1. Reproductive in patient with myoma
Dr Fatemeh Keikha
Fellowshipe of IVF
Faculty of TUMS-IKHC

2. Introduction-
20-40% of women in reproductive age are affected by myomas
Myomas directly or indirectly associated with 5-10% of cases of infertility
Depends on ; Size, Location, Number, Type
→ 20 – 50% with symptoms;
Menorrhagia
Dysmenorrhoea
Infertility
American Fertility Society. Guidelines for practice: myomas and reproductive dysfunction. 1992

3. INTRODUCTION —
 The management of women with uterine leiomyomas depends upon several factors:
patient's age
Symptoms
Obstetrical history
Future childbearing plans
Size and location of the leiomyomas 

4. Uterine Leiomyoma Clinical Manifestations
Asymptomatic
Bleeding
Pain
Pressure
Urinary symptoms
- Infertility
- Recurrent spontaneous abortion
Obstetrical complication

5. Infertility and myoma controversial because ;
Difficult to prove causal relation
Reviews of previous (70-80) studies indicates a pregnancy rate of 50 % after myomectomy in infertile patients
No well controlled randomized studies
No clear description of size, numbers and location
No standardization of diagnostic methods
Different outcome parameters
Results varying between % (Donnez et al.)

6. Infertility and myoma -
More common in IVF patients
Delay of childbearing when fibroids are more common
Age decreases fertility

7. Impact of Uterine Myomas on Fertility
Greater distance for sperm travel
Tubal ostium occlusion
Distortion of uterine cavity, Vascular changes
Interfere normal rhythmic uterine contractions
Impaired implantation
Abnormal endometrial maturation
Alteration on oxytocinase activity
Hunt J Clin.Obstet.Gynecol.Iosif C Acta Obstet.Gynecol.Scan
Vercellini, P Fertil Steril
Verkauf B fertil Steril 1992
Wallach, E.E Obstet.Gynecol.Clin.N.Am.

8. Mechanism of impaired fertility in IM-SS myoma
Richards et al.(Hum Reprod Upd;1998,4) • ↓ numbers of caveolae in host myometr and ↓fibromyoma compared to normal myometr •→ affect calcium metabolism by ↓ calcium extrusion
↑ intracellular calcium • → myometrial irritability and hyperactivity • Result:
disruption of rhythmical contraction process of JZ

9. fertility in IM-SS myoma
Szamatowicz et al 1997:
Myomectomy →
↑ fibromyoma →
↓ contractile pressure

10. Mechanism of impaired fertility IM-SS myoma
Subendometrial tumors → endometrial erosion
inflammation altering the nature of the intra uterine fluid
→ hostile environment
Disrupt the endometrial blood supply
Affecting nidation and sustenance of early embryo
Fertil-sterility et al 1995

11. Uterine Leiomyoma Classification -
Based on the concept that:
fibroids are primarily interstitial and gradually forced outwards or inwards:
-SM- Submucosal
-IM- Intramural
- SS- Subserosal

12. Submucosal (JZ) fibroid - type 0, I, II (ESH-criteria, 1994) - type III : abutting the endometrium
“Outer myometrium” fibroid - type IV: intramural - type V, VI: subserosal, pedunculated

14. ASYMPTOMATIC LEIOMYOMAS —
Myoma in asymptomatic woman is usually an incidental finding
some → naturally regress
Othere → continue to grow
new leiomyomas may develop
LD does not cause myomas to grow; not contraindicated in women with myomas who wish to use this method of contraception
Exception: girls with exposure to es-p contraceptives in years 
In adolescents, the advantages of LD need to be weighed against this potential risk

15. PRECONCEPTIONAL PLANNING —
 women with myomas not postpone pregnancy for a prolonged period of time, if possible
fertility declines with age, especially after 35 yr, and myomas may impair fertility and adversely affect pregnancy outcome
There are no well-designed studies that provide high-quality data on whether myomas adversely affect pregnancy outcome

16. Available information;
observational case series and case reports
in different patient populations;
different criteria regarding the size, location, and number of myomas;
small numbers of adverse events
in selecting study participants
inadequate adjustment of confounders

