1. Benha University Hospital Delta (Mansura) & Benha Fertility Centers E-mail: elnashar53@hotmail.com

2. Types of fibroids (The European Society of Hysteroscopy, 1993) 1.Submucos (SM): Fibroid distorting the uterine 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 & with <50% protrusion into serosal surface 3. Subserosal (SS): >50% protrudes out of the serosal surface

4. 20% to 40% of women of reproductive age

5. Fertility IVF Pregnancy

6. FIBROIDS & INFERTILITY Incidence: Fibroids are associated with infertility in 5% to 10%. When all other causes of infertility are excluded, fibroids are responsible for only 2% to 3% of infertility cases

7. Mechanisms: 1. Interference with sperm or ovum transport. a. Enlargement and deformity of the uterine cavity b.Uterine contractility (Vollenhoven et al, 1990). c. Distortion of the cervix d. Distortion or obstruction of the tubal ostia.

9. 2. 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 However, none of these putative mechanisms has been confirmed to be the etiologic factor.

10. Fibroids & IVF IVF provides a good model to assess the effect of fibroid on implantation rate by excluding other factors such as tubal or male (Donnez & Jadoul, 2002). IVF cannot assess the effect of fibroid on sperm migration & ovum transport.

11. PR/ET%Fibroid(n) 9Submucous(27) 16Intramural(44) 37Subserous(158) 30Control(2413) 1.Type of fibroid: Pregnancy rates with IVF Bajekal & Li (2000) SM fibroid has the most detrimental effect, IM a modest impact & SS has the least impact on PR.

12. PR/ET%Fibroid(n) 9 Distorted cavity (65) 34 Not distorted cavity (487) 40Control(1636) Donnez & Jadoul (2002). No difference in implantation or pregnancy rates unless the uterine cavity itself was distorted by the myomas

13. 2. Size of fibroid: <3 cm (Rice et al, 1988, Rosati et al, 1989) < 5 cm (Li et al, 1999) Ramzy et al, 1998; Jun et al, 2001)<7 cm (Ramzy et al, 1998; Jun et al, 2001) PR/ET (%) Ramzy et al, 1998 Jun et al, 2001 3134 <7 cm 4139Control No statistically significant difference in implantation rate or pregnancy outcome

14. PR (%) 48<7cm 45Control Olivera et al, (2003)Olivera et al, (2003)

15. 3. Number of fibroids: (Feliciani et al, 2003) PR (%) Number of fibroids 37<3 28>3 41Control

17. 4. Distance from the endometrium (Aboulghar et al, 2004) > 5 mm : no effect

18. FIBROID & PREGNANCY Incidence: 1.4% to 8.6% of pregnancies

19. Effect of pregnancy on size of fibroid: 80% of fibroids remain the same size or become smaller (Muram et al, 1980; Lev-Toaf et al, 1987) 20 % increase in size Growth is usually seen only in the first trimester, and many fibroids, particularly large ones, often get smaller late in pregnancy

20. Effect of fibroid on pregnancy: 1. Increased risk of spontaneous abortion {increase uterine contractions and growth or degeneration of myomas}. However, none of these potential mechanisms has been clearly established as the basis for pregnancy wastage.

21. Miscarriage rate (%) 40 33 33 16Fibroid(n)Submucous(27) Intramural(44) Subserous(158) Control(2413) Miscarriage rate: 1. Type Bajekal & Li (2000)

22. Abortion rate (%) Fibroid 34<7cm 29Control 2. Size Olivera et al, (2003)

23. Abortion rate (%) Number of fibroids 34<3 60>3 18Control 3. Number: Feliciani et al, (2003) >3 fibroids are associated with increased risk of abortion

24. 2. Premature labor in 15% to 20% 3. Intrauterine growth restriction in 10% 4. Malpresentation in 20%

25. 5. Location of the myomas is important. Those located adjacent to the placental site were associated with an increased risk of: Bleeding, Abruption, and Premature rupture of membranes

28. Ultrasound: Confirm diagnosis Locate the myomas. TAS may be required for uteri greater than 12 weeks' size as these will be beyond the reach of the TVS.

29. TVS is accurate in excluding endometrial hyperplasia but is often unable to distinguish SM fibroids & polyps (A). TVS and SIS are both more accurate in diagnosing the location of fibroids than hysteroscopy (A).

