Fibroid

and

infertilityProf Aboubakr

ElnasharBenha University Hospital

Egypt

ABOUBAKR ELNASHAR

CONTENTS

1. CLASSIFICATION

2. PREVALENCE

3. MECHANISMS OF ACTION

4. EFFECT OF FIBROID ON IVF

5. EVALUATION

6. TREATMENT

1. Medical

2. UAE

3. Myomectomy

4. Current practice

5. Strategy for infertile women with fibroid.

CONCLUSION

ABOUBAKR ELNASHAR

ABOUBAKR ELNASHAR

1. CLASSIFICATIONFIGO, 2011: 10 subtypes

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2. PREVALENCE

General Population

before age of 40 y60% Baird et al, 2003

Associated with infertility

33-40y8% Borgfeld &Andolf, 2000

The sole cause of infertility 2-3% ASRM, 2008

ICS/IVF 25% Serdar & Bulun, 2013

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Increasing number of infertile patients seeking ART

and having myomas

1. The recent trends of women to delay childbirth to

their 30th and 40th

2. Recent changes in the life style of women(Petraglia et al, 2013)

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3. MECHANISMS OF ACTION

1. Changes of Anatomy:

1. Distortion of the endometrial cavity

2. Obstruction of the fallopian tubes.

2. Changes of Histologically

1. Elongation and distortion of the glands

2. Cystic glandular hyperplasia

3. Polyposis and endometrial venule ectasia(Somigliana et al, 2007).

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3. Changes of physiology

1. Increased uterine contractility

2. Impairment of the endometrial blood supply

3. Chronic endometrial inflammation.

4. Glandular atrophy and ulceration(Somigliana et al, 2007).

5. Endocrine changessupported by the theory of an abnormal local hormonal

milieu

(Galliano et al, 2015)

6. Paracrine changes on the adjacent endometriumsecretion of

vasoactive amines

local inflammatory substances(Mukhopadhaya et al, 2007).

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More than one of these mechanisms:

may be present at the same time

The most important:

location of fibroids(Cook et al, 2010)

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Any of the above, may lead to impaired

Gamete transport : impaired fertilization

Implantation (Cook et al, 2010)

1. Impairment of fertilization

Interference with sperm or ovum transport.

a. Enlargement& deformity of uterine cavity

b.Uterine contractility

c. Distortion of the cervix

d. Distortion or obstruction of tubal ostia.

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2. Impairment of 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

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4. EFFECT OF FIBROID ON IVF OUTCOME

Effect of fibroid on reproduction

1. Infertility

2. Decrease success of IVF

3. Pregnancy1. Spontaneous abortion

2. PTL

3. IUGR

4. Malpresentation

5. Bleeding

6. Abruption

7. PROM

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Depend upon

1. Site.

2. Size

3. Number

4. Proximity to the endometrium

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1. Subserous Myoma

impact is not significant

(common OR = 1, 95% CI: 0.7 – 1.5)(Somigliana et al, 2007; meta-analysis13 studies)

(Pritts et al 2009, meta-analysis. 18 studies)

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2. Submucosal

statistically significant negative effect on CPR

(common OR = 0.3; 95% CI: 0.1 – 0.7)(Somigliana et al, 2007; meta-analysis13 studies)

Reducing the CPR up to 70% (RR=0.36;95% CI: 0.18-0.74) (7).

(Pritts et al 2009, meta-analysis. 18 studies)

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3. IM Fibroid

lesser extent

(common OR = 0.8; 95% CI: 0.6 – 0.9). (Somigliana et al, 2007; meta-analysis13 studies)

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PR/ET%Fibroid (n)

9Distorted cavity(65)

34Not distorted cavity (487)

40Control(1636)

1. Distorting cavity

(Donnez & Jadoul, 2002).

Not distorting:

No difference in implantation or CPR

Ddistorting

adverse pregnancy outcomes

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Not distorting cavity:

significantly lower LBR (RR=0.78; 95% CI: 0.69-0.88) and

higher miscarriage rates (RR=1.89; 95% CI:1.47-2.43)

(Pritts et al 2009, meta-analysis. 18 studies)

significantly lower CPR (RR=0.85; 95% CI: 0.77-0.94) and

lower LBR (RR=0.79; 95% CI: 0.70-0.88)

(Sunkara et al 2010, meta-analysis19 trials)

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2. Not distorting cavity but Size

Adverse pregnancy outcomes in women undergoing

IVF

≥3 cm

(Rice et al, 1988, Rosati et al, 1989, Yan et al 2014; Christoponles et

al., 2016)

≥ 4 cm

(Oliveira et al, 2004 ; Khalaf et al, 2006; Vimercati et al 2007)

≥ 5 cm

(Li et al, 1999; Somigliana et al, 2011.)