17. PRECONCEPTIONAL PLANNING —
In a large retrospective cohort of 2058 women with myoma at the second trimester of pregnancy;
Risks of preterm birth < 37 wk (15.1% versus 10.5%, odds ratio [OR] 1.5, 95% CI
IUFD in women with IUGR fetuse (3.9 % versus 1.5 %, OR 2.5, 95% CI ) were higher compared with those without myoma
In absence of high-quality data →
 Not perform prophylactic myomectomy to prevent pregnancy complications
Myomectomy can be considered in:
selected patients with a history of obstetrical complications that appear related to the presence of myomas
Perform myomectomy before pregnancy if it is symptomatic

18. INFERTILITY AND MISCARRIAGE —
Myomas are estimated to account for 1 -2 % of infertility
Fibroids, particularly those that impinge upon the endometr, may affect fertility by:
Interfer with implantation over the myoma site
Rapidly distending the uterus in early pregnancy
Impairing uterine contractility

19. The location of a fibroid, and not its size, is the key factor regarding fertility
Myomas that distort uterine cavity (SM/IM with an intracavitary component)→
Difficulty conceiving pregnancy
↑ risk of Ab.
SS fibroids do not impact fertility
Role of IM fibroids in infertility is controversial

20. Meta-analysis of 23 studies
Compared infertile women +/- myomas ( one randomized trial)
Women with SM/ IM + intracavitary component were:
less likely to become pregnant (RR 0.36, 95% CI 0.18–0.74)
more likely to have a spontaneous abortion (RR 1.7, 95% CI 1.4–2.1)
Myomectomy in women with cavity-distorting fibroids →
↑ significant conception rate (RR 2.03, 95% CI 1.08–3.83)
No significant ↓ in risk of Ab. (38.5 versus 50 percent; RR 0.77, 95% CI 0.36–1.66)
this result was based on a single study of 52 women and lacks adequate statistical power

21. Myoma and Infertility: Review (Pritts EA 2009 Fertil Steril 91, 4:1215-1223)
SS do not affect fertiltiy or spontaneous abortion rates
SM lowers fertility rates, myomectomy →↑ rates of conception and live births
IM myoma +/- distortion of the uterine cavity may cause a detrimental effect on conception and reaching viability with pregnancy
Effect of myomectomy is unclear.

22. INFERTILITY AND MISCARRIAGE —
The data regarding IM fibroids are less clear
Overall, studies of women with fibroids that did not distort the uterine cavity were less likely to become pregnant (RR 0.81, 95% CI 0.70–0.94) and more likely to have a spontaneous abortion (RR 1.7, 95% CI 1.2–2.5)
most of these studies included women with fibroids causing intracavitary distortion since fibroid location was determined by imaging methods (HSG, Us) less reliable than hysteroscopic documentation → biasing the results.

23. Clinical questions remain about the effects of IM fibroid positions other than extension into the uterine cavity
A fibroid near a fallopian tube ostium or near the Cx may impede fertilization.
Two small series evaluated whether treatment of occluding fibroids improves fertility reported conflicting results
Couples should complete a full infertility evaluation before addressing the role of myomas in their infertility

24. Preparing for IVF —
 Effect of myomas on IVF is dependent on their location:
SM myomas decrease the chance of success
SS myomas do not appear to have any effect
Observational data suggest that IM myomas may also have a negative impact on IVF outcomes

25. Summary of the data of the IVF model shows that:
patients with fibroid distorting the endometrial cavity have impaired implantation and pregnancy rates
(Somigliana E. et al Hum reprod Update2007,13)
Rackow, B, Taylor H (Fertil Steril,2008) found that:
SM myoma →↓ endometrial Hox gene expression (molecular marker of endometrial receptivity)

26. Effect of IM myoma - IM fibroids negatively affects IVF results
A mechanism for IM fibroids not distorting the cavity;
disruption of the JZ within the myometrial layer at the initial stages of embryo invasion and placentation.
(Horne AW, Critchley HO, Semin reprod Med, 2007,25: 483)
IM fibroids negatively affects IVF results
Hart R et al Hum reprod 11: Khalaf Y et al Hum Reprod 10:
Intramural fibroids do not affect IVF results
Ng EH, Ha PC, , Hum Reprod 3: Oliveira Fg et al Fertil Steril 81: Klatsky Pc et al , Hum Reprod 2:

