1. Uterine Leiomyomata به نام یگانه هستی بخش Uterine Leiomyomata DR_FIROUZABADI DR_FIROUZABADI

2. commonly termed fibroids the most common benign tumors of the female genital tract and likely are the most common soft tissue tumors of all. 200,000 hysterectomies and 20,000 myomectomies annually in the United States. 50% of women having identifiable fibroids at menopause.

3. Clinical Presentation  While fibroids can cause symptoms at any age after puberty, they typically do so in the early to mid 30s.  The symptoms caused by leiomyomata vary depending on the size, number, and location of the tumors.

4. TABLE 55.1 Symptoms of Leiomyomata * *Menorrhagia *Dysmenorrhea *Pelvic pressure (pressure on adjacent pelvic viscera) Urinary frequency Constipation Dyspareunia *Infertility *Repetitive pregnancy loss First trimester Second and third trimester (preterm labor) *Abdominal Distension

5. oligomenorrhea, regardless of the amount, or metrorrhagia does not suggest fibroids but rather an underlying endocrine abnormality (e.g., anovulation). Furthermore, the typical scenario encountered with fibroids is not a sudden heavy bleeding episode but rather gradually increasing menstrual bleeding, paralleling tumor growth.

6. Leiomyomata may undergo rapid enlargement during pregnancy, outstripping their blood supply and resulting in central avascular necrosis, the so-called red degeneration. The pain may be severe, requiring hospitalization and narcotics, but rarely puts a pregnancy at risk.

7. Ph/E

8. Anatomic Features Leiomyomata are benign, sex steroid- responsive, smooth muscle tumors of the uterus originating as clonal expansions of individual myometrial cells. The histology is virtually indistinguishable from normal myometrium except for a discrete circular whorling pattern with the cellularity and mitotic activity being highly variable.

9. Leiomyosarcomas do not arise from preexisting leiomyomata and present much later in life, well after menopause.

10. Types of leiomyoma

11.  There is virtually no neovascularity within fibroids  Collateral vascular channels are comparably maximally engorged and may represent a surgical challenge.

12. Influence of Sex Steroids  There is little doubt that the growth of leiomyomata is dependent on sex steroids as they: (a) are not noted prior to puberty. (b) typically regress after menopause. (c) possess sex steroid receptors (estrogen and progesterone).

13. (d) often dramatically enlarge during pregnancy when estrogen and progesterone levels are very high. (e) can be made to shrink with medically induced hypogonadism.

14. myomatous tissue has the same number of estrogen receptors but a higher number of progesterone receptors than the adjacent normal myometrium.

15. Situations that increase lifetime exposure to estrogen such as obesity and early menarche are associated with increased risk with the interval from the last delivery inversely related to risk.

16. oral contraceptives hormone replacement therapy Tamoxifen

17. Genetic Inheritance Pattern more than 40% of first-degree female relatives of women with leiomyomata common in all races, especially black women the most frequent indication for gynecologic surgery. multifactorial genetic inheritance pattern

18. Molecular Mechanisms and Genetic Dysregulation monoclonal neoplasms The most common aberrant patterns are translocations between chromosomes 12 and 14 (larger myomas), deletions of the short arm of chromosome 7 (smaller tumors), and rearrangements of the long arm of chromosome 6.

19. Impact of Leiomyomata on Reproduction TABLE 55.2 Mechanisms of Infertility with Leiomyomata *Impaired implantation Submucous Intracavitary Enlarged uterine cavity volume *Impaired tubal transport Obstruction Distension

20. Intramural leiomyomata and ART first-trimester pregnancy loss, preterm labor, or intrauterine growth restriction abruption placental classic cesarean delivery The need to perform a cesarean following myomectomy needs to be considered in any risk-benefit analysis.

21. Diagnostic Studies The majority of leiomyomata are detected on pelvic examination performed because of gynecologic symptoms. The uterus is typically noted to be enlarged and irregular on bimanual examination. It is important to distinguish leiomyomata from other pelvic masses, and it may be difficult to do so in the presence of a large uterus. This is most easily done with an endovaginal or abdominal ultrasound scan, as the leiomyomata appear echogenic with similar acoustic impedance to the normal myometrium. Computerized tomography and magnetic resonance imaging (MRI) may prove useful in selected circumstances, but they are much more expensive and yield little more useful information than office sonography.

