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Fibroid and infertility


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Fibroids & infertility

Published in: Health & Medicine

Fibroid and infertility

  1. 1. Benha University Hospital, EgyptAboubakr elnashar
  2. 2. Types of fibroids (The European Society of Hysteroscopy, 1993) 1.Submucos (SM): Fibroid distorting ut cavity. Type 0: pedunculated without intramural extension Type I: Sessile with intramural extension <50% Type II: Sessile with intramural extension >50% 2. Intramural (IM): Fibroid not distorting the cavity & <50% protrusion into serosal surface 3. Subserosal (SS): >50% protrudes out of the serosal surface (Sessile or pedunculated) Aboubakr elnashar
  3. 3. Submucous: 0, 1, 2 Intramural: 3, 4: Type 3: totally intramural but abut (touch) the endometrium Type 4: entirely within the myometrium, with no extension to the endometrial surface or to the serosa. Subserous: 5, 6, 7 8: cervical, b lig, parasitic. Aboubakr elnashar
  4. 4. 20- 40% of women of reproductive age Aboubakr elnashar
  5. 5. FIBROIDS & INFERTILITY Aboubakr elnashar
  6. 6. Incidence: Associated with infertility: 5- 10%. Only cause of infertility: 2- 3% Aboubakr elnashar
  7. 7. Mechanisms: 1. Effect on fertilization Interference with sperm or ovum transport. a. Enlargement& deformity of uterine cavity b.Uterine contractility (Vollenhoven et al, 1990). c. Distortion of the cervix d. Distortion or obstruction of tubal ostia. Aboubakr elnashar
  8. 8. 2. Effect on implantation Implantation failure or gestation discontinuation (Buttram & Reiter, 1981) a.Alteration of the endometrial contour b.Persistence of intrauterine blood or clots c. Focal endometrial vascular disturbance d.Endometrial inflammation e.Secretion of vasoactive substances f. Enhanced endometrial androgen environment None of these putative mechanisms has been confirmed to be the etiologic factor. Aboubakr elnashar
  9. 9. Effect on fertilization Effect on implantation Anatomic distortion of the cervix Altered endometrial development Altered uterine contractility Prevention of efflux of discharge or blood Deformity of the endometrial cavity Distortion of the shape of the endometrium Obstruction of tubal ostia Mechanisms By Which Fibroids Affect Reproductive Function Aboubakr elnashar
  10. 10. Aboubakr elnashar
  11. 11. Fibroids & IVF Aboubakr elnashar
  12. 12. IVF provides a good model to assess the effect of fibroid on IR by excluding other factors such as tubal or male (Donnez & Jadoul, 2002). IVF cannot assess the effect of fibroid on sperm migration & ovum transport. Type Size Number Aboubakr elnashar
  13. 13. PR/ET % Fibroid (n) 9Submucou s (27) 16Intramural (44) 27Subserous (158) 30Control (2413) 1.Type of fibroid: Bajekal & Li (2000) PR with IVF SM: Most detrimental effect IM: Modest impact SS: Least impact on PR. Aboubakr elnashar
  14. 14. PR/ET%Fibroid (n) 9Distorted cavity(65) 34Not distorted cavity (487) 40Control(1636) Donnez & Jadoul (2002). No difference in implantation or PR unless the uterine cavity itself was distorted by the myomas distorting intramural fibroids: adverse pregnancy outcomes in women undergoing IVF (Sunkara et al, 2010) Aboubakr elnashar
  15. 15. Intramural fibroid halves the chances of ongoing pregnancy following IVF(Hart et al, 2001) Metwally M, Farquhar, 2011 (SR &MA) No evidence of a significant effect for intramural fibroids on CPR, LBR or miscarriage rate No evidence for a significant effect for myomectomy on CPR or the miscarriage rate Aboubakr elnashar
  16. 16. 2. Size of fibroid: intramural No statistically significant difference in IR or pregnancy outcome •<3 cm (Rice et al, 1988, Rosati et al, 1989) •< 4 cm (Oliveira et al, 2004 ) • < 5 cm (Li et al, 1999; Somigliana et al, 2011.) •<7 cm (Ramzy et al, 1998; Jun et al, 2001; Olivera et al, 2003) PR/ET (%) Ramzy et al, 1998 Jun et al, 2001 Olivera et al,2003 483134<7 cm 454139Control Aboubakr elnashar