27. Effect of large IM fibroids (>5 cm) Hart R et al Hum Reprod 2001 16(11): 2411
Results of IVF where all significantly reduced:
Implantation rate dropped from 20.2 to 11.9 % (p=0.018)
Pregnancy rate dropped from 34.1 % to 23.3 % (p=0.016)
Ongoing pregnancy rate dropped from 28.3 to 15.1 % (p=0.003)
Large IM myoma negatively affects pregnancy outcome after IVF
Large intramural myomas should be removed before IVF

28. If myomectoy is beneficial in patients before IVF;
it do not necessarily mean that ;
? myomectomy should be performed systematically in women trying to conceive not needing an IVF treatment because risks of adhesion formation after myomectomy.

29. IM fibroids < 5 cm
Should they be disregarded? Should we operate before IVF? Should we operate after IVF failure? and so yes after how many failures? Should we operate before any infertiltiy treatment? Should the decision be influenced according to the cost of IVF in different countries?

30. IM fibroids < 5 cm Checketal.(Hum.reprod,2002);
No difference in implantation rates and pregnancy rates
lower delivery rate
higher rate of miscarriage
conclusion: study needed
Oliveira et al. (Fertil Steril 2004)
No effect on pregnancy rates
No higher incidence of miscarriages,
( but only one cycle )

31. IM fibroids < 5 cm IM fibroid should be classified as;
outer myometrium or JZ fibroid

32. OPTIONS FOR TREATMENT OF MYOMAS: Medical therapy —
 Most medical therapies for myomas;
Preclude conception
Adverse effects when employed long-term
Rapid symptom rebound when discontinued
→ medical treatment of myomas in infertile patients attempting to become pregnant is usually unsuccessful

33. Ulipristal: selective progesterone modulator ↓ rapid in VB
slight reduction in myoma size
minimal menopausal symptoms
5 mg /po/ day x3mo
If needed → another x3 mo after x2 menstrual periods
longest treatment; x4 courses

34. Myomectomy versus embolization —
Myomectomy is prefer to UAE for treatment of most women with myomas who wish to conceive
UAE:
in women at high surgical risk
previous multiple laparotomies
diffuse uterine leiomyomas where myomectomy might not be technically feasible

35. Myomectomy/ UAE — Avoid UAE in women who wish to conceive
safety of procedure with respect to subsequent pregnancy outcome has not been established
<150 pregnancies following UAE have been reported

36. Cohort studies →
↑Ab. after UAE rather than after myomectomy (17-30 versus 15%)
↑ rate of preterm delivery following UAE than myomectomy ( versus 3%)
↑ PPH in two studies (18 versus 1-5% in general obstetrical population), related to abnormal placentation
data is limited
All of the studies involved a small number of patients and had no age-matched controls
Women in the UAE group were of older age, which could at least partially account for these results

37. Route of myomectomy Hysteroscopic myomectomy — choice for SM myomas
Abdominal myomectomy — choice for:
multiple myomas
>3 myomas >5 cm
uterus is significantly enlarged (>18 wks)
operative time, blood loss, and hospital stay are comparable to that with abdominal hysterectomy
Risk of unplanned hysterectomy at the time of myomectomy is <1% for experienced surgeons

38. Abdominal myomectomy —
After abdominal myomectomy, the risk of uterine rupture prior to labor is very low (0.002%) compared to classical C/s (3.7%)
These data are based upon small series without complete pregnancy follow-up
The common clinical practice of counseling women who have had a myomectomy with a transmural uterine incision to undergo an elective C/s clearly biases and under- reports the risk of rupture at term.
Women who undergo myomectomy with significant uterine disruption should wait several months before attempting to conceive
recommendations for delay range from 3-6 mo
If a woman is having difficulty conceiving following a myomectomy → early HSG R/O obstruction
Myomectomy, particularly near tubes → adhesions → impair fertility.
Pregnancy rates reported from 2-14 yr after abdominal myomectomy range from %, depending on age and history of infertility

