2. LEIOMYOMA
Dr . Zahra Panahi

3. INTRODUCTION
Uterine leiomyomas (also referred to as fibroids or myomas) are the most common pelvic tumor in women .They are benign monoclonal tumors arising from the smooth muscle cells of the myometrium. 

4. INTRODUCTION
 They arise in reproductive-age women and typically present with symptoms of abnormal uterine bleeding and/or pelvic pain/pressure. Uterine fibroids may also have reproductive effects (eg, infertility, adverse pregnancy outcomes).

5.  LOCATION 
The International Federation of Gynecology and Obstetrics (FIGO) classification system for fibroid location is as follows :
Intramural myomas (FIGO type 3, 4, 5) – These leiomyomas are located within the uterine wall. They may enlarge sufficiently to distort the uterine cavity or serosal surface. Some fibroids may be transmural and extend from the serosal to the mucosal surface.

6. LOCATION
Submucosal myomas (FIGO type 0, 1, 2) – These leiomyomas derive from myometrial cells just below the endometrium (lining of the uterine cavity). These neoplasms protrude into the uterine cavity. The extent of this protrusion is described by the FIGO/European Society of Hysteroscopy classification system and is clinically relevant for predicting outcomes of hysteroscopic myomectomy.

7. LOCATION Type 0 – Completely within the endometrial cavity
Type 1 – Extend less than 50 percent into the myometrium
Type 2 – Extend 50 percent or more within the myometrium

8. LOCATION
Subserosal myomas (FIGO type 6, 7) – These leiomyomas originate from the myometrium at the serosal surface of the uterus. They may have a broad or pedunculated base and may be intraligamentary (ie, extending between the folds of the broad ligament).

9. LOCATION
Cervical myomas (FIGO type 8) – These leiomyomas are located in the cervix rather than the uterine corpus.

10. PREVALENCE
PREVALENCE — Uterine leiomyomas are the most common pelvic tumor in women.

11. CLINICAL FEATURES The majority of myomas are small and asymptomatic.
Heavy or prolonged menstrual bleeding
.Bulk-related symptoms, such as pelvic pressure and pain
.Reproductive dysfunction (ie, infertility or obstetric complications)

12. CLINICAL FEATURES
The presence and degree of uterine bleeding are determined, in large part, by the location of the fibroid; size is of secondary importance 
Submucosal myomas that protrude into the uterine cavity (eg, types 0 and 1) are most frequently related to significant heavy menstrual bleeding.

13. CLINICAL FEATURES
Intramural myomas are also commonly associated with heavy or prolonged menstrual bleeding, but subserosal fibroids are not considered a major risk for heavy menstrual bleeding.
Cervical fibroids that are close to the endocervical canal may be related to AUB.

14. Bulk-related symptoms
Pelvic pressure or pain — pelvic discomfort is common in women with fibroids but less common than AUB. If discomfort is present, it is likely to be chronic, intermittent, dull pressure or pain.
Urinary tract or bowel issues.
Venous compression .

15. Other pain or discomfort
Painful menses.
Painful intercourse.
Fibroid degeneration or torsion.

16. Infertility or obstetric complications
 Leiomyomas that distort the uterine cavity (submucosal or intramural with an intracavitary component) result in difficulty conceiving a pregnancy and an increased risk of miscarriage.
 leiomyomas have been associated with adverse pregnancy outcomes (eg, placental abruption, fetal growth restriction, malpresentation, and preterm labor and birth).

17. DIAGNOSTIC EVALUATION
History — A medical history is taken, including:
Symptoms related to fibroids .
Obstetric and gynecologic history, including prior history of uterine fibroids, history of pelvic pain, obstetric or gynecologic surgeries, and risk factors for uterine malignancies other than endometrial carcinoma . .Relevant medical and surgical history

18. DIAGNOSTIC EVALUATION
Physical examination — The physical examination includes an abdominal and pelvic examination.

19. DIAGNOSTIC EVALUATION
Imaging and endoscopy — Pelvic ultrasound is the imaging study of choice for uterine leiomyomas, based on the ability to visualize genital tract structures and cost-effectiveness.
Step one: Pelvic ultrasound — Pelvic ultrasound is the first-line study used to evaluate for uterine fibroids. Transvaginal ultrasound has high sensitivity (95 to 100 percent) for detecting myomas in uteri less than 10 gestational weeks' size.

20. DIAGNOSTIC EVALUATION
If fibroids are thought to be causing urinary tract obstruction, then a renal ultrasound can be obtained to assess for hydronephrosis.

21. DIAGNOSTIC EVALUATION
Step two: Evaluate the uterine cavity
Saline infusion sonography:Saline infusion sonography is helpful when planning a hysteroscopic resection of a fibroid or evaluating the potential risks of fertility associated with a fibroid.

22. DIAGNOSTIC EVALUATION
Hysteroscopy :Hysteroscopy can help in the planning of a hysteroscopic resection of a submucosal fibroidand rule out small polyps not seen on ultrasound.

