Adenomyosis is a benign disease of the uterus characterized by ectopic endometrial glands and stroma within the myometrium. It is associated with myometrial hypertrophy and may be either diffuse or focal.

1. Adenomyosis
and Assisted Conception
Marwan Alhalabi MD PhD
Professor in Reproductive Medicine
Faculty of Medicine
Damascus University
And
Medical Director
Orient Hospital
Assisted Reproduction Center
Damascus – Syria

2. Adenomyosis
A Neglected
Disease

3. Karl, baron von Rokitansky
( 1804 – 1878)
In 1860 German
Pathologist
The 1st description on
“Adenomyosis”

4. Thomas Stephen Cullen
1896
• Gynecologist.
• In his book “Adenomyosis
of the uterus” published
in 1908 was the first
systematic description of
what is today known as
adenomyosis

5. Definition
Adenomyosis is a benign disease of the uterus characterized
by ectopic endometrial glands and stroma within the
myometrium.
It is associated with myometrial hypertrophy and may be
either diffuse or focal. (Bird et al, 1972)

6. Definition

7. Definition of Adenomyosis
1- Presence.
2- Depth Of Penetration.
3- Degree Of Spread.
4- Configuration of Lesions
(diffuse or nodular / Focal ).

8. Adenomyosis: Epidemiology
§ About 1% of female patients.
§ 5 - 70% of hysterectomy specimens.
§ More often in multiparous women.
§ History of Uterine Surgery.
§ Less in smokers ( Low E2).

9. Adenomyosis : Epidemiology
• The prevalence of adenomyosis is
unknown:
The available data? is based on
histological diagnosis following
hysterectomy.
Pathologists do not adhere to clear set
of criteria since there is no clinical
impact on the individual patient.

10. The typical symptoms include
• Pelvic pain.
• Dysmenorrhea.
• And menorrhagia unresponsive to hormonal therapy or uterine
curettage.
• Dyspareunia.
• Subfertility. And pregnancy termination.
Cyclic, cramping uterine pain beginning later in reproductive life
(generally after age 35) and often associated with prolonged and
heavy menses
classic presentation

11. Adenomyosis
Possible Association with :
• Infertility
• Early Pregnancy Loss
• Preterm Labor

12. Diagnosis
First Step to Successful Therapy
• Achieving the right diagnosis is probably the most
important task of the physician!
• Without the right diagnosis the choice of treatment is
inadequate and “guess work”.
• The right diagnosis allows the physician to present to the
patient the choice of available treatments and to
determine together the right therapy for the right
patient – a prerequisitefor success!

13. Diagnosis
Major Problem of treatment of
Adenomyosis
• Differential diagnosis with a major and very common
“other” uterine disease:
- uterine leiomyomas35 – 55 % coexistence).
• Knowledge and use of radiological diagnosis (TVUS,
MRI) not yet routine.
• Definitive diagnosis is in the hands of the pathologist!
- many diagnosis (post hysterectomy!)

14. Diagnosis
The diagnosis can only be proven by the
pathologists
A good gynecologist may suspect adenomyosis based on the
clinical factors, but the final diagnosis usually has to wait
until hysterectomy is performed.
(Discepoli S, Leocata P, Giangregorio F).examined 1500 surgical bits had been
histologically examined.. In all they have found 310 cases of adenomyosis (20,6%);

15. If you do not think
“adenomyosis”,
you will not find
“adenomyosis”
Diagnosis

16. transvaginal sonography (TVS)
the sensitivity 80%–86%,
the specificity 50%–96%,
overall accuracy 68%–86%
MR imaging
sensitivity and specificityof 86%–100% overall
accuracy of 85%–90.5%
MR imaging is highly accurate in diagnosis of
adenomyosis,

17. Ultrasound Diagnosis
The technique is strongly
operator dependent
TVUS

18. Adenomyosis: TVUS Morphology
Asymmetrical uterine enlargement
(or globular appearing uterus)

19. Adenomyosis: TVUS Morphology

20. Adenomyosis: TVUS Morphology

21. Sign found in 75%
of patients
Adenomyosis: TVUS Morphology

22. Asymmetrical uterine enlargement
defined hyperechoic & hypoechoic areas
(heterogeneous myometrial echotexture)
Adenomyosis: TVUS Morphology