  17. 17. Small intramural fibroids significant reduction in the cumulative pregnancy, ongoing pregnancy and LBR after three IVF/ICSI cycles (Khalaf et al, 2006) fibroids >4cm required an increased number of cycles to obtain an ongoing pregnancy. Aboubakr elnashar
  18. 18. 3. Number of fibroids (3-5 cm): (Feliciani et al, 2003) PR (%)Number of fibroids 37<3 28>3 41Control Aboubakr elnashar
  19. 19. Aboubakr elnashar
  20. 20. 4. Distance from the endometrium (Aboulghar et al, 2004) > 5 mm: No effect Aboubakr elnashar
  21. 21. Aboubakr elnashar
  22. 22. • Ultrasound: Confirm diagnosis Locate the myomas. • TAS: uteri >12 w {Beyond the reach of the TVS}. Aboubakr elnashar
  23. 23. •TVS: Accurate in excluding endometrial hyperplasia Inaccurate in dd SM fibroids & polyps (A). •TVS or SIS Vs hysteroscopy More accurate in location of fibroids (A). Aboubakr elnashar
  24. 24. •SIS: If the location is unclear in AUB -When the relationship between the myoma and the uterine cavity is unclear -100% sensitive& specific -SIS Vs office hysteroscopy: •easier •less uncomfortable •less expensive Aboubakr elnashar
  25. 25. Aboubakr elnashar
  26. 26. •Endometrial biopsy: Irregular or intermenstrual bleeding. Abnormal endometrial thickening on TVS Aboubakr elnashar
  27. 27. •MRI: Uncommon presentations. Uncertain location after TVS & SIS when the number of lesions >5, MRI exceeds ultrasound’s technical limitation in precise fibroid mapping and characterization. Aboubakr elnashar
  28. 28. MRI (T2) scan Multiple leiomyomas extending up to L4. Two leiomyomas were present, one fundal subserosal with broad attachment to the body and a left posterior wall fibroid extending into the broad ligament. Also a 7.5-cm pedunculated component was found extending from the right body Aboubakr elnashar
  29. 29. Differentiation of an adenomyoma from a fibroid Adenomyoma: absence of a lesion margin presence of lacunae When doubts persist: MRI Aboubakr elnashar
  30. 30.  Bromley et al (2000) 2 or more of the followings: 1. Mottled heterogeneous myometrial texture: All cases. 2. Globular uterus: 95% of cases. 3. Small myometrial lucent areas: 82%. 4. “Shaggy” indistinct endometrial strips: 82%. The most predictive: ill-defined heterogeneous echotexture within the myometrium (Brosen et al, 2004) Aboubakr elnashar
  31. 31. • Standard infertility evaluation: HSG -If the uterine cavity is normal: no advantage in performing hysteroscopy tt plan should be recommended after the couple has been fully evaluated Aboubakr elnashar
  32. 32. Aboubakr elnashar
  33. 33. In some women, no treatment is better than treatment (Fletcher & Frederick, 2005) Aboubakr elnashar
  34. 34. Aboubakr elnashar
  35. 35. I. Expectant Management • Indications: 1.Infertile patients without any identifiable etiology except uterine myomas 2. Asymptomatic fibroid Aboubakr elnashar
  36. 36. II. Medical Treatment Not effective in improving infertility •Progestin therapy, including oral contraceptive pills •Androgens (gestrinone or danazol) • Mifepristone •GnRH analogs Aboubakr elnashar
  37. 37. ulipristal acetate (UPA) One medical treatment of uterine leiomyoma is a selective progesterone modulator, ulipristal. It is associated with rapid decrease in uterine bleeding, reduction in myoma size and minimal menopausal symptoms an oral selective progesterone-receptor modulator (SPRM): reduction in pain, bleeding, and size of fibroids. (Daniell, 2014) UPA provides more prolonged volume reduction after treatment is discontinued, as compared with the rapid regrowth observed in GnRH agonist treatments. Employing UPA, some benign endometrial changes have been described and resolved 6 months after treatment. Aboubakr elnashar
  38. 38. Correction of 1,25-dihydroxyvitamin D3 (Vitamin D) insufficiency has been proposed as an emerging therapeutic option for uterine fibroids. Epidemiological investigations reveal an association between low vitamin D reserve and presence of fibroids. The link between vitamin D deficiency and ovarian hormones upon fibroids might be the canonical Wnt (wingless-type)/ β-catenin signaling pathway that have been shown to be of importance mediating the estrogen/progesterone-dependent tumorigenesis of fibroids. Aboubakr elnashar