≥ 7 cm

(Ramzy et al, 1998; Jun et al, 2001; Olivera et al, 2003)

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3. Not distorting cavity but Number of fibroids (3cm):

≥3

(Feliciani et al, 2003)

≥2

(Christoponles et al., 2016)

PR (%)Number of

fibroids

37<3

28>3

41Control

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4. Not distorting cavity: Distance from the endometrium

(Aboulghar et al, 2004)

≤5 mm: significant decrease in PR

No. Pregnancy Rate

Total No of patients 184

Patient with Intramural fibroids 63

A- Myomectomy before IVF 19 50%

B- No Myomectomy before IVF 44 27%

β1 Fibroid at a distance < 5mm 11 9%

β2 Fibroid at a distance > 5mm 33 30%

C- Matched age group- No fibroids 100 36%

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5. PATIENT EVALUATION

Adequately evaluate and classify fibroids

1. TVS

2. hysteroscopy

3. HSG or

4. MRI

(III-A)(SOGC CLINICAL PRACTICE GUIDELINE, 2015)

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Preoperative assessment of submucosal fibroids

should include

1. size

2. site within the uterine cavity

3. degree of invasion of the cavity (0, 1, 2)

4. thickness of residual myometrium to the serosa.

A combination of

1. hysteroscopy and

2. TVS or

3. hysterosonography are the modalities of

choice. (III-B)

HSG

is not an appropriate exam to evaluate and

classify fibroids. (III-D)

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1. Ultrasound: Confirm diagnosis

Locate the myomas.

TAS:

uteri >12 w

{Beyond the reach of the TVS}.

TVS: Accurate in excluding endometrial hyperplasia

Inaccurate in dd SM fibroids & polyps (A).

SIS: 1. If the location is unclear in AUB

2. When the relationship between the myoma and the

uterine cavity is unclear

100% sensitive& specific

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2. MRI:

1. Uncommon presentations.

2. Uncertain location after TVS & SIS

3. Number >5:

precise fibroid mapping and characterization.

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3. Differentiation of an adenomyoma from a fibroid

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1. TVS: 2 or more of the followings:

1. Globular uterus: 95% of cases.

2. Asymmetrical thickening: Anterior or posterior myometrial wall appearing thicker

than its counterpart

3. Mottled heterogeneous myometrial texture: All cases.

4. Small myometrial hypoechoic cysts:

cystic glands within ectopic endometrial foci: 82%.

5. “Shaggy” indistinct endometrial strips: 82%.

6. Striated projections extending from the

endometrium into the myometrium

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Adenomyosis. Sagittal TVS

Globular uterine enlargement

Asymmetric thickening

Heterogeneity of the myometrium (arrows)

Poor definition of the endomyometrial junction

(arrowheads). E = endometrium.ABOUBAKR ELNASHAR

2. Color or power Doppler

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AdenomyosisFibroid

Diffuse vascularityPeripheral vascularity

4. Standard infertility evaluation:

1. Semen analysis

2. Mid luteal P

3. HSG

-If the uterine cavity is normal:

no advantage in performing hysteroscopy

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5. Endometrial biopsy:

1. Irregular or intermenstrual bleeding.

2. Abnormal endometrial thickening on TVS

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6. TREATMENT

In some women, no treatment is better than

treatment

(Fletcher & Frederick, 2005)

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1. Medical management

No role for medical therapy as stand-alone treatment

for fibroids in the infertile population.

(III)(SOGC CLINICAL PRACTICE GUIDELINE, 2015)

Current medical therapy for fibroids:

1. Suppression of ovulation

2. Reduction of estrogen production, or

3. Disruption of target action of estrogen or

progesterone at the receptor level

interfere in endometrial development and

implantation

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2. Uterine artery embolization

UAE Vs. myomectomy:

lower PR

Higher miscarriage rates

More adverse pregnancy outcomes

(II-3)

loss of ovarian reserve, especially in older patients.

(III)

Women, fertile or infertile, seeking future

pregnancy should not be offered UAE as a treatment

option for uterine fibroids.

(II-3E)(SOGC CLINICAL PRACTICE GUIDELINE, 2015)

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3. Myomectomy

Does myomectomy restore reproductive potential?