22. Diagnostic Imaging Techniques 1.Endovaginal ultrasonography 2.Sonohysterography 3.Hysterosalpingography 4.Hysteroscopy 5.Computerized tomography 6.Magnetic resonance imaging

23. Diagnostic Studies (cont’d) sonography: The proximity of the leiomyomata to the endometrial cavity can usually be demonstrated by taking advantage of the acoustic differences between normal myometrium, fibroid tumors, and the endometrial cavity. The endometrial stripe is a reliable marker of the endometrial cavity, and finding a smooth, continuous endometrial stripe with normal underlying myometrium between the cavity and any fibroids suggests that they are not submucosal.

24. Diagnostic Studies (cont’d) Simultaneously injecting saline into the endometrial cavity while performing an endovaginal ultrasound examination (sonohysterography) improves the ability to delineate submucous and intracavitary leiomyomata. However, it is not possible to distinguish an endometrial polyp from an intracavitary myoma by virtually any imaging technique.

25. Diagnostic Studies (cont’d) Hysterosalpingography is often undertaken if infertility is present concurrently, as this technique can identify intracavitary tumors or a large but otherwise normal endometrial cavity caused by the stretching the normal myometrium around leiomyomata. This radiographic technique has the added advantage of determining tubal patency as well.

26. Diagnostic Studies (cont’d) Increasingly, office hysteroscopy is being used when tubal patency is not an issue, as this technique allows clear differentiation between leiomyomata and other intracavitary pathology such as endometrial adhesions, uterine septae, and endometrial polyps.

27. Diagnostic Studies (cont’d) Adenomyosis can occasionally be difficult to distinguish clinically from leiomyomata. Imaging studies may not be helpful. The true diagnosis only made at surgery. MRI has been reported to be useful in differentiating adenomyosis from leiomyomata.

28. When to Treat Despite the fact that fibroids are responsible for a large number of gynecologic surgeries, treating these benign tumors requires the same risk- benefit analysis as any other therapeutic decision. Often, simply using a prostaglandin synthetase inhibitor or oral contraceptives will adequately relieve the symptoms.

29. When to Treat (cont’d) It may be appropriate to remove asymptomatic, extremely large leiomyomata in an effort to prevent anticipated reproductive problems. Large tumors that fill the pelvis can impinge on the pelvic sidewalls, causing hydronephrosis, and their removal is critical to prevent renal impairment.

30. When to Treat (cont’d) The growth characteristics of individual fibroids remain highly unpredictable. Many have limited growth potential. Some leiomyoma have already experienced rapid growth and have undergone aseptic necrosis and replacement by fibrosis, so they have no further growth potential and will not regress after menopause. Many fibroids may gradually enlarge and cause symptoms well before the anticipated regression at menopause.

31. When to Treat (cont’d) Gradually worsening dysmenorrhea and menorrhagia are more frequently linked than other symptoms. When these symptoms are mild, nonsteroidal anti- inflammatory agents and oral contraceptives are often useful.

32. When to Treat (cont’d) Location of the fibroids is important with regard to the development of symptoms: The closer the proximity to the endometrial cavity, the greater and earlier the symptoms are observed. Intramural, submucosal, and intracavitary fibroids are far more likely to be responsible for dysmenorrhea and menorrhagia than pedunculated or subserosal myomas. Severe symptoms may warrant intervention at a relatively small size, particularly when an intracavitary or submucosal fibroid is present. Similarly, the closer to the serosal surface the fibroids are located, the larger the size will be attained before being detected. Indeed, some extremely large leiomyomata will not be associated with any symptoms aside from increased abdominal girth.

33. When to Treat (cont’d) Because the bladder is adjacent to the uterus, the most frequent symptom associated with a large myomatous uterus is increased urinary frequency. Rarely, compression of the colon against the sacrum may cause difficulty with defecation; however, more often than not, complaints of constipation are not completely relieved by removing or shrinking the leiomyomata.

34. Selecting the Appropriate Therapy When clear indications for treatment are present, the most critical questions to ask before making a therapy decision pertain to (a) whether future reproduction is desired (b) how soon menopause can be anticipated.

