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1. ADENOMYOSIS
DR REJI MOHAN, MD(JIPMER) DNB
CONSULTANT IN OBS,GYN& INFERTILITY
ASSISTANT PROFESSOR
GOVT.MEDICAL COLLEGE,
THIRUVANANTHAPURAM
2. • Graduated from Government Medical College
Trivandrum in 1997.
• Finished MD and DNB in 2001 from JIPMER Pondicherry.
• Worked as a specialist in CIMAR Edappal later joined
Government services .
• Trained in ART from CIMAR,IKDRC ,Ahmedbad &Prof
BNC,Calcutta
• Trained in laparoscopy –CIMAR,IKDRC
• Assistant professor SAT Hospital, Government Medical
College ,Trivandrum.
• Was part of the team in starting the first ART unit and
First IVF-ICSI baby in Government sector in South India
along with Prof.Sheila Balakrishnan.
• Team member of third ART center in govt: GMC
,Kottayam
• Special interest in Infertility management and minimally
invasive surgery.
• Presented papers in various national and international
conferences
• Winner of best infertility paper in AKCOG 2014
9 March 2017 drrejimohan@gmail.com 2
4. Introduction
Karl Rokitansky, Pathologist who First
described Adenomyosis In 1860
“CYSTOSARCOMA ADENOID
UTERINUM”
Adenomyosis is a benign condition of the uterus that is
characterized by the presence of ectopic endometrial
glands and stroma within the myometrium.
It is associated with myometrial hypertrophy and
hyperplasia of the surroundings
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5. Epidemiology and pathophysiology
Predominantly affects the women
in the late reproductive age(35-50)
30 % of population
70% of hysterectomy specimen
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6. Four proposed Theories regarding
aetiology of adenomyosis
Invagination of endometrial glands into
the myometrium
Embryologically misplaced toti potential
mullerian remnants
Endometrium invaginates and proceeds
along the myometrial lymphatics
Misplaced bonemarrow stem cells
displaced through the vasculatureAdenomyosis grows and regress in an estrogen-dependent
fashion due to the presence of estrogen receptors in
adenomyotic tissues.
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7. Junctional Zone(jz)
• JZ: Endomyometrial interface
• Usually less than 5mm
• Hormone dependent that governs uterine
peristalsis.
• In follicular and periovulatory phase peristalsis
is in the cervicofundal region
• In luteal phase the frequency is short and
intensity is reduced
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8. • JZ plays an important role in
• Sperm transport
• Implantation
• Recurrent miscarriages
• Unexplained infertility
• Ectopic gestation
Hall mark OF ADENOMYOSIS is disruption of JZ,
JZ is thickened and more than 12mm
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9. Risk factors
Incidence of AM is increased in
• Postuterine surgery
• Caesarean section
• Postpartum endometritis
• Pregnancy
• Uterine trauma(d&c,d&e)
It is postulated that after the initial insult, the pathological
process is propagated by some combination of favourable
hormonal and immunological conditions which occur
alongside cell adhesion abnormalities.+ gene dysregulation9 March 2017 drrejimohan@gmail.com 9
12. Symptomatology
• 30 to 50 % are assymptomatic
• Dysmenorhoea
• Menometrorrhagia
• Chronic pelvic pain
• Menorrhagia unresponsive
to hormonal therapy or uterine curettage curettage
• subfertility
• Dysparunia
• Enlarged tender uterus
Clinical diagnosis is
difficult
Vague symptoms
Co existing
conditions(80 %) like
fibroids,PID,endometri
osis,DUB
SYMPTOMS DEPENDS ON THE EXTENT AND DEPTH OF AM
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13. Work up
If You Do Not Think Of Adenomyosis
You Will Not Find Adenomyosis
Clinical Suspiscion
Transvaginal Sonogram
Sen 80to 88%,speci 50 to 95%
68 to 86% accuracy
MRI
Sen 86 TO 100%,speci67 to 93%
50 to 95% accuracy
At present there is no single diagnostic test that is both sensitive
and specific for adenomyosis
MRI is a good complement to ultrasound when ultrasound is
indefinite or in difficult cases.9 March 2017 drrejimohan@gmail.com 13
14. Ultrasound
• First step
• Widely available,less expensive,more time
efficient
• Disadvantage is highly operator dependent
• 2D or 3D
• Appears as heterogenous hypoechogenic
poorly defined areas in the myometrium
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15. Sonographic findings justifying AM
diagnosis
1. Myometrial anteroposterior assymmetry
2. Globular uterine configuration
3. Heterogenous Myometrial Texture-Hypo And
Hyperechoic
4. Small intramyometrial Anechoic Cysts
5. Poor /Indistinct Endometrial Myometrial
interface
6. Subendometrial Linear echogenic Striations /Sub
Endometrial Stripes
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18. Linear Striations From Endometrium /Sub Endometrial
Stripes.Most Specific(95.5%) And With Highest Positive
Predictive Value(80%)
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20. MRI
• The JZ is well demonstrated on T2-weighted MRI
images
• Features predictive are JZ >12mm and
hemorrhagic high signal myometrial spots.