23. DIAGNOSTIC EVALUATION
Step three: Additional imaging
Magnetic resonance imaging — Magnetic resonance imaging (MRI) is the most effective modality for visualizing the size and location of all uterine myomas and can distinguish among leiomyomas, adenomyosis, and adenomyomas.

24. DIAGNOSTIC EVALUATION
 its use is best reserved for procedural planning for complicated procedures. For instance, for women with type 3 through 6 uterine fibroids, an MRI can help the surgeon plan for laparoscopic myomectomy to know the expected depth into the myometrium.
 It may also be useful in differentiating leiomyomas from leiomyosarcomas and before uterine artery embolization since imaging patterns predict uterine artery embolization outcome.

25. DIFFERENTIAL DIAGNOSIS
The differential diagnosis of an enlarged uterus includes both benign and malignant conditions:
Myometrial lesions:
Benign leiomyoma.
Adenomyosis (diffuse infiltration of the myometrium) or adenomyoma.
Leiomyoma variant.
Leiomyosarcoma.
Metastatic disease – This is very rarely the cause of an enlarged uterus and typically from another reproductive tract primary; these lesions are likely to be myometrial but may invade the endometrium 

26. DIFFERENTIAL DIAGNOSIS
Endometrial lesions:
Endometrial polyp – These tend to be small and are unlikely to cause an enlarged uterus.
Endometrial carcinoma (may invade into the myometrium) or hyperplasia.
Carcinosarcoma – Considered an epithelial neoplasm.
Endometrial stromal sarcoma (mimics endometrium but invades the myometrium).
Pregnancy
Hematometra (blood within the uterine cavity, usually following an intrauterine procedure, eg, dilation and curettage)

27. MANAGEMENT
Relief of symptoms (eg, abnormal uterine bleeding, pain, pressure) is the major goal in management of women with significant symptoms .The type and timing of any intervention should be individualized, based upon factors such as :
Type and severity of symptoms
Size of the myoma(s)
Location of the myoma(s)
Patient age
Reproductive plans and obstetrical history

28. MANAGEMENT
EXPECTANT MANAGEMENT:asymptomatic uterine leiomyomas can usually be followed without intervention .  evidence-based guidelines support not treating asymptomatic fibroids.

29. MEDICAL THERAPY 
A trial of medical therapy in premenopausal women with mild symptoms and/or mildly enlarged uteri can also be useful for helping to distinguish symptoms primarily related to leiomyomas from those primarily due to a concurrent problem, such as oligoovulation, which may be contributing to abnormal uterine bleeding or infertility.

30. Hormonal therapies
 Combined hormonal contraceptives and progestational agents are commonly prescribed to regulate abnormal uterine bleeding, but appear to have limited efficacy in the treatment of uterine leiomyomas .
These drugs can be useful in some women with heavy menstrual bleeding, particularly those with coexisting problems (eg, dysmenorrhea or oligoovulation); but they do not appear to be effective in decreasing bulk symptoms.

31. Estrogen-progestin contraceptives
clinical experience suggests some women with heavy menstrual bleeding associated with leiomyomas respond to OC therapy.
 The purported mechanism of action is via endometrial atrophy.
This approach should be reassessed if a woman has exacerbation of bulk-related symptoms on Ocs.

32. Levonorgestrel-releasing intrauterine system
Observational studies and systematic reviews have shown a reduction in uterine volume and bleeding, and an increase in hematocrit after placement of this IUS .
A second advantage of this treatment is that it provides contraception for women who do not desire pregnancy.
 The presence of intracavitary leiomyomas amenable to hysteroscopic resection is a strong relative contraindication to use. 

33. Progestin implants, injections, and pills
progestin-only contraceptives cause endometrial atrophy and thus provide relief of menstrual bleeding-related symptoms. They can be considered for treatment of mild symptoms, especially for women who need contraception.

34. Gonadotropin-releasing hormone agonists
 Gonadotropin-releasing hormone (GnRH) agonists are the most effective medical therapy for uterine myomas.
 Most women will develop amenorrhea, improvement in anemia (if present), and a significant reduction (35 to 60 percent) in uterine size within three months of initiating this therapy, thus achieving improvement in both categories of myoma symptomatology.

35. Gonadotropin-releasing hormone agonists
However, there is rapid resumption of menses and pretreatment uterine volume after discontinuation of GnRH agonists.

36. Gonadotropin-releasing hormone agonists
Because of the rapid rebound in symptoms and side effects, GnRH agonists are primarily used selectively as preoperative therapy. 
 GnRH agonists are approved for administration for three to six months prior to leiomyoma- related surgery in conjunction with iron supplementation to facilitate the procedure and enable correction of anemia.

37. Gonadotropin-releasing hormone agonists
 GnRH-agonists are used to provide short-term relief to women close to menopause or with acute medical contraindications to surgery .

38. Progesterone receptor modulators
Ulipristal acetate — Ulipristal acetate is a progesterone receptor modulator (PRM) that is approved outside the United States both for three months of preoperative therapy and short intermittent courses interrupted by menstruation.

