- There is consensus that submucosal fibroids interfere with fertility and should be removed in infertile patients, regardless of size or symptoms. Subserosal fibroids do not impact fertility. - The impact of intramural fibroids on fertility is still uncertain. Some studies show they may reduce clinical pregnancy and increase miscarriage rates, while other studies show no effect. - The benefits of myomectomy for interstitial or intramural fibroids are unclear, as evidence is limited and conflicting. Myomectomy may be considered for failed IVF cycles or large fibroids distorting the cavity. - There are ongoing controversies around the impact of fibroid number, location and size,

1. Fibroid & Infertility
Is there any consensus?
Hesham Al-Inany, M.D, PhD

2. Aim of this talk
• Not to discuss incidence, prevalence, diagnosis , management of
fibroid
• To know what is agreed upon
• To discuss what is not yet settled upon

3. The question
• Is there any consensus regarding fibroid?

4. Yes : there is
• Infertile Women are more likely to present with uterine fibroids
• Simply because of delayed marriage ) Gambadauro 2012)

5. Another one
• Subserous myoma : Nothing to be done
• No evidence of impact on fertility

6. Most important
• Submucous myoma : interfere with fertility and should be removed
in infertile patients
• regardless of the size or the presence of symptoms

7. Localization
Number of studies
includeda
Breslow–Day test (P-
value)
Common OR (95% CI)
Clinical pregnancy rate
Submucosal 2 0.92 0.3 (0.1–0.7)
Intramural 7 0.38 0.8 (0.6–0.9)
Subserosal 3 0.92 1.2 (0.8–1.7)
Intramural and/or
subserosal
11 0.30 1.0 (0.8–1.2)
All types 16 0.24 0.8 (0.7–1.0)
Delivery rate
Submucosal 2 0.79 0.3 (0.1–0.8)
Intramural 7 0.09 0.7 (0.5–0.8)
Subserosal 3 0.94 1.0 (0.7–1.5)
Intramural and/or
subserosal
11 0.68 0.9 (0.7–1.1)
All types 16 0.43 0.8 (0.6–0.9)
Meta-analysis on the influence of fibroids on IVF outcome according to the localization of the lesions
(Somigliana et al, 2007)

8. Number of fibroids (3 or more):
No. of fibroids PR%
• <3 37
• >3 28
• Control 41 Feliciani et al

9. Also agreed upon
• magnetic resonance-guided focused ultrasound surgery and fibroid
myolysis require further investigation
• Not in routine practice

10. Controversies
• Interstitial myoma
• Myomectomy : is it really useful
• Which type of surgery
• Uterine artery embolization
• Medical management

11. Why such controversies?
• Simply because we do not know:
• How fibroid originates
• How fibroid affect fertility (Unsolved association)
• How to reach it without affecting surrounding structures
• Size and location may vary

12. Why not solved??
• Paucity of “good evidence”
• i.e RCT

13. Interstitial myoma
• Likely to reduce fertility
• Likely to increase miscarriage rate
• However, this depends on its size, number and relation to uterine
cavity

14. Clinical pregnancy rate
• Sunkara et al. showed reduced CPR in a meta-analysis on the effect of
IM fibroids on IVF (n = 18, RR 0.85, 95%CI 0.77–0.94).

15. Miscarriage
• The rate of miscarriage is increased in women with IM fibroids when
compared with women without fibroids; Pritts et al. (n = 8, RR 1.747
(95%CI 1.22–2.489)

16. Does Myomectomy help?
• No sufficient evidence
• the influence of uterine scar formation on embryo implantation is
unknown
• Postoperative adhesion formation.
• Can end in hysterectomy !!!!

17. Effect of myomectomy
• does not have a significant effect upon
• CPR when compared to controls with fibroids in situ ( RR 3.765, 95%CI
0.470–30.136),
• MR (RR 0.758, 95%CI 0.296–1.943) or
• OPR⁄LBR (n = 1, RR 1.671, 95%CI 0.750–3.723). (kroon et al, 2013)

18. Unlike SM
• When comparing women who underwent myomectomy for SM
fibroids to those for whom fibroids were left in situ, Pritts et al. report
an increase in CPR (RR 2.034, 95%CI 1.081–3.826),

19. So what to do with IM
• Myomectomy only if :-
• Failed IVF cycle (twice or more)
• If close to endometrium
• If size > 3cm distorting uterine cavity
• Otherwise conservative management

20. Which type of surgery?
• Laparotomy vs laparoscopic
• Alternative surgery

21. Laparotomy vs laparoscopy : unknown
• No RCT compared both for myomectomy
• Laparoscopic myomectomy takes longer time but needs high skills
• Robotic surgery is seldom used in myomectomy (usually in
hysterectomy)

22. FDA warning against laparoscopic
myomectomy
• On November 24, 2014 the FDA issued a statement warning against
using laparoscopic power morcellators in women undergoing
myomectomy for uterine fibroids.
• Based on claims of intraperitoneal dissemination of cancerous cells.

23. Alternative surgery : UA occlusion
• Permanent : laparoscopic ligation
• Temporary : transvaginal ligation

24. Doppler guided
• transvaginal clamp on uterine artery for almost 6 hrs has been
reported (Tropeanno et al, Human Reprod Update)
• Induce transient ischaemia that cause fibroid to shrink without
permanent effect on myometrium
• No data

25. Uterine artery embolisation
• Emerging evidence does not support it :-
• May cause damage to collateral ovarian vasculature
• Reported adverse effects in women who got pregnant

26. Post embolization syndrome

27. Therefore
• it is an option for symptomatic fibroids in women who do not want to
become pregnant (marret et al, 2012)
• Waiting for the results FEMME (A randomised trial of treating Fibroids
with either Embolisation or Myomectomy to Measure the Effect on
quality of life among women wishing to avoid hysterectomy) trial

28. Medical management
• GnRHa
• Mifeprostone
• Aromatase inhibitors
• SERM
• SPRM
• Reduce size of fibroid temporarily and their effect on fertility is unclear

29. GnRHa
• 7 RCT
• Reduction in size
• 6 RCTs- improvement in Hb levels
• Not enough evidence on blood loss during surgery or subsequent
fertility

30. Medical management

31. Any consensus on future????
• To direct research
• To raise funds

32. Emerging drug : Ulipristal acetate
• successfully completed two Phase III clinical trials (PEARL I and II) in
Europe, demonstrating its efficacy and safety for the treatment of
symptomatic uterine fibroids in patients eligible for surgery

33. Why specifically: Ulipristal acetate
• PEARL II was a double-blind, non-inferiority RCT trial,
• three months of daily therapy with oral UA (at a dose of either 5 mg
or 10 mg) or once monthly intramuscular injections of the GnRH
analog leuprolide acetate (at a dose of 3.75 mg).
• Uterine bleeding was controlled in 90% of patients receiving 5 mg of
UA, in 98% of those receiving 10 mg, while the figure for leuprolide
acetate was 89%.
• significantly less likely to cause hot flushes

34. Emerging device : (Acessa™)
• laparoscopic ultrasound-guided radiofrequency volumetric thermal
ablation of uterine myomas
• immediate proximity of the transducer to the target (fibroid)
• Safety index is high

35. Real demonstration

36. Conclusion : Infertile woman with myoma
• Irrespective of symptoms:-
• SM fibroid : hysteroscopic myomectomy
• SS fibroid : nothing
• IM fibroid : if distorting the cavity, if multiple, 3-5 cm in diameter,
previous IVF failure : open myomectomy,
• Emerging alternatives : Ulipristal, Acessa™

37. THANK YOU