• Esp.in presence of fibroids this is better than TVS
for identifying AM,localise myoma,enumerate
myoma so that a well planned surgery can be
done.
• More interobserver agreement
• Cost and time is the main disadvantage
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21. Three objective parameters for diagnosing AM
on MRI
1.Thickening of JZ>=12mm
2.A ratio of max thickness of the JZ/total
maximum myometrialthickness >40%
3.A difference between JZ max and JZ min
>5mm- most trust worthy criteria
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23. Sagittal T2-weighted MR image shows diffuse, even thickening
of the junctional zone (arrows), a finding consistent with
diffuse adenomyosis
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27. focal thickening of the JZ (short arrows).
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28. Treatment-options
• No general agreement regarding the most
appropriate therapeutic method.
• Only definitive management :
HYSTERECTOMY
MEDICAL
• Hormonal
• Non hormonal
SURGICAL
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29. Medical
• Non Hormonal are targeted at symptomatic relief:
NSAIDS,Tranexamic acid
• Hormonal treatment is aimed at inhibiting
gonadotrophin release from the pituitary, estrogen
surge midcycle and cyclical changes of ovarian steroids
• Progestogens
• Levonorgestrel (LNG) Intrauterine System
• Oral Contraceptive Pills
• Gonadotrophin-releasing Hormone Analogs
• Danazol-loaded intrauterine devices (IUDs)
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30. OCP
Reduces dysmenorrhea,
Reduces the size of adenomyosis lesions
Safe and economical treatment
An alternative to surgery
Best accomplished by constant regimens over
long periods of time
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31. PROGESTINS
• Inhibit estradiol-induced vascular endothelial
growth factor & stromal cell-derived factor 1
• Modulation of mitotic activity
• Local growth factors and growth factor receptors
• Paracrine mechanisms and anti-inflammatory
reactions
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32. LNG IUS
• Less menstrual blood loss,
• Reduction in uterine size,
• Improvement in dysmenorrhea.
• The main disadvantage of this treatment is the
irregular menstrual bleeding in the first few months
of treatment.
• High rate of patient satisfaction
• Rise in hemogloblobin and quality of life.
• Viable and effective treatment option for AUB in
women after 35 years.
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33. GNRH AGONIST
• Directly suppress the survival and growth of
ectopic endometrial by decreasing the release of
VEGF
• Induce medical menopause and leads to atrophy
of adenomyotic nodules resulting in reduction of
uterine size and symptomatic relief.
• Its use is limited to short term (3 to 6 months)
because of its menopausal and skeletal side
effects.
• Once the treatment is discontinued, the
condition reccurs
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34. Surgery
• Radical –HYSTERECTOMY which is the
definitive treatment
• Conservative is the choice in young and
infertile patients.
• Excision of affected myometrium can be
performed in patients where the extent of
disease is well-defined.
• This is a viable option in patients who desire
fertility.
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36. Role Of Pre Op Gnrh
• Is not clear
• Advantages:
• correction of anemia,
• decreases vascularity
• reduces intra op bleed
Disadv :
• Difficult recognition of AM foci
• Demarcation is difficult
• Cavity perforation is more
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37. • Difficult planes
• “Woody consistency "
• Suturing is difficult
• Laparotomy or laparoscopy
• Depends on skill,extent and suturing
• The classical technique -uterine incision followed by
step-wise resection of adenomyotic tissue and closure.