35. Selecting the Appropriate Therapy (cont’d) As a simple hysterectomy represents a definitive cure, this is an attractive option for many symptomatic women when: 1. maintenance of reproduction is not desired, 2. menopause is not imminent, 3. and more conservative measures have failed to alleviate the symptoms.

36. Selecting the Appropriate Therapy (cont’d) When the preservation of future childbearing is desired, a myomectomy is the primary choice.

37. Extirpative Options Endoscopic techniques Laparoscopically assisted supracervical hysterectomy Laparoscopically assisted total hysterectomy Laparoscopic myomectomy Hysteroscopic resection of leiomyomata Abdominal approach Supracervical hysterectomy Total hysterectomy Myomectomy Vaginal approach Hysterectomy Myomectomy

38. Hysterectomy When: future childbearing is not desired, the symptoms are severe enough to warrant treatment, and the woman has no contraindications, a simple hysterectomy is often chosen.

39. Hysteroscopic Myomectomy Most intracavitary leiomyomata and a substantial number of submucous leiomyomata can be resected via surgical hysteroscopy in an ambulatory setting.

40. Abdominal Myomectomy When symptomatic leiomyomata are not amenable to a hysteroscopic approach, an abdominal approach usually is required.

41. Abdominal Myomectomy (cont’d) An elective cesarean section is the preferred route of delivery for the vast majority of women with a previous abdominal myomectomy.

42. Minimally Invasive Myomectomy Pedunculated, serosal, and selected intramural leiomyomas can be dissected free from the surrounding myometrium, morcellated, and the incision closed via laparoscopy.

43. Recurrence of Leiomyomata Since there is a genetic basis for the development of leiomyomata, even when all of the palpable leiomyomata have been surgically removed, the rate of recurrence and/or persistence with continued growth has been variably reported to be as high as 30% to 40%, depending on the: Number of tumors removed The length of follow-up.

44. Recurrence of Leiomyomata (cont’d) Indeed, between 10% and 25% of women undergoing myomectomies require another surgical procedure within the next decade.

45. Recurrence of Leiomyomata (cont’d) Isolated large fibroids have lower recurrence rates than when multiple small tumors are present, despite an overall smaller volume of leiomyomata.

46. Postoperative Pelvic Adhesions The frequency of postoperative adhesions following myomectomy exceeds 50% and can result in reduced fertility, pain, or bowel obstruction. Careful surgical technique to minimize the degree of surgical trauma, confining the incisions to the anterior uterine surface so as to prevent contact with the bowel and adnexal structures, and covering the posterior uterine incisions with surgical barriers, have been advocated to minimize the rate of postoperative adhesions.

47. Non-extirpative Options Myolysis UAE MRI-guided HIFU Medically induced hypogonadism GnRH agonist GnRH agonist with “add-back”‌ therapy

48. Medical Suppression Many medicinal agents have been considered for the treatment of symptomatic leiomyomata, including: 1.estrogen antagonists, 2.progesterone antagonists (mifepristone), 3.androgens (danazol), 4.pituitary down-regulation with GnRH agonists.

49. Medical Suppression (cont’d) Hypogonadism cannot be sustained for a prolonged interval because of the significant side effects such as: vasomotor hot flashes, accelerated bone loss, genital tract atrophy, and loss of the cardiovascular protection.

50. Medical Suppression (cont’d) The important question to ask is, “What is the goal of medical suppression?” Currently, the most relevant clinical use of GnRH agonists is to stop excessive vaginal bleeding and improve the hemogram prior to surgery or in order to delay surgery to correct other medical problems that are posing an increased surgical risk.

51. Myolysis There have been many attempts at inducing therapeutic necrosis of cells within the center of a fibroid (e.g., myolysis), thereby shrinking the tumor size, relieving symptoms, and preventing progressive growth of the tumors.

52. Myolysis (cont’d) The aseptic necrosis may cause significant pain in the immediate post-treatment interval, comparable to that observed with degeneration of leiomyomata seen in pregnancy.

53. Myolysis (cont’d) Myolysis should be confined to those women who are not interested in subsequent pregnancy until well-designed, long-term comparative trials demonstrate safety.

