Adenomyosis has a negative impact on reproductive outcome, there is a correlation between extent of the disease and reproductive outcome .Strict diagnostic criteria and classification of disease are needed for an image diagnosis of adenomyosis.
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Adenomyosis & Infertility - A Webseries Talk
1. Dr Aditya Das
Fertility Consultant & Trainer
Keya FERTILITY & Embryoedu
Bhubaneswar, India
Member , Neoindia Fertility Society (NIFS)
Member , ISAR , ESHRE,ISMAAR
2.
3. an American actress
a voice artist
an activist
an author
She began her career in the 1990s, appearing on
television sitcoms, before landing supporting roles in
teenage comedic films She's All That and 10 Things I
Hate About You.
Her breakthrough role was in the 2000 film Bring It On.
5. Gabrielle Union,45 has been incredibly open
about her fertility struggles, and even revealed in
her book We’re Going to Need More Wine
that she’s had “eight or nine” miscarriages.
7. “Everyone said ‘You’re a career woman, you’ve
prioritized your career, you waited too long and now
you’re just too old to have a kid—and that’s on you for
wanting a career,’ ” she said.
“The reality is I actually have adenomyosis. "There is
nothing you can do about adenomyosis. The gag is
that I had adenomyosis in my early 20s,"
8. Gabrielle waited years for an adenomyosis diagnosis
and that’s not uncommon, since so much about the
condition, including what causes it, is still unknown.
9. Dr Aditya Das
Fertility Consultant & Trainer
Keya FERTILITY & Embryoedu
Bhubaneswar, India
Member , Neoindia Fertility Society (NIFS)
Member , ISAR , ESHRE,ISMAAR
10. OVERVIEW
What is Adenomyosis ( AD) ?
What are the causes ?
Evaluation ?
What are the treatment options?
Medical Vs Surgery Vs ART ?
Guidelines & Evidences
Take home messeges
11. What’s really Adenomyosis
• Karl, baron von Rokitansky
In 1860 German Pathologist The
1st description on “Adenomyosis”
• Thomas Stephen Cullen 1896
Gynecologist. In his book
“Adenomyosis of the uterus”
published in 1908
12. What’s really Adenomyosis
• Adenomyosis (AD) is regarded as a
disease of the endomyometrial
junction defined by the presence
of heterotopic endometrial glands
and stroma in the myometrium.
• Migration of endometrial cells
into the myometrium is
accompanied by a varying degree
of muscular hypertropia.
13. What’s really Adenomyosis
• AD should be understood as a two-
component
1. disease consisting of an element
of ectopic endometrial glands and
stroma
2.element of muscular change
(hypertropia, hyperplasia, and
fibrosis).
14. Adenomyosis & Infertility
• Classical form : Fourth or fifth decades of life, dysmenorrhea
and menorrhagia.
• AD can coexist with endometriosis in younger women
• AD has been suggested to cause implantation failure in younger
women with endometriosis .
• Infertility is a less frequent complaint in the classic form,
• women delay their pregnancy until their late 30s or 40s, the
relation between AD and infertility is becoming increasingly
relevant.
15. PROPOSED MECHANISM OF INFERTILITY IN
PATIENTS WITH ADENOMYOSIS
• 1. Abnormal Uterotubal Transport
• 2. Altered Endometrial Function and Receptivity
- Altered Endometrial Steroid Metabolism
- Abnormal Inflammatory Response
- Altered Expression of Estrogen and Progesterone Receptors
- Altered Uterine Oxidative Stress Environment
- Lack of Expression of Adhesion Molecules
- Reduced Expression of Implantation Markers
- Altered Function of the Gene for Embryonic Development HOXA 10 gene
17. Right Diagnosis – Right Therapy
• Diagnosis Major Problem of treatment of Adenomyosis •
• uterine leiomyomas35 – 55 % coexistence).
• Definitive diagnosis is by pathologist! - many diagnosis (post
hysterectomy!)
• Knowledge and use of radiological diagnosis (TVUS, MRI) not
yet routine.