23. Adenomyosis: TVUS Morphology

24. Asymmetrical uterine enlargement
defined hyperechoic & hypoechoic areas
Small anechoic cysts.
Adenomyosis: TVUS Morphology

25. Adenomyosis: TVUS Morphology

26. The presence of dilated cystic glands or hemorrhagicfoci within the heterotopic
endometrial tissue results in the presence of small myometrial cysts (usually <5
mm in diameter)in approximately 50% of patients
Adenomyosis: TVUS Morphology

27. Adenomyosis: TVUS Morphology

28. Myometrial Veins

29. Asymmetrical uterine enlargement.
Ill defined hyperechoic & hypoechoic areas.
Small anechoic cysts.
Indistinct endometrial-myometrialborder.
Adenomyosis: TVUS Morphology

30. Adenomyosis: TVUS Morphology

31. Linear Striations from Endometrium
( Kepkep et at. Ultrasound Obstet Gynecol, in press)
Adenomyosis: TVUS Morphology

32. Sub endometrial stripes
Adenomyosis: TVUS Morphology

33. 4D Ultrasound

34. MRI
widening of the
junctional zone.
bright foci.

35. •The normal width of the junctional zone is up to 8 mm.
• Widening of the junctional zone from 8 mm up to 12 mm is suggestive
of focal adenomyosis
•a junctional zone that is 12 mm wide or greater is diagnostic of diffuse
adenomyosis
5mm 16mm
MRI

36. The low-signal intensity thickening of the junctional zone represents
pathologic hypertrophy of smooth muscle surrounding islands of
heterotropic endometrial glands
MRI

37. Bright, tiny foci are often noticed on T1- or T2-weighted
images
MRI

38. Diagnosis of Adenomyosis
• In a Cochrane Review
• MRI was superior than TVUS
in the diagnosis.
• The combination of MRI and
TVUS produce higher level
of accuracy.

39. Junctional Zone (JZ)
• The junction between the endometrial mucosa and
myometrium“interface”.
• In recent years this interface “JZ” has proven to be
critically governs many reproductive functions.
• Its smooth muscle cells is under ovarian hormones
control and shows cyclic changes (fujii S et al 1989).
• JZ almost disappear on MRI during OC, GnRh, Post-
menopausal and reappear with HRT.

40. Junctional Zone (JZ)
A disruption of Endometrial – Myometrial interface may lead
to adenomyosis and may occur after mechanical damage.
(Mori et al 1984, Azziz 1989, Levgure et al 2000)

41. Junctional Zone Function
JZ plays an important role in :
- Sperm transport.
- Implantation.
- Ectopic pregnancy.
- Recurrent miscarriages.
- Unexplained infertility.
(Evers JL, et al 1996,Ijland MM et al 1997)
- IVF/ET

42. Uterotubal transport disorder in
adenomyosis --- a cause for infertility
(kissler et al 2006 BJOC)
• MRI + HSG ( Hystero Salpingo Graphy)
in 41 infertility Patient Laparoscopically proven
endometriosis and patent tube, 35 (85%) had
Adenomyosis.
• The data showed that adenomyosis is commonly
associated with endometriosis and has direct effects
on uterotubal transport capacity.
• The data explains the reduced fertility in subjects
with intact tubo-ovarian anatomy.
We call it Unexplained infertility !!!

43. Hysteroscopic Diagnosis

44. Hysterosalpingogram

45. Adenomyosis and infertility
ØStrong association between adenomyosis and
longlife infertility in the baboon (Barrier et al, 2005)
ØAssociation between pelvic endometriosis and
adenomyosis 54% (de Souza et al, 1995) to 97-90% (Kuntzet
al, 2005)
ØIncreased preterm labor (Juang et al, 2006)

46. • Uterine hypermotility: alteration of sperm transport
(Kissper et al, 2006)
• Alteredoxydative stress
(Ota et al, 1998, 2000, 2001)
• Increased microvessel density
(schindl et al, 2001)
• Alteredgene pattern expression
(Heres et el, 2006)
Adenomyosis and infertility