54. Uterine Artery Embolization When menorrhagia is the primary clinical symptom and either the surgical risk is judged unacceptable or the patient declines extirpative surgery, therapeutic embolization of the uterine arteries can be utilized to reduce symptoms. This strategy is to simultaneously deprive the uterus and the fibroids of their blood supply, induce necrosis, and reduce the symptoms.

55. UAE (cont’d) Since UAE has only been widely utilized for only slightly over a decade, the long-term safety and efficacy remain to be demonstrated.

57. 57 Adenomyosis

58. 58 Definition A benign uterine condition in which endometrial glands and stroma are present within the uterine musculature

59. 59 Etiology The cause of adenomyosis is unknown uterine trauma caesarean section tubal ligation pregnancy Basal endometrial hyperplasia invading a hyperplastic myometrial stroma.

60. Four primary theories Heredity Trauma Hyperestrogenemia Viral transmission 60

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64. 64 The thickened and spongy appearing myometrial wall of this sectioned uterus is typical of adenomyosis. There is also a small white leiomyoma at the lower left.

65. Adenomyosis, Hysterectomy Specimen 65

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67. Adenomyosis correlates with abnormal amounts of multiple substances, possibly indicating a causative link in its pathogenesis: Endometrial IL-18 receptor mRNA and the ratio of IL-18 binding protein to IL-18 are significantly increased in adenomyosis patients in comparison to normal peopleIL-18 receptorIL-18 binding proteinIL-18 67

68. 68 Clinical features1 Asymptomatic Classic symptoms ： secondary dysmenorrhea abnormal uterine bleeding Chronic pelvic pain may occur

69. 69 Clinical features2 ： Most common physical sign a diffusely enlarged uterus particularly tender during menstruation

70. 70 Diagnosis ： History Pelvic examinations Ultrasonography MRI Serum markersCA-125 definitive diagnosis can only be made from histological examination of a hysterectomy specimen

71. 71 Treatment Hormone therapy NSAIDs Hysterectomy the only uniformly successful treatment for adenomyosis is necessary.

72. Endometrial polyps 72

73. Definition Benign localised overgrowth of endometrial glands and stroma, covered by epithelium, projecting above the adjacent epithelium 73

74. epidemiology 12-80 Years old Most occur in women in their 40s and 50s Endometrial polyps occur in up to 10% of women It is estimated that they are present in 25% of women with abnormal vaginal bleeding Large endometrial polyps can also be associated with tamoxifen use(associated with a higher risk of neoplasia and different molecular alterations) 74

75. Risk factors Risk factors include obesity high blood pressure history of cervical polypscervical polyps tamoxifen hormone replacement therapy 75

76. Pathological findings Sessile or pedunculated Size: 1mm and beyond – may fill the endometrial cavity and project through the cervical os red/brown color,large ones can appear to be a darker red May be multiple May originate anywhere, but most commonly fundus 76

77. etiology No definitive cause of endometrial polyps is known affected by hormone levels and grow in response to circulating estrogenestrogen 77

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82. symptoms They often cause no symptoms Where they occur, symptoms include "spotting" between menstrual periods, or after menopause irregular menstrual bleeding bleeding between menstrual periods excessively heavy menstrual bleeding vaginal bleeding after menopausemenopause If the polyp protrudes through the cervix into the vagina, pain (dysmenorrhea) may resultdysmenorrhea 82

83. Diagnosis vaginal ultrasound (sonohysterography) vaginalultrasound hysteroscopy dilation and curettage 83

84. Treatment IntraUterine System containing levonorgestrel in women taking Tamoxifen may reduce the incidence of polyps IntraUterine Systemlevonorgestrel Polyps can be surgically removed using curettage or hysterescopy curettage If it is a large polyp, it can be cut into sections before each section is removed If cancerous cells are discovered, a hysterectomy may be performedcancerous hysterectomy 84

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86. Prognosis and complications Endometrial polyps are usually benign although some may be precancerous or cancerousbenignprecancerouscancerous About 0.5% of endometrial polyps contain adenocarcinoma cells adenocarcinoma Polyps can increase the risk of miscarriage in women undergoing IVF treatmentmiscarriageIVF Although treatments such as hysterescopy usually cure the polyp concerned, recurrence of endometrial polyps is frequent Untreated, small polyps may regress on their own 86

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