39. Laparoscopic myomectomy —
 With advances in laparoscopic suturing technique and instrumentation → most myomectomies can be performed laparoscopically
The results are comparable to those of myomectomy by laparotomy
laparoscopic approach is associated with faster recovery, and less adhesion formation
Without proper suturing of the uterine defect, there is a risk of uterine rupture during the subsequent pregnancy or in labor
Multi-layered closure and meticulous hemostasis are mandatory
Only surgeons who are familiar with laparoscopic suturing should perform laparoscopic myomectomy

40. Laparoscopic myomectomy —
Indication: uterus <18 wk
≤3 IM or SS leiomyomas of ≤5 cm in diameter
Factors lead to↑ risk of conversion to an open procedure include:
size ≥5.0 cm
IM myoma
anterior location
preoperative use of a GnRH-agonist
surgeon's experience and laparoscopic skills

41. Whether reapproximation of the myometr via laparoscopic suturing gives the uterine wall the same strength as multilayer closure at laparotomy is an area of controversy
Ten cases of uterine rupture in women who underwent laparoscopic myomectomy have been reported, one was at 17 wk and the remainders were at wk
One of the largest series of pregnancies after laparoscopic myomectomy reported no uterine ruptures in 106 deliveries; 27 of the deliveries were vaginal. Only 10 uterine cavities in this series had been entered at myomectomy
Differences are due to different surgical technique and skill of the laparoscopist.

42. Miscellaneous techniques —
Myoma coagulation or myolysis:
is associated with adhesion formation
increase the risk of uterine rupture in pregnancy
→ most gynecologists no longer perform this procedure
Efficacy and safety of other procedures, especially in young women who wish to conceive, have not been proven
occlusion of uterine vessels:
via laparoscopy or a vaginally-placed clamp
high intensity focused ultrasound (HIFU)
Cryomyolysis
radiofrequency ablation
magnetic resonance imaging-directed cryotherapy

43. SUMMARY :
●Women with asymptomatic myomas not postpone pregnancy, if possible, since leiomyomas, combined with advanced maternal age, may impair fertility and adversely impact pregnancy (Grade 2C)
●In women planning pregnancy, not performing prophylactic myomectomy to prevent pregnancy complications (Grade 2C)
●The relationship between IM myomas and infertility is controversial. Couples should complete a full infertility evaluation before addressing the role of leiomyomas in their infertility

44. For women with asymptomatic myomas who are infertile or have a history of recurrent pregnancy loss:
●For SM / IM with intracavitary component → suggest myomectomy (Grade 2C)
For SS myoma → suggest against myomectomy (Grade 2C).
•For IM fibroids that do not distort cavity → complete infertility evaluation prior to a myomectomy

45. •The decision to perform a myomectomy for a large IM myoma is made based on;
patient preference
clinical factors
fallopian tube compression
distortion of the uterine cavity and the cervical canal
failure of infertility treatments including IVF

46. ●Suggest myomectomy for women planning to undergo IVF who have a SM fibroid or an IM fibroid that deforms the uterine cavity (Grade 2C)
●Suggest surgical myomectomy over medical therapy or UAE for women planning future pregnancies (Grade 2C)

47. Leiomyomas and infertility Conclusions:
It is rarely probably that myoma cause infertility but ... It has been described:
A longer seeking of pregnancy (Hasanetal.1990)
A reduction of the success of ART (Stovall et al. 1998;
Khalaf et al. 2006)
• Relation with spontaneous abortion (Muhieddine et al. 1992) (Matsunaga et al. 1980)
• A same probability of pregnancy after myomectomy compared to patients with no uterine pathology (Buttram & Reiter 1981)

48. Conclusions I - SM myoma
Despite the lack of randomized studies
sharp decline in pregnancy rates in case of SM myoma → myomectomy should be performed before ART
Decreased:
clinical pregnancy rate
implantation rate
live birth rates
Increased abortion rates

49. Conclusion II- IM myoma:
more controversial ; lack of hemogeneous opinion
Decreased fertility
increased pregnancy loss
effect of myomectomy ?
IM > 5cm advice to operate before ART
(mostly distorting cavity?)
intramural < 5 cm?
reported outcome varies between no differences and significant decreased cumulative pregnancy rates?