47. Ø Fewer follicles and corpora lutea.
Ø MII oocytes with scattered chromosomes.
Ø Cytoplasmic fragmentation.
Ø Formation of pseudopronuclei.
Ø Spontaneous oocyte activation.
Ø Reduced fertilization and abnormal pronuclei.
Ø Delayed-arrested embryo cleavage.
Ø No microtubules in blastocysts.
Woods-Marshall et al. Reprod Sci 2007;14.
ART and Adenomyosis

48. ART and Adenomyosis
• When to offer IVF?
• Does it affect IVF outcome?
• Is medical therapy pre IVF useful?
• Should ICSI always be used?
• If surgery is needed, which technique?

49. Variabla Healthy Adenomyosis
Cycles 33 25
Embryos 4.1 4
Implantation (%) 16 14.8
Pregnancy (%) 45.5 40
Miscarriage (%) 16 20
Live birth (%) 27.2 28
Healthy
Recipient
Recipient With
Severe Adenomyosis
Diaz et al, Fertil Steril 2000
ART and Adenomyosis

50. Adenomyosis & oocyte donation
ADENOMYOSIS LOW RESPONDER P value
Patients (cycles) 30 (53) 54(68)
Age 36.9±5.8 37.0±0.5 NS
Yrs infertility 4.8±0.6 3.8±1.0 NS
Embryos replaced 3.1±1.2 3.6±0.8 NS
Implantation (%) 28/158(17.7) 59/246(24.0) NS
Clinical pregn.(%) 18/53(33.9) 30/68(44.1) NS
Miscarriage (%) 6/53(11.3) 7/68(10.3) NS
Term pregn. (%) 12/53(22.6) 23/68(33.8) NS
Camargo et al, ESHRE 2000

51. Adenomyosis & oocyte donation
ADENOMYOSIS CONTROL P value
Patients (cycles) 40 (60) 60(60)
Age 38.7±6.8 37.9±5.9 NS
Yrs infertility 2.8±2.1 2.7±1.6 NS
Embryos replaced 2.7±1.5 2.7±1.6 NS
Implantation (%) 27/160(16.9) 40/161(24.8) NS
Clinical preg. (%) 18/60(30.0) 23/60(38.3) NS
Miscarriage (%) 3/60(5.0) 5/60(8.3) NS
Term pregn. (%) 15/60(25.0) 18/60(30.0) NS
Camargo et al, ASRM 2001

52. Junctional Zone in IVF-ET
Ø The important of JZ contractility on pregnancy rate has
been studied in IVF-ET.
(Lesny P et al 1998, Fanchin et al 1998, Lensy et al 2004, Kido A et al 2005).
Ø ART may expose the embryo to a higher JZ activity as
consequence of :
ü High hormone level associated with the ovarian hyperstimulation.
ü Uterine manipulation during ET.
Ø AbnormalJZ as result of Adenomyosis.

53. ART & Adenomyosis
• In large Meta analysis (Barnhart 2002)
Women with adenomyosis undergoing ART have a
significant lower pregnancy rate compared with
women with tubal factor infertility.
Moreover; women with stage 3 and 4
endometriosis have much lower pregnancy rate
than stage 1 and 2
Barnhart k et al, Fertil Steril 2002;77:114-1155

54. Implantation in ART
Embryo quality
Endometrial
Receptivity
Transfer
Efficiency
Adenomyosis

55. Treatment Options
• Medical treatment.
• Surgical treatment.
• Combined surgical and Medical Treatment.
• Vessel embolisation.
• High-intensity focused Ultrasound (HIFU).

56. Medical Treatment
• GnRH agonist (Lin et al, 2000; Huarg et al, 1999) .
• Levonorgestrel – releasing intra-uterine system
(LNG-IUS) Mirena.
• Danazol loaded intra-uterine device.
(igarishi et al 2000)
• Aromatase inhibitors.

57. Medical Treatment

58. Adenomyosis – IVF
Is medical therapy pre IVF useful?
Sallam, Garcia-velascoet al, Cochrane database 2006
GnRHa reduces NK cell activity in vitro

59. conservative surgery for adenomyosis
The conservative surgery for adenomyoma can reduce
symptom and raise pregnancy rate significantly, it can
be accepted by young women who want to preserve
their reproductive capacity.

