morcellation should not be performed if there is a concern for malignancy and patients should be counseled regarding the potential risks associated with this procedure. The minimally invasive techniques associated with morcellation result in shorter recovery and less blood loss than an open procedure. At this time, there is an active discussion on morcellation techniques and strategies to reduce this risk.
Radiological procedures
Several radiological treatments including uterine artery embolization (UAE) magnetic resonance guided-focused ultrasound (MRg-FUS), and energy based leiomyoma ablation have been used to treat AUB. As UAE is well researched and the most commonly performed radiological procedure, the most extensive discussion will be on UAE.
Uterine artery embolization
Uterine artery embolization is an endovascular procedure performed to produce hemorrhagic infarction of symptomatic uterine fibroids while maintaining endometrial and myometrial perfusion. The primary symptom for which women seek treatment for fibroids is menorrhagia.[45] Symptomatic fibroids usually result in heavy menstrual cycles with an increase in the length of the cycle and the number of days of heavy bleeding. Additional symptoms include pain and pressure associated with the mass effect of large uterine fibroids.
Magnetic resonance (MR) imaging should be used to evaluate patients before and after UFE. The assessment should include fibroid location, number, and size and the presence or absence of enhancement. Contrast enhanced MR also allows for the evaluation of the pelvic vasculature with assessment of the origins of the uterine arteries. MRI is used to identify patients that might be at a higher risk of a complication, such as fibroid expulsion, and have an effect on outcome, such as adenomyosis.[45] Pre-procedural MRI has been shown to affect case management, as evidenced by increased diagnostic confidence and allowing for an immediate change in treatment plan.[46] MR imaging is the most accurate imaging modality for detection of mimics of fibroids including adenomyosis, solid adnexal masses, focal myometrial contractions, and occasionally uterine leiomyosarcomas.[47]
Certain anatomic fibroid subtypes may affect management decisions. Intracavitary fibroids are more likely to be expelled after embolization and may present with lower abdominal pain and cramping and possible infection. These patients may require further gynecologic intervention. Pedunculated subserosal fibroids with a narrow stalk have been suggested to be a contraindication to embolization due to the risk of detachment, but the risk has been studied and no instances of detachment were noted. Cervical fibroids may be resistant to complete hemorrhagic infarction due to alternative blood supply to the cervix.[45]
Absolute contraindications include current pregnancy, known or suspected gynecologic malignancy, and current uterine or adnexal infection. Relative contraindications include contrast material allergy, coagulopathy, and renal failure.
Uterine artery embolization is accomplished via a catheter-based approach in which the common femoral artery is accessed and then the ipsilateral and contralateral uterine arteries are selected, usually with a microcatheter, and then embolized with particles.
The internal iliac artery terminates into anterior and posterior divisions. The branches of the anterior division include the inferior gluteal, obturator, internal pudendal, vesical, middle hemorrhoidal, uterine, and vaginal arteries. The branches of the posterior division include the superior gluteal, iliolumbar, and lateral sacral arteries. Due to the anterior and posterior orientation of the divisions, the selection of the anterior division is facilitated with a contralateral anterior oblique projection.
The uterine artery is the first or the second branch of the anterior division of the internal iliac artery in 51% of cases.[47] In 6% of cases, the uterine artery is the first branch of the internal iliac artery above the level of the inferior gluteal and superior gluteal arteries; and in 15%–40% of the general population, the internal iliac artery terminates in a trifurcation with the uterine artery origin positioned between the anterior and posterior divisions.[47] In the latter two cases, the selection of the uterine artery is facilitated by an ipsilateral anterior oblique projection.
The presence of uterine fibroids usually results in the hypertrophy and distortion of the uterine arteries, which supply both the normal myometrium and the fibroids. The uterine artery has a characteristic ∪ shape with a descending portion extending along the lateral pelvic wall, a transverse portion extending medially into the lower pelvis across the distal ureter at the level of the cervix, and an ascending portion extending superiorly along the lateral margin of the uterus. The uterine artery will typically have a corkscrew type appearance beginning in the ascending portion that will perfuse numerous collaterals to hyper-enhancing fibroids. The vesical and vaginal arteries usually originate from the transverse portion of the uterine artery. Safety of the procedure necessitates selection of the uterine artery into the ascending portion of the vessel to prohibit misadministration of embolic material into the vesical and vaginal arteries. Selection of the uterine artery into the distal corkscrew portion of the vessel assures a safe working position for embolization. A flush pelvic aortogram may be necessary if the characteristic uterine artery is not visualized, as the supply to the fibroids may originate from the ovarian arteries (see Figure 16-6).
Complete occlusion of the uterine arteries with stasis of contrast material is the usual angiographic endpoint when embolization is performed with nonspherical polyvinyl alcohol particles (see Figure 16-7).[47] Embolization is stopped when a standing column of contrast material is observed or when reflux of contrast is noted within the proximal ascending portion of the uterine artery (see Figure 16-8). With the administration of microspheres, the target of the embolization is the perifibroid arterial plexus, and embolization of the main uterine artery may be spared, with the angiographic endpoint becoming “near stasis” of the uterine artery with a “pruned-tree” appearance.[47]
UAE of selected uterine artery.
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