Based on the available evidence (Surrey et al, 2005; Pritts et al, 2009, MA; Cochrane SR Metwally et al, 2012)

1. Submucosal myomas

restore fertility potential

PR after surgery are similar to normal controls

significant increase in PR (from 27.2% to

43.3%)

decrease in miscarriage rate (from 50% to

38.5%).(Pritts et al, 2009, SR)

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2. Intramural myomas

≥5cm:

higher PR than in non-operated controls

Evidence: insufficient

3.Previous myomectomy

does not negatively affect PR

supporting the concept that surgery per se is not

detrimental

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4. Abdominal and laparoscopic approach

equally effective in fertility restoration

Laparoscopy:

better postoperative course

less morbidity. (Galliano et al , 2015)

5. Subserosal myomas

of reasonable size is not necessary for fertility

reasons.

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4. Current practice

Approach

An integrated personalized

Taking into account the

1. Age

2. Site

3. Size

4. Number

of the fibroids.

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The following parameters should be assessed:

1. What is the impact of fibroid on patient’s fertility?

2. How effective myomectomy is?

3. Are there additional clinical indications related to

the presence of the myoma?

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1. Subserosal fibroids

Myomectomy

no benefit on fertility

not recommended for fertility reasonsCould be justified if:

1. it is associated with symptoms due to its size or location

2. it could create complications during pregnancy, taking into

account its volume increase

3. there is another type of co-existing myoma.

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2. Submucosal fibroids

Hysteroscopic myomectomy:

improves fertility potential and IVF outcome (Pritts et al 2009, meta-analysis. 18 studies; Galliano et al, 2015)

Associated AUB

usual independent indication for myomectomy

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3. Intramural fibroids

Grey zone: An ongoing, debate regarding their role

in fertility and reproductive outcomes.

1. Distorting the endometrial cavity, may lead to poor

IVF outcome(Galliano et al 2015)

2. >4cm, even without cavity distortion, may also

negatively influence fertility (Oliveira et al, 2004 Pritts et al 2009, meta-analysis. 18 studies; Galliano

et al, 2015; Sunkara et al , 2010 meta-analyzed 19 trials; Somigliana et al,

2011; Yan et al, 2014)

3. Severe pregnancy complications(Klatsky et al, 2008),

Myomectomy should be considered

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Myomectomy is recommended in

FIGO types

0, 1, 2, 3, 2-5

4, 5 if ≥4 cm(Zepiridis et al, 2016)

Myomectomy

1. Smaller fibroids after multiple IVF failures

2. Complications of operation are not expected (Galliano et al, 2015)

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CONCLUSION(Zepiridis et al, 2016)

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You can get this lecture from:1.My scientific page on Face book:

Aboubakr Elnashar Lectures.

https://www.facebook.com/groups/2277

44884091351/

2.Slide share web site

3. elnashar53@hotmail.com

4.My clinic: Althwara st, Mansura, Egypt

5. Strategy for management(Serour and Serour. 2016).

Myomectomy or ART can be an appropriate first line of

treatment or complimentary to each other.

Choice of the strategy depends upon size

site

number of myomas,

other associated causes of infertility,

ovarian reserve

age of the woman

duration of infertility

outcome of previous treatment if any.

Appropriate counseling is necessary for the choice

of the most appropriate patient’s centered strategy.

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1. Myomectomy first choice

Myoma the sole possible cause of infertility

particularly if the patient is young.

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2. ART first choice.

1. Subserous myomas.

2. Small single interstitial myoma not distorting the

uterine cavity.

3. Other confounding factors as tubal or male factor

infertility in the absence of distortion of uterine

cavity.

4. Advanced maternal age or long term infertility with

small myomas not distorting uterine cavity .

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3. Myomectomy followed by ART

1. ART associated infertility factors as male or tubal

factor infertility.

2. Failure to get pregnant after myomectomy

particularly in elderly women.

3. Young women with long duration of infertility and

previously subjected to myomectomy.

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4. ART followed by myomectomy

1. A woman in her late thirties or early forties with

a small fibroid (<3cm) not distorting the uterine

cavity deserves one or two trials of ART to get

pregnant without myomectomy

2. If this trial fails or ends in a miscarriage, she

may be counseled for sugary before repeat

trial.

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5. ART/ Myomectomy/ET

An infertile woman with poor ovarian reserve, in her

late thirties or early forties, having multiple large

fibroids distorting the uterine cavity may have COS,

OPU, and vetrification of her embryos prior to

myomectomy.

Differed embryo transfer of cryopreserved embryos

can be performed 3-6 months following

myomectomy.

The same strategy can also be used for younger

women with multiple large fibroids with poor ovarian

reserve before subjecting them to myomectomy .

ABOUBAKR ELNASHAR

You can get this lecture from:1.My scientific page on Face book:

Aboubakr Elnashar Lectures.

https://www.facebook.com/groups/2277

44884091351/

2.Slide share web site

3. elnashar53@hotmail.com

4.My clinic: Althwara st, Mansura, Egypt