• HPE : (20.6%) cases show eo adenomyosis
Think of “adenomyosis”, you will find “adenomyosis”
18. a. The diagnosis of AD is made by histopathology.
b. TVS, 3D-TVS and MRI has made it possible to perform an
image diagnosis of AD
The inner myometrium adjacent to the endometrium, or
junctional zone (JZ)
JZ is displayed as a thin hypoechoic zone by TVS
low signal band adjacent to the endometrium by MRI.
19. Diagnosis : Hysterosalpingogram HSG Findings
- small diverticula
extending into the
myometrium
- The opacified uterine
cavity presents irregular
contour with small
outpouchings of contrast.
21. Diagnosis : Sonographic Features
Two or more of the following:
- a mottled inhomogeneous myometrial texture,
- globular appearing uterus,
- small cystic spaces within the myometrium
- "shaggy" indistinct endometrial stripe.
26. • numbers of sonographic criteria and the symptoms of
menorrhagia .
• Signs of ectopic endometrium are highly specific, whereas signs
of muscular changes are less specific both by TVS and MRI .
• Changes in the JZ : MRI or 3D-TVS
• 3D-TVS slightly more efficient than 2D-TVS
27. Diagnosis : MRI Findings
• Widened JZ (at least 12 mm)
• Heterogenous myometrium
• Intramyometrial cyst(s)
“Thickened junctional zone is by far the most sensitive
(95%), specific (94%) and accurate (95%) sign to diagnose
adenomyosis in MRI.”
Ahmed Hamimi etal,EJRNM,2015
28. 1. Focal uterine adenomyosis
showing focal thickening of
the jz along the posterior wall
(arrow),
2.Myometrium :heterogenous
3.small cervical cyst
29. 1. Multiple uterine fibroids
seen in a bulky uterus.
2. Diffusely thickened
posterior junctional zone
showing multiple cystic areas
suggestive of adenomyosis.
30. sensitivity specificity
• TVU 72% (65–79) 81% (77–85)
• MRI 77% (67–85) 89% (84–92)
• 23–28% false-negative results and 11–19% false-positive .
• diagnostic efficiency of imaging techniques may be different in
infertile populations
• proportion of women with minimal disease may be more
pronounced.
31. MRI is superior to sonography in the diagnosis of uterine
adenomyosis though we still recommend to start with the
latter owing to its availability.
32. Diagnosis : Hysteroscopic Findings
can detect adenomyosis in 10% to 20% of cases
cannot detect whether focal or extensive adenomyosis
33. Classic hysteroscopic findings :
diffuse gland openings
hemosiderin deposits within the endometrium
glands with blood seen entering the gland-like openings
Diagnosis : Hysteroscopic Findings
34. Importance of Junctional zone in Adenomyosis
• Smooth muscle changes (microtraumas in the endo-myometrial
border )in the JZ may precede AD.
• maximum JZ thickness of ≥8 and <12 mm : hyperplasia,“stage 0”
• Fertile women seem to have a regular, thin JZ (median 5.2mm)
35. Importance of Junctional zone in Adenomyosis
• slight localized expansion of the JZ to massive myometrial
hyperplasia and fibrosis
• change the plasticity and tonus of the uterus as well as the
contour of the endometrial cavity
• effect on peristalsis, uterine contraction, and fertility
There is no consensus on a classification system regarding the
extent of the disease based on image morphology .
36. Importance of Junctional zone in Adenomyosis
• increase in JZ thickness significantly correlated with implantation failure at IVF.
• PR : JZ thickness (AJZ) <7 mm 63%
>7 mm 26%
JZmax <10mm 63 %
>10mm 14 %
• Implantation failure rate : 96% JZ thickness >7-10 mm
38% in other patient groups.
• JZ thickness <12 mm (JZ hyperplasia) may have an adverse effect .
However, more studies are needed.