  39. 39. Other anti-uterine fibroid agent still under investigation is Epigallocatechin gallate (EGCG) – green tea extract that has been shown to inhibit fibroid cell proliferation in vitro. Finally, growth factor receptor antagonist under laboratory investigation, such as AG 1478 and TKS050 have been shown to control fibroid cell proliferation in vitro and they might serve as future therapeutic options. Aboubakr elnashar
  40. 40. Aboubakr elnashar
  41. 41. III. Surgical Treatment Myomectomy: -Indications: To maintain fertility. 1. Distorting the uterine cavity  Submucous regardless of the size or the presence of symptoms (Gambadauro,2012).  Intramural distorting the cavity reduce the chances of conception, not distorting the cavity: controversial results. {uterine wall is no more than 2 cm in thickness}: all the intramural fibroids ≥ 5 cm have some submucous component: deserve surgical consideration. Aboubakr elnashar
  42. 42.  Subserosal No indication 2. Intramural: >5-7cm ≥3(3-5 cm) (Bajekal & Li, 2000) Aboubakr elnashar
  43. 43.  Myomectomy of of submucous fibroids: significant increase in PR (from 27.2% to 43.3%) and a decrease in miscarriage rate (from 50% tom38.5%).  (Pritts et al, 2009, SR)  Insufficient evidence from RCT to evaluate the role of myomectomy to improve fertility (Metwally M et al. Cochrane Database Syst Rev 2012).  The data do not support pre-IVF myomectomy in women with small to moderate uterine fibroids, regardless of their location (Vimercati et al, 2007) Aboubakr elnashar
  44. 44. -GnRHa for 3 to 4 months prior to myomectomy (Cochrane library, 2001) Reduce both uterine volume & fibroid size. Correct preoperative iron deficiency anemia Reduce blood loss Blood transfusion rates& complication rates are not different. No significant impact on operative time, difficulty or complications. Aboubakr elnashar
  45. 45. Aboubakr elnashar
  46. 46. -Pregnancy after myomectomy 75% in 1st y PR drops sharply after this time (Dessole et al, 2001). If possible, therefore, myomectomy should be timed when a woman is ready to start a family Aboubakr elnashar
  47. 47. 10-75% (mean: 50%) (Donnez & jadoul, 2000). The differences may be attributed to: 1. Age & other infertility factors 2. Factors related to fibroid 3.Technical factors Aboubakr elnashar
  48. 48. 1. Age >35 y& other infertility factors Decreases PR (Ramzy et al, 1998; Li et al, 1999; Zollner et al, 2001) Aboubakr elnashar
  49. 49. 2. Factors related to the fibroid a.Number: More fibroids removed: lower PR (Sudik et al, 1996; Dessolle et al, 2001) No difference (Vercellini et al, 1999; Rossetti et al, 2001) Aboubakr elnashar
  50. 50. b. Size: Removal of fibroid >8 cm: Better PR (Sudik et al, 1996). No difference (Vercellini et al, 1999; Rossetti et al, 2001) Aboubakr elnashar
  51. 51. C. Site: Posterior wall: lower PR (Fauconnier et al, 2000) Distortion of the cavity: Better PR (Dessolle et al, 2001) No influence (Sudik et al, 1996) Aboubakr elnashar
  52. 52. 3. Technical factors: The approach depend on: Fibroid: Site, number & size Surgeon: Expertise Patient: preference Aboubakr elnashar
  53. 53. Open myomectomy (Bajekal & Li, 2000) The route of choice: Large SS or IM(>7 cm) Multiple fibroids (>5) When entry into uterine cavity is to be expected Aboubakr elnashar
  54. 54. b. Hysteroscopic myomectomy: The route of choice: SM fibroids. Compared to laparotomy, it is associated with a lower risk of scar rupture & no pelvic adhesion (Bajekal & Li, 2000) Large (>5 cm) type II SM fibroids may be unsuitable for hysteroscopic surgery. A significant benefit of removing SM fibroid >2cm (Varasteh et al, 1999) Aboubakr elnashar
  55. 55. effect of hysteroscopic myomectomy on fertility outcomes. (Metwally M et al. Cochrane Database Syst Rev 2012). Aboubakr elnashar
  56. 56. European Society for Gynaecological Endoscopy (ESGE) and STEPW classifications(size, topography, extension, penetration, wall) Aboubakr elnashar