39. Progesterone receptor modulators
Mifepristone :antiprogestin mifepristone (RU-486) is the most widely studied PRM and reduces uterine volume by 26 to 74 percent in women with leiomyomas, comparable to the reduction observed with GnRH agonists.
 Regrowth occurs slowly following cessation of the drug.
 Mifepristone is not approved by the FDA for the treatment of uterine myomas. 

40. Progesterone receptor modulators
 As with ulipristal acetate, an impediment to use of mifepristone for treatment of leiomyomas is that currently available doses are not appropriate (200 mg once for termination of pregnancy versus 5 to 50 mg/day for three to six months for myoma reduction).

41. Progesterone receptor modulators
 true endometrial hyperplasia and atypical hyperplasia have not been observed following PRM therapy, and no woman has developed endometrial carcinoma.
Endometrial thickening has been detected on ultrasound as early as three months after doses of mifepristone ranging from 5 to 10 mg daily . It has also been reported with ulipristal 

42. selective estrogen receptor modulators
Raloxifene — The efficacy of selective estrogen receptor modulators for treatment of leiomyomas is unclear.

43. Aromatase inhibitors
Aromatase inhibitors :Small series and one randomized clinical trial have described shrinkage of symptomatic leiomyomas and a decrease in leiomyoma symptoms in women in the menopausal transition given aromatase inhibitors .
 their potential role in management of uterine myomas requires further study to establish the duration of response, risks, and cost-effectiveness.

44. OTHER MEDICATIONS
Antifibrinolytic agents — Antifibrinolytic agents, which are useful in the treatment of idiopathic menorrhagia, have not been well studied in leiomyoma–related menorrhagia.
Nonsteroidal antiinflammatory drugs:. NSAIDs do not appear to reduce blood loss in women with myomas ,but because they decrease painful menses, they can be useful in this population.

45. OTHER MEDICATIONS
Danazol and gestrinone — Androgenic steroids may be an effective treatment of leiomyoma symptoms in some women, but are associated with frequent side effects.
 Danazol may control anemia related to leiomyoma- related menorrhagia, but it does not appear to reduce uterine volume. Side effects are common (eg, weight gain, muscle cramps, decreased breast size, acne, hirsutism, oily skin, decreased high density lipoprotein levels, increased liver enzymes, hot flashes, mood changes, depression).

46. OTHER MEDICATIONS
 gestrinone, decreases myoma volume and induces amenorrhea in women with leiomyomas .

47. SURGERY
 Surgery is the mainstay of therapy for leiomyomas. Hysterectomy remains the most utilized procedure and still accounts for at least 70 percent of all fibroid procedures in the United States.

48. Indications Abnormal uterine bleeding or bulk-related symptoms
Infertility or recurrent pregnancy loss 
Evaluation for malignancy is not an indication for surgery in most women with leiomyomas.

49. SURGERY
Hysterectomy — We suggest hysterectomy for (1) women with acute hemorrhage who do not respond to other therapies; (2) women who have completed childbearing and have current or increased future risk of other diseases (cervical intraepithelial neoplasia, endometriosis, adenomyosis, endometrial hyperplasia, or increased risk of uterine or ovarian cancer) that would be eliminated or decreased by hysterectomy; (3) women who have failed prior minimally invasive therapy for leiomyomas; and (4) women who have completed childbearing and have significant symptoms, multiple leiomyomas, and a desire for a definitive end to symptomatology.

50. SURGERY
Myomectomy — Myomectomy is an option for women who have not completed childbearing or otherwise wish to retain their uterus.
Hysteroscopic myomectomy is the procedure of choice for removing intracavitary myomas (submucosal and intramural myomas that protrude into the uterine cavity).

51. SURGERY
 When a fibroid prolapses through the cervix, myomectomy can be performed vaginally. 
Endometrial ablation — In women who have completed childbearing, endometrial ablation, either alone or in combination with hysteroscopic myomectomy, is an option for management of bleeding abnormalities. Since intramural and subserosal leiomyomas are not affected by this procedure, bulk or pressure symptoms are unlikely to improve.

52. SURGERY
Myolysis — Myolysis refers to laparoscopic thermal, radiofrequency, or cryoablation (cryomyolysis) of leiomyoma tissue.
localized tissue destruction without repair may increase the chance of subsequent adhesion formation or rupture during pregnancy. 

53. INTERVENTIONAL RADIOLOGY
Uterine artery embolization — Uterine artery embolization (UAE), or uterine fibroid embolization (UFE), is a minimally invasive option for management of leiomyoma-related symptoms.
. It is an effective option for women who wish to preserve their uterus and are not interested in optimizing future fertility.

54. INTERVENTIONAL RADIOLOGY
UFE results in shrinkage of myomas of approximately 30 to 46 percent .

55. INTERVENTIONAL RADIOLOGY
 women with larger uteri and/or more leiomyomas at baseline are at greater risk of failure

56. INTERVENTIONAL RADIOLOGY
Magnetic resonance guided focused ultrasound — Magnetic resonance guided focused ultrasound surgery (MRgFUS) is a more recent option for the treatment of uterine leiomyomas in premenopausal women who have completed childbearing.

57. INTERVENTIONAL RADIOLOGY
The maximum size of a leiomyoma for this procedure is uncertain .