37. Treatment of Adenomyosis in Infertile Patients
• Medical Therapy ( GnRHa , Progestins , Dienogest , Mirena)
• Surgical Therapy
• ART
• Others
38. Medical Therapy
• GnRH-a :
- decreases the size and demarcation of adenomyotic lesions,
- positive effect on endometrial implantations markers .
• GnRH-a pretreated women :
CPR, IR , and ongoing PRs were significantly higher
39. Surgical Therapy
• UTERINE SPARING CYTOREDUCTIVE SURGERY :
feasible and can be efficacious in carefully selected women <40 years old
• LAPAROSCOPIC CYTOREDUCTIVE SURGERY :
localized adenomyosis who failed the usual infertility treatments and
assisted reproductive technology (ART). - Wang et val
• the risk of uterine rupture after surgery
• the limited evidence of improved outcome
• should reserve surgery to centers in which well-designed studies are
performed and the benefit is validated.
40. Surgical Therapy
• Conservative surgery or combination treatment Vs GnRHa alone :
significant benefits for not only controlling symptoms but also for
increasing the pregnancy rate
• The combination of microsurgical cytoreduction and GnRH-a
treatment could be appropriate for patients who failed GnRH-a
alone or would not tolerate long-term GnRH-a treatment for
presumed severe adenomyosis.
- Wang PH, Fuh JL, Chao HT, et al. J Obstet Gynaecol Res. 2009;35:495–502.
42. Hysteroscopy
• A technique that involves hysteroscopic treatment of
myometrial cysts by ultrasound-guided incision, excision or
coagulation has been described.
• However, there are no studies evaluating the benefit of this
treatment on fertility .
43. ART in adenomyosis
• Fewer follicles and corpora lutea.
• MII oocytes with scattered chromosomes.
• Cytoplasmic fragmentation.
• Formation of pseudopronuclei.
• Spontaneous oocyte activation.
• Reduced fertilization and abnormal pronuclei.
• Delayed-arrested embryo cleavage.
• No microtubules in blastocysts.
Woods-Marshall et al. Reprod Sci 2007;14. ART and Adenomyosis
44. ART in adenomyosis
• Lower PR : women with adenomyosis who underwent IVF.
• No significant differences in IVF/ICSI outcome :
with and without adenomyosis with pretreatment with GnRHa
for more than 3months .
• age and coexistence of endometriosis alongwith adenomyosis :
may be related to a lower pregnancy rate.
• patients with adenomyosis who previously had multiple
unsuccessful IVF cycles promptly resulted in successful
pregnancy with ART after prolonged down-regulation with
GnRH-a.
45. HIFU & UAE
• Principle : necrosis in the involved adenomyotic tissue
• Challenge : to control the size and location of the necrosis.
• Consequently, the myometrial tissue is affected, which may reduce
the strength of the uterine wall and induce a risk of rupture in
pregnancy.
• Still in experimental stage
• No larger studies on pregnancy outcome and only cases of
pregnancy are reported
• Not been recommended for women with AD and a wish to
conceive.
47. Summary
- Adenomyosis has a negative impact on reproductive outcome,
there is a correlation between extent of the disease and
reproductive outcome .
-Strict diagnostic criteria and classification of disease are needed
for an image diagnosis of adenomyosis.
-In a case of Unexplained infertility , don’t forget to rule out
adenomyosis .
48. Summary
Case series seem to confirm a positive effect of gonadotropin-releasing
hormone analog treatment and surgery on reproductive outcome, but there
are no controlled trials.
Adenomyosis may reduce implantation so severely that surgical or other
treatment options should be recommended, but the benefit of these
treatment options needs to be verified.
49. Summary
• At present, GnRH-a pretreatment before natural conception is
suggested in women without diminished ovarian reserve.
• In women with diminished ovarian reserve, immediate IVF or ICSI
with long protocol or oocyte retrieval can be followed by frozen
embryo transfer after GnRH-a treatment is performed.
• Insemination may not be the right option .
• Surgery should only be an option for symptomatic women with
repeated miscarriage or repeated IVF/ICSI failure .