  57. 57. Aboubakr elnashar
  58. 58. C. Laparoscopic myomectomy:  Pedunculated or SS: not candidate for removal {not the cause of infertility or recurrent miscarriage} (Bajekal & Li, 2000).  IM: depending on: size, position of the fibroid skills of the surgeon, suturing skills instruments available Aboubakr elnashar
  59. 59. Aboubakr elnashar
  60. 60. Live birth (%)PR (%)Route (n) 7960Laparotomy (465) 8055Hysteroscopy (198) 7647Laparoscopy (191) No significant difference between the laparoscopic and open approach regarding fertility performance. (Metwally M et al. Cochrane Database Syst Rev 2012). Results of hysteroscopic& laparoscopic myomectomy are similar to those following abdominal myomectomy (Bajekal & Li, 2000). Aboubakr elnashar
  61. 61. • Prevention of adhesion: 1. Surgical technique: anterior incisions 2. Adhesion barriers are effective GnRH analogs prior to surgery will not reduce postoperative adhesions Aboubakr elnashar
  62. 62. -Pregnancy outcome after myomectomy 1.Miscarriage rates Reduced from 41 to 19% (Li et al, 1999; Vercellini et al, 1999) Aboubakr elnashar
  63. 63. 2. Uterine scar complications Pathologically adherent placenta Placenta praevia Uterine rupture Aboubakr elnashar
  64. 64. 3. Cesarean section: Recommended (Friedman et al, 1996; Seineira et al, 1997) Not routine (Daria et al, 1997, Ribeiro et al, 1999; Dubuisson et al, 2000). {No uterine ruptures after myomectomy in 212 deliveries, 83% of which were vaginal}. Aboubakr elnashar
  65. 65. Uterine Artery Embolization (UAE) Aboubakr elnashar
  66. 66. IV. Other techniques 1.Uterine artery embolization (UAE) 2.Myolysis Should be avoided in women who desire pregnancy {fertilization & delivery rates are a matter of speculation} (Donnez & jadoul, 2000). Until more information is available, these approaches should not be considered standard treatment for women who wish to maintain their fertility. Aboubakr elnashar
  67. 67. Kim& Baer, Up To Date, April. 2013 National Guideline Clearinghouse American College of Radiology May 2012 Uterine fibroid embolization (UFE) Indicated premenopausal women with symptomatic fibroid Desire to retain their uterus. Not recommend in: 1. Plans for future pregnancy (Grade 2 C) 2. Postmenopausal women 3. Pedunculated or submucosal fibroids >6 cm 4. Fibroid >24 w or multiple fibroids > 10 cm 5. Eextensive adenomyosis, Aboubakr elnashar
  68. 68. Kim& Baer, Up To Date, April. 2013  Occlusion of uterine vessels either via laparoscopy or a vaginally-placed clamp has been proposed as an alternative to uterine artery embolization (UAE) UAE is preferable to laparoscopic uterine artery occlusion and less invasive. Transvaginal occlusion of the uterine arteries was associated with the need of ureteric stent due to clamping of the ureters in some cases Aboubakr elnashar
  69. 69. Magnetic Resonance-Guided Focused Ultrasound (FUS) Kim& Baer, Up To Date, April. 2013 NICE interventional procedure guidance 413, Nov. 2011 UFE is indicated for premenopausal women with symptomatic fibroid and have the desire to retain their uterus. It is not recommend:  Fibroid resectable with a hysteroscope  Heavily calcified fibroid  Fibroid >10 cm (Not absolute)  When intervening bowel or bladder could be damaged by treatment Aboubakr elnashar
  70. 70. Aboubakr elnashar
  71. 71. CONCLUSIONS •Myomas are the cause of infertility in a relatively small percentage of patients. •Medical therapy of myomas is not effective in improving infertility •Surgical therapy should be recommended after complete evaluation of other potential factors. Aboubakr elnashar
  72. 72. •If myomas are thought to be unrelated to reproductive dysfunction or if they are asymptomatic, no treatment is indicated. •Patients with recurrent miscarriages or pregnancy complications due to myomas should be treated after thorough evaluation of all other potential factors has been completed. Aboubakr elnashar
  73. 73. CAVITY Distorted Not distorted SIZE ≥5 cm ≤5 cm NUMBER(3-5cm) ≥3 ≤3 Aboubakr elnashar