60. conservative surgery for
adenomyosis
. Though the pregnancy rate of conservative surgery
for diffused adenomyosis was low, it still has
therapeutic value

61. Hysteroscopic management

62. In Site Distruction

63. Combined Surgical and Hormonal
treatment
• Surgical complete resection of the visible
adenomyosis area followed by GnRHa 2-6m
resulted in the birth of 4 cases.
(Hung et al, 1998; Wang et al, 2000; Ozaki et al, 1999)
• Laparoscopic excision of adenomyosis
Followed by live birth. (Lin et al, 2000)
• Laparoscopic cytoreductive surgery resulted in 2
live births. (Wang et al, 2006)

64. Vessel Embolisation

65. Vessel Embolisation
• Siskin et al, 2001 reported on 15 cases
diagnosed with MRI, improvement of
quality of life in 12 out of 13.
• The reported series are small and so far
No successful pregnancy has been
reported.

66. UAE is an effective and safe method
in the treatment of Adenomyosis.
BUT the recurrence rate is not yet
evaluated.
Vessel Embolisation

67. High – Intensity Focused
Ultrasound (HIFU)
HIFU give a combination of Coagulation
and tissue destruction in a non-invasive,
bloodless manner, under MRI guiding.

68. High – Intensity Focused
Ultrasound (HIFU)

69. High – intensity Focused
Ultrasound (HIFU)
• Pregnancy and live birth reported after HIFU
for symptomatic focal adenomyosis.
(Robinovici et al, Hum Reprod 2006).
• The early results indicate the safe and
effective ablation of adenomyosis tissue by
HIFU the procedure also resulted in the
improvement in clinical symptoms during the
6 month of follow – up.
(Fukunishi et al, 2008).

70. Summary
• The prevalence of adenomyosis in infertility is not known.
• The aetiology, pathogenesis are unclear.
• The diagnosis before hysterectomy is difficult.
• The options of treatment are limited
• Further studies are needed to explore:
- The relation of unexplained infertility and adenomyosis
- How adenomyosis effect IVF outcome
- Diagnostic, non-invasive and reliable tools.

71. Conclusion 1
• Adenomyiosis is strongly associated with endometriosis
and uterine fibromas, thus being frequently diagnosed in
infertile patients.
• In women with adenomyosis the receptivity of the eutopic
endometrial to embryo implantation appears normal.
• Adenomyosis might impair the mechanism of directed
sperm transport.

72. Conclusion 2
• Adenomyosis might compromise the intrafollicular
development of oocytes and thus represents a
causal factor of subfertility.
• Alterations in the gene expression pattern of the
endometrium of women with adenomyosis have
been described.

73. Conclusion 3
• The infertility in women with adenomyosis is
best treated by hormonal stimulation and IVF,
not by insemination.

74. Conclusion 4
• There are novel “uterus-preserving”
treatment options for adenomyosis !
- LNG-IUS.
- Vessel embolisation .
- HIFU.

75. Conclusion: take home
Massage
• Before you make the diagnosis of
unexplained infertility, or you have
failure of assisted conception :
Try to exclude the possibility of
Adenomyosis.
“ Particularly in infertility women with heavy periods
or chronic pelvic pain”

76. Acknowledgement
Clinical Team
S. Samawi
N. Kafri
S. Modi
M. Mousa
IVF Lab
J. Sharif
R. Doghoz
A. Kadri
A. Konali
Fetal Med.
A. Taha
M. Khalaf
M. Hazemah
Andrology Lab
W. Hamad
N. Assaf
M. Othman
N. Mazzawi
S. Sheko
Bio-Ginitic Lab
A. Khatib
M. Kinj
A. Sakr
A. Othman Administration
F. Hamad
R. Qamar
M. Haj hasan
N. Olabi
E. Fayad
W. Saker
Med Engineering
Y. Khabori
S. Khayat
Anesthesia
R. Tarko
Y. Lakkis
M. Khadra
H. Sulaiman