• The newer technique H shaped incision followed by
raising serosal flaps and excision of the
adenomyomatous tissue
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39. Surgical procedure to conserve
the uterus for future pregnancy in
patients suffering from massive
adenomyosis
Hisao Osada a,*,
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40. • No technique is better
• But should ensure :
• Maximum removal and should empower
uterine wall integrity
• Effective –
Improves dysmennorhoea by 80%,
Menorrhagia 50% reduction
Pregnancy rate improved by 46 %
Longer symptom control
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42. Magnetic Resonance Imaging–guided Focused
Ultrasound Surgery (MRgFUS)/HIFU
Focal lesions
• Precisely focused USG waves to generate high
intensity acoustic beam and maintain high
temperatures within the targeted tissue
• protein denaturation and coagulative necrosis.
• Monitored using MRI images acquired in real-
time in three planes.
• Significant reduction in menorrhagia and
dysmennorhea .
• Also decreased uterine size.
Pregnancy and live birth reported after HIFU for
symptomatic focal adenomyosis
Robinovici et al HR 2006
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43. EMERGING TRENDS…..
• INHIBITORS OF ANGIOGENESIS
1. DOPAMINE Agonists- Cabergoline
• Promote endocytosis of VEGF -2
• Reduces neoangiogenesis
• Significant decrease in active disease & cellular
proliferation index and modification of gene expression.
2. PENTOXYPHILLINE
• Phosphodiesterase inhibitor
• VEGF and tyrosine kinase.
• 800mg/day x 6 months
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44. EMERGING TRENDS
3.RU486- A Potent Antiprogestin
• 25 mg/day
• Inhibit the genesis of uterine adenomyosis
• Shrinkage of the vascular system.
4.Aromatase inhibitors –LEROZOLE 2.5mg od
– Effective in reducing adenomyoma volume and
improving symptoms.
5. Dienogest
• Each tablet contains 2 mg Dienogest Od x 6 months
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46. Pathophysiology of AM induced
infertility
• Dysregulation of myometrial architecture and
function
• Altered endometrial function and receptivity
• Gene dysregulation
• Altered uterine peristaltic activity
• Impaired implantation
• Altered decidualisation
• Abnormal concentrations of intrauterine free
radicals. Campo et al
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47. ART and AM
• Fewer Follicles
• Mii Oocytes With Scattered chromosomes
• Cytoplasmic Fragmentation
• Pseudopronuclei
• Reduced Fertilisation Rates
• Delayed Arrested Embryo Cleavage
• No Microtubules In Blastocysts
Woods-Marshall et al Reprod Sci2007;14
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49. To conclude
• Adenomyosis is not uncommon in women
• MRI and TVS-similar sensitivity, MRI-higher specificity.
• Medical treatment with GnRH@ depot for atleast 3
months prior to IVF appears to minimise any inhibitory
effect on implantation.
• LNG-IUS appears to be a promising.Not enough
evidence.
• Not enough evidence regarding efficacy or safety of
conservative adenomyomectomy.
• More Evidence by RCTs and meta analysis required in
future
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50. Thank you
And
God bless you
9447044485
drrejimohan@gm
ail.com
9 March 2017 drrejimohan@gmail.com 50
Editor's Notes
, unlike other minor surgical procedures and also other medical treatments known to cause bone loss with repeated use.
An advantage of this treatment modality is that, if symptoms recur after discontinuation of NA
As a part of their routine evaluation, we documented the presence and severity of dysmenorrhea by grading it on a visual analogue scale of 0 to 10 (0: no pain, 10: worst possible pain; 1–3: mild, 4–6: moderate, 7–10: severe). The dysmenorrhea score was developed by multiplying the grade by the number of days that the patient pain (0–10, multiplied by the number of days). Bleeding scores (O. Muneyyirci-Delale modified menstrual calendar, added scale 4: heavy with clots), documented on a scale of 0–4, were used to estimate the amount of bleeding (scale of 0–4: heavy with clots = 4, heavy = 3, normal = 2, light = 1, no bleeding = 0, all the individual days’ scores were added). Patients with scale of 3 and 4 were treated with NA.
Response to hormonal treatment was ascertained verbally from patient for bleeding and pain scores obtained during the follow-up visits. Bleeding and pain scores, before and after treatment, were compared. Student’s T-test was used for statistical analysis.
which was related to the adenomyosis angiogenesis.
so that surgical excision akin to myomectomy is performed with difficulty
precisely focused on a target area with MRI guidance to cause thermal coagulation.
Aromatase inhibitor anastrozole given orally (1.0 mg or 2.0 mg daily) for 16 weeks and GnRH agonist given monthly (injected SC, 1.8 mg) for 4 months.