30. SIS: -If the location of the myoma is unclear in patients with abnormal bleeding or in those who are not trying to conceive - Almost 100% sensitive and specific in identifying intrauterine lesions easier, less uncomfortable, and less expensive than office hysteroscopy

32. Endometrial biopsy: If there is irregular or intermenstrual bleeding or abnormal endometrial thickening on TVS If cycles are regular and the woman has moliminal symptoms, it may be assumed that she is ovulatory. A mid-luteal serum progesterone of 3 ng/ml or more supports this clinical impression. In such cases, endometrial biopsy is rarely indicated because the risk of hyperplasia or malignancy is remote

33. MRI Not commonly indicated. May be indicated in: uncommon presentations. uncertain location of fibroid after TVS & SIS

34. Standard infertility evaluation: HSG -Assess the uterine cavity. -If the uterine cavity is normal, there is no advantage in performing hysteroscopy -Inject the contrast with a device attached to the cervix rather than an instrument which has an intrauterine component which may obscure intrauterine pathology. A treatment plan should be recommended after the couple has been fully evaluated

37. I. Expectant Management Indications: 1.Infertile patients without any identifiable etiology except uterine myomas 2. Asymptomatic fibroid

38. II. Medical Treatment is not effective in improving infertility Progestin therapy, including oral contraceptive pills Androgens (gestrinone or danazol) Mifepristone GnRH analogs

39. III. Surgical Treatment Myomectomy: - Indication: # Women who wish to maintain potential fertility. # SM or IM fibroid distorting the uterine cavity Fibroids >5cm Multiple fibroids (Bajekal & Li, 2000)

40. Myomectomy & fertility outcome 75% of conceptions following myomectomy occur in the first year (Dessole et al, 2001), with PR drops sharply after this time. If possible, therefore, the surgery should be timed to take place when a woman is ready to start a family

41. PR after myomectomy varies between 10 & 75% with mean of 50% (Donnez & jadoul, 2000). The differences may be attributed to 1.Age & other infertility factors 2.Factors related to fibroid 3.Technical factors

42. 1.Age & other infertility factors Age >35 & an association with other infertility factors decreases PR (Ramzy et al, 1998; Li et al, 1999; Zollner et al, 2001)

43. 2. Factors related to the fibroid a.Number: A lower PR when more fibroids were removed ( Sudik et al, 1996; Dessolle et al, 2001), Others noted no difference (Vercellini et al, 1999; Rossetti et al, 2001)

44. b. Size: PR were better after removal of fibroid with a volume of >100 ml (>8 cm diameter) (Sudik et al, 1996). Others found no difference (Vercellini et al, 1999; Rossetti et al, 2001)

45. c. Site: No influence of myoma location (Sudik et al, 1996) A lower PR with posterior wall fibroid (Fauconnier et al, 2000) A better PR when there was distortion of the cavity (Dessolle et al, 2001)

46. 3. Technical factors: The approach depend on: The site, number & size of fibroid, The expertise of the surgeon & The patient preference

47. Open myomectomy (Bajekal & Li, 2000) The route of choice for: large SS or IM fibroids (>7 cm), when multiple fibroids (>5) & when entry into uterine cavity is to be expected

48. b. Hysteroscopic myomectomy: The route of choice for 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)

50. c. Laparoscopic myomectomy: Pedunculated or SS fibroids are not candidate for removal because they are not the cause of infertility or recurrent miscarriage (Bajekal & Li, 2000). IM fibroids: Uterine rupture: 2 reports both at 34 weeks {inability to effectively close the myometrium laparoscopically} Uterine indentation Uterine fistula Very experienced laparoscopic surgeon

52. Live birth (%) PR (%) Route (n) 7960 Laparotomy (465) 8055 Hysteroscopy (198) 7647 Laparoscopy (191) Results of hysteroscopic and laparoscopic myomectomy are similar to those following abdominal myomectomy (Bajekal & Li, 2000).

53. GnRH analogues for 3 to 4 months prior to myomectomy (Cochrane library, 2001) 1.Reduce both uterine volume & fibroid size. 2.Correct preoperative iron deficiency anemia, if present 3. No significant impact on operative time or complications. Myomectomy is not either easier or more difficult than surgery without such treatment. 3. Reduce blood loss, though transfusion rates and complication rates are not different. Beneficial in patients with a 14- to 18-week-size uterus who would require abdominal hysterectomy if not treated with analog but have an 80% chance of successfully undergoing vaginal hysterectomy with pre-treatment.

54. Prevention of adhesion: 1. Surgical technique: anterior incisions should be used whenever possible. 2. Adhesion barriers are effective GnRH analogs prior to surgery will not reduce postoperative adhesions

55. Myomectomy & pregnancy outcome 1.Miscarriage rates are significantly reduced from 41 to 19% (Li et al, 1999; Vercellini et al, 1999)

56. 2. Uterine scar complications Pathologically adherent placenta Placenta praevia Uterine rupture:

57. 3. Cesarean section: CS is recommended (Friedman et al, 1996; Seineira et al, 1997) & it is 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. No difference between open & laparoscopic myomectomy in the incidence of C S ( 60% Vs 78%) (Seracchioli et al, 2000)

58. Myomectomy is rarely indicated, but case reports suggest that myomectomy can be performed safely in pregnancy when necessary

59. 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.

60. CONCLUSIONS Myomas are the cause of infertility in a relatively small percentage of patients. Medical therapy of myomas is not effective in improving infertility, and surgical therapy should be recommended after complete evaluation of other potential factors.

61. 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.

62. Fibroid 1. Cavity Distorted Not distorted 2. Size >7 cm <7 cm 3. Number >3 <3

63. Benha University Hospital, Egypt Delta (Mansura) & Benha Fertility Centers Email: elnashar53@hotmail.com WWW.obgyn.net