  74. 74. Proposed flow chart for the management of women seeking conception in the presence of uterine myomas Edgardo Somigliana, 2008Aboubakr elnashar
  75. 75. Summary Statements 1. Subserosal fibroids do not appear to have an impact on fertility; the effect of intramural fibroids remains unclear. If intramural fibroids do have an impact on fertility, it appears to be small and to be even less significant when the endometrium is not involved. (II3) Aboubakr elnashar
  76. 76. 2. Because current medical therapy for fibroids is associated with suppression of ovulation, reduction of estrogen production, or disruption of the target action of estrogen or progesterone at the receptor level, and it has the potential to interfere in endometrial development and implantation, there is no role for medical therapy as a standalone treatment for fibroids in the infertile population. (III) Aboubakr elnashar
  77. 77. 3. Preoperative assessment of submucosal fibroids is essential to the decision on the best approach for treatment. (III) 4. There is little evidence on the use of Foley catheters, estrogen, or intrauterine devices for the prevention of intrauterine adhesions following hysteroscopic myomectomy. (II3) 5. In the infertile population, cumulative pregnancy rates by the laparoscopic and the minilaparotomy approaches are similar, but the laparoscopic approach is associated with a quicker recovery, less postoperative pain, and less febrile morbidity. (II2) Aboubakr elnashar
  78. 78. 6. There are lower pregnancy rates, higher miscarriage rates, and more adverse pregnancy outcomes following uterine artery embolization than after myomectomy. (II3) 7. Studies also suggest that uterine artery embolization is associated with loss of ovarian reserve, especially in older patients. (III) Aboubakr elnashar
  79. 79. Recommendations 1. In women with infertility, an effort should be made to adequately evaluate and classify fibroids, particularly those impinging on the endometrial cavity, using transvaginal ultrasound, hysteroscopy, hysterosonography, or magnetic resonance imaging. (IIIA) 2. Preoperative assessment of submucosal fibroids should include, in addition to an assessment of fibroid size and location within the uterine cavity, evaluation of the degree of invasion of the cavity and thickness of residual myometrium to the serosa. A combination of hysteroscopy and transvaginal ultrasound or hysterosonography are the modalities of choice. (IIIB) Aboubakr elnashar
  80. 80. 3. Submucosal fibroids are managed hysteroscopically. The fibroid size should be < 5 cm, although larger fibroids have been managed hysteroscopically, but repeat procedures are often necessary. (IIIB) 4. A hysterosalpingogram is not an appropriate exam to evaluate and classify fibroids. (IIID) 5. In women with otherwise unexplained infertility, submucosal fibroids should be removed in order to improve conception and pregnancy rates. (II2A) Aboubakr elnashar
  81. 81. 6. Removal of subserosal fibroids is not recommended. (IIID) 7. There is fair evidence to recommend against myomectomy in women with intramural fibroids (hysteroscopically confirmed intact endometrium) and otherwise unexplained infertility, regardless of their size. (II2D) If the patient has no other options, the benefits of myomectomy should be weighed against the risks, and management of intramural fibroids should be individualized. (IIIC) Aboubakr elnashar
  82. 82. 8. If fibroids are removed abdominally, efforts should be made to use an anterior uterine incision to minimize the formation of postoperative adhesions. (II2A) 9. Widespread use of the laparoscopic approach to myomectomy may be limited by the technical difficulty of this procedure. Patient selection should be individualized based on the number, size, and location of uterine fibroids and the skill of the surgeon. (IIIA) 10. Women, fertile or infertile, seeking future pregnancy should not generally be offered uterine artery embolization as a treatment option for uterine fibroids. (II3E). Aboubakr elnashar